@article {pmid41787359,
year = {2026},
author = {Dumbrell, J and Masterton, W and Carver, H and Parkes, T},
title = {Realist review of nature-based interventions for men: understanding the contexts and mechanisms necessary for successful outcomes.},
journal = {BMC public health},
volume = {26},
number = {1},
pages = {},
pmid = {41787359},
issn = {1471-2458},
abstract = {BACKGROUND: Men face significant health disparities, including higher rates of premature death, mental health challenges, and substance use disorders. Nature-based interventions hold promise for improving men’s health and wellbeing by leveraging natural environments and structured activities aligned with men’s preferences for practical, action-oriented solutions. This realist review explores the contexts, mechanisms, and outcomes of nature-based interventions, providing a gender-specific perspective on how these interventions benefit men.

METHODS: A realist synthesis was conducted following Pawson et al.’s iterative framework and the RAMESES reporting standards. Initial programme theories were constructed through early interrogation of the men’s health and greenspace literatures, and expert consultations. Data extraction focused on identifying context-mechanism-outcome configurations to refine programme theories. Analysis involved synthesising findings from qualitative, quantitative, and grey literature to demonstrate how nature-based interventions influence men’s wellbeing.

RESULTS: The review identified nine refined programme theories, encompassing three domains: Being, Doing, and Growing Together. Calming natural settings (PT1) and tailored physical activities (PT2) reduced stress, improved fitness, and enhanced resilience. Purposeful engagement (PT3) and skill development in peer-led, supportive environments (PT4) fostered self-efficacy, identity reformation, and empowerment. Strengths-based, inclusive approaches (PT5, PT6) built social bonds and community cohesion, while structured cognitive engagement (PT7) enhanced problem-solving and collaborative skills. Foundational contexts, including safe, non-judgemental, culturally sensitive spaces (PT8) and tailored, multidisciplinary support (PT9), underpinned these mechanisms, enabling sustained health and wellbeing outcomes.

CONCLUSIONS: Nature-based interventions offer a powerful and gender-responsive solution to men’s mental health challenges, combining restorative natural environments, purposeful activities, and peer-led support. Tailored interventions that align with men’s cultural identities and values significantly enhance engagement, self-efficacy, and social cohesion. These findings provide actionable insights for designing inclusive, impactful nature-based interventions, addressing longstanding health disparities. Future research should explore adapting nature-based interventions to diverse populations and contexts to maximise their reach and effectiveness.

PROTOCOL REGISTRATION: CRD42023487594

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-026-26867-7.},
}

@article {pmid41787423,
year = {2026},
author = {Öngü, İN and Arkan, B and Kirli, S},
title = {The Turkish version of the quality in psychiatric care-inpatient scale: translation, cross-cultural adaptation, and psychometric evaluation.},
journal = {BMC health services research},
volume = {26},
number = {1},
pages = {},
pmid = {41787423},
issn = {1472-6963},
abstract = {BACKGROUND: Effective mental health services require high-quality psychiatric inpatient care. To evaluate care from patients’ perspective, culturally validated tools are needed that also reflect local healthcare and psychiatric nursing services. This aim of this study was to validate the Turkish version of Quality in Psychiatric Care-Inpatient scale, to support its use by psychiatric nurses in assessing the quality of inpatient care.

METHODS: This methodological study included 280 psychiatric inpatients from two hospitals. The scale was translated, back-translated and reviewed by experts following Beaton et al.’s adaptation framework and the Consensus-based Standards for Selecting Health Status Measurement Instruments guidelines. Content validity, construct validity, and internal consistency were assessed.

RESULTS: The Turkish scale comprised 22 items across four sub-dimensions, explaining 53.5% of the total variance. The alpha coefficient was 0.86, demonstrating high internal consistency. Fit indices supported the four-factor model.

CONCLUSIONS: The scale demonstrated promising psychometric properties and is suitable for psychiatric inpatient nursing practice.

CLINICAL TRIAL NUMBER: Not applicable.},
}

@article {pmid41974001,
year = {2026},
author = {Beaulieu, D and Smith, K and Ross, C and Yip, S and Felizardo, TC and Fournier, C and Glass, JD and Berry, JD and Fowler, DH and Ennist, DL and , },
title = {Development of a machine learning-based survival prediction model for ALS inclusive of the advanced-stage population.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/21678421.2026.2652322},
pmid = {41974001},
issn = {2167-9223},
abstract = {OBJECTIVE: Develop a machine learning-based model for survival prediction in ALS, including advanced-stage patients (≤50% predicted normal vital capacity [VC50]).

METHODS: Training data from the PRO-ACT Database (n = 6896) was supplemented with advanced-stage ALS patients (n = 678), with model validation on distinct advanced-stage ALS patients (n = 403). Baseline patient characteristics, including slopes from symptom onset, were used to train a random forest model to identify parameters with the greatest relative importance (RI) for predicting survival outcomes. These parameters were used to train a gradient-boosting machine (GBM) model that generated patient-level survival predictions (log-hazard). Model discrimination and calibration were quantified by C-index and calibration-in-the-large plus calibration slope, respectively. Kaplan-Meier curves were generated, with patient stratification into tertiles based on the predicted survival risk score.

RESULTS: Baseline characteristics with the highest RI for driving survival predictions included: VC% slope (20.2%); age (12.4%); VC% (9.9%); VC(L) (7.5%); ALSFRS-R (6.6%); and ALSFRS-R slope (5.1%). Model performance upon external validation was satisfactory for both discrimination (C-index, 0.709 [95% CI, 0.671-0.746]) and calibration (calibration-in-the-large, 0.083 [95% CI, -0.073-0.232]; calibration slope, 0.992 [95% CI, 0.789-1.198]). At 8-months from baseline, the model successfully stratified patients by survival prognosis, with low-, average-, and high-risk population tertiles having observed median survival probabilities of 85, 69, and 43%, respectively.

CONCLUSIONS: This model accurately predicts survival prognosis in ALS, including patients with severely impaired respiratory function. This new understanding of patient-specific factors that drive survival prognostication will be invaluable for reducing patient heterogeneity in clinical trials evaluating novel therapeutic modalities in early- and advanced-stage ALS.},
}

@article {pmid41974046,
year = {2026},
author = {Willemse, SW and Hollak, CEM and Reijnhout, ND and Reparon-Schuijt, CC and Pisters-van Roy, AAMG and Demaegd, KC and van Eijk, RPA and van Den Berg, LH and van Es, MA},
title = {Fast and controlled access to tofersen for SOD1-related amyotrophic lateral sclerosis in The Netherlands; experiences using the orphan drug access protocol.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2655738},
pmid = {41974046},
issn = {2167-9223},
}

@article {pmid41974458,
year = {2026},
author = {Facciabene, A and Ellsworth, SG},
title = {Gut-targeted strategies at the intersection of radiotherapy and immunotherapy.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {4},
pages = {},
doi = {10.1136/jitc-2025-014211},
pmid = {41974458},
issn = {2051-1426},
mesh = {Humans ; *Gastrointestinal Microbiome/radiation effects/immunology ; *Immunotherapy/methods ; *Neoplasms/immunology/therapy/radiotherapy ; *Radiotherapy/methods ; },
abstract = {The gut microbiota has emerged as a critical determinant of therapeutic immunity, shaping responses to immune checkpoint inhibitors, adoptive cellular therapies, and radiotherapy (RT). Interest has grown in whether interventions targeting the microbiota might deliberately amplify anticancer immunity.Chen and colleagues recently proposed an unconventional approach: using low-dose intestinal irradiation (ILDR) to remodel the gut microbiota and thereby enhance responsiveness to programmed death-ligand 1 blockade in patients with metastatic cancer. Their report, though preliminary, suggests that directed RT to the intestine can in fact act to favorably modulate the intestinal microbiota. Importantly, current evidence remains largely correlative and does not establish a causal relationship between ILDR, microbiota remodeling, and enhanced systemic antitumor immunity. This concept is provocative, but it raises fundamental questions: does gut-directed RT truly enhance systemic antitumor immunity, or might additional confounding variables, organ-specific effects, and potential toxicities influence the signal?In this Commentary, we balance enthusiasm with caution. We first outline the conceptual framework linking RT, microbiota, and immune activation; then highlight the specific pitfalls revealed by Chen et al's study, including challenges in attribution, heterogeneity, and immunosuppression. We also discuss complementary translational approaches, including direct microbiota modulation through targeted antibiotics and other gut-directed strategies, as potential tools to experimentally interrogate the microbiota-RT-immunotherapy axis in patients.},
}

Humans
*Gastrointestinal Microbiome/radiation effects/immunology
*Immunotherapy/methods
*Neoplasms/immunology/therapy/radiotherapy
*Radiotherapy/methods

@article {pmid41975445,
year = {2026},
author = {Xue, FS and Wang, DF and Zheng, XC},
title = {Intraoperative use of sodium oxybate to prevent postoperative delirium in older patients undergoing major orthopedic surgery.},
journal = {BMC medicine},
volume = {24},
number = {1},
pages = {},
pmid = {41975445},
issn = {1741-7015},
mesh = {Humans ; *Orthopedic Procedures/adverse effects ; Aged ; *Delirium/prevention & control/etiology ; *Sodium Oxybate/therapeutic use/administration & dosage ; *Postoperative Complications/prevention & control ; *Intraoperative Care/methods ; },
abstract = {BACKGROUND: This matters arising article addresses the recently published article in BMC Medicine by Cui et al., titled "Prophylactic effect of intraoperative sodium oxybate on postoperative delirium in older patients undergoing major orthopedic surgery: a randomized clinical trial."

MAIN BODY: The work by Cui et al. demonstrated that intraoperative administration of sodium oxybate only significantly reduced postoperative delirium (POD) incidence in the participants undergoing morning surgery but not in those with afternoon surgery. Although this trial provided evidence that sodium oxybate may reduce POD, we raise several concerns regarding methodology and generalizability, such as incomplete control of perioperative risk factors, underestimated incidence of POD, subgroup analysis without multiple adjustments of confounding factors, and inadequate postoperative pain strategy. To verify the findings of this trial in further researches, we advocate the implementation of multi-center randomized clinical trials with large sample sizes, strict control of perioperative confounding factors, precise assessment of POD episodes, and the inclusion of subgroup analysis with multiple adjustments.

CONCLUSION: This matters arising does not seek to deny the results of Cui et al.'s trial. The main purpose of the authors is to emphasize that above methodological refinements are crucial for translating this valuable evidence into generally clinical practice and improving final outcomes of patients.},
}

Humans
*Orthopedic Procedures/adverse effects
Aged
*Delirium/prevention & control/etiology
*Sodium Oxybate/therapeutic use/administration & dosage
*Postoperative Complications/prevention & control
*Intraoperative Care/methods

@article {pmid41975461,
year = {2026},
author = {Abbas, AEF and Talib, NFA and Elghobashy, MR and Al Kamaly, O and Halim, MK},
title = {Candexch algorithm-enhanced chemometric determination of a novel anti-COVID-19 therapeutics in plasma and paxlovid formulation using advanced multivariate modeling: a sustainability-centered bioanalytical approach.},
journal = {BMC chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13065-026-01788-z},
pmid = {41975461},
issn = {2661-801X},
support = {PNURSP2026R917//Princess Nourah Bint Abdulrahman University/ ; },
abstract = {This work reports the development of an algorithm-assisted chemometric spectrophotometric method for the concurrent quantification of anti-COVID-19 therapeutics nirmatrelvir, ritonavir, and the active molnupiravir metabolite N4-hydroxycytidine in pharmaceutical formulations and human plasma. A structured fractional five-level factorial calibration design consisting of 25 mixtures was employed to construct the calibration dataset, while the external validation set was generated using D-optimal sample selection via the Candexch algorithm to ensure uniform coverage of the experimental domain and minimize sampling bias relative to random dataset partitioning. Quantitative modeling was performed using four multivariate regression strategies: Principal Component Regression (PCR), Genetic Algorithm-assisted Partial-Least Squares (GA-PLS), Firefly Algorithm-assisted Partial-Least Squares (FA-PLS), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). Model optimization, including latent variable selection, wavelength selection, and parameter tuning, was performed exclusively using the calibration dataset through internal cross-validation (LOO-CV) based on minimum RMSECV, while the external validation set was kept completely independent and used only for final prediction. Among the models that were assessed, the MCR-ALS algorithm demonstrated the best overall predictive performance, yielding correlation coefficients exceeding 0.9997 and root mean square prediction errors ranging from 0.076 to 0.213 µg mL[-1]. NAS-based sensitivity assessment produced detection limits between 0.109 and 0.876 µg mL[-1], demonstrating adequate sensitivity within the investigated concentration ranges. Matrix-matched validation employing 25 calibration and 13 external validation mixtures prepared in fortified human plasma confirmed predictive robustness across both plasma and Paxlovid[®] dosage matrices. Multidimensional sustainability appraisal revealed favorable environmental and operational attributes. The method satisfied all National Environmental Methods Index criteria, achieved a Greenness Evaluation Metric for Analytical Methods score of 7.502, and displayed a calculated carbon footprint of 0.021 kg CO2/sample. Complementary operational and innovation assessments yielded Blue Applicability Grade Index and Violet Innovation Grade Index scores of 90.00 and 80.00, respectively, while the integrated Normalized Quality Score reached 83%. Collectively, the developed platform provides a cost-efficient and environmentally considerate analytical approach suitable for pharmaceutical quality control and preliminary bioanalytical screening in fortified plasma matrices, particularly in laboratories lacking access to advanced chromatographic instrumentation.},
}

@article {pmid41975595,
year = {2026},
author = {Tedeschi, V and Ciancio, R and Piccirillo, S and Preziuso, A and Serfilippi, T and Terenzi, V and Magi, S and Lariccia, V and Castaldo, P and Vinciguerra, A and Piccialli, I and Canzoniero, LMT and Pannaccione, A and Secondo, A},
title = {Organelles storing Ca2+ in the brain cells: New druggable targets in neurodegenerative diseases.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01754},
pmid = {41975595},
issn = {1673-5374},
abstract = {Several lines of evidence suggest that targeting dysfunctional calcium (Ca2+)-storing organelles and their defective connections may represent a promising therapeutic strategy counteracting neurodegeneration. Dysfunction in these compartments converges to promote oxidative and endoplasmic reticulum stress, energy failure, autophagy blockade or hyperactivation, and progressive neurodegeneration. Within the intracellular scenario, several dysfunctional organelles have been characterized in terms of their capability to hijack Ca2+ signaling during neurodegeneration to deadly impact on neuronal tasks in amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, brain ischemia, and neonatal hypoxic injury. This review has focused on the endoplasmic reticulum, mitochondria, and lysosomes, as well as their functional interconnection able to maintain the physiological processes such as lysosomal-dependent autophagy and function, lipid trafficking, and protein quality control. Clinically, looking ahead from the already existing therapies, drugs that enhance mitochondrial Ca2+ efflux or modulate mitochondrial Ca2+ uniporter regulation at mitochondria-associated membranes-endoplasmic reticulum sites represent innovative opportunities for next-generation strategies aimed at restoring mitochondrial homeostasis and protecting dopaminergic neurons in Parkinson's disease. Furthermore, functional stabilization of the lysosomal channel transient receptor potential mucolipin 1 by the lipid-based formulation of PI(3,5)P2 may extend the lifespan of amyotrophic lateral sclerosis mice by stimulating the nuclear translocation of the master regulator of autophagy activated by lysosomal Ca2+ release, namely transcription factor EB. Moreover, dysfunction of lysosomal-dependent autophagy can cause mutant huntingtin accumulation in Huntington's disease through the repression of transcription factor EB and lysophagy induction. Collectively, this growing focus may highlight a shift toward recognizing mitochondria, lysosomes, and endoplasmic reticulum, as well as their ionic machinery and interconnections, as a unifying strategy to maintain neuronal viability and mitigate the neurodegeneration progression in amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, lysosomal storage diseases, brain ischemia, and neonatal hypoxic insult.},
}

@article {pmid41975602,
year = {2026},
author = {Szewczyk, B and Hermann, A and Zimyanin, V},
title = {From cell cycle re-entry to checkpoint failure: Rethinking DNA damage response in amyotrophic lateral sclerosis.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01740},
pmid = {41975602},
issn = {1673-5374},
}

@article {pmid41976821,
year = {2026},
author = {Suzuki, H},
title = {Speculum-Induced Intraocular Pressure Elevation During Cataract Surgery and Its Association with Axial Length: A Retrospective Clinical Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {7},
pages = {},
pmid = {41976821},
issn = {2077-0383},
abstract = {Background/Objectives: This study aimed to characterize eyelid speculum-induced intraocular pressure (IOP) elevation during cataract surgery and identify ocular biometric factors that stratify susceptibility to this pressure response. This study was conducted at Zengyo Suzuki Eye Clinic, Kanagawa, Japan. Methods: In this retrospective observational study, we analyzed 100 eyes that underwent routine cataract surgery. IOP was measured immediately before and within 10 s of speculum opening in the seated position using a rebound tonometer. The eyelid speculum was opened to a maximal opening position, and the opening width was recorded. Biometric parameters included axial length (AL), central corneal thickness, white-to-white distance, anterior chamber depth, and temporal angle-opening distance. Associations between IOP elevation and biometric factors were analyzed. IOP elevation rate was quantified as the percentage increase from baseline. The discriminatory performance of axial length was evaluated using receiver operating characteristic (ROC) analysis. Results: Overall, 100 patients (100 eyes) were included in the analysis. Mean IOP increased significantly from 15.75 ± 2.77 mmHg before speculum placement to 21.42 ± 5.54 mmHg after placement. The mean IOP elevation rate was 36.0 ± 27.4%. Shorter AL was consistently associated with a greater proportional IOP elevation. ROC analysis demonstrated consistent stratification of IOP elevation susceptibility by AL (area under the curve [AUC] = 0.645), with eyes shorter than 23.84 mm showing greater pressure elevation (sensitivity, 73.1%; specificity, 56.0%). Eyes in the upper quartile of the IOP elevation rate exhibited relatively greater pressure elevation. Conclusions: Eyelid speculum placement imposes a clinically meaningful IOP load during cataract surgery, with shorter ALs making eyes more biomechanically susceptible to IOP elevation.},
}

@article {pmid41977262,
year = {2026},
author = {Mîndreanu, R and Chiș, IC and Sevastre-Berghian, A and Login, C and Stan, A and Stan, T and Clichici, S and Suciu, Ș},
title = {N-Acetylcysteine in Neurological Disorders: A Systematic Review of Clinical and Translational Evidence Across Seven Disorders.},
journal = {International journal of molecular sciences},
volume = {27},
number = {7},
pages = {},
doi = {10.3390/ijms27073076},
pmid = {41977262},
issn = {1422-0067},
mesh = {*Acetylcysteine/therapeutic use/pharmacology ; Humans ; *Nervous System Diseases/drug therapy ; *Neuroprotective Agents/therapeutic use ; Parkinson Disease/drug therapy ; Translational Research, Biomedical ; Antioxidants/therapeutic use ; Alzheimer Disease/drug therapy ; Oxidative Stress/drug effects ; Amyotrophic Lateral Sclerosis/drug therapy ; Multiple Sclerosis/drug therapy ; Brain Injuries, Traumatic/drug therapy ; },
abstract = {N-acetylcysteine (NAC) is a glutathione precursor with established antioxidant and anti-inflammatory properties that has been investigated as a neuroprotective agent across multiple neurological conditions. This systematic review systematically mapped the clinical evidence for NAC across seven neurological disorders. PubMed and Cochrane Library were searched for studies published between 1 January 1995 and 31 December 2025. Twenty-three studies were included: traumatic brain injury (TBI, n = 6), Alzheimer's disease (AD, n = 5), Parkinson's disease (PD, n = 5), multiple sclerosis (n = 4), amyotrophic lateral sclerosis (n = 2), and migraine (n = 1); no eligible epilepsy studies were identified. The strongest evidence emerged for acute mild TBI, where early NAC administration significantly improved symptom resolution, and for PD, where combined intravenous/oral NAC improved dopamine transporter binding. In AD, nutraceutical formulations including NAC and other active compounds showed trends toward cognitive stabilization. Most included studies had a high or serious risk of bias, and only eight of 23 assessed oxidative stress biomarkers. NAC demonstrated a favorable safety profile across all conditions. Despite fragmented and heterogeneous evidence, the encouraging signals identified warrant large-scale randomized controlled trials with a standardized biomarker assessment.},
}

*Acetylcysteine/therapeutic use/pharmacology
Humans
*Nervous System Diseases/drug therapy
*Neuroprotective Agents/therapeutic use
Parkinson Disease/drug therapy
Translational Research, Biomedical
Antioxidants/therapeutic use
Alzheimer Disease/drug therapy
Oxidative Stress/drug effects
Amyotrophic Lateral Sclerosis/drug therapy
Multiple Sclerosis/drug therapy
Brain Injuries, Traumatic/drug therapy

@article {pmid41977439,
year = {2026},
author = {Bougea, A},
title = {Targeting Non-Coding RNAs as a Potential Therapeutic and Delivery Strategy Against Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {27},
number = {7},
pages = {},
doi = {10.3390/ijms27073260},
pmid = {41977439},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy ; Animals ; *RNA, Untranslated/genetics ; MicroRNAs/genetics ; RNA, Long Noncoding/genetics ; Genetic Therapy/methods ; },
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS), represent a growing global health challenge characterized by progressive neuronal loss and a lack of definitive disease-modifying treatments. This review explores the emerging potential of targeting non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and exosomal RNAs, to modulate pathogenic molecular pathways and address the underlying molecular origins of neurodegeneration. We evaluate the integration of advanced computational techniques for RNA structure prediction and gene regulatory network analysis, alongside chemical engineering strategies-such as Locked Nucleic Acids (LNAs) and phosphorothioate modifications-aimed at enhancing the stability and specificity of RNA-based molecules. Furthermore, we analyze cutting-edge delivery and editing technologies, including nanotechnology-driven solutions for precise neuronal targeting and the CRISPR/Cas13 system for direct ncRNA manipulation.The findings indicate that while challenges in delivery efficiency and long-term efficacy persist, the synergy of chemical engineering and computational modeling significantly improves the therapeutic profile of ncRNAs, with exosomal pathways offering a novel route for intercellular signaling modulation and biomarker discovery. Therapeutic interventions directed at specific clinical targets, such as miR-34a and BACE1-AS, demonstrate the capacity to influence protein aggregation and neuroinflammatory cascades. Although ncRNA-based therapies are currently in nascent stages, ongoing technological advancements in RNA editing and nanotechnology offer a transformative framework that could redefine the future of ND treatment and successfully halt disease progression rather than merely managing symptoms.},
}

Humans
*Neurodegenerative Diseases/genetics/therapy
Animals
*RNA, Untranslated/genetics
MicroRNAs/genetics
RNA, Long Noncoding/genetics
Genetic Therapy/methods

@article {pmid41978251,
year = {2026},
author = {Malmström, N and Ozanne, A and Nilsson, S and Öhlén, J and Jakobsson Larsson, B},
title = {Support interventions for families facing parental life-threatening illness - A scoping review.},
journal = {Palliative & supportive care},
volume = {24},
number = {},
pages = {e78},
doi = {10.1017/S1478951526101837},
pmid = {41978251},
issn = {1478-9523},
mesh = {Humans ; Child ; *Parents/psychology ; *Social Support ; Infant ; },
abstract = {OBJECTIVES: Despite the urgent need for support interventions for families facing parental life-threatening illness, research is limited - particularly in progressive neurological diseases. This scoping review aimed to systematically map existing interventions to inform the development of tailored support in the neurological context.

METHODS: A scoping review was conducted, including articles published between 2013 and 2025, identified through searches in PubMed, CINAHL, PsycINFO, and Web of Science, along with manual screening of reference lists. Extracted data were systematically charted and descriptively summarized.

RESULTS: Of 5172 articles, 15 were included, describing 6 unique interventions aimed at supporting children (0-25 years) and/or parents in families where a parent had a life-threatening illness. While cancer was the predominant diagnosis among ill parents, progressive neurological diseases, such as amyotrophic lateral sclerosis (ALS) and Huntington's disease, were represented to a limited extent. The interventions targeted children (n = 4), parents in their parenting role (n = 4), or the entire family (n = 7) and were primarily based on psychosocial, psychoeducational, or peer support. Overall, the interventions were positively received by both children and parents and perceived as helpful in navigating their challenging life situations in various ways.

SIGNIFICANCE OF RESULTS: This review confirms a particular lack of knowledge and tailored support for families affected by progressive neurological diseases. While support interventions for other life-threatening illnesses are also limited, those that exist may offer valuable insights to inform the development of support within neurological care contexts. The findings underscore the need for early, proactive, and accessible approaches that address both individual and family needs across the disease trajectory, aligning with core principles of high-quality palliative care.},
}

Humans
Child
*Parents/psychology
*Social Support
Infant

@article {pmid41978357,
year = {2026},
author = {La, N and Rattanapitoon, NK and Thanchonnang, C and Rattanapitoon, SK},
title = {Refining interpretation of national trends in lung cancer screening discussions.},
journal = {Translational behavioral medicine},
volume = {16},
number = {1},
pages = {},
doi = {10.1093/tbm/ibag012},
pmid = {41978357},
issn = {1613-9860},
mesh = {Humans ; *Lung Neoplasms/diagnosis ; *Early Detection of Cancer/trends ; United States ; *Mass Screening/trends ; *Physician-Patient Relations ; Practice Guidelines as Topic ; },
abstract = {This letter comments on Williamson et al.'s nationally representative analysis of patient-clinician discussions on LCS across the 2013-2021 USPSTF guideline periods. We highlight that changes in survey wording and approximated eligibility criteria may partially explain the reported decline in discussions, rather than a true reduction in clinician engagement. We emphasize the behavioral and measurement implications of terminology awareness and eligibility approximation, and propose analytic considerations for future surveillance efforts to support equitable translation of LCS guidelines.},
}

Humans
*Lung Neoplasms/diagnosis
*Early Detection of Cancer/trends
United States
*Mass Screening/trends
*Physician-Patient Relations
Practice Guidelines as Topic

@article {pmid41978444,
year = {2026},
author = {Stokholm, JB and Küchen, SHL and Møller, K and Gätke, MR and Svenstrup, K and Staehr-Rye, AK},
title = {Outpatient versus inpatient initiation of home mechanical ventilation in patients with amyotrophic lateral sclerosis - a protocol for a randomised trial.},
journal = {Danish medical journal},
volume = {73},
number = {4},
pages = {},
doi = {10.61409/A09250733},
pmid = {41978444},
issn = {2245-1919},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Noninvasive Ventilation/methods ; Telemedicine ; *Hospitalization ; *Home Care Services ; Quality of Life ; *Ambulatory Care/methods ; Male ; Randomized Controlled Trials as Topic ; Female ; Patient Satisfaction ; Middle Aged ; Patient Compliance ; *Hypoventilation/therapy/etiology ; },
abstract = {INTRODUCTION: In-home non-invasive ventilation (NIV) is associated with prolonged life and improved quality of life in patients with hypoventilation due to amyotrophic lateral sclerosis (ALS). The initiation of NIV is scheduled for a 1-2-night hospital stay. Telemedicine enables remote monitoring and adjustment of respiratory treatment. These possibilities should be examined to improve patients' experiences and adherence to treatment while freeing up resources in the healthcare system. We hypothesise that outpatient initiation of NIV combined with close telemonitoring in patients with ALS is non-inferior to standard initiation of NIV in adherence to treatment.

METHODS: This is a randomised, controlled, non-inferiority study. A total of 46 patients with ALS scheduled for initiation of NIV are randomised to start NIV either as an outpatient combined with close telemonitoring or during hospitalisation for 1-2 nights. The primary outcome is NIV adherence after three months, measured as minutes per day for the past seven days. Secondary outcomes are patient satisfaction with NIV treatment and its initiation after three months, assessed on a 1-5 rating scale.

CONCLUSIONS: The study is the first randomised, controlled study assessing the combination of outpatient initiation of NIV and close telemedical follow-up in patients with a progressive neuromuscular disease. The results may be applicable to other patient populations initiating NIV, e.g., patients with obesity hypoventilation syndrome.

FUNDING: The study was supported by grants from ALS-fonden and Muskelsvindfonden.

TRIAL REGISTRATION: NCT05829330.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/complications
*Noninvasive Ventilation/methods
Telemedicine
*Hospitalization
*Home Care Services
Quality of Life
*Ambulatory Care/methods
Male
Randomized Controlled Trials as Topic
Female
Patient Satisfaction
Middle Aged
Patient Compliance
*Hypoventilation/therapy/etiology

@article {pmid41979429,
year = {2026},
author = {Patel, J and Eisenberg-Godsey, SR and Tipton, PW},
title = {Exploring the phenotypic spectrum of frontotemporal lobar degeneration.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.109796},
pmid = {41979429},
issn = {0028-3843},
abstract = {Frontotemporal lobar degeneration (FTLD) refers to a spectrum of neuropathology preferentially affecting the frontal and temporal lobes manifesting with progressive behavioral, language, and motor impairment. These clinical symptoms linked to FTLD are collectively referred to as frontotemporal spectrum disorders (FTSD) and include behavioral-variant frontotemporal dementia, nonfluent/agrammatic primary progressive aphasia, semantic variant primary progressive aphasia, right temporal variant frontotemporal dementia, corticobasal syndrome, progressive supranuclear palsy, and amyotrophic lateral sclerosis-frontotemporal spectrum disorders. While some patients with FTLD present with a single, well-defined syndrome, others exhibit features of multiple syndromes, and clinical phenotypes frequently evolve over time. Moreover, there is substantial phenotypic overlap between FTSD and other neurological disorders, contributing to frequent misdiagnosis and diagnostic delays. To address these challenges, we provide a practical, clinically oriented framework for the diagnosis of FTSD. We review common and nuanced clinical features, pertinent diagnostic testing, and the role of genetic testing in the context of current understanding of neuropathological correlates. Despite the absence of disease-modifying therapies, we also outline evidence-informed strategies for the symptomatic management of FTSD.},
}

@article {pmid41980047,
year = {2026},
author = {Hawkins, SC and Williams, J and Bennett, BL and Islas, A and Quinn, R},
title = {Out-of-Hospital Management of Suspected Spinal Cord Injuries: How Much Evidence Does it Take to Change Practice?.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/10903127.2026.2655989},
pmid = {41980047},
issn = {1545-0066},
abstract = {We read with interest Millin et al.'s literature review and analysis as well as the letter in response from Calland et al. We were particularly interested in their contention that multidisciplinary teams, including spine surgeons, should be assembled to address this important question. Directly addressing Calland et al.'s concerns about multidisciplinary teams, the Wilderness Medical Society has assembled clinical practice guidelines expert panels addressing spinal injuries since 2011. This analysis included at least one emergency physician, EMS physician, sports medicine physician, paramedic, PhD, EMT, wilderness physician, and military medical specialist as well as orthopaedic surgeon. The lead/senior author of the original 2013 and 2014 guidelines, and co-author on all subsequent versions, is an academic orthopaedic department chair who has decades of experience managing spine trauma and performing spine surgery. Additionally, he led the evidence-based medicine unit (and the associated clinical practice guidelines) of the American Academy of Orthopaedic Surgeons for five years. Inclusion of authors from those subspecialties (a much broader collection than suggested by Calland et al.) still did not change an analysis or recommendation similar to Millin et al.'s: that spinal immobilization was an inappropriate intervention which was demonstrably harmful and had no evidence-based demonstrable benefit. Calland et al. also cite "decades of accumulated clinical experience" as evidence that further study is needed, not "premature abandonment of established practice." What is the degree to which evidence becomes mature enough to change established practice? We have now passed the quarter century mark of accumulated evidence. As Millin et al. have demonstrated, that quarter century of "further study" has only further confirmed the same conclusion. Millin et al. ask how many more peer-reviewed manuscripts need to be published demonstrating harm before spinal immobilization is discarded. We would add, how many decades of data are needed before it is considered "mature"? Additionally, how many professional societies and multidisciplinary teams need to be assembled that come to this same conclusion before the harmful practice of spinal immobilization is discontinued? And finally, to frame this in its most appropriate and patient-centered context-how many patients need to be harmed?},
}

@article {pmid41980219,
year = {2026},
author = {Galizzi, G},
title = {MAMs as a promising therapeutic strategy for age-related neurodegenerative diseases.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1342},
pmid = {41980219},
issn = {2152-5250},
abstract = {Aging is a natural process leading to the slow and progressive deterioration of numerous physiological functions. It is the main risk factor for several neurodegenerative diseases. Mitochondria-associated membranes (MAMs) or mitochondria-ER contacts (MERCs) are essential and dynamic sites of contact between mitochondria and the endoplasmic reticulum (ER) and are involved in numerous cellular processes, such as calcium (Ca[2+]) homeostasis, reactive oxygen species (ROS) production, autophagy, inflammation, mitochondrial dynamics, apoptosis, lipid biosynthesis, and trafficking. As a result, they play a significant role in maintaining cellular functionality regulating metabolism and ensuring proper stress responses. Recently, MAMs have been widely investigated to understand their critical role in cell physiology as well as in different pathological conditions. Increasing evidence indicates that alterations in ER-mitochondria communication contribute to aging and the development of age-related diseases. However, the cellular mechanisms underlying this link remain unclear. Understanding how these interactions change with age could provide further insights into the aging process and the mechanisms underlying age-related diseases, suggesting potential new therapeutic strategies. This review summarizes the current knowledge on MAM biology, focusing on their role in the pathogenesis of age-related brain disorders. Their therapeutic potential in limiting the progression of some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, and slowing the physiological aging process are also explored.},
}

@article {pmid41967717,
year = {2026},
author = {Erol Mart, HM and Akay, BN},
title = {Response to Navarrete-Dechent et al.'s "Ultraviolet-induced fluorescent dermoscopy for the diagnosis of skin tumors: A multicenter study.".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.01.106},
pmid = {41967717},
issn = {1097-6787},
}

@article {pmid41968313,
year = {2026},
author = {Ghanem, HN and El-Zaher, AA and Taha, EA and Abbas, AEF and Mahmoud, ST},
title = {MATLAB-candexch algorithm-enhanced UV spectrophotometric-chemometric models for green, blue, and white determination of cinnarizine, domperidone, and carcinogenic impurity in pharmaceuticals: NQS assessment and UN-SDGs integration.},
journal = {BMC chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13065-026-01779-0},
pmid = {41968313},
issn = {2661-801X},
abstract = {Novel analytical methodologies integrating UV spectrophotometric techniques with chemometric models were developed for the simultaneous determination of cinnarizine (CIN), domperidone (DOM), and benzophenone (BNZ), a carcinogenic degradation product of CIN, without prior separation. Despite their clinical significance, no existing methods have been reported for their simultaneous quantification. This approach aligns with green and white analytical chemistry principles, offering an environmentally sustainable solution. Predictive models were constructed using Classical Least Squares (CLS), Partial Least Squares (PLS), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). A key methodological advancement was the application of D-optimal design via MATLAB's Candexch algorithm, generating a strategically balanced validation dataset of 13 mixtures and overcoming limits of conventional data splitting in chemometric modelling. The methods demonstrated robust linearity across concentration ranges of 4-20 µg/mL for CIN, 3-15 µg/mL for DOM, and 1-5 µg/mL for BNZ. Calibration performance was excellent, with root mean square errors of calibration (RMSEC) values of 0.036-0.062 for CLS, 0.013-0.024 for PLS, and 0.009-0.012 for MCR-ALS. Notably, MCR-ALS exhibited the smallest and most consistent RMSEC range, demonstrating superior accuracy and stability compared to other chemometric models. Validation studies confirmed excellent method performance with recovery rates between 98 and 102%. The root mean square errors of prediction (RMSEP) for the validation set were 0.042-0.201 for CLS, 0.035-0.187 for PLS, and 0.022-0.154 for MCR-ALS, with MCR-ALS consistently exhibiting exceptional predictive capability. The environmental sustainability credentials of the methodology were comprehensively evaluated using nine distinct evaluation tools: NEMI, Complex GAPI, AGREE, BAGI, RGB12, SDAGI, Carbon Footprint Analysis, GSST, and NQS. These rigorous assessments confirmed the method's exceptional environmental compatibility while maintaining analytical excellence, positioning this approach as an ideal sustainable alternative for pharmaceutical quality control applications aligned with UN Sustainable Development Goals.},
}

@article {pmid41968317,
year = {2026},
author = {Algmaal, SE and Boltia, SA and El Saharty, YS and Ghoniem, NS},
title = {Chemometric and learning-based multivariate models for quantifying a challenging quaternary mixture of bupropion, dextromethorphan, and their related impurities by UV-Vis spectrophotometry.},
journal = {BMC chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13065-026-01784-3},
pmid = {41968317},
issn = {2661-801X},
abstract = {This study presents a robust, green, sustainable and time-efficient approach for the simultaneous determination of Bupropion HCl (BUP) and Dextromethorphan HBr (DEX) along with their related impurities 3-Chlorobenzoic acid and N, N-Dimethylaniline. Principal component regression (PCR) and partial least-squares (PLS), in addition to advanced chemometric models, namely multivariate curve resolution-alternating least squares (MCR-ALS), and artificial neural networks (ANN), are the four green smart multivariate spectrophotometric models that were proposed and validated. The suggested models were successful in examining the mixture of BUP and DEX in the presence of their impurities. Therefore, the suggested analytical methods can be applied to pharmaceutical formulation analysis without the need for a separation step. The proposed strategy offers a novel analytical platform for quality control laboratories to manage complex formulations involving interfering substances. To further ensure greenness and sustainability of the proposed approach, several assessment tools were applied, including the Modified National Environmental Methods Index (NEMI), Eco-Scale, the Analytical GREEnness (AGREE) metric, the Hexagon algorithm, the Green Analytical Procedure Index (GAPI), the Modified GAPI (MoGAPI), the Blue Applicability Grade Index (BAGI), White Analytical Chemistry (WAC), and the Click Analytical Chemistry Index (CACI). Many traditional analytical techniques pose undesirable dangers to the environment and the analyst, such as using hazardous solvents. This gave analysts the incentive to use green methodologies that take into account the use of safe chemicals, the production of the least amount of trash, substantial time savings, and enhanced analyst safety.},
}

@article {pmid41968679,
year = {2026},
author = {Li, A and Xiao, X and Qin, D and Su, H},
title = {Discovery of a novel TFEB activator targeting lysosomal dysfunction in amyotrophic lateral sclerosis using artificial intelligence-based virtual screening.},
journal = {Autophagy},
volume = {},
number = {},
pages = {},
doi = {10.1080/15548627.2026.2659295},
pmid = {41968679},
issn = {1554-8635},
abstract = {Lysosomal dysfunction is a defining feature of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), yet effective pharmacological strategies to restore lysosomal homeostasis remain limited. Transcription factor EB (TFEB), a master transcriptional regulator of lysosomal biogenesis, has emerged as an attractive therapeutic target. In our recent study published in Pharmacological Research, we established a robust artificial intelligence (AI) - driven virtual screening pipeline and identified isoginkgetin (ISO) as a potent TFEB activator that effectively promotes lysosomal biogenesis and enhances lysosomal function. Importantly, ISO exhibits potent neuroprotective effects against motor neuron degeneration in ALS models. Using this AI-driven strategy, we identified a previously unrecognized neuroprotective mechanism by which ISO protects motor neurons through TFEB-dependent restoration of lysosomal function, validating lysosomal function as a promising therapeutic target for ALS. Collectively, this work establishes that AI-powered screening to identify mTORC1-independent TFEB agonists is a valuable paradigm for the discovery and development of therapeutic agents against ALS and other neurodegenerative diseases.},
}

@article {pmid41969219,
year = {2026},
author = {Byrd, EJ and Crossley, JA and Chau, CCC and Actis, P and Calabrese, AN},
title = {An ALS-associated mutation in the C-terminal α-helix of TDP-43 uncouples condensate formation and amyloid assembly.},
journal = {Protein science : a publication of the Protein Society},
volume = {35},
number = {5},
pages = {e70565},
doi = {10.1002/pro.70565},
pmid = {41969219},
issn = {1469-896X},
support = {220628/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; 090932/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; WT104918MA/WT_/Wellcome Trust/United Kingdom ; RGS\R2\222357//Royal Society/ ; BB/Y00034X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/X003086/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M012573/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *DNA-Binding Proteins/genetics/chemistry/metabolism ; *Amyloid/chemistry/genetics/metabolism ; Protein Conformation, alpha-Helical ; Mutation ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) plays a critical role in RNA metabolism and is incorporated into biomolecular condensates called stress granules. In amyotrophic lateral sclerosis (ALS) and several other neurodegenerative disorders, TDP-43 undergoes aberrant phase transitions, forming insoluble amyloid aggregates, including fibrils composed of solely its intrinsically disordered C-terminal domain (CTD). Despite its central role in disease, the conformational dynamics of the CTD remain poorly understood due to its heterogeneous and transient conformational landscape. Here, we employ native ion mobility-mass spectrometry (IM-MS) using nanopipette sub-micron nano electrospray ionization (nanoESI) emitters to characterize the conformational landscape of wild-type and ALS-associated TDP-43 CTD variants (Q331K and R361S) under different solution conditions. Our data suggest that mutations and salt concentration modulate the CTD's conformations. Combined with thioflavin T fluorescence, light scattering, and microscopy, we reveal that these conformational shifts correlate with altered amyloid assembly kinetics and propensity to form condensates. Notably, the Q331K variant, which has a mutation in the transient α-helical region in the CTD, has reduced propensity to form biomolecular condensates but can undergo amyloid assembly in the absence of condensate formation, suggesting that sequence alterations in this α-helical region can tune the molecular mechanism of amyloid assembly. This study demonstrates the power of IM-MS in probing disordered proteins and reveals mechanistic insights into how disease-associated mutations differentially tune TDP-43 CTD amyloid assembly mechanisms.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism
Humans
*DNA-Binding Proteins/genetics/chemistry/metabolism
*Amyloid/chemistry/genetics/metabolism
Protein Conformation, alpha-Helical
Mutation

@article {pmid41969305,
year = {2026},
author = {Chan, KO and Grismer, LL},
title = {Extending GroupStruct2: a Bayesian and machine-learning framework for testing taxonomic hypotheses using morphometric data.},
journal = {ZooKeys},
volume = {1276},
number = {},
pages = {125-138},
pmid = {41969305},
issn = {1313-2989},
abstract = {Despite considerable advances in statistical methods, taxonomic delimitation using morphometric data (morphometric delimitation) has not significantly progressed beyond the use of simple summary statistics or univariate tests to quantify differences among predefined operational taxonomic units (OTUs). These methods typically rely on visual inspection of graphs or p-value thresholds to determine if character means are statistically different. Tiburtini et al. (2025) introduced a conceptually different approach for morphometric delimitation using Bayesian model-testing and Gaussian Mixture Models (GMM). This approach can infer morphological clusters with or without a priori OTU groupings and jointly evaluates the fit of alternate taxonomic hypotheses to the data, providing a probabilistic, model-based framework that moves beyond traditional significance testing. Additionally, a machine-learning method was proposed to identify diagnostic characters based on a Random Forest classification algorithm. Initially developed for plant morphometrics, we adapted Tiburtini et al.'s approach for any morphometric dataset and integrated it into GroupStruct2, a Shiny R-based application with a full graphical user interface that also includes conventional statistical methods (e.g. univariate/multivariate tests, PCA, DAPC, MFA). We demonstrate that a more robust, nuanced, and comprehensive perspective on morphological variation and character diagnoses can be achieved using GroupStruct2's integrative workflow that combines classical statistical analyses with Bayesian GMM and machine-learning methods. The integration of frequentist and Bayesian methods within a user-friendly graphical interface democratizes access to robust statistical analyses and enables researchers to adopt quantitative rigor in taxonomic studies.},
}

@article {pmid41970050,
year = {2026},
author = {Ren, Y and Han, X and Zhang, K and Niu, S and Chen, B and Wang, X and Jian, F and Pan, H and Zhang, Z and Chen, X},
title = {MRI abnormal patterns of lumbar paraspinal muscles in patients with amyotrophic lateral sclerosis and lumbosacral radiculopathy: a comparative study.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1751139},
pmid = {41970050},
issn = {1664-2295},
abstract = {BACKGROUND: Recent evidence highlights the potential predictive value of paraspinal muscle degeneration in amyotrophic lateral sclerosis (ALS). However, the magnetic resonance imaging (MRI) characteristics of degeneration in lumbar paraspinal muscles in ALS and lumbosacral radiculopathy (LR) remain unclear.

METHODS: Comparison of fatty infiltration (FI) and relative cross-sectional area (rCSA) of the paraspinal muscles was conducted between 38 ALS patients and 32 LR patients.

RESULTS: The mean rCSA of the multifidus (MF), erector spinae (ES), and psoas major (PM) muscles was lower on the symptomatic onset side compared to the contralateral side at the L3-L5 segments in patients with ALS. On the symptomatic onset side, the FI of the ES (L1-L4 segments), MF (L4 segment), and PM muscles (L1, L2, and L4 segments) was significantly higher in ALS patients who had pathological spontaneous activity (PSA) than in those without PSA. At the L3-L5 segments on the symptomatic onset side, the mean rCSA of the MF, ES, and PM muscles was significantly higher in LR patients compared to ALS patients (p < 0.01). Similar differences in the rCSA of the MF, ES, and PM muscles were observed between lower limb-onset ALS patients and LR patients (p < 0.05). In addition, mild associations were observed between declines in the ALS functional rating scale (ALSFRS)-lower score and decreases in the rCSA of MF and PM muscles, as well as increased FI of the MF and ES muscles.

CONCLUSION: The decrease in the rCSA of the paraspinal muscles on the symptomatic onset side suggests progressive involvement of muscle fibers in ALS patients. The presence of PSA in the paraspinal muscles appears to be more valuable and sensitive for evaluating fatty substitution than muscle atrophy in ALS. MRI parameters of the paraspinal muscles may be useful for monitoring disease progression in ALS and distinguishing ALS, especially lower limb-onset cases, from pauci-symptomatic LR.},
}

@article {pmid41971996,
year = {2026},
author = {Apostol, CV and Li, A and Daniels, P and Griffith, L and Cooper-Knock, J and Aguilar-Martinez, E and Yonchev, ID and Whelan, AGR and Shaw, PJ and Sudbery, IM and Wilson, SA},
title = {hnRNPUL1 has a dead polynucleotide kinase domain that regulates RNA and protein interactions.},
journal = {iScience},
volume = {29},
number = {4},
pages = {115360},
pmid = {41971996},
issn = {2589-0042},
abstract = {hnRNPUL1 is a nuclear RNA-binding protein involved in both pre-mRNA splicing and DNA double-strand break repair. Using AlphaFold, we show that hnRNPUL1 has a central folded region consisting of tightly juxtaposed SPRY and dead polynucleotide kinase (dPNK) domains flanked by intrinsically disordered regions (IDRs). The dPNK domain binds both nucleotides and RNA. Remarkably, polynucleotide kinase activity can be reactivated with a single amino acid substitution. Mutations altering nucleotide binding also change the ability of the entire protein to bind RNA and regulate homotypic versus heterotypic protein interactions driven by the IDRs. A mutation that prevents nucleotide binding also destabilizes the protein. In a small number of amyotrophic lateral sclerosis patients, we identify rare coding variants in the HNRNPUL1 gene, which alter the ability of hnRNPUL1 to bind nucleotides, RNAs, and FUS. Together, these data establish that hnRNPUL1 utilizes its dPNK domain to regulate interactions with itself, RNA, and other proteins.},
}

@article {pmid41973722,
year = {2026},
author = {Ge, D and Wu, L and Yang, J and Sun, J and Wang, J and Wang, J and Song, H and Wei, R and Xu, Z and Zhao, B and Sun, R and Wang, Y},
title = {Adverse events in different administration routes of Edaravone: A pharmacovigilance study based on the FDA adverse event reporting system.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0346797},
doi = {10.1371/journal.pone.0346797},
pmid = {41973722},
issn = {1932-6203},
mesh = {*Edaravone/adverse effects/administration & dosage ; Humans ; United States ; United States Food and Drug Administration ; *Adverse Drug Reaction Reporting Systems ; *Pharmacovigilance ; Female ; Male ; Middle Aged ; Administration, Oral ; Amyotrophic Lateral Sclerosis/drug therapy ; Aged ; Administration, Intravenous ; Adult ; *Drug-Related Side Effects and Adverse Reactions/epidemiology ; },
abstract = {The U.S. Food and Drug Administration (FDA) approved intravenous edaravone for the treatment of amyotrophic lateral sclerosis (ALS) in 2017, followed by the approval of the oral formulation in 2022. This study aims to utilize the FDA#39;s Adverse Event Reporting System (FAERS) to investigate the spectrum and timing of adverse events (AEs) associated with edaravone administration, employing repeatability analysis, the Reporting Odds Ratio (ROR) approach, Weibull distribution, and stratification methods. The investigation focuses on data collected from the first quarter of 2017 through the fourth quarter of 2024, aiming to identify adverse event signals and their temporal patterns related to both intravenous and oral edaravone administration. In total, 3,262 records of edaravone-related adverse reactions were identified; among these, 1,534 incidents were associated with intravenous administration, while 453 incidents pertained to oral administration. The analysis revealed distinct adverse reaction profiles for the two routes of administration. Notably, the spectrum of adverse reactions resulting from oral administration predominantly involved the respiratory system, digestive system, and skin damage. In contrast, intravenous administration was more frequently linked to complications associated with invasive procedures and local tissue damage. Furthermore, the timing of adverse reactions exhibited significant variability between the two routes. Weibull distribution analysis indicated that the median onset time for adverse reactions following intravenous administration was 35 days, whereas for oral administration, it was 27 days. Both analytical approaches identified early failure signals, suggesting that the risk of adverse events diminishes over time.},
}

*Edaravone/adverse effects/administration & dosage
Humans
United States
United States Food and Drug Administration
*Adverse Drug Reaction Reporting Systems
*Pharmacovigilance
Female
Male
Middle Aged
Administration, Oral
Amyotrophic Lateral Sclerosis/drug therapy
Aged
Administration, Intravenous
Adult
*Drug-Related Side Effects and Adverse Reactions/epidemiology

@article {pmid41973791,
year = {2026},
author = {Kindbom Land, J and van den Berg, R and Hofvander, B and Sellbom, M and Pauli, M},
title = {Field reliability of the Psychopathy Checklist-Revised among life-sentenced prisoners in Sweden: A follow-up study.},
journal = {Law and human behavior},
volume = {},
number = {},
pages = {},
doi = {10.1037/lhb0000664},
pmid = {41973791},
issn = {1573-661X},
abstract = {OBJECTIVE: The Psychopathy Checklist-Revised (PCL-R) is widely used in forensic and clinical contexts, yet its reliability in high-stakes legal settings remains uncertain. In Sweden, it is routinely applied in court-ordered assessments for life-sentenced prisoners seeking commutation, making score consistency crucial. Sturup et al. (2014) found lower interrater reliability in this context compared with controlled research studies. This study examines whether reliability has increased since their publication and evaluates the incremental contribution of these assessments to structured professional judgment risk classifications.

HYPOTHESES: Due to increased training and experience, we expected improved reliability compared with that of Sturup et al.'s study.

METHOD: We estimated interrater reliability of PCL-R total and facet scores using intraclass correlation coefficients (ICC) for 76 life-sentenced prisoners (75 males, one female) who had participated in 217 risk assessments by the Swedish National Board of Forensic Medicine (2013-2023). Associations between PCL-R, Historical-Clinical-Risk Management-20, and structured professional judgment risk classifications were tested with ordinal mixed-effects models.

RESULTS: The results mirror those of Sturup et al., indicating no substantial improvement in interrater reliability over the last decade. Specifically, the PCL-R total score had an ICC = .73, and the facet-level ICCs were .88 (antisocial), .65 (interpersonal), .59 (affective), and .59 (lifestyle). Only 27% of score differences between assessments fell within one standard error of measurement, indicating more variability than expected based on the manual. Moreover, Historical-Clinical-Risk Management-20 scores were better predictors of the risk classification than the PCL-R scores, indicating limited incremental value of the latter.

CONCLUSIONS: Reliability of the PCL-R in Swedish forensic assessments has not improved over the past decade and remains moderate. Moreover, structured violence risk factors may weigh more heavily in final judgments than psychopathy ratings. While this reliance may limit the impact of variability in PCL-R scoring, caution is warranted when using psychopathy assessments in high-stakes legal decisions. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid41963814,
year = {2026},
author = {Sýkora, R and Chvojka, J and Kukačková, N and Šimečková, V and Smetana, J},
title = {Early resuscitation priorities in two-provider EMS crews: an interpretive commentary.},
journal = {BMC emergency medicine},
volume = {26},
number = {1},
pages = {},
pmid = {41963814},
issn = {1471-227X},
abstract = {BACKGROUND: International resuscitation guidelines are grounded in physiological principles and outcome-based evidence, but they implicitly assume staffing levels that allow multiple time-critical interventions to be delivered in parallel. In many emergency medical systems, however, advanced life support is initially provided by a two-provider crew working alone for a substantial period. Under these conditions, the parallel task execution described in guidelines may become structurally impossible because of capacity constraints. This commentary therefore focuses on adult non-traumatic out-of-hospital cardiac arrest managed according to standard adult ALS guidelines.

INTERPRETIVE FRAMEWORK: This article is presented as an interpretive commentary and is intended to provide an explanatory perspective on how early guideline-consistent care is enacted under conditions of limited personnel and cognitive capacity, rather than as a prescriptive care algorithm. It applies exclusively to the initial, transient phase of out-of-hospital resuscitation in which advanced life support is delivered by a two-provider professional crew working alone. Its applicability ends once additional trained personnel arrive, stable task allocation becomes possible, or the initial defibrillation cycles have been completed. Deviations from ideal task sequencing are conceptualised as forced deviations, an emergent property of system-level capacity limits rather than individual performance failure. Resuscitation actions are therefore considered in terms of their relative short-term physiological penalty when delayed or interrupted: (1) critical perfusion-dependent actions, where interruption is associated with immediate physiological harm; (2) actions with lower short-term physiological penalty when briefly deferred; and (3) bounded uncertainty domains, particularly ventilation, where physiological effects are non-linear and context dependent.

CONCLUSION: This interpretive commentary does not modify existing resuscitation guidelines. Instead, it clarifies how their physiological intent may be understood and preserved during the earliest phase of two-provider advanced life support, when parallel task execution is not feasible. By providing a shared interpretive model for early resuscitation under capacity constraint, this approach may help reduce harmful variability, cognitive overload, and misinterpretation of performance at a system level in real-world emergency medical systems.},
}

@article {pmid41964251,
year = {2026},
author = {Anastasakis, DG and Hafner, M},
title = {RNA G-Quadruplex-protein interactions: from nuclear RNA processing to cytoplasmic stress response and neurodegeneration.},
journal = {RNA biology},
volume = {},
number = {},
pages = {},
doi = {10.1080/15476286.2026.2658922},
pmid = {41964251},
issn = {1555-8584},
abstract = {RNA G-quadruplexes (rG4s) are stable secondary structures formed by non-canonical Hoogsteen base-pairing of guanine-rich sequences in precursor and mature messenger and non-coding RNAs. We review evidence that rG4s exist in two functionally distinct worlds. In the nucleus, rG4s fold co-transcriptionally to regulate gene expression and RNA processing and organizing membraneless organelles through liquid-liquid phase separation. Splicing regulation by rG4s is restricted to vertebrates and co-evolved with transcriptome complexity. In the cytoplasm, rG4s are actively maintained in an unfolded state by dedicated helicases and RNA-binding proteins, but fold upon stress to nucleate stress granules, that sequester mRNAs and sustain cell survival. When compartmentalization of rG4-protein interactions fails, cells lose both nuclear RNA processing control as well as cytoplasmic translational regulation and proper stress response. The same biophysical properties that make rG4s effective scaffolds for reversible phase separation in RNA processing, proteostasis, and acute stress become liabilities under chronic conditions: in ageing neurons, failure of rG4-protein homoeostasis transforms protective condensates into irreversible aggregates associated with α-synuclein, tau, TDP-43, and FUS pathology. We discuss the implications of a dynamic equilibrium of folded and unfolded rG4s in health and disease, with particular focus on their emerging roles in neurodegeneration.},
}

@article {pmid41964384,
year = {2026},
author = {Hodgson, AKO and McDermott, CJ and Shaw, PJ and Alix, JJP},
title = {The Diagnostic Potential of Axon Excitability Is Consistent Across Hand Muscles in Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70239},
pmid = {41964384},
issn = {1097-4598},
support = {//NIHR Sheffield Biomedical Research Center (BRC)/ ; },
abstract = {INTRODUCTION/AIMS: Recent work suggests that nerve excitability testing has diagnostic potential in amyotrophic lateral sclerosis (ALS). The diagnostic performance of nerve excitability across hand muscles is currently unknown. This study aimed to assess if muscles of the so-called split hand (abductor pollicis brevis [APB], first dorsal interosseous [FDI], and abductor digiti minimi [ADM]) manifest differences in diagnostic performance.

METHODS: We prospectively recruited 60 consecutive patients investigated for ALS. Nerve excitability, motor unit number and size (MScanFit), needle electromyography (EMG), and standard clinical data were collected. ALS and non-ALS groups were compared using t tests, area under receiver operating characteristic curves (AUROC), and multivariate modeling.

RESULTS: Forty-eight patients completed testing of all three muscles, 25 were diagnosed with ALS. The most prominent nerve excitability changes were in superexcitability (APB p = 0.001, FDI p = 0.0001, ADM p = 0.002). Diagnostic performance with superexcitability was similar across the three muscles (p > 0.05). Reductions in motor unit number were observed in ALS patients. Changes in excitability were evident without loss of motor units, most frequently in APB (40% of recordings). Improvements to the AUROC were obtained using combined excitability/motor unit parameters from APB/FDI (AUROC 0.97, p = 0.01 vs. FDI superexcitability alone). Combined excitability and motor unit modeling outperformed detection of EMG abnormalities.

DISCUSSION: Disturbances to nerve excitability are similar across the split hand muscles at the time of ALS diagnosis. These occurred prior to motor unit loss and traditional EMG changes. Combining excitability and motor unit parameters in the lateral hand can identify early pathology and potentially lead to earlier diagnosis.},
}

@article {pmid41964401,
year = {2026},
author = {Baron, L and Diba, K and Amarasingham, A},
title = {The Role of Plasticity in Replay: Stability Through Anti-Hebbian Rules.},
journal = {Hippocampus},
volume = {36},
number = {3},
pages = {e70089},
pmid = {41964401},
issn = {1098-1063},
support = {R01MH139216/MH/NIMH NIH HHS/United States ; 2423995//National Science Foundation/ ; PHY-230195//National Science Foundation/ ; },
mesh = {*Neuronal Plasticity/physiology ; *Models, Neurological ; *Hippocampus/physiology ; Animals ; Action Potentials/physiology ; Humans ; Synapses/physiology ; *Neurons/physiology ; Memory/physiology ; },
abstract = {Hippocampal replay is now considered to be a cornerstone of memory consolidation, yet the synaptic plasticity rules governing its dynamics remain elusive. Under the standard asymmetric Hebbian spike-timing dependent plasticity (STDP) model, the same spike patterns that promote activity propagation along one direction of sequential activation undermine propagation in the reverse direction, compromising "bidirectional" replay. On the other hand, symmetric potentiation rules, as recently proposed for region CA3, risk corrupting the memory trace by saturating synaptic weights. Using Ecker et al.'s recurrent network model of place cells that spontaneously generate replays during ripples, we systematically investigated how different STDP plasticity rules modulate offline replays. We developed a classification framework to study the mechanisms relating different STDP kernels to key replay characteristics, including directionality, speed, and stability. Our results confirmed that symmetric potentiation rules during offline states saturate synapses, inducing rigid attractors that corrupt the memory trace, and that an asymmetric Hebbian STDP kernel induces strong biases in the directionality of replay, leading to rapid replay acceleration and replay degradation. Notably, we found that an asymmetric anti-Hebbian STDP kernel preserves replay bi-directionality and stabilizes replay speed. We further identified the negative timing component of the STDP rule as the primary driver of replay speed: potentiation causes deceleration, while depression causes acceleration. These findings provide a mechanistic explanation for empirically observed replay deceleration and suggest a role for anti-Hebbian synaptic depression in stabilizing replay dynamics.},
}

*Neuronal Plasticity/physiology
*Models, Neurological
*Hippocampus/physiology
Animals
Action Potentials/physiology
Humans
Synapses/physiology
*Neurons/physiology
Memory/physiology

@article {pmid41964735,
year = {2026},
author = {Matsuda, C and Nakayama, Y and Haraguchi, M and Morishima, R and Itagaki, Y and Bokuda, K and Hayashi, K and Takahashi, K and Shimizu, T},
title = {Weight maintenance following enteral nutrition is associated with prolonged survival in amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {5},
pages = {},
pmid = {41964735},
issn = {1432-1459},
support = {Grant-in-Aid for Scientific Research [B] No. 23K24656//Japan Society for the Promotion of Science/ ; Grant-in-Aid for Scientific Research[C] No. 23K09948//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/therapy/physiopathology ; Male ; Female ; *Enteral Nutrition ; Retrospective Studies ; Middle Aged ; Aged ; Body Mass Index ; *Energy Intake/physiology ; *Body Weight/physiology ; Kaplan-Meier Estimate ; Proportional Hazards Models ; Adult ; },
abstract = {OBJECTIVE: To investigate the association between energy intake at the initiation of enteral nutrition (EN), subsequent changes in body mass index (BMI), and survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: This retrospective study included 121 patients with ALS who received EN. Annual BMI decline rates (∆BMI, kg/m[2]/year) were calculated for three periods: from symptom onset to diagnosis (T1-T2), from diagnosis to EN initiation (T2-T3), and from EN initiation to post-EN assessment (T3-T4). Energy intake per weight (E/W, kcal/kg/day) at EN initiation was also assessed. Survival after EN initiation was analyzed using Kaplan-Meier methods and Cox proportional hazards models.

RESULTS: Post-EN BMI decline (∆BMIT3-T4) showed a significant negative correlation with E/W at T3 (p < 0.001). Patients with lower post-EN BMI decline (∆BMI < 0.8 kg/m[2]/year) had significantly longer survival after EN initiation than those with greater BMI decline (p < 0.001). Multivariate Cox analysis identified ∆BMIT3-T4 and pre-EN respiratory decline as independent predictors of post-EN survival. Subgroup analyses demonstrated that patients who maintained body weight after EN had better survival irrespective of energy intake at EN initiation.

CONCLUSION: Weight maintenance following EN was associated with prolonged survival in ALS, whereas energy intake at EN initiation alone was not. These findings suggest that the survival benefit of nutritional intervention may be mediated through stabilization of body weight rather than caloric intake per se.},
}

Humans
*Amyotrophic Lateral Sclerosis/mortality/therapy/physiopathology
Male
Female
*Enteral Nutrition
Retrospective Studies
Middle Aged
Aged
Body Mass Index
*Energy Intake/physiology
*Body Weight/physiology
Kaplan-Meier Estimate
Proportional Hazards Models
Adult

@article {pmid41966055,
year = {2026},
author = {Russell, ND and Downie, JM and Bromberg, MB and Pulst, SM and Jorde, LB},
title = {Genetic contributions to mitochondrial dysfunction in amyotrophic lateral sclerosis etiology.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100614},
doi = {10.1016/j.xhgg.2026.100614},
pmid = {41966055},
issn = {2666-2477},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with multiple genetic causes. Given the strong evidence of mitochondrial dysfunction in ALS, this study aimed to identify genetic contributors to ALS by focusing on genes involved in mitochondrial function. Whole-genome and exome sequencing data from 1,034 ALS cases were analyzed using two distinct computational tools, which ranked candidate genes based on functional relevance to ALS. POLG, the sole mitochondrial DNA polymerase, emerged as a top candidate gene. RNA-seq analysis revealed that among genes upregulated in samples with a POLG variant, there was an enrichment for mitochondrial pathways such as translation, localization, and mitophagy. It also revealed variants in POLG and SOD1, a well-known ALS gene, to be the most enriched in samples with expression profiles of mitochondrial-related genes that differed most from those of unaffected controls. POLG variant carriers also exhibited an increased burden of mitochondrial genome variants, a pattern shared by carriers of variants in other genes involved in mitochondrial DNA maintenance. Additionally, POLG variant carriers had elevated mitochondrial DNA copy number (mtDNA-CN), similar to carriers of variants in mitophagy-related genes, suggesting impaired mitophagy. Together, these findings implicate POLG as an ALS-associated gene and link mitochondrial DNA maintenance defects, altered expression of mitochondrial-related pathways, and impaired mitophagy to ALS etiology.},
}

@article {pmid41967177,
year = {2026},
author = {Dhandapani, R and Bakavayev, S and Armoza, A and Bersudsky, M and Shlifer, A and Yehezkel, G and Tsitrina, A and Barak, Z and Sintov, AC and Engel, S},
title = {Nose-to-brain delivery of a SOD1-stabilizing small molecule ameliorates pathology in an ALS mouse model.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {3},
pages = {e00904},
doi = {10.1016/j.neurot.2026.e00904},
pmid = {41967177},
issn = {1878-7479},
abstract = {Exposure of a pathogenic β6/β7 loop neo-epitope has been proposed to contribute to the pathogenesis of misfolded Cu/Zn superoxide dismutase (SOD1) in amyotrophic lateral sclerosis (ALS) by mediating early events in its noxious structural transformation and prion-like activity. Antibody-mediated blockade of this epitope was shown to ameliorate disease phenotype in an ALS animal model. Here, as an alternative strategy, we sought to block this epitope using a small molecule designed to occupy the inter-subunit cavity framed by the two β6/β7 loops. Using a structure-based virtual screen targeting this cavity, we identified a small molecule, N-[3-(3-methylimidazo[2,1-b][1,3]thiazol-6-yl)phenyl]-4-sulfamoylbenzamide (C7), that preferentially bound the native-like conformation of SOD1, reduced β6/β7 loop epitope accessibility, and inhibited irreversible apo-SOD1 misfolding in vitro. Delivered to presymptomatic hSOD1[G93A] mice via a nanoparticle-based nose-to-brain delivery system, C7 significantly delayed the onset of motor abnormalities and modestly extended survival. At disease onset, spinal cord analysis revealed reduced misfolded SOD1 inclusions and attenuated astro- and microgliosis. Analysis of C7 concentrations in combined brain and spinal cord tissue indicated rapid but saturable nose-to-CNS uptake and slow clearance. Our findings demonstrate that targeting the surface cavity shaped by the β6/β7 loops of SOD1 with a reversibly-binding small molecule can ameliorate ALS-like disease in vivo, potentially by counteracting early misfolding events and/or limiting prion-like propagation of molecular pathology. However, saturable nose-to-CNS uptake of C7 restricts CNS exposure and likely constrains therapeutic efficacy, underscoring the need to define the rate-limiting pharmacokinetic step and to optimize the nanoparticle formulation and/or physicochemical properties of the C7 scaffold.},
}

@article {pmid41961863,
year = {2026},
author = {Emond, A and Laflamme, C and Therrien, M and Liao, M and Maios, C and Labarre, A and Drapeau, P and Parker, JA},
title = {Characterization of a C9orf72 Knockout Danio rerio model for ALS and cross-species validation of potential therapeutics screened in Caenorhabditis elegans.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0346613},
pmid = {41961863},
issn = {1932-6203},
mesh = {Animals ; *Zebrafish/genetics ; *Caenorhabditis elegans/genetics ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/pathology ; Disease Models, Animal ; Gene Knockout Techniques ; Humans ; CRISPR-Cas Systems ; Motor Neurons/pathology/metabolism ; Larva ; Animals, Genetically Modified ; Phenotype ; },
abstract = {Intronic hexanucleotide repeat expansions in the C9orf72 gene represent the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. This expansion decreases C9orf72 expression in affected patients, indicating that loss of C9orf72 function (LOF) acts as a pathogenic mechanism. Several models using Danio rerio (zebrafish) for C9orf72 depletion have been developed to explore disease mechanisms and the consequences of C9orf72 LOF. However, inconsistencies exist in reported phenotypes, and many have yet to be validated in stable germline ablation models. To address this, we created a zebrafish C9orf72 knockout model using CRISPR/Cas9. The C9orf72 LOF model demonstrates, in a generally dose-dependent manner, increased larval mortality, persistent growth reduction, and motor deficits. Additionally, homozygous C9orf72 LOF larvae exhibited mild overbranching of spinal motoneurons. To identify potential therapeutic compounds, we performed a screen on an established Caenorhabditis elegans (C. elegans) C9orf72 homologue (alfa-1) LOF model, identifying 12 compounds that enhanced motility, reduced neurodegeneration, and alleviated paralysis phenotypes. Motivated by the shared motor phenotype, 2 of those compounds were tested in our zebrafish C9orf72 LOF model. Pizotifen malate was found to significantly improve motor deficits in C9orf72 LOF zebrafish larvae. We introduce a novel zebrafish C9orf72 knockout model that exhibits phenotypic differences from depletion models, providing a valuable tool for in vivo C9orf72 research and ALS therapeutic validation. Furthermore, we identify pizotifen malate as a promising compound for further preclinical evaluation.},
}

Animals
*Zebrafish/genetics
*Caenorhabditis elegans/genetics
*C9orf72 Protein/genetics
*Amyotrophic Lateral Sclerosis/genetics/drug therapy/pathology
Disease Models, Animal
Gene Knockout Techniques
Humans
CRISPR-Cas Systems
Motor Neurons/pathology/metabolism
Larva
Animals, Genetically Modified
Phenotype

@article {pmid41962593,
year = {2026},
author = {Ran, X and Wang, M and Huang, J and Kuang, N and Tian, P and Wu, J and Feng, F and Luo, Y and Huang, N},
title = {Mechanistic Research and Therapeutic Prospects of Alternative Splicing in Neurodegenerative Diseases.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103133},
doi = {10.1016/j.arr.2026.103133},
pmid = {41962593},
issn = {1872-9649},
abstract = {One essential post-transcriptional regulatory mechanism that increases protein diversity in eukaryotes is alternative splicing. This process is crucial for maintaining nervous system function and is highly active in neurons. Dysregulation of alternative splicing is a common pathogenic factor in many neurodegenerative diseases. For example, splicing variants of tau protein and amyloid precursor protein are implicated in Alzheimer's disease; aberrant splicing of α-synuclein (SNCA) and upregulation of specific transcript variants of the Parkin (PARK2) gene occurs in Parkinson's disease; and aberrant splicing of Stathmin-2 (STMN2) pre-mRNA leads to the loss of axonal maintenance proteins in amyotrophic lateral sclerosis and frontotemporal dementia. This process is precisely regulated by trans-acting factors, a class of RBPs that specifically recognize and bind to cis-acting elements on precursor mRNA (pre-mRNA). These factors are primarily categorized into two major groups: serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs). Although hnRNPs and SR proteins have been shown to regulate neuronal alternative splicing, their complex regulatory networks and associated disease mechanisms remain incompletely understood, hindering the development of targeted therapies. This review summarizes the molecular mechanisms of alternative splicing and its regulatory features in neurodegenerative diseases. It also summarizes recent advances in splicing-based therapies and biomarkers, providing insights into disease mechanisms and therapeutic development.},
}

@article {pmid41964083,
year = {2026},
author = {Viswanathan, M and Yin, L and Kurmi, Y and Chai, S and Jiang, X and Huo, Y and Xu, J and Chen, L and Gore, JC and Zu, Z},
title = {Enhanced Quantitative Phosphocreatine MR Imaging of Skeletal Muscle Using a Global-Local Two-Branch Deep Learning Model.},
journal = {Magnetic resonance in medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/mrm.70386},
pmid = {41964083},
issn = {1522-2594},
support = {R01NS140757/NH/NIH HHS/United States ; R01EB036574/NH/NIH HHS/United States ; R01EB029443/NH/NIH HHS/United States ; R21AG089699/NH/NIH HHS/United States ; },
abstract = {PURPOSE: Phosphocreatine (PCr) is an essential marker of muscle metabolism, and accurate quantification of its (fs) and its exchange rate (ksw) is essential for diagnosing various muscular and neuromuscular diseases. Although chemical exchange saturation transfer (CEST) MRI can detect the saturation transfer effect from PCr, quantification of the underlying PCr fs and ksw, particularly at low fields, remains challenging due to significant overlapping confounding effects in tissues when using conventional fitting approaches. Deep learning (DL) presents a promising alternative, yet traditional DL models often struggle to capture subtle PCr-specific variations induced by changes in fs or ksw. Furthermore, these models are typically trained on either fully synthetic data, which may not adequately mimic tissues, or in vivo data which lack ground truth.

METHODS: This study introduces a global-local two-branch DL model to effectively eliminate confounding effects and capture subtle variations in the PCr CEST effect. Furthermore, our model was trained on partially synthetic data that offers both simulation flexibility and fidelity. Model accuracy was evaluated by using both digital and physical phantoms, and the model was applied to skeletal muscle of healthy rats and rats with amyotrophic lateral sclerosis (ALS).

RESULTS: Phantom experiments demonstrate that our approach surpasses all fitting methods, the state-of-the-art model, and other combinations of DL models and training data. In vivo, the model identified a significant reduction in PCr fs in ALS rats, which other methods fail to detect.

CONCLUSIONS: Our global-local two-branch DL model trained using partially synthetic data enhances PCr quantification in skeletal muscle.},
}

@article {pmid41964193,
year = {2026},
author = {Grabarczyk, Ł},
title = {Comprehensive Review of Anesthetic Strategies for Patients With Neurodegenerative Diseases.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {32},
number = {},
pages = {e950453},
doi = {10.12659/MSM.950453},
pmid = {41964193},
issn = {1643-3750},
mesh = {Humans ; *Neurodegenerative Diseases/surgery/physiopathology ; *Anesthesia/methods ; *Anesthetics/therapeutic use ; Neuromuscular Blockade/methods ; Perioperative Care/methods ; },
abstract = {Patients with neurodegenerative diseases (NDDs) represent a unique and challenging population from an anesthesiological perspective due to their neurological vulnerability. This issue is becoming increasingly relevant as the incidence of certain NDDs rises with population aging. Effective perioperative management in patients with NDDs requires detailed preoperative evaluation, with emphasis on neurological status, cardiopulmonary function, and a thorough review of current medications. Intraoperatively, careful selection of anesthetic agents and monitoring strategies is essential because of altered drug sensitivity, increased susceptibility to malignant hyperthermia, and potential drug interactions. Particular attention must be given to neuromuscular blockade. The use of nondepolarizing neuromuscular blocking agents is generally risky due to their potentially prolonged and unpredictable effects; their use may be considered under strictly controlled conditions. In contrast, propofol and inhalational agents have demonstrated safety and efficacy in this patient population. This article aims to review the perioperative anesthetic management of patients with NDDs, including Huntington disease, (spino)cerebellar ataxia, Friedreich ataxia, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis.},
}

Humans
*Neurodegenerative Diseases/surgery/physiopathology
*Anesthesia/methods
*Anesthetics/therapeutic use
Neuromuscular Blockade/methods
Perioperative Care/methods

@article {pmid41956875,
year = {2026},
author = {Ye, M and Song, C},
title = {Microbiome eavesdropping: root-knot nematodes decode rhizosphere volatile dialogues.},
journal = {Trends in plant science},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tplants.2026.03.007},
pmid = {41956875},
issn = {1878-4372},
abstract = {Root-knot nematodes navigate the underground chemical landscape to find their hosts. Building on Wu et al.'s discovery that plant metabolites shape microbial cues guiding nematode behavior, this commentary explores how rhizosphere chemical communication integrates plant, microbial, and parasite interactions within a shared 'information network'.},
}

@article {pmid41956959,
year = {2026},
author = {Koterazawa, Y and Goto, H and Aoki, T and Sugita, Y and Ikeda, T and Harada, H and Otowa, Y and Urakawa, N and Hasegawa, H and Kanaji, S and Yamashita, K and Matsuda, T and Kakeji, Y},
title = {Biological Age Reflects Physical Condition and Predicts Postoperative Complications Beyond Chronological Age in Patients With Esophageal Squamous Cell Carcinoma Undergoing Minimally Invasive Esophagectomy.},
journal = {World journal of surgery},
volume = {},
number = {},
pages = {},
doi = {10.1002/wjs.70363},
pmid = {41956959},
issn = {1432-2323},
support = {24K19359//JSPS KAKENHI/ ; },
abstract = {BACKGROUND: Chronological age is an important indicator of the physical condition; however, it may not fully capture their physiological status. Recently, biological age has gained attention as a more accurate predictor of physical condition. This study aimed to investigate the association between biological age and postoperative outcomes in patients with esophageal squamous cell carcinoma (ESCC).

METHODS: This study included 345 patients with ESCC who underwent minimally invasive esophagectomy at Kobe University Hospital. Biological age was estimated using Levine et al.'s model based on data from nine commonly used blood tests. Patients were stratified by biological age: ≥ 75 years and < 75 years.

RESULTS: Patients with biological age ≥ 75 years (N = 59) were more likely to be male (p = 0.012) and had lower serum albumin levels (p = 0.0003) and higher creatinine levels (p = 0.0009) than those with biological age < 75 years (N = 286). Regarding postoperative complications, patients aged ≥ 75 years had higher rates of pulmonary complications (p = 0.032) and anastomotic leakage (p = 0.038). No significant differences were observed in overall survival between the ≥ 75 and < 75 age groups, regardless of disease stage. In patients with advanced ESCC, 93% of those with chronological age < 75 years and biological age ≥ 75 years (N = 27) received preoperative chemotherapy. Conversely, only 80% of patients with chronological age ≥ 75 years and biological age < 75 years (N = 20), who had better general condition, received preoperative chemotherapy.

CONCLUSIONS: Biological age is associated with postoperative complications. Assessing physical condition using biological age may help determine patients' eligibility for preoperative chemotherapy.},
}

@article {pmid41957276,
year = {2026},
author = {Fang, L and Bai, Z and Yang, D and Sun, B and Zhao, X and Deng, J},
title = {Elimination of senescent cells fails to attenuate disease progression in an ALS mouse model.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {5},
pages = {},
pmid = {41957276},
issn = {1590-3478},
support = {2025NSFJQ0057//the Department of Science and Technology of Sichuan Province/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/therapy/physiopathology/genetics ; Mice, Transgenic ; Disease Progression ; Disease Models, Animal ; *Cellular Senescence/physiology ; Mice ; Humans ; Superoxide Dismutase-1/genetics ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder involving progressive motor neuron degeneration, resulting in muscle weakness and paralysis. Current therapeutic options provide only modest benefit, and the etiology of ALS remains incompletely understood. Emerging evidence implicates cellular senescence in the central nervous system (CNS) of ALS pathogenesis, with senescent astrocytes identified in both animal models and patients.

METHODS: We employed transgenic mice overexpressing the human superoxide dismutase 1 gene with a glycine-to-alanine substitution at codon 93 (hSOD1[G93A]) as the experimental model. To eliminate senescent cells, mouse-derived natural killer group 2, member D (NKG2D) chimeric antigen receptor T (CAR-T) cells were engineered to target NKG2D ligands (NKG2DLs) [+] senescent cells. The efficacy of senescent cell clearance was assessed by SA-β-gal staining on frozen tissue sections and by quantifying the expression of senescence-associated markers (e.g., p16[INK4a], p21). Disease progression in mice was evaluated by monitoring changes in body weight, behavioral performance, and motor function.

RESULTS: We found that NKG2DLs[+] senescent cells accumulate in symptomatic transgenic mice. NKG2D CAR-T cells can selectively eliminate senescent cell populations in symptomatic hSOD1[G93A] mice. A single infusion effectively reduced senescent cell burden and suppressed Senescence-Associated Secretory Phenotype (SASP) features within central nervous system tissues. However, no significant improvements in motor function or survival were observed.

CONCLUSION: These results indicate that while senescence is a pathogenic feature of ALS, it operates within an integrated disease network. Early senolytic intervention or combinatorial approaches may represent promising future strategies for ALS.},
}

Animals
*Amyotrophic Lateral Sclerosis/pathology/therapy/physiopathology/genetics
Mice, Transgenic
Disease Progression
Disease Models, Animal
*Cellular Senescence/physiology
Mice
Humans
Superoxide Dismutase-1/genetics
NK Cell Lectin-Like Receptor Subfamily K/metabolism

@article {pmid41957959,
year = {2026},
author = {Jha, I and Arora, S and Ravi, SK},
title = {Comparison of Neurophysiological Parameters Between Menstruating and Menopausal Females at Different Frequencies.},
journal = {Annals of African medicine},
volume = {},
number = {},
pages = {},
doi = {10.4103/aam.aam_835_25},
pmid = {41957959},
issn = {0975-5764},
abstract = {INTRODUCTION: An important impact of gonadal hormones on the auditory pathway has been found. Few neurophysiological research study has been done during different phases of menstrual cycle and menopause. This study was conducted to compare the brainstem auditory evoked potential (BAEP) between menstruating females during the follicular phase and the menopausal group.

MATERIALS AND METHODS: This was a case-control study. Group 1 included n = 30 menstruating females in the follicular phase and aged between 18 and 25 years. Group 2 included 30 menopausal females and aged between 42 and 50 years. For analysis, Student's unpaired t-test and Chi-square test were applied. BAEP recording was done using standard protocol. Mean wave latencies: I, III, and V and interpeak latencies (IPLs): I-III, III-V, and I-V were recorded.

RESULTS: Mean ± standard deviation of absolute latencies (ALs) of brainstem auditory evoked potential (BERA) waves III and V and all IPL at 80 dB and 2, 4, 6 KHz in Group 2 menopausal females were delayed and significant as compared to Group 1 menstruating females. All parameters were highly significant at 6 KHz as compared to 2 KHz in menopausal Group 2.

CONCLUSION: Brainstem audiometry evoked potential detects hearing loss early in menopausal females at higher frequencies, i.e. at 6 KHz, due to a decrease in estrogen level.},
}

@article {pmid41958917,
year = {2026},
author = {Rifai, OM and Waldron, FM and O'Shaughnessy, J and Read, FL and Gilodi, M and Pastore, A and Shneider, NA and Tartaglia, GG and Zacco, E and Spence, H and Gregory, JM},
title = {Amygdala TDP-43 pathology is associated with behavioural dysfunction and ferritin accumulation in amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag104},
pmid = {41958917},
issn = {2632-1297},
abstract = {Cognitive and behavioural symptoms associated with amyotrophic lateral sclerosis and frontotemporal spectrum disorders (ALS-FTSD) are thought to be driven, at least in part, by the pathological accumulation of TDP-43. Here we examine post-mortem tissue from six brain regions associated with cognitive and behavioural symptoms in a cohort of 30 people with sporadic ALS (sALS), a proportion (12/30) of which underwent standardized neuropsychological behavioural assessment as part of the Edinburgh Cognitive ALS Screen (ECAS). Overall, the behavioural screen performed as part of the ECAS predicted accumulation of pathological phosphorylated TDP-43 (pTDP-43) with 100% specificity and 86% sensitivity in behaviour-associated brain regions. Notably, of these regions, pathology in the amygdala was the most predictive correlate of behavioural dysfunction in sALS. In the amygdala of sALS patients, we show variation in morphology, cell-type predominance and severity of pTDP-43 pathology. Further, we demonstrate that the presence and severity of intra-neuronal pTDP-43 pathology, but not astroglial pathology, or phosphorylated Tau pathology, is associated with behavioural dysfunction. Cases were also evaluated using a TDP-43 aptamer (TDP-43[APT]), which revealed that pathology was not only associated with behavioural symptoms, but also with ferritin levels, a measure of brain iron. Intra-neuronal pTDP-43 and cytoplasmic TDP-43[APT] pathology in the amygdala is associated with behavioural symptoms in sALS. TDP-43[APT] staining intensity is also associated with increased ferritin, regardless of behavioural phenotype, suggesting that ferritin increases may occur upstream of clinical manifestation, in line with early TDP-43[APT] pathology, representing a potential region-specific imaging biomarker (e.g. volumetric or susceptibility-weighted MR imaging) of early disease in ALS.},
}

@article {pmid41959630,
year = {2026},
author = {Renga, V and Jeffreys, CA and Kersey, GE and Stommel, EW},
title = {Connectivity in ALS II (CoALS II): a study of structural and functional connectivity in ALS.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1743723},
pmid = {41959630},
issn = {1664-2295},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a network-level neurodegenerative disease involving distributed disruptions across structural and functional systems. While previous studies have often examined white matter integrity or functional connectivity in isolation, the nature of structure-function coupling and its reorganization in ALS remains poorly understood.

METHODS: We conducted a multimodal connectomic analysis in ALS patients and matched controls, integrating cortical thickness-based structural covariance networks, diffusion MRI tractography, and resting-state and task-based functional MRI. Graph-theoretical metrics were derived, and cross-modal structure-function correspondence was quantified using ROI-wise correlation analyses. A comprehensive 104-node parcellation scheme based on the Desikan-Killiany atlas was employed.

RESULTS: ALS participants showed preserved global network topology (p > 0.05 for efficiency and small-worldness) but evidence of selective reorganization, particularly within motor and interhemispheric pathways. Cortical covariance networks exhibited minimal association with functional dynamics, whereas diffusion-derived white matter connectivity remained closely aligned with functional organization. This structure-function coupling was maintained or even enhanced during task performance (p = 0.005), suggesting adaptive reconfiguration rather than uniform disconnection.

CONCLUSIONS: Structure-function coupling in ALS is not globally diminished but reorganized, with robust white matter-functional relationships coexisting alongside weak cortical covariance-functional associations. These findings refine the traditional disconnection model and highlight the utility of multimodal metrics for understanding disease mechanisms and developing biomarkers for progression and therapeutic response.},
}

@article {pmid41960733,
year = {2026},
author = {Han, JJ and Hayward, LJ and Adams, C and Perez-Ibarra, J},
title = {Reachable Workspace as a Clinical Outcome for Upper Extremity Function: A Narrative Review.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70190},
pmid = {41960733},
issn = {1097-4598},
support = {U01 AR065113-01/AR/NIAMS NIH HHS/United States ; //Fulcrum Therapeutics/ ; },
abstract = {Motion sensing technology can be utilized to capture detailed upper extremity (UE) motion to reconstruct an individual's three-dimensional (3D) reachable workspace (RWS). The RWS can be quantified as relative surface area (RSA), providing an innovative surrogate measure to assess UE mobility and function. Numerous studies have shown that RSA can reliably distinguish between healthy and impaired UE function and also is able to detect clinically relevant longitudinal changes, with sufficient sensitivity to detect small differences even in slowly-progressive conditions. After more than a decade of experience in clinical studies, RWS has been shown to be a valid, reliable, and sensitive UE clinical outcome assessment (COA) tool, with clinical utility in various neuromuscular diseases in which UE impairment is significant, including facioscapulohumeral dystrophy (FSHD), Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis (ALS). RWS and its performance outcome (PerfO) measure RSA have demonstrated strong associations with established clinical measures of disease severity, patient-reported outcomes (PROs), and functional performance, further supporting its clinical relevance. As an UE functional assessment tool, RWS has also shown its generalizable application in various other conditions with UE impairment, such as stroke, orthopedic conditions, and other musculoskeletal disorders. With significant body of work supporting sensor-based RWS as a clinically useful assessment of UE function, future developments incorporating increasingly-capable mobile sensing technologies for remote monitoring and applying machine learning and artificial intelligence (AI) approaches to the sensor-acquired motion data promise further exciting possibilities to enhance clinical studies and patient care.},
}

@article {pmid41862849,
year = {2026},
author = {Elfe, C and Meer, T and Hövener, C and Theuring, S},
title = {Understanding barriers for refugees and migrants when accessing abortion care in Europe: a scoping review.},
journal = {BMC public health},
volume = {26},
number = {},
pages = {},
pmid = {41862849},
issn = {1471-2458},
abstract = {BACKGROUND: Access to safe abortion care has been the subject of international policy deliberation for several decades and was included in the World Health Organization’s essential healthcare services in 2020. It differs across Europe, with legal barriers like gestational age limits and the conscientious objection persisting in most European countries. Refugees and migrants can encounter additional barriers when accessing healthcare services for various reasons, such as health system exclusion and language barriers. The aim of this study was to map existing evidence on refugees’ and migrants’ access to abortion care in Europe.

METHODS: Adopting a scoping review methodology, we conducted a systematic search in PubMed, complemented by web-based hand searches and citation tracking to identify the relevant literature. We included qualitative and quantitative studies as well as grey literature published in English between 2014 and 2025, addressing how refugees and migrants accessed abortion services across Europe. Data were charted according to Levesque et al.’s dimensions of healthcare access framework. Results were reported using a narrative synthesis approach.

RESULTS: We identified 19 studies in eleven different European countries and one EU-wide report (n = 20), including twelve qualitative, five mixed, and three quantitative designs. While some studies focused specifically on migrant women seeking reproductive healthcare, others focused on abortion seekers in general while highlighting barriers unique to migrant populations. Prominent barriers were lack of information and insufficient availability of translation services. Availability of services was often restricted by regional disparities and restrictive laws. Affordability issues were amplified by variations in cost entitlements and the precarious status of undocumented migrants. Quality of care was compromised by discriminatory attitudes held by providers.

CONCLUSIONS: Refugees and migrants in Europe face barriers in access to abortion tied to their migration context. Gaps in coverage for refugees and migrants constitute a violation of universal human rights. Ensuring access requires improved outreach efforts, free availability of translation services, decriminalization, and integration of abortion care into a Universal Health Coverage framework, while combating racism in health care and amplifying the voices of marginalized groups.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-026-27031-x.},
}

@article {pmid41951265,
year = {2026},
author = {Marques Couto, C and Gomes, SAMC and Carvalho, RS and Nascimento, OJ},
title = {Disappearing corticospinal tract on routine MRI: dynamic signal evolution in primary lateral sclerosis.},
journal = {BMJ case reports},
volume = {19},
number = {4},
pages = {},
pmid = {41951265},
issn = {1757-790X},
mesh = {Humans ; *Pyramidal Tracts/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; Middle Aged ; *Motor Neuron Disease/diagnostic imaging ; Female ; Male ; *Motor Cortex/diagnostic imaging/pathology ; Disease Progression ; },
abstract = {Primary lateral sclerosis (PLS) may show corticospinal tract (CST) hyperintensity on fluid-attenuated inversion recovery and motor cortex hypointensity on susceptibility-weighted imaging (SWI); however, its longitudinal evolution remains poorly understood. Here, we describe two cases with definite PLS, who were followed up for 15 and 6 years and assessed using qualitative visual magnetic resonance imaging (MRI) scores. Both patients initially exhibited CST hyperintensity. Despite progressive clinical deterioration due to wheelchair/walker dependence, serial MRI demonstrated complete CST normalisation (score 0/16). Concurrently, SWI revealed progressive motor cortex hypointensity, consistent with iron deposition. These cases illustrate a possible dissociation between conventional and susceptibility-based MRI markers, suggesting dynamic pathophysiological processes and potentially early inflammation followed by gliotic remodelling, although technical factors cannot be excluded. A normal-appearing CST should not exclude advanced PLS, and progressive motor cortex hypointensity may provide a more stable marker. Prospective studies with standardised protocols are required to validate these observations.},
}

Humans
*Pyramidal Tracts/diagnostic imaging/pathology
*Magnetic Resonance Imaging/methods
Middle Aged
*Motor Neuron Disease/diagnostic imaging
Female
Male
*Motor Cortex/diagnostic imaging/pathology
Disease Progression

@article {pmid41951934,
year = {2026},
author = {Spinelli, G and Lupker, S},
title = {Focusing on conflict in item-specific adaptive control: Insights from a proportion-neutral manipulation.},
journal = {Memory & cognition},
volume = {},
number = {},
pages = {},
pmid = {41951934},
issn = {1532-5946},
support = {A6333//Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada/ ; },
abstract = {Jacoby et al. (Psychonomic Bulletin & Review, 10, 638-644, 2003) reported that, in Stroop tasks, stimuli that more frequently involve targets combined with a congruent distractor (e.g., the word RED in the color red) produce larger Stroop effects than stimuli that more frequently involve targets combined with an incongruent distractor (e.g., RED in green). This pattern suggests that adaptive control can be item-specific in addition to item-nonspecific, and reactive in addition to proactive (although this conclusion has been challenged). This adaptive-control process has often been assumed to be driven by the conflict associated with incongruent stimuli; however, the typical experimental manipulations investigating this issue allow the facilitation associated with congruent stimuli to also play a role. Here, we modified those manipulations in order to focus exclusively on conflict, removing any impact of congruency facilitation, by contrasting targets presented with either neutral (letter strings) or incongruent distractors. Neutral stimuli were presented more frequently than incongruent ones in the Mostly-Neutral (MN) condition and vice versa in the Mostly-Incongruent (MI) condition. Paralleling the original pattern, Stroop interference was larger in the MN condition, suggesting that item-specific conflict frequency can be used to adapt attention accordingly. Importantly, this effect was replicated after experimentally controlling for stimulus frequency, a confound that was found to explain part, but not all, of the general pattern. These results support Jacoby et al.'s claims that (a) control can be adapted in an item-specific fashion and (b) conflict plays a key role in that process.},
}

@article {pmid41952063,
year = {2026},
author = {Saim, M},
title = {Letter to the Editor: Methodological Concerns in Bryant et al.'s Network Meta-Analysis on Residual Disease Thresholds in Advanced Ovarian Cancer.},
journal = {American journal of therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1097/MJT.0000000000002133},
pmid = {41952063},
issn = {1536-3686},
}

@article {pmid41952193,
year = {2026},
author = {Linse, K and Lulé, D and Schöberl, F and Reilich, P and Ilse, B and Metelmann, M and Eickhoff, C and Bublitz, S and Lorenzl, S and Boentert, M and Petri, S and Rödiger, A and Smesny, U and Wolf, J and Weyen, U and Zeller, D and Dorst, J and Maier, A and Meyer, T and Lingor, P and Hermann, A and Regensburger, M and Großkreutz, J and Runge, C and Lapp, HS and Freigang, M and Vidovic, M and Aust, E and Weber, C and Günther, R},
title = {Between guidelines and reality: expert neurologists' perspectives on structural resources for ALS care in Germany.},
journal = {Neurological research and practice},
volume = {8},
number = {1},
pages = {},
pmid = {41952193},
issn = {2524-3489},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, leading to an inexorable decline in voluntary muscle function, and finally to death within 2–4 years. The provision of professional ALS care is a multifaceted and continually evolving challenge, including the management of symptoms, advanced care planning, and the provision of psychosocial support. The core objective is to minimize suffering by optimizing symptom management and preserving quality of life. European and German guidelines recommend a specialized, multidisciplinary, and multiprofessional team, including collaborations with palliative care providers. While this is a validated approach to ensure optimal care and patient satisfaction, real-world experience suggests that the German healthcare system may not fully meet these requirements.

METHODS: This study assessed resources of specialized ALS centres in Germany, focusing on the structural prerequisites for the provision of multidimensional care and collaboration with specialised palliative care (SPC) providers. A mixed methods design was used, comprising remote video interviews with neurologists specialized in ALS, including standardised questions and an open section.

RESULTS: Sixteen neurologists representing their ALS centres were interviewed. The findings indicated a substantial discrepancy in the allocation of time and personnel resources among the centres. The majority of interviewees regarded resources to be inadequate and reported deficiencies in multidisciplinarity and networking. Consequently, certain components of ALS care - particularly psychosocial concerns - have been documented as being occasionally disregarded due to limitations in time or human resources. A number of interviewees expressed criticism regarding the inadequate access to and suboptimal collaboration with SPC providers. The compensation for patient care and interprofessional communication was not perceived as cost-effective.

CONCLUSIONS: Our results suggest that limited resources may prevent the provision of guideline-based care for people living with ALS and their families, even in specialized outpatient clinics. To facilitate the delivery of comprehensive care by ALS centers throughout the entire disease course, the establishment of operational standards concerning their multi-professional staffing and adequate compensation is imperative. Further research is needed to develop feasible concepts of how specialized neurological palliative care can be made reliably accessible to all patients in need.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42466-026-00481-9.},
}

@article {pmid41952858,
year = {2026},
author = {Calderón-Garcidueñas, L and Hernández-Luna, J and Galaz-Montoya, CI and Clouston, SAP and Aiello-Mora, MV and Amaro de Gante, J and Stommel, EW and Torres-Jardón, R and Nalbantoglu, OU},
title = {Cortical, subcortical, and cerebellar atrophy and cognition deficits in Metropolitan Mexico City teens and young adults exposed to fine particulate matter (PM2.5) - neurodegeneration is in progress.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1772916},
pmid = {41952858},
issn = {1664-2295},
abstract = {Exposure to environmental fine particulate matter (PM2.5), ultrafine PM (UFPM) and nanoparticles (NPs) are associated with accumulation of amyloid-β1-42 peptides, phosphorylated-Tau, alpha-synuclein and transactive response DNA binding-protein-43 misfolded aberrant proteins, consistent with the biological definitions of overlapping Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS) in 99% of ≤40-year-old Metropolitan Mexico City (MMC) forensic autopsies. Structural and volumetric brain responses in vivo are critical in young MMC residents. We performed volumetric and whole-brain correlation analyses in 75 healthy volunteers: 45 MMC 31.2 ± 14.7 y old and 30 low-pollution 31.8 ± 4.8 y old controls, matched by ethnicity, socioeconomic status, nutrition, and BMI. MMC residents exhibited fronto-parietal and temporal lobes, precentral gyrus, hippocampi, basal ganglia, thalamus, amygdala and cerebellar atrophy. The most common atrophy pattern was cortical first parietal and fronto-parietal lobes, combined with gray matter (GM) atrophy in cerebellar lobules IV and V left and right III, IV and V and VI.MMC participants had mild cognitive impairment (Montreal Cognitive Assessment Score 22.8 ± 3.2). GM atrophy involving right globus pallidus and pulvinar and cerebellar white matter (WM) bilaterally were associated with lower cognitive performance and high BMI to subiculum, posterior orbital gyrus and insula, inferior temporal gyrus, supplementary motor cortex, and cuneus WM atrophy. PM2.5 exposure and BMI appear to play key roles in early neurodegenerative disease biology and may contribute to adverse effects on academic and occupational performance, neuropsychiatric disorders, behavioral regulation, risk of substance use initiation, and psychopathy. Neuroradiologists across the world need to know cortical and subcortical, including extensive hippocampal, stratium and cerebellar atrophy identifies overlapping patterns of regional atrophy associated with MCI, AD, bvFTD, PD and ALS, in young urbanites. There is an urgent need for early pediatric neuroprevention interventions, non-invasive AD, PD and TDP-43 biomarkers, in-depth characterization of emission pollutants exposures and their effective control. Denial is no longer an option.},
}

@article {pmid41953830,
year = {2026},
author = {Baby, P and John, J and Binesha, PB and Keerthipriya, MS and Ramazanu, S and Nashi, S and Menon, D and Vengalil, S and Thomas, PT and Nalini, A},
title = {Amyotrophic Lateral Sclerosis: A Cross-sectional Survey on Sialorrhoea.},
journal = {Indian journal of palliative care},
volume = {32},
number = {1},
pages = {85-90},
pmid = {41953830},
issn = {0973-1075},
abstract = {OBJECTIVES: One of the major distressing symptoms related to Amyotrophic Lateral Sclerosis (ALS) is excessive drooling of saliva, also termed sialorrhoea. Evaluating its prevalence and severity among Indian patients with ALS is essential for understanding the magnitude and impact of the problem. A cross-sectional survey was conducted to estimate the prevalence and severity of sialorrhoea among individuals diagnosed with ALS. We also intended to assess the current pharmacological management practice for sialorrhoea in ALS patients.

MATERIALS AND METHODS: Patients with ALS enrolled in the Neuropalliative Registry of a quaternary care centre for neurological disorders were included in the study. As part of routine follow-up, telephonic interviews were conducted with either the patients or their next of kin. The extent of sialorrhoea was assessed using the sialorrhoea scoring scale.

RESULTS: Seventy patients were included in the study. The mean age at presentation was 51.8 (standard deviation [SD]-12.8) years. The majority were males (74.3%). The mean duration of illness was 21.6 (SD 15.7) months. The majority (80%) had limb onset ALS. Forty per cent of the patients in the study had some degree of sialorrhoea. Mild drooling was present in 15 patients (21.4%), moderate in 9 (12.9%), severe in 2 (2.9%) and profuse drooling in another 2.9% of patients. A total of 9 patients (12.9%) were receiving anticholinergic medication. Patients diagnosed with bulbar onset ALS had a significantly greater degree of sialorrhoea than those with limb onset presentation (P = 0.008). In addition, a longer duration of illness showed a positive correlation with the severity of sialorrhoea (r = 0.30, P = 0.012).

CONCLUSION: Sialorrhoea is a prevalent and clinically significant symptom in individuals with ALS. The severity of sialorrhoea is greater in patients with bulbar onset ALS and tends to increase with longer illness duration. A substantial proportion of patients may benefit from recommended treatment for excessive salivation and saliva-related issues. This study underscores the need for screening of distressing symptoms as sialorrhoea, in ALS patients. The treating teams need to have a heightened awareness regarding the same so that treatment options can be offered to the patients.},
}

@article {pmid41953903,
year = {2026},
author = {Ansari, MS and Heidari, S and Pourgholi, E and Bahramian, S and Tootoonchi, N and Vahabi, SM},
title = {Janus Kinase Inhibitors for Treatment of Palmoplantar Pustulosis, Generalized Pustular Psoriasis, and Palmoplantar Pustular Psoriasis: A Systematic Review of the Literature.},
journal = {Health science reports},
volume = {9},
number = {4},
pages = {e72301},
pmid = {41953903},
issn = {2398-8835},
abstract = {INTRODUCTION: Palmoplantar pustulosis (PPP) is a chronic, recurrent, inflammatory disease and assumed to be a subtype of psoriasis. Pustular psoriasis (PP) is a chronic inflammatory disease that is further subclassified into various entities with different presentations including generalized pustular psoriasis (GPP) and palmoplantar pustular psoriasis (PPPP). Given the central role of the JAK-STAT pathway in cytokine signaling, this systematic review evaluated the effectiveness and safety of Janus kinase inhibitors (JAK-I) in these PP subtypes.

METHODS: Following PRISMA 2020 guidelines, a systematic search was conducted across PubMed/Medline, Scopus, Web of Science, and Embase up to November 13, 2025. Eligible studies included assessing JAK-I in PPP, GPP, or PPPP. Exclusion criteria were reviews, articles without full-text, SAPHO syndrome, and animal/in vitro studies. Risk of bias was assessed using the NHLBI quality assessment tool for clinical studies and Murad et al.'s checklist for case reports/series.

RESULTS: Thirty-seven studies were included (29 case reports, 4 case series, and 4 clinical studies), encompassing 157 patients (60.5% female; mean age 46.8 years). Treatments involved tofacitinib, upadacitinib, baricitinib, abrocitinib, and topical ruxolitinib. In PPP, pooled meta-analysis demonstrated a PPPASI-50 response rate of 85.5% (95% CI, 71.3-93.3), with upadacitinib achieving 90.9% (95% CI, 81.7-95.7). Case reports and series showed 88.1% clearance or near-clearance within a mean of 2.5 months. GPP patients (n = 5) achieved rapid clearance or marked improvement within 2-12 weeks. Adverse events (18.7%) were generally mild, most commonly acneiform eruptions, headache, and transient liver enzyme elevations, with no severe events reported.

CONCLUSION: JAK-I demonstrate high response rates and rapid improvement with manageable safety profiles. However, the current evidence is limited by small sample sizes, short follow-up durations, and reliance on case-based data. They represent a promising therapeutic option and warrant further evaluation in larger controlled studies to establish long-term efficacy and safety.},
}

@article {pmid41954708,
year = {2026},
author = {Luo, S and Zheng, Q and Wang, M and Wang, X and Ma, B and Liu, D and Li, L and Lu, Y and Sang, D and Yang, L},
title = {Synergistic Neuroprotection of MFSD2A Overexpression and DHA Supplementation in Amyotrophic Lateral Sclerosis.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41954708},
issn = {1559-1182},
support = {202304295107020076//Clinical Medicine Research and Translational Project of Anhui Province/ ; 2022AH051480//University Natural Science Research Project of Anhui Province/ ; 2022//Anhui Province "Jianghuai Famous Doctors" Cultivation Project/ ; 2020byzd169//Natural Science Key Project of Bengbu Medical College/ ; BB21B032//Bengbu Think Tank Construction and Social Science Planning Project/ ; 20230131//Bengbu science and technology innovation guidance project/ ; BBWK2024B204//Bengbu Health and Health Research Project Intestinal Transplantation Technology Clinical Special General Project/ ; AHWJ2024Aa30089//Anhui Province Health and Health Research Project Youth Project/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; *Docosahexaenoic Acids/pharmacology/therapeutic use/administration & dosage ; Male ; *Neuroprotection/drug effects ; *Dietary Supplements ; *Neuroprotective Agents/pharmacology/therapeutic use ; Mice ; Mice, Transgenic ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Humans ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss, with limited effective therapies. Docosahexaenoic acid (DHA) exhibits neuroprotective effects, but its limited transport across the blood-brain barrier (BBB) restricts clinical utility. Major facilitator superfamily domain-containing protein 2A (MFSD2A) is the primary transporter of DHA into the central nervous system, yet its role in ALS remains unclear. This study investigated the therapeutic potential and mechanisms of MFSD2A overexpression combined with DHA supplementation in male SOD1^G93A ALS mice. We found that MFSD2A expression was markedly reduced in ALS mice and correlated with impaired motor function and neuronal damage. DHA supplementation or MFSD2A overexpression partially improved behavioral deficits, while their combination produced synergistic benefits. Histological analyses revealed attenuated neuronal degeneration and reduced muscle fibrosis following combined treatment. Furthermore, MFSD2A physically interacted with the E3 ubiquitin ligase TRIM21, regulating glycolytic metabolism by modulating key enzymes (GLUT1, HK2, LDHA, PDK1) and products (lactate/pyruvate and NADH/NADPH ratio). TRIM21 knockdown reversed MFSD2A-mediated neuroprotection and impaired glycolytic metabolism, indicating its critical role in this pathway. The combined intervention also suppressed systemic inflammation and oxidative stress by decreasing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and restoring antioxidant enzyme activities (GSH-Px), while reducing lipid peroxidation (MDA). These findings suggest that MFSD2A facilitates DHA's neuroprotective effects by enhancing glycolytic metabolism and mitigating neuroinflammation. This study highlights MFSD2A and DHA as promising therapeutic targets in ALS and provides novel insights into overcoming BBB transport limitations for neurodegenerative disease treatment.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics
*Docosahexaenoic Acids/pharmacology/therapeutic use/administration & dosage
Male
*Neuroprotection/drug effects
*Dietary Supplements
*Neuroprotective Agents/pharmacology/therapeutic use
Mice
Mice, Transgenic
Mice, Inbred C57BL
Oxidative Stress/drug effects
Humans

@article {pmid41954773,
year = {2026},
author = {Zhu, Y and Ma, J},
title = {Concerns Regarding Baseline Balance, Blinding Validity, and Clinical Relevance in Aktan et al.'s Study on Home-Based Inspiratory Muscle Training for Stress Urinary Incontinence.},
journal = {International urogynecology journal},
volume = {},
number = {},
pages = {},
pmid = {41954773},
issn = {1433-3023},
}

@article {pmid41955555,
year = {2026},
author = {Katzberg, HD and Bril, V and Zinman, L and Abrahao, A and Cherney, D and Shah, H and Mendoza, MG and Alfaidi, N and Alnajjar, S and Barnett-Tapia, C},
title = {The Muscle Cramp Impact Index: A Patient-Centered Scale for the Assessment of Muscle Cramps.},
journal = {Neurology},
volume = {106},
number = {9},
pages = {e214835},
doi = {10.1212/WNL.0000000000214835},
pmid = {41955555},
issn = {1526-632X},
mesh = {Humans ; *Muscle Cramp/diagnosis/psychology ; Female ; Male ; Middle Aged ; Adult ; Reproducibility of Results ; *Patient Reported Outcome Measures ; Aged ; Prospective Studies ; Psychometrics ; },
abstract = {BACKGROUND AND OBJECTIVES: Muscle cramps are common, variably disabling, and lack a comprehensive validated tool to assess their multidimensional effect. Previous cramp studies have relied primarily on cramp frequency and intensity, despite qualitative work demonstrating that sleep disturbance, daytime functioning, and mental health are also important to patients. Guided by these findings, the aim of this study was to develop and validate a patient-reported outcome measure, the Muscle Cramp Impact Index (MCII), to assess the effect of muscle cramps across diverse etiologies and clinical settings.

METHODS: This was a multisite, prospective scale-development and validation study conducted in neuromuscular, amyotrophic lateral sclerosis, hepatology, and kidney clinics at the University Health Network/Mount Sinai Hospital and Sunnybrook Health Sciences Centre (2018-2022). MCII item generation was based on a previous qualitative study, literature review, and cognitive interviews with affected patients. Content validity was assessed through review by 27 international neuromuscular and muscle cramp experts. Adult patients experiencing muscle cramps within the preceding 2 weeks were enrolled. Draft items were evaluated for missing data, floor/ceiling effects, and exploratory factor analysis (EFA). Test-retest reliability was assessed in clinically stable patients over a 2-week interval using weighted κ and intraclass correlation coefficients (ICCs). Construct validity was examined through predefined hypotheses correlating MCII scores with established measures of sleep disturbance, mood, pain, stiffness, and quality of life.

RESULTS: A total of 105 patients (40% female individuals; mean age 60.0 ± 14.2 years) completed the field testing. Eighteen draft items were refined to 16 after patient and expert review. All items demonstrated low missingness (<6%). EFA identified 3 domains-cramp frequency/distribution, sleep interference, and interference with daily life-and 2 items were removed for floor effects or low factor loadings, yielding a final 14-item measure (score range 0-42). The MCII demonstrated moderate correlations with EuroQol 5 Dimension, Epworth Sleepiness Scale, Beck Depression Inventory, and Sleep Disturbance scores. Test-retest reliability was excellent (n = 57; ICC 0.83, 95% CI 0.72-0.89), confirming strong measurement stability.

DISCUSSION: The MCII is a patient-centered, psychometrically robust measure capturing the multidimensional effect of muscle cramps. Limitations include reliance on self-reported clinical stability and inability to verify respondent identity for mailed questionnaires. Further evaluation of responsiveness and validation in additional cramp populations is warranted to support broader implementation.},
}

Humans
*Muscle Cramp/diagnosis/psychology
Female
Male
Middle Aged
Adult
Reproducibility of Results
*Patient Reported Outcome Measures
Aged
Prospective Studies
Psychometrics

@article {pmid41955837,
year = {2026},
author = {Song, Y and Zhao, Z and Dai, Y and Li, C and He, X and Wang, Y and Xu, ZD and Yang, Y},
title = {The m7G modification: An emerging player in neurological diseases.},
journal = {Pathology, research and practice},
volume = {282},
number = {},
pages = {156465},
doi = {10.1016/j.prp.2026.156465},
pmid = {41955837},
issn = {1618-0631},
abstract = {With the growing researches on RNA epigenetics, the importance of 7-methylguanosine (m7G) modification is increasingly recognized. The m7G modification is known as a kind of post-transcriptional modifications of RNA and present in many types of RNAs, including mRNAs, microRNAs, ribosomal RNA, and transfer RNAs. Increasing evidence indicates that m7G modifications are involved in a variety of critical biological processes through affecting the stability of RNA, nucleoplasmic transfer and translation efficiency. In the central nervous system (CNS), m7G modification is catalyzed by three major methyltransferase complexes: METTL1/WDR4, RNMT/RAM, and WBSCR22/TRMT112. Dysregulation of this modification is tightly associated with the pathogenesis of various neurological diseases, such as Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), epilepsy, glioblastoma, ischemic stroke (IS), etc. Here, we review the current knowledge regarding the latest findings on the distribution, regulatory factors, detection techniques and prediction methods of m7G. We further highlight critical knowledge gaps, especially the limited understanding of m7G "readers," the absence of validated "erasers," and the scarcity of cell-type-resolved profiling in the brain. In addition, we also discuss the translational opportunities and challenges, including biomarker discovery, therapeutic targeting of m7G regulators, and specificity concerns in precision neurological medicine.},
}

@article {pmid41956140,
year = {2026},
author = {Wang, P},
title = {Response to Tahir et al.'s commentary on our BSRS causal framework for longitudinal well-being data.},
journal = {Journal of biomedical informatics},
volume = {},
number = {},
pages = {105037},
doi = {10.1016/j.jbi.2026.105037},
pmid = {41956140},
issn = {1532-0480},
abstract = {We thank Tahir et al. for their respectful and constructive commentary on our article proposing the Behaviour Self-Regulation Score (BSRS) and a causally-informed workflow for longitudinal self-report well-being data (Wang et al., 2026). We clarify that (i) the completeness threshold was established a priori to support stable estimation, and we reported included-versus-excluded baseline comparisons showing no statistically significant differences on key measured variables; (ii) while treatment- and outcome-related items were collected via an evening daily questionnaire, we defined day-level temporal ordering and stated identification assumptions; and (iii) our causal interpretation is conditional on standard assumptions, which we complemented with exposure-specific backdoor adjustment and three refutation checks (random common cause, placebo permutation, and data-subset stability), while transparently noting remaining limitations including self-report bias and potential time-varying confounding. We welcome the opportunity to clarify these points in response to the Letter to the Editor.},
}

@article {pmid41956387,
year = {2026},
author = {Klemmer Chandía, S and Wellge, B and Barzen, G and Aghamiry, H and Manini, C and Bauer, M and Ivantsits, M and Walczak, L and Hahn, K and Hennemuth, A and Spethmann, S and Tzschätzsch, H and Sack, I and Meyer, T},
title = {Cardiac Multifrequency Time-harmonic Elastography: In Silico Validation and In Vivo Application.},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2852-6188},
pmid = {41956387},
issn = {1438-8782},
abstract = {PURPOSE: To introduce and validate optimized multifrequency cardiac time-harmonic elastography (THE) with portable drivers and multiple-heartbeat acquisitions for detecting abnormal diastolic stiffness using in silico testing and investigating participants with confirmed cardiac wild-type transthyretin amyloidosis (ATTRwt), a model disease for myocardial stiffness, compared to healthy controls.

MATERIALS AND METHODS: Cardiac THE was performed using continuous vibrations of 60, 70, and 80 Hz induced by a portable driver. Shear wave speed (SWS) maps, as a proxy for myocardial stiffness, were acquired over 4 seconds in a parasternal long axis view. Cardiac ultrasound simulations with CT-data-based anatomies were used for in silico validation and parameter optimization. Diagnostic performance was assessed using the area under the ROC curve (AUC) with 95% confidence interval (95%-CI).

RESULTS: Healthy controls (N=10; median age: 32 years [range: 27-56]; five men) and participants with ATTRwt (N=11; median age: 83 years [range: 64-86]; ten men) were investigated, resulting in accurate amyloidosis detection (AUC: 1.00; 95%-CI: 0.94-1.00). In-silico-estimated SWS agreed with ground-truth values (r²=0.94; median error: 5.6% [range: -26.2-19.7]) across various stiffnesses [range: 1.3-4.0 m s[-1]] and thicknesses [range: 10-20 mm]. A trend towards underestimation was only observed in the unlikely scenario of thin and very stiff septa.

CONCLUSION: For the first time, the accuracy of cardiac THE was quantified both in silico and in vivo, specifically in a cohort including patients with ATTRwt. Multifrequency shear waves induced by portable drivers and encoded in standard ultrasound provide a rapid, low-cost echocardiographic contrast that aids the detection of cardiomyopathies such as amyloidosis. Ziel: Vorstellung und Validierung einer optimierten multifrequenten kardialen zeit-harmonischen Elastographie (THE) mit tragbaren Schwingungstreibern und Mehrfach-Herzschlag-Akquisitionen zur Detektion abnormer diastolischer Steifigkeit. Dies erfolgte durch in-silico-Tests sowie durch Untersuchungen an Probanden mit bestätigter kardialer Wildtyp-Transthyretin-Amyloidose (ATTRwt) -einer Modellerkrankung für myokardiale Steifigkeit- im Vergleich zu gesunden Kontrollpersonen.

MATERIAL UND METHODEN: Kardiale THE wurde unter Verwendung kontinuierlicher Vibrationen von 60, 70 und 80 Hz durchgeführt, die durch einen tragbaren Schwingungstreiber erzeugt wurden. Scherwellengeschwindigkeits-(SWS)-Karten als Stellvertretermaß für die myokardiale Steifigkeit wurden über 4 Sekunden in einer parasternalen Längsachsendarstellung akquiriert. Ultraschallsimulationen des Herzens basierend auf CT-Daten anatomischer Modelle wurden für die in-silico-Validierung und Parameteroptimierung eingesetzt. Die diagnostische Leistungsfähigkeit wurde anhand der Fläche unter der ROC-Kurve (AUC) mit 95%-Konfidenzintervall (95%-CI) bewertet. Ergebnisse: Gesunde Kontrollpersonen (N=10; Medianalter: 32 Jahre [Bereich: 27-56]; fünf Männer) und Teilnehmende mit ATTRwt (N=11; Medianalter: 83 Jahre [Bereich: 64-86]; zehn Männer) wurden untersucht. Dies führte zu einer präzisen Detektion der Amyloidose (AUC: 0.99; 95%-CI: 0.93-1.00). Die in-silico geschätzten SWS-Werte stimmten gut mit den Referenzwerten überein (r²=0,94; Medianfehler: 5,6% [Bereich: -26.2-19.7]) über verschiedene Steifigkeiten [Bereich: 1.3-4.0 m s[-1]] und Wanddicken [Bereich: 10-20 mm]. Eine Tendenz zur Unterschätzung zeigte sich nur im unwahrscheinlichen Fall dünner und sehr steifer Septen. Schlussfolgerungen: Zum ersten Mal wurde die Genauigkeit der kardialen THE sowohl in silico als auch in vivo quantifiziert -insbesondere in einer Kohorte, die Patientinnen und Patienten mit ATTRwt einschließt. Multifrequente Scherwellen, die durch tragbare Schwingungstreiber induziert und in Standard-Ultraschall codiert werden, ermöglichen einen schnellen, kostengünstigen echokardiographischen Kontrast, der die Detektion von Kardiomyopathien wie Amyloidose unterstütz.},
}

@article {pmid41636971,
year = {2026},
author = {Bignami, EG and Russo, M},
title = {From promising prototypes to "instructions for use": embedding LLMs safely in perioperative and intensive care.},
journal = {Journal of clinical monitoring and computing},
volume = {40},
number = {2},
pages = {301-304},
pmid = {41636971},
issn = {1573-2614},
abstract = {Large language models (LLMs) show promise for supporting clinical decision‑making in perioperative and intensive care settings. The recent study by Xu et al. on pre‑trained language models for preoperative anesthesia triage demonstrates that such models can effectively integrate structured and unstructured clinical data to support triage decisions. However, the translation of these tools from research prototypes to routine clinical use requires more than technical validation; it demands explicit, operationalised “instructions for use” analogous to those required for pharmaceuticals and medical devices. We argue that responsible deployment of LLMs in ICU and perioperative workflows must clarify: (1) intended clinical scope and non‑indications; (2) role in the decision‑making hierarchy and when clinicians should override model recommendations; and (3) mechanisms for transparency, governance, and staff training. Drawing on Xu et al.‘s methodological rigor and Bignami et al.‘s AI policy checklist framework, we outline a concise, practice‑oriented approach to embedding LLMs safely in critical care. We emphasise that without explicit instructions for use, clear governance structures, and comprehensive training, there is a risk of introducing inscrutable systems into the heart of critical care. The time to define these safeguards is now, before ad hoc, ungoverned adoption becomes the norm.},
}

@article {pmid41945266,
year = {2026},
author = {Pouliquen, O},
title = {Non-local rheology in granular media: a perspective on the 2015 EPJE Paper by Bouzid et al.},
journal = {The European physical journal. E, Soft matter},
volume = {49},
number = {4},
pages = {},
pmid = {41945266},
issn = {1292-895X},
support = {101097842//HORIZON EUROPE European Research Council/ ; },
abstract = {The study "Non-local rheology in dense granular flows: Revisiting the concept of fluidity," published in 2015 in The European Physical Journal E (vol. 38) by Mehdi Bouzid and collaborators, stands as an important contribution to the rheology of granular materials. In their work, the authors critically discuss the differences between proposed non-local models and provide clear pathways to discriminate between them. This perspective paper revisits the state of the art at the time of the Bouzid et al's publication, highlighting its role in inspiring subsequent research. We then explore recent advancements since 2015, which, while significant, have not yet fully resolve the questions originally raised by Bouzid et al.},
}

@article {pmid41945652,
year = {2026},
author = {Schmidt, J and Lampe, D and Poppe, A and Meyer, I and Söling, S and Köberlein-Neu, J and Grandt, D and Düvel, L and Greiner, W and , },
title = {Enhancing Continuous Medication Safety Through e-Prescription and Clinical Decision Support Systems in Outpatient Practices and Pharmacies: Protocol for a Multiperspective Study (eRIKA Study).},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e87277},
pmid = {41945652},
issn = {1929-0748},
mesh = {Humans ; *Decision Support Systems, Clinical ; *Electronic Prescribing/standards ; *Pharmacies ; Polypharmacy ; Outpatients ; },
abstract = {BACKGROUND: Increased life expectancy is associated with increasing multimorbidity and polypharmacy, leading to a heightened risk of drug-drug interactions and adverse events, especially when multiple health care providers are involved. To address the urgent need for safer medication management in this population, tools such as medication plans (MP), electronic prescriptions (e-prescriptions), and clinical decision support systems (CDSS) offer valuable support. These instruments have the potential to enhance medication safety by providing physicians and pharmacists with a comprehensive overview of a patient's overall medication regimen and by assisting health care professionals in making informed prescribing decisions.

OBJECTIVE: This study aims to improve medication therapy safety by combining e-prescriptions, the use of claims data, MPs, CDSS, and interprofessional communication. To comprehensively evaluate this complex intervention, a holistic multiphase study will be conducted, examining (1) the effectiveness of the intervention and (2) health-economic and (3) implementation-related aspects.

METHODS: A multiphase study design is used. In the first phase, the intervention is implemented in selected outpatient practices (n=10) and pharmacies (n=10) in 2 regions in Germany as part of a cluster-randomized controlled trial to assess process-related outcomes. The primary outcome is the congruence between the MP and claims data. In phase 2, the intervention is scaled up in 3 regions and evaluated in a quasi-experimental study. The required sample size for the intervention group is 3528 patients, with a synthetic control group matched from existing claims data. The primary outcome is a combined end point of all-cause mortality and hospitalization within 3 months of an index prescription. Quantitative methods (descriptive, regression-based methods using claims data, calculation of the incremental cost-effectiveness ratio, and survey-based analyses of implementation-related aspects) and qualitative methods (interviews and focus groups to capture experiences of health care professionals and patients) are used.

RESULTS: In phase 1, a total of 187 patients were recruited (74 in the intervention group and 113 in the control group) by June 2025. Phase 2 is currently ongoing, with data collection continuing through December 31, 2025. Final analyses are planned by March 2027.

CONCLUSIONS: Medication safety in polypharmacy remains a critical challenge in Germany. This study provides multiperspective evidence supporting the nationwide implementation of the eRIKA (e-prescription as an element of interprofessional care pathways for continuous medication therapy management [eRezept als Element interprofessioneller Versorgungspfade für kontinuierliche AMTS]) intervention.},
}

Humans
*Decision Support Systems, Clinical
*Electronic Prescribing/standards
*Pharmacies
Polypharmacy
Outpatients

@article {pmid41945799,
year = {2026},
author = {Barnwal, N and Dubey, S and Tiwari, P},
title = {Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases.},
journal = {ChemMedChem},
volume = {21},
number = {7},
pages = {e202500869},
doi = {10.1002/cmdc.202500869},
pmid = {41945799},
issn = {1860-7187},
mesh = {Humans ; *Benzimidazoles/chemistry/pharmacology/therapeutic use/chemical synthesis ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/chemistry/pharmacology/therapeutic use/chemical synthesis ; Animals ; Molecular Structure ; Structure-Activity Relationship ; },
abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss, leading to severe cognitive and motor dysfunction. Benzimidazole, a privileged heterocyclic scaffold, has emerged as a promising pharmacophore in modulating key pathological targets across these disorders. In AD, benzimidazole derivatives inhibit cholinesterases, glycogen synthase kinase-3β (GSK-3β), and glutaminyl cyclase (QC), thereby addressing cholinergic dysfunction, tau phosphorylation, and amyloid aggregation. In PD and HD, they act as monoamine oxidase-B (MAO-B) inhibitors, dopamine D1/D2 receptor modulators, and N-methyl D-aspartate receptor antagonists, improving dopaminergic signalling and reducing excitotoxicity. In ALS, benzimidazoles regulate acetylcholine dysfunction and inhibit receptor-interacting protein kinase 1 (RIPK1), limiting neuroinflammation and cell death. Preclinical studies demonstrate potent enzyme inhibition, often with IC50 values in the nanomolar to micromolar range, alongside favourable ADMET properties enabling blood-brain barrier penetration. Clinically, the glutaminyl cyclase inhibitor Varoglutamstat has advanced to Phase II trials for AD, while Riluzole remains the only food and drug administration (FDA)-approved benzimidazole drug for ALS. The structural versatility of benzimidazoles supports their development as multi-target-directed ligands, addressing overlapping mechanisms such as protein aggregation, oxidative stress, and neuroinflammation. Emerging strategies including hybrid molecules, nanocarrier delivery, and AI-driven design may accelerate their clinical translation.},
}

Humans
*Benzimidazoles/chemistry/pharmacology/therapeutic use/chemical synthesis
*Neurodegenerative Diseases/drug therapy/metabolism
*Neuroprotective Agents/chemistry/pharmacology/therapeutic use/chemical synthesis
Animals
Molecular Structure
Structure-Activity Relationship

@article {pmid41947254,
year = {2026},
author = {Passmore, JS and Nieves Delgado, A and Happel, AU},
title = {Ethical design as a prerequisite for translational microbiome science.},
journal = {Microbiome},
volume = {14},
number = {1},
pages = {},
pmid = {41947254},
issn = {2049-2618},
support = {INV-037612/GATES/Gates Foundation/United States ; VI.Vidi.221F.014//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; K43TW012864/NH/NIH HHS/United States ; },
mesh = {Humans ; *Microbiota ; *Translational Research, Biomedical/ethics ; *Translational Science, Biomedical/ethics ; Research Design ; },
abstract = {Human microbiome research is expanding globally, yet remains dominated by samples, institutions, and leadership from the Global North. This imbalance undermines scientific validity, as microbiomes are shaped by socio-ecological context and temporal dynamics, and risks producing diagnostics and therapeutics that are not applicable across diverse populations. In this comment, we engage with van Daele et al.'s framework of co-laboration and argue for ethical, interdisciplinary, and locally led research models that center community participation, context-rich metadata, and equitable authorship. We outline structural requirements-governance tools, funding mechanisms, and accountability systems-needed to ensure these frameworks are implemented and advance both scientific integrity and global health equity. Video Abstract.},
}

Humans
*Microbiota
*Translational Research, Biomedical/ethics
*Translational Science, Biomedical/ethics
Research Design

@article {pmid41947659,
year = {2026},
author = {Vaudroz, V and Hübers, A and Kiliaridis, S and Antonarakis, GS},
title = {The Repercussions of Amyotrophic Lateral Sclerosis on the Orofacial Sphere: A One-Year Prospective Longitudinal Study.},
journal = {Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry},
volume = {46},
number = {2},
pages = {e70170},
doi = {10.1111/scd.70170},
pmid = {41947659},
issn = {1754-4505},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Male ; Longitudinal Studies ; Female ; Middle Aged ; Prospective Studies ; Disease Progression ; *Malocclusion/etiology ; Aged ; *Oral Health ; Adult ; },
abstract = {AIM: The aim of this longitudinal study was to evaluate the repercussions of amyotrophic lateral sclerosis (ALS) on orofacial function, dental health, and the development of malocclusions, in order to assess whether disease progression influences oral and craniofacial outcomes.

SUBJECTS AND METHODS: Thirteen patients diagnosed with ALS according to the Gold Coast criteria were enrolled to be examined at two time points (T1 and T2), with a one-year interval. The ALS Functional Rating Scale-Revised (ALS-FRS-R), the Nordic Orofacial Test Screening (NOT-S), the Decayed Missing and Filled Teeth (DMFT) index, Plaque Index, and standard orthodontic assessments were used to quantify changes in disease progression, orofacial function, dental health, and occlusal parameters, respectively. Statistical evaluation: Paired sample t-tests were performed to evaluate differences between T1 and T2 for continuous variables. Chi-square and Fisher's exact tests were used for categorical data. Multiple linear regression analyses were carried out to assess potential associations between general disease progression, ALS type, and orofacial functional or dental health decline. A significance level of p < 0.05 was adopted for all analyses.

RESULTS: Thirteen patients were examined at T1, 10 of whom completed both evaluations. A significant deterioration in the general disease condition was observed (ALS-FRS-R: mean difference -6.0 ± 6.98; p = 0.024). Orofacial function worsened significantly as reflected by an increase in NOT-S total score (+2.3; p = 0.001). Dental health also declined, with a significant increase in DMFT (+1.8; p = 0.014) and Plaque Index (+0.4; p = 0.004). However, occlusal parameters remained stable over the 12-month period, with no significant changes in overjet (p = 0.860) or overbite (p = 0.347). The bulbar type of ALS seems to show worse deterioration of orofacial function over time, and individuals with more significant general disease progression also showed worse orofacial functional decline.

CONCLUSIONS: ALS has a significant impact on orofacial function and dental health, characterized by neuromuscular deterioration, increased plaque accumulation, and a higher number of affected teeth. Despite this decline, dental occlusion appears to remain stable in the short term. These findings highlight the need for interdisciplinary and preventive oral care strategies in the management of patients with ALS, aiming to preserve oral function and quality of life in a progressively disabling disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
Male
Longitudinal Studies
Female
Middle Aged
Prospective Studies
Disease Progression
*Malocclusion/etiology
Aged
*Oral Health
Adult

@article {pmid41949165,
year = {2026},
author = {Xu, X and Xu, J and Xue, F and Li, W and Liu, H and Zhang, Z and Chen, S},
title = {Isoform-specific function underlies differential herbicide resistance of the W574L mutation in peanut AhALS isozymes.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.70798},
pmid = {41949165},
issn = {1526-4998},
support = {//S&T Program of Hebei/ ; //Shijiazhuang City Modern Agricultural Innovation Special Project of the Key R & D and Small and medium-sized enterprises Innovation Program/ ; //National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Peanut (Arachis hypogaea) is an important cash crop with high oil yield per unit area; it is considered an excellent source for producing premium edible oil and a variety of processed foods. Weed infestation poses a critical challenge to peanut cultivation. Although the acetolactate synthase (ALS)-inhibiting herbicide imazethapyr is extensively applied for weed control in peanut fields, it also causes significant phytotoxicity to the crop. The development of herbicide-resistant varieties through gene editing represents a promising sustainable solution; however, the identification of efficient gene-editing targets for conferring high herbicide resistance in peanut remains limited. Plant resistance to imazethapyr arises primarily from mutations in the target gene ALS.

RESULTS: In this study, a total of four AhALS genes (AhALS1a, AhALS1b, AhALS2a and AhALS2b) with high homology were identified in cultivated peanut. Importantly, we demonstrated for the first time that all four AhALS proteins localize to the chloroplast. Using site-directed mutagenesis, we introduced mutations at position 574 (W574L) in AhALS1a, AhALS2a, AhALS1b and AhALS2b. Both petri-dish and whole-plant bioassays revealed that transgenic Arabidopsis thaliana expressing AhALS2b-W574L remained susceptible to imazethapyr. By contrast, lines expressing AhALS1a-W574L, AhALS2a-W574L or AhALS1b-W574L exhibited high herbicide resistance. The reduced binding ability of resistance AhALS isoforms to imazethapyr was mainly responsible for transgenic lines resistance to imazethapyr. Furthermore, enzymatic and molecular interaction analyses critically showed that the W574L mutation in AhALS2b, unlike its paralog AhALS1b, did not reduce binding affinity to imazethapyr and thus conferred no resistance.

CONCLUSIONS: This demonstrates marked functional divergence among peanut ALS isozymes, where an identical mutation yields different phenotypic outcomes depending on the protein structure. Consequently, position 574 in AhALS2b is an ineffective editing target, underscoring the need for isozyme-specific screening to develop herbicide-resistant peanut varieties. © 2026 Society of Chemical Industry.},
}

@article {pmid41950410,
year = {2026},
author = {Koyya, R and O'Brien, C and Drennan, IR and Cheskes, S and von Vopelius-Feldt, J},
title = {Paramedics' decisions to withhold resuscitation in traumatic cardiac arrest: accuracy of paramedic assessments compared with autopsy findings.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/10903127.2026.2655289},
pmid = {41950410},
issn = {1545-0066},
abstract = {OBJECTIVES: Trauma remains the leading cause of death among Canadians under 45, with over 70% of these deaths occurring in the prehospital setting. In Ontario, Canada, paramedics' decision to initiate or withhold resuscitation in traumatic cardiac arrest (TCA) is governed by basic life support (BLS) and advanced life support (ALS) patient care standards. This study explores paramedics' decisions to withhold cardiopulmonary resuscitation (CPR) in cases of prehospital TCA.

METHODS: We conducted a retrospective review of case files relating to coroner investigations of prehospital TCA across two emergency medical services (EMS) covering a mixed urban/suburban region in Ontario, Canada, with a population of approximately 4.3 million people, from January 2018 to July 2022. We reviewed all deaths where EMS records were available in the death investigation files and where paramedics did not provide CPR. Paramedics' documentation of reasons to withhold CPR was reviewed and compared to post-mortem findings. Descriptive statistics were used to describe the findings.

RESULTS: We identified 90 cases of prehospital TCA where no CPR was provided by paramedics. Of these, 55 cases (61%) had documented, injuries incompatible with life (decapitation, open head or torso wounds with visible outpouring of brain or abdominal contents) or signs of irreversible death (rigor mortis, lividity, decomposition). Post-mortem examination confirmed paramedics' findings of injuries incompatible with life in 29 cases (89%). For the remaining 35 cases (39%), CPR was withheld due to a combination of prolonged time from TCA to EMS contact, severity of injuries deemed non-survivable, significant external blood loss, and following remote physician agreement in 31 (89%) cases. Of these, 29 (83%) had post-mortem findings demonstrating anatomical injuries that made the TCA irreversible.

CONCLUSIONS: The majority of decisions to withhold CPR in prehospital TCA cases are based on signs that are clearly incompatible with life, identified by paramedics with high specificity. In the absence of such findings, paramedics consider factors like prolonged time intervals, overall injury severity, and seek guidance through remote physician supervision before deciding whether to withhold resuscitation efforts.},
}

@article {pmid41950600,
year = {2026},
author = {Yoo, HE and Issenberg, SB and Roh, YS},
title = {Effects of distinct prebriefing and debriefing on learning outcomes in advanced life support training for ward nurses: A randomized controlled trial.},
journal = {Nurse education today},
volume = {163},
number = {},
pages = {107094},
doi = {10.1016/j.nedt.2026.107094},
pmid = {41950600},
issn = {1532-2793},
abstract = {BACKGROUND: Effective training in advanced life support (ALS) is crucial for improving ward nurses' ALS performance and patient outcomes during in-hospital cardiac arrest. However, the comparative effects of prebriefing and debriefing strategies in ALS education remain unclear.

OBJECTIVE: This study aimed to determine whether differences in prebriefing and debriefing strategies in ALS training result in significant variations in metacognition, self-efficacy, ALS performance, and learning satisfaction among novice ward nurses.

METHODS: In this randomized controlled trial, 205 novice ward nurses were assigned to four ALS training groups. Groups 1 and 2 received prebriefing with a role-modeling video, whereas Groups 3 and 4 received prebriefing with self-directed learning. Instructor-led (Groups 1 and 3) or peer-led (Groups 2 and 4) debriefings followed the prebriefing methods. Participants completed baseline and post-intervention assessments that measured metacognition, self-efficacy. ALS performance and learning satisfaction was measured only at the posttest.

RESULTS: All groups demonstrated improved self-efficacy following ALS training. However, Groups 1 and 2, who received prebriefing with a role-modeling video, achieved greater gains in both metacognition and self-efficacy than Groups 3 and 4, regardless of the debriefing method. Among all groups, Group 1 showed the highest ALS performance and learning satisfaction, followed by Group 2.

CONCLUSION: This study highlights the effectiveness of structured prebriefing using a role-modeling video for enhancing critical ALS competencies among novice ward nurses. These findings provide evidence to inform the design of more effective simulation-based resuscitation training programs in clinical settings.},
}

@article {pmid41941997,
year = {2026},
author = {Cai, ZW and Zhuang, SP and Huang, ZY and Shi, JY and Huang, NX and Chen, S and Zou, ZY and Chen, HJ},
title = {Abnormal cortical hierarchy revealed by gradient dysfunction in patients with definite amyotrophic lateral sclerosis.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111850},
doi = {10.1016/j.brainresbull.2026.111850},
pmid = {41941997},
issn = {1873-2747},
abstract = {PURPOSE: Cortical multisystem dysfunction in amyotrophic lateral sclerosis (ALS) has been investigated, but disruptions in unimodal-to-transmodal cortical hierarchy remained unexplored. We identified cortical hierarchy abnormalities using functional connectivity gradient (FCG) analysis and evaluated their clinical relevance in ALS.

METHODS: Resting-state functional MRI images were acquired from 17 definite ALS patients and 29 healthy controls. Unimodal-to-transmodal cortical gradient values were derived from functional connectivity matrices using diffusion map embedding, a nonlinear dimensionality reduction method. Intergroup differences were examined with two-sample t tests at the voxel and network levels.

RESULTS: Gradients primarily in transmodal areas (including the bilateral frontal and parietal cortex and anterior cingulate gyrus) decreased, and gradients primarily in unimodal areas (including the bilateral precentral and postcentral gyrus and occipital cortex) increased in ALS patients (false discovery rate (FDR)-corrected P < 0.05). Network-level gradients in ALS were elevated in the sensorimotor (SMN) and visual networks (VN) but reduced in the frontoparietal (FPN) and limbic networks (FDR-corrected P < 0.05). Among ALS patients, the gradient values in SMN (r = 0.506; P = 0.038), VN (r = 0.534; P = 0.027) and FPN (r = -0.792; P < 0.001) correlated with disease duration, and the gradient value in FPN correlated with disease severity (r = 0.532; P = 0.028). Gradient measures demonstrated moderate accuracy for diagnosing ALS (AUC = 0.712-0.866).

CONCLUSION: Aberrant cortical hierarchy may elucidate pathophysiological mechanisms of multisystem dysfunction in ALS. FCG analysis may provide biomarkers related to hierarchical functional systems for assessing ALS progression and diagnosis.},
}

@article {pmid41942009,
year = {2026},
author = {Song, L and Li, W and Li, H and Zhang, L},
title = {Comment on Gao et al.'s "Eggshell Fragments as a High-Yield Diagnostic Target in Microscopic Examination of Scabies: A Retrospective Study.".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.01.105},
pmid = {41942009},
issn = {1097-6787},
}

@article {pmid41942654,
year = {2026},
author = {Muhr, P},
title = {Seeing Oneself Seize: A Case Study on the Affordances of a Video-Based Diagnostic Encounter for a Patient with Functional Seizures.},
journal = {Culture, medicine and psychiatry},
volume = {50},
number = {2},
pages = {},
pmid = {41942654},
issn = {1573-076X},
mesh = {Humans ; Adolescent ; *Video Recording ; *Seizures/diagnosis/psychology ; Male ; Female ; *Physician-Patient Relations ; },
abstract = {This paper examines how integrating clinical video recordings into the diagnostic encounter shapes a patient's experience of functional seizures, a contested neurological condition historically known as hysterical attacks. Drawing on James Gibson's theory of affordances and de Haan et al.'s account of how individuals perceive affordances based on their needs and concerns, the study analyzes a single in-depth interview with an 18-year-old patient recently diagnosed with functional seizures. It explores what viewing seizure videos with a doctor offers the patient-in clinical, epistemic, emotional, and experiential terms. The interview was subjected to a close reading, attending to how video-mediated communication of diagnosis intersects with the patient's prior illness history, sociocultural context, and understanding of self. The analysis identified three positive (epistemic insight, diagnostic validation, trauma recollection) and three negative affordances (shame, vulnerability, resignation). These affordances emerged not only from what the videos showed but also from how they were viewed, framed, and interpreted during the diagnostic encounter. The study concludes that the videos' affordances cannot be separated from an individual patient's interpretive resources and biography. Clinical video viewing can generate meaningful diagnostic insights, but it also risks harm unless embedded within a carefully structured dialogical process that attends to the patient's specificities.},
}

Humans
Adolescent
*Video Recording
*Seizures/diagnosis/psychology
Male
Female
*Physician-Patient Relations

@article {pmid41943205,
year = {2026},
author = {Beers, DR and Lin, YY and Thonhoff, JR and Thome, AD and Faridar, A and Zhao, W and Wen, S and Appel, SH},
title = {Longitudinal Assessment of Biomarkers in ALS: Discriminative Biomarkers for Disease Progression and Survival.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70381},
pmid = {41943205},
issn = {2328-9503},
abstract = {OBJECTIVE: To assess the association and discriminative performance of serum biomarkers with clinical disease progression and survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: This retrospective study, conducted at Houston Methodist Hospital, Houston, TX, used longitudinal serum samples collected between January 2018 and December 2022. A cohort of 100 patients with sporadic or familial ALS was randomly selected and assayed by ELISAs for biomarkers 4-hydroxy-2-nonenal (4-HNE), lipopolysaccharide binding protein (LBP), and neurofilament light chain (NfL) levels.

RESULTS: Each biomarker was increased in patients. 4-HNE and LBP were increased at diagnosis and continued to increase as the disease progressed; both correlated with progression rates and survival. NfL was increased at diagnosis, then plateaued relatively. LBP correlated with ALSFRS-R at diagnosis; NfL did not correlate. 4-HNE and LBP were increased in bulbar onset patients who survived a shorter period of time; NfL levels for bulbar/limb onsets were not different. Receiver operating characteristic analyses with apparent and optimism-adjusted area-under-the-curve (AUC) demonstrated that 4-HNE and LBP discriminated rapid progression and survival, whereas NfL showed modest discrimination for rapid progression. The combination of biomarkers yielded improved AUCs as depicted in Venn diagrams across individual and combined biomarkers.

INTERPRETATION: 4-HNE, LBP, and NfL are biomarkers of lipid peroxidation, systemic inflammation, and axonal integrity. 4-HNE and LBP correlated with disease burden, disease progression, and survival. In the bulbar onset, survival was shortened and associated with increased 4-HNE and LBP. This exploratory longitudinal study suggests the utility of combining biomarkers to discriminate disease progression and survival and monitor clinical trial outcomes.},
}

@article {pmid41943580,
year = {2026},
author = {Ye, Y and Zhang, Z and Xiao, Y and Zhu, C and Wright, N and Asbury, J and Huang, Y and Wang, W and Gomez-Isaza, L and Troncoso, JC and He, C and Sun, S},
title = {DCPS modulates TDP-43-linked neurodegeneration through P-body-mediated RNA decay.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.01.018},
pmid = {41943580},
issn = {1097-4199},
abstract = {The proteinopathy of the RNA-binding protein TDP-43, characterized by nuclear clearance and cytoplasmic inclusion, is a hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). Through CRISPR interference (CRISPRi) screening in human neurons, we identified the decapping scavenger enzyme (DCPS) as a novel genetic modifier of TDP-43 loss-of-function (LOF)-mediated neurotoxicity. Our findings reveal that TDP-43 LOF leads to aberrant mRNA degradation via dysregulating the properties and activity of processing bodies (P-bodies). TDP-43 interacts with P-body component proteins, potentially influencing their dynamic equilibrium and assembly into ribonucleoprotein (RNP) granules. Loss of TDP-43 hyperactivates P-bodies, increasing mRNA association and RNA decay. Reducing DCPS restores P-body integrity and RNA turnover, ultimately improving neuronal survival. Overall, this study highlights a novel role of TDP-43 in RNA processing through P-body regulation and identifies DCPS as a potential therapeutic target for TDP-43 proteinopathy-related neurodegenerative diseases.},
}

@article {pmid41943810,
year = {2026},
author = {Khandelwal, N and Geremakis, C and Riaz, F and Ryan, G and Saundankar, V and Sheer, R and Suehs, B},
title = {Epidemiology, Patient Characteristics, Real-World Treatment Patterns, and Healthcare Utilization and Spending for Patients with Multifocal Motor Neuropathy: A US Claims-Based Analysis.},
journal = {Journal of health economics and outcomes research},
volume = {13},
number = {1},
pages = {111-119},
pmid = {41943810},
issn = {2327-2236},
abstract = {BACKGROUND: Multifocal motor neuropathy (MMN) is a rare, progressive neurological disease characterized by asymmetrical limb weakness. The real-world healthcare burden of MMN is not well established.

OBJECTIVES: To characterize the epidemiology, diagnostic procedures, treatment patterns, healthcare resource utilization (HCRU), and healthcare spending associated with MMN in patients in the US.

METHODS: This retrospective, observational claims study extracted data from the Humana Healthcare Research Database, comprising US Medicare Advantage plan members. Eligible patients were aged 18-89 years, had ≥2 nondiagnostic medical claims (the first being the index date) associated with an MMN diagnosis code (January 1, 2017-June 30, 2022), and continuous enrollment for 12 months pre-index (baseline) and post-index (follow-up). Patients with amyotrophic lateral sclerosis, chronic inflammatory demyelinating neuropathy, or immunosuppressant use were excluded. Outcomes were assessed during the baseline and follow-up periods.

RESULTS: Deidentified data were extracted for 248 patients with MMN. Median (Q1, Q3) age at index was 70.0 (62.0, 77.0) years; most patients were male (53.6%) and White (78.2%). Diagnostic procedures included (baseline/follow-up periods) spinal magnetic resonance imaging (21.4%/18.1%), nerve conduction studies (19.8%/14.5%), and electromyography (17.7%/15.3%). Anticonvulsants, pain medications, corticosteroids, and central muscle relaxants were the most commonly used medications. Overall, 5.2% of patients had intravenous immunoglobulin (IVIG) during follow-up. Mean (standard deviation [SD]) time from index to IVIG initiation was 63.1 (52.2) days, with 6.5 (5.4) administrations, 28.7 (22.9) days between administrations, and 147.5 (133.9) days of total treatment. For all-cause HCRU, 23.8% of patients had ≥1 inpatient stay in the baseline period, with mean (SD) length of stay of 12.7 (14.5) days; during follow-up, 27.8% of patients had ≥1 inpatient stay (length of stay, 13.4 [16.2] days). During the baseline/follow-up periods, 43.1%/46.8% of patients had ≥1 emergency department visit, and 18.5%/28.6% used telehealth services. Median all-cause spending (baseline/follow-up) was 11   299 / 16 074 for total healthcare, 6745 / 10 630 for medical resources, and 1374 / 1701 for pharmacy.

DISCUSSION: Further studies are needed to enhance our understanding of the real-world diagnostic and treatment patterns associated with MMN and to determine long-term clinical outcomes.

CONCLUSION: These real-world data highlighted the considerable burden associated with MMN on the healthcare system and patients.},
}

@article {pmid41943905,
year = {2026},
author = {Gera, P and Temkar, S and Deb, AK and Sahi, A},
title = {Letter to the Editor: Comment on Upadhyaya et al.'s "Intravitreal Clindamycin as an Adjuvant Therapy in Congenital Toxoplasma Retinochoroiditis in a Neonate - A Case Report".},
journal = {Ocular immunology and inflammation},
volume = {},
number = {},
pages = {1-2},
doi = {10.1080/09273948.2025.2497485},
pmid = {41943905},
issn = {1744-5078},
abstract = {The novel work by Upadhyaya et al. suggests a potential use of intravitreal clindamycin for treating congenital toxoplasma retinochoroiditis. We share our clinical experience of encountering a sudden spike in intraocular pressure (IOP) after administering intravitreal clindamycin (5 mg/0.5 mL) in a neonate. Intravitreal injections are known to cause an increase in IOP immediately, which reduces in a few minutes. However, a smaller vitreous volume in neonates can cause an exponential increase in IOP immediately post-injection, posing a risk of optic nerve damage and compromise in retinal perfusion. We suggest modifying the intravitreal preparation of clindamycin to 0.5 mg/0.025 mL when used in neonates to reduce this risk while maintaining therapeutic efficacy.},
}

@article {pmid41944768,
year = {2026},
author = {Pang, XY and Wang, HF and Bai, JM and Huang, XS},
title = {Integration of Single-cell RNA Sequencing and Mendelian Randomization Analysis for Identifying Potential Immune Therapeutic Targets in Amyotrophic Lateral Sclerosis.},
journal = {Biomedical and environmental sciences : BES},
volume = {39},
number = {3},
pages = {327-341},
doi = {10.3967/bes2026.011},
pmid = {41944768},
issn = {2214-0190},
mesh = {*Amyotrophic Lateral Sclerosis/immunology/genetics/therapy ; Humans ; *Mendelian Randomization Analysis ; Sequence Analysis, RNA ; Single-Cell Analysis ; Male ; Middle Aged ; Female ; Genome-Wide Association Study ; CD4-Positive T-Lymphocytes/immunology ; Leukocytes, Mononuclear ; },
abstract = {OBJECTIVE: Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In this study, we investigated the functional mechanisms of T cell subtypes and assessed the causal links between CD4+ cytotoxic T cell-related genes and ALS risk.

METHODS: Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from patients with ALS and healthy controls (HC) was used to identify differentially expressed genes (DEGs) in CD4+ cytotoxic T cells. Comprehensive analyses of CD4+ cytotoxic T cells, including pseudotemporal trajectory, intercellular communication, and metabolic pathway analysis, were performed. Mendelian randomization (MR) analysis evaluated the causal effects of DEGs on ALS risk, with validation using independent genome-wide association study (GWAS) data. Expression patterns of the causal genes were further verified using scRNA-seq, bulk-seq, and clinical samples.

RESULTS: CD4+ cytotoxic T cells were significantly expanded in patients with ALS. The upregulated genes S100A6, SERPINB6, SMAD7, and TPST2 were positively correlated with ALS susceptibility, whereas DIP2A showed a protective association.

CONCLUSION: S100A6, SERPINB6, SMAD7, TPST2, and DIP2A were identified as causal genes and potential therapeutic targets in ALS, implicating CD4+ cytotoxic T cells in the disease mechanisms. Further studies targeting these genes and neuroinflammatory pathways are warranted.},
}

*Amyotrophic Lateral Sclerosis/immunology/genetics/therapy
Humans
*Mendelian Randomization Analysis
Sequence Analysis, RNA
Single-Cell Analysis
Male
Middle Aged
Female
Genome-Wide Association Study
CD4-Positive T-Lymphocytes/immunology
Leukocytes, Mononuclear

@article {pmid41945020,
year = {2026},
author = {Qin, K and Xu, Y and Liang, W},
title = {Letter to the editor regarding "Comparison of the therapeutic effects of modified 15-mm incision minimally invasive approach with the conventional approach in the treatment of AO 23-B3 distal radius fractures".},
journal = {Injury},
volume = {},
number = {},
pages = {113224},
doi = {10.1016/j.injury.2026.113224},
pmid = {41945020},
issn = {1879-0267},
abstract = {This letter comments on Liu et al.'s study comparing a modified 15 mm mini-incision volar plating approach to conventional ORIF for AO 23-B3 distal radius fractures. While endorsing the reported cosmetic and recovery benefits of MIPO, we highlight the need for longitudinal functional data during early rehabilitation and detailed classification of postoperative complications. Addressing these gaps would enhance the understanding of the early recovery trajectory and safety profile of this minimally invasive technique.},
}

@article {pmid41935163,
year = {2026},
author = {Sheikhpour, Z and Seyedalipour, B and Ataei, F and Baziyar, P and Akhlaghi, M and Hosseinkhani, S},
title = {Inhibitory effect of epigallocatechin-3-gallate as a potent anti-amyloidogenic agent against the G138E mutant of SOD1.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42742-2},
pmid = {41935163},
issn = {2045-2322},
abstract = {SOD1 misfolding leads to protein aggregation, which is a common feature of neurodegenerative diseases such as ALS. The effect of epigallocatechin gallate (EGCG) as a potent anti-amyloidogenic polyphenol on the G138E-SOD1 mutant was investigated using computational/experimental approaches. MD simulation results (RMSD, RMSF, Rg, SASA, PCA, and FEL) showed that EGCG binding stabilizes the mutant in a structure closer to the native structure, which was consistent with the FTIR and DSSP results. Intrinsic fluorescence spectroscopy calculated Ksv and Kq values as 1.8 × 10[4] M[-1] and 5.8 × 10[12] M[-1]s[-1], respectively, indicating the participation of a static quenching mechanism. TEM images provide compelling evidence for the potential inhibitory effect of EGCG on protein aggregates in the G138E mutant, confirming the results of the ThT assay. DLS results showed a reduction in the size of aggregated particles in the presence of 80 μM EGCG, confirming the inhibition of amyloid aggregation by this compound. Finally, MTT assay on SH-SY5Y cells showed that cell survival in the presence of SOD1-G138E aggregates was approximately 40%, which increased to 60% with the addition of 80 μM EGCG. Taken together, this study suggests that EGCG may inhibit amyloid aggregation and reduce cytotoxicity by affecting nucleation and structural stabilization, making it a promising compound for ALS therapeutic strategies.},
}

@article {pmid41936785,
year = {2026},
author = {Bao, A and Liu, J and Bian, B and Gao, T and Zhou, H},
title = {U-Mamba-Spectra: A novel generative and explainable framework for camel milk adulteration detection using near-infrared spectral learning.},
journal = {Food chemistry},
volume = {514},
number = {},
pages = {149054},
doi = {10.1016/j.foodchem.2026.149054},
pmid = {41936785},
issn = {1873-7072},
abstract = {Camel milk is vulnerable to adulteration due to its high value and limited supply. This study proposes an interpretable framework, U-Mamba-Spectra, for qualitative and quantitative detection of camel milk adulteration using near-infrared (NIR) spectroscopy. A total of 460 samples (0-100% adulteration) were analyzed within 780-1830 nm. The proposed U-Mamba classifier, integrating U-Net and Mamba modules to capture local and global spectral dependencies, achieved superior classification performance compared with conventional machine learning and deep learning models. SHAP analysis identified chemically meaningful bands associated with water, protein, and fat. For quantitative analysis, a two-stage MCR-ALS-RF model enabled accurate and chemically interpretable concentration prediction, with validation according to ICH Q2 (R1) demonstrating recoveries of 96.8-99.5%, RSD < 5%, and detection limits of 0.025-0.060 g/100 g. To improve robustness under limited sample conditions, a hybrid generative model (CVAE-CWGAN-GP-SAM) was introduced for spectral augmentation, increasing classification accuracy from 95.21% to 98.60%.},
}

@article {pmid41937028,
year = {2026},
author = {Spindler, A and Maas, D and Zappi, I and Shapiro, J and Lo Sicco, KI},
title = {Response to Lampert et al.'s "Hormonal versus Copper Intrauterine Devices: A Retrospective Analysis of Association with Androgen-related Dermatologic Disorders using the TriNetX Database".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.01.104},
pmid = {41937028},
issn = {1097-6787},
}

@article {pmid41937301,
year = {2026},
author = {Laine, M and Raitanen, J and Auvinen, A},
title = {Mortality From Amyotrophic Lateral Sclerosis in Finland 1987-2022.},
journal = {European journal of neurology},
volume = {33},
number = {4},
pages = {e70586},
doi = {10.1111/ene.70586},
pmid = {41937301},
issn = {1468-1331},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality ; Finland/epidemiology ; Female ; Male ; Aged ; Middle Aged ; Adult ; Aged, 80 and over ; Mortality/trends ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. We assessed changes in the mortality from ALS in Finland from 1987 to 2022.

METHODS: Numbers of deaths caused by ALS (ICD-10 code G12.2) and population sizes by sex, age group, and year were obtained from Statistics Finland. Crude and age-standardized mortality rates were calculated. The annual percentage change was estimated using Poisson regression, and joinpoint regression was used to identify changes in trend during the study period.

RESULTS: Mortality from ALS increased in Finland from 1987 to 2022. The age-standardized ALS mortality in the entire population was 2.24/100,000 in 1987 and 4.21/100,000 in 2022. The male: female ratio in mortality was 1.18. The age-standardized mortality increased on average by 1.7% (95% CI 1.5%-2.0%) annually. In men, the age-standardized mortality increased on average by 1.2% (95% CI 0.9%-1.6%) annually and in women by 2.0% (95% CI 1.6%-2.3%). The largest increase occurred in the oldest age group (70+ years), with an average annual increase of 2.4% (95% CI 2.0%-2.8%). In joinpoint regression, no changes in trend were identified overall or in men, but in women, the annual percentage change (APC) was 5.5% (95% CI 3.0%-8.0%) in 1987-1997 and 1.0% (95% CI 0.5%-1.4%) during 1997-2022.

CONCLUSION: Similar to some other countries, mortality from ALS has increased in Finland, nearly doubling in 35 years. Further research on possible reasons is needed.},
}

Humans
*Amyotrophic Lateral Sclerosis/mortality
Finland/epidemiology
Female
Male
Aged
Middle Aged
Adult
Aged, 80 and over
Mortality/trends

@article {pmid41938070,
year = {2026},
author = {Samokhina, E and Buskila, Y},
title = {Astrocytic K[+] regulation during neurodegenerative diseases.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1782460},
pmid = {41938070},
issn = {1663-4365},
abstract = {Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in specific areas of the central nervous system. Historically, a "neurocentric" paradigm viewed glial cells, such as astrocytes, as cells that provided adequate support for neuronal energy metabolism and controlled local cerebral blood flow. However, studies from the past two decades found that astrocytes are involved in synaptic function through different mechanisms, including the uptake of extracellular glutamate molecules and potassium ions following synaptic neuronal transmission. Also, astrocytes respond to neurotransmitters and neuromodulators through alterations of intracellular ion concentrations (e.g., Na[+], Ca[2+], K[+]) and the release of gliotransmitters. Astrocytes play a pivotal role in preserving potassium homeostasis within the central nervous system through their potassium channels, a process known as "potassium clearance." Impaired astrocytic potassium clearance mechanisms can result in neuronal hyperexcitability, leading to increased glutamate release, overactivation of glutamate receptors, and cytotoxicity. Recent studies suggest that these factors can cause cell death and neurodegeneration, and further indicate a region-specific glial dysfunction in neurodegeneration, which reflects the heterogeneity of glial cell function and sensitivity across different brain regions. Overall, this manuscript offers novel insights into a relatively new concept that glial cells can actively shape neuronal activity and survival.},
}

@article {pmid41939038,
year = {2026},
author = {Chow, CJ and Curtis, S and Chen, M and Purdy, JC and Stanfield, GM and Rojas, E and Wadsworth, R and Sisler, S and Simonetti, J},
title = {"It Honestly Took Me About Two Years": Minoritized Students' Experiences in Navigating Pathways Between High School, College, and Health Science Graduate Programs.},
journal = {Medical science educator},
volume = {36},
number = {1},
pages = {295-304},
pmid = {41939038},
issn = {2156-8650},
abstract = {INTRODUCTION: This study explores the resources needed by minoritized students-particularly students of color and first-generation college students-to succeed in the pathway toward advanced health sciences degrees. Using Teemant et al.'s equity framework, we investigated how partnerships among key stakeholders-including students, parents, school leaders, and community members-contribute to these students' academic success in the health sciences.

METHODS: We conducted four focus groups (total = 31 participants) with the following groups: (1) parents of first-generation college students, (2) community college students, (3) graduate students in health sciences, and (4) academic advisors. An additional four participants provided perspectives through individual interviews. Focus groups and interviews were transcribed verbatim and coded inductively by a subset of the authors.

RESULTS: Using Teemant et al.'s framework, our analysis illustrated three overarching themes: barriers, supports, and capacities. Key barriers included limited access to information about applying to higher-education programs and facing skepticism from teachers and advisors regarding the potential to succeed in health sciences. Supportive factors included university-based diversity programs and bridge programs that provided target guidance, resources, and information to both students and their families. Data also indicated that higher-education systems often fall short in ensuring that resources are truly accessible and relevant to diverse student populations.

CONCLUSIONS: Our study illuminates how the success of minoritized individuals in advanced health sciences hinges on bolstering both students' and their parents' navigational capital, while addressing the complex interplay of structural barriers and targeted supports that shape their educational journeys.},
}

@article {pmid41940896,
year = {2026},
author = {Tang, Z and Lei, Y and Huang, J and He, R and Wu, Y and Li, M and Ye, Z and He, X and Heng, H and Zha, Y and Wei, J},
title = {Accuracy of muscle ultrasonography in detecting fasciculations for the diagnosis of amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of neurology},
volume = {273},
number = {4},
pages = {},
pmid = {41940896},
issn = {1432-1459},
support = {2020ZYYD024//Local Development Project of Science and Technology guided by the Central Commission/ ; EWT201947//Hubei Province Leading Medical Talents and Hubei Province Famous Doctor Studio Program/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis/complications ; Humans ; *Fasciculation/diagnostic imaging/etiology ; Ultrasonography/standards/methods ; *Muscle, Skeletal/diagnostic imaging ; Sensitivity and Specificity ; },
abstract = {PURPOSE: This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of muscle ultrasonography in detecting fasciculations for the diagnosis of amyotrophic lateral sclerosis (ALS).

METHODS: Following PRISMA-DTA guidelines, we systematically searched PubMed, Embase, Cochrane Library, Ovid Medline, Sinomed, Web of Science, CNKI and VIP for studies published up to July 8, 2025 that evaluated muscle ultrasonography to detect fasciculations for ALS diagnosis. The study protocol was registered in PROSPERO (CRD420251057866). Studies were screened using predefined inclusion and exclusion criteria and data were extracted. Risk of bias was assessed with QUADAS-2. Statistical analyses (Stata 16.0 and R 4.5.1 with the "midas," "metandi," and "mada" packages) were used to calculate pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR). We constructed forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, summary ROC (SROC) curves and calculated the area under the SROC curve (AUC). Univariate meta-regression and subgroup analyses explored sources of heterogeneity. Publication bias was assessed using Deeks' funnel plot asymmetry test. Fagan nomograms were also used to illustrate the changes from pre-test to post-test probability and to enhance clinical interpretability.

RESULTS: Thirteen studies involving 1176 participants met the inclusion criteria. Muscle ultrasonography for fasciculation detection in ALS yielded a pooled sensitivity of 0.87 (95% CI 0.83-0.91) and specificity of 0.91 (95% CI 0.86-0.94). The pooled LR+ was 9.81 (95% CI 6.25-15.40) and LR- was 0.14 (95% CI 0.10-0.19), with a DOR of 70.03 (95% CI 41.72-117.56). The area under the SROC curve was 0.94 (95% CI 0.91-0.95). Meta-regression identified scan duration as a primary factor influencing diagnostic accuracy, with scan durations ≥ 30 s associated with higher sensitivity but relatively lower specificity. Deeks' funnel plot showed no significant asymmetry (p = 0.61), indicating no notable publication bias. Fagan nomograms showed that, at a pre-test probability of 30%, the post-test probability increased to 81% after a positive MUS result and decreased to 6% after a negative result.

CONCLUSION: Muscle ultrasonography demonstrates good pooled diagnostic accuracy for detecting fasciculations in ALS and may serve as a useful adjunct to electrodiagnostic evaluation. Scan duration appears to significantly affect the diagnostic performance, with longer scanning improving sensitivity at the cost of reduced specificity. We speculate that prolonged scanning may be more useful in clinical scenarios where fasciculations are subtle or atypical, whereas shorter scanning may be sufficient when fasciculations are already readily apparent. Nevertheless, further large-scale prospective studies are needed to validate standardized scanning protocols and to better define the clinical role of MUS in ALS diagnostic pathways.},
}

*Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis/complications
Humans
*Fasciculation/diagnostic imaging/etiology
Ultrasonography/standards/methods
*Muscle, Skeletal/diagnostic imaging
Sensitivity and Specificity

@article {pmid41941281,
year = {2026},
author = {Subramanian, I and Surajambika, RR and Sekar, D and Natarajan, R and Nagarajan, NC},
title = {A Systematic Review on Isoquinoline Derivatives as Emerging Multi-target Agents in Alzheimer's and Parkinson's Disorder Therapy.},
journal = {Central nervous system agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715249401454260108062419},
pmid = {41941281},
issn = {1875-6166},
abstract = {INTRODUCTION: Neurodegenerative disorders, including Alzheimer's, Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease, are characterized by progressive neuronal loss driven by damage or apoptosis. Although their precise etiologies remain unclear, neuronal degeneration is a common pathological hallmark.

METHODS: This review compiles and critically evaluates studies investigating the potential of isoquinoline derivatives to mitigate neurodegeneration. Particular attention is given to their inhibitory effects on key enzymes implicated in these disorders and structural modifications aimed at improving potency and reducing toxicity.

RESULTS: Experimental findings demonstrate that isoquinoline derivatives exhibit significant inhibitory activity against several neurodegeneration-related enzymes. These compounds show promise in attenuating disease progression in preclinical models, supporting their potential as therapeutic leads.

DISCUSSION: Isoquinoline derivatives display multitarget properties, and structural optimization has enhanced their efficacy and safety profiles. Their multifunctional nature could offer advantages over current single-target therapies by improving efficacy and reducing adverse effects.

CONCLUSION: Isoquinoline derivatives represent promising scaffolds for developing novel therapeutics targeting neurodegenerative disorders. However, most data are limited to in vitro and earlystage preclinical studies. Comprehensive mechanistic investigations, standardized in vivo evaluations, and early-phase clinical trials are required to establish their pharmacokinetics, blood-brain barrier permeability, safety, and therapeutic potential.},
}

@article {pmid41941533,
year = {2026},
author = {Zhuolin, D and Chun, H and Su, X},
title = {Association between allostatic load and thyroid function in U.S. adults: a cross-sectional study based on NHANES data.},
journal = {Stress (Amsterdam, Netherlands)},
volume = {29},
number = {1},
pages = {2653858},
doi = {10.1080/10253890.2026.2653858},
pmid = {41941533},
issn = {1607-8888},
mesh = {Humans ; Female ; Male ; *Allostasis/physiology ; Cross-Sectional Studies ; Middle Aged ; Adult ; Nutrition Surveys ; United States ; *Thyroid Gland/physiopathology/physiology ; Thyrotropin/blood ; Aged ; Thyroid Function Tests ; Thyroxine/blood ; Biomarkers/blood ; *Thyroid Diseases/physiopathology ; Triiodothyronine/blood ; *Stress, Psychological/physiopathology ; },
abstract = {Chronic stress may contribute to endocrine dysregulation. The allostatic load (AL), an indicator of cumulative physiological burden across multiple systems, has unclear associations with thyroid function. We analyzed 5525 adults (2678 men and 2847 women) from NHANES 2007-2010. The participants were categorized into allostatic load score (ALS) quartiles: Q1 (n = 2582), Q2 (n = 1394), Q3 (n = 1003), and Q4 (n = 546). The ALS was constructed from eight cardiovascular, metabolic, and inflammatory biomarkers. Thyroid function was assessed (TSH, FT3, FT4, TgAb, and TPOAb) and categorized as thyroid dysfunction. Survey-weighted multivariable linear and logistic models estimated associations; trend tests and restricted cubic splines (RCS) assessed linearity. Subgroup and interaction analyses examined effect modification, and sensitivity analyses evaluated robustness. ALS was positively associated with higher TSH (β = 0.038, 95% CI: 0.019-0.057, p = 0.001) and FT3 (β = 0.005, 95% CI: 0.003-0.008, p < 0.001). No significant associations were observed for FT4, TPOAb, or TgAb. TSH increased linearly across ALS quartiles (p-trend < 0.001). Restricted cubic splines indicated no overall departure from linearity; in sex-stratified analyses, the association was linear in women and nonlinear in men. Significant interactions with age and race (p < 0.05) indicate that the ALS-TSH association differs by demographics. The results were consistent across the subgroup and sensitivity analyses. Our study suggested a significant positive association between AL and TSH levels. Further research is needed to clarify the mechanisms linking stress and thyroid function.},
}

Humans
Female
Male
*Allostasis/physiology
Cross-Sectional Studies
Middle Aged
Adult
Nutrition Surveys
United States
*Thyroid Gland/physiopathology/physiology
Thyrotropin/blood
Aged
Thyroid Function Tests
Thyroxine/blood
Biomarkers/blood
*Thyroid Diseases/physiopathology
Triiodothyronine/blood
*Stress, Psychological/physiopathology

@article {pmid41932651,
year = {2026},
author = {Scaricamazza, S and Nesci, V and Fenili, G and Tiberi, M and Percio, A and Rosina, M and Salvatori, I and Riggio, F and Candelise, N and Pieroni, L and Greco, V and Chiurchiù, V and Ferri, A and Valle, C},
title = {The hypothalamus is an early site of mitochondrial failure and neuro-immune circuit disruption in amyotrophic lateral sclerosis.},
journal = {Molecular metabolism},
volume = {},
number = {},
pages = {102360},
doi = {10.1016/j.molmet.2026.102360},
pmid = {41932651},
issn = {2212-8778},
abstract = {BACKGROUND: Metabolic dysfunction is a defining feature of amyotrophic lateral sclerosis (ALS), emerging early and strongly associated with disease progression and prognosis. While systemic hypermetabolism is well documented, the central mechanisms underlying energy imbalance remain poorly understood. The hypothalamus, a key regulator of whole-body energy homeostasis, has recently been implicated in ALS, but its mechanistic contribution to metabolic failure and disease progression remains unclear.

METHODS: We analyzed the hypothalamus SOD1-G93A mouse model using proteomics (ProteomeXchange ID: PXD070931), mitochondrial bioenergetic assays, immunofluorescence, flow cytometry, and gene expression to assess hypothalamic mitochondrial function, glial activation, and melanocortin system integrity. Limited analyses in the hFUS model confirmed the presence of key hypothalamic alterations, supporting a shared vulnerability across ALS models. In SOD1-G93A mice, the metabolic modulator trimetazidine (TMZ) was administered presymptomatically to evaluate effects on hypothalamic pathology, metabolic regulation, disease onset, and survival.

FINDINGS: We provide the first evidence that mitochondrial bioenergetic defects arise specifically in the hypothalamus of ALS models before symptom onset. Proteomic profiling revealed dysregulation of mitochondrial pathways, while functional assays confirmed impaired bioenergetics in the hypothalamus. These deficits were accompanied by local pro-inflammatory activation of astrocytes and microglia, mitochondrial dysfunction in glial cells, and early disruption of the arcuate nucleus melanocortin system. Limited analyses in hFUS mice confirmed selective hypothalamic vulnerability. Early TMZ treatment in SOD1-G93A mice specifically restored hypothalamic bioenergetics, normalized local glial activation and melanocortin signaling, delayed disease onset, and extended survival.

INTERPRETATION: These findings establish the hypothalamus as an early and selectively vulnerable site in ALS, where region-specific mitochondrial dysfunction contributes to metabolic and neuroinflammatory alterations. Targeting hypothalamic bioenergetics represents a promising therapeutic strategy.},
}

@article {pmid41934600,
year = {2026},
author = {Landers, SE and Sun, Y and Tolegenova, A and McNabb, K and Zhao, Y and Kuskulov, A and Nyblade, L and Tucker, JD and Balabekova, O and Gryazev, D and Mergenova, G and Davis, A and , },
title = {A Content Analysis of Digital Crowdsourced Messages to Reduce HIV Stigma and Promote Testing Among Adolescents and Young Adults in Kazakhstan.},
journal = {AIDS and behavior},
volume = {},
number = {},
pages = {},
pmid = {41934600},
issn = {1573-3254},
support = {R21TW012017//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 2T32 MH078788/MH/NIMH NIH HHS/United States ; K01DA044853/DA/NIDA NIH HHS/United States ; K24AI143471//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {In Kazakhstan, almost a quarter of HIV infections are estimated to be among adolescents and young adults (AYA). However, AYA have low testing rates, partially due to stigma. A nationwide digital crowdsourcing open call invited AYA ages 13-29 years old to create media content that could reduce HIV stigma in order to promote testing among peers. This study examines the format and content of entries to the open call, exploring whether AYA address key points about stigma and testing identified by public health professionals. The content analysis framework was informed by Nyblade et al.'s concept of immediately actionable drivers of stigma: awareness of stigma, fear of HIV acquisition, attitudes, and institutional environment. Additional codes examined content type, tone, AYA-specific appeal, social support, and testing messages. The open call received 96 entries, representing almost all provinces in Kazakhstan. AYA submitted more videos/images (67%) compared to other types of content. Most content was emotive in tone (60%) and included features with AYA-specific appeal (80%). Nearly a third of entries referenced the impact of social support. Eighty-eight percent included at least one driver of stigma; most addressed them in a positive way, but some perpetuated stigmatizing ideas. Finally, 60% explained the importance of HIV testing, mainly focusing on health implications. Findings suggest AYA are willing to submit to open calls and can produce creative, relevant content to address HIV stigma and promote testing. A minority of entries included potentially stigmatizing content, highlighting the importance of a structured, multi-phase judging process in crowdsourcing.},
}

@article {pmid41931746,
year = {2026},
author = {Chalitsios, CV and Rudolf, O and Gao, J and Turner, MR and Thompson, AG},
title = {Long-Term Exposure to Ambient Air Pollution and Incident Amyotrophic Lateral Sclerosis: A Prospective Cohort Analysis of the UK Biobank.},
journal = {Neurology},
volume = {106},
number = {8},
pages = {e214858},
doi = {10.1212/WNL.0000000000214858},
pmid = {41931746},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics/etiology ; Middle Aged ; Female ; Male ; United Kingdom/epidemiology ; *Air Pollution/adverse effects ; Aged ; Prospective Studies ; Adult ; Biological Specimen Banks ; *Environmental Exposure/adverse effects ; Incidence ; Particulate Matter/adverse effects ; Gene-Environment Interaction ; *Air Pollutants/adverse effects ; Cohort Studies ; Nitrogen Oxides ; C9orf72 Protein/genetics ; UK Biobank ; },
abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex etiology. Although a range of genetic and lifestyle factors have been implicated, the potential role of environmental airborne pollution exposure is uncertain. This study examined the association between long-term ambient exposure to air pollutants and the incidence of ALS in UK Biobank participants.

METHODS: This prospective cohort study was based on the UK Biobank participants aged 40-69 years. The analytical sample comprised participants free of ALS at baseline and had complete data on air pollution exposure. Long-term exposure (2006-2021) to nitrogen dioxide (NO2), nitrogen oxides (NOX), fine particulate matter (PM2.5; <2.5 µm), and coarse particulate matter (PM10; <10 µm) was assessed using data from the UK Department for Environment, Food and Rural Affairs at a spatial resolution of 1 × 1 km. To evaluate the association between these pollutants and ALS risk, we used multivariable time-varying Cox proportional hazards models. Several sensitivity analyses were conducted to assess the robustness of the results. We also examined for gene-environment interaction stratified by C9orf72 status and UNC13A genotype.

RESULTS: Among the 501,308 participants with a mean age of 56.5 (SD 8.1) years at baseline, 272,764 (54.4%) were female. Over a median follow-up of 8.4 years, 687 individuals developed ALS. We did not observe any associations for any of the examined pollutants and ALS risk. Specifically, the hazard ratios per SD increment for PM10, PM2.5, NOX, and NO2 were 1.03 (95% CI 0.92-1.15), 1.00 (95% CI 0.88-1.14), 1.01 (95% CI 0.90-1.13), and 1.00 (95% CI 0.89-1.12), respectively. Individuals living in areas with the highest tertile of air pollutant exposure, compared with those in the lowest tertile, did not show a higher risk of ALS across any of the pollutants examined (p for trend >0.05). Restricted cubic spline analyses revealed no nonlinear associations between air pollution and ALS risk (all p for nonlinearity >0.05). These results remained robust in various subgroup and sensitivity analyses. No evidence of gene-environment interaction was found.

DISCUSSION: In this large population-based study with high statistical power, ambient air pollution was not a risk factor for the development of ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/genetics/etiology
Middle Aged
Female
Male
United Kingdom/epidemiology
*Air Pollution/adverse effects
Aged
Prospective Studies
Adult
Biological Specimen Banks
*Environmental Exposure/adverse effects
Incidence
Particulate Matter/adverse effects
Gene-Environment Interaction
*Air Pollutants/adverse effects
Cohort Studies
Nitrogen Oxides
C9orf72 Protein/genetics
UK Biobank

@article {pmid41932459,
year = {2026},
author = {Biscardi, T and Pepe, R and Cortini, E and Luongo, D and Notariale, R and Sharbafshaaer, M and Trojsi, F and Bergamo, P},
title = {Supplementation with Conjugated Linoleic Acid ameliorates the level of some Nrf2-activated systemic markers in patients with amyotrophic lateral sclerosis: a proof-of-principle study.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.03.067},
pmid = {41932459},
issn = {1873-4596},
}

@article {pmid41925964,
year = {2026},
author = {Oriquat, G and H, M and Maharana, L and Dhyani, A and Al-Hasnaawei, S and Singh-Chauhan, A and Arora, V and Sharma, J and Sadeghi-Samarjan, R},
title = {The Gut Microbiome in Amyotrophic Lateral Sclerosis: Emerging Mechanisms and Therapeutic Potential.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41925964},
issn = {1559-1182},
mesh = {*Amyotrophic Lateral Sclerosis/microbiology/therapy ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Dysbiosis ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive loss of motor neurons and a median survival of 2 to 3 years after symptom onset. Despite advances in genetics, particularly the identification of mutations in C9ORF72, SOD1, and TDP 43, substantial variability in disease onset and progression remains unexplained. Mounting evidence points to the gut microbiome as a potential modifier of ALS biology. Microbial communities within the intestine influence systemic and central immune responses, energy metabolism, and the bioavailability of nutrients and therapeutic agents. Animal studies reveal that dysbiosis contributes to intestinal barrier dysfunction, immune activation, and altered metabolite production, while supplementation with beneficial metabolites such as butyrate or nicotinamide can delay disease progression and extend survival. Human studies, though inconsistent in their findings, consistently identify microbial imbalances and loss of diversity in subsets of patients. The gut-brain axis provides a plausible framework for these effects, as microbial products can signal through endocrine, neural, and immune pathways to influence central nervous system function. Beyond motor decline, microbiota alterations may also contribute to non-motor symptoms such as depression, anxiety, and gastrointestinal dysfunction, further shaping quality of life. While methodological variability complicates interpretation, integration of microbiome research with host genomics and metabolomics offers a path toward precision medicine. Targeting microbial composition and function may ultimately represent a novel therapeutic approach capable of modifying both disease biology and patient outcomes in ALS.},
}

*Amyotrophic Lateral Sclerosis/microbiology/therapy
Humans
*Gastrointestinal Microbiome/physiology
Animals
Dysbiosis

@article {pmid41926450,
year = {2026},
author = {Christoforidou, E and Rowe, JS and Simoes, FA and Cassel, R and Dupuis, L and Leigh, PN and Hafezparast, M},
title = {Impaired dynein function preserves spinal interneuron survival and positioning in an ALS-like mouse model.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0346246},
pmid = {41926450},
issn = {1932-6203},
mesh = {Animals ; *Interneurons/metabolism/pathology ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Spinal Cord/metabolism/pathology ; Disease Models, Animal ; Male ; Cell Survival ; *Dyneins/metabolism/genetics ; *Cytoplasmic Dyneins/metabolism/genetics ; },
abstract = {Impaired cytoplasmic dynein function has been implicated in amyotrophic lateral sclerosis (ALS) pathogenesis, yet the contributions of spinal interneurons to disease phenotypes remain unclear. We tested the hypothesis that hypomorphic dynein function in cholinergic neurons disrupts the development, survival, or positioning of inhibitory interneuron populations in the lumbar spinal cord. Using ChAT-Cre recombination, we generated four mouse genotypes with graded reductions in dynein activity in ChAT+ cells: Dync1h1+/+ (wildtype), Dync1h1-/+ (hemizygous wildtype), Dync1h1+/Loa (heterozygous Loa mutation), and Dync1h1-/Loa (hemizygous Loa). At 52 weeks of age, lumbar spinal cords (L3-L6) were harvested, cryosectioned, and immunostained for ChAT, GAD-67, Parvalbumin, and Calbindin. Cell counts were performed on confocal images from eight sections per mouse (N = 3 male mice/genotype), and radial distances from the central canal were normalised to gray matter width. Angular distributions were analysed via circular statistics. There were no significant genotype-dependent differences in the numbers of ChAT+, GAD-67+, Parvalbumin+, or Calbindin+ cells, nor in ChAT+ subpopulations (motor neurons versus interneurons) or double-positive interneuron subsets (e.g., ChAT+-GAD-67+, Parvalbumin+-GAD-67+, Parvalbumin+-Calbindin+). Radial positioning relative to the central canal was similarly preserved across all markers and genotypes. Circular-median tests revealed statistically significant shifts in mean angle for ChAT+, GAD-67+, and certain double-positive cells, but these amounted to only 5-10° displacements, translating to lateral shifts of ~10-20 µm, well within single laminar bands, and are unlikely to impact circuit connectivity. Despite substantial motor deficits and hallmark TDP-43 pathology previously seen in these models, impaired dynein function does not precipitate interneuron loss or gross migratory defects in the lumbar spinal cord. Instead, our findings suggest that the primary contributions of dynein to ALS-like phenotypes likely arise from functional disruptions in axonal transport, synaptic maintenance, and neuronal physiology rather than from structural alterations or loss of interneuron populations.},
}

Animals
*Interneurons/metabolism/pathology
Mice
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*Spinal Cord/metabolism/pathology
Disease Models, Animal
Male
Cell Survival
*Dyneins/metabolism/genetics
*Cytoplasmic Dyneins/metabolism/genetics

@article {pmid41926608,
year = {2026},
author = {Mori, F and Kon, T and Itazawa, R and Akatsu, A and Miki, Y and Arai, A and Kurotaki, H and Tomiyama, M and Wakabayashi, K},
title = {Relationship between promyelocytic leukemia protein nuclear bodies and TAR DNA-binding protein-43 aggregation in spinal anterior horn cells in sporadic amyotrophic lateral sclerosis.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag029},
pmid = {41926608},
issn = {1554-6578},
support = {23K06802 (F.M.), 25K10784 (T.K.), 24K10654 (Y.M.), and 23K24209 (K.W.)//JSPS KAKENHI Grant/ ; },
abstract = {Promyelocytic leukemia protein nuclear bodies (PML-NBs) and stress granules serve as deposition sites for stress-induced, aggregation-prone proteins. We previously reported that TAR DNA-binding protein 43 (TDP-43) colocalizes with stress granules during early aggregation in sporadic amyotrophic lateral sclerosis (ALS), and recent studies have noted PML-NB loss in familial ALS. To explore the role of PML-NBs in TDP-43 inclusion maturation, we analyzed spinal cord specimens from 12 patients with sporadic ALS and 5 controls using immunostaining for PML and TDP-43. PML-NB counts in anterior horn cells (AHCs) were significantly lower in patients with ALS than in controls (P < 0.05), especially in AHCs with TDP-43 inclusions (P < 0.01). Average numbers of PML-NB decreased progressively with inclusion type (3.1 in diffuse punctate cytoplasmic staining, 2.3 in round inclusions, and 0.8 in skein-like inclusions); all of these were significantly lower than those in inclusion-free AHCs (controls: 4.6; ALS: 5.5; P < 0.01). AHCs in ALS without inclusions showed higher PML-NB counts than in controls (P < 0.05), suggesting an early protective response. In contrast, reduced PML-NBs in mature inclusions may reflect diminished cellular defense. These findings implicate PML-NBs in the pathogenesis of sporadic ALS.},
}

@article {pmid41928488,
year = {2026},
author = {Andersen, B and Krarup, C},
title = {Reappraisal of the Diagnostic Significance of Transcranial Magnetic Stimulation and Triple Stimulation in Amyotrophic Lateral Sclerosis.},
journal = {European journal of neurology},
volume = {33},
number = {4},
pages = {e70560},
doi = {10.1111/ene.70560},
pmid = {41928488},
issn = {1468-1331},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; *Transcranial Magnetic Stimulation/methods ; Male ; Middle Aged ; Female ; Evoked Potentials, Motor/physiology ; Aged ; Electromyography ; Adult ; Prospective Studies ; Neural Conduction/physiology ; Motor Neurons/physiology ; },
abstract = {OBJECTIVE: To reassess the importance of transcranial magnetic stimulation (TMS), including the triple stimulation technique (TST), to detect upper motor neuron (UMN) involvement in amyotrophic lateral sclerosis (ALS).

METHODS: In this single-center prospective study, 144 consecutive patients suspected of having motor neuron disease were included over 5 years at the time of diagnosis. All patients were examined clinically and with EMG to assess UMN and lower motor neuron (LMN) involvement, and survival was ascertained 2 years after inclusion of the last patient. Our TMS protocol consisted of TST in both arms and conventional motor evoked potentials (MEP) in arms and legs to assess central motor conduction time (CMCT).

RESULTS: The TST could be performed in 142 patients who showed central conduction failure in 63%, which was often markedly asymmetrical, and 50% had prolonged CMCT in the legs. Combining TST in the arms and conventional MEP in the legs showed central abnormalities in 77%. In 62 patients with only signs of LMN involvement at clinical and EMG assessment, the TST amplitude ratio was reduced in 45%, and combined TST to the arms and conventional MEP to the legs disclosed a central abnormality in 61%.

CONCLUSION: The main clinical significance was the subclinical corticospinal involvement at TMS with TST in a large proportion of patients without clinical UMN involvement. TMS with TST is a sensitive, non-invasive electrophysiological method to detect corticospinal dysfunction in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
*Transcranial Magnetic Stimulation/methods
Male
Middle Aged
Female
Evoked Potentials, Motor/physiology
Aged
Electromyography
Adult
Prospective Studies
Neural Conduction/physiology
Motor Neurons/physiology

@article {pmid41928634,
year = {2026},
author = {Dahshan, A and Khalil, MIM and Deraz, HADA},
title = {From theory to practice: physicians' knowledge, attitudes, and practices regarding amyotrophic lateral sclerosis in Egypt - a cross-sectional study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2652326},
pmid = {41928634},
issn = {2167-9223},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with heterogeneous presentations that often mimic other conditions, leading to frequent misdiagnosis and delayed recognition. Physician awareness and diagnostic confidence are critical for early detection, yet little is known about these factors in the Middle East and North Africa (MENA) region, where ALS services and specialized centers remain limited.

METHODS: We conducted a nationwide cross-sectional survey of 1,320 physicians in Egypt. A validated online questionnaire assessed demographics, knowledge, attitudes, and practice patterns regarding ALS. Data were analyzed using appropriate statistics, with multivariate regression to identify predictors of knowledge, attitudes, and practices.

RESULTS: Overall, 41.0% of physicians demonstrated poor knowledge of ALS, while only 8.8% achieved good knowledge. Nearly half (46.5%) reported little or no diagnostic confidence, and 93.7% expressed a strong need for additional educational programs. Most respondents identified MRI (78.3%) as the main diagnostic test, whereas only 2.0% selected electrophysiological studies. Nevertheless, practice scores were higher: 65.7% reported good practice levels and 48.4% indicated they would directly refer suspected cases to specialists. Knowledge strongly correlated with attitudes (r = 0.610, p < 0.001) and both were moderately correlated with practice. Multivariate analysis identified neurology specialty, postgraduate ALS training, and urban practice as independent predictors of better knowledge and attitudes, while greater experience predicted improved practice.

CONCLUSION: Egyptian physicians show limited ALS knowledge and low diagnostic confidence despite reasonable practice behaviors. Training and structured referral pathways are urgently needed to improve ALS preparedness in Egypt and the wider MENA region.},
}

@article {pmid41928799,
year = {2026},
author = {Ouyang, Z and Walmsley, K and Luo, S and Tippett, D and Wyse-Sookoo, K and Fifer, M and Vansteensel, MJ and Angrick, M and Ramsey, N and Crone, NE},
title = {Stable speech BCI performance during slow progression of ALS: A longitudinal ECoG study.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9156039/v1},
pmid = {41928799},
issn = {2693-5015},
abstract = {Background Electrocorticographic (ECoG) speech brain-computer interfaces (BCIs) show promise for restoring communication in amyotrophic lateral sclerosis (ALS), but the long-term stability of speech-related neural signals and decoding performance during disease progression remains unclear. We tracked signal characteristics and decoding over 25 months in a participant with ALS to determine how high-gamma (HG, 70-170 Hz) activity changes over time and whether these changes affect offline speech decoding. Methods We implanted two 8×8 subdural ECoG grids over left sensorimotor cortex (SMC) in a participant with slowly progressive bulbar variant ALS. Across 25 months, the participant performed an overt syllable-repetition task (12 consonant-vowel tokens) during simultaneous ECoG and audio recording. We quantified HG activation ratio (ActR), spectral signal-to-noise ratio (SNR; HG/HF, where HF = 300-499 Hz), and peak z-scored HG responses. Speech acoustics were evaluated using first/second formants (F1/F2) and the triangular vowel space area (tVSA). Offline EEGNet-based decoders were assessed in two stages: models trained on post-implant months 1-6 were tested on months 7-25, while models trained on stabilized data (months 7-11) were tested on the remaining period (months 12-25). Electrode-level saliency assessed spatial contributions to decoding. Results Acoustic analyses showed a significant reduction in tVSA over two years (-44.6 Hz[2]/day; P < 10 [-] [7]), consistent with mild intelligibility decline. Neural metrics (ActR and SNR) followed a biphasic trajectory: increasing during the first 6 months, after which ActR stabilized (0.041%/day; P = 0.13), and SNR declined gradually (-0.46%/day, P < 10 [- 4]). The model trained on months 1-6 achieved 55.7% accuracy (chance: 8.33%), but performance declined over time (-0.019%/day; P = 2.1×10 [-] [4]). Conversely, the model trained on months 7-11 achieved higher accuracy (65.9%) on subsequent data with no significant temporal decline (P = 0.23). Conclusions Speech-related HG features exhibited an initial unstable period followed by a long-term gradual SNR reduction, potentially reflecting disease progression. Models trained after signal stabilization generalized robustly to data recorded over a year later. These findings confirm that despite reduced absolute HG power and mild acoustic degradation of speech, cortical features remain stable enough to support durable ECoG speech BCIs without frequent recalibration. These findings will motivate future adaptive calibration algorithms that account for slow signal changes while leveraging stable spatial representations in ventral SMC. ClinicalTrials.gov Identifier NCT03567213.},
}

@article {pmid41928938,
year = {2026},
author = {Michels, S and Chen, C and Ruf, WP and Garcia Garcia, MM and Arnold, FJ and Wu, Z and Bennett, CL and Shams, D and Thompson, LM and Walker, AC and Dickson, DW and Petrucelli, L and Dorst, J and Prudencio, M and Li, W and La Spada, AR},
title = {Multimodal analysis of cell-free DNA identifies epigenetic biomarkers for amyotrophic lateral sclerosis diagnosis and progression.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.20.711195},
pmid = {41928938},
issn = {2692-8205},
abstract = {The role of the epigenome in age-related neurodegenerative disorders remains understudied. Here, we analyzed circulating cell-free DNA (cfDNA) from blood to detect methylation changes as a liquid-biopsy for Amyotrophic Lateral Sclerosis (ALS). Our study included 20 patients with sporadic ALS, 10 patients with C9orf72-associated ALS, 10 asymptomatic carriers of the C9orf72 repeat expansion mutation, and 21 non-disease controls. Following targeted enzymatic methyl-sequencing (EM-seq) of ∼4 million CpG sites, we detected numerous differentially methylated genes, including several implicated in ALS disease risk and pathogenesis. By integrating multiple epigenetic features, we delineated a distinct epigenetic signature, which achieved an average area under the curve (AUC) of 0.91 ± 0.10 upon receiver operator characteristic (ROC) analysis, which enabled detection of ∼70% of ALS patients with close to 100% specificity. Furthermore, we also identified a set of genes whose methylation status significantly correlated with clinical disease progression and cerebrospinal fluid (CSF) neurofilament levels. Our results reveal the potential of cfDNA-based biomarkers to accurately diagnose ALS and potentially predict disease progression.},
}

@article {pmid41929081,
year = {2026},
author = {Fodder, K and Murthy, M and de Silva, R and Raj, T and Farrell, K and Humphrey, J and Bettencourt, C},
title = {Cross-disease genetic and epigenetic architecture of the MOBP locus shows convergence in ALS-PSP.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.25.714147},
pmid = {41929081},
issn = {2692-8205},
abstract = {Myelin oligodendrocyte basic protein (MOBP) is an abundant oligodendrocyte gene implicated in multiple neurodegenerative diseases. Genetic variation at the MOBP locus has been associated with risk for progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTD), corticobasal degeneration (CBD), Alzheimer's disease (AD), Lewy body dementia (LBD), and Creutzfeldt-Jakob disease (CJD). Epigenetically, MOBP promoter hypermethylation and reduced expression have been reported in multiple system atrophy (MSA). Although MOBP is thought to play a role in oligodendrocyte morphology and myelin structure, how genetic and epigenetic variation at this locus influences gene regulation and contributes to disease risk remains poorly understood across neurodegenerative disorders. Here, we investigated whether shared or disease-specific genetic mechanisms at MOBP converge on altered DNA methylation and expression across neurodegenerative disorders. We analysed MOBP variants using summary statistics from recent GWAS for ALS, PSP, FTD, LBD, PD, MSA, AD, and CJD. Colocalisation (COLOC and SuSiE-coloc) was used to test whether disease-associated variants overlapped between diseases, and with oligodendrocyte expression quantitative trait loci (eQTLs) and bulk brain methylation quantitative trait loci (mQTLs). To further investigate mQTL effects at this locus, rs1768208, a variant previously associated with PSP, was genotyped in an overlapping brain methylation cohort, allowing direct testing of genotype-methylation associations in frontal white matter tissue. ALS and PSP GWAS demonstrated strong association at MOBP , with most strongly associated SNPs (e.g. rs631312, rs616147, rs1768208) shared between both disorders. Colocalisation analyses indicated high posterior probability that ALS and PSP share the same causal variant, with weaker overlap with FTD. mQTL colocalisation highlighted cg15069948, located near an exon junction within MOBP , as strongly colocalising with the ALS/PSP risk variants. In complementary tissue analyses, rs1768208-T carriers showed hypomethylation at cg15069948 in PSP brains. No genotype-methylation effects were detected in MSA or Parkinson's disease. Together with prior evidence of promoter hypermethylation and reduced expression in MSA, our findings identify cg15069948 as a regulatory methylation site linking ALS/PSP risk variants to altered MOBP methylation, and support MOBP dysregulation as a shared feature of neurodegeneration. However, the underlying mechanisms appear disease-specific, highlighting the complexity of involvement of this gene across neurodegenerative disorders.},
}

@article {pmid41929167,
year = {2026},
author = {Mahrous, AA and Heit, BS and Heckman, CJ},
title = {Riluzole treatment paradoxically increases motoneuron excitability in ALS due to hyperactive homeostasis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.23.713695},
pmid = {41929167},
issn = {2692-8205},
abstract = {Riluzole is the most commonly prescribed among the limited approved therapies for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by progressive motoneuron loss and paralysis. It is thought to act by suppressing motoneuron excitability and glutamate release, but its clinical benefits are modest and often diminish over time. We previously showed that homeostatic mechanisms in the SOD1 [G93A] (mSOD1) mouse model of ALS are hyperactive and prone to overcompensation. Here, we tested whether such dysregulated homeostasis antagonizes the effects of riluzole. Wild-type (WT) and presymptomatic mSOD1 mice received therapeutic doses of riluzole in drinking water for 10 days, with untreated littermates of both genotypes serving as controls. Motoneuron excitability and synaptic inputs were then examined using intracellular recordings from the isolated sacral spinal cord. The data showed that chronic riluzole treatment increased motoneuron excitability and polysynaptic inputs in mSOD1 mice but produced no detectable changes in WT motoneurons. These results suggest that hyperactive homeostatic mechanisms in ALS counteract the suppressive effects of riluzole. Notably, mSOD1 motoneurons exhibited larger membrane capacitance than WT, consistent with their increased cell size at this disease stage. Riluzole treatment reduced motoneuron membrane capacitance in mSOD1 mice to the range observed in WT animals, indicating normalization of cell size and potentially reduction in metabolic demand. Together, these findings help explain the limited clinical efficacy of riluzole while revealing a previously unrecognized neuroprotective mechanism of the drug in ALS.},
}