@article {pmid42583074,
year = {2026},
author = {Glynne-Jones, R and Mawdsley, S},
title = {The historical perspective on anal cancer therapy: what have we learnt, where did we fail?.},
journal = {ESMO gastrointestinal oncology},
volume = {13},
number = {Pt A},
pages = {100151},
pmid = {42583074},
issn = {2949-8198},
abstract = {Squamous-cell cancer of the anus is a rare entity. Fifty years ago, understanding the natural history was limited by the lack of an agreed staging system and a largely irrelevant but complex histological categorisation. Retrospective reports described a small number of patients, generally with small tumours, treated by diverse methods with limited follow-up. The use of therapeutic radiation was limited by observed acute toxicity. Some centres gained substantial experience with interstitial radiation, but knowledge and expertise regarding the natural history and optimal methods of treatment were difficult to accumulate and hand on. Radiotherapy (RT) with or without interstitial radiation as the primary treatment, chemoradiotherapy (CRT) both definitive and preoperative, local excision for residual after CRT and small margin carcinomas and 'prophylactic' groin dissections after radical surgery all had advocates in different centres. The dogma in Europe at the time favoured split-course treatments. Early experiments combining fluoropyrimidines and RT were refined with Nigro et al.'s landmark study in 1974. Subsequent regimens are variations and today CRT with concurrent fluoropyrimidines and mitomycin C is accepted as the standard primary treatment. Early randomised phase III trials proved CRT to be more effective than external beam RT alone, but uncertainty remained over the optimal integration of chemotherapy, the type of chemotherapy, the ideal RT doses and potential late effects. These questions were imperfectly addressed and led to subsequent pragmatic phase III trials testing the impact of induction and consolidation chemotherapy and dose escalation. We describe the historical perspective and examine the opportunities we failed to grasp.},
}

@article {pmid42583247,
year = {2026},
author = {Klyk, C and Wohnrade, C and Petri, S and Haghikia, A and Körner, S and Volk, LH},
title = {Gold coast criteria but not neurofilaments improve diagnostic sensitivity in a specialized ALS university center.},
journal = {Clinical neurophysiology practice},
volume = {11},
number = {},
pages = {512-521},
pmid = {42583247},
issn = {2467-981X},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by upper and lower motor neuron loss. Diagnosing ALS may still be challenging due to the absence of specific biomarkers and requires thorough clinical evaluation, comprehensive electromyography (EMG), and exclusion of differential diagnoses by laboratory analyses and imaging. The Gold Coast criteria (GCC) replaced the revised El Escorial (rEEC) and Awaji criteria (AC), simplifying ALS diagnosis and standardizing communication with patients.

METHODS: This retrospective study compared the sensitivity of the GCC with the rEEC and AC in a specialized neuromuscular center.

RESULTS: 431 patients with suspected ALS were included, and 426 patients ultimately received an ALS diagnosis. The GCC showed higher sensitivity than both the rEEC and AC. The explorative inclusion of neurofilament levels into an extended diagnostic framework did not increase the sensitivity of rEEC and AC.

CONCLUSIONS: Continued clinical use of the GCC should be considered the standard for ALS diagnosis. Careful clinical and electrophysiological examination is particularly essential in this context, supplemented by biomarkers such as neurofilaments.

SIGNIFICANCE: This retrospective real-world study demonstrates a high sensitivity of the GCC in a specialized neuromuscular clinic.},
}

@article {pmid42583548,
year = {2026},
author = {Suazo, JRP and Piuvezam, G and Pimenta, IDSF and Ferrándiz, LL and Ríos, MP and Castro-Delgado, R},
title = {Effectiveness of extended reality-based cardiopulmonary resuscitation training for healthcare students: A systematic review.},
journal = {Turkish journal of emergency medicine},
volume = {26},
number = {3},
pages = {223-233},
pmid = {42583548},
issn = {2452-2473},
abstract = {BACKGROUND: Cardiopulmonary resuscitation (CPR) is a lifesaving intervention where timely, effective actions improve survival. However, traditional Basic and Advanced Life Support (BLS and ALS) training often lacks realism, limiting preparedness among healthcare students. Extended Reality (XR) technologies, including Virtual, Augmented, and Mixed Reality, offer promising tools to enhance CPR training. The aim is to assess the effects of XR on CPR training outcomes among healthcare students.

METHODOLOGY: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines, PubMed/MEDLINE, EMBASE, CINAHL, Cochrane, Web of Science, and Scopus were searched for randomized controlled trials and quasi-experimental studies. Two reviewers independently extracted data, with disagreements resolved by a third. Risk of bias was evaluated using Cochrane ROB 2 and ROBINS-I. Due to heterogeneity, findings were synthesized narratively.

RESULTS: Eight studies from six countries were included. Evidence showed mixed outcomes: XR improved confidence and reduced anxiety in Basic Life Support and ALS training, but results on technical performance, including CPR knowledge and quality, were inconsistent. Variability in study design and concerns about bias limited generalizability.

CONCLUSION: XR shows potential as a valuable complement to traditional CPR training, particularly in blended learning approaches aligned with modern pedagogy. However, inconsistent findings highlight the need for standardized assessments, evaluation of long-term outcomes, and integration of haptic torso simulators to improve technical skills and clarify XR's role in resuscitation education.},
}

@article {pmid42584174,
year = {2026},
author = {Wang, BN and Van Der Spek, RAA and Van Nispen Tot Sevenaer, JDAM and Van Vugt, JJFA and Munnik, FA and Bakker, MK and , and Van Es, MA and Van Den Berg, LH and Van Rheenen, W and Veldink, JH},
title = {Lessons from a systematic review of family-based studies in ALS.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2713969},
pmid = {42584174},
issn = {2167-9223},
abstract = {ALS is genetically heterogeneous, with many causal genes identified through family-based gene-discovery studies. To evaluate this progress, we systematically reviewed these studies and identified unresolved genomic regions across five pedigrees. Reexamination resolved two pedigrees, nominating FUS and SYNE1 as the causal genes. The remaining three pedigrees exhibited linkage to four unresolved regions, which we reanalyzed using large-scale genetic datasets. We found no convincing evidence for new ALS-causing variants in these regions. These unresolved regions originated from complex pedigrees-consanguineous, isolated, or containing only a few affected individuals-whereas successful linkage was observed in larger, multigenerational families with ALS. Our findings confirm that family-based methods are robust in typical ALS pedigrees but lack power in small pedigrees with few affected individuals or in phenotypically heterogeneous families. Given these challenges and the rare-variant architecture of ALS, we propose a 'super-pedigree' framework to identify extended families with ALS to discover shared genetic risk factors and help develop gene-based therapies.},
}

@article {pmid42585674,
year = {2026},
author = {Godage, P and Giggins, OM and Doyle, J and Byrne, A},
title = {Integrating psychological support into gestational diabetes self-management: Development of a user-centred digital mindfulness programme.},
journal = {Women's health (London, England)},
volume = {22},
number = {},
pages = {17455057261473448},
pmid = {42585674},
issn = {1745-5065},
mesh = {Humans ; *Mindfulness/methods ; Female ; *Diabetes, Gestational/psychology/therapy ; Pregnancy ; *Self-Management/methods/psychology ; Adult ; Qualitative Research ; Focus Groups ; Digital Media ; Stress, Psychological ; Needs Assessment ; User-Centered Design ; Digital Health ; Social Support ; },
abstract = {BackgroundGestational diabetes mellitus (GDM) presents significant psychological and behavioural challenges, with diagnosis often triggering stress, anxiety, and fear. Despite these burdens, structured psychosocial support remains limited within existing GDM care. Mindfulness-based interventions (MBIs) show promise for reducing distress in perinatal contexts, but few are tailored to the unique needs of individuals with GDM, and digital delivery remains rare.ObjectivesThis study aimed to develop a digitally delivered mindfulness programme tailored to the psychological needs of individuals with GDM using a user-centred, multi-phase design approach.DesignA qualitative, multi-phase participatory design study involving needs assessment and co-design workshops, guided by the Obesity-Related Behavioural Intervention Trials (ORBIT) model for behavioural intervention development and Loucks et al.'s evidence-based adaptation framework for Mindfulness-Based Programmes (MBPs).MethodsA qualitative needs assessment was conducted through focus groups with individuals with GDM (n=11) and healthcare professionals (n=4) to identify psychological experiences, mental health support, and the feasibility of a digital mindfulness intervention. Findings informed the initial mindfulness programme framework, which was further refined through participatory co-design workshops (n=10) and iterative tailoring of scripts and multimedia content.ResultsParticipants reported high levels of emotional distress following GDM diagnosis, citing a strong desire for brief, flexible, and supportive psychosocial interventions. Co-design feedback highlighted preferences for short audio-guided sessions, soft and calming voice characteristics, and seamless integration into daily routines. The final one-month programme comprised 20 mindfulness exercises, delivered via audio and video for integration within a holistic GDM self-management app.ConclusionA systematically developed, contextually relevant digital mindfulness programme may address critical gaps in GDM care, supporting psychological well-being and self-management.},
}

Humans
*Mindfulness/methods
Female
*Diabetes, Gestational/psychology/therapy
Pregnancy
*Self-Management/methods/psychology
Adult
Qualitative Research
Focus Groups
Digital Media
Stress, Psychological
Needs Assessment
User-Centered Design
Digital Health
Social Support

@article {pmid42585850,
year = {2026},
author = {Alencar, MA and Gonçalves, JMW and D Allembert, D and Rangel, MFA and Gomes, PCF and de Souza, LC},
title = {Falls in people with amyotrophic lateral sclerosis: A prospective study.},
journal = {Brazilian journal of physical therapy},
volume = {30},
number = {5},
pages = {101623},
doi = {10.1016/j.bjpt.2026.101623},
pmid = {42585850},
issn = {1809-9246},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness. Falls are common and may lead to dependence, reduced quality of life, higher healthcare costs, and death. Few studies have examined falls in ALS.

OBJECTIVES: To investigate the frequency of falls in individuals with ALS with and without functional ambulation, and to identify predictors of falls at three and six months among those with functional ambulation.

METHODS: A longitudinal prospective study included 66 individuals with ALS. Falls were assessed through interviews at three- and six-month follow-ups. Demographic and clinical characteristics, functional capacity, lower limb strength, fatigue, mobility, and balance were assessed. Descriptive, bivariate, and logistic regression analyses were performed.

RESULTS: At baseline, 42 participants were ambulatory and 24 non ambulatory (wheelchair-dependent). Among ambulatory participants, 38 were assessed at three months (18 fallers, 47%) and 37 at six months (22 fallers, 59%). Among non-ambulatory participants, 22 were assessed at three months (4 fallers, 18%) and 20 at six months (2 fallers, 10%). Losses in both groups were due to death. Predictors of falls in the ambulatory group were lower limb strength (Odds Ratio [OR]: 0.844; p = 0.016) and fatigue (OR: 7.800; p = 0.037) at three months, and lower limb strength (OR: 0.856; p = 0.009) at six months.

CONCLUSION: Falls can occur across functional profiles in ALS and are most frequent among ambulatory individuals. These findings highlight the importance of assessing fall risk and considering strategies. In ambulatory participants, interventions focusing on lower limb strength and fatigue may contribute to fall prevention.},
}

@article {pmid42586199,
year = {2026},
author = {Pecorari, C and Montagna, C and Cozzolino, M and D'Ambrosi, N and Benassi, B and Cirotti, C and Filomeni, G},
title = {Nuclear SOD1 links ATM-CHK2 signaling to ADH5/GSNOR transcription in SHSY-5Y SOD1[G93A] cellular models of ALS.},
journal = {Nitric oxide : biology and chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.niox.2026.08.001},
pmid = {42586199},
issn = {1089-8611},
abstract = {The activity of S-nitrosoglutathione reductase (ADH5/GSNOR) has been proposed being essential to limit oxidative stress and preserve mitochondrial quality control. Here we identify a redox-dependent ATM-CHK2-SOD1 signaling axis that drives ADH5/GSNOR transcription in SH-SY5Y cells expressing the ALS-associated SOD1[G93A] mutant. ATM-CHK2 activation promotes the interaction of SOD1 with CHK2, leading to SOD1 nuclear translocation and binding to the ADH5 promoter. Pharmacological inhibition of ATM or CHK2 abolishes these effects. ADH5/GSNOR overexpression protects cells from SOD1[G93A]-induced toxicity suggesting that the modulation of GSNOR activity may represent a potential strategy to restore redox homeostasis in ALS.},
}

@article {pmid42586267,
year = {2026},
author = {Tognaccini, C and Thomas, LE and Ghanim, D and Ghebrial, M and Ansari, Z and Gupta, K and Wu, JJ},
title = {Comment on Chen et al.'s "Disparities of itch severity in outpatient clinics as measured by the ItchyQuant".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.07.127},
pmid = {42586267},
issn = {1097-6787},
}

@article {pmid42586268,
year = {2026},
author = {Ghanim, D and Ghebrial, M and Tognaccini, C and Thomas, LE and Ansari, Z and Gupta, K and Wu, JJ},
title = {Comment on Gao et al.'s "A Multicenter, Randomized, Double-blinded, Placebo-Controlled Phase III Trial to Evaluate Efficacy and Safety of Picankibart in Moderate-to-Severe Plaque Psoriasis".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.06.151},
pmid = {42586268},
issn = {1097-6787},
}

@article {pmid42586271,
year = {2026},
author = {Rundle, CW and Lukowiak, TM and Maher, IA},
title = {Response to Wang et al.'s: Cartilage grafts for alar reconstruction in nasolabial interpolation flap surgery may negatively affect breathing function and cosmesis: A retrospective study.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.07.126},
pmid = {42586271},
issn = {1097-6787},
}

@article {pmid42586272,
year = {2026},
author = {Chen, RF and Chen, SC},
title = {Response to Tognaccini et al., "Comment on Chen et al.'s 'Disparities of itch severity in outpatient clinics as measured by the ItchyQuant'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.08.022},
pmid = {42586272},
issn = {1097-6787},
}

@article {pmid42586274,
year = {2026},
author = {Shi, Y},
title = {Response to the letter by Ghanim et al, "Comment on Gao et al.'s 'A Multicenter, Randomized, Double-blinded, Placebo-Controlled Phase III Trial to Evaluate Efficacy and Safety of Picankibart in Moderate-to-Severe Plaque Psoriasis'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.08.025},
pmid = {42586274},
issn = {1097-6787},
}

@article {pmid42586324,
year = {2026},
author = {Palumbo, F and Iazzolino, B and Canosa, A and Manera, U and Vasta, R and Grassano, M and Ilardi, A and Cabras, S and Matteoni, E and Maccabeo, A and Pede, FD and De Mattei, F and Pellegrino, G and Minerva, E and Riva-Rovedda, F and Clari, M and Zocco, G and Pascariu, D and Testa, M and Arcari, M and Veronese, S and Chiò, A and Moglia, C and Calvo, A},
title = {Advance Care Planning in Amyotrophic Lateral Sclerosis: a retrospective population-based study.},
journal = {Journal of pain and symptom management},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jpainsymman.2026.08.002},
pmid = {42586324},
issn = {1873-6513},
abstract = {BACKGROUND: . In recent decades, autonomy and self-determination in Amyotrophic Lateral Sclerosis (ALS), have gained increasing attention, and Advance Care Planning (ACP) has been incorporated into ALS guidelines. In Italy, Law 219 emphasizes the role of ACP in respecting patients' healthcare preferences. However, longitudinal data on ACP prevalence and impact remain limited.

AIM: . To assess the prevalence of ACP discussions in a population of ALS patients, their effectiveness in end-of-life management, and the impact of Law 219/2017.

METHODS: . Demographic and clinical data from the PARALS Register (2008-2020) were retrospectively examined, with particular focus on ACP discussions, tracheostomy preferences, and end-of-life outcomes.

RESULTS: . Of 1219 ALS patients, 655 (53.7%) had ACP discussions, with 90.8% concordance between expressed choices and outcomes. The ACP prevalence increased over time from 51.6% to 61.94% (p = 0.025). Cognitive impairment, including fronto-temporal dementia and intermediate cognitive-behavioural impairment, and absence of NIMV use were negatively associated with ACP (p = 0.029 and p < 0.001). Older age was associated with tracheostomy placement (p < 0.001). ACP discussion was positively associated with gastrostomy placement, Palliative Care activation, and home death.

CONCLUSIONS: . ACP plays a crucial role in ALS care, with high alignment between expressed choices and outcomes. Cognitive impairment reduced ACP participation, highlighting the need for earlier, tailored interventions. The ACP increase over the last decade reflects a growing emphasis on patient autonomy in Italy. Further efforts are needed to expand ACP adoption in ALS care, to support self-determination despite cognitive decline and disease progression.},
}

@article {pmid42586601,
year = {2026},
author = {Chai, X and Zheng, Z and Wang, N and He, Q and Jia, Y and Wan, K and Zhu, S and Zhang, B and Niu, H and Zhai, Y and Zhao, J and Yang, Y},
title = {Real-world clinical characteristics of motor disorders for personalised brain-computer interfaces: phenotypic insights from a specialised clinic.},
journal = {Stroke and vascular neurology},
volume = {},
number = {},
pages = {},
doi = {10.1136/svn-2026-005290},
pmid = {42586601},
issn = {2059-8696},
abstract = {Motor dysfunction caused by neurological disorders such as stroke, spinal cord injury and amyotrophic lateral sclerosis has become a major global public health issue. Conventional rehabilitation approaches yield limited efficacy, highlighting the urgent need for innovative therapies. Brain-computer interface (BCI) technology offers a promising avenue for motor function restoration by decoding motor intentions and driving external devices or providing sensory feedback. However, current BCI development has predominantly emphasised technical performance metrics, lacking systematic investigation into the clinical characteristics of real-world patient populations. This disconnect between technological advancement and genuine clinical demands persists because existing studies often recruit idealised subjects while neglecting prevalent conditions like stroke and lack standardised assessments of clinically meaningful outcomes. Consequently, system designs frequently fail to align with patient-specific profiles. To address this gap, our study established a prospective BCI evaluation outpatient cohort, comprehensively collecting data from patients presenting with motor dysfunction throughout 2025. Among the total of 1641 patients with motor dysfunction, the majority were patients with chronic-phase stroke (1087, 66.24%). The cohort was primarily middle-aged, with a mean age of 45.93±11.23 years. The study further detailed patterns of muscle strength, joint range of motion and sensory impairments. The goal is to construct the first clinical profile characteristics to inform precise patient selection and guide personalised system design.},
}

@article {pmid42586726,
year = {2026},
author = {Quasdorf, T and Brenner, S and Kramer, I and Kotkowski, K and Gutenberg, J},
title = {Developing organisational capacity building for person-centred dementia care in nursing homes: a multiphase co-design study protocol.},
journal = {BMJ open},
volume = {16},
number = {8},
pages = {e123820},
doi = {10.1136/bmjopen-2026-123820},
pmid = {42586726},
issn = {2044-6055},
mesh = {*Nursing Homes/organization & administration ; Humans ; *Patient-Centered Care/organization & administration ; *Dementia/therapy ; *Capacity Building/organization & administration ; Research Design ; Organizational Culture ; Qualitative Research ; },
abstract = {INTRODUCTION: Person-centred dementia care (PCdC) is widely recognised as a core principle of high-quality dementia care and is embedded in national and international dementia care guidelines. However, translating PCdC into routine practice in nursing homes (NHs) continues to pose a significant challenge. This reflects both the theoretical complexity of PCdC and the fact that its delivery relies less on discrete care techniques and more on an underlying organisational culture and shared approach to care. Implementing PCdC therefore requires an organisational perspective that acknowledges the interplay between staff, leadership and organisational conditions. Although several approaches exist to strengthen organisational capacity for PCdC, NHs often lack guidance on how to identify and apply approaches that fit their specific context. This study aims to develop a toolbox that supports NHs in systematically building the organisational capacity required to implement and sustain PCdC in their specific context.

METHODS AND ANALYSIS: The toolbox will be developed through three consecutive studies:Study 1: An exploratory qualitative study of the perspectives of managers and staff in NHs on organisational capacity building (OCB) for implementing and sustaining PCdC.Study 2: A co-design study involving workshops to develop a first version of the OCB toolbox, informed by insights from a preliminary scoping review (conducted separately and published as a protocol on Open Science Framework) and Study 1.Study 3: A qualitative consensus-building study using a nominal group technique with stakeholders and PCdC experts to refine and finalise the OCB toolbox (validation phase).The toolbox development is conceptualised as the development of a complex intervention and will therefore be informed by O'Cathain et al's guidance for developing complex health interventions. While co-design principles guide the overall development process, Study 2 represents the dedicated co-design phase involving collaborative workshops, ensuring that the resulting OCB toolbox integrates research evidence with practice-based insights.

ETHICS AND DISSEMINATION: The Cantonal Ethics Committee Zurich confirmed that the study is exempt from formal ethical approval under the Swiss Human Research Act (Req-2025-00812). Findings will be disseminated through peer-reviewed publications, conference presentations and practice-oriented outputs, including a toolbox for NHs.},
}

*Nursing Homes/organization & administration
Humans
*Patient-Centered Care/organization & administration
*Dementia/therapy
*Capacity Building/organization & administration
Research Design
Organizational Culture
Qualitative Research

@article {pmid42586744,
year = {2026},
author = {Shijo, T and Suzuki, N and Warita, H and Ikeda, K and Namioka, Y and Kato, M and Aoki, M},
title = {Emergency Tracheostomy with Invasive Ventilation in Patients with Amyotrophic Lateral Sclerosis Increases Hospitalization Duration and Long-Term Complications.},
journal = {The Tohoku journal of experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1620/tjem.2026.J085},
pmid = {42586744},
issn = {1349-3329},
}

@article {pmid42587315,
year = {2026},
author = {Farghaly, A and Al-Khateeb, LA and Kanaan, BM and Magdy, G and Khashoqji, MM and Tantawy, MA and Abbas, AEF},
title = {Spectrophotometric determination of cefepime and enmetazobactam in pharmaceutical formulations and human plasma using chemometric modeling, metaheuristic wavelength selection, and comprehensive sustainability assessment.},
journal = {BMC chemistry},
volume = {20},
number = {1},
pages = {},
pmid = {42587315},
issn = {2661-801X},
support = {R-2026-XX//Deanship of Postgraduate Studies and Scientific Research, Majma'ah University/ ; },
abstract = {The recently introduced cefepime-enmetazobactam (CEF-ENM) combination requires reliable analytical methods for pharmaceutical quality control and proof-of-concept bioanalytical evaluation. Existing methods are predominantly chromatographic and rely on large volumes of organic solvents, costly instrumentation, and high energy consumption. In this work, a UV spectrophotometric approach integrated with chemometric analysis was established for the simultaneous quantification of CEF and ENM in pharmaceutical formulations and processed post-extraction-fortified human plasma. Calibration samples were prepared according to the Brereton multilevel experimental design, whereas an independent external validation set was constructed using the Maximin Distance Design (MMD) algorithm. The analytical performance of six chemometric models (CLS, PCR, PLS, GA-PLS, FA-PLS, and MCR-ALS) was evaluated to resolve the severe spectral overlap between both analytes. Matrix-specific calibration models were developed for processed plasma samples. The developed models showed excellent analytical performance, with MCR-ALS providing the highest predictive accuracy and robustness. Sustainability was comparatively evaluated using the integrated Multi-color Assessment (MA) Tool together with complementary greenness metrics. The proposed method demonstrated superior overall sustainability compared with previously reported chromatographic methods while maintaining reliable quantitative performance. The proposed approach offers a rapid, cost-effective, and environmentally sustainable alternative for routine pharmaceutical quality control and proof-of-concept evaluation in processed post-extraction-fortified human plasma. Further comprehensive bioanalytical validation is warranted to support routine clinical application.},
}

@article {pmid42587774,
year = {2026},
author = {Garza, TN and Abisambra, JF},
title = {The Interactions of Tau, RNA, and Stress Granules in Neurodegenerative Disease: A Comprehensive Review.},
journal = {Cells},
volume = {15},
number = {15},
pages = {},
doi = {10.3390/cells15151365},
pmid = {42587774},
issn = {2073-4409},
support = {5T32AG061892-07/AG/NIA NIH HHS/United States ; 1R01AG075900-04/NH/NIH HHS/United States ; 1R01AG074584-05/NH/NIH HHS/United States ; 1R21AG093972-01/NH/NIH HHS/United States ; 5I50RX003000-07//United States Department of Veterans Affairs/ ; },
mesh = {Humans ; *tau Proteins/metabolism ; *Neurodegenerative Diseases/metabolism/genetics/pathology ; *Stress Granules/metabolism ; *RNA/metabolism ; Animals ; RNA-Binding Proteins/metabolism ; },
abstract = {The discovery of RNA in the late 19th century revolutionized the understanding of cell biology. Subsequent discoveries over the next six decades revealed a key role for RNA in protein synthesis. Nevertheless, today, the mechanisms driving RNA metabolism remain enigmatic. Given its fundamental cellular role, RNA alterations are strongly linked to disease, including devastating neurodegenerative disorders pathologically defined by the accumulation of RNA-binding proteins. For example, the mislocalization of TDP-43, an RNA-binding protein, is a pathological feature of amyotrophic lateral sclerosis and frontotemporal dementia TDP-43. Another group of more than 20 neurodegenerative disorders, called tauopathies, is characterized by the aberrant accumulation of the protein tau. Similarly, the emerging concept that tau binds RNA, facilitating the formation of pathological structures, highlights the importance of RNA stability in tauopathies. However, the dynamics and consequences of RNA-tau interactions remain unclear. This review comprehensively catalogs key findings linking tau, RNA, and stress granules. These findings are important because they could offer novel opportunities to design therapeutic strategies.},
}

Humans
*tau Proteins/metabolism
*Neurodegenerative Diseases/metabolism/genetics/pathology
*Stress Granules/metabolism
*RNA/metabolism
Animals
RNA-Binding Proteins/metabolism

@article {pmid42588274,
year = {2026},
author = {Paynter, C and Mathers, S and Vogel, A and Cruice, M},
title = {Foregrounding Communication Access in Person-Centred Decision Making for People with Motor Neurone Disease: A Narrative Review.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {15},
pages = {},
doi = {10.3390/healthcare14152307},
pmid = {42588274},
issn = {2227-9032},
support = {1133541//NHMRC/MNDRA Postgraduate Scholarship/ ; FT220100253//Australian Research Council/ ; },
abstract = {Effective motor neurone disease (MND) management depends on patient and carer involvement in decisions about interventions and future care. Communication and cognitive impairments are common in MND and have under-recognised consequences for shared decision making and autonomy. This narrative conceptual review draws on empirical qualitative research with people living with MND and unpaid family carers and the literature specifically concerning shared decision making and communication in MND. Themes relating to communication, information use, and decision making styles were mapped onto an ALS/MND multidisciplinary decision making model. Enhancements to the model include expanding the decision making context beyond in clinical activity, embedding communication and cognitive skills and accommodations across stages, and acknowledging risks to collaborative decision making. Practical strategies for clinicians, healthcare services, people living with MND, and family carers are proposed to ensure that communication is foregrounded in-person-centred MND care. Observational and implementation research is required to evaluate and refine the proposed approaches.},
}

@article {pmid42588882,
year = {2026},
author = {Faburrieta, RA and López Ruiz, BA and Rosas, U and Davis, KJ and Richards, CL and Banta, JA},
title = {Partial Reproducibility and Pleiotropic Epigenetic QTLs in Arabidopsis Recombinant Inbred Lines.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {15},
pages = {},
doi = {10.3390/plants15152379},
pmid = {42588882},
issn = {2223-7747},
support = {DEB-1419960//U.S. National Science Foundation/ ; IOS-397 1556820//U.S. National Science Foundation/ ; //The University of Texas at Tyler/ ; //Universidad Nacional Autónoma de México/ ; //Mexican Academy of Sciences/ ; //Secretaría de Ciencia, Humanidades, Tecnología e Innovación/ ; },
abstract = {Unlike conventional genetic polymorphisms, many induced epigenetic polymorphisms can be reset across generations, raising uncertainty about how consistently the same epigenetic loci and associated phenotypic effects can be recovered among independent studies. To address this problem, we designed our study specifically to maximize a lineage-matched, environmentally aligned cross-study comparability with the foundational work of Cortijo et al. by using seeds derived from the same epiRIL generation and grown under broadly similar environmental conditions. We mapped flowering time, as well as five non-flowering traits that had not previously been mapped in this epiRIL population: rosette diameter, basal branch number, lateral branch number, fruit number, and rosette leaf number. We detected significant epiQTLs for all traits except lateral branch number. We also reproduced a facsimile of the original computational pipeline. This design provides an approximate upper bound on expected reproducibility before additional generations of methylation resetting or divergence among seed stocks could substantially influence the results. We recovered two of Cortijo et al.'s previously reported epiQTLs, failed to recover another, and found a different one, with power analyses suggesting that the discrepancies may reflect statistical power. Within overlapping epiQTL intervals across the five traits that had significant intervals, we identified 69 candidate genes exhibiting gene body methylation. Overall, our results reproduced some but not all previous epiQTL signals when comparisons were made using closely matched source material under similar conditions.},
}

@article {pmid42589639,
year = {2026},
author = {Wu, Y and Li, L and Tian, J and Liu, L and Du, K and Shao, Z and Cheng, T and Cao, X and Wang, T},
title = {RAN Translation-Coupled Decay of the C9orf72 GGGGCC Repeat Transcript by the RNA Exosome Suppresses Dipeptide Repeat Production.},
journal = {International journal of molecular sciences},
volume = {27},
number = {15},
pages = {},
doi = {10.3390/ijms27156986},
pmid = {42589639},
issn = {1422-0067},
support = {STI2030-Major Projects-2022ZD0212600//National Science and Technology Innovation 2030 Major Projects of China/ ; 32271000//National Natural Science Foundation of China/ ; 32471008//National Natural Science Foundation of China/ ; 32300796//National Natural Science Foundation of China/ ; 23ZR1413800//Natural Science Foundation of Shanghai/ ; },
mesh = {*C9orf72 Protein/genetics/metabolism ; *RNA Stability ; *Protein Biosynthesis ; Humans ; RNA, Messenger/genetics/metabolism ; *Dipeptides/genetics/metabolism ; *Exosome Multienzyme Ribonuclease Complex/metabolism/genetics ; *DNA Repeat Expansion/genetics ; Induced Pluripotent Stem Cells/metabolism/cytology ; Neurons/metabolism ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Frontotemporal Dementia/genetics/metabolism ; },
abstract = {The RNA exosome plays a critical role in surveilling nuclear mRNA biogenesis and regulating co-translational mRNA decay in the cytoplasm. Unlike canonical translation, repeat-associated non-AUG (RAN) translation of a GGGGCC hexanucleotide repeat expansion (HRE) within an intron of the C9orf72 locus leads to the synthesis of neurotoxic dipeptide-repeat (DPR) proteins, contributing to the pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis (C9-ALS/FTD). However, it remains unclear whether aberrant RAN translation is monitored and regulated co-translationally or how C9orf72 HRE (C9-HRE) mRNA is degraded during this process. Here, we demonstrate that RAN translation triggers the rapid decay of C9-HRE mRNA. During this process, the RNA exosome engages the translating ribosome-C9-HRE mRNA complex to mediate RAN translation-coupled mRNA decay. Moreover, overexpression of EXOSC3, a key subunit of the RNA exosome cap, promotes RAN translation-coupled decay of C9-HRE mRNA and suppresses DPR production. In iPSC-derived neurons, a reduction in EXOSC3 levels blocks C9-HRE mRNA decay in a translation-dependent manner, further confirming its role in RAN translation surveillance. These findings highlight the essential function of the RNA exosome, particularly EXOSC3, in mitigating RAN translation-associated toxicity and preventing pathological DPR production. This work provides insights into potential therapeutic strategies for C9-ALS/FTD and may have broader implications for other disorders involving RAN translation.},
}

*C9orf72 Protein/genetics/metabolism
*RNA Stability
*Protein Biosynthesis
Humans
RNA, Messenger/genetics/metabolism
*Dipeptides/genetics/metabolism
*Exosome Multienzyme Ribonuclease Complex/metabolism/genetics
*DNA Repeat Expansion/genetics
Induced Pluripotent Stem Cells/metabolism/cytology
Neurons/metabolism
Amyotrophic Lateral Sclerosis/genetics/metabolism
Frontotemporal Dementia/genetics/metabolism

@article {pmid42591225,
year = {2026},
author = {Vöhringer, K and Müller, MS and Yildiz, CB and Zimmer-Bensch, G},
title = {DNMT1 as an environmental sensor: epigenetic pathways linking environmental exposures, sex hormone signaling, and vulnerability to neurodevelopmental and neurodegenerative diseases.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1883887},
pmid = {42591225},
issn = {1664-2295},
abstract = {DNA methyltransferase 1 (DNMT1) has classically been viewed as the canonical maintenance methyltransferase, yet accumulating evidence positions it as a multifaceted hub that integrates environmental, hormonal, and metabolic signals with chromatin regulation in the developing and adult brain. This review highlights DNMT1 as an environmentally responsive epigenetic sensor across the lifespan. We examine how psychosocial stress, early-life adversity, inflammation, nutritional and microbiome-derived metabolites, and environmental toxicants modulate DNMT1 expression, subcellular localization, and post-translational modifications, thereby reshaping DNA methylation landscapes in neurons and glia. We further discuss how sex hormone signaling, particularly estrogen receptor alpha α (ERα)-DNMT1 feedback loops, introduces sex-specific dimensions to epigenetic responsiveness, and how lncRNAs serve as intermediaries linking environmental cues to targeted DNMT1 recruitment at specific genomic loci. Building on this framework, we review how DNMT1 dysregulation contributes to neurodevelopmental and neuropsychiatric disorders-including schizophrenia, autism spectrum disorder, and depression-and to neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and DNMT1-associated monogenic neurodegenerative disorders. By positioning DNMT1 as a molecular interface between genetic predisposition, environmental exposure, and circuit-level vulnerability, this review highlights the need for integrated, sex-stratified, and longitudinal approaches to understanding epigenetic risk in neurological disease.},
}

@article {pmid42573939,
year = {2026},
author = {Khadilkar, V and Mondkar, S and Baalaaji, ARM and Bhutada, A and Dhongade, A and Lad, SS and Lad, P and Jain, MK and Patnaik, S and Sarkar, M and Shaikh, F and Sharma, M and Shetty, R and Upadhyay, N and Vohra, R and Wagle-Patki, S and Khadilkar, A and Patki, V and James, EJG and Shah, S and Bansal, A},
title = {A Multicenter Study for Validation of the New Pediatric Advanced Life Support Tape for Indian Children.},
journal = {Indian pediatrics},
volume = {},
number = {},
pages = {},
pmid = {42573939},
issn = {0974-7559},
abstract = {OBJECTIVE: Accurate weight estimation is essential for drug dosing and equipment selection in pediatric emergencies. A new Pediatric Advanced Life Support (ALS) tape was developed using Indian growth references. The present study was performed to validate its performance in critically ill children across multiple centers in India.

METHODS: A prospective, cross-sectional, multicenter observational study was conducted in 13 pediatric intensive care units (PICUs) across five zones of India in children aged < 12 years. Recumbent length was measured using the new ALS tape, and color-band-based estimated weight recorded. Weight was measured using a digital scale. The primary outcomes were bias, precision, and accuracy of the tape in predicting weight. Secondary outcomes included correlation between estimated and measured weight, agreement using Bland-Altman analysis, center-wise subgroup analyses, and interrater reliability for color-band assignment.

RESULTS: Out of 2740 children measured, 2253 were included in the final analysis. Correct color-band concordance was observed in 79.9% of children. Overall, 78.6% of estimates were within ± 10% and 84.6% within ± 15% of measured weight. The mean difference between estimated and measured weight was - 0.6 kg (0.08%). Lower color bands showed modest underestimation (13.1%), while higher bands showed mild overestimation (- 10.3%). Regional concordance ranged from 65.9% to 91.4%. Interrater reliability demonstrated strong agreement (κ = 0.84; 95% CI 0.61, 1.00).

CONCLUSIONS: The Indianized Pediatric ALS tape demonstrated acceptable accuracy, minimal overall bias, and strong interrater reliability in critically ill Indian children. Although some variability was observed across regions and lower weight bands, the new ALS tape represents a practical and reasonably accurate indigenous alternative for emergency weight estimation in diverse PICU settings across India.},
}

@article {pmid42574200,
year = {2026},
author = {Mirg, S and Elavarasi, A and Das, A and Vibha, D and Singh, RK and Parihar, J and Sharma, MC and Tripathi, M},
title = {Myofibrillar Myopathy with Pyramidal Signs Mimicking Amyotrophic Lateral Sclerosis.},
journal = {Annals of Indian Academy of Neurology},
volume = {},
number = {},
pages = {},
doi = {10.4103/aian.aian_1333_25},
pmid = {42574200},
issn = {0972-2327},
}

@article {pmid42574250,
year = {2026},
author = {Tithi, SS and Cooper-Knock, J and Benatar, M and Wuu, J and Taylor, JP and Wu, G and Chen, W},
title = {CoCoRV-nf: a powerful and cost-effective tool for rare variant analysis leveraging external biobank sequence data identified new candidate predisposition genes in amyotrophic lateral sclerosis and neuroblastoma.},
journal = {Human molecular genetics},
volume = {35},
number = {17},
pages = {},
doi = {10.1093/hmg/ddag076},
pmid = {42574250},
issn = {1460-2083},
support = {R03OD039975/NH/NIH HHS/United States ; U54 NS092091/NH/NIH HHS/United States ; P30 CA021765/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Genetic Predisposition to Disease ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Neuroblastoma/genetics/pathology ; Biological Specimen Banks ; Cost-Benefit Analysis ; Genetic Variation/genetics ; *Software ; Genetic Association Studies ; },
abstract = {Although sequencing costs have steadily decreased with advances in technology, they remain high for large scale studies. The design of traditional individual-disease sequencing studies is either case only or cases with relatively few controls, resulting in potential loss of statistical power for discovery of disease associated genes. Here we show that for a given number of sequenced cases, a large control sample size is critical to maximize power for rare variant burden analysis. Furthermore, we have developed an end-to-end workflow based tool (CoCoRV-nf) to facilitate the use of external biobank sequence resources as controls. The modules include consistent variant QC, variant annotation, ancestry population prediction, and gene based burden analysis using summary genotype information, and combined analysis from multiple independent results. The tool supports exomes and genomes from gnomAD and All of Us as controls with preprocessed datasets. We apply the tool in two rare neurological diseases: amyotrophic lateral sclerosis and neuroblastoma. For each disease, two case cohorts are paired with gnomAD and All of Us data, respectively, followed by a combined analysis. Not only did we recapture known genes, but also, we identified new candidate genes for both diseases. By leveraging multiple large external biobank sequence data, we demonstrate the feasibility of using our tool to maximize statistical power to identify new disease predisposition genes.},
}

Humans
*Genetic Predisposition to Disease
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Neuroblastoma/genetics/pathology
Biological Specimen Banks
Cost-Benefit Analysis
Genetic Variation/genetics
*Software
Genetic Association Studies

@article {pmid42574885,
year = {2026},
author = {Inan, B},
title = {Comment on "Association of anti-glycolipid IgG with respiratory function decline in amyotrophic lateral sclerosis".},
journal = {Journal of the neurological sciences},
volume = {490},
number = {},
pages = {126131},
doi = {10.1016/j.jns.2026.126131},
pmid = {42574885},
issn = {1878-5883},
}

@article {pmid42575772,
year = {2026},
author = {Russo, AG and Hawkshaw, MJ and Sataloff, RT},
title = {Voice Disorders as Early Biomarkers of Cognitive Decline.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2026.07.037},
pmid = {42575772},
issn = {1873-4588},
abstract = {BACKGROUND: Dementia affects greater than 57 million people worldwide. With an aging population and limited disease-curing treatments available, early identification of biomarkers is crucial. The 2020 Lancet Commission identified hearing loss as the largest modifiable risk factor for dementia globally, and a randomized controlled trial found that hearing intervention reduced 3-year cognitive change in older adults who were at increased risk for cognitive decline. Similarly, studies have found that abnormalities in acoustic measures of voice are correlated with cognitive status and can potentially predict decline. The association between hearing loss and cognitive decline might have both social and neurological mechanisms. Dysphonia might pose similar problems. Socially, voice disorders may reduce engagement in social and cognitively stimulating activities. Neurologically, one example is in Parkinson's disease in which the vagus nerve is one of the earliest sites of Lewy body pathology in Braak staging, and dysphonia and dysarthria can precede motor symptoms by years. Voice changes have been associated with different neurological conditions such as amyotrophic lateral sclerosis, multiple system atrophy, and Alzheimer's disease. Despite this, no prior large-scale study has examined whether diagnosed voice disorders are associated independently with incident cognitive decline. Our study is the first to examine this potential association, using the TriNetX US Collaborative Health Network platform to compare patients with diagnosed voice disorders and matched controls, with a hearing loss cohort as a standard of comparison given that it is the largest established modifiable risk factor for dementia, as dysphonia is also a modifiable condition.

RESULTS: This study included 833,417 total patients in the voice disorders and control cohorts. Voice disorders were associated with a significantly elevated risk of incident cognitive decline compared to controls (HR=1.291, 95% CI 1.155-1.443, P<0.0001). Hearing loss alone was associated with a slightly lower risk of cognitive decline (HR=1.267, 95% CI 1.203-1.334, P<0.0001). Voice disorders without concurrent hearing loss were associated with an elevated risk of incident cognitive decline compared to hearing loss alone (HR=1.261, 95% CI 1.121-1.419, P=0.0001), while voice disorders with hearing loss were associated with the highest risk among all cohorts (HR=2.038 vs controls; HR=1.545 vs hearing loss). Both voice disorder subgroups did not differ when compared with each other (HR=1.088, P=0.376).

CONCLUSION: The results from our study indicate that voice disorders are associated with an elevated risk of incident cognitive decline and may represent a stronger early biomarker than hearing loss alone. These findings highlight otolaryngology and family medicine/internal medicine encounters as potential entry points for cognitive assessment, and early voice treatment needs to be investigated for possible beneficial cognitive effect.},
}

@article {pmid42576069,
year = {2026},
author = {Saleem, M and Khan, MS and Syed Khaja, AS and Alraey, Y and Ahmad, I and Almuzaini, Y and AlShammari, A and Alshamamri, YM and Alharbi, T},
title = {Prevalence, antifungal susceptibility, and virulence determinants of Candida species causing vulvovaginal candidiasis in pregnant women in Saudi Arabia.},
journal = {Antonie van Leeuwenhoek},
volume = {119},
number = {9},
pages = {},
pmid = {42576069},
issn = {1572-9699},
support = {RGP.01/146/46//the Deanship of Research and Graduate Studies at King Khalid University/ ; },
mesh = {Humans ; Female ; *Candidiasis, Vulvovaginal/epidemiology/microbiology/drug therapy ; Saudi Arabia/epidemiology ; *Antifungal Agents/pharmacology ; Pregnancy ; Prevalence ; *Virulence Factors/genetics ; Microbial Sensitivity Tests ; *Candida/drug effects/pathogenicity/genetics/classification/isolation & purification ; Adult ; Young Adult ; Adolescent ; *Pregnancy Complications, Infectious/microbiology/epidemiology ; Drug Resistance, Fungal ; Virulence ; },
abstract = {Vulvovaginal candidiasis (VVC) is a common opportunistic fungal infection of the female genital tract, primarily associated with Candida overgrowth influenced by host factors, hormonal changes, microbial imbalance, and environmental conditions. This study examined the prevalence, antifungal susceptibility, and virulence factors of Candida species in 440 pregnant women (ages 18-55) with vulvovaginitis and vaginal discharge at a Saudi Arabian hospital. The study was conducted from March 2022 to February 2023 at a tertiary hospital in Hail, Saudi Arabia, including 440 pregnant women with vaginitis. Vaginal swabs were cultured for Candida, with species identification and antifungal susceptibility testing performed using the Vitek-2 Compact system against five antifungals. Multiplex PCR was used to detect virulence genes (Hwp, Als, Sap, Hlp). Among them, 114 (25.9%) tested positive for Candida species, with Candida albicans being most prevalent (42.1%), followed by C. glabrata (19.3%) and C. tropicalis (12.3%). Most cases occurred during the second trimester (67%), with an average age of 27 years. Antifungal susceptibility testing showed that nystatin exhibited 49.1% susceptibility, 19.3% susceptible-dose dependence (SDD), and 31.6% resistance. Clotrimazole demonstrated 40.4% susceptibility, 26.3% SDD, and 33.3% resistance. Itraconazole showed 50.9% susceptibility, 28% SDD, and 21.1% resistance. Fluconazole exhibited 43.8% susceptibility, 8.8% SDD, and the highest resistance rate (47.4%). Voriconazole was the most effective antifungal agent, with 93% susceptibility, 3.5% SDD, and 3.5% resistance. Virulence analysis showed C. albicans had high Hwp (91.7%) and Sap (54.2%) gene detection, while C. glabrata and C. tropicalis exhibited elevated Hlp and Als levels, respectively. This study highlights the high prevalence of VVC in the second trimester and emphasizes the importance of virulence factors in pathogenicity. Voriconazole emerges as the most effective treatment, emphasizing the need for targeted diagnostics and therapies.},
}

Humans
Female
*Candidiasis, Vulvovaginal/epidemiology/microbiology/drug therapy
Saudi Arabia/epidemiology
*Antifungal Agents/pharmacology
Pregnancy
Prevalence
*Virulence Factors/genetics
Microbial Sensitivity Tests
*Candida/drug effects/pathogenicity/genetics/classification/isolation & purification
Adult
Young Adult
Adolescent
*Pregnancy Complications, Infectious/microbiology/epidemiology
Drug Resistance, Fungal
Virulence

@article {pmid42576087,
year = {2026},
author = {Oyedokun, PA and Gbadero, JO and Ajao, DI and Olorunsesan, MD and Oyesiji, AI and Ayilara, GO and Ogunsina, MK and Justus, BS and Ademola, FM and Adetunji, EA and Okodio, PS and Amedu, NO},
title = {The Amino Acid-Neurodegeneration Axis: Excitotoxicity and Oxidative Stress as Context-Dependent Amplifiers of Metabolic Dysfunction.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42576087},
issn = {1559-1182},
mesh = {*Oxidative Stress/physiology ; Humans ; Animals ; *Amino Acids/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; *Nerve Degeneration/metabolism/pathology ; Mitochondria/metabolism ; },
abstract = {Homeostasis of amino acids is essential for the integrity of the CNS, and is maintained by a tightly regulated transport and metabolic circuit that ensures efficient neurotransmission, mitochondrial bioenergetics and redox homeostasis. Disruption of this equilibrium is associated with the pathogenesis of the major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Excessive glutamatergic stimulation and impaired glycine or homocysteine metabolism result in pathological Ca[2][+] influx, loss of mitochondrial membrane potential and production of reactive oxygen species, which are hallmarks of these disorders. It also limits cysteine availability and causes glutathione depletion, which affects antioxidant defence, and disrupts tryptophan-kynurenine metabolism, further affecting neurotoxic and neuroprotective signalling. Though there are disease-specific molecular triggers, the convergent pathogenesis of metabolic disruption makes neurons susceptible to disease. The convergent pathways link amino acid dysregulation to the reinforcement of each other's mechanisms of excitotoxicity, oxidative stress, mitochondrial dysfunction, and protein aggregation. Correcting the amino acid balance has clear translational potential for developing new therapies, such as glutathione augmentation, modulation of NMDA receptors, targeting of transporters, and regulation of metabolic enzymes. In addition, the use of metabolic biomarkers alongside neuroprotective endpoints in clinical trials could improve detection rates, patient stratification, and therapeutic precision. The concept of amino acid metabolism as a mechanism of neurodegeneration, therefore, provides a systems-level perspective and targets potential areas for continued neuroprotection and disease modification.},
}

*Oxidative Stress/physiology
Humans
Animals
*Amino Acids/metabolism
*Neurodegenerative Diseases/metabolism/pathology
*Nerve Degeneration/metabolism/pathology
Mitochondria/metabolism

@article {pmid42576199,
year = {2026},
author = {Zheng, F and Guan, R and Yu, X and Yang, J and Zhao, H and Yang, F},
title = {ADAR-mediated RNA editing in CNS disorders: from pathogenic mechanisms to therapeutic opportunities.},
journal = {Cellular & molecular biology letters},
volume = {31},
number = {1},
pages = {},
pmid = {42576199},
issn = {1689-1392},
mesh = {Humans ; *RNA Editing/genetics ; *Adenosine Deaminase/metabolism/genetics ; *Central Nervous System Diseases/genetics/therapy/pathology/metabolism ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; },
abstract = {The adenosine deaminases acting on RNA (ADAR) family of enzymes (ADAR1 and ADAR2) catalyze adenosine-to-inosine (A-to-I) RNA editing. This post-transcriptional change is remarkably prevalent in the central nervous system (CNS). ADAR-mediated editing is critical for proper brain development, synaptic plasticity, and immunological homeostasis in the central nervous system (CNS) via recoding neurotransmitter receptors and ion channels. Conversely, a wide range of CNS disorders, such as neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis), neuropsychiatric conditions (schizophrenia, bipolar disorder, and major depression), cerebrovascular diseases, and gliomas, are now linked to dysregulation of ADAR activity, whether through loss-of-function mutations, altered expression, or mislocalization. To address the main question of whether altered RNA editing is a fundamental driver of pathogenesis, a compensatory response, or a context-dependent modulator, this review critically synthesizes existing evidence. The basic processes of ADAR enzymes and their regulation throughout neurodevelopment are first described. Next, we thoroughly assess the unique molecular fingerprints of ADAR dysregulation across several CNS disorders, emphasizing recurring themes such as Alu RNA hypo-editing, induction of innate immunity, and GRIA2 editing, which can cause excitotoxicity. Lastly, we examine new treatment approaches that use or reinstate ADAR activity, such as small-molecule modulators and site-directed RNA editing tools (leveraging endogenous ADAR for programmable editing of RNA [LEAPER], clustered ADAR-recruiting guide RNAs (gRNAs) for effective RNA editing [CLUSTER], and mimicking inverted repeats to recruit ADARs using engineered oligoribonucleotides [MIRROR]). We summarize by reviewing key obstacles to clinical translation, including crossing the blood-brain barrier, the risks of off-target editing, and the challenges of achieving spatiotemporal accuracy. We also list important open topics for further investigation.},
}

Humans
*RNA Editing/genetics
*Adenosine Deaminase/metabolism/genetics
*Central Nervous System Diseases/genetics/therapy/pathology/metabolism
Animals
*RNA-Binding Proteins/metabolism/genetics

@article {pmid42576610,
year = {2026},
author = {Yang, Y and Yang, Y and Tang, Y and Yang, W},
title = {Myokines, Microbiota, and Neuroinflammation: Physical Activity Modulates the Gut-Brain Axis.},
journal = {Immunological investigations},
volume = {},
number = {},
pages = {1-28},
doi = {10.1080/08820139.2026.2689670},
pmid = {42576610},
issn = {1532-4311},
abstract = {BACKGROUND: Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are increasingly recognized as disorders influenced not only by intrinsic neural pathology but also by systemic physiological networks, including the gut-brain axis. Emerging evidence highlights physical activity as a potent modulator of this bidirectional communication system, with muscle-derived signals particularly myokines, metabolites, and extracellular vesicles playing a central role.

METHODS: This narrative review synthesizes current knowledge on how exercise-induced molecular mediators influence gut microbiota composition, intestinal barrier integrity, immune signaling, and neuroinflammatory pathways. Findings were integrated across the disciplines of neuroscience, microbiology, and exercise physiology to evaluate mechanistic links between muscle-secreted factors and gut-mediated responses.

RESULTS: Mechanistic links exist between muscle-secreted factors such as irisin, cathepsin B, BDNF-inducing pathways, and lactate with microbial metabolites including short-chain fatty acids. These interacting pathways demonstrate a combined impact on neuroprotection, synaptic plasticity, and the modulation of disease progression in neurodegenerative conditions.

CONCLUSION: Physical activity represents a promising non-pharmacological strategy for modulating the gut-brain axis in neurodegenerative conditions. Understanding the interplay between muscle-derived signals and gut-mediated pathways may open new avenues for targeted interventions aimed at slowing or preventing neurodegenerative decline.},
}

@article {pmid42578424,
year = {2026},
author = {Shen, D and Yang, X and Zhang, K and Liu, S and Sun, X and Li, J and Cai, Z and Liu, M and Zhang, X and Liu, Q and Cui, L},
title = {Clinical and genetic characteristics of 536 young-onset amyotrophic lateral sclerosis in China: a single-center retrospective study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2712723},
pmid = {42578424},
issn = {2167-9223},
abstract = {Objective: Young-onset amyotrophic lateral sclerosis (ALS), defined as symptom onset at or before 45 years, remains poorly characterized in Chinese patients. We aimed to describe its clinical and genetic features and compare them with adult-onset ALS. Methods: We retrospectively analyzed 536 young-onset ALS patients registered at Peking Union Medical College Hospital (2014-2022) alongside 1136 adult-onset patients (onset >45 years). Whole exome sequencing targeting 41 established ALS-related genes was performed in all young-onset patients. Results: Young-onset ALS accounted for 32.0% of the cohort, with a median onset age of 39.5 years (IQR 34.25-44.0). Compared with adult-onset patients, young-onset cases had less bulbar onset (14.2% vs. 19.5%, p = 0.008), more frequent predominant upper motor neuron phenotype (25.9% vs. 15.4%, p < 0.001), higher baseline ALSFRS-R scores (p < 0.001), slower progression (p = 0.001), and longer median survival (36 vs. 30 months, p = 0.009). Familial ALS was more common in the young-onset group (8.4% vs. 3.8%, p < 0.001). Rare variants were identified in 20.0% of young-onset patients across 32 genes; pathogenic or likely pathogenic variants were predominantly in SOD1 and FUS. Compared with adult-onset patients, SOD1 was proportionally more common in adult-onset disease, whereas FUS variants were markedly enriched among young-onset cases, suggesting age-dependent differences in genetic architecture. Conclusion: Young-onset ALS in China is characterized by a slower clinical course and a distinct genetic profile dominated by SOD1 and FUS, with near-absent C9orf72 expansions. Routine genetic testing and age-stratified trial design are warranted in this population.},
}

@article {pmid42578530,
year = {2026},
author = {Zhou, Z and Ma, Y and Wang, L},
title = {Development and Psychometric Validation of the Chinese Online Disinhibition Scale for Adolescents.},
journal = {PsyCh journal},
volume = {15},
number = {4},
pages = {e70117},
pmid = {42578530},
issn = {2046-0260},
mesh = {Humans ; Adolescent ; *Psychometrics ; China ; Female ; Reproducibility of Results ; Male ; *Internet Addiction Disorder/psychology/diagnosis ; Surveys and Questionnaires ; *Internet ; *Cyberbullying/psychology ; *Adolescent Behavior/psychology ; },
abstract = {Online disinhibition significantly influences adolescents' communication and behaviors in digital environments, yet culturally adapted measurement tools remain limited in China. This study aimed to develop and validate a Chinese version of the Online Disinhibition Scale (ODS-C) based on Suler's (2004) theoretical framework. We translated and adapted Cheung et al.'s (2020) questionnaire through rigorous forward and backward translation protocols. Using a calibration sample (n = 686), we tested the scale's internal structure, reliability, and construct validity. A cross-validation sample (n = 687) was subsequently employed to verify and select the optimal internal structure of the ODS-C, assess measurement invariance across gender, and examine criterion validity based on relationships with internet addiction and cyberbullying perpetration. The final ODS-C demonstrated a hierarchical five-factor structure, in which dissociative anonymity and invisibility functioned as two distinct first-order factors subsumed under a higher-order anonymity factor, while the remaining four dimensions-asynchronicity, solipsistic introjection, dissociative imagination, and minimization of authority-operated as independent first-order factors. Results indicate that the ODS-C demonstrates high internal consistency, robust construct validity, and significant criterion validity. Evidence of measurement invariance confirmed the stability of the factor structure, loadings, and variances across genders. The ODS-C provides researchers and practitioners with a reliable and valid tool for assessing online disinhibition among Chinese adolescents, facilitating more culturally informed interventions and policies addressing digital behavior.},
}

Humans
Adolescent
*Psychometrics
China
Female
Reproducibility of Results
Male
*Internet Addiction Disorder/psychology/diagnosis
Surveys and Questionnaires
*Internet
*Cyberbullying/psychology
*Adolescent Behavior/psychology

@article {pmid42579090,
year = {2026},
author = {Filippi, L and Nuvoli, S and Spanu, A and Palumbo, B},
title = {Mapping the Synaptome in Neurodegeneration: Emerging Clinical Applications of SV2A PET Imaging.},
journal = {Molecular diagnosis & therapy},
volume = {},
number = {},
pages = {},
pmid = {42579090},
issn = {1179-2000},
support = {Ricerca Corrente//Ministero della Salute/ ; },
abstract = {Synaptic loss is a core pathological feature of neurodegenerative disorders and closely relates to cognitive and functional decline. Positron emission tomography (PET) targeting synaptic vesicle glycoprotein 2A (SV2A) has recently emerged as a promising tool for the indirect assessment of presynaptic alterations in the living human brain. This leading article discusses the evolving clinical landscape of SV2A PET across the neurodegenerative spectrum, emphasizing its translational trajectory and emerging applications. Current evidence spans Alzheimer's disease (AD), other dementias, movement disorders, Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The literature is currently dominated by PET with [[11]C]UCB-J, while [[18]F]-labeled tracers, particularly [[18]F]SynVesT-1, are expanding clinical feasibility through longer half-life and broader distribution potential. Across disorders, PET consistently detected SV2A reductions that frequently correlated with cognition, disease severity, and complementary biomarkers, including amyloid, tau, glucose metabolism, and dopaminergic imaging. Although the field remains limited by small cohorts, heterogeneous quantification strategies, and incomplete longitudinal validation, SV2A PET is rapidly evolving into a promising translational tool for studying synaptopathies and monitoring disease progression.},
}

@article {pmid42580389,
year = {2026},
author = {Bu, J and Nie, X and Luo, H and Wang, J and Jiang, D and Xu, N and Zhuang, P and Zhang, Y and Yin, Q},
title = {Neuron-Derived Neuroinflammation in Neurodegenerative Diseases: Mechanisms and Intervention Prospects.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108383},
doi = {10.1016/j.phrs.2026.108383},
pmid = {42580389},
issn = {1096-1186},
abstract = {Neurodegenerative diseases represent a major global public health challenge, imposing substantial societal and economic burdens. Their complex pathogenesis and limited therapeutic options underscore an urgent need for new paradigms. Emerging evidence indicates that dysregulation of the brain's immune microenvironment is a critical driver of disease progression. Conventional wisdom posits that peripheral immune cells and central glial cells serve as the primary initiators of neuroimmune responses, whereas neurons are regarded merely as passive recipients of inflammatory damage. Emerging evidence suggests that upon receiving pathological signals in the central nervous system, neurons may become more vulnerable and participate in the onset of neuroimmune processes, positioning them as potential targets for early intervention in neurodegenerative diseases. This article systematically reviews the contribution of neuron-derived immune-inflammatory responses in neurodegenerative diseases and potential intervention strategies. We first outline the capacity of neurons to regulate neuroimmune responses and detail the underlying molecular mechanisms. Then we compare the specific mechanisms by which neurons with different susceptibility drive and amplify neuroinflammation in various neurodegenerative diseases such as alzheimer's disease, parkinson's disease, amyotrophic lateral sclerosis, vascular cognitive impairment, and transformed these mechanisms into intervention strategies targeting neurons,. This article aims to break through the traditional concept of passive neuronal damage, systematically integrate intervention strategies that shift from targeting peripheral immune and glial cells to regulating neuron-derived immunity, thereby providing a new theoretical framework for overcoming current clinical limitations and identifying effective therapeutic targets for the prevention and treatment of neurodegenerative diseases.},
}

@article {pmid42580558,
year = {2026},
author = {Armoundas, AA and Piperi, C},
title = {Epigenetic Drift and LINE-1 Activation in Aging Brain: Implications for Neurodegenerative Disease.},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112235},
doi = {10.1016/j.mad.2026.112235},
pmid = {42580558},
issn = {1872-6216},
abstract = {Brain aging and age-associated neurological diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS), are largely attributed to epigenetic drift which is characterized by the gradual accumulation of alterations in neural cell methylation patterns over time. These methylation changes are particularly evident in transposable element (TE)-derived sequences such as Long interspersed element-1 (LINE-1) which comprises approximately 17% of the human genome. During aging, LINE-1 elements gradually lose their methylation, as well as the regulatory safeguard mechanisms that usually keep them inactive. This repression loss can lead to LINE-1 reactivation, contributing to harmful effects including genomic instability, neuroinflammation, and more. Together these findings indicate that impaired epigenetic maintenance, especially in repetitive genome regions, plays a key role in biological aging of neurons and glial cells. In this narrative review, we discuss the methylation dynamics and regulatory mechanisms of LINE-1 retrotransposons, their activation processes during aging, and contribution to age-associated neurological diseases. We also highlight the potential of targeting LINE-1 methylation to restore methylation homeostasis, epigenetic stability and delay brain aging.},
}

@article {pmid42580784,
year = {2026},
author = {Souza, HJBC and Souza, KM and Dos Santos, MB and Silva, MAP and Grassi, TF and Destro, MV and Braz, MG},
title = {Evaluation of genetic instability in patients with amyotrophic lateral sclerosis.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {913},
number = {},
pages = {503953},
doi = {10.1016/j.mrgentox.2026.503953},
pmid = {42580784},
issn = {1879-3592},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Female ; Male ; Case-Control Studies ; Middle Aged ; *Genomic Instability ; Mouth Mucosa/pathology ; Micronucleus Tests ; Aged ; Chromosomal Instability ; Micronuclei, Chromosome-Defective ; },
abstract = {Genetic instability has been reported in several neurodegenerative diseases, such as Alzheimer's and Parkinson's, but only a few studies have addressed sclerosis. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Micronuclei (MNi) and nuclear buds (NBUDs) are established markers of chromosomal instability, yet no data are available regarding a possible link between genetic instability and ALS. The novelty of this case-control study lies in the assessment of genetic instability in oral exfoliated cells from ALS patients (n = 20) and matched controls (n = 20), contributing to the identification of potential novel markers related to the molecular pathogenesis of this severe disorder. Groups were matched for age, sex, and lifestyle (p > 0.05). No significant differences were observed in MNi or NBUD frequencies between groups (p > 0.05). These findings suggest no association between ALS and MN/NBUD frequencies in oral cells.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
Female
Male
Case-Control Studies
Middle Aged
*Genomic Instability
Mouth Mucosa/pathology
Micronucleus Tests
Aged
Chromosomal Instability
Micronuclei, Chromosome-Defective

@article {pmid42580829,
year = {2026},
author = {Gaube, LM and Sparks, ED and Iten, M and Knapp, J and Fürholz, M and Schefold, JC and Hunziker Munsch, L and Hänggi, M and Krummrey, G and Müller, M and Hautz, WE},
title = {In-hospital cardiopulmonary resuscitation with balloon occlusion of the descending aorta: protocol of the randomised controlled CPReboa study.},
journal = {BMJ open},
volume = {16},
number = {8},
pages = {e119691},
doi = {10.1136/bmjopen-2026-119691},
pmid = {42580829},
issn = {2044-6055},
mesh = {Humans ; *Balloon Occlusion/methods ; *Cardiopulmonary Resuscitation/methods ; Prospective Studies ; *Heart Arrest/therapy/mortality ; *Aorta, Thoracic ; Randomized Controlled Trials as Topic ; Return of Spontaneous Circulation ; Female ; Adult ; },
abstract = {INTRODUCTION: Cardiac arrest (CA) remains a major health burden with poor survival and poor neurological outcomes despite decades of advances in resuscitation science. Although high-quality cardiopulmonary resuscitation is essential, it provides only limited cerebral and coronary perfusion, and current strategies relying on high-dose epinephrine may adversely affect cerebral microcirculation. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has emerged as a potential adjunct to improve coronary and cerebral perfusion without compromising microvascular blood flow. Although animal studies and small human case series suggest physiological and clinical benefits of REBOA in CA, randomised clinical trials are lacking.

METHODS AND ANALYSIS: This prospective, randomised controlled, single-centre clinical trial investigates the effect of REBOA during the treatment of CA. The planned study duration is 36 months, with a total of 98 patients to be randomised to either standard advanced life support (ALS) or ALS plus REBOA. Adult patients with an in-hospital CA, successful placement of a femoral artery introducer sheath and any electrical cardiac activity in the initial rhythm analysis are eligible for inclusion. Exclusion criteria comprise traumatic CA, asystole as the initial rhythm, pregnancy and CA occurring on intensive care units, in the operating room or in cardiac catheter laboratory. The primary outcome is sustained return of spontaneous circulation lasting for at least 20 min. Secondary and exploratory outcomes include survival, neurological outcome, changes in aortic blood pressure, end-tidal CO₂ and near-infrared spectroscopy values as well as causes of death and vascular complications related to the intervention. Statistical analyses will be performed on a modified intention-to-treat basis.

ETHICS AND DISSEMINATION: The study protocol (Version 2.1, 11.02.2026) was approved by the Cantonal Ethics Committee of Cantone Bern (2025-D0108). Study results will be disseminated through peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT07434726.},
}

Humans
*Balloon Occlusion/methods
*Cardiopulmonary Resuscitation/methods
Prospective Studies
*Heart Arrest/therapy/mortality
*Aorta, Thoracic
Randomized Controlled Trials as Topic
Return of Spontaneous Circulation
Female
Adult

@article {pmid42581113,
year = {2026},
author = {Jomova, K and Alomar, SY and Valko, R and Nepovimova, E and Kuca, K and Valko, M},
title = {Oxidative stress and inflammation in neurodegenerative disorders.},
journal = {Archives of toxicology},
volume = {},
number = {},
pages = {},
pmid = {42581113},
issn = {1432-0738},
abstract = {The brain's consumption of approximately 20% of the body's oxygen contributes to oxidative stress, a significant pathological factor in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This oxidative stress, linked to low levels of antioxidant enzymes, drives neuronal death by facilitating membrane peroxidation of fatty acids, proteins, and DNA. Alzheimer's disease is characterized by amyloid-beta (Aβ) plaque accumulation and hyperphosphorylated tau aggregates, both of which interact with mitochondria to generate reactive oxygen species (ROS). Aβ peptides bind metals such as iron and copper, catalyzing the formation of damaging hydroxyl radicals. Peripheral markers of oxidative damage, such as elevated malondialdehyde and protein carbonyls, are correlated with these processes in affected patients. In Parkinson's disease, the loss of dopaminergic neurons in the substantia nigra is associated with pathological iron accumulation and mitochondrial complex I dysfunction, which are worsened by misfolded α-synuclein and mutations in antioxidant genes such as PINK1 and Parkin. The autooxidation of dopamine also drives oxidative stress through the generation of hydrogen peroxide and reactive quinones. Huntington's disease involves the degeneration of medium spiny neurons in the striatum due to a polyglutamine repeat expansion in the huntingtin gene, which disrupts mitochondrial function and downregulates antioxidants, leading to excitotoxicity and ROS spikes. Amyotrophic lateral sclerosis primarily affects motor neurons due to the mutations in SOD1, which result in the production of aggregates that impair mitochondria and generate reactive nitrogen species (RNS), such as peroxynitrite. Mitigating oxidative stress in neurodegenerative disorders presents a considerable translational challenge. While low-molecular-weight antioxidant therapies for neurodegenerative disorders have shown promising results in preclinical and animal studies because they mitigate oxidative stress, their clinical efficacy is hampered by low bioavailability and difficulty in penetrating the blood‒brain barrier. To overcome these limitations, current medical research is focused on alternative delivery systems. Innovations such as nanoparticle-based drug delivery are being actively studied to help transport low-molecular-weight antioxidants across the blood‒brain barrier more safely and effectively. Several promising epidemiological trials linked high dietary intake of vitamins C and E to a reduced risk of Parkinson's disease, and plant-derived antioxidants such as polyphenols were explored for their ability to combat neuroinflammation and reduce cognitive decline. Refined oxidative stress-suppressing strategies involve the (ii) application of mitochondrial-targeted agents to preserve ATP production; (ii) boosting the Nrf2 pathway may trigger a cascade of detoxifying enzymes; (iii) supplementation with polyphenols such as quercetin, resveratrol, and curcumin can suppress oxidative stress and dampen microglial activation (neuroinflammation); (iv) and the use of substances affecting the bidirectional network linking oxidative stress and autophagy can clear ROS-generating components. Despite some promising epidemiological data, translating oral or systemic antioxidant therapy into effective clinical treatments for humans requires further effort. A survey of current knowledge of oxidative stress and antioxidant therapy in neurodegenerative diseases is the main subject of this review.},
}

@article {pmid42581131,
year = {2026},
author = {Rahim, A and Zubair, SM and Ahamed, M and Das, S and Patel, R and Debnath, B and Porel, P},
title = {cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders.},
journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology},
volume = {21},
number = {1},
pages = {},
pmid = {42581131},
issn = {1557-1904},
mesh = {Humans ; cGAS-STING Signaling Pathway ; Animals ; *Nucleotidyltransferases/metabolism/immunology ; *Membrane Proteins/metabolism/immunology ; *Nervous System Diseases/immunology/metabolism/drug therapy ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; STING Protein ; Signal Transduction ; },
abstract = {The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an essential cytosolic DNA-sensing system that plays an important role in the regulation of innate immune and inflammatory responses in the central nervous system (CNS). It was first discovered as a promising antiviral defense cascade and has since been shown to execute broader functions in neuroinflammation and neurodegeneration. The pathway can become hyperactive with the release of endogenous DNA from damaged nuclei, mitochondria, or genomic instability, leading to chronic production of type I interferon (TI-IFN), various pro-inflammatory cytokines, and eventually contributing to chronic neuroinflammatory diseases. Recent studies have found that dysregulated cGAS-STING signaling is associated with several neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), stroke, and age-related neurodegeneration. In the CNS, chronic activation of this pathway leads to activation of microglia, oxidative stress, breakdown of the blood-brain barrier (BBB), impaired function of the synapses, and neuronal death. Mitochondrial dysfunction and cytosolic release of mitochondrial DNA (mtDNA) further promote inflammatory signaling, thus perpetuating neurodegeneration. This review highlights the molecular and pathological mechanisms of cGAS-STING signaling in a broader aspect of neurological disorders and appraises the novel therapeutics already under development to inhibit this pathway to regulate neuroinflammation and enhance neurological outcomes.},
}

Humans
cGAS-STING Signaling Pathway
Animals
*Nucleotidyltransferases/metabolism/immunology
*Membrane Proteins/metabolism/immunology
*Nervous System Diseases/immunology/metabolism/drug therapy
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
STING Protein
Signal Transduction

@article {pmid42581247,
year = {2026},
author = {Zhang, X and Zhang, L and Chen, L and Yu, W and Zhao, Y and Huang, Y and Xu, Z},
title = {LXR Pathway Activation by T0901317: A Novel Potential Experimental Strategy for ALS-Related Cognitive and Motor Impairments via Suppression of Necroptosis-associated RIPK1/RIPK3/MLKL Markers.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42581247},
issn = {1559-1182},
mesh = {Animals ; *Liver X Receptors/metabolism/agonists ; *Sulfonamides/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/metabolism/complications/drug therapy/physiopathology ; Fluorocarbons ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Benzenesulfonamides ; Mice, Transgenic ; *Hydrocarbons, Fluorinated/pharmacology/therapeutic use ; *Signal Transduction/drug effects ; Humans ; *Necroptosis/drug effects ; *Cognitive Dysfunction/drug therapy/metabolism/complications ; DNA-Binding Proteins/metabolism ; Biomarkers/metabolism ; Male ; Mice ; Motor Neurons/metabolism/drug effects/pathology ; },
abstract = {To investigate the effects and mechanism of a synthetic LXR agonist, T0901317, on neuronal necroptosis-related signaling pathways in NSC-34 mouse neuronal cells transfected with the TDP-43-A315T plasmid, TDP-43-A315T transgenic mice of amyotrophic lateral sclerosis (ALS). SWATH proteinomics analysis was used to compare ALS patients with cognitive impairment (CI) and non-cognitive impairment (NOCI). TDP-43 abnormal aggregation and necroptosis-related protein expression were assessed with immunofluorescence and western blotting, while apoptosis and inflammatory cytokines were measured through TUNEL assay and ELISA, muscle and motor neuron degeneration were examined with H&E and Toluidine Blue staining. Additionally, the Y-maze and Rotarod tests were used to evaluate cognitive and motor functions. Our study indicates that the LXR pathway was more downregulated in the ALS patients with cognitive impairment. RIPK1, p-RIPK3, and p-MLKL protein levels were upregulated in the TDP-43-A315T plasmid-transfected neuron cells and the TDP-43-A315T transgenic mouse model. The LXR agonist T0901317 reduced the abnormal aggregation of TDP-43 protein and downregulated the protein levels of RIPK1, p-RIPK3, and p-MLKL in vivo and in vitro. Furthermore, T0901317 attenuated motor neuron death and ameliorated muscle degeneration in TDP-43-A315T mice. T0901317 significantly prolonged survival, ameliorated cognitive and motor deficits, and shifted microglial activation marker profiles. The beneficial effects of T0901317 were abolished by LXR antagonist GSK 2033, accompanied by upregulation of necroptotic signaling. The neuroprotective effects of activating LXR may involve the regulation of the RIPK1-RIPK3-MLKL axis and TDP-43 aggregation.},
}

Animals
*Liver X Receptors/metabolism/agonists
*Sulfonamides/pharmacology/therapeutic use
*Amyotrophic Lateral Sclerosis/metabolism/complications/drug therapy/physiopathology
Fluorocarbons
*Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
Benzenesulfonamides
Mice, Transgenic
*Hydrocarbons, Fluorinated/pharmacology/therapeutic use
*Signal Transduction/drug effects
Humans
*Necroptosis/drug effects
*Cognitive Dysfunction/drug therapy/metabolism/complications
DNA-Binding Proteins/metabolism
Biomarkers/metabolism
Male
Mice
Motor Neurons/metabolism/drug effects/pathology

@article {pmid42581415,
year = {2026},
author = {Goehring, K and Abler, E and Vavra, J and Mayer, K and Dorst, J and Elmas, Z and Wiesenfarth, M and Richter, L and Petri, S and Regensburger, M and Reilich, P and Bjelica, B and Lumi, R and Süß, P and Tumani, H and Otto, M and Weishaupt, JH and Ludolph, AC and Oeckl, P},
title = {Blood SOD1 Activity in ALS Patients Receiving Tofersen Treatment.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78328},
pmid = {42581415},
issn = {1531-8249},
abstract = {OBJECTIVE: The antisense oligonucleotide tofersen is the first disease-modifying drug for SOD1-related amyotrophic lateral sclerosis (ALS) and was approved because of its ability to reduce SOD1 protein and neurofilament levels. The effect of tofersen on SOD1 activity is unclear but of clinical relevance because homozygous SOD1 mutations, linked to reduced SOD1 activity, cause severe motor neuron impairment and tofersen-induced reduction could be deleterious. Therefore, monitoring of SOD1 activity is urgently needed.

METHODS: SOD1 activity was analyzed in blood samples from a discovery (n = 120) and a validation cohort (n = 208), including controls, patients with sporadic ALS (sALS), C9orf72 mutation carriers (c9ALS), asymptomatic (SOD1-asym), and symptomatic SOD1 mutation carriers (SOD1-ALS). SOD1 activity was characterized in 18 patients receiving tofersen treatment.

RESULTS: SOD1 activity was significantly lower in both SOD1-asym (median = 7.5 U/mg, interquartile range [IQR] = 7.0-9.0 U/mg) and SOD1-ALS (median = 7.9 U/mg, IQR = 7.1-9.1 U/mg) relative to controls (median = 9.2 U/mg, IQR = 8.9-10.0 U/mg, p < 0.0001), c9ALS (median = 9.4 U/mg, IQR = 8.9-10.2 U/mg, p < 0.0001) and sALS (median 9.5 U/mg, IQR 8.8-9.9 U/mg, p < 0.0001). SOD1 activity was significantly lower in individuals with deleterious SOD1 variants than in individuals with neutral variants. During tofersen treatment, neurofilament and SOD1 protein levels decreased, whereas SOD1 activity remained stable.

INTERPRETATION: The data indicate that the positive tofersen treatment effect is independent of SOD1 activity. Lower SOD1 activity is specific to SOD1-ALS, already present in the asymptomatic phase and depends on the mutation type. Future studies should determine whether tofersen treatment affects cerebrospinal fluid (CSF) SOD1 activity. ANN NEUROL 2026.},
}

@article {pmid42581651,
year = {2026},
author = {Vinceti, M and Till, C and Goodman, PJ and Filippini, T and Rothman, KJ and Thompson, IM},
title = {The selenium and vitamin E cancer prevention trial (SELECT): a secondary, post-intervention analysis on potential excess chronic disease incidence induced by selenium administration.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwag189},
pmid = {42581651},
issn = {1476-6256},
abstract = {The potential for trace amounts of selenium supplements to prevent prostate cancer and other neoplasms was studied in SELECT, a randomized trial conducted in North America for 7-12 years. 34 887 eligible men age 55 or older were assigned to take either 200 μg selenium from L-selenomethionine, 400 IU vitamin E, both selenium and vitamin E, or placebo. The trial was stopped for futility and concerns about adverse effects. Subsequently, we used incidence and mortality data from Medicare through 2019 and the National Death Index through 2024 to investigate the extent to which selenium administration was associated with increased long-term risk of cancer and neurodegenerative disease, during 341 697 person-years of follow-up. Lung cancer showed little increased risk. Associations were near null for leukemia, non-Hodgkin lymphoma and Parkinson's disease, and there was a lower risk for melanoma and colorectal cancer. In contrast, we found a higher risk for Hodgkin lymphoma, multiple myeloma and amyotrophic lateral sclerosis, which has been associated with selenium overexposure in some nonexperimental studies. Though these latter associations were based on few cases, they were consistent with findings from a range of other studies, possibly indicating long-term adverse effects of this organic selenium compound. (Registration no. NCT00006392).},
}

@article {pmid42568821,
year = {2026},
author = {Okano, H},
title = {From neural development to regenerative medicine: A research journey in stem cell biology, spinal cord repair, and iPSC-based drug discovery.},
journal = {Regenerative therapy},
volume = {33},
number = {},
pages = {101157},
pmid = {42568821},
issn = {2352-3204},
abstract = {This commemorative article reflects on a research journey spanning neural development, stem cell biology, regenerative medicine, and iPSC-based drug discovery. My early work focused on RNA-mediated regulation in the nervous system, including studies on myelin basic protein gene regulation and the identification and functional characterization of the RNA-binding protein Musashi. These studies contributed to the conceptual foundation of neural stem cell biology and helped establish methods for identifying and isolating neural stem/progenitor cells, including those present in the adult human brain. Building on this foundation, my colleagues and I pursued translational research in spinal cord injury, ranging from analyses of injury pathophysiology and molecular interventions to preclinical studies using rodent and non-human primate models. These efforts ultimately led to the first-in-human clinical study of induced pluripotent stem cell-derived neural stem/progenitor cell transplantation for subacute spinal cord injury. In parallel, we developed patient-derived iPSC platforms for neurological disease modeling and drug discovery, particularly for amyotrophic lateral sclerosis, where iPSC-based screening identified Ropinirole as a therapeutic candidate and enabled reverse translational research linking cellular phenotypes with clinical responses. Looking ahead, I argue that the future of regenerative therapy will depend on the continued integration of developmental biology, stem cell science, disease modeling, rehabilitation, and clinical translation to address unmet medical needs in disorders of the central nervous system.},
}

@article {pmid42568823,
year = {2026},
author = {Ding, M and Lu, J},
title = {The Influence of Applied Voltage on Drying Kinetics, Quality, and Mathematical Modeling of Ginger During Electrohydrodynamic (EHD) Drying.},
journal = {Food science & nutrition},
volume = {14},
number = {8},
pages = {e72218},
pmid = {42568823},
issn = {2048-7177},
abstract = {This paper systematically evaluated the effects of electrohydrodynamic (EHD) on the drying characteristics, color, texture, moisture state, volatile components, and drying kinetics model of ginger. The results showed that EHD significantly increased the drying rate, rehydration rate, and effective moisture diffusion coefficient (D eff) of ginger. Among all the evaluated parameters, a voltage of 17 kV can produce the highest quality ginger. The drying rate of the 21 kV treatment group was 4.48 times higher than that of the control group (CG). ln[MR] showed a highly linear relationship with time (R [2] > 0.9). Among the ten thin-layer drying kinetics models, Midilli et al.'s model performed the best. Under 17 kV conditions, the best color retention was achieved for dried ginger. EHD drying significantly improved the texture of ginger. LF-NMR results showed a significant decrease in free water and an increase in bound water. Compared with the CG group, EHD showed good retention of most terpenoid compounds in dry ginger. SwissADME predicted six volatile compounds with good drug-like properties. Based on this study, it has been confirmed that the EHD technology has a good application in the ginger industry, providing theoretical support and experimental basis for the further expansion of EHD technology in the field of food drying.},
}

@article {pmid42569815,
year = {2026},
author = {Kondo, A and Hokkoku, K and Kanbayashi, T and Nakayama, T and Sasaki, T and Matsuno, H and Iguchi, Y and Fukutake, T and Ando, T and Kamiyama, T and Kim, P and Hasegawa, T and Hatanaka, Y and Kobayashi, S and Sonoo, M},
title = {"Abductor Sparing": A New Selective Involvement in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70374},
pmid = {42569815},
issn = {1097-4598},
support = {JP22K15738//Japan Society for the Promotion of Science/ ; 22K07524//Ministry of Education, Science, Sports and Culture of Japan/ ; 26K10419//Ministry of Education, Science, Sports and Culture of Japan/ ; 20FC1030//Ministry of Health, Labour and Welfare of Japan/ ; },
abstract = {INTRODUCTION/AIMS: Various signs of selective muscle involvement have been reported in amyotrophic lateral sclerosis (ALS) but such studies for the lower limbs are scarce. We formed a preliminary impression that hip abductors (Ab) are often preserved in ALS. We named this phenomenon "abductor sparing", and this study aimed to verify our findings.

METHODS: Patients with a confirmed diagnosis of ALS (ALS group) and patients with pyramidal weakness other than ALS (pyramidal group) were retrospectively identified. Medical Research Council (MRC) scores of 10 muscle groups in the lower limbs were evaluated. The proportion of patients with weakness (MRC score 4 or less) was compared between different groups.

RESULTS: We enrolled 61 patients in the ALS group and 27 patients in the pyramidal group. The most frequently weak muscle groups in both groups were big toe extensors and hip flexors. Ab was the third (70%) in the pyramidal group, whereas it was weak only in 30% of patients with ALS. This held true also for patients with ALS with shorter duration or less severity. "The lower limb flexor pattern", i.e., flexor muscles being weaker than extensor muscles, was observed both in ALS and pyramidal groups.

DISCUSSION: Patients with ALS generally showed similar muscle weakness patterns to those with pyramidal syndrome, except for abductor sparing. The reason for the latter phenomenon is unclear. Abductor sparing may be useful for early diagnosis of ALS, although larger studies with blinded evaluators are needed to confirm these findings.},
}

@article {pmid42570648,
year = {2026},
author = {Ye, P and Guo, B},
title = {Identification of Glycolysis-Related Diagnostic Biomarkers for Amyotrophic Lateral Sclerosis Using Machine Learning.},
journal = {Clinical laboratory},
volume = {72},
number = {8},
pages = {},
doi = {10.7754/Clin.Lab.2025.250766},
pmid = {42570648},
issn = {1433-6510},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/metabolism/blood ; *Biomarkers/metabolism/blood ; *Glycolysis/genetics ; *Machine Learning ; Predictive Learning Models ; Boosting Machine Learning Algorithms ; Blood Glucose/analysis/metabolism ; },
abstract = {BACKGROUND: Glycometabolism has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), yet the precise molecular mechanisms underlying this association remain poorly understood. The identification of reliable biomarkers for ALS diagnosis represents a critical unmet need in clinical practice, as early detection and intervention could significantly improve patient outcomes.

METHODS: We employed a comprehensive analytical approach combining two-sample Mendelian randomization analysis to investigate the causal relationship between blood glucose levels and ALS. Additionally, we integrated differential expression analysis, multiple machine learning algorithms, and correlation analyses to identify potential diagnostic biomarkers for ALS. The machine learning framework utilized gradient boosting tree methodology to construct predictive models, with performance evaluation conducted through cross-validation procedures.

RESULTS: Mendelian randomization analysis demonstrated a significant negative causal relationship between blood glucose levels and ALS risk. Through bioinformatic analysis and machine learning approaches, we successfully identified candidate genes and constructed a high-performance predictive model using gradient boosting tree methodology, achieving an average area under the curve (AUC) of 0.8782 in cross-validation. Validation studies utilizing both bulk and single-cell RNA sequencing datasets revealed that COL5A1 and VCAN genes play significant roles in ALS pathogenesis, likely through their involvement in glycolytic pathways.

CONCLUSIONS: Our findings provide novel insights into the molecular mechanisms linking glycometabolism and ALS, while identifying potential diagnostic biomarkers for the disease. The identified genes, COL5A1 and VCAN, represent promising targets for further investigation in ALS pathogenesis. However, the clinical translation of these findings requires validation through additional datasets and prospective clinical trials to establish their diagnostic utility and therapeutic potential.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/genetics/metabolism/blood
*Biomarkers/metabolism/blood
*Glycolysis/genetics
*Machine Learning
Predictive Learning Models
Boosting Machine Learning Algorithms
Blood Glucose/analysis/metabolism

@article {pmid42572287,
year = {2026},
author = {Okunomiya, T and Sakasai, T and Tsukita, K and Shimizu, R and Okusa, A and Adachi, M and Tomita, S and Tanaka, A and Kondo, T and Imamura, K and Inoue, H},
title = {Generation of mutant human SOD1 knock-in mouse lines at the Rosa26 locus as a platform for developing genome-editing therapies for amyotrophic lateral sclerosis.},
journal = {Experimental animals},
volume = {},
number = {},
pages = {},
doi = {10.1538/expanim.26-0040},
pmid = {42572287},
issn = {1881-7122},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of upper and lower motor neurons, resulting in progressive paralysis and death within a few years of symptom onset. Although current treatments modestly slow the disease progression, effective disease-modifying and curative therapies remain an urgent unmet need. SOD1 mutations are one of the major genetic causes of familial ALS. The p.Leu127Ser (L126S) and p.Gly94Ser (G93S) variants are clinically relevant pathogenic variants for which appropriate animal models are needed for preclinical evaluation of gene-editing therapies. However, most existing SOD1 models rely on high copy overexpression of mutant SOD1. Therefore, animal models carrying a single copy mutant human SOD1 allele are required for evaluating the in vivo efficacy of genome editing therapies. Here, we used CRISPR/Cas9-mediated homology-directed repair to generate a knock-in mouse line at the Gt(ROSA)26Sor (Rosa26) locus carrying a single-copy, 11-kb human SOD1 genomic fragment, including all exons and introns, with the L126S mutation. The Rosa26-hSOD1[L126S] mice did not develop ALS-like phenotypes during the limited observation period. However, they faithfully retained a single-copy mutant human SOD1 genomic allele, providing a valuable preclinical platform for evaluating genome-editing therapies. We also generated Rosa26-hSOD1[G93S] mice carrying the SOD1 G93S mutation with comparable efficiency. Together, these mutant human SOD1 knock-in mouse lines provide a versatile and clinically relevant platform for the preclinical evaluation of genome-editing therapies targeting heterozygous SOD1 mutations.},
}

@article {pmid42572464,
year = {2026},
author = {Cannedy, S and Lesser, R and Yano, EM and Hamilton, AB and Fenwick, KM},
title = {Staff Perspectives on Optimising Organisational Responses to Patient-Initiated Workplace Violence.},
journal = {Journal of advanced nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jan.70713},
pmid = {42572464},
issn = {1365-2648},
support = {PPO 21-272//US Department of Veterans Affairs/ ; RCS 05-195//US Department of Veterans Affairs/ ; RCS 21-135//US Department of Veterans Affairs/ ; },
abstract = {AIMS: To identify existing and ideal practices for responding to patient-initiated workplace violence in the US Veterans Health Administration.

DESIGN: Cross-sectional, descriptive qualitative design.

METHODS: Qualitative interviews with staff (n = 31) in eight veteran healthcare facilities located in the western United States (2023-2024). Guided by Spelten et al.'s model of strategies to reduce patient-initiated workplace violence, thematic analysis examined post-incident interventions with patients and identified recommendations for improvement.

RESULTS: Educating and setting limits with patients varied by facility. Most respondents were unaware of patient education/support that occurred post-incident. Respondents disagreed about the role that patients' clinical status should play; some wanted more leeway for certain patients (e.g., those diagnosed with dementia) and others wanted a consistent response (regardless of clinical status) to create a culture of respect.

CONCLUSION: Patient education and limit-setting are important elements in addressing patient-initiated workplace violence, but they are inconsistently used. Offering resources to patients is underutilised. Staff have differing perspectives on what constitutes ideal post-incident interventions for medically complex patients.

When responding to patient violence, healthcare systems may benefit from clear and consistently implemented protocols and tailored educational interventions and support for different patient populations (e.g., dementia). Staff may benefit from guidance on balancing patient care with limit-setting during encounters with medically complex patients.

IMPACT: We examined existing practices for responding to patient-initiated workplace violence and staff suggestions for improvement in a large healthcare system. Participants wanted additional and consistent patient interventions; opinions varied on how patient clinical status and intent should shape organisational responses. Staff can benefit from consistently implemented protocols for responding to patient violence. Healthcare systems may need to provide staff guidance on balancing patient care with limit-setting.

REPORTING METHOD: SRQR guidelines for qualitative studies.

No patient or public contribution.},
}

@article {pmid42572514,
year = {2026},
author = {Sheehy, TP and Sia, T and Morgan, PE and Zhao, Y and Mathieson, SR and Gibb, RM and Smith, AA and Wools, CA},
title = {Relationship between neck weakness in motor neurone disease and respiratory function: a retrospective study.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/17582024.2026.2705867},
pmid = {42572514},
issn = {1758-2032},
abstract = {AIMS: The primary aim was to explore the relationship between neck weakness in people with motor neurone disease (MND) and their respiratory function. The secondary aim was to identify whether neck weakness can be a prognostic factor.

METHODS: This was a retrospective observational cohort study. Data was collected from patient records on MND characteristics, neck weakness, respiratory function, and noninvasive ventilation (NIV) use. Multivariate modeling explored the effect of neck weakness on respiratory variables.

RESULTS: MND-related neck weakness was evident in 41% of 324 participants. Fifty-four percent used NIV and 17% became dependent on NIV during disease progression. The presence of neck weakness in MND was predictive of time to respiratory function decline, for respiratory outcomes (forced vital capacity (FVC) <65%, FVC <50% and NIV use) as well as having an effect on time to death. Median time from neck weakness onset to death was 8 months (IQR 10 months; range 0 to 60 months) with bulbar onset the quickest, median of 7 months (IQR 7 months, range 0 to 43 months).

CONCLUSIONS: The presence of neck weakness is associated with a more rapid respiratory function decline in MND. In addition, neck weakness can be considered a prognostic factor in MND survival.},
}

@article {pmid42573583,
year = {2026},
author = {Yeow, A and Cleland, J and Soh, C and Balete, C},
title = {Sociotechnical Misalignments in Hospital AI System Implementation: Qualitative Case Study.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e87534},
pmid = {42573583},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; Qualitative Research ; },
abstract = {BACKGROUND: Implementing AI into real-world health care settings is known to be challenging, particularly regarding how well AI is embedded into the existing knowledge, practices, and procedures of a context. Understanding this process is critical for maximizing the successful implementation of AI tools and planning the time, costs, and resources needed for their successful implementation.

OBJECTIVE: This study sought to examine the contextual challenges of implementing an AI chatbot, ChatAI (which provided quick access to clinical and operational information without relying on the intranet), in a large tertiary government hospital by analyzing the impact of sociotechnical factors on its sustained use.

METHODS: We used an instrumental case study approach, utilizing interviews and meeting minutes. A total of 16 semistructured interviews were conducted with the implementation team and hospital staff who interacted with ChatAI. Interviews were audio-recorded and transcribed. Sociotechnical systems (STS) theory, specifically Davis et al's (2014) framework, was adopted to examine ChatAI's implementation and use.

RESULTS: Multiple misalignments among 5 of Davis et al's sociotechnical elements (goals, people, processes, technology, and infrastructure) limited ChatAI's user adoption and sustainability. Although the hospital's innovation center team attempted to address these initial misalignments, contextual changes such as new regulatory mandates, infrastructure changes, and evolving stakeholder practices introduced further misalignments between ChatAI and the hospital-eventually leading to its discontinuation.

CONCLUSIONS: This study highlights how sociotechnical misalignments can undermine the use and sustainability of large-scale implementation of AI systems. These findings will inform future efforts to implement AI tools in real-world health care settings, increasing awareness of the need to align sociotechnical dimensions of goals, people, processes, technology, and infrastructure. It highlights the particularly challenging aspect of aligning continually evolving infrastructure with regulatory requirements. Future research should focus on how infrastructure and infrastructure changes, as well as external regulatory requirements, influence AI implementation and use.},
}

Humans
*Artificial Intelligence
Qualitative Research

@article {pmid42573824,
year = {2026},
author = {Su, B and Li, L and Zheng, X and Ma, H and Li, X and Feng, X},
title = {Clinical significance of SQSTM1 variants in ALS: report of p.Arg119Cys and literature review.},
journal = {Neurogenetics},
volume = {27},
number = {1},
pages = {},
pmid = {42573824},
issn = {1364-6753},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Sequestosome-1 Protein/genetics ; Male ; Middle Aged ; Pedigree ; Mutation, Missense ; Genetic Association Studies ; Adaptor Proteins, Signal Transducing/genetics ; },
abstract = {We analyzed the clinical features of a patient with amyotrophic lateral sclerosis (ALS) carrying a novel variant in the sequestosome 1 (SQSTM1) gene and explored the genotype-phenotype association of SQSTM1 gene variants in combination with previous literature. Clinical data and genetic testing results of an ALS patient treated at our hospital were collected. Whole-exome sequencing was used to screen for ALS-related genes, and candidate variants were validated by Sanger sequencing and family analysis. A systematic search was conducted in the PubMed database using the keywords ("amyotrophic lateral sclerosis") OR ("motor neuron disease") AND ("SQSTM1") to summarize the clinical and genetic characteristics of previously reported ALS patients with SQSTM1 variants. The patient was a 49-year-old male with progressive weakness in both lower limbs for one year and weakness in the left upper limb for the past three months. Electromyography showed extensive neurogenic damage. Genetic testing identified a novel heterozygous missense variant, c.355 C > T (p.Arg119Cys), in the SQSTM1 gene. Family verification revealed that his phenotypically normal mother carried the same variant. The literature search identified 58 cases of ALS associated with SQSTM1 variants. Missense variants were the most common type. We identified a novel SQSTM1 variant, c.355 C > T (p.Arg119Cys), in a ALS patient. Although this finding expands the variant spectrum, its pathogenicity remains uncertain and requires further functional validation and pedigree confirmation. Our literature review further shows that SQSTM1-associated ALS predominantly presents with limb onset, with a subset of patients exhibiting frontotemporal dementia or Paget's disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
*Sequestosome-1 Protein/genetics
Male
Middle Aged
Pedigree
Mutation, Missense
Genetic Association Studies
Adaptor Proteins, Signal Transducing/genetics

@article {pmid42561511,
year = {2026},
author = {Al Ojaimi, Y and Dupuis, A and Palla, M and Lanznaster, D and Hergesheimer, R and Galineau, L and Serriere, S and Chami, AA and Martineau, P and Alouane, T and Marouillat, S and Dupuy, C and Schneider, BL and Veyrat-Durebex, C and Masse, F and Trovero, F and Andres, CR and Corcia, P and Vourcʼh, P and Blasco, H},
title = {Intrabody B1 targeting TDP-43 modulates neuroinflammatory and metabolic pathways in a preclinical ALS model.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e01032},
doi = {10.1016/j.neurot.2026.e01032},
pmid = {42561511},
issn = {1878-7479},
abstract = {TDP-43 pathology is a hallmark of Amyotrophic Lateral Sclerosis (ALS), yet no therapeutic strategy effectively targets its upstream molecular consequences. Here, we investigated whether the anti-TDP-43 intrabody scFv B1 modulates neuroinflammatory and metabolic pathways in a preclinical ALS model, and whether these effects translate into functional benefit after symptom onset. Using phage display, we previously identified single-chain variable fragments (scFvs) binding TDP-43, including the candidate therapeutic scFv B1. In NSC-34 motor neuron-like cells overexpressing human wildtype TDP-43, B1 reduced NF-κB activation, consistent with disruption of TDP-43-driven inflammatory signaling. For in vivo assessment, B1 was delivered via AAV-CAP.B10 after symptom onset in the hTDP-43(WTxA315T) transgenic mouse model, enabling neuro-specific expression. Two cohorts were analyzed - longitudinal (nine months) and terminal (six months post-treatment) - through behavioral testing, PET imaging, metabolomics, transcriptomics, and plasma biomarker analyses. B1 achieved robust CNS expression and modulated several disease-relevant molecular pathways. RNA-sequencing revealed attenuation of NF-κB-related inflammatory signatures and partial normalization of metabolic and trophic gene expression. Metabolomic profiling identified shifts toward wild-type-like levels in oxidative stress, mitochondrial, and membrane phospholipid metabolites. Despite these molecular effects, symptomatic B1 administration did not improve motor behavior or reduce plasma neurofilament light chain (NfL) concentrations. Notably, plasma TDP-43 levels were stabilized, indicating systemic target engagement. Collectively, scFv B1 modulates upstream pathogenic processes associated with TDP-43 proteinopathy but is insufficient to reverse established neurodegeneration after symptom onset, underscoring the need for earlier and likely combinatorial intervention strategies in ALS.},
}

@article {pmid42561943,
year = {2026},
author = {Rostalski, H and Hietanen, T and Hoffmann, D and Heikkinen, S and Huber, N and Dhingra, A and Rodriguez-Nieto, S and Kuulasmaa, T and Ohtonen, S and Jäntti, H and Pekkala, V and Leskelä, S and Mäkinen, P and Katisko, K and Hartikainen, P and Lehtonen, Š and Solje, E and Koistinaho, J and Malm, T and Portaankorva, AM and Natunen, T and Martiskainen, H and Takalo, M and Hiltunen, M and Haapasalo, A},
title = {C9orf72-associated and sporadic FTD patient iPSC-microglia show differences in phagocytosis and gene expression.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {103026},
doi = {10.1016/j.stemcr.2026.103026},
pmid = {42561943},
issn = {2213-6711},
abstract = {C9orf72 hexanucleotide repeat expansion (C9-HRE) is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (FTD). However, approximately half of the FTD patients are sporadic without a clear genetic background. To compare characteristics of microglia from different FTD subtypes, we generated induced pluripotent stem cell-derived microglia (iMG) from sporadic and C9-HRE-carrying behavioral variant FTD (bvFTD) patients and healthy controls. C9-HRE iMG displayed C9-HRE-associated RNA foci and dipeptide repeat proteins. All bvFTD iMG had fewer LAMP2-A-positive vesicles compared to control iMG. Additionally, C9-HRE iMG showed significantly increased LC3BII/I conversion after bafilomycin A1 treatment and altered phagocytic activity. The gene expression profile of C9-HRE iMG only modestly differed from the control iMG, but was greatly different from the sporadic bvFTD patient iMG. Our data show alterations in phagocytic and autophagosomal/lysosomal pathways and gene expression profiles between C9-HRE and sporadic bvFTD iMG for the first time.},
}

@article {pmid42561977,
year = {2026},
author = {Helmold, B and Armon, C and Benatar, M and Bertorini, T and Bromberg, M and Brown, A and Cadavid, JM and Carbunar, O and Carter, GT and Crayle, J and Feldman, E and Foucher, J and Glass, J and Greenstein, E and Jhooty, S and Jiang, N and Kochen, NN and McDermott, C and Olby, N and Pattee, G and Porter, D and Premasari, A and Rao, A and Ratner, D and Staats, K and Tito, E and Vieira, F and Wicks, P and Bedlack, R},
title = {ALSUntangled #84 - ivermectin.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/21678421.2026.2714724},
pmid = {42561977},
issn = {2167-9223},
abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). In this review, we explore the possibility of using ivermectin to slow ALS progression. Ivermectin's ability to modulate neuroinflammation and excitotoxicity give it plausible mechanisms for treating ALS, though it does not get into the brain very well. One preclinical study demonstrated that ivermectin lengthened lifespan within a mouse model of mSOD1 genetic ALS. This finding has not been replicated. The 2 PALS we found who had data comparing ALSFRS-R progression on and off ivermectin appeared to have no benefit from it. We found no trials of ivermectin in PALS. Ivermectin is low cost and generally well tolerated with most adverse effects being mild and transient, but serious side effects can rarely occur, and it has not been carefully studied in PALS. We cannot at present endorse ivermectin as an ALS treatment.},
}

@article {pmid42562736,
year = {2026},
author = {Chan, SC and Tung, CW and Chang, CY and Su, CC and Chen, YC and Wu, PM and Tung, CY and Chen, SF and Kuo, HY and Cheng, PH and Chen, CM and Yang, SH},
title = {Wild-type C9orf72 drives proteasomal dysfunction and mutant aggregates via a Stat1-Isg15 axis in Huntington's disease.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {},
number = {},
pages = {e00970},
doi = {10.1016/j.neurot.2026.e00970},
pmid = {42562736},
issn = {1878-7479},
abstract = {Mutant C9orf72 has been extensively studied as a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia, and is also known to generate Huntington's disease (HD)-like phenocopies. However, despite this strong disease association, the role of wild-type C9orf72 (wt-C9orf72) in neurodegeneration remains largely unexplored. HD is a neurodegenerative disease, and characterized by the accumulation of misfolded mutant Huntingtin (mHTT) and impaired proteostasis, yet the upstream mechanisms driving ubiquitin-proteasome system (UPS) dysfunction are not fully understood. Here, we identify a previously unrecognized modulatory role of wt-C9orf72 in regulating mHTT aggregation in experimental HD models. Analysis of public transcriptomic datasets reveal context-dependent C9ORF72 expression changes across HD-related human datasets, while C9orf72 levels are increased in R6/2 mouse brain lysates. Functional analyses reveal that overexpression of wt-C9orf72 increases mHTT aggregation and is accompanied by increased apoptotic signaling and reduced cell viability. Unbiased proteomic profiling identifies Stat1 as a key downstream effector. Mechanistically, wt-C9orf72 promotes Stat1 activation and nuclear translocation, leading to transcriptional upregulation of Isg15, a ubiquitin-like modifier. Elevated Isg15 disrupts UPS function, resulting in accumulation of polyubiquitinated proteins and impaired proteasomal degradation. Importantly, genetic suppression of Stat1 or Isg15 significantly attenuates C9orf72-associated mHTT aggregation, supporting a functional C9orf72-Stat1-Isg15 axis. Consistent with these cell-based findings, Stat1, phosphorylated Stat1 and Isg15 levels are elevated in the cortex and striatum of R6/2 HD mouse brains. Collectively, our findings identify a novel wt-C9orf72-Stat1-Isg15 axis that promotes proteasomal dysfunction and mHTT aggregation, providing new insights into wt-C9orf72-associated protein homeostasis.},
}

@article {pmid42562773,
year = {2026},
author = {Zheng, X and Zhang, N and Wang, L and Zhao, H and Liu, C and Wang, J and Zhao, W and Zhao, J and Yang, P and Robinson, L and Hunt, L and Lokken, A and Lin, L and Nelson, PT and Kofler, J and Xie, H and Xia, H and Mao, Q},
title = {A phosphorylation‑independent monoclonal antibody improves detection of TDP‑43 pathology across frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and limbic predominant age related TDP‑43 encephalopathy neuropathological change.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag085},
pmid = {42562773},
issn = {1554-6578},
support = {GC-202008-2020689//Alzheimer's Drug Discovery Foundation/ ; R21AG080502/AG/NIA NIH HHS/United States ; R21AG088509/AG/NIA NIH HHS/United States ; R01AG097508/AG/NIA NIH HHS/United States ; },
abstract = {TDP-43 proteinopathies encompass frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), amyotrophic lateral sclerosis (ALS-TDP), and limbic predominant age related TDP-43 encephalopathy neuropathological change (LATE-NC). These proteinopathies exhibit subtype-specific aggregate architectures that may constrain epitope accessibility in situ. We compared a phosphorylation-independent monoclonal antibody targeting a C-terminal epitope (MAb No. 9) with the phospho-specific pSer409/410 antibody to determine whether its signal relates to regional neurodegeneration in a multicenter autopsy cohort spanning FTLD-TDP types A-C, ALS-TDP, and Alzheimer disease neuropathologic change (ADNC) with or without LATE-NC. Immunolabeling with MAb No. 9 detected pathological TDP-43 across all diagnostic groups with enhanced labeling of dystrophic neurites and thread/dot-like pathology in FTLD-TDP types A/B and in ALS-TDP. MAb No. 9 performance was equivalent to p409/410 in FTLD-TDP type C. In ADNC with stage 3 LATE-NC, MAb No. 9 revealed a greater limbic burden and labeled both α type and β type inclusions. Dual label immunofluorescence demonstrated strong spatial overlap with p409/410 but additionally highlighted fine punctate pathology. MAb No. 9 burden in FTLD-TDP type A correlated strongly with cortical neurodegeneration but showed weaker and variable associations, particularly in severely atrophic cortex. These findings indicate that filament architecture governs C-terminal epitope accessibility and that MAb No. 9 may be a complementary tool for subtype refinement, clinicopathologic correlation and translational biomarker development in TDP-43 proteinopathies.},
}

@article {pmid42562776,
year = {2026},
author = {Wan, Y and Gao, C and Li, J and Luan, M and Lu, Y and Wang, J and Yang, B and Zheng, J and Yuan, Y and Wei, J and Wang, Z and Deng, J},
title = {Neural stem cell-derived small extracellular vesicles ameliorate disease progression in the SOD1 G93A murine model of amyotrophic lateral sclerosis.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag013},
pmid = {42562776},
issn = {1554-6578},
support = {2025ZD0217600//Brain Science and Brain-like Intelligence Technology-National Science and Technology Major Project/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects motor neurons leading to muscle weakness, paralysis, and ultimately, respiratory failure. Extracellular vesicles (EVs) facilitate intercellular communication by mimicking the functions of their parent cells. In this study, we found that repeated administration of neural stem cell-derived extracellular vesicles (NSC-derived EVs) improved motor performance and provided protection to lumbar motor neurons, the neuromuscular junctions, and muscle morphology in the SOD1 G93A transgenic mouse model of ALS. Furthermore, by analyzing the RNA-sequencing of muscle specimens from ALS-SOD1 patients, we demonstrated that the rescue effects of NSC-derived EVs might be linked to the p53 pathway. Compared to the PBS control treatment group, both TP53 and the p53 upregulated modulator of apoptosis (PUMA) were downregulated in the spinal cord of mice treated with NSC-derived EVs. These data provide additional knowledge for the promising use of NSC-derived EVs as a potential therapy for ALS.},
}

@article {pmid42564086,
year = {2026},
author = {Zhang, G and Li, Z and Yao, X and Ding, M and Liu, X},
title = {Observed changes in clinical proxy measures of airway protection after cervical epidural spinal cord stimulation in neurological disorders: a preliminary retrospective case series.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1875581},
pmid = {42564086},
issn = {1664-2295},
abstract = {OBJECTIVES: Although spinal cord stimulation (SCS) has been investigated for cough and respiratory motor output after neurological injury, its relationship with clinical proxy measures of airway protection remains unclear. We explored observed changes in aspects of airway protection after cervical SCS in patients with neurological disorders.

MATERIALS AND METHODS: We retrospectively analyzed six patients who underwent cervical SCS for spinal cord injury, amyotrophic lateral sclerosis, or disorders of consciousness. Clinical proxy measures included the Semi-quantitative Cough Strength Score (SCSS), Functional Oral Intake Scale (FOIS), Water Swallow Test (WST), and Chinese Swallowing Quality of Life Questionnaire (cSWAL-QoL). SCSS was available for all six patients, whereas FOIS, WST, and cSWAL-QoL were limited to the four conscious patients. SCSS, FOIS, and WST were descriptively compared across preoperative, stimulation ON, and stimulation OFF conditions when clinically permissible. cSWAL-QoL was compared between preoperative and postoperative follow-up.

RESULTS: During active stimulation, SCSS scores were higher in all six patients, with the median score changing from 3.0 preoperatively to 4.0 during stimulation ON (nominal p = 0.031). SCSS was also higher during stimulation ON than OFF (4.0 vs. 3.0; nominal p = 0.031). Among the four conscious patients, FOIS changed from 4.0 to 5.0 and WST changed from 3.5 to 2.5 during stimulation ON, while cSWAL-QoL changed from 91.0 to 151.5 postoperatively. No stimulation-related adverse events occurred.

CONCLUSION: Clinical proxy measures related to airway protection showed exploratory state-associated changes during cervical epidural SCS, particularly in cough-strength scores. These preliminary findings do not establish efficacy or mechanism.},
}

@article {pmid42564438,
year = {2026},
author = {Diovu, EO and Nnadi, CO and Paul-Chima, UO},
title = {Pharmaceutical wastewater irrigation and metabolite-based environmental pharmacognosy: a perspective on quality and safety risks for medicinal plants.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1878168},
pmid = {42564438},
issn = {1663-9812},
abstract = {Medicinal plants are increasingly cultivated in agroecosystems irrigated with treated or untreated wastewater, biosolids and contaminated surface water. Pharmaceutical residues are recognised contaminants of emerging concern, but their implications for botanical-drug quality, therapeutic consistency and safety remain insufficiently characterised. This Perspective argues that pharmaceutical wastewater irrigation is a plausible yet underexamined driver of metabolite reprogramming in medicinal plants. Chronic exposure to antibiotics, non-steroidal anti-inflammatory drugs, antiepileptics, antidepressants, hormones and transformation products may alter secondary metabolism through oxidative stress, xenobiotic detoxification, rhizosphere microbiome disturbance and modified nutrient signalling. These processes may change phenolic, flavonoid, alkaloid, terpenoid, glycoside and volatile metabolites that underpin pharmacognostic quality and ethnopharmacological reliability. Medicinal plants may also accumulate parent pharmaceuticals, transformation products and, under some conditions, microbial signatures associated with antibiotic resistance. Building on Carter et al.'s source-pathway-receptor framework and Helmecke et al.'s regulatory risk synthesis, we shift attention from residue burden to how exposure history alters the medicinal metabolome. Evidence from antibiotic-induced metabolite changes in Pinellia ternata supports this proposition, while indicating compound- and context-specific effects. We advance a balanced position: metabolite reprogramming is biologically credible, but food-crop studies often report de minimis residue risks and inconsistent rhizosphere-resistome effects. Future work should integrate wastewater profiling, matched controls, targeted and untargeted metabolomics, transformation-product discovery, microbiome analysis, digestion and bioaccessibility testing, bioactivity assays and probabilistic mixture-risk assessment.},
}

@article {pmid42565285,
year = {2026},
author = {Semendric, I and Munn, Z and Jenkins, T and Edwards, A and Tull, V and Travlos, V and Hutchinson, K and Krikheli, L and Sheers, N and Hall, LA and Chua, P and Hatch, N and Allcroft, P and Werth, B and Saffrett, A and Yoong, J and Cooper, L and Signorelli, M and Farrugia, E and Devenney, E and Douglas, A and Gibb, A and Macshane, M and Gardiner, M and Collins, A and Yang, J and Rogerson, B and Schultz, D and Lim, D and Fisher, F and Herz, H and Puckering, H and Swain, I and Cameron, J and Donnelly, L and Davis, L and Anderson, L and Acampora, M and Heatley, R and Taubert, S and Sheehy, T and Sia, T and Aiyappan, V and Huynh, W and Stern, C and , },
title = {Issues in the clinical assessment and management of people living with motor neurone disease (MND): a survey of Australian healthcare professionals.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2710550},
pmid = {42565285},
issn = {2167-9223},
abstract = {Objective: To inform the development of the Australian MND Guideline, this study aimed to identify challenges Australian healthcare professionals (HCPs) face in the clinical assessment and management of people living with MND (plwMND) including where practice varies from evidence or is underrepresented in the literature and challenges that arise when supporting non-MND specialists. Methods: An anonymous online survey was developed on Qualtrics (Provo, UT) and distributed in July 2025 to members of the Australian MND Guideline Clinical and Content Advisory Group. Demographic data were analyzed using descriptive statistics and verbatim responses were analyzed thematically to a pre-defined framework of guideline scopes and topics. Results: Fifty HCPs, predominantly allied health professionals, completed the survey (55% response rate). HCPs reported diagnostic delays, difficulties accessing timely multidisciplinary support, and challenges coordinating care, particularly outside MND clinic catchment areas. HCPs perceived uncertainty in respiratory support, nutrition, saliva management, and psychological and cognitive care. Variations from guidance reflected gaps and inconsistencies in the evidence base, the need for individualized care, and systemic constraints including funding, workforce shortages, and inequities in access. Non-MND specialists sought guidance on prognosis, referral pathways, symptom management, and end-of-life care. Conclusion: This survey identified areas of clinical practice uncertainty and variability in the clinical assessment and management of plwMND from the perspective of Australian HCPs. These findings will inform the development of the Australian MND Guideline, including prioritization of topics and questions, and consideration of areas where expert consensus is required.},
}

@article {pmid42566133,
year = {2026},
author = {Thompson, JC and Kobylecki, C and Jones, M and Haigh, J and Larbey, M and Langheinrich, TC and Thomasson, R and Richardson, AMT and Snowden, JS},
title = {Frontotemporal dementia with right temporal predominance: a clinical comparison with left-predominant FTD.},
journal = {Journal of neurology},
volume = {273},
number = {9},
pages = {},
pmid = {42566133},
issn = {1432-1459},
mesh = {Humans ; *Frontotemporal Dementia/physiopathology/diagnostic imaging/pathology/psychology/classification ; Female ; Male ; *Temporal Lobe/pathology/diagnostic imaging ; Middle Aged ; Aged ; Retrospective Studies ; Neuropsychological Tests ; Magnetic Resonance Imaging ; *Functional Laterality/physiology ; Atrophy ; },
abstract = {BACKGROUND: The right-temporal variant of frontotemporal dementia (FTD) is well characterised. Whether it should be considered a distinct clinical entity, separate from other syndromes of FTD, remains an open question. The study addressed the issue through a retrospective comparison of clinical characteristics of patients with predominant atrophy in right or left anterior temporal lobe (R-ATL vs. L-ATL).

METHODS: Patients were identified from a clinical database, diagnosed with FTD, and reported to show temporal lobe atrophy on imaging. Fifty-one patients were selected in whom independent ratings of atrophy were greatest in right or left anterior temporal lobe. Presenting symptoms, cognitive and behavioural characteristics, neuropsychological findings, and diagnostic classification were recorded.

RESULTS: Difficulty recognising people, impaired decision-making, perseverative preoccupations, disinhibition, and loss of empathy characterised the R-ATL group, in keeping with the previous reports. There was, however, overlap in cognitive and behavioural symptomatology in R-ATL and L-ATL, and sensitivity and specificity values were modest. Group differences diminished with disease progression. The most common clinical classification at first assessment in both groups was semantic dementia (SD), with other patients being classified as behavioural-variant FTD (bvFTD), FTD with amyotrophic lateral sclerosis or mixed FTD/SD. Not all patients with L-ATL met criteria for semantic variant primary progressive aphasia (svPPA).

CONCLUSIONS: The data question the notion that R-ATL and L-ATL presentations are separate entities. We argue that a common diagnostic framework for the two is warranted, with classification being based on cognitive/behavioural characteristics rather than neuroradiological grounds.},
}

Humans
*Frontotemporal Dementia/physiopathology/diagnostic imaging/pathology/psychology/classification
Female
Male
*Temporal Lobe/pathology/diagnostic imaging
Middle Aged
Aged
Retrospective Studies
Neuropsychological Tests
Magnetic Resonance Imaging
*Functional Laterality/physiology
Atrophy

@article {pmid42567782,
year = {2026},
author = {Risby-Jones, G and Lee, JD and Fung, JN},
title = {Interleukin-6 trans-signalling as a selectively targetable driver of neurodegeneration.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2026.07.002},
pmid = {42567782},
issn = {1878-108X},
abstract = {Interleukin-6 (IL-6) exerts protective and pathogenic effects in the central nervous system through distinct receptor-signalling modes. Classical signalling via membrane-bound IL-6 receptor (IL-6R) is often associated with homeostatic and reparative functions, whereas trans-signalling, mediated by soluble IL-6R, expands IL-6 responsiveness to gp130-expressing cells and may promote chronic inflammation. Emerging evidence implicates dysregulated IL-6 trans-signalling in amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. Here, we review mechanisms linking IL-6 trans-signalling to immune, glial, neuronal, and vascular dysfunction in neurodegeneration. We highlight key knowledge gaps and discuss whether selective targeting of trans-signalling can limit inflammatory pathology while preserving beneficial classical IL-6 functions.},
}

@article {pmid42559804,
year = {2026},
author = {Bonde, JP and Skaaby, S and Flachs, EM and Dollard, M and Keyes, K and Rosengren, A and Mehlum, IAS and Mikkelsen, S},
title = {Lavigne-Robichaud et al: Job strain and ischemic heart disease: the balance of methodological bias and implications for prevention. Author reply.},
journal = {Scandinavian journal of work, environment & health},
volume = {},
number = {},
pages = {},
doi = {10.5271/sjweh.4324},
pmid = {42559804},
issn = {1795-990X},
abstract = {We appreciate Lavigne-Robichaud et al`s critical remarks (1) to our systematic review addressing the epidemiological evidence for causal relations between job strain and the risk of ischemic heart disease (IHD) (2). Their main concern relates to the strength of the hypothesized association between job strain and IHD and, by extension, the magnitude of the population attributable fraction. They argue that our overall conclusion places too much emphasis on biases that inflate risk estimates and underrates biases that attenuate estimates towards the null. However, we believe it is premature to discuss in detail the strength of associations before a causal link is established with reasonable confidence. The main objective of our review was to evaluate the epidemiological evidence that observed associations are indeed causal. We concluded that the current evidence neither substantiates nor excludes a causal association for several reasons, including, but not limited to, the presence of inflating or deflating biases (2). That said, we appreciate the opportunity to discuss the sources of bias raised by Lavigne-Robichaud et al (1). First, it is argued that dichotomizing exposure into "high" and "no-high" job strain deflates risk estimates because a subgroup of the no-high job strain group (passive jobs with low demands and low control) might also be associated with increased risk. However, others have found that results are broadly similar when different non-strain groups are used as reference (3). Thus, at present, the evidence for effects of passive jobs is not strong enough to deviate from the parsimonious use of "all others" as reference. Second, the notion that the pooled risk estimate may be attenuated by sex because women develop IHD at older ages than men is supported by our review indicating slightly lower risk estimates among women. However, the confidence intervals substantially overlap [(2), table 4] and the small difference, if valid, may be due to several other factors and thus considered of minor importance. Third, the use of job-exposure matrices (JEM) is not associated with attenuated risk estimates if the average exposure in the job groups is close to the true average (4). This condition is probably violated in most instances and may lead to attenuated risk estimates if the exposure misclassification is non-differential. However, misclassification may depend on potential confounders (eg, sex, socioeconomic status and psychosocial and lifestyle factors) in ways that inflate or deflate risk estimates. Note also that the JEM studies do not provide the independent assessment of exposure that is needed for stronger conclusions to be drawn. This is because most studies are based on JEM established by population-based questionnaire studies. We consider the lack of independent exposure assessment a major obstacle for causal inference. Fourth, we agree that the prospective cohort study design in principle eliminates recall bias caused by later occurring manifest disease. But it is not obvious that subclinical or early stages of the disease cannot confound the association, potentially leading to inflated risk estimates even in prospective studies (3). Fifth, self-reported psychosocial work exposures are inherently vulnerable to respondents` individual interpretations, particularly when they are asked to rate the intensity or frequency of subjective experiences. We acknowledge the references provided by Lavigne-Robichaud et al, but these studies do not rule out potential confounding by personality (5, 6). The influence of social context, attitudes, life experiences and personality traits remains unresolved and likely constitute bias regardless of study design (7). We are aware that our review may be misused to discourage sound efforts to improve the psychosocial work environment. While this unfortunate risk is inherent to all critical appraisals of the literature, we believe it remains incumbent on researchers to provide the most evidence-based assessments possible so that we can collectively endeavor to improve science. References 1. Lavigne-Robichaud M, Landsbergis P, Brisson C, Sembajwe G, Gilbert-Ouimet M, Li J, Milot A, Trudel X. Job strain and ischemic heart disease: the balance of methodological bias and implications for prevention. Response to: Bonde JP et al. The demands-control-support work stress model and risk of ischemic heart disease: causal inference based on observational epidemiology. Scand J Work Environ Health - online first. https://doi.org/10.5271/sjweh.4315. 2. Bonde JP, Skaaby S, Flachs EM, Dollard M, Keyes K, Rosengren A et al. The demands-control-support work stress model and risk of ischemic heart disease: causal inference based on observational epidemiology. Scand J Work Environ Health 2026 Jul;52(4):360-70. https://doi.org/10.5271/sjweh.4299. 3. Kivimäki M, Nyberg ST, Batty GD, Fransson EI, Heikkilä K, Alfredsson L et al.; IPD-Work Consortium. Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data. Lancet 2012 Oct;380(9852):1491-7. https://doi.org/10.1016/S0140-6736(12)60994-5. 4. Armstrong BG. Effect of measurement error on epidemiological studies of environmental and occupational exposures. Occup Environ Med 1998 Oct;55(10):651-6. https://doi.org/10.1136/oem.55.10.651. 5. Spector PE, O'Connell BJ. The contribution of personality traits, negative affectivity, locus of control and Type A to the subsequent reports of job stressors and job strains. J Occup Organ Psychol 1994;67:1-2. https://doi.org/10.1111/j.2044-8325.1994.tb00545.x. 6. Shipley BA, Weiss A, Der G, Taylor MD, Deary IJ. Neuroticism, extraversion, and mortality in the UK Health and Lifestyle Survey: a 21-year prospective cohort study. Psychosom Med 2007 Dec;69(9):923-31. https://doi.org/10.1097/PSY.0b013e31815abf83. 7. Kasl SV. Measuring job stressors and studying the health impact of the work environment: an epidemiologic commentary. J Occup Health Psychol 1998 Oct;3(4):390-401. https://doi.org/10.1037/1076-8998.3.4.390.},
}

@article {pmid42560011,
year = {2026},
author = {Abrar, F and Martin, DDO},
title = {Molecular switches of SQSTM1: the impact of post-translational modifications on autophagy and neurodegeneration.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/15548627.2026.2711593},
pmid = {42560011},
issn = {1554-8635},
abstract = {SQSTM1/p62 (sequestosome 1) is an important receptor protein involved in many cellular signaling processes, including macroautophagy/autophagy. It is a molecular hub for cellular homeostasis and cellular responses. Within autophagy, SQSTM1 targets ubiquitinated cargo for degradation, maintaining cellular proteostasis. Structurally, SQSTM1 consists of several domains that facilitate its binding to ubiquitinated cargo, the formation of SQSTM1 aggregate inclusions, interactions with MAP1LC3/LC3, and the mediation of clearance via the autophagy pathway. Beyond its structure, post-translational modifications of SQSTM1 dynamically regulate its function within a cell. Post-translational modifications - such as phosphorylation, ubiquitination, acetylation, S-acylation, and S-nitrosylation - are crucial for regulating SQSTM1 function, localization, and interaction with autophagic components, thereby influencing SQSTM1's role in the autophagy pathway. Understanding the role of these protein modifications in modulating autophagy may provide better insight into developing therapeutic strategies for diseases with dysregulated autophagy, such as neurodegenerative diseases. This review will discuss the role of these post-translational modifications in controlling SQSTM1's localization and function in autophagy.Abbreviations: ABHD = α/β-hydrolase domain; AD = Alzheimer Disease; ALS = amyotrophic lateral sclerosis; ATG = autophagy related ; CSNK2/CK2 = casein kinase 2; HD = Huntington Disease; HDAC/KDAC = histone deacetylase/lysine deacetylase; HTT = huntingtin; KAT = lysine acetyltransferase; KEAP1 = kelch like ECH associated protein 1; KIR = KEAP1-interacting region; LIR = LC3-interacting region; LYPLA/APT = lysophospholipase/acyl-protein thioesterase; MAP1LC3/LC3 = microtubule associated protein 1 light chain 3; MEF = mouse embryonic fibroblast; mHTT = mutant huntingtin; MTORC1 = MTOR complex 1; NBR1 = NBR1 autophagy cargo receptor; NEDD4 = NEDD4 E3 ubiquitin protein ligase ; NO = nitric oxide; NFE2L2/Nrf2 = nuclear factor erythroid 2-factor 2; PAT = palmitoyl acyltransferase; PB1 = Phox-BEM1 domain; PE = phosphatidylethanolamine; PLEKHM1 = pleckstrin homology and RUN domain containing M1; PLK2 = polo like kinase 2; PRKA/PKA = protein kinase cAMP-activated; PPT1 = palmitoyl-protein thioesterase 1; RB1CC1 = RB1 inducible coiled-coil 1; SNCA/α-synuclein = synuclein alpha; SNO = S-nitrosothiol; SOD1 = superoxide dismutase 1; SQSTM1 = sequestosome 1; TARDBP/TDP-43 = TAR DNA binding protein ; TBK1 = TANK binding kinase 1; TAX1BP1 = Tax1 binding protein 1; TRIM = tripartite motif containing ; UBA = ubiquitin-associated domain; UBE = ubiquitin-conjugating enzyme; ULK1 = unc-51 like autophagy activating kinase 1; UPS =ubiquitin-proteasome system; USP8 = ubiquitin specific peptidase 8; ZDHHC = zDHHC palmitoyltransferase.},
}

@article {pmid42560418,
year = {2026},
author = {León-Ruiz, M and Castañeda-Cabrero, C and Benito-León, J},
title = {Response to "Palpebral ptosis as the initial symptom of amyotrophic lateral sclerosis": the potential usefulness of cortical excitability and motor band sign as biomarkers of upper motor neuron degeneration.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {9},
pages = {},
pmid = {42560418},
issn = {1590-3478},
}

@article {pmid42561134,
year = {2026},
author = {Ehn, E and Thonberg, H and Nennesmo, I and Lindstrand, A and Kvarnung, M and Graff, C},
title = {Clinical genome sequencing in neurodegenerative diseases-outcome in the first 500 patients.},
journal = {Human molecular genetics},
volume = {35},
number = {16},
pages = {},
doi = {10.1093/hmg/ddag072},
pmid = {42561134},
issn = {1460-2083},
mesh = {Humans ; *Whole Genome Sequencing/methods ; *Neurodegenerative Diseases/genetics/diagnosis ; Amyotrophic Lateral Sclerosis/genetics/diagnosis ; Female ; C9orf72 Protein/genetics ; DNA Copy Number Variations/genetics ; Male ; Middle Aged ; Alzheimer Disease/genetics/diagnosis ; Genetic Predisposition to Disease ; Frontotemporal Dementia/genetics/diagnosis ; Aged ; DNA Repeat Expansion/genetics ; Adult ; Polymorphism, Single Nucleotide ; Phenotype ; },
abstract = {Neurodegenerative diseases (NDDs) are clinically and genetically heterogeneous, requiring neuropathology or molecular testing for a definitive diagnosis. Clinical whole genome sequencing (WGS) enables comprehensive variant calling across flexible gene lists that can be tailored to the clinical presentation. By allowing simultaneous detection of single-nucleotide variants, copy-number variants, structural variants, and repeat expansions, WGS has the potential to improve diagnostic yield, facilitate genetic counseling and support clinical trial inclusion. This study assesses the diagnostic performance of WGS in individuals with NDD. WGS in 500 individuals representing a wide spectrum of NDDs identified a disease-causing variant in 61 cases, resulting in a diagnostic yield of 12%. These variants were found in 16 different genes, with C9orf72 being the most prevalent. Repeat expansions represented the largest variant class, accounting for 35 of 61 LP/P cases (57%); most of which were C9orf72 expansions (31/35). In the largest phenotype groups, frontotemporal dementia (FTD) had the highest diagnostic yield (19%) followed by amyotrophic lateral sclerosis (ALS, 13%), whereas an underlying monogenic cause was expectedly low in Alzheimer disease (AD, 4%). A positive family history was present in the majority (74%) of FTD, ALS, combined ALS-FTD and AD cases with an LP/P finding. Clinical WGS provides a clear diagnostic advantage in NDDs marked by substantial clinical and genetic overlap. WGS enables comprehensive variant detection and mapping of genotype-phenotype relationships across the disease continuum. In FTD and ALS, these results support universal access to genetic testing independent of age at onset or family history.},
}

Humans
*Whole Genome Sequencing/methods
*Neurodegenerative Diseases/genetics/diagnosis
Amyotrophic Lateral Sclerosis/genetics/diagnosis
Female
C9orf72 Protein/genetics
DNA Copy Number Variations/genetics
Male
Middle Aged
Alzheimer Disease/genetics/diagnosis
Genetic Predisposition to Disease
Frontotemporal Dementia/genetics/diagnosis
Aged
DNA Repeat Expansion/genetics
Adult
Polymorphism, Single Nucleotide
Phenotype

@article {pmid42557952,
year = {2026},
author = {Acharya, A and Thurman, M and Sutar, D and Olasunkanmi, OI and Malik, JR and Dyavar, SR and Végvári, Á and Byrareddy, SN},
title = {In-Vitro Evaluation of HIV/SARS-CoV-2 Co-Infection Mediated Proteomic Changes in Astrocytes and Pericytes Reveals Altered Signaling Pathways Associated With Neurodegenerative Disorders.},
journal = {Journal of medical virology},
volume = {98},
number = {8},
pages = {e71086},
pmid = {42557952},
issn = {1096-9071},
support = {R01DA05284/NH/NIH HHS/United States ; R01DA061678/NH/NIH HHS/United States ; },
mesh = {*Pericytes/virology/metabolism ; *Astrocytes/virology/metabolism ; Humans ; *Signal Transduction ; *HIV Infections/metabolism/complications/virology ; *SARS-CoV-2/physiology ; *Coinfection/virology/metabolism ; *Neurodegenerative Diseases/metabolism/virology ; *COVID-19/metabolism/complications/virology ; Proteomics ; Microglia/virology/metabolism ; Post-Acute COVID-19 Syndrome ; Virus Replication ; Proteome ; },
abstract = {Coronavirus disease 2019 (COVID-19) survivors frequently experience a wide range of symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID. Importantly, complications arising from microvascular dysfunction, blood-brain barrier (BBB) disruption, and chronic neuroinflammation have been implicated in driving PASC within the central nervous system (CNS), known as neuro-PASC. Notably, people with HIV (PWH), who suffer from chronic neuroinflammation, BBB impairment, and glial cell dysfunction, collectively known as neuro-HIV, are generally at higher risk of neuro-PASC. The overlap between neuro-PASC and neuro-HIV raises concerns that HIV and SARS-CoV-2 co-infection may exacerbate neurological dysfunctions among PWH. In this study, using an in-vitro cell culture model, we examine the effects of HIV and SARS-CoV-2 mono- and co-infection in microglia, astrocytes, and pericytes. Our results demonstrated that majority of brain cell types support SARS-CoV-2 replication, in the presence and absence of HIV infection. Furthermore, in both mono- and co-infected cells, there were varying degree of up- and downregulation of SARS-CoV-2 host cell entry factors, such as ACE2, TMPRSS2, NRP1, and TRIM28, and inflammatory cytokines including IL-6, TNF-α, and IL-1β. Moreover, conditioned media collected from HIV, SARS-CoV-2, and HIV/SARS-CoV-2 co-infected astrocytes and pericytes were shown to be neurotoxic. Additionally, proteomic analysis has revealed a unique set of proteins significantly up/down regulated in HIV/SARS-CoV-2 co-infected astrocytes and pericytes. The gene set enrichment analysis of these proteins indicates dysregulation of lipid, energy, and immune metabolism pathways linked to neurodegenerative disorders like Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis. These in-vitro findings indicate that astrocytes and pericytes from HIV/SARS-CoV-2 co-infection exhibit altered protein expression profiles, implicating dysregulated signaling pathways associated with neurodegenerative dysfunction.},
}

*Pericytes/virology/metabolism
*Astrocytes/virology/metabolism
Humans
*Signal Transduction
*HIV Infections/metabolism/complications/virology
*SARS-CoV-2/physiology
*Coinfection/virology/metabolism
*Neurodegenerative Diseases/metabolism/virology
*COVID-19/metabolism/complications/virology
Proteomics
Microglia/virology/metabolism
Post-Acute COVID-19 Syndrome
Virus Replication
Proteome

@article {pmid42558399,
year = {2026},
author = {Okethwangu, D and Venkateswaran, M and Ario, AR and Nabatanzi, S and Asio, E and Ocom, F and Okot, CL and Nyisomeh, A and Nankabirwa, V and Rutebemberwa, E and Mayega, RW and Kiwanuka, SN},
title = {Resilience as recovery: stakeholder perspectives on Uganda's health system response to infectious disease shocks.},
journal = {Frontiers in health services},
volume = {6},
number = {},
pages = {1888814},
pmid = {42558399},
issn = {2813-0146},
abstract = {BACKGROUND: The conceptualization, definition, and measurement of health system resilience remain contested, hindering policy integration. Country-specific empirical evidence from sub-Saharan Africa, where infectious disease shocks recur, is limited. This study explored how national-level Ugandan stakeholders conceptualize health system resilience to infectious disease shocks and its attributes.

METHODS: We conducted a descriptive exploratory qualitative study using semi-structured key informant interviews with 15 purposively selected national-level stakeholders from the Ministry of Health, academia, and development and implementing partners between May and July 2025. Data were analyzed using a hybrid deductive-inductive (abductive) thematic analysis approach, drawing on Kruk et al.'s and the WHO's resilience frameworks while remaining open to emergent themes. Reporting follows the Consolidated Criteria for Reporting Qualitative Research (COREQ).

RESULTS: Participants conceptualized resilience across five capacities: preparedness, absorptive, adaptive, transformative, and recovery. Recovery-dominated narratives prevailed, while transformative capacity was least articulated, indicating a system oriented toward "bouncing back" rather than reform: A resilient system in Uganda is one that anticipates and prepares for infectious disease shocks; absorbs them while sustaining essential services; adapts through innovation and operational adjustment; recovers core functioning; and institutionalizes learning to transform structures, financing, and service delivery models in preparation for future shocks. Seven interconnected attributes were identified: (1) governance and leadership, (2) preparedness, (3) service delivery, (4) community involvement, (5) adaptability, (6) collaboration and partnerships, and (7) soft skills. Governance and leadership emerged as foundational; preparedness, service delivery, community involvement, adaptability, and collaboration as structural; and soft skills (trust, communication, cultural sensitivity) as relational enablers.

CONCLUSIONS: From the perspective of national-level actors, Uganda's health system is predominantly reactive, with recovery prioritized over transformation. Strengthening resilience requires institutionalizing learning, anticipatory financing, empowered subnational structures, and multisectoral partnerships. Future research should triangulate these perspectives with subnational, frontline, and community voices.},
}

@article {pmid42558527,
year = {2026},
author = {Li, S and Cao, T and Zhang, Q},
title = {Oxidative stress as a driver of organelle cascade damage in neurological diseases.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1892923},
pmid = {42558527},
issn = {1663-4365},
abstract = {As a core driver in the pathological progression of neurological diseases, oxidative stress contributes to the onset and development of multiple disorders, including traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), by inducing interconnected and bidirectional damage among mitochondria, endoplasmic reticulum, lysosomes, and the nucleus. This review systematically summarizes the oxidative stress-mediated inter-organelle crosstalk network: Mitochondria act as one of the earliest and central hubs, and their dysfunction (e.g., reactive oxygen species burst, calcium overload, and respiratory chain impairment) induces endoplasmic reticulum stress via ROS diffusion and calcium signaling disturbance. The disruption of endoplasmic reticulum calcium homeostasis further exacerbates mitochondrial damage, forming a vicious cycle. Lysosomes exhibit reduced membrane stability and impaired autophagic flux under oxidative stress, failing to clear damaged organelles and aggravating oxidative stress accumulation. Ultimately, oxidative stress signals are transmitted to the nucleus, resulting in DNA damage, aberrant epigenetic modifications, and activation of pro-inflammatory/pro-apoptotic genes, thereby accelerating disease progression. Notably, this organelle injury transmission is not a rigid unidirectional linear cascade; primary lysosomal or MAM defects can independently initiate the full organelle damage loop without preceding mitochondrial dysfunction. This review integrates current studies, clarifies context-dependent and disease-specific characteristics of organelle interactions, and discusses potential therapeutic strategies with critical consideration of translational challenges and limitations, providing a theoretical foundation for mechanistic research and clinical intervention of neurological diseases.},
}

@article {pmid42558984,
year = {2026},
author = {Pourasghari, M and Babaie, S and Markazi-Movaghar, R and Salehpour, S and Eftekharsadat, B and Farshbaf-Khalili, A},
title = {The Effectiveness Based on Optimal Dose and Administration Route, and Safety Profiles of Stem Cells and Derived Products in the Treatment of Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.},
journal = {Stem cells international},
volume = {2026},
number = {},
pages = {4122493},
pmid = {42558984},
issn = {1687-966X},
abstract = {BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effectiveness of stem cell therapies for patients with amyotrophic lateral sclerosis (ALS) based on optimal dosing and administration routes, as well as the safety profiles of stem cells and their derived products.

METHODS: The review followed PRISMA guidelines and involved a comprehensive literature search up to October 2025, receiving ethical approval from Tabriz University of Medical Sciences and registration in PROSPERO. It utilized international databases, including PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ProQuest, ClinicalTrials.gov, and Science Direct. The included studies comprised randomized controlled trials (RCTs), quasi-experimental studies, and other interventional designs involving ALS patients treated with stem cell therapies. In total, 31 studies were analyzed, featuring 7 controlled trials with 370 participants and 24 non-controlled pre-post studies with 460 participants. Heterogeneity was evaluated using I [2] statistics, and subgroup analyses were conducted based on treatment duration and dosing.

RESULTS: A pooled analysis (treatment group: n = 93; control group: n = 90) demonstrated a significant attenuation in the progression of disease severity, as measured by the ALS Functional Rating Scale (ALSFRS), in stem cell groups versus controls (weighted mean difference [WMD]: 8.89 95% CI: 4.12-13.67; p = 0.0003), which was beneficial for both the ≥10 × 10[6] and <10 × 10[6] dose sub-groups. However, a meta-analysis of single-arm studies in two control (pre-intervention) and intervention phases (n = 88) demonstrated no significant difference in progression of ALSFRS between study phases by time: month 3 (WMD: -1.27 (-3.01 to 0.47); p = 0.15), month 6 (WMD: -2.69 (-5.62 to 0.25); p = 0.07), month 9 (WMD: -1.55 (-3.49 to 0.39); p = 0.12), and month 12 (WMD: -7.59 (-13.95 to -1.26); p = 0.02). An accelerated decline in forced vital capacity (FVC) was observed during the intervention phase, with statistically significant reductions at month 3 (WMD: -10.91; 95% CI: -16.39 to -5.43; p < 0.0001) and month 6 (WMD: -15.97; 95% CI: -28.60 to -3.33; p = 0.01) compared with the pre-intervention control phase. Nevertheless, sensitivity analyses excluding studies involving high-dose mesenchymal stem cell (MSC) therapies demonstrated that these differences were no longer statistically significant. Moreover, no significant change in progression rate was observed at month 9 (WMD: -8.10 (-18.25 to 2.06); p = 0.12). The route of MSCs administration (intrathecal [IT], intramuscular [IM], and intravenous [IV]) had no effect on the results of ALSFRS and FVC, reinforced by sensitivity analyses. Adverse events were mostly mild, with headaches most frequent in high-dose groups.

CONCLUSION: Stem cell therapy for ALS appears to be safe, with preliminary evidence suggesting potential therapeutic benefit in slowing disease progression in selected patients. Nevertheless, the existing evidence base remains exploratory, and definitive conclusions regarding clinical effectiveness cannot yet be drawn. Future research should prioritize large-scale and multicenter RCTs with standardized cell manufacturing protocols and longer follow-up periods.},
}

@article {pmid42559389,
year = {2026},
author = {Murray, G and Dupuis, M and Hagan, J and Laroche, M and Peters, J},
title = {Arbeitnehmer:innen als Klima-Akteure: Was können Gewerkschaften gegen den Klimawandel unternehmen? Einleitung.},
journal = {Transfer (Brussels, Belgium)},
volume = {32},
number = {2},
pages = {141-151},
doi = {10.1177/10242589261467970},
pmid = {42559389},
issn = {1024-2589},
}

@article {pmid42314945,
year = {2026},
author = {Goldberg, MS and Lebwohl, MG},
title = {Response to Baharuddin et al.'s Comment on ''The 487-gene expression profile test guides systemic therapy selection to improve outcomes for patients with atopic dermatitis: Results from a prospective trial''.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.06.061},
pmid = {42314945},
issn = {1097-6787},
}

@article {pmid42551425,
year = {2026},
author = {Petrescu, J and Gouveia Roque, C and Jackson, CA and Daly, AC and Butti, Z and Kang, K and Casel, O and Leung, M and Reilly, L and Eschbach, J and Gebremedhin, B and McDade, K and Gregory, JM and Bonneau, R and Smith, C and Phatnani, H},
title = {Distinct cellular phenotypes of language and executive decline in amyotrophic lateral sclerosis.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2026.07.008},
pmid = {42551425},
issn = {1097-4172},
abstract = {Cognitive manifestations, including impairments in language and executive functions, are seen in amyotrophic lateral sclerosis (ALS), but the underlying mechanisms remain unclear. We mapped prefrontal cortex regions from ALS patients by integrating spatial and single-nucleus transcriptomics in a cognitively stratified patient cohort. We uncover that cognitive impairment in ALS is associated with distinct patterns of neuronal dysfunction and glial-vascular dysregulation that vary by region and cognitive subtype. Executive dysfunction is linked to reduced mitochondrial and synaptic activity in deep-layer dorsolateral prefrontal cortex neurons, whereas language-related deficits track with a diffuse pan-regional response involving glial and vascular abnormalities. Our analyses, validated by multiplexed imaging, further identify signatures in the prefrontal cortex that span both motor and cognitive phenotypes, including a multicellular gliosis response. The findings reveal that clinical heterogeneity in ALS is driven by phenotype-specific cellular interactions in motor and non-motor regions of the brain.},
}

@article {pmid42551655,
year = {2026},
author = {Toyama, G and Koide, S and Yamagishi, T and Washida, A and Hanyu, R and Onodera, O and Sugai, A},
title = {Persistent export bias of TDP-43 under native autoregulation links insoluble accumulation to nuclear dysfunction.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107560},
doi = {10.1016/j.nbd.2026.107560},
pmid = {42551655},
issn = {1095-953X},
abstract = {Nuclear depletion and cytoplasmic mislocalization of TDP-43 are central pathological features of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. TDP-43 protein levels are normally maintained by autoregulation through its native 3' untranslated region (3' UTR), but whether this feedback remains protective during chronic cytoplasmic bias is unclear. To address this, we engineered full-length human TDP-43 carrying an N-terminal nuclear export signal (NES) while retaining the native 3' UTR autoregulatory module. In HEK293T cells, NES insertion imposed cytoplasmic bias and promoted detergent-insoluble TDP-43 species. In differentiated SH-SY5Y cells, nuclear splicing defects and autoregulatory changes scaled with export-biased load; detergent-insoluble accumulation was already detectable within a low-load range, defined by whole-cell RIPA-soluble exogenous TDP-43 ≤ 30% of endogenous levels. Human iPSC-derived neurons showed a comparable cytoplasmic shift, discrete TDP-43-immunoreactive foci, and TDP-43-dependent splicing defects. Endogenous TARDBP depletion provided a functional rescue test: nuclear-competent WT-TDP-43-3' UTR restored TDP-43-dependent nuclear readouts, whereas NES-TDP-43-3' UTR did not. In the NES condition, weakened autorepression increased transgene-derived TARDBP transcripts, but the added output failed to expand the soluble, splice-competent pool and instead partitioned into insoluble fractions. Increasing soluble NES-TDP-43 to endogenous-equivalent levels likewise did not normalize splicing, indicating that abundance alone is insufficient when output remains export-biased. These findings support a model in which persistent export bias converts native TARDBP autoregulation into maladaptive feedback: compensatory output is uncoupled from productive nuclear recovery and diverted toward cytoplasmic insoluble/fragmented species.},
}

@article {pmid42551865,
year = {2026},
author = {Dalle, S and Vanderbeke, K and Burg, T and Schouten, M and Lauriks, W and Hersmus, N and Van Den Bosch, L and Koppo, K},
title = {Early and Divergent Lipid Mediator Remodelling in Fast Versus Slow Skeletal Muscles of Female hSOD1[G93A] Mice.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {17},
number = {4},
pages = {e70357},
pmid = {42551865},
issn = {2190-6009},
support = {G086823N//Fonds Wetenschappelijk Onderzoek/ ; 12Z8622N//Fonds Wetenschappelijk Onderzoek/ ; 11PRA24N//Fonds Wetenschappelijk Onderzoek/ ; PDMt1/24/001//Onderzoeksraad, KU Leuven or KU Leuven Research Council/ ; },
mesh = {Animals ; Female ; Mice ; Mice, Transgenic ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Muscle, Skeletal/metabolism/pathology ; Endocannabinoids/metabolism ; Disease Models, Animal ; *Superoxide Dismutase-1/genetics ; *Lipid Metabolism ; *Muscle Fibers, Slow-Twitch/metabolism ; },
abstract = {BACKGROUND: Skeletal muscle atrophy in amyotrophic lateral sclerosis (ALS) drives loss of muscle strength, function and quality of life in ALS patients. The endocannabinoid system (ECS) regulates muscle homeostasis via regenerative and metabolic processes, and although ECS alterations have been reported in ALS neural tissues, ECS remodelling within ALS skeletal muscle has never been studied. This study investigated temporal and muscle type-specific ECS changes in ALS.

METHODS: Female hSOD1[G93A] transgenic mice and nontransgenic littermates were studied at presymptomatic and symptomatic ages (56-138 days of age; n = 7-8/group). Endocannabinoids, N-acyl-ethanolamine congeners and inflammatory lipid mediators were quantified using targeted LC-MS/MS in the tibialis anterior (TA) and soleus (SOL) muscles. ECS-related enzymes and receptors were assessed by immunoblotting and integrated with transcriptomic analyses of skeletal muscle biopsies from ALS patients (n = 5/group; ~63 years). To evaluate therapeutic relevance, ALS mice were treated with the fatty acid amide hydrolase (FAAH) inhibitor URB937 or vehicle (n = 10-11/group), and survival, body weight, welfare and motor function were assessed longitudinally.

RESULTS: ALS caused severe atrophy in the predominantly fast-twitch TA muscle (-76.5%; p < 0.01), while the slow-twitch soleus was largely preserved (-14.4%; p < 0.01). Accordingly, the lipid perturbation due to ALS was more pronounced in the TA, reflected by extensive alterations in unsaturated fatty acids, hydroxy- and epoxy-fatty acids (TA: 63% and SOL: 22% of lipid mediators different between ALS vs. NTG) and marked ECS remodelling, including elevated anandamide (+37.3%; p = 0.03) and multiple N-acyl-ethanolamine congeners (+76-102%; p < 0.05), reduced 2-arachidonoylglycerol (-28%; p = 0.06), increased CB1 receptor expression (+93%; p < 0.01) and dynamic, age-dependent regulation of FAAH (presymptomatic: -68%; p = 0.04, symptomatic: +21%; p = 0.02). In contrast, the SOL showed modest or opposite changes, consistent with its relative resistance to atrophy. Notably, ECS remodelling in the TA was already evident at presymptomatic age (e.g., CB1: +76%; p = 0.01) and the same ECS enzymes were affected in human ALS skeletal muscle transcriptomes (e.g., twofold decrease in FAAH; pFDR = 0.010). Despite evidence for a therapeutic potential, chronic peripheral FAAH inhibition with URB937 did not improve weight loss, motor functions and survival of ALS mice (all p > 0.05).

CONCLUSIONS: Muscle type-specific endocannabinoid system remodelling in ALS precedes overt neurological decline and might relate to degenerative features such as metabolic disturbance and inflammation. Although peripheral FAAH inhibition alone was insufficient to modify disease outcomes, these findings identify the endocannabinoid system as an integral component of ALS muscle pathology and support skeletal muscle lipid signalling as a potentially relevant early target for adjunctive therapeutic strategies.},
}

Animals
Female
Mice
Mice, Transgenic
*Amyotrophic Lateral Sclerosis/metabolism/pathology
Humans
*Muscle, Skeletal/metabolism/pathology
Endocannabinoids/metabolism
Disease Models, Animal
*Superoxide Dismutase-1/genetics
*Lipid Metabolism
*Muscle Fibers, Slow-Twitch/metabolism

@article {pmid42552039,
year = {2026},
author = {Venu, G and A, VP and Justin, A},
title = {Molecular insights of peroxisome proliferator-activated receptor-γ signalling in amyotrophic lateral sclerosis and Huntington's disease.},
journal = {International review of neurobiology},
volume = {188},
number = {},
pages = {113-143},
doi = {10.1016/bs.irn.2026.05.014},
pmid = {42552039},
issn = {2162-5514},
mesh = {Humans ; *PPAR gamma/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *Signal Transduction/physiology ; Animals ; *Huntington Disease/metabolism ; },
abstract = {Progressive neuronal loss is a hallmark of neurodegenerative diseases like Huntingtons disease (HD) and Amyotrophic lateral sclerosis (ALS) which are caused by convergent mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy and dysregulated cell death pathways. Both conditions share significant disruptions in metabolic and inflammatory signalling despite having different genetic origins and clinical manifestations; underscoring the necessity of pathway-oriented treatment approaches. In the central nervous system, peroxisome proliferator-activated receptor-γ (PPAR-γ), a ligand-activated nuclear receptor has become an important regulator of inflammation, redox homeostasis, mitochondrial biogenesis and cellular stress responses. After giving a thorough overview of PPAR-γ structure activation and transcriptional regulation and the PGC-1α-mediated mitochondrial biogenesis axis, this chapter delves deeply into its interactions with major signalling pathways such as NF-κB, Wnt/β-catenin Nrf2/ARE and the autophagy-apoptosis networks. With a focus on experimental data showing PPAR-γ signaling's neuroprotective, anti-inflammatory, antioxidant and metabolic regulatory roles the pathophysiology of ALS and HD is critically investigated. Lastly the need for improved biomarkers, tailored multi-target strategies and selective modulators is highlighted in the discussion of current therapeutic limitations and translational difficulties.},
}

Humans
*PPAR gamma/metabolism
*Amyotrophic Lateral Sclerosis/metabolism
*Signal Transduction/physiology
Animals
*Huntington Disease/metabolism

@article {pmid42552041,
year = {2026},
author = {Khodve, G and Raval, S and Banerjee, S},
title = {Intestinal microbiota in neurodegeneration and ageing: Mechanisms, pathways, and therapeutic interventions.},
journal = {International review of neurobiology},
volume = {188},
number = {},
pages = {199-229},
doi = {10.1016/bs.irn.2026.05.015},
pmid = {42552041},
issn = {2162-5514},
mesh = {Humans ; *Neurodegenerative Diseases/microbiology/metabolism/immunology/diet therapy/therapy ; *Aging/metabolism/immunology ; *Gastrointestinal Microbiome/physiology ; Animals ; *Dysbiosis/metabolism/immunology ; *Brain-Gut Axis/physiology ; Probiotics ; Brain/metabolism ; },
abstract = {The human gut microbiota represents a complex ecosystem of trillions of microorganisms with profound implications for neurological health. Emerging evidence demonstrates that dysbiosis, an imbalance in microbial composition and function, plays a crucial role in the pathogenesis of neurodegenerative diseases and age-related cognitive decline. This chapter summarizes current knowledge of the microbiota-gut-brain axis (MGBA) and elucidates how intestinal microbes and their metabolites communicate with the central nervous system via neural, immune, endocrine, and metabolic pathways. We examine the mechanistic links between gut dysbiosis and specific neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Multiple sclerosis (MS). Furthermore, we explore age-related changes in the microbiota and their contributions to neuroinflammation, immunosenescence, and cognitive decline. Finally, we evaluate therapeutic interventions targeting the microbiota, including probiotics, prebiotics, synbiotics, and dietary modulation as promising strategies to prevent and ameliorate neurodegenerative pathology. The chapter provides a comprehensive summary of how microbiota-targeted approaches may delay ageing and neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/microbiology/metabolism/immunology/diet therapy/therapy
*Aging/metabolism/immunology
*Gastrointestinal Microbiome/physiology
Animals
*Dysbiosis/metabolism/immunology
*Brain-Gut Axis/physiology
Probiotics
Brain/metabolism

@article {pmid42552132,
year = {2026},
author = {Labrèche, F and Prud'homme, P and Gagnon, M and Dupré, N and Gravel, S},
title = {Occupational exposure to pesticides increases the risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Occupational and environmental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1136/oemed-2025-110662},
pmid = {42552132},
issn = {1470-7926},
abstract = {OBJECTIVE: To systematically review the evidence on the association between occupational exposure to pesticides and the risk of amyotrophic lateral sclerosis (ALS).

METHODS: A systematic search, conducted in eight bibliographic databases for publications between 1990 and 2025, identified observational studies estimating the risk of ALS after occupational pesticide exposure. Study quality was assessed using the WHO Risk of Bias (RoB) assessment instrument for systematic reviews, with the ROBINS-E (RoB in non-randomised studies of exposure) tool domains of bias. Pooled risk estimates were produced using random-effects models with restricted maximum likelihood, heterogeneity was assessed with I² statistics, and meta-regressions and publication bias explored with funnel plots and Egger's test.

RESULTS: Eight case-control studies (1734 cases) were retained for meta-analysis from 767 initially screened articles. 'Ever' occupational exposure to pesticides was associated with an increased risk of ALS (n=6 studies, pooled OR (pOR)=1.6; 95% CI 1.1, 2.2; I²=57%), for combined sexes. The risk for exposure to herbicides was slightly greater (pOR=1.7, I[2]=0.0%) than for exposure to insecticides or fungicides (pORs=1.6, I[2]=0.0%). Based on three studies, ever exposure to high levels of pesticides was associated with a higher risk (pOR=2.7; 95% CI=1.4, 5.0) than exposure to low levels (pOR=1.9; 95% CI=1.0, 3.7). Self-reported exposure assessment methods and older publication dates (<2015) were statistically significant predictors of the effect size.

CONCLUSION: Despite the small number of studies and some heterogeneity, our results add to the evidence suggesting that occupational exposure to pesticides may increase the risk of ALS.},
}

@article {pmid42552521,
year = {2026},
author = {Aradhya, L and Lath, V and Sirur, FM and Balakrishnan, JM and Hebbar, A and Shetty, AK},
title = {Evaluation of safety, comfort, and design ergonomics in ambulance retrieval vehicles: a survey in Southern India.},
journal = {International journal of emergency medicine},
volume = {19},
number = {1},
pages = {},
pmid = {42552521},
issn = {1865-1372},
abstract = {BACKGROUND: Ambulance interior design influences the safety, comfort, and operational efficiency of Emergency Medical Services (EMS) personnel. However, evidence regarding ergonomic challenges faced by EMS providers in the Indian prehospital setting remains limited.

OBJECTIVE: To evaluate EMS personnel perspectives on ambulance ergonomics, safety, comfort, and factors affecting patient care during transport.

METHODS: A multicentre, cross-sectional survey-based observational study was conducted among Emergency Medical Technologists (EMTs) and paramedics, recruited by convenience sampling, who were involved in patient transport using standard Advanced Life Support (ALS) ambulances across Southern India. Data on ergonomic challenges, safety concerns, occupational injuries, and patient-care factors were collected using a questionnaire developed from existing literature and refined through focused-group discussion and expert content review. Data were analysed using descriptive statistics and chi-square tests in jamovi.

RESULTS: A total of 130 EMS providers participated. Limited patient-cabin space (60%) and difficulty accessing equipment (50%) were the most frequently reported factors affecting safety and comfort. Half of the respondents reported concerns regarding EMT seat positioning during patient care. Uneven roads (49.23%) and sudden vehicle breakdowns (41.53%) were the leading causes of transport-related injuries. CPR was the procedure most commonly associated with injuries to the care giver (53.84%), while back pain was the predominant occupational health hazard (57.69%). Significant associations were observed between work experience and perceptions of ambulance ergonomics, injury mechanisms, patient safety concerns, and occupational health hazards (p < 0.05).

CONCLUSION: EMS personnel reported substantial concerns regarding ambulance ergonomics, particularly seat positioning, equipment accessibility, cabin workspace, and occupational safety. These findings emphasize the importance of further ergonomic research in ambulance design to enhance operational ease during in transit care while assuring provider and patient safety.},
}

@article {pmid42553257,
year = {2026},
author = {Ammar, FI and Aljahdali, E and Alshrif, A and Alshareef, A and Faidah, D and Almohammadi, M and Makkawi, S},
title = {Association of therapeutic plasma exchange with functional outcomes in selected neurological disorders: a retrospective cohort study from a single tertiary center in Saudi Arabia.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1876331},
pmid = {42553257},
issn = {1664-2295},
abstract = {BACKGROUND: Neurological disorders are associated with considerable morbidity and healthcare impact. Therapeutic plasma exchange (TPE) is an intervention that removes pathogenic antibodies, immune complexes, and other plasma constituents from circulation. Previous studies have suggested that TPE could be associated with improved outcomes in selected neurological disorders.

OBJECTIVES: To evaluate functional outcomes following therapeutic plasma exchange in patients with selected neurological disorders at National Guard Health Affairs (NGHA) in Jeddah, Saudi Arabia.

METHODS: This retrospective cohort study analyzes 133 patients diagnosed with various neurological disorders who received TPE between August 2015 and December 2022 at NGHA. Diagnoses included multiple sclerosis (MS), myasthenia gravis (MG), Guillain-Barré syndrome (GBS), neuromyelitis optica spectrum disorder (NMOSD), chronic inflammatory demyelinating polyneuropathy (CIDP), autoimmune encephalitis (AE), and other neurological conditions including amyotrophic lateral sclerosis (ALS), transverse myelitis, cerebellar ataxia, paraneoplastic neurologic syndrome, polymyositis, and central nervous system (CNS) infections. The effectiveness of TPE was assessed using the Modified Rankin Scale (mRS) before and 90 days following the final TPE session. Statistical analysis included Wilcoxon signed-rank tests and Mann-Whitney U test, with significance set at (p < 0.05).

RESULTS: Significant improvements in mRS scores were observed following TPE for MS, MG, and GBS (all p < 0.001), as well as for NMOSD (p = 0.008), CIDP (p = 0.007), and AE (p = 0.018), but not in other neurological disorders (p = 0.234). Overall mortality was 6.8%, with no TPE-related deaths. Comorbidities among deceased patients included hypertension, diabetes mellitus, malignancy, chronic kidney disease, and cardiovascular disease.

CONCLUSION: TPE was associated with improved functional outcomes in selected neurological disorders. Comorbidities were common among patients with poorer outcomes. Due to the retrospective design and potential confounding factors, causal inferences cannot be established. Further prospective studies are warranted to evaluate the role of TPE and optimize patient selection.},
}

@article {pmid42553297,
year = {2026},
author = {Li, Q and You, M},
title = {Targeting mitochondria for the treatment of neurodegenerative diseases.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1835506},
pmid = {42553297},
issn = {1662-4548},
abstract = {Mitochondria are central regulators of cellular metabolism, redox balance, calcium signaling, and cell survival, making them essential for neuronal function. Because neurons rely heavily on mitochondrial oxidative phosphorylation to meet their high energetic demands, mitochondrial dysfunction has emerged as a key pathogenic driver in major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Defects in mitochondrial bioenergetics, excessive reactive oxygen species production, impaired mitochondrial dynamics, disrupted mitophagy, and dysregulated calcium handling collectively contribute to neuronal damage, synaptic dysfunction, and neuroinflammation. These insights have prompted growing interest in therapeutic strategies that directly target mitochondria to restore organelle homeostasis. Recent advances in chemical biology and nanomedicine have enabled the development of mitochondria-targeted ligands, peptide-based targeting systems, and carrier or nanotechnology-enabled delivery platforms designed to overcome biological barriers and selectively deliver therapeutic cargos to mitochondria within the central nervous system. In this Review, we summarize mitochondrial pathological mechanisms in neurodegenerative diseases and discuss emerging mitochondria-targeted therapeutic strategies, highlighting delivery technologies, therapeutic modalities, and translational challenges. Although most strategies remain at the preclinical or proof-of-principle stage, these advances are beginning to shape a conceptual framework for precision mitochondrial medicine, with the longer-term goal of developing disease-modifying interventions for neurodegenerative disorders.},
}

@article {pmid42554090,
year = {2026},
author = {Silva, STD and de Souza, AA and de Melo, LP and de Oliveira Cacho, R and de Holanda, LJ and Ortiz, LDN and Dourado Júnior, MET and Farias, IB and Gonçalves, F and Nagem, DAP and de Medeiros Valentim, RA and Lindquist, ARR and Ribeiro, TS},
title = {Evidence-based physiotherapy recommendations for the management of motor aspects in amyotrophic lateral sclerosis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/17582024.2026.2713034},
pmid = {42554090},
issn = {1758-2032},
abstract = {AIM: To provide evidence-based recommendations for the physiotherapy management of Amyotrophic Lateral Sclerosis (ALS).

MATERIALS AND METHODS: Evidence-based recommendations were developed by a multidisciplinary team, including PhDs and master's-level researchers, physicians, and experienced physiotherapists specializing in neurological rehabilitation.

RESULTS: After the selection process, 23 studies were included. Eighteen recommendations addressing motor aspects in ALS were formulated.

CONCLUSIONS: Therapeutic exercise should be considered to improve or maintain ALSFRS-R scores in people with ALS. However, the effects of other interventions examined in this study remain uncertain with respect to motor aspects.},
}

@article {pmid42554285,
year = {2026},
author = {Benussi, A and Bracca, V and Premi, E and Cantoni, V and Palacino, F and Saccavini, A and Cotelli, MS and Binetti, G and Manenti, R and Alberici, A and Gasparotti, R and Ashton, NJ and Zetterberg, H and Blennow, K and Ghidoni, R and Borroni, B},
title = {Temporal order of clinical, imaging, and biomarker changes in frontotemporal lobar degeneration-associated syndromes.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71722},
pmid = {42554285},
issn = {1552-5279},
support = {//University of Brescia, Italy/ ; //Italian Ministry of Health (Ricerca Corrente)/ ; },
mesh = {Humans ; Female ; *Biomarkers/blood ; Male ; Magnetic Resonance Imaging ; *Frontotemporal Lobar Degeneration/pathology/diagnostic imaging/blood ; Aged ; Middle Aged ; Neurofilament Proteins/blood ; Disease Progression ; Glial Fibrillary Acidic Protein/blood ; Atrophy/pathology ; Brain/pathology/diagnostic imaging ; Neuropsychological Tests ; Supranuclear Palsy, Progressive/pathology ; },
abstract = {BACKGROUND: The temporal sequence of clinical, imaging, and biological changes in sporadic frontotemporal lobar degeneration (FTLD)-associated syndromes remains poorly characterized, and a comprehensive biomarker cascade model is lacking.

METHODS: We developed a data-driven biomarker cascade model in 489 patients across the FTLD spectrum (211 behaviorial variant frontotemporal dementia [bvFTD], 129 primary progressive aphasia [PPA], 71 corticobasal syndrome [CBS], 66 progressive supranuclear palsy [PSP], and 12 FTD associated with amyotrophic lateral sclerosis [FTD-ALS]; 1904 patient-visit observations). Plasma, magnetic resonance imaging (MRI), and clinical biomarkers were modeled using sigmoid trajectories fitted to covariate-adjusted longitudinal data.

RESULTS: Plasma glial fibrillary acidic protein departed from normality earliest, followed by Trail Making Test Part B (TMT-B), white matter lesion volume, and neurofilament light chain. Insular atrophy showed the steepest transition among MRI measures; clinical dementia rating dementia staging instrument plus National Alzheimer's Coordinating Center behavior and language domains sum of boxes declined most steeply overall. TMT-B inflected earliest in bvFTD, whereas insula atrophy dominated in PPA.

CONCLUSIONS: This first data-driven temporal cascade of multimodal biomarkers in sporadic FTLD-associated syndromes offers a framework for disease staging and stage-specific clinical trial design.},
}

Humans
Female
*Biomarkers/blood
Male
Magnetic Resonance Imaging
*Frontotemporal Lobar Degeneration/pathology/diagnostic imaging/blood
Aged
Middle Aged
Neurofilament Proteins/blood
Disease Progression
Glial Fibrillary Acidic Protein/blood
Atrophy/pathology
Brain/pathology/diagnostic imaging
Neuropsychological Tests
Supranuclear Palsy, Progressive/pathology

@article {pmid42554695,
year = {2026},
author = {Krajewski, TJ and Koch, GG},
title = {Randomization-based covariance analysis for hypothesis testing of treatment comparisons based on restricted mean survival time with categorized time-to-event data.},
journal = {Journal of biopharmaceutical statistics},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/10543406.2026.2699854},
pmid = {42554695},
issn = {1520-5711},
abstract = {This paper introduces randomization-based analysis of covariance (RB-ANCOVA) for hypothesis testing of restricted mean survival time (RMST) differences between two randomized treatments in trials with categorized time-to-event data. RMST treatment differences over a prespecified time period are clinically meaningful and avoid assumptions like proportional hazards. The proposed method tests the strong null hypothesis that each participant's time-to-event would remain unchanged regardless of treatment assignment. Covariate adjustment is achieved by constraining baseline covariate means to be equal across arms, which reduces variance. The follow-up period is partitioned into mutually exclusive intervals, and RMST is approximated as the area under the survival curve. Under the strong null hypothesis, the joint asymptotic covariance structure of RMST and covariate means is known and used to construct a chi-squared test statistic for the covariate-adjusted RMST difference. The method accommodates stratified trial designs and supports hypothesis testing over single or several time intervals, enabling testing within internal intervals. The difference in RMSTs over an interval can be divided by its length to yield an average survival rate difference. Additionally, the approach allows the computation of essentially exact p-values via re-randomization. We illustrate the method with data from a randomized, placebo-controlled trial evaluating a test treatment for amyotrophic lateral sclerosis. This method provides a hypothesis testing approach for RMST treatment differences that leverages RB-ANCOVA to adjust for their correlations with baseline covariate differences. Under the strong null hypothesis, it enables hypothesis testing with clear control of Type I error and reduced variance without relying on model-based assumptions.},
}

@article {pmid42554905,
year = {2026},
author = {Colín-Martínez, E and Ramírez-Jarquín, UN and Tapia, R and Arias, C},
title = {Inhibition of Glutamate Decarboxylase in the Spinal Cord Induces Motor Deficits and Motor Neuron Degeneration.},
journal = {Neurotoxicity research},
volume = {44},
number = {4},
pages = {},
pmid = {42554905},
issn = {1476-3524},
support = {IN206719//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; A1-S12135//Secretaría de Ciencia, Humanidades, Tecnología e Innovación/ ; },
mesh = {Animals ; *Glutamate Decarboxylase/metabolism/antagonists & inhibitors ; *Spinal Cord/drug effects/pathology/enzymology ; *Motor Neurons/drug effects/pathology/enzymology ; *Enzyme Inhibitors/toxicity/pharmacology ; *Nerve Degeneration/pathology/chemically induced/enzymology ; Male ; Rats ; gamma-Aminobutyric Acid/metabolism ; },
abstract = {Motor neuron (MN) diseases such as amyotrophic lateral sclerosis (ALS) are characterized by the loss of cortical and spinal MNs. Although the precise mechanisms of MN degeneration are still unknown, downregulation of GABAergic circuits has been identified in both ALS patients and transgenic models of the disease. GABA synthesis depends on the activity of the enzyme glutamate decarboxylase (GAD), of which two isoforms are known: GAD65 and GAD67. To study the effects of decreased GABA synthesis on spinal cord motor function, we analyzed the effects of administering three selective inhibitors of GAD: 3-mercaptopropionic acid (MPA), a competitive inhibitor of GAD, thiosemicarbazide (TSC), and pyridoxal phosphate γ-glutamyl hydrazone (PLPGH), two GAD cofactor blockers. A single dose of any of these inhibitors did not affect motor behavior or MN morphology. However, subchronic (3 days) and chronic (10 days) administration of MPA, TSC or PLPGH in rats caused motor alterations and cellular changes, including episodic myoclonus-like movements, flaccidity in the ipsilateral phalanges, loss of 35-50% of MNs, reactive astrogliosis and decreased GAD activity. These findings suggest that chronic inhibition of GAD can lead to MN degeneration and further suggest that GABA metabolism in the spinal cord may participate in the mechanisms that cause MN death in patients with neurodegenerative diseases such as ALS.},
}

Animals
*Glutamate Decarboxylase/metabolism/antagonists & inhibitors
*Spinal Cord/drug effects/pathology/enzymology
*Motor Neurons/drug effects/pathology/enzymology
*Enzyme Inhibitors/toxicity/pharmacology
*Nerve Degeneration/pathology/chemically induced/enzymology
Male
Rats
gamma-Aminobutyric Acid/metabolism

@article {pmid42555669,
year = {2026},
author = {Hubbard, I and Dubnau, J},
title = {Glial cell toxicity in a Drosophila C9orf72 neurodegeneration model.},
journal = {PLoS genetics},
volume = {22},
number = {8},
pages = {e1011909},
doi = {10.1371/journal.pgen.1011909},
pmid = {42555669},
issn = {1553-7404},
abstract = {The most common genetic cause of both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an expanded G4C2 repeat in the first intron of the gene C9orf72. The C9orf72 repeat expansion is bidirectionally transcribed into sense and anti-sense RNA foci, and also produces dipeptide repeats (DPRs) via a non-canonical translation mechanism known as repeat-associated (RAN) translation. Each of these components of the G4C2 repeat expansion cause neurodegenerative effects in animal models when expressed in neurons, but impacts from glial expression are more poorly understood. Here, we use glial cell type-specific expression of individual DPRs, of RNA repeat-only, or of the G4C2 repeat, that produces both DPRs and RNA repeats, to systematically investigate glial toxicity of each component. We find that as with neurons, the GR and G4C2 transgenes produce the highest degree of toxicity when expressed in glia. Each of these transgenes are capable to produce the GR DPR, which also is the most toxic factor in neurons. We demonstrate that both the GR and G4C2 transgenes cause activation of mdg4, an endogenous retrovirus (ERV). Such ERV expression is a hallmark of TDP-43 dysfunction that is commonly observed in C9orf72 patients. We find that glial expression of either the GR or the G4C2 transgene is toxic to glial cells, but such expression does not cause loss nearby neurons. However, blocking apoptotic signaling within glia that express either GR or G4C2 via expression of the p35 caspase inhibitor further exacerbates effects on lifespan and ablating such glia via expression of the proapoptotic reaper gene partially ameliorates these effects. Together, these results indicate that expression of toxic C9orf72 components in glia produces deleterious effects on lifespan, though potentially through different mechanisms than seen in TDP-43 models of ALS/FTD.},
}

@article {pmid42556002,
year = {2026},
author = {Tekan, ÜY and Aksoy, E and Kargın, F and Küçük, RS and Saltürk, C and Çiyiltepe, F and Yavuz, D and Güngör, G and Adıgüzel, N and Karakurt, Z},
title = {Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {153},
number = {},
pages = {112228},
doi = {10.1016/j.jocn.2026.112228},
pmid = {42556002},
issn = {1532-2653},
abstract = {BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF).

METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis.

RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p < 0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p = 0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia.

CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.},
}

@article {pmid42556722,
year = {2026},
author = {Jiang, H and Ding, L and Yang, C and Guo, G and Zhong, C and Ma, Z and Zhu, H and Zhang, J and Luo, Y and Liu, Z and Liu, R and Ding, Y},
title = {Distinct competitive and allosteric binding modes of nanobodies targeting EphA4.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {113394},
doi = {10.1016/j.jbc.2026.113394},
pmid = {42556722},
issn = {1083-351X},
abstract = {EphA4 signaling is a key negative regulator of axonal regeneration and a genetic modifier of amyotrophic lateral sclerosis (ALS), making EphA4 an attractive but mechanistically underexplored therapeutic target. Although EphA4-targeting nanobodies have shown inhibitory potential, the structural principles governing their binding and inhibitory mechanisms remain largely unknown. Here, we report high-resolution crystal structures of the EphA4 ligand-binding domain (LBD) in complex with four nanobodies (Nb50, Nb53, Nb57, and Nb60), resolved at 1.34-2.21 Å. Nb50, Nb53, and Nb57 competitively engage the canonical ephrin-binding pocket through deep CDR3 insertion, directly mimicking ephrin recognition. In contrast, Nb60 adopts a previously unrecognized binding mode, contacting two EphA4 molecules at noncanonical sites in the crystal structure through framework-dominated interactions and supporting a structural model for steric and allosteric restriction of ephrin access. Integrated biophysical analyses reveal distinct thermodynamic and kinetic signatures underlying these binding mechanisms. Together, our findings uncover unexpected structural diversity in nanobody-mediated EphA4 recognition and provide a framework for rational development of EphA4-targeted modulators for ALS and related neurodegenerative conditions.},
}

@article {pmid42556956,
year = {2026},
author = {Rahman, U and Yang, SC},
title = {Management of Anastomotic Leaks: Endoscopic, Interventional, and Surgical Strategies.},
journal = {Advances in surgery},
volume = {60},
number = {1},
pages = {259-270},
doi = {10.1016/j.yasu.2026.03.017},
pmid = {42556956},
issn = {1878-0555},
mesh = {Humans ; *Anastomotic Leak/therapy/surgery/etiology ; },
abstract = {Anastomotic leaks (ALs) are a significant source of morbidity and mortality. Every step should be implemented to prevent AL, including careful patient selection, optimizing patient's clinical and nutritional status, and ensuring proper technique. The appropriate management of an AL depends on several factors, such as patient's clinical status, the type of surgery, location of the AL, induction therapies, and the resources available. Surgeons should be familiar with the armamentarium of treatment modalities available to manage AL and use a patient-tailored approach when selecting the most appropriate treatment.},
}

Humans
*Anastomotic Leak/therapy/surgery/etiology

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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