@article {pmid42621238,
year = {2026},
author = {Palakkot, S and Banik, A},
title = {Auditory Biomarkers in Neurodegenerative Disorders: A Literature Review.},
journal = {Journal of otology},
volume = {21},
number = {3},
pages = {160-166},
pmid = {42621238},
issn = {2524-1753},
abstract = {The prevalence of neurodegenerative diseases is escalating globally. However, the conventional diagnostic framework fails to identify the pathology until substantial neuronal damage occurs. The evidence from the recent literature indicates that auditory dysfunction commonly precedes motor and cognitive symptoms across multiple neurodegenerative diseases. The pathophysiology involves both the peripheral and cortical auditory structures, which produce distinctive patterns reflects systemic neurodegeneration. Hence, this suggests auditory assessment as a valuable tool for early identification of neural degeneration. This review synthesises the contemporary literature on auditory dysfunctions and underlying pathophysiology in Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, Amyotrophic lateral sclerosis, etc. The analysis included the temporal trajectories of auditory impairment, subjective-objective measurements, and evaluated the importance of early identification and longitudinal tracking. Objective measures of central auditory processing, including Auditory Brainstem Responses, P300, Mismatch Negativity, and speech-in-noise testing, provide objective, non-invasive diagnostic tools and its sensitivity comparable to established biomarkers. Integration of standardised auditory assessment batteries into clinical protocols could enable the early identification of pathology, differential diagnosis and the development of novel therapeutic strategies for both auditory and cognitive deficits. Current review suggests that future longitudinal studies with neurodegenerative conditions should focus on the clinical utility of auditory, cognitive, and neuroimaging biomarkers and facilitate clinical translation of these findings.},
}

@article {pmid42621473,
year = {2026},
author = {Sabnis, RW and Sabnis, AR},
title = {Novel Compounds as TREM2 Agonists for Treating Parkinson's Disease, Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Nasu-Hakola Disease, and Stroke.},
journal = {ACS medicinal chemistry letters},
volume = {17},
number = {8},
pages = {1723-1724},
pmid = {42621473},
issn = {1948-5875},
abstract = {Provided herein are novel compounds as TREM2 agonists, pharmaceutical compositions, use of such compounds in treating Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Nasu-Hakola disease, and stroke, and processes for preparing such compounds.},
}

@article {pmid42621714,
year = {2026},
author = {Wang, SL and He, L and Yang, J and Zhang, N and Sun, YZ and Liu, GP},
title = {["Jiaji" (EX-B2) electroacupuncture modulates NLRP3 inflammasome activation to improve limb dysfunction in amyotrophic lateral sclerosis mice].},
journal = {Zhen ci yan jiu = Acupuncture research},
volume = {51},
number = {8},
pages = {1044-1052},
doi = {10.13702/j.1000-0607.20251237},
pmid = {42621714},
issn = {1000-0607},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/therapy/genetics/immunology/physiopathology/metabolism ; *Electroacupuncture ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism/immunology ; Mice ; Humans ; *Inflammasomes/genetics/metabolism/immunology ; Male ; Acupuncture Points ; Disease Models, Animal ; Interleukin-1beta/genetics/immunology ; *Extremities/physiopathology ; Female ; Spinal Cord/metabolism ; Mice, Inbred C57BL ; },
abstract = {OBJECTIVES: To investigate the regulatory effect of "Jiaji" (EX-B2) electroacupuncture (EA) on the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome in the lumbar spinal cord and to explore its mechanism in improving limb dysfunction in amyotrophic lateral sclerosis (ALS) mice.

METHODS: Fifty-four mice carrying the human superoxide dismutase 1 G93A (hSOD1[G93A]) gene were randomly divided into model, Jiaji EA, and inhibitor groups, with 18 mice per group. Eighteen mice not carrying the hSOD1[G93A] gene served as wild group. At 60 d of age, the Jiaji EA group was given EA at L1-L2 and L5-L6 EX-B2 points with continuous wave, 1 mA, 2 Hz. The needles retained for 20 min, twice every week. The inhibitor group received intraperitoneal injection of the NLRP3 inhibitor (10 mg/kg, twice every week). All treatments were administered for 4 consecutive weeks. The survival period of mice in each group was observed to assess disease progression；the rotarod test was conducted to evaluate motor coordination and limb motor function；HE staining was used to observe pathological changes in the gastrocnemius, and muscle atrophy was assessed by measuring the cross-sectional area of the gastrocnemius fiber；Nissl staining was performed to evaluate the number of motor neurons in the lumbar spinal cord anterior horns；the protein expressions of NLRP3, Caspase-1, apoptosis-associated speck-like protein (ASC), interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in the lumbar spinal cord were detected by Western blot；the mRNA expressions of NLRP3, Caspase-1, ASC, IL-1β, IL-18, and TNF-α were detected by real-time quantitative PCR.

RESULTS: Compared with the wild group, mice in the model group exhibited shortened survival time (P<0.01)；reduced time spent on the rotating rod starting from the 13[th] week of age (P<0.05)；significantly shorter and rounded gastrocnemius fibers with enlarged inter-fiber spaces, nuclear translocation and leakage. The cross-sectional area of the gastrocnemius fibers was reduced (P<0.01)；the number of motor neurons in the spinal anterior horns was decreased (P<0.01)；protein and mRNA expressions of NLRP3, Caspase-1, ASC, IL-1β, IL-18, and TNF-α were increased in the lumbar spinal cord (P<0.01). Compared with the model group, survival time was prolonged in the Jiaji EA and inhibitor groups (P<0.01)；rotarod time was prolonged starting from the 13[th] week of age (P<0.05)；gastrocnemius fibers exhibited more regular margins and larger morphology, with reduced inter-fiber spaces, and reduced number of rounded fibers and improvement in nuclear translocation and leakage；cross-sectional areas of gastrocnemius fiber were increased (P<0.01)；the numbers of motor neurons in the spinal anterior horns were increased (P<0.01)；protein and mRNA expressions of NLRP3, Caspase-1, ASC, IL-1β, IL-18, and TNF-α decreased in the lumbar spinal cord (P<0.05, P<0.01). Compared with the inhibitor group, mice in the Jiaji EA group exhibited prolonged rotarod time from the 17[th] week of age (P<0.05)；the cross-sectional area of the gastrocnemius fiber increased (P<0.05)；protein and mRNA expressions of NLRP3, Caspase-1 and IL-18 in the lumbar spinal cord were higher (P<0.05, P<0.01), while protein and mRNA expressions of TNF-α were lower (P<0.05, P<0.01).

CONCLUSIONS: EX-B2 EA improves limb function and prolongs survival in ALS mice, with its underlying mechanism potentially involving the alleviation of neuroinflammation through inhibition of NLRP3 inflammasome activation.},
}

Animals
*Amyotrophic Lateral Sclerosis/therapy/genetics/immunology/physiopathology/metabolism
*Electroacupuncture
*NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism/immunology
Mice
Humans
*Inflammasomes/genetics/metabolism/immunology
Male
Acupuncture Points
Disease Models, Animal
Interleukin-1beta/genetics/immunology
*Extremities/physiopathology
Female
Spinal Cord/metabolism
Mice, Inbred C57BL

@article {pmid42616178,
year = {2026},
author = {Nolen, A and Zweig, N and Selby, D and Bonares, MJ},
title = {Factors associated with requests for Medical Assistance in Dying (MAiD) referral among patients with amyotrophic lateral sclerosis receiving specialist palliative care.},
journal = {Journal of neurology},
volume = {273},
number = {9},
pages = {},
pmid = {42616178},
issn = {1432-1459},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Female ; Male ; *Palliative Care/statistics & numerical data ; *Referral and Consultation/statistics & numerical data ; Retrospective Studies ; Aged ; Middle Aged ; *Suicide, Assisted/statistics & numerical data ; Noninvasive Ventilation/statistics & numerical data ; Cohort Studies ; Canada ; },
abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) have among the highest rates of medical assistance in dying (MAiD), yet factors associated with requesting MAiD remain poorly understood. We examined sociodemographic and clinical characteristics associated with MAiD referral and receipt among patients with ALS receiving specialist palliative care.

METHODS: We conducted a retrospective sequentially matched cohort study of patients attending a multidisciplinary ALS clinic at a Canadian tertiary care center. Patients who requested a MAiD referral were matched with the next consecutive patient without a MAiD request. Multivariable logistic regression identified factors associated with MAiD referral and, among referred patients, receipt of MAiD.

RESULTS: The cohort included 272 patients (130 MAiD referrals; 142 no referral). Rural residence was independently associated with higher odds of requesting a MAiD referral (adjusted odds ratio [aOR] 2.38, 95% confidence interval [CI] 1.02-5.58), whereas non-invasive ventilation (NIV) was associated with lower odds (aOR 0.56, 95% CI 0.32-0.90). Gastrostomy tube use demonstrated a non-significant trend toward lower odds of MAiD referral (aOR 0.59, 95%CI 0.33-1.07). Age, sex, and limb and bulbar symptom severity were not associated with MAiD referral. Among patients referred for MAiD, no factors were independently associated with receipt of MAiD.

CONCLUSION: In patients with ALS receiving specialist palliative care, use of NIV was associated with a lower likelihood of requesting a MAiD referral, while rural residence was associated with higher odds of referral. These findings suggest that decisions regarding MAiD may be influenced less by disease severity than by preferences regarding life-prolonging interventions and warrant further investigation.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy
Female
Male
*Palliative Care/statistics & numerical data
*Referral and Consultation/statistics & numerical data
Retrospective Studies
Aged
Middle Aged
*Suicide, Assisted/statistics & numerical data
Noninvasive Ventilation/statistics & numerical data
Cohort Studies
Canada

@article {pmid42617572,
year = {2026},
author = {Tang, WX and Yang, C and Zhang, M and Kushida, CA and de Lecea, L and Li, SB},
title = {Sleep-wake control with age and neurodegenerative diseases.},
journal = {Sleep medicine reviews},
volume = {90},
number = {},
pages = {102352},
doi = {10.1016/j.smrv.2026.102352},
pmid = {42617572},
issn = {1532-2955},
abstract = {Aging causes dramatic alterations in bodily functions. Among them, sleep quality declines with age, particularly in individuals with neurodegenerative diseases. In this review, we first describe alterations in sleep-wake architecture and discuss potential mechanisms underlying sleep disorders that arise with age. We discuss evidence linking sleep disorders with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) syndrome. Even though the causes of AD, PD, PSP, and HD are diverse, several shared symptoms including difficulty falling asleep, fragmented sleep, and disrupted circadian rhythm collectively suggest their pathologies disrupt sleep-wake control. Hyperexcitability of implicated neurons is commonly observed prior to neurodegeneration. Upregulated neuronal excitability in the early phase of these diseases appears as a potential shared mechanism among neurodegenerative diseases. Abnormal protein accumulation and aggregation in these diseases exacerbate neuronal circuit hyperactivity by increasing neurons' intrinsic excitability or dampening inhibitory inputs to neurons controlling sleep-wake cycles. A better understanding of the mechanisms underlying sleep disorders that emerge with age may greatly benefit the development of novel preventative and therapeutic strategies for neurodegenerative diseases, and therefore improve the life quality of older adults.},
}

@article {pmid42618027,
year = {2026},
author = {Wolter, A and Ritz, L and Wolter, JS and Kurkevych, A and Thul, J and Bedei, I and Schenk, J and Königbauer, JT and Weichert, A and Axt-Fliedner, R},
title = {Prenatally diagnosed Ebstein's anomaly and tricuspid valve dysplasia: associated anomalies and predictors of outcome in a multicenter cohort study.},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2932-8445},
pmid = {42618027},
issn = {1438-8782},
abstract = {PURPOSE: To describe associated anomalies and outcomes of prenatally diagnosed Ebstein's anomaly (EA)/tricuspid valve dysplasia (TVD) in a multicenter cohort and to identify predictors of adverse outcome (intrauterine or postnatal death).

MATERIALS AND METHODS: In this retrospective study, cardiothoracic ratio, aortic valve diameter (AVD), pulmonary and atrioventricular valve measurements, ventricular dimensions, vena contracta, chamber areas, Celemajer index, peak tricuspid regurgitation velocity (TR_max), and pulmonary flow direction between survivors and non-survivors were compared across three gestational intervals.

RESULTS: Among 87 fetuses, 7 (8.0%) intrauterine deaths and 7 (8.0%) terminations occurred; 14 (16.1%) were lost to follow-up. Fifty-nine (67.8%) live births with follow-up were documented; 52 (88.1%) underwent active postnatal management, with a survival rate of 69.2% (36/52). Non-survivors more frequently had hydrops, earlier delivery, and lower birth weight. z-score AVD (zAVD) was lower and pulmonary flow more often retrograde in non-survivors before 32 weeks. TR_max was lower in interval 1 (<24 weeks), and right atrial area and vena contracta were larger in interval 2 (24-32 weeks). No significant differences were observed after 32 weeks.

CONCLUSION: This is one of the largest prenatal multicenter cohorts employing a longitudinal design, with echocardiographic data evaluation across three gestational intervals. Established predictors (pulmonary flow, TR_max) were confirmed and zAVD was identified as a simple, clinically applicable parameter, highlighting the relevance of left ventricular involvement in EA/TVD. Zusammenfassung: Ziel: Ziel dieser retrospektiven, multizentrischen Studie war es, assoziierte Anomalien und das Outcome bei pränatal diagnostizierter Ebstein-Anomalie /Trikuspidalklappendysplasie (EA/TVD) zu analysieren sowie Prädiktoren für ein ungünstiges Outcome (intrauteriner Fruchttod (IUFT), postnataler Tod) zu identifizieren.

MATERIAL UND METHODEN: Retrospektiv wurden kardiothorakale Ratio, Aortenklappendurchmesser (AVD), pulmonale und atrioventrikuläre Klappen, Ventrikeldimensionen, Vena contracta, Vorhof-/Ventrikelflächen, Celemajer-Index, maximale Trikuspidalinsuffizienzgeschwindigkeit (TR_max) und Pulmonalflussrichtung zwischen Überlebenden und Nicht-Überlebenden in drei3 Gestationsintervallen verglichen. Ergebnisse: Von 87 Feten traten 7 (8,0%) IUFT auf, 7 (8,0%) Schwangerschaftsabbrüche erfolgten, 14 (16,1%) waren lost to follow-up. Insgesamt wurden 59/87 (67,8%) Lebendgeburten dokumentiert; 52 (88,1%) erhielten ein aktives postnatales Management mit einer Überlebensrate von 69,2% (36/52). Nicht-Überlebende zeigten häufiger Hydrops, frühere Entbindung und geringeres Geburtsgewicht. Der Z-Score des AVD (zAVD) war <32 Wochen niedriger, der Pulmonalfluss häufiger retrograd. TR_max war <24 Wochen niedriger, rechte Vorhoffläche und Vena contracta zwischen 24-32 Wochen größer. Nach 32 Wochen bestanden keine signifikanten Unterschiede. Schlussfolgerung: : Dies ist eine der größten pränatalen, multizentrischen Kohorten mit longitudinaler Auswertung über drei3 Gestationsintervalle. Etablierte Prädiktoren (Pulmonalfluss, TR_max) wurden bestätigt, und zAVD als einfacher, klinisch anwendbarer Parameter identifiziert, der die Relevanz der linksventrikulären Beteiligung bei EA/TVD unterstreicht.},
}

@article {pmid42618698,
year = {2026},
author = {Shrestha, N and Munn, Z and Calma, A and Pavey, N and Tsuji, Y and Menon, P and Padovani, A and Risi, B and Ferullo, L and Filosto, M and Jewett, G and Shibuya, K and Otani, R and Shimizu, T and Kuwabara, S and Noto, YI and Kitaoji, T and Johnsen, B and Shen, D and Cui, L and van den Berg, LH and van Eijk, RPA and van Damme, P and Kiernan, MC and Giles, L and Vucic, S},
title = {Gold Coast criteria for ALS diagnosis: individual participant data meta-analysis.},
journal = {Journal of neurology},
volume = {273},
number = {9},
pages = {},
pmid = {42618698},
issn = {1432-1459},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Humans ; Sensitivity and Specificity ; },
abstract = {BACKGROUND: To evaluate the diagnostic accuracy of the Gold Coast criteria (GCC) and compare their performance with the revised El Escorial (rEEC) and Awaji criteria in patients with suspected amyotrophic lateral sclerosis (ALS).

METHODS: Embase, MEDLINE, and Scopus were searched for English-language studies published between January 1, 2020, and August 11, 2025. Eligible studies assessed the diagnostic accuracy of GCC compared with rEEC and Awaji criteria in suspected ALS. Authors were invited to contribute individual participant data. Data were checked, harmonised, and recoded. A one-stage individual-participant data meta-analysis, adjusted for age and sex, was performed. Diagnostic performance was assessed using pooled sensitivity, specificity, and area under the receiver operating characteristic curve. Risk of bias was assessed using QUADAS-2 and QUADAS-C, and certainty of evidence using GRADE for diagnostic test accuracy. The study was registered with PROSPERO, CRD420251123597.

RESULTS: Individual participant data were available for 3007 participants from five international studies. GCC demonstrated higher sensitivity than rEEC and Awaji criteria: 0.96 (95% confidence interval [CI] 0.93-0.98) versus 0.87 (95% CI 0.78-0.92) and 0.87 (95% CI 0.78-0.93), respectively. Certainty of evidence for sensitivity was moderate at pre-test probabilities of 50% and 75%, and low at 25%. Specificity was numerically lower for GCC at 0.68 (95% CI 0.53-0.81) compared with rEEC at 0.73 (95% CI 0.59-0.83) and the Awaji criteria at 0.72 (95% CI 0.57-0.83). The certainty of evidence for specificity was rated as very low across all assessed pre-test probabilities (25%, 50%, and 75%).

CONCLUSIONS: GCC provide a sensitive framework for suspected ALS and may support earlier diagnosis in specialist settings. Specificity was imprecise and heterogeneous, supporting use with mimic exclusion and longitudinal reassessment.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Humans
Sensitivity and Specificity

@article {pmid42618940,
year = {2026},
author = {Saka, AK and Godhwani, K and Ramasamy, V and Soh, BL and Lingam, M and Lofters, A and Gerstle, D and Selby, P and LeBlanc, A and Pritlove, C and Sayani, A},
title = {The use of deliberative dialogue in health services research: a scoping review.},
journal = {Research involvement and engagement},
volume = {12},
number = {1},
pages = {},
pmid = {42618940},
issn = {2056-7529},
support = {TLP - 185094/CAPMC/CIHR/Canada ; },
abstract = {INTRODUCTION: Deliberative Dialogue (DD) is a structured participatory approach that brings together research evidence, professional expertise, and lived/living experience to support informed discussion and decision-making in health research. DD is increasingly used in the co-design, co-implementation, and co-evaluation of health-promoting interventions, where decisions must be both evidence-informed and responsive to local contexts, priorities, and needs. However, published studies vary considerably in how DD is described and reported, particularly in relation to facilitation, evidence use, participant preparation, power dynamics, and follow-up. This scoping review examined the application of DD in health services research, focusing on its methodological processes, reported outcomes and challenges, engagement of different interest-holders, and the rationales underlying its use.

METHODS: A scoping review was conducted following Arksey and O'Malley's framework and reported in accordance with PRISMA-ScR guidelines. Searches of OVID Medline, PsycINFO, PubMed, CINAHL, and Scopus identified 1,793 records. After screening and consolidating duplicate reports, 15 unique studies met the inclusion criteria. Data were extracted using a template informed by the Guidance for Reporting Involvement of Patients and the Public (GRIPP2), the Consolidated Standards of Reporting Trials (CONSORT), and Boyko et al.'s model of DD. The review was conducted using a critical Patient-Oriented Research (cPOR) approach, which centres lived/living experience, promotes shared decision-making between patient partners and researchers, and attends to the influence of power and structural contexts on knowledge production. The interdisciplinary team, including patient partners, researchers, clinicians, policymakers, and decision-makers, co-developed the study, contributed to data interpretation, and collaboratively refined the findings through iterative and reflexive discussion.

FINDINGS: The 15 included studies were published between 2012 and 2024 and represented diverse geographic and health-system contexts. DD was used to support intervention co-design, implementation planning, evaluation, priority-setting, guideline development, and service improvement. Studies consistently reported the involvement of multiple interest-holder groups and the development of practical outputs, including curricula, decision aids, care models, action plans, guidelines, and priority-setting frameworks. However, reporting of methodological processes was inconsistent. Only a minority of studies described facilitation protocols, participant preparation, strategies to address power dynamics, accessibility supports, or follow-up activities. While DD was associated with enhanced trust, mutual understanding, contextual relevance, and collaborative decision-making, evidence of longer-term impacts was limited. The synthesis also revealed substantial variation in how studies reported participant engagement, evidence use, consensus-building processes, and the translation of deliberative outputs into intervention-related decisions.

This review highlights DD as a valuable approach for collaborative, evidence-informed, and context-sensitive health services research. Across the included studies, DD was used to bring together diverse forms of knowledge and generate practical outputs to support intervention development and improvement. However, methodological details related to facilitation, accessibility, participant support, management of power dynamics, decision-making processes, and longer-term impacts were often underreported. These gaps point to the need for more transparent and equity-oriented reporting of DD, particularly in relation to how people with lived/living experience are engaged and how their contributions influence intervention-related decisions. Strengthening reporting in these areas may improve the transparency, reproducibility, and accountability of DD in the co-design, co-implementation, and co-evaluation of health interventions.},
}

@article {pmid42619018,
year = {2026},
author = {Davias, A and Knekt, P and Rantakokko, P and Hansen, J and Weisskopf, MG},
title = {Associations between Pre-Disease Biomarkers of Persistent Organic Pollutants and Amyotrophic Lateral Sclerosis Survival in the Danish Diet, Cancer and Health Study Cohort.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78334},
pmid = {42619018},
issn = {1531-8249},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons in the brain and spinal cord. Most patients survive 3 to 5 years after diagnosis, although some live 10 years or more. Prognostic factors are incompletely understood, but previous case-control studies suggest that exposure to persistent organic pollutants (POPs) may be associated with ALS survival, but this has not been explored within prospective analysis of POP biomarkers. In this study, we aimed to prospectively investigate the relationship between exposure to POPs-assessed in pre-disease plasma samples-and survival with ALS in the Danish Diet, Cancer, and Health study cohort.

METHODS: We identified 166 incident ALS cases using the Danish National Patient Register via International Classification of Diseases (ICD) codes. We measured concentrations of 13 polychlorinated biphenyls (PCBs), 9 organochlorine pesticides, and 3 polybrominated diphenyl ethers in plasma samples collected at inclusion in the study (baseline). To assess the relationship between POP exposures and ALS survival, we used separate Cox models for each POP group adjusting for diagnosis age, sex, smoking status, body mass index, and marital status. We selected the most relevant POP groups for ALS survival using an elastic net penalized Cox proportional hazards regression model and then ran a model using a summary environmental risk score (ERS).

RESULTS: Single-pollutant Cox models showed that exposure to non-dioxin like PCBs, hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and chlordane compounds were associated with shorter survival. Elastic net penalized Cox proportional hazards regression selected HCB and chlordane compounds as the most relevant POPs for survival. The ERS Cox model showed a significant association with shorter survival (hazard ratio [HR]: 1.4, 95% confidence interval [CI]: 1.1-1.7). A 1 standard deviation (SD) higher ERS score was associated with an HR for death of 1.4 (95% CI: 1.1-1.7). Predicted median survival for those with an ERS score 1 SD higher than the mean was 12 months shorter (26 vs 38 months).

INTERPRETATION: Our study suggests that pre-disease exposure to some POPs such as HCB and chlordane compounds could negatively influence ALS survival. ANN NEUROL 2026.},
}

@article {pmid42619255,
year = {2026},
author = {Gadhave, DG and Jadhav, AB and Waghamode, NB and Khot, S and Khan, R and Hole, R and Dhobale, SM and Aswar, M and Paudel, KR},
title = {Mitochondria-Targeted Nanotherapies in Aging Neurodegenerative Disorders: Emerging Prospects and Clinical Potential.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e71594},
doi = {10.1002/adhm.71594},
pmid = {42619255},
issn = {2192-2659},
abstract = {Aging is a significant risk factor of neurodegenerative disorders (NDs) such as Huntington's, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Although several clinical, neuroimaging, and biomarker-based diagnostic approaches are available for NDs, their limited sensitivity for early-stage detection, disease specificity, and prediction of disease progression continue to present significant clinical challenges, often resulting in delayed diagnosis and therapeutic intervention. According to previously published works, the preliminary pathological feature of such disorders is mitochondrial dysfunction. This may lead to elevated oxidative stress, impaired mitophagy, unbalanced mitochondrial function, and bioenergetic failure. This review examines how mitochondria-targeted nanotherapeutic approaches can overcome these pathological barriers and improve therapeutic outcomes in aging-associated neurodegeneration. Targeted delivery of drug-loaded nanocarriers, such as gene-delivery, lipid-based, metallic, and polymeric nanoparticles, has emerged as a potential platform to deliver medication directly to defective mitochondria. It may increase mitochondrial biogenesis, maintain redox balance, and protect against neuronal degeneration. This work incorporates disease-specific mitochondrial pathology with current progress in targeted nanotherapeutics, age-associated delivery barriers, clinical revolution, and emerging artificial intelligence (AI)-enabled precision therapeutic approaches. Mitochondria-targeted nanotherapeutics depict a potential disease-modifying strategy for aging-related NDs. However, further advancements in targeting efficacy, scalable production, long-term safety, and clinical validation can facilitate a successful clinical revolution.},
}

@article {pmid42619804,
year = {2026},
author = {Spillman, AM and Alsop, EB and Gittings, LM and Garcia-Mansfield, K and Piras, I and Bonfitto, A and Martinez, MN and Sharma, R and Preller, KR and Huentelman, M and Pirrotte, P and Van Keuren-Jensen, K and Sattler, R},
title = {Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72 -Frontotemporal Dementia.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.07.26.740405},
pmid = {42619804},
issn = {2692-8205},
abstract = {Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are linked neurodegenerative diseases characterized by both synaptic dysfunction and TDP-43 pathology. A hexanucleotide repeat expansion (HRE) in the C9ORF72 (C9) gene represents the most common genetic cause of FTD and ALS, yet the synapse-specific mechanisms underlying disease pathogenesis remain poorly understood. Here, we performed integrated multi-omic profiling of synaptosomes enriched from postmortem frontal cortex and patient-derived induced pluripotent stem cell (iPSC)-derived cortical neurons to define molecular alterations associated with C9-FTD-mediated synaptic dysfunction. Proteomic profiling of frontal cortex-derived synaptosomes identified 1,324 differentially abundant proteins (p<0.05) enriched in pathways regulating synaptic vesicle transport and synapse organization, while synaptosomal RNA sequencing revealed 2,835 differentially expressed protein-coding genes. C9-FTD iPSC-cortical neurons exhibited reductions in excitatory and inhibitory postsynaptic markers, accompanied by progressive impairment of neuronal network activity, supporting both structural and functional deficits. iPSC-derived synaptosomes recapitulated key molecular pathways observed in patient brain, revealing convergent dysregulation of synaptic signaling pathways. Comparative analyses revealed divergence between protein and RNA alterations, consistent with the disruption of regulatory processes that link RNA and protein abundance diseased synapses. Consistent with TDP-43 loss-of-function pathology we identified cryptic exon (CE)-containing transcripts within C9-FTD frontal cortex-derived synaptosomes, including KALRN and STMN2, providing evidence that aberrantly spliced RNAs localize to synaptic compartments. Together, these findings define convergent molecular pathways underlying synapse vulnerability in both C9-FTD model systems and identify synaptic localization of CE-containing transcripts as a previously unrecognized feature of TDP-43 proteinopathy.},
}

@article {pmid42619860,
year = {2026},
author = {Barretto, N and Fullerton, BT and Daly, AC and Casel, O and Kuksenko, O and Kang, K and Petrescu, J and Xia, M and Eschbach, J and Leung, M and Khiste, S and Gebremedhin, B and Smith, C and Jackson, CA and Phatnani, H},
title = {A multi-omics characterization reveals distinct molecular signatures in the human motor cortex and lumbar spinal cord in ALS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.07.24.740361},
pmid = {42619860},
issn = {2692-8205},
abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease characterized by the loss of upper motor neurons in the motor cortex (MTC) and lower motor neurons in the spinal cord, leading to muscle atrophy and ultimately respiratory failure. While motor neurons (MNs) are the selectively vulnerable cell type, their interactions with glia contribute to the progression of ALS pathology. However, it remains unclear whether the site of ALS symptom onset influences the molecular alterations underlying MN and glial dysfunction and whether these alterations are shared between the MTC and lumbar spinal cord (LSC). To address these questions, we constructed spatially-resolved gene expression maps of the MTC and LSC by combining spatial and single-nucleus transcriptomic profiles from a cohort of non-neurological controls and ALS donors clinically stratified by site of symptom onset. In the ventral horn of the LSC, we see a decrease in genes associated with MNs and synaptic signaling in ALS donors. We also identify region-specific alterations in endothelial- and glial-related functions. Notably, the severity of these MN deficits and endothelial-related functions is influenced by the site of symptom onset, whereas alterations in glial function largely are not. In contrast to the LSC, we observe layer-specific increases in synaptic signaling in the MTC of ALS donors. Comparing the molecular and cellular changes within the LSC and MTC in ALS indicates that they are predominantly non-overlapping, and have different molecular signatures.},
}

@article {pmid42620667,
year = {2026},
author = {Hawley, ZCE and Guise, AJ and Pardo, ID and Chowdhury, T and Hana, S and Zavodszky, MI and Engle, L and Wiltberger, K and Bartlett, D and Raitcheva, D and Bommegowda, S and Lee, WH and Chen, SK and Sheehy, A and Driscoll, R and Peterson, M and Sebalusky, J and Hamann, S and Marsh, G and Doherty, J and Chicoine, KE and Cundiff, P and Dwyer, S and Clarner, P and Zeng, W and Ferretti, D and Tuczkewycz, T and Isaza, I and Patrovanie, M and Mcgladrigan, C and Chu, J and Morrison, JP and Arnold, HM and Shen, S and Hurt, JA and Trapa, P and Graham, DL and Plowey, ED and Lo, SC},
title = {Antisense oligonucleotide treatment following viral delivery of artificial SOD1-targeting miRNA shows improved efficacy in SOD1-G93A mice.},
journal = {Molecular therapy. Advances},
volume = {34},
number = {3},
pages = {201818},
pmid = {42620667},
issn = {3117-387X},
abstract = {Adeno-associated virus (AAV) artificial microRNAs (amiRNAs) targeting superoxide dismutase 1 (SOD1) have been proposed as a therapeutic strategy for people living with amyotrophic lateral sclerosis (ALS) who harbor toxic gain-of-function variants in the SOD1 gene. Clinical efforts have primarily focused on AAV delivery via the cerebrospinal fluid (CSF), as blood-brain-barrier-crossing capsids are still being developed preclinically. However, intra-CSF delivery has been shown to be highly variable and increases the risk for AAV-related adverse events such as dorsal root ganglion (DRG) toxicity. Here, we show that immunosuppressants (IMS) following intra-CSF delivery of AAV9-amiR-SOD1 in non-human primates (NHPs) prevented AAV-related DRG toxicity, and this benefit was maintained for over 300 days even after immunotherapy stopped at 90 days post-AAV treatment. In line with prior literature, we found intra-CSF delivery of AAV9-amiR-SOD1 to be highly variable in adult mice and NHPs, requiring higher doses of virus to achieve efficacious endpoints. To address this concern, we developed a proof-of-principle study showing that AAV9-amiR-SOD1, in combination with a SOD1-targeting antisense oligonucleotide, provided an additive therapeutic benefit in SOD1-G93A mice compared with AAV9-amiR-SOD1 alone. This combinatorial approach lowered the viral load needed to reach efficacious endpoints, which could mitigate AAV-related adverse events alongside IMS.},
}

@article {pmid42621206,
year = {2026},
author = {Couto, CM and de Melo Queiroz, E and da Cunha, MC and Santos, SCL and Ferreira, AR and Nascimento, OJM},
title = {Genetic profile of motor neuron disease in a multiregional Brazilian cohort: an 18-year real-world experience in 1,911 patients.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1883977},
pmid = {42621206},
issn = {1664-2295},
mesh = {Humans ; Brazil/epidemiology ; Female ; *Motor Neuron Disease/genetics/epidemiology ; Male ; Retrospective Studies ; Middle Aged ; Genetic Testing ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Aged ; *Genetic Profile ; C9orf72 Protein/genetics ; Cohort Studies ; Adult ; Superoxide Dismutase-1/genetics ; },
abstract = {BACKGROUND: Genetic testing in amyotrophic lateral sclerosis (ALS) is increasingly recommended for all patients, but real-world implementation in middle-income countries remains heterogeneous. Brazilian motor neuron disease genetics has largely been characterized through protocol-based cohorts focused on the founder VAPB p.Pro56Ser variant (amyotrophic lateral sclerosis type 8, ALS8). The broader genetic landscape beyond ALS8 in Brazilian clinical populations has not been described in a large multiregional cohort. We aimed to characterize this profile.

METHODS: We retrospectively analyzed 1,911 patients with motor neuron disease followed at six SARAH Network rehabilitation hospitals across Brazil between 2007 and 2024. Genetic testing was clinically directed; ALS8 cases (n = 78) were characterized separately. We assessed characteristics of genetically tested versus untested patients, the temporal evolution of testing modalities, and the diagnostic yield by gene and by Byrne family history classification.

RESULTS: Of 1,833 patients without ALS8, 318 (17.3%) underwent genetic testing, with selection bias toward younger age, higher educational attainment, and positive family history of ALS or frontotemporal dementia (all p < 0.001). Testing expanded markedly after 2020, particularly C9orf72 screening and next-generation sequencing panels. Panel/exome sequencing identified pathogenic or likely pathogenic variants in 13 of 66 patients (19.7%), consistent with international literature for mixed familial-sporadic cohorts. Across all modalities, 30 patients without ALS8 carried pathogenic or likely pathogenic variants in six genes: SOD1 (n = 15), C9orf72 (n = 11; 7.0% of 157 tested), and VCP, FUS, TBK1, and SETX (n = 1 each). ATXN2 intermediate-length CAG repeats were identified in 15 of 230 patients tested (6.5%), replicating the 6.3% previously reported in a Brazilian multicenter sample. Yield by Byrne classification followed a marked gradient (Definite: 89.7%, Probable: 24.0%, Possible: 15.4%, Sporadic: 4.9%; p < 0.001). The SOD1 spectrum included recurrent variants of likely Iberian/European origin.

CONCLUSION: This 18-year cohort defines a real-world genetic profile of motor neuron disease beyond ALS8, with diagnostic yield comparable to the literature and a Byrne gradient supporting universal testing. Beyond family history, socioeconomic factors appeared to shape access to testing, reinforcing the importance of equitable genetic testing for diagnostic precision, family counseling, and access to gene-targeted therapy.},
}

Humans
Brazil/epidemiology
Female
*Motor Neuron Disease/genetics/epidemiology
Male
Retrospective Studies
Middle Aged
Genetic Testing
*Amyotrophic Lateral Sclerosis/genetics/epidemiology
Aged
*Genetic Profile
C9orf72 Protein/genetics
Cohort Studies
Adult
Superoxide Dismutase-1/genetics

@article {pmid42612795,
year = {2026},
author = {Li, J and Duan, H and Hao, P and Zhao, W and Gao, Y and Yang, Z and Li, X},
title = {Regenerative medicine for neurodegenerative diseases:History, Strategies, and Clinical Advances.},
journal = {Translational research : the journal of laboratory and clinical medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.trsl.2026.08.005},
pmid = {42612795},
issn = {1878-1810},
abstract = {In the context of global ageing, the prevalence of neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), is rapidly increasing. However, current symptomatic treatments have achieved limited benefits in clinical settings and fundamentally fail to reverse the progressive loss of specific neuronal populations. Halting neurodegeneration and restoring impaired cognitive, motor or visual functions through nerve regeneration and circuit reconstruction represent the clinically meaningful goals for treatments of NDDs. Regenerative medicine has emerged as a promising paradigm to address this unmet need. In this review, we trace the historical evolution of regenerative therapies for NDDs - from early exploratory cell transplantation to modern approaches involving pluripotent stem cells (PSCs) and in vivo direct reprogramming. Furthermore, we elucidate the core strategies of regenerative medicine within an integrated framework encompassing "Replacement", "Regeneration", and "Rejuvenation". Finally, we highlight recent advances in clinical research, particularly milestone trials in cell replacement therapy for PD, as well as the application of mesenchymal stem cells (MSCs) in AD and ALS.},
}

@article {pmid42612865,
year = {2026},
author = {Gerrit Noordergraaf, GJ and Przemek Jakubowski, P},
title = {SpO2 during CPR: from distraction towards a physiological goal.},
journal = {Resuscitation},
volume = {},
number = {},
pages = {111260},
doi = {10.1016/j.resuscitation.2026.111260},
pmid = {42612865},
issn = {1873-1570},
}

@article {pmid42613144,
year = {2026},
author = {Valverde, A and Blasco, H and Corcia, P and Herault, O and Magistretti, P and Herault, L and Cali, C and Bartesaghi, L and Stone, J and Mitrofanis, J},
title = {Exploring the effect of red and near-infrared light on neurodegenerative disease: A focus on amyotrophic lateral sclerosis, Charcot's devastating disease of the motor system.},
journal = {International review of neurobiology},
volume = {189},
number = {},
pages = {205-236},
doi = {10.1016/bs.irn.2026.01.013},
pmid = {42613144},
issn = {2162-5514},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/radiotherapy ; Animals ; *Infrared Rays/therapeutic use ; Red Light ; *Neurodegenerative Diseases/therapy ; },
abstract = {All neurodegenerative diseases, from Alzheimer's disease to amyotrophic lateral sclerosis (ALS), are characterised by a relentless and progressive degeneration of neurones. The degenerating neurones suffer from mitochondrial dysfunction, glutamate excitotoxicity, metabolic disorder and atypical protein aggregations; there is also widespread neuroinflammation and damage to the neurovascular unit across the nervous system. Unfortunately, there is no current treatment option that addresses all, if not many, of these striking abnormalities, one that stops or even slows the progression of the disease (ie neuroprotective). In this chapter, we explore the potential effectiveness of red and near infrared light (R-NIr) on ALS, one of the most devastating of all the neurodegenerative diseases. This condition impacts the motor system, from the cerebral cortex and brainstem to the spinal cord, as well as many skeletal muscles. Individuals suffer greatly and the survival period after onset of the first signs is often very short, averaging just over 2 years, as against 4-8 years in dementia. We outline two main reasons why R-NIr may have positive outcomes in ALS; (1) R-NIr has been shown to be neuroprotective in many other neurodegenerative diseases, improving cell function and survival, and; (2) unlike many other treatments attempted previously, R-NIr addresses many, if not all features of pathology associated with ALS. In summary, we suggest that R-NIr, with its multi-modal effect, could be a valuable treatment option for patients with ALS, particularly if the treatment is started early, before the development of excessive cellular damage.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/radiotherapy
Animals
*Infrared Rays/therapeutic use
Red Light
*Neurodegenerative Diseases/therapy

@article {pmid42613225,
year = {2026},
author = {Light, A and Peters, M and Ahmed, HU and Shah, TT},
title = {Reply to Marcio C. Moschovas, Ugo Falagario, Francesco Pellegrino, et al's Letter to the Editor re: Alexander Light, Max Peters, Manit Arya, et al's Salvage Focal Therapy vs Radical Prostatectomy for Localized Radiorecurrent Prostate Cancer. JAMA Oncol 2026;12:364-73.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.07.033},
pmid = {42613225},
issn = {1873-7560},
}

@article {pmid42613627,
year = {2026},
author = {Jamali, MC and Shafie, A and Alqahtani, AJ and Al-Samawi, RI and Alyami, HM and Ashour, AA and Felemban, MF and Mansuri, N and Tayeb, FJ and Ahmad, I and Mudhafar, M and Sheweita, SA},
title = {Advances in the clinical application of mesenchymal stem cells for neurological disorders.},
journal = {Stem cell research & therapy},
volume = {17},
number = {1},
pages = {},
pmid = {42613627},
issn = {1757-6512},
mesh = {Humans ; *Mesenchymal Stem Cell Transplantation/methods ; *Mesenchymal Stem Cells/cytology/metabolism ; *Nervous System Diseases/therapy/pathology ; Animals ; Amyotrophic Lateral Sclerosis/therapy/pathology ; Alzheimer Disease/therapy/pathology ; },
abstract = {Therapeutic approaches employing mesenchymal stem cells (MSCs) have emerged as a promising avenue for investigating treatments for neurological disorders. This strategy aims to capitalize on the biological properties of MSCs to support the repair of damaged neural tissue and modulate pathological processes. This review provides a comprehensive overview of the current clinical evidence regarding MSC applications in major neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other pertinent disorders. Across clinical studies, MSC administration has generally demonstrated a favorable safety profile and procedural feasibility. However, therapeutic efficacy remains variable and inconsistent across trials. Importantly, differences in MSC sources, manufacturing procedures, delivery routes, dosing strategies, and patient selection contribute substantially to the heterogeneity of reported outcomes. Therefore, the current body of evidence supports the safety of MSC-based interventions, but their clinical effectiveness has not yet been consistently demonstrated. Future progress will depend largely on the standardization of cell preparation and treatment protocols, improved biomarker-driven patient stratification, and rigorously designed large-scale randomized trials.},
}

Humans
*Mesenchymal Stem Cell Transplantation/methods
*Mesenchymal Stem Cells/cytology/metabolism
*Nervous System Diseases/therapy/pathology
Animals
Amyotrophic Lateral Sclerosis/therapy/pathology
Alzheimer Disease/therapy/pathology

@article {pmid42613642,
year = {2026},
author = {Wang, JDJ and Teo, AYT and Xiao, B and Chao, Y and Zhou, ZD and Tan, BJ and Chan, LL and Rosalie, E and Tan, EK},
title = {PCSK9 inhibitors in neurodegenerative disorders: mechanisms, therapeutic potential, and clinical implications.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {42613642},
issn = {2047-9158},
support = {LCG//National Medical Research Council/ ; STaR//National Medical Research Council/ ; },
mesh = {Humans ; *PCSK9 Inhibitors ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Proprotein Convertase 9/metabolism/genetics ; Animals ; },
abstract = {Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in hepatic cholesterol metabolism via low density lipoprotein receptor degradation. PCSK9 inhibitors have revolutionized lipid-lowering therapy, providing robust reduction of cardiovascular risk. Large-scale randomized controlled trials and long-term extensions (e.g., FOURIER and EBBINGHAUS trials) have shown no significant adverse effects of PCSK9 inhibitors on neuropsychological testing or patient-reported cognitive outcomes, even with prolonged and intensive lowering of low-density lipoproteins. Pre-clinical studies also suggest PCSK9 as a key regulator of neurobiological processes, including synaptic plasticity, amyloid-beta clearance, neuroinflammation, and blood-brain barrier integrity. Human genetic studies revealed complex, sometimes conflicting associations between PCSK9 variants and risk of Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis. In this review, we highlight the pathophysiologic mechanisms, emerging experimental therapeutics and clinical implications of PCSK9 inhibition in neurodegenerative disorders. Long-term adequately powered trials with robust neuropsychological, biomarker, and imaging endpoints, as well as mechanistic studies in human-derived models are needed to establish the cardiovascular and neurocognitive implications of PCSK9 inhibition and guide precision medicine strategies for those at elevated risk of neurodegeneration.},
}

Humans
*PCSK9 Inhibitors
*Neurodegenerative Diseases/drug therapy/metabolism
*Proprotein Convertase 9/metabolism/genetics
Animals

@article {pmid42613694,
year = {2026},
author = {Shukla, S and Srivastava, V and Gaur, H and Rai, A},
title = {Myelin and Oligodendrocyte Dysfunction in Demyelinating and Neurodegenerative Disorders: Signaling Pathways and Therapeutic Targets.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273437393260729093129},
pmid = {42613694},
issn = {1996-3181},
abstract = {INTRODUCTION: Oligodendrocytes (OLs) synthesize myelin, a substance that plays a significant role in ensuring proper functioning of the Central Nervous System (CNS). Myelin abnormalities are involved in disease pathogenesis in AD, MS, and ALS. In contrast, MS involves autoimmune reactions directed against myelin. On the other hand, AD and ALS are characterized by neurodegeneration. This article seeks to give a critical discussion on myelin and OL dysfunction in these diseases, among others.

METHODS: A narrative literature search was carried out in various databases including Scopus, Google Scholar, Web of Science, and PubMed, focusing on papers relating to myelination, remyelination, and OLs, particularly those addressing signaling pathways and treatment strategies.

RESULTS: MS is an autoimmune disease characterized by inflammation that causes demyelination and OL dysfunction. Oxidative stress and mitochondrial dysfunction play roles in the pathogenesis of ALS, whereas AD is a result of disrupted neuronal supportive functions and myelin damage. Important signaling pathways involved in OL formation and myelin repair include the Wnt/β-catenin, AKT/mTOR, and ERK/MAPK pathways. Drugs like edaravone, ocrelizumab, and siponimod have been identified for promoting myelin repair.

DISCUSSION: The relationship between abnormal oligodendrocyte function, demyelination, and specific disease-related pathological processes demonstrates that although there is a similarity among MS, AD, and ALS, each condition possesses its own unique molecular foundation. One potential treatment approach would be targeting shared signaling pathways relevant to myelination and remyelination. Nonetheless, disease variability and specific pathogenic characteristics demand a targeted therapy approach.

CONCLUSION: Myelin integrity and oligodendrocyte function are central to the progression of demyelinating and neurodegenerative diseases. Targeting molecular pathways involved in myelination offers significant potential for improving disease outcomes and developing advanced therapeutic strategies.},
}

@article {pmid42613775,
year = {2026},
author = {Nalicho, JC and Mabeyo, PE and Paluch, AS and Paul, L},
title = {Integrated In Silico Discovery of Thymoquinone Analogs Targeting the Keap1-Nrf2 Pathway for Amyotrophic Lateral Sclerosis Therapy.},
journal = {ChemistryOpen},
volume = {15},
number = {9},
pages = {e70286},
doi = {10.1002/open.70286},
pmid = {42613775},
issn = {2191-1363},
mesh = {*NF-E2-Related Factor 2/metabolism/antagonists & inhibitors/chemistry ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Benzoquinones/chemistry/pharmacology/metabolism/therapeutic use ; *Kelch-Like ECH-Associated Protein 1/metabolism/antagonists & inhibitors/chemistry ; Humans ; Quantitative Structure-Activity Relationship ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Signal Transduction/drug effects ; Drug Discovery ; Oxidative Stress/drug effects ; },
abstract = {Oxidative stress drives neuronal vulnerability in amyotrophic lateral sclerosis (ALS), making the Keap1-Nrf2 pathway a vital therapeutic target. While thymoquinone (TQ) modulates this axis, its efficacy is limited by low potency and poor drug-likeness. We utilized an integrated in silico workflow-including validated QSAR modeling (R[2] = 0.68, Q[2] ext = 0.66), ADMET profiling, docking, 200 ns molecular dynamics, and MM-PBSA analysis-to identify improved TQ-derived Keap1 inhibitors. Screening 64 analogs prioritized three leads (CHEMBL3416163, CHEMBL4636830, and CHEMBL221598) with favorable safety and blood-brain barrier permeability. Docking and dynamics confirmed these analogs form stable interactions with Kelch domain hotspots. MM-PBSA calculations revealed significantly enhanced binding free energies (-75.10 to -93.79 kJ mol[-1]) compared to parent TQ (-21.05 kJ mol[-1]), driven primarily by van der Waals and hydrophobic forces. This study identifies structurally tractable TQ analogs with improved predicted potency and establishes a robust computational framework for neuroprotective discovery. The prioritized leads are compelling candidates for in vitro and in vivo validation as redox-modulating agents in ALS.},
}

*NF-E2-Related Factor 2/metabolism/antagonists & inhibitors/chemistry
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism
*Benzoquinones/chemistry/pharmacology/metabolism/therapeutic use
*Kelch-Like ECH-Associated Protein 1/metabolism/antagonists & inhibitors/chemistry
Humans
Quantitative Structure-Activity Relationship
Molecular Docking Simulation
Molecular Dynamics Simulation
Signal Transduction/drug effects
Drug Discovery
Oxidative Stress/drug effects

@article {pmid42614000,
year = {2026},
author = {Wei, LC and Lee, CH},
title = {Healthcare Resilience Should Include the Worker-Patient Safety Loop: A Taiwan Psychiatric Hospital Perspective.},
journal = {The International journal of health planning and management},
volume = {},
number = {},
pages = {},
doi = {10.1002/hpm.70130},
pmid = {42614000},
issn = {1099-1751},
abstract = {Research before and during COVID-19 has framed health-system resilience as the capacity to absorb shocks, adapt, transform and learn while sustaining essential functions. Building on this broader literature, including Meredith et al.'s account of local public-health adaptation under political and resource constraints, we propose a worker-patient safety loop from a Taiwan psychiatric hospital perspective: workforce strain can weaken safety-critical care; near misses, adverse events and continuity failures should trigger reporting, organisational learning and corrective action; and the resulting changes should protect workers, patients and care continuity. The loop can be monitored through indicators of workforce wellbeing and safety, safety-event learning, and continuity across settings, supported by digital incident, staffing and handoff systems with safeguards for privacy and data quality. Informed by professional experience and published evidence, this conceptual framework applies to acute shocks and continuing operational pressures. Its proposed domains require prospective empirical validation before they can be treated as established measures of hospital resilience.},
}

@article {pmid42614182,
year = {2026},
author = {Shevchuk, DV and Nuzhnyi, EP and Fedotova, EY and Ershova, MV and Minaev, IV and Anikin, GA and Protsenko, AR and Abramycheva, NY and Zakharova, MN and Illarioshkin, SN},
title = {Cerebellar ataxia-onset ALS with SOD1 D91A mutation: a rare phenotype.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1889931},
pmid = {42614182},
issn = {1664-2295},
mesh = {Humans ; *Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology/complications/diagnostic imaging ; *Cerebellar Ataxia/genetics/physiopathology/diagnostic imaging ; Phenotype ; Male ; Middle Aged ; Female ; Adult ; Mutation/genetics ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) associated with mutations in the superoxide dismutase 1 (SOD1) gene is recognized for phenotypic variability, yet cerebellar ataxia as a presenting feature has been reported only in isolated cases.

METHODS: We describe four unrelated patients: three men and one woman, aged 35 to 49 years at symptom onset, who carried the SOD1 D91A (p.Asp91Ala) mutation. Two patients were heterozygous and two homozygous for the D91A variant. Clinical, neuroimaging, electrophysiological and genetic data were reviewed.

RESULTS: All patients presented with progressive gait ataxia as their initial and predominant symptom, with upper and lower motor neuron signs emerging months to years later and ultimately meeting criteria for ALS. Diagnostic latencies from ataxia onset to recognition of ALS ranged from 3 to 9 years. Cerebellar signs included gait and limb ataxia, dysmetria, intention tremor, and oculomotor abnormalities; neuroimaging revealed mild cerebellar atrophy only in one case, and electrophysiological evidence of lower motor neuron involvement was often limited at initial assessment. To our knowledge, this is the largest reported case series of patients homogeneous for a single SOD1 mutation and a shared cerebellar ataxia-onset ALS phenotype.

CONCLUSION: The findings expand the clinical spectrum of SOD1-associated ALS and underscore the importance of SOD1 genetic testing in patients with progressive adult-onset ataxia of undetermined origin, particularly given the emerging availability of SOD1-targeted therapies.},
}

Humans
*Superoxide Dismutase-1/genetics
*Amyotrophic Lateral Sclerosis/genetics/physiopathology/complications/diagnostic imaging
*Cerebellar Ataxia/genetics/physiopathology/diagnostic imaging
Phenotype
Male
Middle Aged
Female
Adult
Mutation/genetics

@article {pmid42614249,
year = {2026},
author = {Sheppard, B and Durnell, L and Haufler, AJ},
title = {From emergence to amplification: an analysis of lifecycle models to address health mis-disinformation in the digital environment.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1814102},
pmid = {42614249},
issn = {2296-858X},
abstract = {Health misinformation and disinformation (mis-disinformation) on social media presents a growing threat to individual and population health, societal resilience, and national security. While social media enables the rapid dissemination of health information, it also facilitates the spread of health mis-disinformation, a challenge further compounded by foreign influence campaigns, AI-generated content, and divergent regulatory environments. Effective interventions require tailoring to local socio-cultural and geo-political contexts. This article proposes a lifecycle model for health professionals that conceptualizes how content creation, dissemination, exposure, belief formation, and behavioral outcomes interact and can be targeted through strategic interventions to improve health outcomes and mitigate adverse behavioral effects. To achieve this, the article characterizes the challenges posed by the current and emerging health information environment; identifies and evaluates mis-disinformation lifecycle models in order to strengthen the existing knowledge base; and assesses the current state of knowledge and gaps on comparing intervention strategies to elicit desired behavioral responses, with an emphasis on individual approaches (e.g., debunking, media literacy, fact checking). A review of literature (2020-2025) identified 13 cross-comparative intervention studies which focused on key findings. Four lifecycle models were identified and assessed against six criteria derived from the lifecycle literature to identify the most suitable framework for adaptation in the public health domain. Kruijver et al.'s C5 Interaction Model emerged as the framework that satisfied the greatest number of criteria and was selected for adaptation. The model was extended to account for diverse socio-political and information environments, emerging technological interventions, and the distinct challenges posed by both mis-disinformation. Adaptation involved integrating concepts from risk perception, the Social Amplification of Risk Framework, and Social Judgment Theory, alongside health-specific examples to enhance relevance and practical applicability. To help translate the insights gained to strategy, we also convey the information in an Integrated Framework for Managing Health Mis-disinformation. By linking the evolution of health mis-disinformation to targeted interventions, the model and framework provide a foundation for promoting healthier behaviors and mitigating the adverse effects of misleading health information across diverse socio-demographic and cultural settings to improve health outcomes.},
}

@article {pmid42614372,
year = {2026},
author = {Watanabe, N and Kawahori, Y and Ta, V and Wang, D and Ohgi, KA and Wang, H and Kleschevnikova, N and Ishikawa, E and Head, BP},
title = {i.c.v. delivery of AAV9-synapsin-promoted caveolin-1 attenuates neuromuscular deficits and neuromuscular degeneration in hSOD1[G93A] mice.},
journal = {Molecular therapy. Advances},
volume = {34},
number = {3},
pages = {201820},
pmid = {42614372},
issn = {3117-387X},
abstract = {Practical and broad biodistributable gene delivery interventions are essential for advancing therapeutic strategies targeting neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We previously demonstrated that subpial delivery of AAV9-synapsin-promoted caveolin-1 (SynCav1) afforded significant neuroprotective effects in mutant superoxide dismutase (SOD)-1-induced ALS pathology. However, subpial delivery is regionally restricted, technically challenging, and highly invasive. This study evaluated whether the intracerebroventricular (i.c.v.) route of administration (ROA), an alternative CNS delivery strategy less invasive than direct spinal cord injections, could achieve broader CNS biodistribution and produce functional or histological benefits in hSOD1[G93A] mice. i.c.v. administration of AAV9-SynCav1 achieved widespread Cav-1 overexpression in the motor cortex and spinal cord. SynCav1-treated male mice exhibited improved running wheel (RW) performance and better motor-evoked potentials. Immunofluorescence revealed attenuated degeneration of cholinergic motor neurons (MNs) in the cervical and lumbar ventral horn, as well as preserved diaphragm neuromuscular junction (NMJ) innervation in SynCav1-treated mice. These findings serve as preclinical proof of concept that i.c.v. delivery of AAV9-SynCav1 can achieve CNS target engagement and produce selective functional and anatomical benefits in hSOD1[G93A] mice.},
}

@article {pmid42614391,
year = {2026},
author = {Gomes-Duarte, A and Wong, JK and Moro, A and Pasteuning-Vuhman, S and Pos, W and Haselberg, R and Sogorb-González, M and Pascoal, S and Borst, L and Chatterjee, M and Giera, M and Tsimikas, S and Sadiq, SA and van Deventer, S},
title = {Neutralization of pathogenic PC-OxPL by AAV-delivered scFv as a therapeutic strategy for amyotrophic lateral sclerosis.},
journal = {Molecular therapy. Advances},
volume = {34},
number = {3},
pages = {201822},
pmid = {42614391},
issn = {3117-387X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder defined by progressive motor neuron loss and TDP-43 proteinopathy, yet the upstream drivers of this pathology remain unclear. Oxidized phosphatidylcholines (PC-OxPL) have emerged as potent inducers of proteinopathy in the central nervous system (CNS), but their role in ALS has not been systematically explored. We identify a distinct PC-OxPL signature in the cerebrospinal fluid (CSF) of patients with sporadic ALS (sALS) and show that apolipoprotein E (apoE)-containing particles are the primary PC-OxPL carriers in this compartment. In human iPSC-derived motor neurons, PC-OxPL exposure triggered disease-relevant transcriptional alterations and TDP-43 pathology, establishing PC-OxPL as a mediator of ALS-like neurodegeneration in vitro. To counteract this toxicity, we engineered an Adeno-Associated Virus (AAV)-delivered single-chain antibody fragment (scFv), PC-OxPL-VecTab, targeting PC-OxPL neoepitopes. PC-OxPL-VecTab neutralized PC-OxPL-induced neurotoxicity, reduced TDP-43 aggregation, and prevented motor neuron death and behavioral deficits in a sALS CSF transfer mouse model. Intrathecal delivery of PC-OxPL-VecTab in minipigs achieved broad CNS biodistribution and transgene expression, supporting the feasibility of CNS delivery. These findings position PC-OxPL as a mechanistic contributor to ALS pathogenesis and establish PC-OxPL-VecTab as a therapeutic strategy for ALS with potential broader applicability to disorders associated with PC-OxPL accumulation.},
}

@article {pmid42615765,
year = {2026},
author = {Khazaal, M and Stretavská, P and Kuźma-Kozakiewicz, M and Nieporęcki, K and Betík, A and Vlčková, E and Koprušáková, MT and Petrovic, R and Cetin, H and Keritam, O and Löscher, W and Eggers, C and Iglseder, S and Orenčák, R and Molnár, MJ and Grosz, Z and Szlepák, T and Koritnik, B and Koszewicz, MA and Baumgartner, D and Slachtova, L},
title = {SOD1 Variants in Patients With Amyotrophic Lateral Sclerosis in Central Eastern Europe: From Genetic Testing to SOD1 Targeted Therapy.},
journal = {European journal of neurology},
volume = {33},
number = {8},
pages = {e70717},
doi = {10.1111/ene.70717},
pmid = {42615765},
issn = {1468-1331},
support = {PRIMUS UK 21/MED/012//Univerzita Karlova v Praze/ ; OP JAK MSCA GOALS//Ministerstvo Školství, Mládeže a Tělovýchovy/ ; 65269705//Fakultni nemocnice Brno/ ; MUNI/A/1728/2025//Masarykova Univerzita/ ; TKP2021 NVA-15//Nemzeti Kutatási Fejlesztési és Innovációs Hivatal/ ; OTKA139010//Nemzeti Kutatási Fejlesztési és Innovációs Hivatal/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology/therapy/drug therapy ; *Superoxide Dismutase-1/genetics ; Female ; Middle Aged ; Male ; Genetic Testing ; Adult ; Europe, Eastern/epidemiology ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is one of the most devastating fatal motor neuron diseases, characterized by progressive degeneration of motor neurons in the brain and spinal cord. A significant advance in ALS therapy was achieved with the recent European Medicines Agency approval of Tofersen, the first antisense oligonucleotide (ASO) specifically targeting SOD1 mRNA, a key genetic determinant of the disease. Yet, despite its clinical relevance, data on SOD1-ALS in Central Eastern Europe remain scarce.

METHODS: Here, we present a multicentric study across six countries-Austria, Czechia, Poland, Hungary, Slovakia, and Slovenia-representing approximately 16% of the European Union's population. We report all pathogenic, likely pathogenic, and uncertain SOD1 variants, along with the phenotypic features, including heritability, age, site of onset, and survival. We also assessed the availability of genetic testing, counseling, and access to Tofersen therapy across the region.

RESULTS: Out of 1200 patients with confirmed ALS, we identified 24 distinct pathogenic SOD1 variants in a total of 67 patients (median age at onset 47 [40-55] years), of whom 65.7% had familial ALS (fALS) and 34.3% had sporadic ALS (sALS). We characterized the associated phenotypes and reported that 42 patients are currently receiving Tofersen therapy.

CONCLUSION: This study provides the first comprehensive overview of SOD1-ALS in Central Eastern Europe. Our findings underscore the importance of genetic testing and counseling, as well as equitable access to targeted therapies such as Tofersen to advance patient-specific care in this region.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/epidemiology/therapy/drug therapy
*Superoxide Dismutase-1/genetics
Female
Middle Aged
Male
Genetic Testing
Adult
Europe, Eastern/epidemiology

@article {pmid42615866,
year = {2026},
author = {Horton, DK and Raymond, J and Larson, T and Goutman, SA and Mehta, P},
title = {Multidisciplinary clinic attendance and patterns of care in the U.S. National ALS Registry, 2013-2023.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2717968},
pmid = {42615866},
issn = {2167-9223},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) multidisciplinary clinics (MDCs) are the standard model of care, but national-level data on utilization and outcomes in the United States are lacking.

OBJECTIVE: To compare baseline characteristics and symptoms, clinical interventions and specialized care processes, and healthcare utilization among U.S. National ALS Registry (Registry) participants by MDC attendance.

METHODS: Registry data from 2013 to 2023 were analyzed for participants completing demographic and clinical surveys, stratified by MDC attendance (attendance vs. no attendance by survey completion).

RESULTS: Among 4764 participants, 77.0% reported attending an MDC. Baseline characteristics were similar between groups, including sex, age at diagnosis, and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. MDC attendees reported lower prevalence of dysphagia (23.6% vs. 27.5%, p = 0.007) and bowel/bladder issues (10.7% vs. 14.3%, p = 0.001). Attendees were more likely to use evidence-based interventions, including wheelchairs/scooters, noninvasive ventilation, percutaneous endoscopic gastrostomy (PEG), communication devices, and ALS disease-modifying therapies, specifically riluzole (72.7% vs. 48.1%) and edaravone (10.5% vs. 2.6%) (all p < 0.001). MDC attendees also demonstrated higher rates of specialized care processes, including advance directive completion, genetic testing, and prior research participation (all p < 0.001). For healthcare utilization, MDC attendance was associated with fewer emergency department visits among those with any use (RR 0.90, 95% confidence interval (CI) 0.82-0.99) and shorter hospital stays (β = -2.67 days, 95% CI -4.56 to -0.78).

CONCLUSION: MDC attendance was associated with greater uptake of evidence-based interventions, higher rates of specialized care processes, and reduced healthcare utilization intensity, consistent with previously reported multidisciplinary ALS care outcomes.},
}

@article {pmid42606140,
year = {2026},
author = {Flores, SV and Lillo, P and Briceño-Moya, J},
title = {Population-Level Nucleotide Diversity and Genetic Differentiation at SOD1 Across Global Human Populations.},
journal = {Annals of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1111/ahg.70052},
pmid = {42606140},
issn = {1469-1809},
abstract = {BACKGROUND: The SOD1 gene encodes superoxide dismutase 1, an antioxidant enzyme in which pathogenic variants cause a subset of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although the clinical and molecular consequences of SOD1 variants are well established, its locus-wide population genetic architecture has not been systematically characterized across global populations.

OBJECTIVE: To characterize patterns of genetic diversity, population differentiation, and evolutionary constraint across the SOD1 locus in worldwide human populations.

METHODS: We analyzed genomic variation spanning the SOD1 region in the five continental populations of the 1000 Genomes Project. Nucleotide diversity (π), fixation index (FST), and allele frequency distributions were estimated using sliding-window analyses. Bootstrap resampling was used to compare diversity within and outside the coding region. Recent positive selection was assessed using XP-nSL, and codon-based evolutionary analyses were performed using primate SOD1 orthologs.

RESULTS: The coding region consistently exhibited a twofold to threefold reduction in nucleotide diversity relative to adjacent genomic sequences across all populations. Bootstrap analyses confirmed significantly lower diversity within the locus than in flanking regions (p < 0.05 in all populations). Population differentiation was low (mean FST ≈ 0.03) and showed no pronounced peaks within the coding interval, whereas allele frequency distributions were broadly similar across continental populations. XP-nSL analyses detected no evidence of population-specific recent selective sweeps. Codon-based analyses identified only 31 variable codons among 155 analyzed positions, six codons under negative selection, and no evidence of positive selection.

CONCLUSION: The SOD1 locus exhibits reduced standing genetic variation, limited continental differentiation, and strong evolutionary conservation, consistent with sustained functional constraint. These findings provide a comprehensive population genetic framework for interpreting genetic variation at this medically important locus.},
}

@article {pmid42606797,
year = {2026},
author = {Raghunathan, T and Parthasarathy, B and Prabhu, P and Mahesh, P and Dhanushkodi, A},
title = {Regenerative strategies for ALS: stem cells and extracellular vesicles.},
journal = {Discover nano},
volume = {21},
number = {1},
pages = {},
pmid = {42606797},
issn = {2731-9229},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is caused by progressive degeneration of upper and lower motor neurons. The disease is late onset, and to date, no early diagnosis is possible. Patients with ALS have a 5-year survival rate since diagnosis. Though recent studies highlighted the possible mechanisms of motor neuron degeneration in ALS, the treatment options are extremely limited. This underscores the urgent need to develop effective therapeutic strategies that can prolong patient survival and ultimately slow/halt ALS progression. Extracellular vesicles released from the degenerative milieu contribute to ALS propagation and progression by shuttling misfolded proteins, proinflammatory cytokines, and neurotoxins; thus, they could serve as a biomarker for diagnosis and prognosis. The advancement of stem cell-based therapies for neurodegenerative diseases and the evolving understanding of extracellular vesicles as potential biotherapeutics provide a ray of hope for millions of patients suffering from neurological disorders/neurodegenerative diseases like ALS.},
}

@article {pmid42607915,
year = {2026},
author = {Zhang, Y and Dong, X and Shai, Y and Alam, M and Han, D and Hu, Y and He, Z and Zhou, Z and Jiang, H},
title = {Annexin A1 inhibits neuronal apoptosis in amyotrophic lateral sclerosis by restraining the Hippo pathway.},
journal = {Brain research},
volume = {1891},
number = {},
pages = {150510},
doi = {10.1016/j.brainres.2026.150510},
pmid = {42607915},
issn = {1872-6240},
abstract = {Annexin A1 (ANXA1) is a multifunctional regulatory protein involved in neuroinflammation and cellular homeostasis, but its role in amyotrophic lateral sclerosis (ALS) remains unclear. In this study, we investigated the relationship between ANXA1 and Hippo pathway signaling in ALS. Bioinformatic analysis of transcriptomic data from iPSC-derived motor neurons showed that ANXA1 expression was reduced in ALS and associated with apoptosis and Hippo pathway-related changes. Decreased ANXA1 expression was confirmed in hSOD1^G93A transgenic mice and NSC34 motor neuron-like cells. Phosphorylation levels of MST1/2, LATS1/2, and YAP1 were elevated, indicates activation of the Hippo pathway. Functional experiments showed that ANXA1 overexpression reduced Hippo pathway activation, enhanced cell viability, and decreased apoptosis, as increased Bcl-2 expression and reduced Bax and cleaved caspase-9 levels. In contrast, ANXA1 knockdown further activated Hippo pathway and aggravated apoptotic changes. These findings identify ANXA1 as an upstream regulator associated with Hippo pathway activation in ALS and suggest that the ANXA1/Hippo axis may represent a potential therapeutic target.},
}

@article {pmid42607955,
year = {2026},
author = {Wang, SY and Hunter, ER and Valdes Morales, KL and Perry, NJ and Feldman, E and Sobanko, JF and Etzkorn, JR and Higgins, HW and Zhang, J and Walker, JL and Miller, CJ},
title = {Response to Guan et al.'s, "Letter to the Editor 'Rethinking Routine Cartilage Grafting for Alar Defects'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.08.037},
pmid = {42607955},
issn = {1097-6787},
}

@article {pmid42608759,
year = {2026},
author = {Talukdar, G and Cvetanovic, M},
title = {Relationship of polyglutamine expansion and loss of ataxin-1 function in neurological diseases.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01950},
pmid = {42608759},
issn = {1673-5374},
abstract = {Ataxin-1 (ATXN1) was originally identified as a gene in which abnormal expansion of glutamine encoding CAG repeats causes inherited neurodegenerative disease spinocerebellar ataxia type 1. Spinocerebellar ataxia type 1 is characterized by alterations in movement, cognition, and mood, with severe pathology in the cerebellum and brain stem. Studies in spinocerebellar ataxia type 1 mouse models indicated that CAG expansion predominantly causes pathogenic ATXN1 gain-of-function in the cerebellum. Conversely, mice lacking ATXN1 are severely impaired in cognitive tests and exhibit abnormalities in cortical functions. Subsequent genetic and functional studies have associated ATXN1 with intelligence and several neurological conditions, including Alzheimer's disease, amyotrophic lateral sclerosis, schizophrenia, and multiple sclerosis. In some conditions, association is found with CAG expansions in ATXN1 and in others with the loss of ATXN1 expression. Additionally, recent studies indicate the role of ATXN1 in glial cells. Here, we review current genetic and functional evidence of how ATXN1 CAG expansion and loss of ATXN1 function contribute to brain dysfunction in spinocerebellar ataxia type 1, Alzheimer's disease, and multiple sclerosis, with an emphasis on glial cells.},
}

@article {pmid42608803,
year = {2026},
author = {Xiao, Y and Yao, X and Mao, H and Xu, Y and Liu, Z and Li, Y and Yang, X and Liu, X},
title = {Annual monitoring reveals spatiotemporal dynamics of multiple herbicide resistance in Echinochloa crus-galli populations across Zhejiang Province, China.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71186},
pmid = {42608803},
issn = {1526-4998},
support = {//"Three Rural Areas-Nine Parties" Science and Technology Collaboration Program of Zhejiang Province/ ; //National Key Research and Development Program of China/ ; //National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Echinochloa crus-galli is a damaging weed in global rice production with rapidly evolving herbicide resistance. This study investigated resistance dynamics to six major herbicides across Zhejiang Province, China (2022-2024), to inform region-specific management.

RESULTS: A 3-year systematic monitoring covering 356 populations from 27 counties revealed that the annual resistance frequency of quinclorac consistently exceeded 50.00%. Cyhalofop-butyl resistance ranged from 32.18% to 61.18%. Penoxsulam resistance ranged from 24.14% to 50.59%. Resistance to bispyribac-sodium was detected in 25.00% of populations in 2023 and 81.18% in 2024. Resistance to the newly introduced florpyrauxifen-benzyl was detected in 49.41% of populations in its first monitoring year (2024). Metamifop remains largely effective due to low resistance frequency (6.90%-16.47%). In 2023, four populations resistant to all tested herbicides were detected, increasing to seven in 2024. Molecular analysis identified acetyl-CoA carboxylase (ACCase) target-site mutations I2041N and C2088R and the acetolactate synthase (ALS) mutation W574L as contributing factors, but the majority of cross-resistant populations lacked known target-site mutations, suggesting that non-target-site metabolic resistance is predominant. Under controlled conditions, propanil maintained complete control against all tested multiple-resistant populations.

CONCLUSION: Observed trends in E. crus-galli resistance include the widespread emergence of multiple resistance to ALS and ACCase inhibitors and regional variation linked to cropping intensity. Reported resistance frequencies are conditional estimates from problem fields, not unbiased provincial rates. Non-target-site resistance predominates among cross-resistant populations. Propanil is a promising alternative pending field validation. These findings support developing region-specific resistance management strategies for rice production in Zhejiang. © 2026 Society of Chemical Industry.},
}

@article {pmid42609140,
year = {2026},
author = {Wedgwood, HE and Tuxworth, RI and Ahmed, Z},
title = {Exploring Genetic Therapies Targeting Amyotrophic Lateral Sclerosis in Animal Models: A Systematic Review and Meta-Analysis.},
journal = {The journal of gene medicine},
volume = {28},
number = {8},
pages = {e70106},
pmid = {42609140},
issn = {1521-2254},
support = {//LifeArc/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Animals ; Disease Models, Animal ; *Genetic Therapy/methods ; Humans ; Motor Neurons/pathology/metabolism ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disease, for which there is currently no known cure. ALS primarily affects motor neurons, with rapid deterioration, meaning symptoms develop quickly, from problems with speech and muscle weakness to breathing issues and paralysis. This systematic review aimed to explore the preclinical efficacy of various genetic therapies used to target ALS using in vivo rodent models.

METHODS: In vivo studies of genetic therapies targeting ALS and its symptoms published between January 2015 and December 2025 were included in this review. The following databases were used: Web of Science, Scopus and PubMed. The primary outcome investigated was the total number of motor neurons, with secondary outcomes of rodent survival and muscle function by observing rotarod performance also being analysed. The SYRCLE tool was used to assess risk of bias in included studies.

RESULTS: Of the 451 studies identified by searching the databases, 53 studies were found to be eligible for this systematic review. The articles were divided into subcategories depending on the gene target of each therapy. Meta-analysis of outcomes within appropriate studies showed significant improvements for the majority of selected outcomes (p < 0.05), favouring genetic therapy intervention.

CONCLUSIONS: Results suggest that genetic therapies in rodent models targeting ALS are effective. However, due to a high risk of bias in preclinical studies, further high-quality studies are warranted to support this conclusion and onward translation into the clinic.},
}

*Amyotrophic Lateral Sclerosis/therapy/genetics
Animals
Disease Models, Animal
*Genetic Therapy/methods
Humans
Motor Neurons/pathology/metabolism

@article {pmid42609516,
year = {2026},
author = {Li, T and Zhang, Q and Wu, Y and Huang, R},
title = {Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.},
journal = {MedComm},
volume = {7},
number = {9},
pages = {e70915},
pmid = {42609516},
issn = {2688-2663},
abstract = {Neurodegenerative diseases (NDs) are marked by selective neuronal vulnerability and progressive failure of neural circuits. Increasing evidence indicates that neuronal loss is not driven by a single terminal event, but emerges from interacting regulated cell death (RCD) programs. These programs are closely coupled to mitochondrial injury, proteostatic collapse, lysosomal stress, metabolic imbalance, glial state transitions, and chronic neuroinflammation. Yet, how distinct death pathways are organized across cell types, disease stages, and disease-specific microenvironments remains unresolved. This review examines RCD as an integrated pathogenic network in major NDs. Caspase and B-cell lymphoma 2 (BCL2) family signaling, receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein activation, NOD-like receptor family pyrin domain containing 3 and gasdermin signaling, GPX4-linked lipid peroxidation control, and autophagy lysosomal failure are discussed as convergent stress response modules rather than isolated pathways. Across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, these modules shape neuronal fate through disease-specific interactions with mitochondrial dysfunction, iron dyshomeostasis, inflammasome activation, and microglial metabolic remodeling. We further evaluate emerging therapeutic strategies that target cell death crosstalk, restore autophagy lysosomal competence, or improve delivery to the central nervous system, highlighting the importance of molecular selectivity, cellular context, disease stage, and translational feasibility.},
}

@article {pmid42609692,
year = {2026},
author = {Lazinkaitė, M and Avery, M and Olley, R and Stankūnienė, A and Czabanowska, K and Stankūnas, M},
title = {Authentic Leadership in Lithuanian Healthcare: A Qualitative Exploratory Study of Health Managers' Views and Experiences.},
journal = {Acta medica Lituanica},
volume = {33},
number = {1},
pages = {74-85},
pmid = {42609692},
issn = {1392-0138},
abstract = {Authentic Leadership (AL) is a value-based approach to leadership that focuses on self-awareness, relational transparency, balanced processing, and an internalized moral perspective. AL nurtures a supportive, high-trust work environment that boosts team cohesion, productivity, and ethical standards. In the healthcare workforce, the challenges and demands of person-centred care are significant, making AL a valuable opportunity to enhance the effectiveness of leadership and management. This study explored the key constructs and opportunities of AL within the context of the Lithuanian health system. A qualitative interpretative phenomenological approach was used to conduct semi-structured interviews with senior healthcare managers in Lithuania. The goal was to explore how these leaders understood and practiced AL. Thematic analysis was performed on the transcriptions of study participants' semi-structured interviews about perceptions of AL's four theoretical dimensions. The findings identified that Lithuanian healthcare leaders view self-awareness, moral integrity, and adaptability as central to effective leadership. Leaders emphasized self-reflection, openness to feedback, and moral consistency as crucial to their roles, enabling them to manage complex ethical responsibilities and strengthen organizational trust. AL has been shown to promote resilience in dynamic healthcare settings, thereby enabling adaptability and innovation. Leaders valued transparency and inclusive decision-making to ensure that diverse perspectives informed the team strategies. This study indicates that AL is an effective leadership approach for healthcare management in Lithuania. Our findings suggest that healthcare organizations could benefit from AL-based training programs, which may improve leaders' self-reflective practices, ethical decision-making, and collaboration skills.},
}

@article {pmid42609882,
year = {2026},
author = {Bottale, I and Spinelli, EG and Basaia, S and Ghirelli, A and Gardoni, A and Russo, T and Canu, E and Castelnovo, V and Schito, P and Falzone, Y and Filippi, M and Agosta, F},
title = {Altered perivascular space diffusivity dynamics in motor neuron disease.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag307},
pmid = {42609882},
issn = {2632-1297},
abstract = {Converging evidence supports a key pathogenic role of the glymphatic system in the accumulation of pathological aggregates in several central nervous system proteinopathies, including amyotrophic lateral sclerosis and other motor neuron diseases. This study aimed to investigate potential glymphatic impairment using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) across motor neuron disease phenotypes, to examine its clinical correlates, and to assess its relationship with white matter damage. Fifty-seven patients with motor neuron disease and 32 age- and sex-matched healthy controls underwent a 3 Tesla brain MRI scan, including diffusion tensor imaging sequences. We obtained the DTI-ALPS index from each individual, evaluating its relationship with measures of motor and cognitive disability, site of symptom onset, cognitive status, genetic status and fractional anisotropy of white matter tracts. Comparisons between groups were evaluated using analysis of covariance adjusting for age, sex, local fractional anisotropy and white matter hyperintensity burden. Partial correlations with clinical and cognitive measures were also tested. Patients with motor neuron disease exhibited significantly lower DTI-ALPS index values relative to healthy controls (P = 0.05). Patients with bulbar onset had lower DTI-ALPS values than those with spinal onset (P = 0.017). Comparable DTI-ALPS values were found across patients with classical amyotrophic lateral sclerosis clinical presentation and predominant upper or lower motor neuron clinical presentations, with no effect of cognitive diagnosis or genetic status. DTI-ALPS exhibited a significant correlation with disease duration (r = -0.38, P = 0.01). Motor neuron disease patients presenting insomnia had significantly lower DTI-ALPS values compared to those without sleep disturbances (P = 0.002). Significant positive correlations were found between ALPS index and fractional anisotropy values across major white matter tracts, including the internal and external capsules, superior longitudinal fasciculi, anterior, posterior and superior corona radiata, posterior thalamic radiation, fornix and the genu and body of the corpus callosum. This study confirms the presence of altered interstitial fluid diffusivity dynamics across motor neuron disease phenotypes, with greater impairment observed in bulbar-onset cases, patients with longer disease duration, and those experiencing more pronounced sleep disturbances. These findings may support a potential pathogenic role of glymphatic failure in the accumulation of TAR DNA-binding protein 43 proteinopathy and widespread microstructural axonal damage in motor neuron diseases.},
}

@article {pmid42610023,
year = {2026},
author = {Ettl, F and Eibensteiner, F and Greif, R and Mayhardt, S and Nern, S and Kurz, LM and Daniels, BA and Körmöczi, GF and Anvari-Pirsch, A and Grafeneder, J and Schriefl, C},
title = {Virtual reality, real-world rhythm: evaluating gamified training for medical students.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1833908},
pmid = {42610023},
issn = {2296-2565},
mesh = {Humans ; Male ; *Students, Medical/statistics & numerical data ; *Virtual Reality ; Female ; Surveys and Questionnaires ; *Education, Medical, Undergraduate/methods ; Adult ; Clinical Competence ; Young Adult ; Electrocardiography ; *Video Games ; },
abstract = {BACKGROUND: Virtual reality (VR) and gamification are increasingly recommended as adjuncts in resuscitation education, but their integration into undergraduate medical curricula and data on usability and learner acceptance remain limited. We evaluated a newly developed, gamified VR training application for medical students during their preparation for an Objective Structured Clinical Examination (OSCE).

METHODS: In this single-centre observational questionnaire study, fourth-year medical students completed VR-based advanced life support (ALS) training with randomized electrocardiogram (ECG) rhythms and gamified decision tasks. The primary outcome was usability measured with the Virtual Reality System Usability Questionnaire (VRSUQ; 0-100 points). Secondary outcomes included VR-induced symptoms (VRSQ; 0-100 points), self-rated rhythm-analysis competence before and after training (1-10), self-rated in-app performance (0-10), and trainer-reported feasibility. Continuous variables are presented as median (interquartile range [IQR]). Associations between outcomes were assessed using Spearman rank correlation coefficients.

RESULTS: Of 660 eligible students, 294 (44.5%) participated in the VR-study and completed the questionnaires. Usability was high (VRSUQ 83.3 [IQR 72.2-91.7]). VR-induced symptoms were low (VRSQ 8.3 [IQR 0.0-16.7]). Self-rated competence increased from 5.0 (IQR 4.0-7.0) before training to 8.0 (IQR 7.0-8.0) after training (p < 0.001), corresponding to a competence gain of 2.0 points (IQR 1.0-3.0). Self-rated performance was 7.0 (IQR 5.0-8.0) and correlated with usability (ρ = 0.44, p < 0.001). Overall training quality was rated 9.0 (IQR 8.0-10.0), and 91.9% would participate again. Usability did not differ between genders but was higher among students with prior VR experience. Trainers reported short setup times, manageable supervision ratios, and occasional technical support needs.

CONCLUSION: Gamified VR-based ALS training for medical students is feasible, demonstrates high usability and low symptom burden, and improves self-assessed competence. VR appears to be a well-accepted adjunct to undergraduate resuscitation education.},
}

Humans
Male
*Students, Medical/statistics & numerical data
*Virtual Reality
Female
Surveys and Questionnaires
*Education, Medical, Undergraduate/methods
Adult
Clinical Competence
Young Adult
Electrocardiography
*Video Games

@article {pmid42610209,
year = {2026},
author = {Lv, C and Zhu, W and Wen, X and Da, Y},
title = {Spatiotemporal Dynamics and Cellular States of Neuroinflammation in Amyotrophic Lateral Sclerosis: Implications for Stage‑Specific Therapeutics.},
journal = {ASN neuro},
volume = {18},
number = {1},
pages = {2715625},
pmid = {42610209},
issn = {1759-0914},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/pathology/therapy ; Animals ; *Neuroinflammatory Diseases/immunology/pathology/therapy ; Disease Progression ; Blood-Brain Barrier ; Inflammation ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex and heterogeneous pathogenesis. Accumulating preclinical and clinical evidence indicates that neuroinflammation is an important modulator of ALS pathophysiology, involving activation of resident central nervous system immune cells, dysfunction of glial support systems, disruption of neurovascular barriers, and altered recruitment of peripheral immune cells. ALS-associated neuroinflammation is temporally dynamic and varies across anatomical compartments and cellular contexts. Multiple animal models, human neuroimaging, and post-mortem tissue suggest that relatively regulated or compensatory immune responses during early stage may progressively shift to persistent, maladaptive, and potentially neurotoxic inflammatory circuits in later stage. Although previous studies have described stage-dependent changes in individual immune cell populations, an integrated stage-dependent systematic framework that unifies dynamic alterations in both central and peripheral immune compartments remains insufficiently established. In this review, we propose a four-phase conceptual framework for ALS neuroinflammation across the progressive ALS pathogenesis, aiming to provide theoretical guidance for staging inflammatory therapeutic interventions.},
}

Humans
*Amyotrophic Lateral Sclerosis/immunology/pathology/therapy
Animals
*Neuroinflammatory Diseases/immunology/pathology/therapy
Disease Progression
Blood-Brain Barrier
Inflammation

@article {pmid42611011,
year = {2026},
author = {Zdrowak, KE and Mefferd, AS and Stipancic, KL},
title = {Dissociable Effects of Dysarthria Etiology and Severity on the Minimally Detectable Change of Speech Intelligibility.},
journal = {Journal of speech, language, and hearing research : JSLHR},
volume = {},
number = {},
pages = {1-13},
doi = {10.1044/2026_JSLHR-25-00740},
pmid = {42611011},
issn = {1558-9102},
abstract = {PURPOSE: The minimally detectable change (MDC) provides a threshold for interpreting changes in outcome measures that are outside of measurement error. There is emerging evidence that dysarthria etiology and speech severity impact the MDC of speech intelligibility; however, an investigation of these factors is needed to determine the unique effects of dysarthria etiology and speech severity. The purpose of the current study was to calculate and compare MDCs of speech intelligibility across five dysarthria etiology groups and four severity levels.

METHOD: Speech Intelligibility Test recordings from 200 speakers were used as stimuli, including recordings from healthy controls (n = 40) and individuals with neurodegenerative diseases such as amyotrophic lateral sclerosis (n = 16), Huntington's disease (n = 44), multiple sclerosis (n = 60), and Parkinson's disease (n = 40). Thirty inexperienced listeners provided orthographic transcriptions of 20 speakers each. MDCs were calculated, and speech severity levels were categorized based on empirically defined speech severity levels reported in Stipancic et al. (2021). Statistical analyses, including multiple linear regression, assessed the effects of etiology and severity on MDCs.

RESULTS: Speech severity was a significant predictor of MDCs, with greater impairments to speech intelligibility resulting in higher MDCs. Dysarthria etiology was not a significant predictor of MDCs.

CONCLUSION: The impact of speech severity on MDCs of intelligibility in dysarthria underscores the need to calculate and provide MDCs across severity ranges to enhance the interpretation of patient outcomes.},
}

@article {pmid42612409,
year = {2026},
author = {Iacobelli, V and Vizziello, M and Clementi, L and Anversa, P and Cazzato, D and De Grado, A and Gallone, A and Izzo, MGA and Lanteri, P and Usai, S and Lauria, G and Rossi Sebastiano, D and Dalla Bella, E},
title = {Revisiting somatosensory evoked potentials in motor neuron diseases: neurophysiological insights from a large cohort.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {191},
number = {},
pages = {2112372},
doi = {10.1016/j.clinph.2026.2112372},
pmid = {42612409},
issn = {1872-8952},
abstract = {OBJECTIVE: To systematically investigate Somatosensory Evoked Potential (SEP) abnormalities in a large cohort of patients with Motor Neuron Disease (MND), and to explore their relationship with Motor Evoked Potentials (MEPs) and clinical phenotypes.

METHODS: We retrospectively analyzed 267 patients with confirmed MND who underwent standardized SEPs and transcranial magnetic stimulation. Patients were divided into pure/predominant Upper Motor Neuron (UMN) and pure/predominant Lower Motor Neuron/Amyotrophic Lateral Sclerosis (LMN/ALS) groups. SEP abnormalities were assessed using internal normative data, including prolonged latencies, reduced amplitudes, and increased N20-P25 amplitudes. MEPs were classified semi-quantitatively as normal or abnormal by independent raters.

RESULTS: At least one SEP abnormality was detected in 75 % of patients, with no significant differences between the UMN and LMN/ALS groups. Increased N20-P25 amplitudes were observed in both phenotypes, suggesting widespread sensory cortical hyperexcitability across the MND spectrum. In contrast, abnormal MEPs were significantly more frequent in UMN patients (p < 0.001). No significant association was found between SEP abnormalities and MEP findings. Upper- and lower-limb SEP latencies were strongly correlated (all p < 0.001), whereas increased SEP amplitudes did not correlate with latency abnormalities.

CONCLUSIONS: SEP abnormalities are highly prevalent in MND and appear largely independent from corticospinal dysfunction. Increased SEP amplitudes likely reflect primary cortical sensory hyperexcitability rather than impaired sensory conduction.

SIGNIFICANCE: These findings support the concept of MND as a multisystem network disorder that involves sensory cortical circuits and highlight the role of SEPs in the diagnostic workup.},
}

@article {pmid42597576,
year = {2026},
author = {Maeta, T and Kobayashi, K and Asano, K and Sato, T and Ito, S},
title = {Ruxolitinib-Associated Improvement in Post-transplant Air-Leak Syndrome Complicating Steroid-Dependent Organizing Pneumonia: A Case Report.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e112618},
pmid = {42597576},
issn = {2168-8184},
abstract = {Air-leak syndrome (ALS), including pneumothorax, pneumomediastinum, and subcutaneous emphysema, is a rare but life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, no standard treatment has yet been established. Here, we report the case of a 60-year-old man with acute myeloid leukemia who underwent allogeneic HSCT. He developed chronic graft-versus-host disease (GVHD) and cryptogenic organizing pneumonia (COP) on day 126 after transplantation. Although initial corticosteroid therapy improved the COP, the relapse occurred during tapering, and repeated steroid treatment failed to achieve sustained disease control. The patient subsequently developed pneumomediastinum, consistent with ALS. Ruxolitinib treatment was initiated on day 265 for steroid-dependent chronic GVHD and organizing pneumonia. Following treatment, oxygenation improved, pneumomediastinum improved, and corticosteroids were successfully tapered and discontinued without COP recurrence. Serum Krebs von den Lungen-6 (KL-6) levels decreased in parallel with clinical and radiological improvement. The introduction of ruxolitinib is associated with improvements in ALS and enabled the discontinuation of steroids. Adverse events included cytopenia and mild liver dysfunction, consistent with known safety profiles. The patient died of acute respiratory failure after transfusion, which was not considered a direct complication of the ruxolitinib treatment. This case suggests that ruxolitinib may facilitate corticosteroid tapering and radiographic improvement of organizing pneumonia-associated ALS after allogeneic transplantation.},
}

@article {pmid42598001,
year = {2026},
author = {Tan, Q and Ma, Y and Zhao, J and Hu, H},
title = {Mapping artificial intelligence in problem-based and case-based medical education: a bibliometric analysis (2019-2026).},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1901004},
pmid = {42598001},
issn = {2296-858X},
abstract = {INTRODUCTION: Problem-based learning (PBL) has been a cornerstone of medical education since its introduction at McMaster University in the 1960s. Since the public release of ChatGPT in November 2022, artificial intelligence (AI) tools have increasingly been applied to PBL and case-based learning (CBL) contexts, yet the research landscape at this intersection remains poorly characterized. This study aimed to map the growth trajectory, thematic structure, and collaboration networks of AI-PBL/CBL research from 2019 to 2026.

METHODS: A comprehensive search of Scopus and Web of Science was conducted on June 2, 2026, combining AI-related terms with PBL/CBL frameworks and medical education contexts. Using a PRISMA-guided bibliometric review workflow, 1,616 records were identified; after deduplication and eligibility screening, 735 unique publications (2019-2026, original articles, reviews, conference papers, and other eligible indexed document types) were included. Bibliometric analyses employed VOSviewer for network visualization (keyword co-occurrence, co-authorship, co-citation), CiteSpace for citation burst detection, and Bibliometrix for thematic mapping, three-field plot, and factorial analysis.

RESULTS: Publication output grew from 25 papers in 2022 to 254 in 2025, with 206 papers indexed by June 2, 2026. The United States (n = 70) and China (n = 64) led publication volume. Keyword co-occurrence analysis identified four thematic clusters: a central AI-focused cluster, a medical education and clinical reasoning cluster, a nursing and simulation-oriented cluster, and an educational technology cluster. Kung et al.'s 2023 study evaluating ChatGPT's performance on the USMLE was the most frequently co-cited reference (62 co-citations, betweenness centrality = 0.11). Thematic mapping positioned machine learning as a motor theme, while clinical reasoning, medical education, and self-directed learning appeared in the basic themes quadrant. The country/region collaboration network comprised 33 countries/regions and was led by the United States and China, although collaboration patterns remained uneven across regions.

CONCLUSION: To our knowledge, this is the first bibliometric study specifically focused on the intersection of AI technologies with PBL/CBL in health professions education. The findings reveal rapid growth after 2023, four distinct but interconnected research clusters, and a collaboration network led by the United States and China, with uneven regional participation. These results may inform curriculum design and research priorities in AI-enhanced medical education.},
}

@article {pmid42598675,
year = {2026},
author = {van de Zande, NA and Ruiter, CCC and Polman, MA and Brama, SCM and Roos, RAC and Kremer, PHC and de Bot, ST},
title = {Tracing neuroinflammation in neurodegeneration: insights from a scoping review on biofluid biomarkers.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag289},
pmid = {42598675},
issn = {2632-1297},
abstract = {Neuroinflammation is increasingly recognized as a key pathological process in neurodegenerative disease and can be monitored using biofluid biomarkers. Objective biomarkers may aid diagnosis, prognosis and progression. We conducted a scoping review of neuroinflammation biomarkers across major neurodegenerative diseases covering the past 23 years, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, Lewy body dementia, multiple system atrophy and progressive supranuclear palsy. PubMed and Web of Science were systematically searched for observational studies from 2003 to 2025 reporting neuroinflammation biomarkers in adult human subjects. Included markers encompassed blood, cerebrospinal fluid, saliva and urine, providing possible complementary information. Original studies on non-neuroinflammatory mechanisms, cellular or post-mortem biomarkers, animal models, genetics and comparisons between diseases were excluded. Two reviewers independently screened articles; biomarkers reported in ≥3 independent cohorts per disease were analysed. A total of 388 studies were included, predominantly in Alzheimer's disease/mild cognitive impairment (n = 214) and Parkinson's disease (n = 92). Eight biomarkers were most frequently reported: IL-6, TNF-α, IL-1β, CRP/hs-CRP, IL-10, MCP-1, YKL-40 and neutrophil-to-lymphocyte ratio (NLR), measured in blood or cerebrospinal fluid (CSF) as indicators of inflammatory processes associated with neurodegeneration. Across biomarkers, the strength and scope of evidence varied. Most studies demonstrated higher biomarker levels in disease, with more advanced stages, greater clinical severity and faster progression. NLR showed the most consistent pattern across staging, severity and progression, but is currently under-represented across diseases. CSF YKL-40 generally increased with disease presence and advancement; IL-6 showed consistent increases in advanced stages and with severity, although significant results were limited; MCP-1, CRP and TNF-α were mostly linked to severity and progression; IL-1β and IL-10 remained largely inconsistent. Other markers, including GFAP, showed associations in Alzheimer's disease but remain underexplored in other neurodegenerative diseases. Variability across studies, including differences in biofluid source, assay sensitivity, population characteristics and statistical approaches, limits interpretability and comparability. Although neuroinflammation is elevated in neurodegenerative diseases and generally intensifies as these diseases progress, potentially contributing to downstream pathology, the precise timing, role and predictive value of these biomarkers remain uncertain. A subset of markers, including NLR, YKL-40 and GFAP, shows relatively consistent associations and may warrant further investigation across diseases. In clinical practice, neuroinflammation biomarkers could serve as complementary tools to capture inflammatory processes related to disease heterogeneity and progression. Future longitudinal studies tracking pre-symptomatic and early-stage individuals, with standardized approaches, are needed to define temporal dynamics and explore their utility for monitoring disease progression and therapeutic response.},
}

@article {pmid42599142,
year = {2026},
author = {Etemadifar, M and Salari, M and Kashefi, M and Shams, Y and Heydari Sichani, M and Hojjatipour, F},
title = {Incidence and clinical characteristics of amyotrophic lateral sclerosis during the post-COVID-19 Period: a population-based study from Isfahan, Iran.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/17582024.2026.2718409},
pmid = {42599142},
issn = {1758-2032},
abstract = {AIMS: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Understanding the underlying causes would help further studies on the pathogenesis and treatments. Recent interest has emerged in evaluating whether the COVID-19 pandemic and vaccination have any influence on the epidemiological patterns of ALS.

MATERIALS & METHODS: To assess this association in Isfahan, Iran, during the post-COVID-19 era, we conducted this retrospective study. Newly diagnosed ALS cases were identified, and demographic data, environmental exposures, comorbidities, vaccination history, and other aspects were collected.

RESULTS: A total of 63 patients were diagnosed with definite ALS, yielding an incidence rate of 0.74 per 100,000 person-years (95% CI: 0.57-0.94). The mean age was 59.7 ± 11.6 years, and cases were predominantly male (73%). Of the 63 new ALS-diagnosed cases, 45% of patients reported probable prior COVID-19 infection, and 95.3% mentioned at least one dose of COVID-19 vaccination. Bulbar signs, including facial muscle weakness, tongue atrophy, and fasciculation, were present in 46% of cases, and emotional lability and cognitive decline were observed in 20.6%.

CONCLUSION: We showed a probable relation between COVID-19 infection and the epidemiology of ALS in post-COVID era. However, our results and symptom alterations require further investigation.},
}

@article {pmid42600830,
year = {2026},
author = {Ayala, E and Puigdemasa, J and Platikanov, S and van Drooge, BL and Bedia, C},
title = {Contrasting neurotoxic pathways triggered by PM10 in relation with organic molecular markers in suburban and rural sites in Catalonia.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {128961},
doi = {10.1016/j.envpol.2026.128961},
pmid = {42600830},
issn = {1873-6424},
abstract = {Air pollution, particularly particulate matter (PM), is a major driver of global morbidity and mortality, with increasing evidence linking it to neurological disorders. This study investigates the chemical composition and neurotoxic potential of PM collected simultaneously in three sites in Catalonia (Spain): Bellver de Cerdanya (rural background), Manlleu (suburban), and Mollet del Vallès (suburban-industrial). Fifty-four filter samples collected in 2022 were analyzed by GC-MS for 30 organic molecular tracers, including polycyclic aromatic hydrocarbons (PAHs) and levoglucosan. Extracts were tested in SH-SY5Y human neuroblastoma cells across six toxicity endpoints: cell viability, reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, antioxidant response, xenobiotic response, and p53 activation (DNA damage response). Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) on the combined chemical-biological dataset resolved four components: a winter biomass burning component enriched in levoglucosan, dehydroabietic acid, and PAHs, inducing strong cytotoxicity, oxidative stress, and xenobiotic responses; a traffic component present throughout the year; a spring-summer secondary organic aerosol (SOA) component associated with selective AChE inhibition without cytotoxicity; and a summer primary organic aerosol (POA) component. Partial Least Squares (PLS) regression linked PM10 composition with toxicity responses. Five of six models were statistically significant (R[2]CV = 0.53-0.75), with the highest performance for ROS, p53 activation, and cell death (R[2]CV ≥ 0.62). Biomass burning markers and PAHs were the main predictors of oxidative stress and cytotoxicity, whereas biogenic SOA tracers showed low importance. These findings link specific PM10 sources to distinct neurotoxic effects and highlight the importance of controlling winter emissions.},
}

@article {pmid42600917,
year = {2026},
author = {deAndrés-Galiana, EJ and Fernández-Martínez, JL and Morís, G},
title = {Identifying candidate therapeutic targets in amyotrophic lateral sclerosis through a transcriptome-wide machine-learning consensus approach for drug repurposing.},
journal = {Neuroscience},
volume = {614},
number = {},
pages = {163-179},
doi = {10.1016/j.neuroscience.2026.08.017},
pmid = {42600917},
issn = {1873-7544},
abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease for which effective disease-modifying therapies remain limited. This study aimed to derive internally recurrent ALS-associated transcriptional signatures and generate directionally interpretable drug-repositioning hypotheses using a consensus machine-learning framework. Two publicly available transcriptomic datasets from motor cortex (E-MTAB-2325) and blood (E-TABM-940) were analyzed using four feature-selection methods within 100 repetitions of 4-fold cross-validation. Probes recurrently selected in models achieving an accuracy of at least 0.90 were prioritized and examined using COGENA pathway enrichment and Connectivity Map drug-signature analysis. Fifteen qualifying models were obtained for the motor-cortex dataset and 55 for the blood dataset. No exact prioritized gene or probe identifier was shared between the two top-100 signatures, but pathway-level integration identified complementary evidence involving glial and immune regulation, proteostasis and vesicle trafficking, MAPK-related stress signaling, cytoskeletal and extracellular remodeling, and RNA-related processes. The motor-cortex dataset additionally emphasized astroglial support, glutamate handling, and inclusion-body regulation, whereas the blood dataset highlighted cytokine regulation and directionally heterogeneous immune, mitochondrial, and metabolic signals. Deferoxamine and disulfiram showed the clearest reversal-compatible profiles in motor cortex, whereas yohimbic acid and atovaquone showed reversal-compatible profiles in blood. Ciprofloxacin, prochlorperazine, and a compound group led by androsterone instead showed concordant connectivity. The results provide transparent, hypothesis-generating gene, pathway, and compound priorities, but they do not establish biomarkers, therapeutic efficacy, or clinical suitability and require validation in independent cohorts and experimental ALS models.},
}

@article {pmid42600995,
year = {2026},
author = {Ataei, R and Amini, J and Sanadgol, N and Simon, AF and Duennwald, ML},
title = {Circular RNAs in amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107574},
doi = {10.1016/j.nbd.2026.107574},
pmid = {42600995},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.},
}

@article {pmid42601592,
year = {2026},
author = {Shijo, T and Suzuki, N and Warita, H and Ikeda, K and Kato, M and Aoki, M},
title = {Poor Prognostic Factors After Gastrostomy in Patients With Amyotrophic Lateral Sclerosis: A Two-Center Retrospective Cohort Study.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70378},
pmid = {42601592},
issn = {1097-4598},
support = {JPMH23FC1008//the MHLW/ ; },
abstract = {INTRODUCTION/AIMS: Percutaneous endoscopic gastrostomy (PEG) is widely used to manage dysphagia in patients with amyotrophic lateral sclerosis (ALS). However, some patients experience rapid clinical deterioration following the procedure. Prognostic factors specific to outcomes following PEG remain insufficiently defined.

METHODS: This two-center retrospective cohort study included 117 patients with ALS who underwent PEG prior to tracheostomy between April 2011 and June 2023. Cox proportional hazards modeling was used to identify independent prognostic factors following PEG. Explanatory variables included age, sex, onset site, percent of normal forced vital capacity (%FVC), disease duration from onset to PEG, and body mass index. Optimal cutoff values for continuous variables were determined using time-dependent receiver operating characteristic analyses.

RESULTS: Among six examined clinical variables, four were independently associated with worse outcomes after PEG placement as follows: male sex, spinal onset, lower %FVC at the time of PEG, and shorter duration from onset to PEG. Cutoff values were determined as %FVC < 63% and disease duration < 12 months. Log-rank analyses confirmed significantly shorter post-PEG survival in patients meeting these criteria.

DISCUSSION: Poorer respiratory function and shorter duration from disease onset to PEG were strongly associated with worse prognosis after PEG. Male sex emerged as an independent prognostic factor, suggesting potential biological differences in disease progression after gastrostomy. These findings underscore the importance of comprehensive clinical evaluation when considering PEG in patients with ALS.},
}

@article {pmid42602697,
year = {2026},
author = {Sgobbi, P and de Rezende Pinto, WBV and Seneor, DD and Orsini, M and Chieia, MAT and Oliveira, ASB},
title = {Update and recommendations on genetic testing for amyotrophic lateral sclerosis in clinical practice: a Brazilian expert view.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1928302},
pmid = {42602697},
issn = {1664-2295},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *Genetic Testing/methods/standards ; Brazil ; Genetic Predisposition to Disease ; *Practice Guidelines as Topic/standards ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a complex and progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons. Although most ALS cases occur sporadically, without a known family history of the disease, genetic factors play a major role in its pathogenesis through monogenic, oligogenic, or polygenic mechanisms. It is estimated that 10-15% of ALS cases occur in a familial setting; however, a specific monogenic cause cannot always be identified. Establishing the underlying genetic basis in both sporadic and familial ALS is essential, as it enables individualized and family genetic counseling, facilitates the early identification of at-risk or oligosymptomatic relatives, improves the prediction of gene-specific clinical trajectories, and, more recently, determines eligibility for gene-targeted therapies, such as tofersen for SOD1-associated ALS and ulefnersen, currently under clinical investigation, for FUS-associated ALS. Over the years, differing opinions have existed regarding the role of genetic testing in individuals diagnosed with ALS. However, accumulating clinical evidence has increasingly supported the timely and early implementation of genetic testing as part of the standard clinical management of patients with ALS. In this article, we present the perspective of leading Brazilian neurologists specializing in ALS care regarding the current role of genetic testing in clinical practice.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/diagnosis
*Genetic Testing/methods/standards
Brazil
Genetic Predisposition to Disease
*Practice Guidelines as Topic/standards

@article {pmid42603254,
year = {2026},
author = {Lietzen, LW and Jensen, RD and Chippendale, RZ and Vamdrup-Andersen, AS and Andersen-Ranberg, K and Andersen, LH},
title = {Supporting geriatric thinking and management: adaptation of the Geriatrics 5Ms to Danish healthcare context.},
journal = {European geriatric medicine},
volume = {},
number = {},
pages = {},
pmid = {42603254},
issn = {1878-7649},
abstract = {PURPOSE: Coordinated, person-centred care for older adults is often challenged by multimorbidity, functional decline, and fragmented care trajectories. While Comprehensive Geriatric Assessment (CGA) remains the gold standard, its implementation outside specialised geriatric settings is limited. The Geriatrics 5Ms framework (mind, mobility, medications, multicomplexity, and matters most) offers a structured and accessible alternative. We aimed to adapt the Geriatrics 5Ms to the Danish healthcare context.

METHODS: Using Moore et al.'s ADAPT guidance, we conducted an iterative adaptation process involving academics, clinicians, and patient representatives. The framework was professionally translated and refined through expert workshops and ad hoc consultations. Evaluation activities included focus groups, individual interviews, structured feedback from health professions education and primary and secondary care. Findings informed iterative revisions and development of a core content list to support implementation.

RESULTS: Direct transfer of the original Geriatrics 5Ms was not feasible due to organisational differences and cross-sectoral responsibilities in Danish healthcare. Adaptation resulted in a shift from a physician-centred decision-support tool to an interprofessional reference framework with simplified language and strong emphasis on everyday functioning, care transitions, and shared decision-making. Stakeholders valued the structured, person-centred approach and the potential for a shared cross-sectoral language but highlighted the need for context-specific versions and clear implementation strategies.

CONCLUSION: Stakeholders perceived the Danish adaptation of the Geriatrics 5Ms as relevant and potentially feasible across sectors. Future efforts should focus on structured context-sensitive implementation and education research to ensure sustainable integration into routine clinical practice.},
}

@article {pmid42604810,
year = {2026},
author = {Littger, B and Lorenzl, S and Schuchter, P and Bublitz, S},
title = {An Encouragement to Broaden the Frame: Spiritual Care as a Complementary Perspective on Healthcare Professionals' Emotional Experiences in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70379},
pmid = {42604810},
issn = {1097-4598},
}

@article {pmid42604981,
year = {2026},
author = {Falcone, C and Arckens, L and Baiula, M and Bedini, A and Bocchi, R and Broadhead, MJ and Caprini, M and Cavaliere, F and Cesca, F and Chowdhury, HH and Ciuba, K and Civiero, L and Escartin, C and Ferroni, S and Formaggio, F and Frasca, A and Gratton, R and Holt, M and Iraci, N and Kreft, M and Leggio, L and Lia, A and Malik, AR and Min, R and Müller, FE and Murat, C and Pereira, MJ and Pekowska, A and Petrelli, F and Ramos-Gonzalez, P and Sanchez-Mico, MV and Smole, Z and Sokolova, D and Solas, M and Soldano, A and Szewczyk, LM and Torazza, C and Severino, FPU and Urrestizala-Arenaza, N and Zeug, A and Zhou, J and Zonta, M and Zorec, R and Verkhratsky, A and Gunhanlar, N},
title = {Written in the Stars: Astrocyte Biology From Evolution to Disease.},
journal = {Acta physiologica (Oxford, England)},
volume = {242},
number = {9},
pages = {e70289},
doi = {10.1111/apha.70289},
pmid = {42604981},
issn = {1748-1716},
support = {CNS2025-166813//MICIU/AEI (Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación, Spain)/ ; RYC2021-033202-I//MICIU/AEI (Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación, Spain)/ ; PID2023-146385NA-I00//MICIU/AEI (Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación, Spain)/ ; PID2024-160537OB-I00//MICIU/AEI (Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación, Spain)/ ; 951923//European Commission (H2020)/ ; //European Union - NextGenerationEU/PRTR/ ; 2023.17564.ICDT//FCT (Fundação para a Ciência e a Tecnologia, Portugal)/ ; UMO-2018/01/H/NZ4/00001//National Science Centre (NCN, Poland)/ ; UMO-2021/43/B/NZ2/02934//National Science Centre (NCN, Poland)/ ; UMO-2021/42/E/NZ2/00392//National Science Centre (NCN, Poland)/ ; UMO-2023/51/D/NZ3/02998//National Science Centre (NCN, Poland)/ ; 2024/54/E/NZ4/00134//National Science Centre (NCN, Poland)/ ; 2024/53/B/NZ4/03058//National Science Centre (NCN, Poland)/ ; A2023021F//BrightFocus Foundation/ ; 2023.00418.BD//Fundação para a Ciência e a Tecnologia (FCT) doctoral fellowship/ ; G0C9922N//KU Leuven Research Council (C14/20/071) and the Research Foundation Flanders (FWO), Belgium/ ; },
mesh = {Humans ; *Astrocytes/physiology/pathology ; Animals ; *Biological Evolution ; *Brain ; *Neurodegenerative Diseases/metabolism/pathology ; *Nervous System Diseases ; },
abstract = {In the 21st century, neuroglial research has entered a period of Renaissance, extending the views of prominent neuroanatomists and neurologists of the 19th and early 20th centuries, who assigned to glial cells numerous physiological functions and highlighted their fundamental role in the pathophysiology of nervous system diseases. Astrocytes are highly diversified in structure and function; they control brain homeostasis, support synaptic connectivity, and enable information processing in neural networks. Evolutionary diversification of astrocytes, initially emerging as supportive cells of primitive sensory organs, drove a continuous expansion of astroglial complexity and functional versatility, ultimately making them indispensable neuroprotectors and homeostatic regulators. The large, morphologically elaborate astrocytes of the human brain arguably reflect an evolutionary response to increased neuronal homeostatic demands. Astrocytes are indispensable for synaptic function, serving as the principal regulators of neurotransmitter turnover and neuronal excitability. Astrocytes also govern brain energy metabolism, mitochondrial dynamics, and calcium signaling, thereby actively shaping cortical plasticity and circuits. Astrocytes are fundamental elements of the pathophysiology of neurological, neuropsychiatric, and neurodegenerative diseases, including Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, Rett syndrome, genetic astrocytopathies, and neurotrauma, where they demonstrate complex reactive changes directed at tissue preservation and regeneration, but which can also contribute to disease progression. Advances in single-cell transcriptomics, calcium imaging, chemogenetics, and iPSC-based models have transformed our understanding of astrocyte diversity and disease-specific dysfunction, opening new avenues of investigation. Given that no CNS disorder is known to occur without astrocyte involvement, multiple astrocyte-specific molecules represent compelling targets for cell-directed therapeutic strategies.},
}

Humans
*Astrocytes/physiology/pathology
Animals
*Biological Evolution
*Brain
*Neurodegenerative Diseases/metabolism/pathology
*Nervous System Diseases

@article {pmid42605296,
year = {2026},
author = {Ferdoush, S and Seklani, M and Kumar, P and Abekoon Mudiyanselage, SRJ and Dsouza, A},
title = {Acute Hypercapnic Respiratory Failure as the Initial Presentation of Motor Neuron Disease: A Respiratory Diagnostic Challenge.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e112832},
pmid = {42605296},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by degeneration of the upper and lower motor neurons, with respiratory muscle involvement typically occurring in the later stages of the disease. Presentation with acute hypercapnic respiratory failure as the initial clinical manifestation is uncommon and frequently leads to diagnostic delay or misattribution to primary cardiopulmonary pathology. We present the case of a 60-year-old man with no prior respiratory history who presented with acute dyspnea and was found to have severe hypercapnic respiratory failure requiring urgent noninvasive ventilation. Clinical examination and initial investigations revealed no clear intrinsic pulmonary cause. A detailed history subsequently identified a four-month progression of neurological symptoms, including dysarthria, sialorrhea, asymmetric upper limb weakness, and significant unintentional weight loss. Neurological examination demonstrated tongue fasciculations, widespread muscle wasting, and a combination of upper and lower motor neuron signs. Following acute stabilization and discharge with domiciliary noninvasive ventilation, a specialist neurological assessment confirmed a diagnosis of ALS. This case highlights the clinical importance of considering underlying neuromuscular causes in patients presenting with unexplained hypercapnic respiratory failure, particularly when clinical findings are discordant with the severity of the gas exchange abnormalities. Early recognition of ALS in this context facilitates the timely initiation of ventilatory support and multidisciplinary care, which are essential for optimizing survival and quality of life.},
}

@article {pmid42595782,
year = {2026},
author = {Hetz, C and Thielen, P and Fisher, J and Pasinelli, P and Brown, RH and Korsmeyer, S and Glimcher, L},
title = {Correction: The proapoptotic BCL-2 family member BIM mediates motoneuron loss in a model of amyotrophic lateral sclerosis.},
journal = {Cell death and differentiation},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41418-026-01701-0},
pmid = {42595782},
issn = {1476-5403},
}

@article {pmid42596010,
year = {2026},
author = {Kamphausen, A and Pilz, M and Baumgärtel, M and Kubitz, JC and Engelen, C},
title = {Effect of an app-guided advanced cardiac life support algorithm on teamwork, non-technical skills, and workload in simulated in-hospital cardiac arrest: a randomized controlled feasibility trial.},
journal = {Scandinavian journal of trauma, resuscitation and emergency medicine},
volume = {34},
number = {1},
pages = {},
pmid = {42596010},
issn = {1757-7241},
mesh = {Humans ; *Heart Arrest/therapy ; *Advanced Cardiac Life Support/methods ; Prospective Studies ; Feasibility Studies ; Female ; *Mobile Applications ; Male ; *Algorithms ; *Patient Care Team ; *Workload ; *Clinical Competence ; },
abstract = {BACKGROUND: In-hospital cardiac arrest carries high mortality despite advances in monitoring, rapid response systems, and adherence to advanced life support (ALS) guidelines. Digital decision-support tools, including mobile applications, are increasingly explored to improve guideline adherence, yet their impact on cognitive workload, team performance, and ALS performance remains uncertain.

METHODS: We conducted a prospective, randomized, simulation-based controlled feasibility trial with 40 interprofessional teams (80 participants) comparing ALS performance with and without the use of the 'CPR Leader' app. Two-person teams were randomized 1:1 to intervention or control and followed standardized in-hospital cardiac arrest scenarios (asystole and ventricular fibrillation). Primary outcomes included team performance (TEAM), non-technical skills (ANTS), and subjective workload (NASA-TLX). Secondary outcomes comprised objective resuscitation metrics, including time to rhythm analysis, defibrillation, medication administration, and chest compression quality.

RESULTS: Overall NASA-TLX scores were high but comparable between intervention and control group (mean 49.2 ± 13.6 vs. 54.1 ± 14.6; p = 0.2), with higher effort reported in the app group and higher frustration in the control group. TEAM and ANTS scores showed no evidence of meaningful between-group differences. Across the two scenarios types, ALS performance metrics-including rhythm analysis, defibrillation, medication administration, and chest compression quality-were similar between groups, with the exception of earlier chest compression initiation in the control group during ventricular fibrillation.

CONCLUSIONS: In this exploratory randomized simulation study involving predominantly experienced in-hospital healthcare professionals, the use of a resuscitation support application did not demonstrate a clear improvement in adherence to guideline-recommended ALS algorithms or resuscitation performance compared with standard practice. These findings likely reflect the high level of participants' clinical experience and should not be generalized to novice providers, mixed-experience teams, prehospital settings, or training environments. Further studies are warranted to evaluate the potential benefits of cognitive aids in less experienced populations and in real-world clinical practice.

TRIAL NUMBER: None.},
}

Humans
*Heart Arrest/therapy
*Advanced Cardiac Life Support/methods
Prospective Studies
Feasibility Studies
Female
*Mobile Applications
Male
*Algorithms
*Patient Care Team
*Workload
*Clinical Competence

@article {pmid42596024,
year = {2026},
author = {Reeves, MM and Aviles Carpintero, S and Zanovello, M and Jansen-West, K and Yue, M and Calliari, A and Song, Y and Dunmore, J and Maroto Cidfuentes, C and Ball, S and Kachergus, JM and Killeen, HE and Rawlinson, B and Engelberg-Cook, E and DeTure, M and Day, GS and Graff-Radford, NR and Boeve, BF and Knopman, DS and Petersen, RC and Murray, M and Thompson, AE and Dickson, DW and Fratta, P and Petrucelli, L and Josephs, KA and Prudencio, M},
title = {The UNC13A cryptic exon associates with cognitive impairment in Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {},
pmid = {42596024},
issn = {1758-9193},
support = {R35 NS097273/NS/NINDS NIH HHS/United States ; R01 NS120992/NS/NINDS NIH HHS/United States ; P30AG062677/AG/NIA NIH HHS/United States ; U54NS123743, R35NS097273//NIH/ ; R01NS120992, R01AG037491//NIH/ ; R01NS120992, U54NS123743//NIH/ ; MR/M008606/1 and MR/S006508/1//Lady Edith Wolfson Fellowship/ ; U54 NS123743/NS/NINDS NIH HHS/United States ; U01 AG006786/AG/NIA NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; U01AG006786/AG/NIA NIH HHS/United States ; R01 AG037491/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/genetics/pathology/complications ; Polymorphism, Single Nucleotide/genetics ; Male ; Female ; DNA-Binding Proteins/metabolism ; *Exons/genetics ; *Nerve Tissue Proteins/genetics ; Aged ; Brain/pathology/metabolism ; Aged, 80 and over ; Cohort Studies ; Genetic Predisposition to Disease ; },
abstract = {BACKGROUND: TAR DNA-binding protein of 43 kDa (TDP-43) is often found in the brains of patients with Alzheimer's disease (AD), where it co-occurs with amyloid β plaques and tau neurofibrillary tangles, and associates with accelerated cognitive decline and brain atrophy. TDP-43's function of repressing the inclusion of cryptic exons (CEs) during RNA splicing is compromised in AD. A single-nucleotide polymorphism (SNP) located within the CE in the UNC13A gene [rs12973192 (C > G)] is associated with higher disease risk and reduced survival in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) by weakening TDP-43 binding promoting CE inclusion.

OBJECTIVE: To investigate the influence of the rs12973192 UNC13A CE SNP and UNC13A cryptic splicing on TDP-43 pathology, survival and cognitive impairment in AD.

METHODS: We evaluated the UNC13A CE SNP in a cohort of 1,672 AD, including 643 AD brains with available cognitive measurements and 73 AD cases for which we measured cryptic RNA levels in the amygdala. We also evaluated a cohort of 466,517 from the UK Biobank to determine associations between the UNC13A CE SNP and dementia diagnosis.

RESULTS: In AD, the UNC13A CE SNP associated significantly with cognitive decline, but not with TDP-43 pathology or with survival. UNC13A cryptic RNA levels in the amygdala were a better predictor of cognitive decline than the UNC13A CE SNP itself, while STMN2-another well-known CE target-exhibited no such association.

CONCLUSIONS: These findings point to UNC13A cryptic splicing as a specific driver of cognitive decline in AD, outperforming both genetic risk and other cryptic targets.},
}

Humans
*Alzheimer Disease/genetics/pathology/complications
Polymorphism, Single Nucleotide/genetics
Male
Female
DNA-Binding Proteins/metabolism
*Exons/genetics
*Nerve Tissue Proteins/genetics
Aged
Brain/pathology/metabolism
Aged, 80 and over
Cohort Studies
Genetic Predisposition to Disease

@article {pmid42596047,
year = {2026},
author = {Ohta, K and Fujino, Y and Sada, Y},
title = {Allelic dosage across four functional ALS loci shapes ALS-inhibitor resistance in allotetraploid Pontederia vaginalis.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71188},
pmid = {42596047},
issn = {1526-4998},
abstract = {BACKGROUND: Pontederia vaginalis, carrying four functional ALS genes, is a major weed in Asian rice paddies. Acetolactate synthase (ALS)-inhibitor resistance is caused by target-site mutations, but how resistant allelic dosage affects whole-plant susceptibility in weeds with more than three functional ALS loci remains unclear. This study quantified the effect of resistant allele number on herbicide susceptibility in P. vaginalis using progeny of a cross between two lineages carrying Pro197Ser substitutions in different ALS loci.

RESULTS: Hybridization between lineages carrying Pro197Ser in MvALS1 or MvALS3 yielded F2 progeny with varying resistant allelic dosages, and genotyping confirmed independent segregation of these loci. Dose-response assays with imazosulfuron and bensulfuron-methyl revealed that susceptibility decreased sharply as resistant alleles increased from zero to two (ED90 (effective dose to have 90% reduction of dry weights) shifts ~3000-fold for imazosulfuron), whereas additional alleles beyond two conferred only marginal further resistance (~four- to five-fold). For genotype-confirmed one-resistant-allele plants (n = 25), the bootstrap 95% confidence interval (CI) for ED90 was 16.7-292.0 g active ingredient (a.i.) ha[-1] (median: 92.6 g a.i. ha[-1]), encompassing the registered field dose (90 g a.i. ha[-1]) and non-overlapping with the CIs of the zero- and two-allele classes. The F2 segregation ratios matched theoretical expectations, suggesting non-target-site resistance does not substantially distort inheritance patterns.

CONCLUSION: These results demonstrate a clear allelic dosage effect on ALS-inhibitor resistance in P. vaginalis, with diminishing returns beyond two resistant alleles. The CI for one-resistant-allele plants encompasses the registered field dose, indicating genuinely uncertain control outcomes at standard application rates. These findings challenge fixed dominant/recessive classifications and highlight the need to quantify allelic dosage effects in polyploid weeds for accurate resistance risk assessment. © 2026 Society of Chemical Industry.},
}

@article {pmid42597242,
year = {2026},
author = {Liu, Z and Yang, H and Cui, J and Guan, Z and Gao, D and Feng, P and Yang, H and Li, W and Zhao, Y and Yang, Q and Zheng, X and Liu, Q and Geng, Z},
title = {White matter abnormalities in amyotrophic lateral sclerosis: a free water imaging study.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1899073},
pmid = {42597242},
issn = {1662-4548},
abstract = {OBJECTIVE: To investigate white matter microstructural alterations in amyotrophic lateral sclerosis (ALS) using free-water-corrected diffusion tensor imaging (FW-DTI), compare its findings with those of conventional DTI, and examine the clinical correlations and preliminary diagnostic value of these metrics.

METHODS: 44 ALS patients and 42 healthy controls underwent multi-b-value diffusion MRI. Conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AxD], radial diffusivity [RD]), free-water-corrected metrics (FW-FA, FW-MD, FW-AxD, FW-RD), and the free-water fraction (FWF) were calculated. Tract-based spatial statistics (TBSS) was used for voxelwise group comparisons. Correlations between clinical parameters, including disease progression rate (ΔFS) and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score, and DTI metrics were examined. A diagnostic nomogram was constructed using logistic regression based on imaging markers that showed significant differences between groups.

RESULTS: Conventional DTI identified white matter abnormalities in ALS-related regions, including corticospinal tract-related regions, the corpus callosum, and the cingulate gyrus. FW-DTI showed additional and partially distinct alterations, including changes in the fornix, bilateral superior corona radiata, anterior and posterior corona radiata, and the posterior limb of the internal capsule. The free-water fraction did not differ between groups. Correlation analysis revealed that ΔFS was negatively associated with FA in the left posterior limb of the internal capsule (r = -0.432), and the ALSFRS-R score was positively associated with FW-FA in the right anterior corona radiata (r = 0.389). A diagnostic nomogram combining FA in the right cerebral peduncle and FW-FA in the right anterior corona radiata showed preliminary discriminative performance (area under the curve [AUC] = 0.860).

CONCLUSION: FW-DTI may provide complementary model-derived information for characterizing ALS-related white matter alterations beyond conventional DTI. Specific regional metrics were associated with ΔFS and the ALSFRS-R score, and the preliminary diagnostic nomogram yielded an AUC of 0.860.},
}

@article {pmid42595353,
year = {2026},
author = {Fang, F},
title = {Physical activity in ALS: friend or foe?.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2026-339492},
pmid = {42595353},
issn = {1468-330X},
}

@article {pmid42595317,
year = {2026},
author = {Oliveira, AC and Corrêa, TDS and Vieira, LF and Carvalho, IR and Chaul, DN and Almeida, AECG and Faria, VLG and Simamoto Júnior, PC and Morais, JF and Stelzer, FG and Goulart, IMB and Santos, DFD},
title = {Nocturnal polygraphy in neuromuscular disorders: is it a useful diagnostic tool?.},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {7},
pages = {1-8},
pmid = {42595317},
issn = {1678-4227},
mesh = {Humans ; *Sleep Apnea, Obstructive/diagnosis/epidemiology/etiology/physiopathology ; *Neuromuscular Diseases/complications/physiopathology ; Female ; Prospective Studies ; Male ; *Polysomnography/methods ; Middle Aged ; Prevalence ; Adult ; Surveys and Questionnaires ; Aged ; },
abstract = {BACKGROUND: Patients with neuromuscular diseases (NMDs) have a high incidence of sleep-related breathing disorders. These include obstructive sleep apnea (OSA), which is characterized by recurrent episodes of upper airway obstruction during sleep, resulting in intermittent hypoxemia and sleep fragmentation. Obstructive sleep apnea may be more common in patients with NMDs than in the general population.

OBJECTIVE: To assess the prevalence of OSA through home polygraphy at a public university hospital during respiratory evaluations of patients with NMDs, and its contribution to the indication of non-invasive ventilation. It did not aim to validate a model for early indication.

METHODS: The present prospective study collected data over the period from May 2021 to June 2024, using medical records and tests such as spirometry to evaluate pulmonary respiratory function, home polygraphy, and sleep assessments using the Epworth Sleepiness Scale (ESS) and a symptom questionnaire.

RESULTS: A total of 74 patients were included, 64.7% (n = 48) of whom had OSA. The most prevalent NMDs were muscular dystrophy (n = 22; 29.7%), myasthenia gravis (n = 13; 17.6%), and amyotrophic lateral sclerosis (ALS) (n = 11; 14.9%). Apnea-hypopnea index (AHI) values were higher in the supine position (11.6 ± 12.6) compared to the AHI in the non-supine position (7.0 ± 14.1), which indicates, on average, a mild degree of OSA. The ESS revealed that 40.5% of patients had scores indicating excessive daytime sleepiness (EDS).

CONCLUSION: The findings reinforce the importance of early OSA diagnosis in patients with NMDs.},
}

Humans
*Sleep Apnea, Obstructive/diagnosis/epidemiology/etiology/physiopathology
*Neuromuscular Diseases/complications/physiopathology
Female
Prospective Studies
Male
*Polysomnography/methods
Middle Aged
Prevalence
Adult
Surveys and Questionnaires
Aged

@article {pmid42595324,
year = {2026},
author = {Fustes, OJH and Teive, HAG},
title = {Amyotrophic lateral sclerosis (ALS): new insights 156 years after Charcot's masterful description.},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {7},
pages = {1-4},
pmid = {42595324},
issn = {1678-4227},
mesh = {*Amyotrophic Lateral Sclerosis/history ; History, 19th Century ; Humans ; History, 20th Century ; },
abstract = {In 1869, Charcot and Alix Joffroy published the first detailed clinical and neuropathological description of amyotrophic lateral sclerosis (ALS), establishing the correlation involving muscle weakness, atrophy, spasticity, and degeneration of the lateral corticospinal tracts. Charcot unified the involvement of upper and lower motor neurons into a single clinical entity. His pioneering description was limited to the motor system, reflecting the scientific constraints of his time. Charcot interpreted ALS primarily as a disorder of the motor system, a conclusion consistent with the clinical and pathological methods available in the late nineteenth century. Neurological investigation at that time relied mainly on detailed clinical observation, anatomical correlation at autopsy, and relatively-simple physiological techniques. These approaches were well suited to identify motor dysfunction but were far less capable of revealing subtle cognitive or behavioral alterations. Currently, ALS is recognized as a multisystem neurodegenerative disorder. Thus, Charcot's historical contribution was crucial for the initial understanding of ALS, while modern perspectives acknowledge its broader clinical complexity beyond the motor system.},
}

*Amyotrophic Lateral Sclerosis/history
History, 19th Century
Humans
History, 20th Century

@article {pmid42595352,
year = {2026},
author = {Gao, J and Chalitsios, CV and Bennett, D and Doherty, A and Turner, MR and Thompson, AG},
title = {Associations of self-reported and objectively measured physical activity and amyotrophic lateral sclerosis risk.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2026-339165},
pmid = {42595352},
issn = {1468-330X},
abstract = {BACKGROUND: The role of physical activity in the risk of amyotrophic lateral sclerosis (ALS) is debated. It is also unclear whether the association differs in people at high genetic risk of ALS.

METHODS: The strength and shape of the association between self-reported and device-measured physical activity and incident diagnosis of ALS in the UK Biobank cohort was analysed using Cox regression, adjusting for potential confounders. Cubic splines were used to assess non-linearity. Analyses were performed in the entire cohort and restricted to those with increased genetic risk due to C9ORF72 expansion carriage or C-allele homozygosity at rs12608932 in UNC13A.

RESULTS: Among 384 836 participants with valid questionnaire data, the median age at recruitment was 57.0 years (IQR 50.0-63.0) and median follow-up was for 14.0 years (IQR 13.3-14.6), with 541 incident diagnoses of ALS. Higher self-reported physical activity was associated with a lower risk of ALS (HRhigh vs low=0.77, 95% CI 0.61 to 0.96). The relationship was non-linear, with lowest risk in those in the mid-range self-reported activity. Higher overall device-measured activity was also associated with a lower risk of ALS (HRper 1SD = 0.75, 95% CI 0.58 to 0.97, n=96 570, 98 ALS events) but with a linear dose-response relationship. The association of physical activity with ALS was similar in individuals with C-allele homozygosity at rs12608932 in UNC13A and directionally consistent but not statistically significant in C9ORF72-HRE carriers (n=535, 56 ALS events).

CONCLUSION: Higher self-reported and device-measured overall physical activity were associated with a lower risk of ALS overall, but with a potentially non-linear dose-response relationship.},
}

@article {pmid42533617,
year = {2026},
author = {Rasmussen, LK and Gomes Moreira, D and Okarmus, J and Simonsen, A and Meyer, M},
title = {Mitophagy in neurodegeneration: crosstalk between PRKN/parkin-dependent and PRKN-independent pathways.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-23},
doi = {10.1080/15548627.2026.2711596},
pmid = {42533617},
issn = {1554-8635},
abstract = {Mitochondrial quality control is essential for cellular homeostasis, particularly in neurons, where mitochondrial dysfunction is implicated in the pathogenesis of neurodegenerative diseases. Mitophagy, the selective degradation of damaged or superfluous mitochondria, plays a central role in maintaining mitochondrial integrity and metabolic balance. This review provides a comprehensive overview of the best-characterized PINK1-PRKN/parkin-dependent mitophagy pathway and the expanding repertoire of PRKN-independent mechanisms, including additional ubiquitin-dependent, receptor-mediated, and lipid-mediated pathways. We explore how these pathways intersect and compensate for one another, highlighting the complexity and adaptability of mitochondrial quality control networks. Furthermore, we discuss how dysregulated mitophagy contributes to the onset and progression of neurodegenerative diseases. By examining the interplay between mitophagy pathways and their regulation under physiological and pathological conditions, this review underscores the therapeutic potential of targeting mitophagy in neurodegeneration. Future studies should aim to decode the spatiotemporal dynamics of these pathways to uncover novel opportunities for clinical intervention.Abbreviations: AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; AMBRA1: autophagy and beclin 1 regulator 1; AMFR/GP78: autocrine motility factor receptor; AMPK: AMP-activated protein kinase; ARIH1: ariadne RBR E3 ubiquitin protein ligase 1; ATG: autophagy related; Aβ: amyloid beta; BCL2L13: BCL2 like 13; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAMc: core autophagy machinery components; CSNK2/CK2: casein kinase 2; DUB: deubiquitinase; DNM1L/DRP1: dynamin 1 like; FKBP8: FKBP prolyl isomerase 8; FUNDC1: FUN14 domain containing 1; GABARAP: GABA type A receptor-associated protein; GLP-1: glucagon-like peptide 1; HD: Huntington disease; HUWE1: HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1; IMM: inner mitochondrial membrane; iPSC: induced pluripotent stem cell; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF5: membrane associated ring-CH-type finger 5; MCL1: MCL1 apoptosis regulator, BCL2 family member; MDV: mitochondria-derived vesicle; MFN1: mitofusin 1; MFN2: mitofusin 2; MQC: mitochondrial quality control; mtDNA: mitochondrial DNA; MUL1: mitochondrial E3 ubiquitin protein ligase 1; NBR1: NBR1 autophagy cargo receptor; OMM: outer mitochondrial membrane; OMMAD: outer mitochondrial membrane-associated degradation; OPA1: OPA1 mitochondrial dynamin like GTPase; OPTN: optineurin; OXPHOS: oxidative phosphorylation; PARL: presenilin associated rhomboid like; PD: Parkinson disease; PE: phosphatidylethanolamine; PG: phagophore; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; PINK1: PTEN induced kinase 1; PPARGC1A/PGC-1α: PPARG coactivator 1 alpha; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: phosphatidylinositol 3-kinase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RHOT1/Miro1: ras homolog family member T1; ROS: reactive oxygen species; SIAH1: siah E3 ubiquitin protein ligase 1; SMURF1: SMAD specific E3 ubiquitin protein ligase 1; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TCA: tricarboxylic acid cycle; TFAM: transcription factor A, mitochondrial; TIMM: translocase of inner mitochondrial membrane; TOMM: translocase of outer mitochondrial membrane; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; UPRmt: mitochondrial unfolded protein response; UPS: ubiquitin-proteasome system; USP30: ubiquitin specific peptidase 30; VCP: valosin containing protein; VDAC: voltage dependent anion channel; WIPI: WD repeat domain, phosphoinositide interacting.},
}

@article {pmid42592079,
year = {2026},
author = {Tu, S and Mahoney, CJ and Huynh, W and Vucic, S and Kiernan, MC},
title = {Cortical excitability stratifies neurochemical profiles in amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag292},
pmid = {42592079},
issn = {2632-1297},
abstract = {Transsynaptic deficits arising from an imbalance in excitatory/inhibitory inter-neuronal circuitry have been extensively shown to underlie the phenomena of altered cortical motor excitability in patients with amyotrophic lateral sclerosis (ALS), with glutamate-induced excitotoxicity believed to represent a primary mechanism of ALS pathogenesis. In vivo evidence of glutamate abnormality in ALS patients, however, remains inconsistent, likely reflecting heterogeneity in the severity of underlying cortical dysfunction. The current study assessed the utility of short interval intracortical inhibition (SICI), a validated marker of upper motor neuron (UMN) dysfunction in ALS, to stratify cortical motor metabolite abnormalities, as determined by proton magnetic resonance spectroscopy ([1]H-MRS). Serial [1]H-MRS data were acquired over 2.5 years for two ALS participants with contrasting profiles of progressive motor dysfunction as a pilot study. Longitudinal monitoring of these participants demonstrated stable cortical motor metabolite concentrations in the participant with lower motor predominant disease presentation but progressive changes in glutamate-glutamine (Glx) and N-acetylaspartate (NAA) concentrations in the participant with a classical ALS presentation. Fifty-four participants (34 ALS; 20 control) were prospectively recruited for a formal study. All patients underwent threshold-tracking transcranial magnetic stimulation) and were classified as having high (>5.5%; H-SICI) or low (≤5.5%; L-SICI) cortical motor inhibition. Matching 3T single-voxel [1]H-MRS data were acquired from the hand region of the motor cortex for all participants at baseline, with a subset of patients (n = 10) longitudinally assessed at 6 months. Dissociable patterns of pathological change in NAA and Glx/NAA metabolites were observed at baseline and longitudinally in ALS. At baseline, L-SICI ALS participants with increased cortical motor excitability demonstrated a significant bilateral reduction in NAA and elevated Glx/NAA metabolite concentrations (P-values < 0.03), contrasting to H-SICI ALS participants, where the neurochemical concentration was preserved. At follow-up, H-SICI patients demonstrated a trend towards elevated Glx and Glx/NAA in the left motor cortex (P-values ≤ 0.06). In contrast, L-SICI patients demonstrated stable concentrations of Glx but further reductions in NAA ratio (P = 0.04). Cortical excitability and brain neurochemical profile abnormalities reflect evolving states of UMN dysfunction in ALS. Elevated Glx/NAA metabolite concentration underlies greater cortical motor dysfunction in ALS. Longitudinal [1]H-MRS holds potential prognostic utility for clinical monitoring of ALS disease trajectory.},
}

@article {pmid42592352,
year = {2026},
author = {Vinceti, M and Ferrante, M and Filippini, T and Wise, LA and Urbano, T and Bedin, R and Gianferrari, G and Rapisarda, P and Pulvirenti, E and Oliveri Conti, G and Mandrioli, J},
title = {Central nervous system concentrations of nano- and microplastics and risk of amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag296},
pmid = {42592352},
issn = {2632-1297},
abstract = {Growing evidence suggests that microplastics, particularly nanoplastics, may be neurotoxic. However, there are few studies of neurologic diseases, especially amyotrophic lateral sclerosis (ALS). In a hospital-based case-control study, we measured in vivo concentrations of nano- and microplastics (size 0.1-10 µm) in serum and CSF among 24 newly diagnosed cases of ALS and 20 controls. Adjusting for sex and age, we found a strong positive association between serum and CSF microplastic concentrations and higher microplastic concentrations in the CSF and serum of ALS cases compared with controls. In spline regression analyses, CSF microplastic concentrations showed a positive monotonic association with odds of ALS. Serum microplastic concentrations also showed a positive association with ALS, but only above a certain threshold. Among ALS cases, serum-but not CSF-microplastic concentrations were positively associated with neurofilament light chain, a biomarker of neuroaxonal damage. Given the case-control design, we cannot rule out reverse causation (i.e. that ALS-related factors caused greater bioaccumulation of microplastics) or the possibility that the association reflects changes in lifestyle or other chemical exposures. However, the observed pattern raises the possibility of an aetiologic role of nano- and microplastics in motor neuron degeneration and indicates higher CNS concentrations of these chemicals in ALS cases.},
}

@article {pmid42592497,
year = {2026},
author = {Pal, S and Das, S and Biswas, S and Murugan, SD and Jana, NR and Chattopadhyay, AP and Singh, NDP},
title = {Exploring viscosity sensitivity of π-extended coumarin fluorogen-based PRPGs for precise photorelease of valproic acid: detection and defibrillation of TDP-43 aggregation.},
journal = {Chemical science},
volume = {},
number = {},
pages = {},
pmid = {42592497},
issn = {2041-6520},
abstract = {Alteration of cellular microenvironment viscosity by protein aggregation plays a crucial role as a biophysical parameter that reflects abnormal cellular behaviour, leading to neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), etc. Herein, we report the design and development of a series of coumarin fluorogen-based photoremovable protecting groups (PRPGs, 5a-d) with variations in substitutions tethered with a π-extended linker that integrate viscosity sensing with visible-light-triggered release of bioactive molecules. By introducing π-extended conjugation and systematic substitution, the coumarin fluorogen-based PRPGs exhibit twisted intramolecular charge transfer (TICT)-based fluorescence modulation in response to microenvironmental viscosity. Comprehensive photophysical and photochemical investigations, supported by theoretical calculations, identified PRPG 5d as the most sensitive viscosity-responsive system with green-light absorption. Under viscous conditions, restricted bond rotation suppresses nonradiative decay and photoisomerization, enabling efficient photorelease of the neuroprotective agent valproic acid. The versatility of PRPG 5d was demonstrated in biologically relevant in vitro models, including TDP-43 protein aggregation and Parkinson's disease induced SH-SY5Y neuroblastoma cells. In both extracellular and intracellular neurodegenerative environments, increased viscosity was effectively sensed, triggering light-mediated valproic acid release and subsequent defibrillation. Overall, this work establishes coumarin fluorogen-based PRPGs as a promising platform for viscosity-guided, spatiotemporally controlled drug release, offering potential applications in the diagnosis and targeted therapy of neurodegenerative diseases.},
}

@article {pmid42592720,
year = {2026},
author = {Żur-Wyrozumska, K},
title = {Severe hypersensitivity reaction during tofersen therapy in amyotrophic lateral sclerosis associated with the rare SOD1 p.Val120Phe mutation.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.113584},
pmid = {42592720},
issn = {0028-3843},
}

@article {pmid42592867,
year = {2026},
author = {McFarlane, R and Anneser, J and Al-Chalabi, A and Chiò, A and Mcdermott, CJ and Meyer, T and Mora, G and Sermeus, W and Stavroulakis, T and Tappenden, P and Van Den Berg, LH and Winkler, AS and Galvin, M and Hardiman, O},
title = {The EQ-5D-5L in amyotrophic lateral sclerosis: an international longitudinal exploration as part of ALS-CarE.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2715921},
pmid = {42592867},
issn = {2167-9223},
abstract = {BACKGROUND: The EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) is widely used in health outcomes research, but its longitudinal performance in amyotrophic lateral sclerosis (ALS), particularly across international cohorts, remains poorly characterized. This study examined whether the EQ-5D-5L captures clinically meaningful change over time in ALS and how national value sets influence interpretation of that change.

METHODS: EQ-5D-5L data from 296 patients across six European ALS centers in five countries were analyzed over 18.6 months (IQR 17.9-20.8). Baseline and follow-up assessments were compared using the Paretian Classification of Health Change and Health Profile Grids. Country-specific tariffs were applied to identical health-state transitions. Associations between EQ-5D measures and King's stage were assessed.

RESULTS: Overall health states worsened over time, although mixed change remained common (31.0%-39.0%), reflecting simultaneous improvement and deterioration across dimensions. Pain/discomfort and anxiety/depression were the only domains showing notable improvement at later follow-up. Mean health-state ranks worsened from 619.65 at baseline to 857.20 at follow-up. However, the apparent magnitude of progression differed substantially according to national tariff selection, with pooled mean utility change ranging from -0.081 under the Dutch tariff to -0.112 under the Italian tariff. Both EQ-5D index and visual analog scale scores correlated with progression according to the King's staging system.

CONCLUSIONS: The EQ-5D-5L captures plausible longitudinal deterioration in ALS, but interpretation is strongly influenced by valuation context. National tariffs may materially alter the apparent size of quality-of-life change in multinational ALS studies.},
}

@article {pmid42593908,
year = {2026},
author = {Sanchez-Santos, C and Jimenez-Amor, A and Martinez-Gonzalez, L and Nozal, V and Martin-Morales, R and Aledavood, E and Bausela, D and Merrigan, K and Diaz-Palacios, K and Zhubi, R and Knapp, S and Garcia-Gonzalo, FR and Rodriguez-Cueto, C and Gil, C and de Lago, E and Martinez, A},
title = {Selective Brain-Penetrant TTBK1 Inhibitors Modulate TDP-43 Pathology and Rescue Cognitive Deficits in a Mouse Model of TDP-43 Proteinopathy.},
journal = {Journal of medicinal chemistry},
volume = {69},
number = {15},
pages = {19451-19481},
doi = {10.1021/acs.jmedchem.6c01882},
pmid = {42593908},
issn = {1520-4804},
support = {GA-202205-2023343//Association for Frontotemporal Degeneration/ ; FPU21/01392//Ministerio de Ciencia, Innovaci?n y Universidades/ ; PID2019-105600RB-I00//Ministerio de Ciencia, Innovaci?n y Universidades/ ; PID2023-149472NB-I00//Ministerio de Ciencia, Innovaci?n y Universidades/ ; CB06/05/0089//Instituto de Salud Carlos III/ ; CB06/07/1029//Instituto de Salud Carlos III/ ; CB18/05/00040//Instituto de Salud Carlos III/ ; 1097737//Structural Genomics Consortium/ ; },
mesh = {Animals ; *Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Humans ; *Brain/metabolism/drug effects ; Mice ; Disease Models, Animal ; *TDP-43 Proteinopathies/drug therapy/metabolism/pathology ; *DNA-Binding Proteins/metabolism ; *Protein Kinase Inhibitors/pharmacology/therapeutic use/chemistry/pharmacokinetics ; Structure-Activity Relationship ; *Cognitive Dysfunction/drug therapy ; *Neuroprotective Agents/pharmacology/therapeutic use ; },
abstract = {Transactive response DNA-binding protein of 43 kDa (TDP-43) is a pathological hallmark of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Modulation of TDP-43 pathology represents a promising disease-modifying strategy. Tau tubulin kinase 1 (TTBK1) has emerged as a relevant therapeutic target; however, selectivity over the TTBK2 isoform is required to avoid ciliogenesis-related liabilities. Here, we report the discovery of selective, brain-penetrant TTBK1 inhibitors through a structure-guided medicinal chemistry program. Lead compounds exhibit potent and selective TTBK1 inhibition, no impact on ciliogenesis, and central nervous system exposure. We found that these inhibitors reduce TDP-43 phosphorylation levels in neuroblastoma cells and FTD patient-derived models. The optimized lead compound demonstrated a brain-to-plasma ratio of 3:1, a maximum tolerated dose, and a wide therapeutic window. In vivo, administration restored cognitive deficits, conferred neuroprotection in the frontal cortex, and reduced microglial activation in an FTD-TDP mouse model, supporting its therapeutic potential.},
}

Animals
*Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism
Humans
*Brain/metabolism/drug effects
Mice
Disease Models, Animal
*TDP-43 Proteinopathies/drug therapy/metabolism/pathology
*DNA-Binding Proteins/metabolism
*Protein Kinase Inhibitors/pharmacology/therapeutic use/chemistry/pharmacokinetics
Structure-Activity Relationship
*Cognitive Dysfunction/drug therapy
*Neuroprotective Agents/pharmacology/therapeutic use

@article {pmid42594043,
year = {2026},
author = {Nair, T and Larson, T and Raymond, J and Horton, DK and Mehta, P},
title = {Motor Neuron Disease Mortality in the United States, 2010-2023: A demographic, geographic, and temporal analysis.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1-24},
doi = {10.1159/000551599},
pmid = {42594043},
issn = {1423-0208},
abstract = {INTRODUCTION: Our objective was to calculate age-adjusted motor-neuron disease (MND) mortality rates in the United States, 2010-2023, by year, age, sex, race, origin, period, and state. Amyotrophic lateral sclerosis makes up almost 80% of all MNDs.

METHODS: Multiple cause mortality data was obtained from the National Center for Health Statistics (NCHS) for years 2010-2023. Cases were included if code G12.2, the code for MND listed in the International Classification of Disease, 10th Revision (ICD-10), was listed as a cause of death. Using the direct method, cases were age-adjusted to the 2000 U.S. Standard population and mortality rates were calculated.

RESULTS: The overall national MND associated mortality rate was 2.07 per 100,000 population (95% CI 2.06, 2.09). Rates were highest in those aged 80+ years (13.69, 95% CI 13.49, 13.89) at death, non-Hispanic (2.17, 95% CI 2.15, 2.18), and male (2.50, 95% CI 2.48, 2.52). Northern states had higher rates (2.26, 95% CI 2.23, 2.29) with a rate ratio of (1.05, (95% CI 1.04, 1.07) when compared to the middle state tier (2.14, 95% CI 2.12, 2.17, p<0.01). State rates ranged from 3.07 (95% CI 2.75, 3.42) in Vermont to 1.41 (95% CI 1.27, 1.57) in Hawaii. The average annual percentage change was -1.62, corresponding to a statistically significant negative trend.

CONCLUSION: MND associated mortality rates were higher among northern states, decedents who were male, White, or non-Hispanic, which is consistent with previous studies of U.S. MND mortality. Decreasing mortality rates may indicate longer patient life spans due to increased treatment options and care access, but further research is needed.},
}

@article {pmid42594177,
year = {2026},
author = {Parisien, R},
title = {Epistemic Asymmetry Between Abstracts and Discussion Sections in the Orthopaedic Literature: A Corpus Analysis of 201 Publications.},
journal = {The Journal of bone and joint surgery. American volume},
volume = {},
number = {},
pages = {},
doi = {10.2106/JBJS.26.00433},
pmid = {42594177},
issn = {1535-1386},
abstract = {BACKGROUND: Abstracts and Discussion sections serve distinct functions: Abstracts are optimized for brevity and impact, while Discussion sections contain authors' most explicit engagement with uncertainty and the scope of inference. Whether these sections differ systematically in epistemic stance-the level of confidence or uncertainty with which findings are stated and qualified-has not been formally examined in the orthopaedic literature.

METHODS: All original research articles published in The Journal of Bone and Joint Surgery (JBJS) and Clinical Orthopaedics and Related Research (CORR) during the first half of 2025 were included (total, n = 201; JBJS, n = 153; CORR, n = 48). Editorials, reviews, letters, and case reports were excluded. The densities of hedges (markers of uncertainty and qualification) and boosters (markers of confidence and certainty) were measured per 1,000 words using an automated 233-item lexicon. The epistemic shift index (ESI) quantified the net difference in epistemic stance between sections, with a positive value indicating greater caution in the Discussion. Abstract limitation surfacing (ALS) indicated explicit acknowledgment of limitations in the Abstract.

RESULTS: Discussion sections contained 2.8 times the hedge density of Abstracts, and the ESI was positive in 176 (87.6%) of the 201 articles. The mean ESI was 7.8 (95% confidence interval, 6.9 to 8.8; t[200] = 16.39, p < 0.001; Cohen d = 1.15). Discussions carried more than double the hedge-to-booster ratio of Abstracts (3.58 versus 1.69, p < 0.001). The asymmetry did not differ by open-access status (p = 0.807) or journal (p = 0.142) but varied significantly by study design (Kruskal-Wallis p = 0.034), with the largest asymmetry in diagnostic studies and randomized controlled trials. Only 12 (6.0%) of 201 Abstracts acknowledged study limitations.

CONCLUSIONS: The Discussion sections of the orthopaedic research articles were substantially more epistemically cautious than their Abstracts across journals and access models. In most articles, the Abstract presented findings without caveat, with corresponding limitations appearing only in the Discussion. A limitation of this analysis is that epistemic stance was measured at the word and phrase level only. These findings have implications for clinical decision-making and for artificial intelligence systems trained on freely accessible Abstract text.},
}

@article {pmid42594365,
year = {2026},
author = {Berry-Kilgour, N and Wiseman, R and Grundy, K},
title = {Prescribing and monitoring of riluzole in amyotrophic lateral sclerosis: a retrospective cohort study from Health New Zealand - Te Whatu Ora Waitaha Canterbury.},
journal = {The New Zealand medical journal},
volume = {139},
number = {1640},
pages = {23-30},
doi = {10.26635/6965.7367},
pmid = {42594365},
issn = {1175-8716},
mesh = {Humans ; Retrospective Studies ; *Riluzole/therapeutic use/adverse effects ; New Zealand ; *Amyotrophic Lateral Sclerosis/drug therapy ; Female ; Male ; Middle Aged ; Aged ; *Guideline Adherence/statistics & numerical data ; *Drug Monitoring ; *Neuroprotective Agents/therapeutic use/adverse effects ; Practice Guidelines as Topic ; *Practice Patterns, Physicians'/statistics & numerical data ; Spirometry ; Adult ; },
abstract = {AIM: This retrospective cohort study assessed adherence to the Motor Neurone Disease New Zealand best practice guidelines and Pharmac Special Authority criteria for riluzole in a Canterbury-based amyotrophic lateral sclerosis (ALS) cohort. Secondary objectives included reasons for not prescribing, side effects and treatment initiation relative to diagnosis.

METHOD: A retrospective cohort study was conducted using the Christchurch Hospital respiratory department's ALS database. Patients diagnosed between January 2020 and November 2024 were included. Electronic health records and Special Authority records were reviewed. Patients with incomplete data or non-motor neurone disease (MND) diagnoses were excluded.

RESULTS: Of 115 patients, 69 (60%) were prescribed riluzole. Less than 45% of patients had baseline blood tests, and pre-treatment spirometry was completed in 70% of patients. Delays in prescribing improved rates of baseline spirometry, but not blood test completion. Ongoing monitoring was poor, with less than 60% of patients completing recommended tests across all time points. Eight patients (11.6%) reported side effects, and three discontinued treatment following alanine aminotransferase derangement.

CONCLUSION: Adherence to recommended monitoring and Special Authority criteria for riluzole was inconsistent in this cohort. In the context of emerging evidence supporting broader survival benefit and reduced drug cost, further evaluation of current Special Authority prescribing criteria may be warranted.},
}

Humans
Retrospective Studies
*Riluzole/therapeutic use/adverse effects
New Zealand
*Amyotrophic Lateral Sclerosis/drug therapy
Female
Male
Middle Aged
Aged
*Guideline Adherence/statistics & numerical data
*Drug Monitoring
*Neuroprotective Agents/therapeutic use/adverse effects
Practice Guidelines as Topic
*Practice Patterns, Physicians'/statistics & numerical data
Spirometry
Adult

@article {pmid42594388,
year = {2026},
author = {Griffin, AC and Zulman, DM},
title = {Digital Decisions: Enhancing Chronic Disease Self-Care Through Digital Health and AI-Enhanced Decision-Making.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e106648},
doi = {10.2196/106648},
pmid = {42594388},
issn = {1438-8871},
mesh = {Humans ; *Self Care ; Chronic Disease/therapy ; Digital Health ; *Decision Making ; *Artificial Intelligence ; Telemedicine ; },
abstract = {Advances in digital health have dramatically changed how patients engage with their health. Rather than relying solely on periodic clinical visits, patients now have access to smartphones, patient portals, wearable devices, and mobile apps that provide support for day-to-day self-care decisions. This commentary discusses the findings of Longhini et al's systematic review and meta-analysis on the effectiveness of digital health interventions, which found modest improvements in self-care monitoring but limited effects on self-care maintenance and management behaviors. Reflecting on these findings through the lens of dual-process theory, digital health technologies appear to be effective at supporting fast, intuitive processes, such as symptom monitoring, but are less effective at engaging slower, deliberative processes needed for complex decision-making and behavior change. Digital health technologies should evolve from primarily supporting routine self-care activities to enhancing patients' reflective decision-making processes for sustained behavior change. Emerging AI capabilities offer opportunities to strengthen and bridge these fast and slow cognitive processes by translating complex health information into actionable insights and facilitating patient-clinician communication. Realizing this potential requires careful attention to implementation, including integration into clinical workflows, patient and clinician education, and digital literacy. In addition, digital health teams should adopt standardized implementation frameworks and outcome measures to generate a more robust evidence base. Lastly, human-centered design, patient engagement, and safeguards addressing bias, privacy, and transparency are foundational to ensure that the rapid pace of digital health technology will continue to enhance patient self-care and health outcomes.},
}

Humans
*Self Care
Chronic Disease/therapy
Digital Health
*Decision Making
*Artificial Intelligence
Telemedicine

@article {pmid42594668,
year = {2026},
author = {Nakasako, J and Nishimoto, Y},
title = {Reply to the 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 = {126130},
doi = {10.1016/j.jns.2026.126130},
pmid = {42594668},
issn = {1878-5883},
}

@article {pmid42595080,
year = {2026},
author = {Al-Badaineh, M and Josan, H and Imran, B and Ebeid, I and Mekhail, J and Abdou, M and Dagher, D and Ahmed, AF and Hantouly, A and Khan, M},
title = {Spin in Systematic Reviews on Patch-Augmented Rotator Cuff Repair: Prevalence, Predictors, and Methodological Implications.},
journal = {Journal of shoulder and elbow surgery},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jse.2026.07.030},
pmid = {42595080},
issn = {1532-6500},
abstract = {BACKGROUND: Rotator cuff tears are a major cause of shoulder pain and dysfunction, and surgical repair is often complicated by the risk of retear, especially in patients with large, massive, revision tears and high-risk patients. Biologic or synthetic patch augmentation has emerged to reinforce repair and potentially reduce retears. Despite many systematic reviews and meta-analyses on patch-augmented versus non-augmented repair, concerns remain regarding study heterogeneity, outcome variability, and spin in interpretation and reporting, particularly in abstracts. This study assessed the methodological quality and abstract spin.

METHODS: This systematic review was conducted in accordance with the Cochrane Handbook and PRISMA guidelines. On October 30, 2025, PubMed, Scopus, and Web of Science were searched for English-language systematic reviews and meta-analyses comparing patch- or graft-augmented versus non-augmented rotator cuff repair in clinical studies. Eligible reviews reported at least one clinical, patient-reported, or imaging-based outcome. Two reviewers independently performed duplicate study selection, data extraction, spin assessment, and methodological quality appraisal using Yavchitz et al.'s nine severe spin types and AMSTAR-2.

RESULTS: Sixteen reviews and meta-analyses were included in this study. Spin was identified in 81.3% (n = 13) of the abstracts. The types were 5 (62.5%), 3 (56.2%), and 8 (50.0%). Univariate analysis found no significant associations with the funding status (p = 0.36), quality (p = 1.00), or impact factor (p = 0.95). Each AMSTAR-2 flaw was associated with 61% more spin types (IRR 1.61; 95% CI 1.08-2.49; p = 0.02).

CONCLUSION: Spin is prevalent in the abstracts of systematic reviews on patch augmentation for rotator cuff repair, regardless of funding or journal impact factor. Although spin was widespread, poor methodological quality was linked to a greater spin burden rather than its presence. These findings highlight the importance of critically appraising systematic reviews, as spin may contribute to an overly favorable interpretation of the evidence and potentially influence clinical decision-making. Readers should interpret the conclusions cautiously and verify the claims against the full-text results.

LEVEL OF EVIDENCE: Research Methodology Study, Systematic Review.},
}

@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.},
}