@article {pmid42473037,
year = {2026},
author = {Ban, Y and Wang, T and Zhang, Z and Yuan, WQ and Zhang, M and Shi, K and Li, C and Feng, Z},
title = {Tribenuron-methyl resistance in catchweed bedstraw (Galium aparine): status and MIRA-based rapid detection of ALS D376E mutation.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71132},
pmid = {42473037},
issn = {1526-4998},
support = {2023YFD1400500//National Key Research and Development Program of China/ ; 32372567//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Catchweed bedstraw (Galium aparine) is a highly competitive malignant broadleaf weed that significantly reduces the yield and quality in wheat and rapeseed cropping systems. The prolonged and exclusive use of tribenuron-methyl has led to widespread resistance development, posing a significant threat to the sustainability of weed management practices. To enable timely intervention and support evidence-based decision-making, systematic monitoring of resistance status and the development of a rapid, reliable detection method are urgently required.

RESULTS: We collected 113 populations of G. aparine from major wheat-growing regions across China, among which 83 populations were found to be resistant to tribenuron-methyl. The sequencing of the ALS gene revealed six distinct mutation patterns at sites P197, D376 and W574 within resistant populations, among which D376E was the most frequently observed. To enable rapid field resistance monitoring, the multienzyme isothermal rapid amplification (MIRA) assay was developed for detecting the D376E mutation. This new detection system can assess target-site resistance within 80 min at a constant temperature of 39 °C.

CONCLUSION: This study investigated tribenuron-methyl resistance in 113 G. aparine populations from various provinces of China and generated a comprehensive resistance distribution map. The MIRA-based method for rapidly detecting the ALS D376E substitution in G. aparine was developed. Collectively, our study provides valuable knowledge and a practical tool for the management of G. aparine. © 2026 Society of Chemical Industry.},
}

@article {pmid42473039,
year = {2026},
author = {Koppisetti, RK and Barthélemy, NR and Horie, K and Ly, CV and Roberts, KF and Koutarapu, S and Perrin, RJ and Franklin, EE and Pedicone, C and Orrick, J and Melendez, J and Miller, TM and Sato, C and Ghoshal, N and Goate, AM and Karch, CM and Bateman, RJ and Mukherjee, S},
title = {Distribution of Big Tau Isoforms in the Human Central and Peripheral Nervous System.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78300},
pmid = {42473039},
issn = {1531-8249},
support = {UL1TR004419/TR/NCATS NIH HHS/United States ; 1U54NS123746-01/NS/NINDS NIH HHS/United States ; R01NS095773/NS/NINDS NIH HHS/United States ; R01NS110890/NS/NINDS NIH HHS/United States ; U54NS123985/NS/NINDS NIH HHS/United States ; P41GM103422/GM/NIGMS NIH HHS/United States ; P01AG026276/AG/NIA NIH HHS/United States ; P01AG03991/AG/NIA NIH HHS/United States ; P30AG066444/AG/NIA NIH HHS/United States ; },
abstract = {OBJECTIVE: Tau is widely studied in neurodegeneration, yet most work has focused on canonical brain tau isoforms. A longer isoform, "big tau," produced by inclusion of exon 4a, is expressed in the peripheral nervous system (PNS) and central nervous system (CNS) regions. We sought to characterize big tau composition, anatomic distribution, and disease relevance.

METHODS: Mass spectrometry (MS) was used to sequence big tau and map its distribution across the human nervous system. Postmortem samples included brain tissue from Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and controls; spinal cord and peripheral nerves. Big and canonical ("small") tau isoforms were also quantified in cerebrospinal fluid (CSF) from controls and participants stratified by amyloid status and cognitive impairment.

RESULTS: Human big tau results from insertion of either 355 or 251 amino acids encoded by exon 4a-long and exon 4a-short, respectively. Alternative splicing of exons 2, 3, and 10 generates multiple big tau isoforms. Total tau levels were approximately 1,000-fold higher in the brain than in the PNS; however, the relative abundance of big tau increased from the CNS to the PNS, comprising 50% of the total tau in the periphery and approximately 1% in the brain, primarily localized to the cerebellum. In CSF, big tau levels were unchanged by amyloid abnormalities or cognitive impairment, whereas canonical tau increased with AD pathology.

INTERPRETATION: Big tau represents a distinct tau population enriched in the PNS and uncoupled from disease-associated changes in brain-derived tau, suggesting that distinguishing big tau from canonical tau may improve interpretation of tau biomarkers and help differentiate CNS neurodegeneration from peripheral nerve pathology. ANN NEUROL 2026.},
}

@article {pmid42473218,
year = {2026},
author = {Keskin, A and Mogulkoc, R and Baltaci, AK},
title = {Relationship Between miRNA and Neurodegenerative Diseases Such as Alzheimer's disease, Parkinson's, Huntington's disease, Amyotrophic Lateral Sclerosis.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575484348260702044851},
pmid = {42473218},
issn = {1875-5607},
abstract = {The regulatory roles of miRNAs on CNS homeostasis, neuronal differentiation, and synaptic plasticity make these molecules indispensable for healthy brain functions. miRNA dysregulation, by triggering abnormal neurodevelopment, has a critical impact on the etiology and progression of neurodegenerative diseases. MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, 18 to 24 nucleotides long. They play a role in posttranscriptional gene regulation by binding to complementary sequences on messenger RNA (mRNA), thereby promoting mRNA degradation or preventing translation into protein. MiRNAs are essential regulators of the genome because they bind targets and alter gene expression. MiRNA biogenesis and functions are tightly regulated, and their dysregulation is associated with various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. In particular, disruption of the Blood-Brain Barrier in neurodegenerative diseases allows molecules to leak into the bloodstream, enabling the detection of miRNAs in other body fluids and making these fluids potential biomarker sources. In this context, miRNAs can be measured in blood, cerebrospinal fluid, and other biological samples. It has significant potential for early diagnosis, disease progression monitoring, and evaluation of treatment efficacy. In this review, the relationship between MiRNAs and neuronal degeneration diseases was evaluated. In this review, prepared in light of the current literature scanned through the PubMed database, we examined data from the last 5 years (2021-2026) on neurodegenerative diseases associated with miRNA dysregulation, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD).},
}

@article {pmid42473814,
year = {2026},
author = {Shao, D and Wen, X and Xu, X and Liu, X and Guo, B and Li, B and Wang, G and Liu, X and Men, S},
title = {Cyprosulfamide mitigates nicosulfuron phytotoxicity in maize through activation of GST-associated phase II detoxification involving ZmGST24.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71142},
pmid = {42473814},
issn = {1526-4998},
support = {32370271//National Natural Science Foundation of China/ ; 2026KJCXZX-LYS-14//HAAFS Agriculture Science and Technology Innovation Project/ ; 254Z6303G//Project of Central Guidance for Local Science and Technology Development Funds/ ; 23JCYBJC01180//Natural Science Foundation of Tianjin/ ; 24YFXTHZ00050//Key Research and Development Program of Tianjin/ ; },
abstract = {BACKGROUND: Nicosulfuron is an acetolactate synthase (ALS)-inhibiting herbicide widely used in maize production. However, under unfavorable environmental conditions, its phytotoxicity to maize remains a practical concern. Cyprosulfamide (CSA) is an effective safener for maize, yet the contribution of glutathione S-transferases (GST)-associated phase II detoxification to CSA-conferred protection against nicosulfuron injury remains poorly understood.

RESULTS: CSA markedly alleviated nicosulfuron-induced growth inhibition in maize seedlings and effectively reduced herbicide injury under field conditions. Inhibitor assays showed that both cytochrome P450-mediated phase I metabolism and GST-associated phase II detoxification contribute to maize tolerance to nicosulfuron. Proteomic analysis further revealed that, relative to nicosulfuron treatment alone, co-application of nicosulfuron and CSA significantly enriched the glutathione metabolism pathway in maize leaves. Among the induced GST candidate genes, ZmGST24 showed the strongest transcriptional response. Phylogenetic and conserved motif analyses supported its functional similarity to previously reported GSTs involved in herbicide detoxification. Molecular docking suggested favorable binding of ZmGST24 to nicosulfuron, and heterologous expression in yeast demonstrated that ZmGST24 not only enhanced tolerance to nicosulfuron, but also increased tolerance to several herbicides commonly used in maize fields.

CONCLUSION: These findings indicate that the protective effect of CSA against nicosulfuron phytotoxicity in maize is associated with activation of GST-associated phase II detoxification. The pronounced response of the glutathione metabolism pathway, together with the functional characterization of ZmGST24, identifies this gene as a promising candidate involved in CSA-induced herbicide tolerance and as a potential target for improving herbicide safety in maize. © 2026 Society of Chemical Industry.},
}

@article {pmid42474734,
year = {2026},
author = {Zheng, Y and Bhalala, OG and Chin, KS and Watson, R and Yassi, N},
title = {Use of blood-based neurofilament light chain as an endpoint in clinical trials of neurodegenerative conditions: a scoping review.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42474734},
issn = {1432-1459},
mesh = {Humans ; *Neurofilament Proteins/blood ; *Neurodegenerative Diseases/blood/diagnosis ; Biomarkers/blood ; *Clinical Trials as Topic ; },
abstract = {INTRODUCTION: Neurofilament light chain (NfL) is a structural axonal protein measurable in CSF and blood, increasingly investigated as a biomarker of neuroaxonal injury in clinical and research contexts. This review aims to explore the use of blood-based NfL as an endpoint in clinical trials of neurodegenerative conditions.

METHOD: A database search of MEDLINE and EMBASE was conducted to identify interventional clinical trials and/or related post hoc analyses for neurodegenerative diseases, published between 2013 and 2024 that reported the use of serum or plasma NfL as an endpoint. Additional studies from reference lists of included trials were manually considered for inclusion where relevant. Data were charted descriptively by disease type and summarised.

RESULTS: 49 studies were included, 29 in multiple sclerosis (MS), eight in amyotrophic lateral sclerosis (ALS), six in Alzheimer's disease (AD), and six in other diseases. Across studies, reductions in NfL often paralleled improvements in primary efficacy outcomes, supporting its use as a biomarker of disease activity and treatment response. However, several studies demonstrated a lack of concordance between change in NfL and in clinical outcomes, some of which may be related to the non-disease-modifying mechanisms of the interventions studied. This necessitates careful consideration when applying blood-based NfL as a biomarker endpoint for studies involving such interventions.

CONCLUSION: Blood NfL is a promising biomarker with potential utility as a surrogate endpoint in neurological clinical trials, particularly for diseases with active axonal injury. Further validation, particularly around disease- and intervention-specific interpretation, is needed before blood NfL can be incorporated more routinely as a clinical endpoint.},
}

Humans
*Neurofilament Proteins/blood
*Neurodegenerative Diseases/blood/diagnosis
Biomarkers/blood
*Clinical Trials as Topic

@article {pmid42475136,
year = {2026},
author = {Evans, NG},
title = {Mapping the Scientific Mesolevel: Where Are We Aiming?.},
journal = {The Hastings Center report},
volume = {56},
number = {4},
pages = {48-50},
pmid = {42475136},
issn = {1552-146X},
support = {OT2OD032644/NH/NIH HHS/United States ; },
mesh = {Humans ; *Ethics, Research ; *Science/ethics/organization & administration ; },
abstract = {Susan Wolf et al.'s article "Filling the Network Gap in Research Ethics: Analyzing Ethical Issues at Scale in Big Team Science" aims to provide analysis of ethics at the level of scientific teams. But is the emphasis on formal teams the appropriate target? In this commentary, I argue that we ought to take a much broader view, looking at the "interstitial spaces" of scientific research, including the informal networks of power and esteem that shape scientific careers, the formation and function of large teams, receipt of funding, and publication. I claim that these informal networks do as much, if not more than, formal organizing efforts in structuring scientific inquiry and norms. I conclude that an ethics of team science will be richer, more rigorous, and more effective if it treats the culture of science as a central object of study and then asks which kinds of formal organizing principles best promote and protect our ethical commitments.},
}

Humans
*Ethics, Research
*Science/ethics/organization & administration

@article {pmid42475592,
year = {2026},
author = {Haim, G and Hornstein, E},
title = {The dual face of miR-146a in ALS.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {30},
pages = {e2617170123},
doi = {10.1073/pnas.2617170123},
pmid = {42475592},
issn = {1091-6490},
}

@article {pmid42476327,
year = {2026},
author = {Pattnaik, PP and Prusty, SK and Pati, S and Jew, KA and Bora, AK and Sahoo, J and Sahu, PK},
title = {Exploring shared genetic pathways and gene interplay in major neurodegenerative diseases: a comprehensive review.},
journal = {Gene},
volume = {1010},
number = {},
pages = {150318},
doi = {10.1016/j.gene.2026.150318},
pmid = {42476327},
issn = {1879-0038},
abstract = {Neurodegenerative diseases are progressive disorders that involve the loss and dysfunction of neurons. Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, Frontotemporal dementia are examples of diseases. While different clinically, these disorders have a common genetic, molecular and cellular basis. This review examines the common genetic pathways, along with the interactions between genes of major neurodegenerative diseases, with a focus on the key genes, such as APOE, SNCA, MAPT, TARDBP, LRRK2 and HTT. The common pathogenic mechanisms considered to play a major role in disease progression include protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation, diminished autophagy, and impaired lysosomal function, as well as synaptic degeneration. The review also emphasizes the role of systems biology strategies, such as genome-wide association studies, transcriptomics, proteomics, metabolomics, interactome analysis, and multi-omics integration, to unveiling complex molecular networks in neurodegeneration. Furthermore, the emerging biomarker strategies and therapeutic strategies targeting convergence signaling pathways including NF-κB, PI3K-Akt-mTOR, MAPK and Wnt/β-catenin are summarized. The common genetic basis and the cross-connecting molecular mechanisms of the various neurodegenerative diseases could help in the discovery of new biomarkers and pan-therapeutic targets. Further advances in molecular genetics, computational biology and precision medicine are needed to enhance early detection and the creation of effective disease-modifying treatments.},
}

@article {pmid42476836,
year = {2026},
author = {Mathis, S and Le Masson, G},
title = {When algorithms speak first: The public health risk of consumer AI in ALS diagnosis.},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {126098},
doi = {10.1016/j.jns.2026.126098},
pmid = {42476836},
issn = {1878-5883},
abstract = {BACKGROUND: Consumer AI platforms are increasingly used by patients to interpret medical reports, including ENMG results for ALS. While AI shows promise in controlled clinical settings (e.g., stroke imaging, melanoma detection), consumer-facing tools often provide overconfident, context-free diagnostic assertions (e.g., 'definitive evidence of ALS'), leading to premature and potentially harmful life-altering decisions.

OBJECTIVE: To highlight the clinical, ethical, and regulatory risks of unregulated AI in ALS diagnosis and propose actionable solutions.

DISCUSSION: We present a case of AI-mediated misdiagnosis, analyze the limitations of consumer-facing AI (lack of clinical context, longitudinal data, and specialist oversight), and discuss the "authority paradox" (patients trusting AI outputs over clinicians' nuanced assessments). We propose a structured 4-step clinical approach for managing AI-mediated self-diagnoses and urge regulators to classify such tools as high-risk under the EU AI Act.

CONCLUSION: The uncritical adoption of consumer AI in ALS diagnosis represents a public health risk. Clinicians, regulators, and developers must collaborate to ensure AI serves patients safely and ethically.},
}

@article {pmid42477767,
year = {2026},
author = {Zhang, H and Li, C and Yu, J and Liang, Y and Wu, Y and Cao, F},
title = {Unraveling the role of lipid metabolism in ALS risk: a Mendelian randomization analysis using GWAS data.},
journal = {Orphanet journal of rare diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13023-026-04503-2},
pmid = {42477767},
issn = {1750-1172},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Lipid metabolism is closely related to neuronal function and energy homeostasis, but the genetic association between specific lipid species and ALS risk remains unclear.

OBJECTIVE: This study aimed to investigate the potential causal associations between genetically predicted lipid species and ALS risk using a two-sample Mendelian randomization (MR) approach.

METHODS: Summary-level GWAS data for 179 lipid species were obtained from 7,174 Finnish participants in the GeneRISK cohort. ALS GWAS data included 29,612 ALS cases and 122,656 controls. The inverse variance weighted (IVW) method was used as the primary MR approach, supplemented by MR-Egger, weighted median, weighted mode, and simple mode analyses. False discovery rate (FDR) correction was applied across all lipid traits based on IVW P values. Sensitivity analyses were conducted to assess heterogeneity, horizontal pleiotropy, and robustness.

RESULTS: After FDR correction, genetically predicted higher levels of diacylglycerol (DAG) (18:1_18:1), phosphatidylcholine (PC) (16:1_18:1), PC (18:0_18:1), phosphatidylethanolamine (PE) (O-16:1_18:2), and several triacylglycerol (TAG) species were associated with increased ALS risk. Phosphatidylinositol (PI) (16:0_18:1) showed only a nominal protective association and did not remain significant after FDR correction. Sensitivity analyses did not indicate substantial heterogeneity or horizontal pleiotropy.

CONCLUSION: This MR study provides genetic evidence supporting potential associations between specific lipid species and ALS risk. These findings highlight lipid metabolism as a relevant pathway in ALS susceptibility.},
}

@article {pmid42477825,
year = {2026},
author = {Brenner, D and Ponomarenko, A and Petrut, I and Beyrle, S and Contardo, M and Loss, I and Radke, C and Frank, J and Zimmer, E and Schlesner, M and Achenbach, P and Scheveneels, W and Aly, A and Nazlican, H and Hesebeck-Brinkmann, J and Oeckl, P and Müller, K and Siebert, R and Böckers, T and van Eijk, K and Veldink, J and Kleger, A and Mulaw, M and Andersen, PM and Forsberg, K and Weishaupt, JH and Loghmani, SB and Grehl, T and van Damme, P and Weis, J and Catanese, A},
title = {Correction: A rare missense variant impacting NEK1 kinase function is associated with ALS.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42477825},
issn = {2051-5960},
}

@article {pmid42479532,
year = {2026},
author = {Khan, JS and Mohammadi, M and Ammitzboll, AL and Hagen, EM and Blicher, J and Obai, I and Cardoso, ASS and Kirtas, O and Kaeseler, RL and Rasmussen, J and Struijk, LNSA},
title = {A Tendon-Driven Wrist Abduction-Adduction Joint Improves Performance of a 5 DoF Upper Limb Exoskeleton - Implementation and Experimental Evaluation.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2026.3715599},
pmid = {42479532},
issn = {1558-2531},
abstract = {OBJECTIVE: Wrist function is essential in performing activities of daily living (ADLs). However, there is limited experimental evidence on the functional impact of wrist Abduction-Adduction (Ab-Ad) joint assistance in upper limb exoskeletons (ULEs) during ADLs. This study provides the first implementation and demonstration of a clock spring-based wrist Ab-Ad joint into a five degree of freedom (DoF) ULE, EXOTIC2 exoskeleton and evaluates its effect, to support individuals with severe motor impairments.

METHODS: A compact, lightweight wrist module with tendon-driven abduction and spring-driven adduction was integrated into the EXOTIC exoskeleton. Eight adults with no motor disabilities completed drinking and scratching tasks under randomized wrist-enabled and wrist-locked conditions along with a preliminary feasibility test in one individual with Amyotrophic lateral sclerosis (ALS). Kinematic and task performance metrics including wrist range of motion, task completion time, spillage and leveling metrics were assessed.

RESULTS: Implementing the wrist Ab-Ad DoF improved task success metrics. Spill incidence during the drinking task decreased from 56% to 3%, and leveling success for scratching task improved from 28% to 75%.

CONCLUSION: Integrating wrist Ab-Ad assistance improved key functional task outcomes without increasing execution time.

SIGNIFICANCE: The study provides the experimental evidence that active wrist Ab-Ad control enhances task-level performance in exoskeleton-assisted ADLs and supports the inclusion of wrist deviation in future assistive exoskeletons.},
}

@article {pmid42479906,
year = {2026},
author = {Tahedl, M and Siah, WF and Lope, J and Hengeveld, JC and Doherty, MA and McLaughlin, RL and Hardiman, O and Tan, EL and Toomey, A and Kleinerova, J and Bede, P},
title = {Neurotransmitter-Defined Degeneration Patterns in Sporadic and C9orf72-Associated Amyotrophic Lateral Sclerosis: Predilection to GABAergic, Serotonergic, Opioid, Glutamatergic, Endocannabinoid, and Microglial Systems-Implications for Therapy Development.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78316},
pmid = {42479906},
issn = {1531-8249},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) has a markedly distinctive clinical and neuroradiological signature, with the preferential involvement of specific brain networks and the apparent sparing of others. The molecular underpinnings of the strikingly selective anatomical vulnerability have not been fully elucidated to date despite the potential therapeutic relevance of characterizing neurotransmitter receptor-defined susceptibility to degeneration.

METHODS: A large neuroimaging study was undertaken with 258 participants to systematically evaluate topological associations between neurodegeneration and neurotransmitter expression distributions. Patients were stratified based on their genetic profile into sporadic and C90rf72 hexanucleotide repeat expansion carriers. Anatomical associations were evaluated between patterns of atrophy and topological neurotransmitter receptor distributions. Cross-sectional and longitudinal trends were comprehensively evaluated over 4 consecutive timepoints.

RESULTS: Our analyses reveal topological associations between neurodegeneration in sporadic ALS and GABA-A receptor α5-selective component (GABAa5), serotonin 1a receptor, and kappa opioid receptor expression maps. In addition to these networks, neuronal loss in patients with GGGGCC hexanucleotide repeat expansions exhibit predilection to glutamatergic, endocannabinoid, and microglial systems. Our multi-timepoint longitudinal analyses reveal dynamic temporal associations between focal volume loss and neurotransmitter expression with increasing spatial associations with noradrenaline transporter and GABAa5, but high attrition rates preclude definite longitudinal inferences.

INTERPRETATION: Our data suggest the preferential vulnerability of GABAergic, serotonergic, kappa opioid mediated networks in sporadic ALS. In C9orf72-assocaited ALS, glutamatergic, endocannabinoid circuits are also susceptible and microglia-mediated neuroinflammation is also implicated. The comprehensive evaluation of neurotransmitter-receptor associations not only offer academic insights regarding pathophysiological processes in ALS, but may inform targeted therapy development strategies. ANN NEUROL 2026.},
}

@article {pmid42471133,
year = {2026},
author = {Rojano-Delgado, A and Sohrabi, S and Gherekhloo, J and Domínguez-Valenzuela, JA and Palma-Bautista, C and Alcántara-de la Cruz, R and De Prado, R},
title = {Evolution of multiple resistance under long-term herbicide exposure reshapes Mediterranean perennial agroecosystems.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {128781},
doi = {10.1016/j.envpol.2026.128781},
pmid = {42471133},
issn = {1873-6424},
abstract = {Decades of intensive herbicide use in perennial cropping systems have imposed substantial environmental pressures and accelerated the evolution of herbicide-resistant weed populations. In Andalusia (southern Spain), citrus and olive orchards rely heavily on glyphosate and other herbicide modes of action, resulting in chronic ecosystem exposure, declining herbicide efficacy, and increasing chemical inputs. We surveyed ten dominant weed species across eleven orchards to characterize resistance patterns and investigate underlying physiological mechanisms relevant to environmental persistence and contaminant cycling. Rapid screening assays using six widely applied herbicides (atrazine, 2,4-D, glyphosate, oxyfluorfen, quizalofop-ethyl, and tribenuron-methyl) revealed widespread multiple and cross-resistance in both dicots and monocots. Amaranthus albus, A. viridis, Conyza bonariensis, and Solanum nigrum displayed resistance to atrazine, glyphosate, and tribenuron-methyl, while Lolium rigidum and Sorghum halepense showed broad-spectrum resistance involving target-site alterations and enhanced metabolic detoxification, partially reversed by the cytochrome P450 inhibitor malathion. Complementary biochemical assays targeting PSII, ALS, ACCase, and EPSPS, together with diagnostic tests for PPO- and auxin-related herbicides, indicated diverse non-target-site resistance pathways, suggesting increased herbicide transformation and altered degradation dynamics in soil-plant systems. The emergence of complex resistance mechanisms reflects prolonged selection pressure from intensive herbicide regimes and implies elevated risks of environmental accumulation, off-target effects, and reduced sustainability of chemical-based weed control. These findings highlight the need to reduce herbicide dependence and adopt integrated weed management strategies that minimize pollutant loads in Mediterranean agroecosystems.},
}

@article {pmid42471678,
year = {2026},
author = {Ekowa, JL and Onyekwelu, AI and Fatai, KE},
title = {Physiotherapy and rehabilitation for survivors of female genital mutilation/cutting: a scoping review.},
journal = {BMC women's health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12905-026-04708-4},
pmid = {42471678},
issn = {1472-6874},
abstract = {BACKGROUND: Female genital mutilation/cutting (FGM/C) affects more than 230 million girls and women worldwide and is associated with chronic pelvic pain, pelvic floor dysfunction, lower urinary tract symptoms, psychosexual dysfunction, and reduced quality of life. Although physiotherapy and rehabilitation may contribute to multidisciplinary care, the available evidence has not been comprehensively synthesised.

OBJECTIVE: To map the existing evidence on physiotherapy and rehabilitation for women living with FGM/C and identify evidence gaps relevant to clinical practice and future research.

METHODS: A scoping review was conducted following the Arksey and O'Malley framework, Levac et al.'s methodological enhancements, and PRISMA-ScR guidelines. Electronic databases and grey literature were searched from inception to January 2026. Eligible studies included adolescent (≥ 15 years) and adult women living with FGM/C, together with rehabilitation-relevant studies involving healthcare professionals. Data were charted and synthesised narratively.

RESULTS: Of 872 records identified, 21 studies met the inclusion criteria. Most evidence was observational or descriptive, with only one randomized controlled trial and one rehabilitation-focused case report directly evaluating rehabilitation interventions. Frequently reported rehabilitation-related impairments included psychosexual dysfunction, chronic pelvic pain, pelvic floor dysfunction, lower urinary tract symptoms, dyspareunia, and reduced quality of life. Reported rehabilitation approaches included pelvic floor rehabilitation, bladder retraining, biofeedback, psychosexual rehabilitation, and multidisciplinary care. Only one study included adolescents, and none specifically evaluated rehabilitation interventions for this population.

CONCLUSION: Women living with FGM/C experience substantial rehabilitation needs affecting physical, psychosexual, urinary, and psychosocial health. Although physiotherapy and rehabilitation are increasingly recognised as important components of multidisciplinary care, direct evidence evaluating rehabilitation interventions remains limited. Future research should prioritise rehabilitation-focused intervention studies, implementation research, and standardised outcome measures to strengthen the evidence base and inform comprehensive, survivor-centred care.},
}

@article {pmid42471754,
year = {2026},
author = {Xia, CA and Salarian, M and Gartshore, CJ and Scaglione, A and Hayes, T and Liu, S and Tsai, HM and Echavarren, J and Cid, JM and Matzeu, A and Szardenings, AK},
title = {Development and characterization of a novel TDP-43 positron emission tomography tracer: [[18]F]JNJ-TDP43-1.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71675},
pmid = {42471754},
issn = {1552-5279},
support = {//Johnson & Johnson/ ; },
mesh = {Animals ; *Positron-Emission Tomography/methods ; *DNA-Binding Proteins/metabolism ; *Brain/diagnostic imaging/metabolism ; Rats ; Mice ; Humans ; Male ; Disease Models, Animal ; TDP-43 Proteinopathies/diagnostic imaging ; *Radiopharmaceuticals/pharmacokinetics ; Fluorine Radioisotopes ; },
abstract = {INTRODUCTION: Neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), limbic-predominant age-related TDP-43 encephalopathy (LATE), and Alzheimer's disease (AD) are associated with TAR DNA-binding protein 43 (TDP-43) pathology. A positron emission tomography (PET) tracer targeting TDP-43 aggregates could improve early diagnosis and guide treatment development for TDP-43-related conditions.

METHODS: Specific binding was evaluated using fluorescent labeling of compound, surface plasmon resonance (SPR), and autoradiography (ARG). Brain PET imaging in rats, nonhuman primate (NHP), and a disease mouse model was performed to characterize tracer pharmacokinetics and in vivo target binding.

RESULTS: JNJ-TDP43-1 exhibited high binding affinity for pathological TDP-43 (Kd = 7.1 nM) and remarkable selectivity over other proteinopathies. PET imaging demonstrated robust brain uptake and rapid washout in rodents and NHP. In vivo target engagement was confirmed in an AAV-hTDP43 disease model.

DISCUSSION: [[18]F]JNJ-TDP43-1 is a promising PET ligand for early diagnosis and evaluating therapies in TDP-43-related diseases.},
}

Animals
*Positron-Emission Tomography/methods
*DNA-Binding Proteins/metabolism
*Brain/diagnostic imaging/metabolism
Rats
Mice
Humans
Male
Disease Models, Animal
TDP-43 Proteinopathies/diagnostic imaging
*Radiopharmaceuticals/pharmacokinetics
Fluorine Radioisotopes

@article {pmid42472717,
year = {2026},
author = {Fowler, C and Kaelber, DC and Bliwise, DL and Greer, MK},
title = {Rapid Eye Movement Sleep Suppressing Antidepressant Prescription is Associated with Improved Survival in Amyotrophic Lateral Sclerosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {8},
pages = {},
pmid = {42472717},
issn = {1590-3478},
support = {UM1TR004528//Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/drug therapy ; Female ; Male ; *Antidepressive Agents/therapeutic use/pharmacology ; *Riluzole/therapeutic use ; Middle Aged ; *Sleep, REM/drug effects ; Aged ; },
abstract = {INTRODUCTION: Rapid eye movement (REM) sleep is a period of physiological vulnerability for patients with neuromuscular disease, owing to a generalized loss of muscle tone that spares only the diaphragm. Several antidepressants have been observed to reduce REM sleep fraction on polysomnography. We investigated whether prescription of REM-suppressing antidepressants (RSAs) versus non-REM-suppressing antidepressants (NRSAs) is associated with differential survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: Using the U.S. Collaborative Network of the TriNetX Analytics platform, we compared 1-year mortality in ALS patients prescribed RSAs or NRSAs within 3 months of diagnosis, identified by ICD-10-CM-coded encounter diagnoses with riluzole prescription between May 2014 and May 2024. We used Cox proportional hazards models, Kaplan-Meier analysis, and risk difference analysis, with and without propensity score matching (PSM).

RESULTS: Among 14,441 patients with ALS and riluzole prescription, 5,057 were prescribed either RSAs (N = 4,177) or NRSAs (N = 880). The NRSA cohort had a higher risk of death (HR 1.28, 95% CI 1.11 - 1.46), with 1-year survival of 60.73% versus 68.61% for RSAs (log-rank p<0.001). After PSM, the difference narrowed and was borderline by log-rank test (60.97% vs 65.92%, p=0.035), while the risk-difference analysis was no longer significant (RR 1.07, 95% CI 0.92 - 1.25), indicating an attenuated and statistically fragile association.

CONCLUSIONS: RSA prescription was associated with modestly better survival, but this association weakened markedly after matching and cannot establish causation; residual confounding, particularly by indication, cannot be excluded. These findings are hypothesis-generating, and prospective studies incorporating polysomnography and ALS-specific prognostic factors are needed.},
}

Humans
*Amyotrophic Lateral Sclerosis/mortality/drug therapy
Female
Male
*Antidepressive Agents/therapeutic use/pharmacology
*Riluzole/therapeutic use
Middle Aged
*Sleep, REM/drug effects
Aged

@article {pmid42468019,
year = {2026},
author = {Gou, CY and Smith, SE},
title = {Interventional Procedures for Musculoskeletal Pain in ALS Patients: A Case Series.},
journal = {American journal of physical medicine & rehabilitation},
volume = {105},
number = {8},
pages = {e117-e120},
doi = {10.1097/PHM.0000000000002964},
pmid = {42468019},
issn = {1537-7385},
mesh = {Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications ; Female ; *Musculoskeletal Pain/etiology/therapy/drug therapy ; Retrospective Studies ; *Pain Management/methods ; Aged ; Adult ; },
abstract = {Many patients with amyotrophic lateral sclerosis (ALS) experience musculoskeletal pain, yet data on the safety and efficacy of interventional procedures for pain relief in this population are limited. This study aims to describe the characteristics, outcomes, and procedural considerations of pain interventions performed for musculoskeletal pain in ALS patients. A retrospective chart review was conducted of ALS patients referred for interventional pain management by a neuromuscular physiatrist at a single academic institution's interdisciplinary ALS Center between February 2021 and February 2025. Eleven patients (mean age: 57 y, 64% male) underwent 14 procedures. Shoulder pain was the most common indication (43%), followed by spine (29%) and hip (14%) pain. Procedures mostly consisted of joint and bursal injections peripherally and of epidural injections in the axial spine. Overall, 13 of 14 (93%) procedures provided at least "good" pain relief, and 5 patients elected to repeat their procedures. One patient experienced transient postprocedure hypertension; no major complications occurred. Interventional procedures, particularly corticosteroid injections, appear to be safe and effective for managing focal musculoskeletal pain in patients with ALS. Tailored procedural techniques and multidisciplinary coordination can enhance comfort and optimize outcomes in this complex population.},
}

Humans
Male
Middle Aged
*Amyotrophic Lateral Sclerosis/complications
Female
*Musculoskeletal Pain/etiology/therapy/drug therapy
Retrospective Studies
*Pain Management/methods
Aged
Adult

@article {pmid42468211,
year = {2026},
author = {Seo, Y and Lee, J and Lee, Y and Kim, S and Lee, JS and Ro, H and Cho, SH and Park, JS and Kim, MJ and Park, HC},
title = {FUS-driven zebrafish model of ALS identifies tribenzylamine as a candidate modulator of ALS-associated pathology.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {202},
number = {},
pages = {119761},
doi = {10.1016/j.biopha.2026.119761},
pmid = {42468211},
issn = {1950-6007},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron loss and declining motor function; however, effective therapies remain limited. To support unbiased therapeutic discovery, we aimed to develop a high-throughput phenotypic screening platform based on a transgenic zebrafish model expressing the human ALS-associated FUS-R521C mutant (mtFUS). This model was generated using a modified QF-based binary expression system and exhibited early-onset pathological features, including elevated oxidative stress, progressive neuronal degeneration, and impaired locomotor activity, thereby recapitulating the key aspects of FUS-associated ALS. Transcriptomic profiling revealed molecular signatures resembling those reported in patient-derived motor neurons, including dysregulated neuroactive ligand-receptor signaling, immune activation, and stress-response pathway alterations. Using this platform, we identified tribenzylamine (TBA) as a candidate compound that improves locomotor performance and significantly reduces reactive oxygen species levels. Integrated transcriptomic and biochemical analyses suggested that TBA induces coordinated molecular changes, including normalization of neuronal activity-related gene expression, modulation of immune and metabolic pathways, and restoration of hormone-related signaling. TBA reversed FUS-induced reductions in key neuronally active sex steroids, including estrogen and progesterone, and increased estrogen-responsive gene expression, suggesting a partial recovery of neuronally active sex steroid homeostasis. These findings support the mtFUS zebrafish model as a useful platform for ALS drug discovery and identify TBA as a candidate modulator of ALS-associated phenotypes, with effects linked to transcriptomic remodeling and neuronally active sex steroid signaling.},
}

@article {pmid42468901,
year = {2026},
author = {Halabian, N and Park, C and Omoto, L and Bocca, LF and Palacios, G and Wu, K and Hamani, C and Rabin, J and Abrahao, A and Davidson, B and Lipsman, N and Meng, Y},
title = {Focused ultrasound blood brain barrier opening for targeted therapeutics in neurodegenerative diseases.},
journal = {Biological psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.biopsych.2026.07.008},
pmid = {42468901},
issn = {1873-2402},
abstract = {Therapeutic focused ultrasound (FUS) leverages the non-invasive ultrasonic waves to modify the biological tissue. When administered alongside intravenous microbubbles, low-intensity FUS enables transient, targeted disruption of the blood-brain barrier (BBB), permitting passage of systemically administered therapeutics into the central nervous system (CNS) with high spatial precision. The ability to selectively modulate BBB permeability at the disease site has the potential to substantially expand the number of therapeutics that can be utilized in treating illnesses afflicting the CNS. Herein, we review the current applications of FUS for treating neurodegenerative disorders and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). We discuss the research developments to date and future directions.},
}

@article {pmid42469515,
year = {2026},
author = {Kreß, L and Abuzant, M and Zeller, D and Sommer, C},
title = {Beyond ALS: split-hand syndrome in immune-mediated motor neuropathies.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42469515},
issn = {1432-1459},
support = {Z-2/CSP_22//Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg/ ; Z-3 BC-18//Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg/ ; Z-2/AdvCSP-4//Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg/ ; },
mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Middle Aged ; Aged ; *Muscle, Skeletal/physiopathology ; Prospective Studies ; *Hand/physiopathology ; Adult ; Nerve Conduction Studies ; Diagnosis, Differential ; },
abstract = {BACKGROUND AND AIMS: Split-hand syndrome describes selective wasting and weakness of the abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with relative preservation of the abductor digiti minimi (ADM). Beyond clinical definition, two neurophysiological ratios and one index have been proposed to quantify this pattern. It is considered a potential diagnostic criterion for amyotrophic lateral sclerosis (ALS). Its occurrence in immune-mediated neuropathies, as differential diagnoses, remains unclear. We aimed to investigate clinical and electrophysiological manifestations of split-hand syndrome in multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) compared to ALS.

METHODS: We prospectively examined 26 MMN, 16 MADSAM, and 22 ALS patients. All underwent neurological examination and neurophysiological measurements of compound muscle action potentials (CMAP) from the APB, FDI, and ADM bilaterally after median (APB) and ulnar nerve (FDI, ADM) stimulation. Split-hand ratios (APB/ADM; FDI/ADM) and split-hand index (SI) were calculated.

RESULTS: Clinical split-hand syndrome was present in 16/26 (62%) MMN, 7/16 (44%) MADSAM, and 12/22 (54%) ALS patients. Electrophysiological criteria (abnormal split-hand ratios or SI; ≥ 1 parameter fulfilled) were similarly frequent across groups (MMN 17/26, 65%, MADSAM 11/16, 69%, and ALS 16/22, 73%). CMAP ratios and SI did not differ between groups in the overall analysis and showed no correlation with disease duration or severity. Diagnostic models showed limited discriminatory power (area under the curve ≤ 0.61).

INTERPRETATION: Split-hand syndrome occurs in MMN, MADSAM, and ALS at comparable frequencies and lacks robust or consistent diagnostic discrimination across disease groups.},
}

Humans
Female
Male
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Middle Aged
Aged
*Muscle, Skeletal/physiopathology
Prospective Studies
*Hand/physiopathology
Adult
Nerve Conduction Studies
Diagnosis, Differential

@article {pmid42469634,
year = {2026},
author = {Li, MA and Song, YZ and Li, T and Wu, J and Tao, Y and Hu, R and Qiao, CM and Cui, C and Zhao, WJ and Shen, YQ},
title = {Secretory leukocyte protease inhibitor (SLPI) attenuates TLR4/NF-κB-mediated neuroinflammation in amyotrophic lateral sclerosis: a candidate molecule associated with neuro-pathology.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s10020-026-01572-8},
pmid = {42469634},
issn = {1528-3658},
support = {KYCX25_2743//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; 82171429//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder driven by neuroinflammation involving activated microglia and astrocytes, which accelerates the loss of motor neurons. While Secretory leukocyte protease inhibitor (SLPI) is known for its immunomodulatory properties, its specific role in ALS pathogenesis has not been fully established. This study aimed to characterize the expression patterns and functional significance of SLPI in ALS models.

METHODS: The study utilized SOD1[G93A] mice to analyze the spatiotemporal dynamics of SLPI expression in the gastrocnemius muscle, lumbar spinal cord, and serum across different disease stages. In vitro functional assays were conducted using siRNA-mediated knockdown of SLPI in BV2 (microglia), MA (astrocytes), and NSC-34 (motor neurons) cell lines. Additionally, recombinant SLPI protein was applied to LPS-stimulated BV2 cells to investigate its effect on the TLR4/ NF-κB signaling pathway.

RESULTS: In SOD1[G93A] mice, SLPI was significantly upregulated in the gastrocnemius muscle from the pre-symptomatic stage (60 days) through the late stage (130 days). In the lumbar spinal cord, SLPI showed a transient initial increase but declined sharply by the end-stage; a similar significant reduction was observed in late-stage serum levels. In vitro, SLPI knockdown exacerbated pro-inflammatory cytokine production in all three cell types and impaired the antioxidant capacity of NSC-34 motor neurons. Mechanistically, recombinant SLPI attenuated inflammation in BV2 cells by modulating the TLR4/NF-κB pathway.

CONCLUSIONS: The dynamic changes in SLPI levels suggest its potential relevance as a candidate molecule for disease staging. Meanwhile, its protective effects in regulating inflammation suggest that it could be a promising therapeutic candidate for mitigating ALS-associated neuroinflammation.},
}

@article {pmid42470084,
year = {2026},
author = {Morgado Linares, RY and Rojas-Marcos, Í and Mesa, M and Martínez, E and Cabrera-Serrano, M and Paradas, C},
title = {Impact of Sexuality in Patients With Motor Neuron Disease.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70348},
pmid = {42470084},
issn = {1097-4598},
abstract = {INTRODUCTION: Sexuality is a relevant yet understudied aspect in people living with motor neuron disease (MND). This study aimed to assess whether sexuality in people with MND is influenced by motor, cognitive, behavioral, or mood disturbances, and to explore whether being sexually active impacts caregiver burden.

METHODS: We conducted a cross-sectional observational study involving participants with MND and their primary caregivers from three ALS multidisciplinary units in Seville, Spain. Data were collected between October 2018 and July 2021. Functional, cognitive, behavioral, and mood assessments were conducted. Sexuality was evaluated through sex-specific questionnaires. Caregiver burden was assessed using the Zarit Burden Interview.

RESULTS: Among 66 participants who completed the sexuality assessment, 42.9% reported sexual activity in the previous month. Of these, 70% had no sexual dysfunction, while 26.7% had moderate and 3.3% severe dysfunction. No correlation was found between sexual activity and motor function. Sexual activity was less frequent in participants with apathy (p = 0.026), depression (p = 0.021), and frontotemporal dementia (p = 0.013). Among sexually active patients, those with cognitive impairment-particularly memory dysfunction-had higher rates of orgasm difficulties (p = 0.019). No other clinical parameters were related to sexuality. Sexuality of participants with MND did not influence caregiver burden.

DISCUSSION: Sexuality in MND is more associated with cognitive and mood factors than with motor disability. Addressing sexuality in clinical practice may contribute to improving quality of life and should be integrated into the multidisciplinary care of MND patients.},
}

@article {pmid42471032,
year = {2026},
author = {Barrera-Chamorro, L and Gonzalez-de la Rosa, T and Arzalluz-Luque, J and Torrecillas-Lopez, M and Marquez-Paradas, E and Claro-Cala, CM and Navarro-Hortal, MD and Eichau, S and Garcia-Sanchez, MI and Montserrat-de la Paz, S},
title = {Sustainable next-generation prebiotics for brain health: microbiota-gut-brain axis in neurodegenerative and demyelinating diseases.},
journal = {Critical reviews in food science and nutrition},
volume = {},
number = {},
pages = {1-22},
doi = {10.1080/10408398.2026.2703335},
pmid = {42471032},
issn = {1549-7852},
abstract = {Neurodegenerative and neuroinflammatory diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are increasingly associated with disruption of the microbiota-gut-brain axis. Common alterations include reduced beneficial microbial taxa, impaired short-chain fatty acid production, intestinal and blood-brain barrier dysfunction, and sustained inflammatory responses. These findings support the development of microbiota-targeted dietary interventions. This review summarizes current evidence on polyphenols, bioactive peptides, and pectin-derived oligosaccharides (POS) as prebiotic or prebiotic-like compounds with potential activity through the microbiota-gut-brain axis. Particular attention is given to structure-function relationships, host-microbe interactions, and the sustainable recovery of these compounds from food by-products. Preclinical studies suggest that these bioactives may reduce microglial activation, improve mitochondrial function, strengthen intestinal and blood-brain barrier integrity, and enhance cognitive or motor performance. Early clinical studies also indicate possible benefits on mood, selected cognitive outcomes, metabolic regulation, and inflammatory biomarkers, although evidence remains limited. Microbiota-derived metabolites from polyphenols, such as urolithins, together with glycomacropeptide and POS, appear to be key mediators. However, clinical validation in major neurodegenerative diseases remains fragmented. Standardized formulations, mechanistic trials, harmonized endpoints, and precision-nutrition strategies are required to confirm their therapeutic potential.},
}

@article {pmid42466609,
year = {2026},
author = {Li, D and Zhou, Z and Liang, G and Zeng, D and Zhou, Z and Li, X and Qiu, T and Zhang, Y and Lin, J and Chen, Y and Li, Z},
title = {Association Between Allostatic Load, Genetic Susceptibility, and Liver Cancer Incidence: A Large-Scale Prospective Cohort Study.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.70583},
pmid = {42466609},
issn = {1097-0215},
support = {240421166496919//Shantou Medical Science and Technology Planning Project/ ; A2023481//Medical Scientific Research Foundation of Guangdong Province, China/ ; B2025664//Medical Scientific Research Foundation of Guangdong Province, China/ ; //Shantou University Medical College 2025 Teaching Reform Project/ ; },
abstract = {Allostatic load (AL) reflects the cumulative physiological burden of chronic stress throughout life, potentially influencing cancer onset and prognosis. However, its association with primary liver cancer (PLC) risk and potential interaction with genetic susceptibility remains unclear. To investigate this, we analyzed 374,632 UK Biobank participants. AL was evaluated using a composite score of 13 cardiovascular, metabolic, and immune biomarkers, while a weighted polygenic risk score (PRS) categorized genetic susceptibility. Multivariable Cox proportional hazards models and restricted cubic splines were utilized to estimate hazard ratios (HRs) and evaluate dose-response relationships. Over a median 12.4-year follow-up, a significant dose-response correlation between AL and PLC risk was observed. In the fully adjusted model, a 1-unit increase in AL was associated with a 17% increased risk (HR = 1.17, 95% CI: 1.12-1.23), and participants in the highest AL quartile exhibited a 2.60-times higher risk than those in the lowest (HR = 2.60, 95% CI: 1.72-3.95). Despite no multiplicative interaction, stratified analyses revealed AL's impact was most substantial in individuals with intermediate genetic risk (HR = 2.00, 95% CI: 1.38-2.90), who constitute the population majority. Additionally, the risk was heightened in overweight/obese individuals and more pronounced among non-smokers. Ultimately, cumulative physiological stress, indicated by AL, is strongly associated with PLC, supporting the "wear-and-tear" theory of its development. This research highlights a "malleable zone" in individuals with moderate genetic risk, suggesting that lowering AL may meaningfully aid in preventing PLC.},
}

@article {pmid42467162,
year = {2026},
author = {Barker-Jones, B and Navvuga, P and Baji, P and Marques, E and Hollingworth, W},
title = {Comparing User-Written Codes for Performing Economic Evaluations in Stata.},
journal = {PharmacoEconomics},
volume = {},
number = {},
pages = {},
pmid = {42467162},
issn = {1179-2027},
support = {RP-PG-0610-10048//National Institute for Health and Care Research/ ; PB-PG-0213-30021//National Institute for Health and Care Research/ ; },
abstract = {BACKGROUND: Several user-written Stata codes exist for trial-based economic evaluations, but they lack assessment and guidance. This study aimed to identify and compare publicly available user-written Stata codes for trial-based economic evaluations.

METHODS: A focused literature search of Ovid Medline, SSC Archive, The Stata Journal and Google Scholar was conducted to identify relevant codes to June 2025. Codes were applied to data from two clinical trials, both featuring missing data and covariate adjustment. Codes were compared in terms of their ability to estimate key economic parameters and produce graphical outputs and functionality in handling four common statistical challenges: correlated costs and effects, covariate adjustment, skewed costs and effects, and missing data.

RESULTS: We identified eight codes reported in four publications: codes for assessing health economic agreement (Gallacher et al.), sampling uncertainty for cost-effectiveness analysis (Glick et al.) and codes addressing missing data (Mutubuki et al. and Faria et al.). Gallacher et al.'s codes reported lower incremental quality-adjusted life years (QALYs) and net monetary benefit than Glick's et al.'s codes. Mutubuki et al. and Faria et al.'s codes produced comparable incremental costs and QALYs, though Faria et al. yielded wider confidence intervals in cost estimates.

DISCUSSION: Differences in estimates across statistical approaches show that code choice can influence economic evaluation results. Some codes were better suited for generating basic economic outputs, whereas others provide more comprehensive analyses or address specific statistical challenges including missing data. However, no single code provided all key outputs while addressing the main statistical challenges.},
}

@article {pmid42467293,
year = {2026},
author = {Hassan, MA and Al Amin, M and Sweilam, SH and Abohassan, M and Krishnan, K and Gupta, JK and Jahnavi, P and Vodeti, R and Radha, R and Gupta, PS and Reddy, KTK},
title = {Resveratrol and neuroprotection: modulation of cellular dynamics and signaling networks in neurodegenerative diseases.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42467293},
issn = {1568-5608},
abstract = {Progressive loss of neurons, oxidative stress, neuroinflammation, and mitochondrial dysfunction are hallmarks of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Resveratrol, a polyphenolic phytoalexin mainly found in grapes and red wine, is a promising treatment candidate due to its diverse biological effects and neuroprotective properties. This review demonstrates the regulatory effects of resveratrol on cellular signaling pathways linked to NDs and its neuroprotective mechanisms. Resveratrol enhances neuronal survival, boosts mitochondrial biogenesis, and mitigates oxidative stress by affecting key molecular pathways, including SIRT1/AMPK, PI3K/Akt, MAPK, and Nrf2/ARE. The PI3K/Akt and ERK1/2 pathways promote neuronal regeneration by modulating pro-apoptotic and anti-apoptotic factors. Resveratrol inhibits NF-κB, reducing cytokine release and microglial activation, thereby exhibiting anti-inflammatory properties. It improves cognitive function, synaptic plasticity, and neuronal survival. Despite an increasing pharmacological profile, its practical applicability is limited by inadequate bioavailability, rapid metabolism, and restricted brain penetration. This review demonstrates resveratrol's effect on interconnected signaling networks related to neurodegeneration. We critically compare evidence from preclinical and clinical studies, demonstrating both therapeutic potential and translational limitations. Emerging nanotechnology-based delivery strategies are demonstrated to overcome bioavailability and blood-brain barrier penetration challenges. These insights provide a translational perspective for the future development of resveratrol-based interventions in NDs.},
}

@article {pmid42467750,
year = {2026},
author = {Deressa, JD and Behaksra, SW and Molla, E and Letebo, A and Shumie, G and Adnew, B and Alemayehu, DH and Kassa, FA and Seyoum, T and Tafa, EB and Woldekidan, K and Ejigu, LA and Huwe, T and Keffale, M and Bayissa, GA and Koepfli, C and Chala, B and Asmamaw, Y and Tadesse, FG and Gadisa, E},
title = {Therapeutic efficacy of artemether-lumefantrine plus single low dose primaquine for the treatment of uncomplicated Plasmodium falciparum malaria in a high transmission setting, Western Ethiopia.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0335833},
pmid = {42467750},
issn = {1932-6203},
mesh = {Humans ; *Primaquine/therapeutic use/administration & dosage ; *Artemether, Lumefantrine Drug Combination/therapeutic use/administration & dosage ; *Malaria, Falciparum/drug therapy/transmission/epidemiology/parasitology ; *Antimalarials/therapeutic use/administration & dosage ; Female ; Male ; Ethiopia/epidemiology ; Plasmodium falciparum/drug effects/genetics ; Child, Preschool ; Adolescent ; Treatment Outcome ; Child ; Adult ; Drug Therapy, Combination ; Young Adult ; },
abstract = {BACKGROUND: The development and spread of drug-resistant parasites continue to threaten progress toward malaria elimination. Therapeutic efficacy and molecular resistance marker studies are needed to guide national control programs. In African settings, evidence of partial resistance to artemisinin-based combination therapies (ACTs) associated with Pfkelch13 mutations is accumulating, and World Health Organization (WHO) recommends regular monitoring of first line antimalarial drugs for early detection of resistant parasites. In this study, we evaluated the efficacy of artemether-lumefantrine (AL) combined with a single low dose of primaquine (PQ) for treating uncomplicated Plasmodium falciparum malaria in a co-endemic area where P. falciparum predominates.

METHODS AND FINDINGS: One hundred twenty-three patients with P. falciparum mono-infection were enrolled between November 2020 to March 2021 and treated with artemether-lumefantrine (AL) plus a single low dose of primaquine (PQ) as per the national malaria treatment guideline and followed up for 28 days. Ethical approval was obtained from the AHRI/ALERT ethics committee (Po/23/19), and the study was registered at Pan-African clinical trials registry (PACTR) with unique identification number of PACTR202509595696440. Pfmsp2 capillary electrophoresis (CE) genotyping was used to differentiate recrudescence from new infections. More than half (56.1%) of the participants had high parasitemia (>10,000 parasites/μL) at enrollment. On day 3, 16.9% (20/118) remained parasitemic, and of the 10 individuals with detectable gametocytes at enrollment, only 3.4% remained gametocytemic on day 3, and 100% parasite clearance was observed on day 7, respectively. Multiplicity of infection was 3.8 at enrollment and 1.7 at the time of recurrence. The adequate clinical and parasitological responses at 28-day (ACPR) of per protocol analysis (PPA) was 73.7% for PCR-uncorrected and 91.3% for PCR-corrected, respectively and while, the intention-to-treat analysis (ITA), the Kaplan-Meier estimated treatment success at day 28 was 93.2% (95% CI: 88.5-98.2) after PCR correction, compared with 78.3% (95% CI: 71.0-86.4) in the PCR-uncorrected analysis. In our study assessment, no cases of severe malaria or serious adverse events occurred.

CONCLUSIONS: The efficacy observed in this study, although remaining above the WHO policy change threshold after PCR correction, may indicate a potential decline in AL's effectiveness in this high transmission setting. However, because antimalarial drug concentrations were not measured and evening doses were not fully directly observed, reduced drug exposure or imperfect adherence cannot be excluded as possible contributors to the observed treatment outcomes Therefore, we suggest regular therapeutic efficacy monitoring and further investigation using advanced molecular techniques, such as next-generation sequencing (NGS), to enable early detection of resistance-associated parasite variants that may compromise treatment efficacy.},
}

Humans
*Primaquine/therapeutic use/administration & dosage
*Artemether, Lumefantrine Drug Combination/therapeutic use/administration & dosage
*Malaria, Falciparum/drug therapy/transmission/epidemiology/parasitology
*Antimalarials/therapeutic use/administration & dosage
Female
Male
Ethiopia/epidemiology
Plasmodium falciparum/drug effects/genetics
Child, Preschool
Adolescent
Treatment Outcome
Child
Adult
Drug Therapy, Combination
Young Adult

@article {pmid40364629,
year = {2026},
author = {Sepehrimanesh, M and Xu, W and Ding, B},
title = {Comparative analysis of chemical and lentiviral approaches in the generation of human induced pluripotent stem cell-derived motor neurons.},
journal = {Neural regeneration research},
volume = {21},
number = {7},
pages = {2968-2974},
pmid = {40364629},
issn = {1673-5374},
support = {R56 NS133252/NS/NINDS NIH HHS/United States ; },
abstract = {The generation of human induced pluripotent stem cell–derived motor neurons overcomes limited access to human tissues and offers an unprecedented approach to modeling motor neuron diseases such as dystonia and amyotrophic lateral sclerosis. Motor neurons generated through different strategies may exhibit substantial differences in purity, maturation, characterization, and even neuronal identity, leading to variable outcomes in disease modeling and drug screening. However, very few comparative studies have been conducted to determine the similarities and differences among motor neurons prepared via different protocols. In this study, we prepared human induced pluripotent stem cell–derived motor neurons via lentiviral delivery of transcription factors and chemical induction and performed a systematic comparative analysis. We found that motor neurons generated by both approaches showed typical motor neuron morphology and robustly expressed motor neuron-specific markers, such as nuclear homeobox transcription factor 9 and choline acetyltransferase. The chemical induction protocol utilizes a combination of small molecules to induce motor neuron differentiation, offering a significantly faster maturation time of 35 days compared to 46 days with lentiviral delivery of transcription factors. Additionally, while lentiviral delivery of transcription factors are suitable for downstream biochemical analysis, chemical induction are more applicable for therapeutic approaches as they avoid the use of lentiviruses. Both approaches produce motor neurons with high purity (> 95%) and yield. No significant differences were found between chemical induction and lentiviral delivery of transcription factors in terms of motor neuron markers and maturation markers. These robust methodologies offer researchers powerful tools for investigating motor neuron diseases and potential therapeutic strategies.},
}

@article {pmid42464213,
year = {2026},
author = {Özbilici, Z and Issı, ES},
title = {SYNE1-Related motor neuron disease-like phenotype with mild distal contractures and 24-month clinical stability: a case report.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-05142-7},
pmid = {42464213},
issn = {1471-2377},
abstract = {BACKGROUND: SYNE1 encodes nesprin-1, a nuclear envelope protein involved in cytoskeletal linkage, nuclear positioning, and neuromuscular integrity. Biallelic SYNE1 variants cause a broad spectrum ranging from cerebellar ataxia to arthrogryposis multiplex congenita and motor neuron disease-like phenotypes. Distinguishing these entities can be difficult when subtle distal contractures coexist with neurogenic electrophysiological findings.

CASE PRESENTATION: A 22-year-old woman born to consanguineous parents presented with bilateral intrinsic hand muscle wasting, impaired fine motor performance, and mild gait difficulty. Examination showed distal hand atrophy, mild weakness of the abductor pollicis brevis and first dorsal interosseous muscles, brisk deep tendon reflexes, preserved sensation, and mild distal finger contractures. Sensory nerve conduction studies were normal. Motor studies showed reduced compound muscle action potential amplitude in the right abductor pollicis brevis and borderline-low amplitude on the left. Needle electromyography showed widespread chronic neurogenic motor unit changes affecting the upper and lower extremities, with active denervation most evident in the bilateral abductor pollicis brevis muscles. Genioglossus examination was normal. SMN1 deletion testing and selected familial amyotrophic lateral sclerosis gene testing were negative. Whole exome sequencing identified a homozygous truncating SYNE1 variant, NM_182961.4:c.21009G > A; p.(Trp7003Ter). Segregation analysis confirmed heterozygous carrier status in both parents and two unaffected siblings. At 24-month follow-up, weakness, atrophy, contractures, reflex pattern, and functional status remained clinically stable, without bulbar, cerebellar, sensory, or clinically evident respiratory involvement.

CONCLUSIONS: This case supports classification as a SYNE1-related motor neuron disease-like phenotype with mild distal contractures rather than an isolated arthrogryposis multiplex congenita type 3 (AMC3) phenotype. The case also supports including SYNE1 in genetic testing panels for young patients with unexplained motor neuron disease-like presentations, particularly when consanguinity, normal sensory conduction, and subtle distal contractures coexist.},
}

@article {pmid42464712,
year = {2026},
author = {Gao, N and Cui, B and Yun, Y and Yu, W and Gao, X and Sun, X and Shao, K and Lin, P and Liu, F and Li, W and Zhao, Y and Yu, D and Yan, C and Liu, S and Lou, J},
title = {Corticospinal Subfiber Neurite Density Index Detects Upper Motor Neuron Degeneration in Prediagnostic Patients With Sporadic Amyotrophic Lateral Sclerosis.},
journal = {European journal of neurology},
volume = {33},
number = {7},
pages = {e70703},
pmid = {42464712},
issn = {1468-1331},
support = {82471429//National Natural Science Foundation of China/ ; ZR2024MH013//Natural Science Foundation of Shandong Province/ ; 2025CXPT133//the Key Research and Development Program of Shandong Province, China/ ; Z-2017-24-2509//the Yantu Neuroscience Specialized Research Fund Project/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/blood/diagnosis ; Female ; Male ; *Pyramidal Tracts/diagnostic imaging/pathology ; Middle Aged ; *Neurites/pathology ; Retrospective Studies ; Aged ; Neurofilament Proteins/blood ; Diffusion Magnetic Resonance Imaging ; Diffusion Tensor Imaging ; *Motor Neurons/pathology ; *Nerve Degeneration/pathology/diagnostic imaging ; },
abstract = {BACKGROUND: Using multi-shell diffusion MRI, we aimed to identify whether corticospinal tract (CST) subfiber damage can be detected in prediagnostic amyotrophic lateral sclerosis (ALS) patients. We also explored whether the combination of serum neurofilament light chain (NfL) levels and CST subfiber abnormalities may provide better diagnostic performance in differentiating prediagnostic ALS patients from disease controls (DCs) and healthy controls (HCs) than single markers.

METHODS: In this retrospective study, prediagnostic ALS was used as an operational term for patients who presented at baseline with chronic progressive limb weakness or bulbar symptoms, had no clinically evident typical UMN signs, and were subsequently confirmed to have sporadic ALS according to the Awaji criteria during longitudinal follow-up. Patients whose final diagnosis was not ALS after follow-up were classified as disease controls. Probabilistic tractography was performed on baseline MRI data to assess CST subfiber damage in 47 ALS patients, 20 DCs, and 51 HCs.

RESULTS: Compared with Controls, ALS patients had significantly lower neurite density index (NDI) values of CST subfibers, particularly those originating from the primary and supplementary motor cortex. The diagnostic performance of the combined model incorporating serum NfL and CST subfiber NDI values in differentiating prediagnostic ALS patients from HCs and DCs was 0.925 and 0.928, respectively, which was better than that of single markers (0.634-0.886 and 0.699-0.856, respectively).

CONCLUSIONS: Our findings suggest that CST subfibers NDI values are promising neuroimaging markers for detecting in vivo UMN degeneration in prediagnostic ALS. Moreover, combining blood and neuroimaging markers may further improve early diagnostic performance.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/blood/diagnosis
Female
Male
*Pyramidal Tracts/diagnostic imaging/pathology
Middle Aged
*Neurites/pathology
Retrospective Studies
Aged
Neurofilament Proteins/blood
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
*Motor Neurons/pathology
*Nerve Degeneration/pathology/diagnostic imaging

@article {pmid42465739,
year = {2026},
author = {You, Y and Zhu, H and Zhang, Q and Wang, J and Dong, C and Yang, Z and Zhang, J and Zhang, Y and Zhang, M and Lu, M and Du, C},
title = {Development and efficacy of ex vivo expanded autologous regulatory T cells for the treatment of amyotrophic lateral sclerosis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1854252},
pmid = {42465739},
issn = {1664-3224},
mesh = {*Amyotrophic Lateral Sclerosis/therapy/immunology/genetics ; *T-Lymphocytes, Regulatory/immunology/transplantation/metabolism ; Animals ; Humans ; Mice ; Disease Models, Animal ; Female ; Superoxide Dismutase-1/genetics ; Mice, Transgenic ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited therapeutic options, in which neuroinflammation critically drives disease progression. Regulatory T cells (Tregs) exert potent immunosuppressive and neuroprotective effects, offering great potential for ALS treatment. However, clinical application of Treg therapy is hampered by low peripheral cell abundance and unstable expansion quality. Here, we established and optimized a GMP-grade protocol for sorting and expanding peripheral blood-derived Tregs, and validated cryopreserved apheresis products as feasikble starting materials. Although ALS patient-derived Tregs showed reduced expansion capacity compared with healthy donor counterparts, they maintained comparable purity, stable regulatory phenotypes, and robust immunosuppressive function. Transcriptomic analysis confirmed the lineage fidelity and low pro-inflammatory characteristics of expanded Tregs. Therapeutic efficacy was verified in SOD1G93A ALS and GvHD mouse models with delayed disease progression and relieved inflammation. This study provides standardized GMP manufacturing strategies and solid preclinical evidence to support the ongoing clinical trial (NCT06671236) and facilitate Treg immunotherapy translation for ALS.},
}

*Amyotrophic Lateral Sclerosis/therapy/immunology/genetics
*T-Lymphocytes, Regulatory/immunology/transplantation/metabolism
Animals
Humans
Mice
Disease Models, Animal
Female
Superoxide Dismutase-1/genetics
Mice, Transgenic

@article {pmid42466415,
year = {2026},
author = {Mei, A and Jewett, D and Jewett, A and Kaur, K and Malarkannan, S},
title = {Multi-hit genetic lesions and a stress-imprinted immune transcriptome define the inflammatory pathology in ALS patients.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42466415},
issn = {2693-5015},
abstract = {Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease whose peripheral immune architecture remains incompletely defined. Here, we integrated whole-genome sequencing and single-cell RNA sequencing to define genomic and immune correlates of ALS. Genome-wide analysis of a monozygotic twin pair discordant for ALS pathology identified shared ALS-associated variants, as well as patient-enriched variants in genes linked to RNA metabolism, neurodegeneration, and immune inflammation, supporting a multilayered genetic architecture. Single-cell profiling of 40,484 peripheral blood mononuclear cells from three ALS patients and two healthy individuals, including 33,667 cells retained after quality control, resolved 13 immune clusters and revealed broad remodeling of the peripheral immune compartment, with relative enrichment of natural killer, mucosal-associated invariant T, and γδ T-cell populations. Across immune subsets, ALS samples exhibited inflammatory and stress-adapted transcriptomic programs, including TNF-α/NF-κB, IFN-γ, hypoxia, and ribosomal stress pathways. These data support a model in which multi-hit genetic susceptibility converges on a stress-induced immune transcriptome, marked uniquely by innate lymphocyte activation in ALS patients.},
}

@article {pmid42459525,
year = {2026},
author = {Majumdar, S and Samaiya, PK and Ahmed, S and Prajapati, SK},
title = {Imaging biomarkers in neurodegenerative diseases: advances and challenges.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1813588},
pmid = {42459525},
issn = {1663-4365},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), represent a major global health burden. Imaging biomarkers have emerged as important tools for improving the diagnosis, monitoring, and biological characterization of neurodegenerative diseases. Structural MRI, diffusion tensor imaging (DTI), functional MRI (fMRI), positron emission tomography (PET), hybrid PET/MRI and molecular imaging have transformed our ability to investigate neurodegeneration in vivo non-invasively. This review highlights updated information on how each imaging modality offers a unique window into different disease pathophysiology including regional atrophy, amyloid-β, tau, dopaminergic terminal degeneration, synaptic density (SV2A), and neuroinflammation. We also focused on the translational and evidence supporting biomarkers, appropriate use criteria for amyloid and tau PET imaging, and standardized quantification methods such as the Centiloid scale. The growing role of multimodal fusion, where imaging is increasingly integrated with scalable fluid biomarkers to enable "blood-first" strategies where high-risk patients are selectively referred to advanced imaging, improving feasibility and equity. Despite tremendous progress, there are still issues with their standardization, sensitivity, specificity, and clinical translation. Moreover, the review emphasizes the frontiers of α-synuclein and glial state-specific PET ligands, advanced diffusion models, and dynamic connectivity analysis to support precision medicine and mechanism-based trial design for NDDs.},
}

@article {pmid42459857,
year = {2026},
author = {Hu, M and You, L and Zhang, X and Xuan, Z and Ma, S and Wu, X},
title = {Experimental evidence of electroacupuncture in ALS mouse models: a systematic review and meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1780176},
pmid = {42459857},
issn = {1664-2295},
abstract = {OBJECTIVE: This study aimed to systematically evaluate the therapeutic efficacy of electroacupuncture (EA) in amyotrophic lateral sclerosis (ALS) and to elucidate the underlying neurobiological mechanisms by synthesizing preclinical evidence.

METHODS: According to the PICOS principle, relevant studies were searched in the following databases: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and CNKI. Search terms and strategies were determined based on MeSH terms. The methodological quality of the included studies was assessed using the SYRCLE's Risk of Bias tool and the CAMARADES checklist. Meta-analysis was performed using Stata 15.0 and Rstudio software.

RESULTS: Seventeen studies involving 372 animals were included. The quality scores of the included studies ranged from 5 to 8, with an average score of 7. The meta-analysis of the primary outcome, the rotarod test score, showed a significant improvement in the EA group compared to the control group [SMD = 3.31, 95% CI (2.05, 4.57), Z = 5.151, p < 0.001], indicating that EA can enhance motor function in ALS mice. Regarding secondary outcomes, EA intervention alleviated neuroinflammation, promoted neuronal survival, improved axonal regeneration inhibition, and stabilized RNA metabolism homeostasis. Consequently, it slowed disease progression, improved motor performance, prolonged survival time, and effectively protected motor neurons at the histopathological level (p < 0.05). These findings underscore the potential of EA as a promising multimodal therapeutic strategy for ALS. For the heterogeneity observed in the rotarod test, sensitivity analysis, subgroup analysis, and meta-regression did not identify its source. However, potential publication bias was detected, which might contribute to the heterogeneity. The heterogeneity for other outcome measures might originate from differences in stimulation parameters (e.g., waveform), acupoint selection, or treatment duration.

CONCLUSION: This meta-analysis demonstrates that EA confers significant neuroprotective benefits in preclinical ALS models, primarily through multi-target modulation of key pathological processes such as neuroinflammation, aberrant cell death signaling, and RNA metabolism. These preclinical findings underscore the potential of electroacupuncture as a complementary neuroprotective strategy and warrant further investigation in rigorous clinical trials.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251229183.},
}

@article {pmid42459893,
year = {2026},
author = {Ogino, M},
title = {Single-subject auditory ERP-BCI performance enhancement in ALS via an AI coding assistant prompt.},
journal = {Frontiers in human neuroscience},
volume = {20},
number = {},
pages = {1869918},
pmid = {42459893},
issn = {1662-5161},
abstract = {INTRODUCTION: Auditory event-related potential (ERP) brain-computer interfaces (BCIs) offer communication support for individuals with amyotrophic lateral sclerosis (ALS) who eventually progress to completely locked-in states. However, individual-specific BCI pipeline optimization is technically demanding and time-consuming, leaving substantial room for performance improvement in practice. A central challenge is increasing selection speed while maintaining reliable classification accuracy, since slower selections reduce the sense of agency and undermine the motivational and feedback dynamics essential for sustained BCI use.

METHODS: We investigated whether an AI coding assistant could address this challenge for individual patients. A three-class auditory ERP-BCI was optimized for a single ALS patient using Claude Code (Anthropic, Inc.), which iteratively generated and evaluated 23 optimization scripts over approximately 24 hours with minimal human-in-the-loop oversight. The resulting AI-Designed ERP classifier (AIDE) was evaluated on 189 EEG trials spanning 3.5 years using five cross-validation strategies.

RESULTS: For the baseline models, halving the stimulus repetitions to shorten selection time degraded classification accuracy; AIDE prevented this degradation, achieving 85.03% mean cross-validation accuracy (selection time 17 s; ITR 2.92 bits/min). This doubled the information transfer rate from 1.43 to 2.92 bits/min. Accuracy exceeded 84% across four of five cross-validation strategies. Feature space visualization revealed that the AI autonomously selected and combined EEG features established in prior studies into an effective discriminative architecture, without domain-specific algorithmic guidance from the human researcher. In addition, online test confirmed 66.7% accuracy for AIDE versus 50.0% for the baseline model.

DISCUSSION: These findings provide proof of concept that single-subject BCI performance can be improved via a single prompt, offering an efficient pathway to individualized optimization in clinical and research settings.},
}

@article {pmid42460499,
year = {2026},
author = {Leichsenring, F and Heim, N and Steinert, C},
title = {Conceptual problems and questionable evidence in defining non-inferiority margins - a reply to Flückiger et al.},
journal = {Psychotherapy research : journal of the Society for Psychotherapy Research},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/10503307.2026.2701025},
pmid = {42460499},
issn = {1468-4381},
abstract = {From 19 meta-analyses comparing active bona fide treatments, Flückiger et al. (2026) recently calculated a between-group effect size (SMD) of -0.17 for primary outcomes and of -0.16 for secondary outcomes. They suggested using these effect sizes as empirically derived non-inferiority margins. However, Flückiger et al.'s approach is conceptually problematic and lacks empirical support. Without a rationale, empirically found differences between active treatments cannot per se be regarded as non-inferiority margins.},
}

@article {pmid42460524,
year = {2026},
author = {Cai, X and Bai, Y and Ma, F and Xu, R and Xie, Y and Cao, X},
title = {Mechanisms and Therapeutic Targeting of the cGAS-STING Pathway in Central Nervous System Disorders.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X472988260627201746},
pmid = {42460524},
issn = {1875-6190},
abstract = {OBJECTIVE: The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a core DNA-sensing axis in innate immunity and has been increasingly implicated in the pathogenesis of multiple Central Nervous System (CNS) disorders. This review summarizes current knowledge of cGAS-STING signaling in CNS disorders and evaluates its therapeutic potential.

METHODS: Relevant studies on cGAS-STING signaling in CNS disorders were collected from PubMed and Web of Science, with emphasis on disease mechanisms, neuroinflammatory regulation, and pathway-targeted therapeutic strategies.

RESULTS: In the CNS, cGAS-STING signaling exhibits marked region-, cell-, and pathology-dependent heterogeneity. Aberrant DNA sensing activates this pathway and amplifies neuroinflammation, cellular stress, and tissue injury in Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), ataxia-telangiectasia (A-T), and ischemic and hemorrhagic stroke. Pharmacological inhibition of cGAS, cyclic GMP-AMP (cGAMP), or STING, together with emerging delivery strategies, has shown promise in preclinical models.

DISCUSSION: Clinical translation remains limited by incomplete validation of pathway specificity, limited human evidence, restricted brain delivery, and inconsistent efficacy assessment.

CONCLUSION: The cGAS-STING pathway links aberrant DNA sensing to innate immune activation and CNS pathology. Clarifying its disease-, cell-, and stage-specific roles may support future targeted therapeutic strategies for CNS disorders.},
}

@article {pmid42460525,
year = {2026},
author = {Liu, Y and Yang, J and Su, J and Hao, L},
title = {High Levels of Plasma Neurturin Partially Mediate the Protective Effect of Reduced Ruminococcus2 Abundance on Multiple Sclerosis: A Mendelian Randomization Study.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X468669260626223524},
pmid = {42460525},
issn = {1875-6190},
abstract = {BACKGROUND: Genetic evidence implicates the contribution of the gut-brain axis to neurodegenerative diseases (NDDs). Alterations in gut microbiota and inflammation are key pathophysiological contributors. Elucidating the genetic basis and the role of cytokines can provide insights into mechanisms linking gut microbial composition to neurodegeneration.

METHODS: Using aggregated statistics from five large-scale Genome-Wide Association Studies (GWAS) on Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, multiple sclerosis, and amyotrophic lateral sclerosis, bidirectional two-sample Mendelian Randomization (MR) was used to examine the associations. A two-step multivariable Mendelian randomization approach incorporates data from 91 cytokines to explore potential mediators.

RESULTS: The study reveals 18 positive and 17 negative effects between gut microbiota and NDDs, as well as 10 positive and 10 negative effects between cytokines and NDDs. Remarkably, mediation analysis identified a causal pathway, with evidence that plasma neurturin levels partially mediate the association from genus Ruminococcus2 to multiple sclerosis, with a mediation proportion of 19.19% (OR = 1.038, 95% CI = 1.001-1.086, P = 0.044). No pleiotropy or heterogeneity was detected.

DISCUSSION: These MR findings provide compelling evidence for a genetically anchored gutimmune-brain network in NDDs, with cytokines as intermediates. Bidirectional effects highlight disease-specific microbial signatures and inflammatory contexts. The Ruminococcus2-neurturin pathway in multiple sclerosis may offer mechanistic specificity, aligning with neurotrophic and anti-inflammatory signaling pathways.

CONCLUSION: This study emphasizes the importance of gut microbiota alterations in NDDs and explores inflammation's partial intermediary role. The findings suggest potential targets for personalized neurodegeneration prevention strategies.},
}

@article {pmid42460529,
year = {2026},
author = {Chen, H and Yang, Z and Meng, H and Hu, Z and Ke, Z and Ye, Q and Xu, Y and Wu, J and Liu, Z},
title = {White Matter Functional Dysregulation in Amyotrophic Lateral Sclerosis: Machine Learning-Based Biomarkers and Transcriptomic Signatures.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X465668260629073047},
pmid = {42460529},
issn = {1875-6190},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor system degeneration, yet its white matter (WM) functional pathophysiology remains underexplored.

METHODS: This study utilized resting-state functional magnetic resonance imaging to decode WM functional abnormalities in 50 ALS patients and 55 healthy controls. Next, machine learning analysis was applied to evaluate the utility of these WM functional patterns in diagnosing ALS and predicting disease progression, and their pathophysiological mechanisms were preliminary explored through neurotransmitter mapping and imaging transcriptomics.

RESULTS: ALS patients exhibited reduced activity in central WM regions (including bilateral corticospinal tracts), accompanied by elevated activity in anterior and posterior WM territories. The aberrant topological properties and disrupted functional connectivity are predominantly localized within bilateral precentral/postcentral WM networks. A support vector machine model incorporating these features achieved 75.24% classification accuracy and predicted the rate of disease progression (r = 0.56, p = 0.001). The spatial pattern of WM dysfunction in ALS was associated with both the spatial distribution of disease-related neurotransmitters and the expression profiles of specific genes.

DISCUSSION: Our findings reveal distinct WM functional dysfunction patterns in ALS and their molecular-genetic underpinnings, providing novel insights into the pathophysiological mechanisms of ALS.

CONCLUSION: ALS involves specific patterns of WM dysfunction, and these WM-centric biomarkers may facilitate the development of therapeutic monitoring frameworks for this devastating disease.},
}

@article {pmid42461162,
year = {2026},
author = {Zhang, R and Zhang, N and Li, B and Liu, Q and Xu, C and Li, B and Zhang, J},
title = {Nursing a Patient With Amyotrophic Lateral Sclerosis Stage 4B With Epilepsy: A Case Study.},
journal = {Nursing in critical care},
volume = {31},
number = {4},
pages = {e70573},
pmid = {42461162},
issn = {1478-5153},
support = {25ZZJJLW-015//Medical Research Council Foundation of the 305 Hospital of the PLA/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/nursing/complications ; *Epilepsy/nursing/complications ; Male ; Intensive Care Units ; *Critical Care Nursing/methods ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease characterised by progressive muscle weakness, which can eventually lead to death. So far there is no effective cure for it. This case report discusses the nursing of a patient with stage 4B amyotrophic lateral sclerosis complicated with epilepsy and sudden disturbance of consciousness during his stay in an intensive care unit (ICU). After 34 days of treatment and care, the patient regained consciousness with stable vital signs before being transferred out of the ICU. This report focusses on nursing interventions adopted in terms of respiratory management, nutritional management, psychological care and exercise during both the epileptic seizure and the awake period of the patient in the hope of providing a reference for the nursing of patients with amyotrophic lateral sclerosis with epilepsy in intensive care units.},
}

Humans
*Amyotrophic Lateral Sclerosis/nursing/complications
*Epilepsy/nursing/complications
Male
Intensive Care Units
*Critical Care Nursing/methods

@article {pmid42461445,
year = {2026},
author = {Mitsumoto, H and Cheung, K and Matsumoto, T and Lanza, I and Oskarsson, B and Johnson, S and Petterson, XT and Jang, GE and Andrews, HF},
title = {Metabolomic analyses of amyotrophic lateral sclerosis, muscle cramps, and TJ-68 treatment.},
journal = {Metabolomics : Official journal of the Metabolomic Society},
volume = {22},
number = {4},
pages = {},
pmid = {42461445},
issn = {1573-3890},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/blood ; *Muscle Cramp/drug therapy/metabolism/blood ; *Metabolomics/methods ; Female ; Male ; Middle Aged ; Aged ; Cross-Over Studies ; Medicine, Kampo ; *Drugs, Chinese Herbal/therapeutic use ; },
abstract = {INTRODUCTION: Most patients with amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease, experience painful muscle cramps. Our recent pilot trial of the Japanese Kampo medicine TJ-68 suggested its efficacy in improving muscle cramps in patients with ALS.

OBJECTIVES: This study analyzed plasma metabolomic changes to identify the underlying mechanisms of muscle cramps in ALS and the effects of TJ-68.

METHODS: Plasma was obtained from 11 participants with ALS in the repeated crossover trial at five time points (baseline, two placebo phases, and two TJ-68 phases). Metabolites were analyzed using mass spectrometry. Linear mixed-effects models were applied to identify metabolite changes associated with muscle cramps, determine the effects of TJ-68 on metabolites, and predict which participants would respond to TJ-68.

RESULTS: Higher glutamine/glutamate, arginine, and leucine levels were associated with more severe muscle cramps. TJ-68 treatment increased tryptophan and aconitate levels but reduced serotonin and acetylcarnitine levels. Long-chain acylcarnitine levels were correlated with muscle cramp severity, and their levels tended to decrease with treatment. Uric acid, β-aminoisobutyric acid, α-aminoadipic acid, and acetylcholine emerged as predictors of the efficacy of TJ-68.

CONCLUSION: This study identified the metabolite profile of muscle cramps in ALS and the changes in metabolite levels after TJ-68 treatment. Several baseline metabolites were associated with the prediction of the response to muscle cramps following TJ-68 treatment. Uric acid might be particularly useful because of its easy measurement in standard assays. Our study affirms the value of metabolomic technology for future pharmacotherapy and studies in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/blood
*Muscle Cramp/drug therapy/metabolism/blood
*Metabolomics/methods
Female
Male
Middle Aged
Aged
Cross-Over Studies
Medicine, Kampo
*Drugs, Chinese Herbal/therapeutic use

@article {pmid42461653,
year = {2026},
author = {Kneepkens, SCM and Lingham, G and van Hemert, DJ and Loughman, J and Strang, NC and Tham, YC and Harrington, SC and Guisasola, L and French, A and He, X and Mackey, DA and Hagen, LA and Baraas, RC and Pärssinen, O and Yam, JC and Saunders, KJ and Guggenheim, JA and Saw, SM and Lan, WZ and Klaver, CCW and Flitcroft, DI and , },
title = {Global Axial Length Centile Charts.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2026.2539},
pmid = {42461653},
issn = {2168-6173},
abstract = {IMPORTANCE: Myopia is increasingly common worldwide and poses major public health challenges because axial elongation drives sight-threatening complications. Because axial length (AL) is the primary target for myopia management, population-specific AL reference charts are needed.

OBJECTIVE: To generate region- and sex-specific reference centile charts for AL in children and adolescents.

This was a pooled cohort analysis using individual-participant data from population- and school-based studies conducted in East Asia, Europe, and Australia contributing to the CREAM-Kids Consortium. A total of 147 404 children and adolescents contributing 559 799 AL measurements were included. Most participants were from East Asia (84%; ages 6-18 years), followed by Europe (12%; ages 6-21 years) and Australia (4%; ages 6-21 years). After assessment of comparability, European and Australian datasets were combined. Data were included from 1999 to 2024, with the analysis taking place from December 2024 to May 2026.

EXPOSURES: AL, age, sex, and geographic region.

MAIN OUTCOMES AND MEASURES: Region- and sex-specific AL centiles across age and agreement between modeled centiles and empirical values.

RESULTS: AL distributions among the 147 404 included individuals varied by sex and region. In female individuals, the 50th centile AL at age 7 years was 22.35 mm in Europe and Australia and 22.67 mm in East Asia; by age 18 years, the 50th centile ALs were 23.31 mm and 24.36 mm, respectively. Regional differences were larger at higher centiles: for female individuals at age 7 years, East Asia vs Europe and Australia differences were 0.33 mm at the 3rd centile and 0.50 mm at the 97th centile; at age 18 years, differences were 0.73 mm and 1.27 mm, respectively. Modeled centile curves closely matched empirical values (intraclass correlations >0.99) with minimal bias across sex and region subgroups (-0.08 mm to 0.04 mm).

CONCLUSIONS AND RELEVANCE: While not based solely on population-based cohorts, the region- and sex-specific AL centile charts developed in this pooled cohort study provide reference values for childhood and adolescence that may be used to support clinical and research applications, including identifying atypical axial elongation and informing targeted strategies for myopia prevention and management.},
}

@article {pmid42461927,
year = {2026},
author = {Zhong, F and Ni, C and Wang, B},
title = {Optimal pooling strategies for respiratory virus testing: A comparative cost-effectiveness analysis.},
journal = {PLOS global public health},
volume = {6},
number = {7},
pages = {e0006646},
pmid = {42461927},
issn = {2767-3375},
abstract = {Pooled testing represents a cost-efficient strategy for large-scale respiratory virus screening. However, determining the optimal pool size (OPS) across varying prevalence rates and diagnostic performance metrics remains a critical challenge in respiratory virus surveillance. We evaluated four hierarchical OPS algorithms, all employing the original solution method (OSM), and proposed a modified solution method (MSM) based on objective function optimization. Through Monte Carlo simulations and logit modeling, we generated COVID-19 infection data representative of community transmission patterns. These data were analyzed using a comparative cost-effectiveness framework to assess OSM and MSM approaches. Our analysis across various prevalence rates (0.1-30.0%), sensitivities (0.8-1.0), and specificities (0.97-1.00) revealed Hanel et al.'s algorithm consistently yielded the largest OPS values under OSM. MSM revealed minimal deviations from OSM in most scenarios, though it effectively corrected Kim et al.'s inflated OPS values at high prevalence (~30%) with low sensitivity/specificity. Three algorithms produced comparable OPS configurations, outperforming OSM. Hanel's and Regen's algorithms emerged as the most cost-effective options, with Hanel's method being optimal for low additional costs in second-stage testing and Regen's for high additional costs. MSM significantly reduced inter-algorithm cost differences compared to OSM. This study provides a comprehensive evaluation of OPS determination algorithms in pooled PCR testing for respiratory viruses, demonstrating robust OPS configurations and enhanced cost-effectiveness through MSM implementation. The proposed MSM addresses existing limitations in pooled testing strategies, facilitates efficient resource allocation, and contributes to improved respiratory virus surveillance and pandemic response.},
}

@article {pmid42462180,
year = {2026},
author = {Baskar, K and Steffke, C and Bernsen, S and Elmas, Z and Hesebeck-Brinckmann, J and Schuster, J and Meyer, T and Weydt, P and Weishaupt, J and Brenner, D and Catanese, A},
title = {Multiplex Panel Detects Glial and Inflammatory Biomarker Signatures in Sporadic and C9orf72-ALS.},
journal = {Neurology(R) neuroimmunology & neuroinflammation},
volume = {13},
number = {5},
pages = {e200618},
doi = {10.1212/NXI.0000000000200618},
pmid = {42462180},
issn = {2332-7812},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/genetics ; Biomarkers/cerebrospinal fluid ; Female ; Male ; C9orf72 Protein/genetics ; Middle Aged ; Aged ; Neuroglia ; *Neuroinflammatory Diseases/cerebrospinal fluid ; Neurofilament Proteins/cerebrospinal fluid ; Adult ; *Inflammation/cerebrospinal fluid ; Chitinase-3-Like Protein 1/cerebrospinal fluid ; },
abstract = {BACKGROUND AND OBJECTIVES: CSF proteomics has emerged as a valuable strategy for identifying diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). However, the limited availability and volumes of CSF samples restrict the broader clinical application of CSF-based biomarker panels. To address this challenge, we investigated whether the novel nucleic acid-linked immuno-sandwich assay (NULISA) multiplex platform-capable of quantifying multiple neural, glial, and inflammatory markers from minimal biofluid volumes-could validate previously proposed biomarkers and identify additional candidates relevant to ALS.

METHODS: Using this platform, we measured a targeted panel of 131 biomarkers in cohorts of patients with C9orf72-associated ALS, sporadic ALS (sALS), and matched healthy controls.

RESULTS: The 6 markers neurofilament heavy chain (NEFH) and neurofilament light chain (NEFL), chitinases-particularly chitotriosidase-1 (CHIT1) and chitinase-3-like protein-1 (CHI3L1), and chemokines CCL2 and CCL3 were significantly elevated in both ALS groups compared with controls. These biomarkers correlated with disease progression and demonstrated strong diagnostic performance when combined into aggregate scores, as reflected by a high area under the receiver operating characteristic curve for ALS. Notably, C9orf72-ALS patients exhibited higher levels of the oxidative stress-related markers PRDX6 and ENO2, compared with sALS patients, suggesting a genotype-specific molecular signature.

DISCUSSION: Overall, our findings support the use of a multiplexed panel of diverse, inflammatory, glial, and neurodegeneration-associated biomarkers as a complementary diagnostic and prognostic tool alongside established measurements of neurofilaments. This approach may enhance biomarker robustness while minimizing CSF volume requirements, thereby improving clinical feasibility in ALS research and care.},
}

Humans
*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/genetics
Biomarkers/cerebrospinal fluid
Female
Male
C9orf72 Protein/genetics
Middle Aged
Aged
Neuroglia
*Neuroinflammatory Diseases/cerebrospinal fluid
Neurofilament Proteins/cerebrospinal fluid
Adult
*Inflammation/cerebrospinal fluid
Chitinase-3-Like Protein 1/cerebrospinal fluid

@article {pmid42463858,
year = {2026},
author = {Picchiarelli, G and Demestre, M and Zuko, A and Been, M and Higelin, J and Dieterlé, S and Goy, MA and Mallik, M and Sellier, C and Scekic-Zahirovic, J and Zhang, L and Rosenbohm, A and Sijlmans, C and Aly, A and Mersmann, S and Sanjuan-Ruiz, I and Hübers, A and Messaddeq, N and Wagner, M and van Bakel, N and Boutillier, AL and Ludolph, A and Lagier-Tourenne, C and Boeckers, TM and Dupuis, L and Storkebaum, E},
title = {Author Correction: FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41593-026-02396-9},
pmid = {42463858},
issn = {1546-1726},
}

@article {pmid42454381,
year = {2026},
author = {Mai, R and Zhang, X and Yu, G and Chen, Z and Zhao, W and Shi, Z and Gao, X and Liang, Z and Fu, C},
title = {Robust Covalent Organic Frameworks Comprising Accessible Catalytic Sites Enable Fast-Charging and Long-Cycling Aluminum-Sulfur Batteries.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {},
number = {},
pages = {e74063},
doi = {10.1002/adma.74063},
pmid = {42454381},
issn = {1521-4095},
abstract = {Rechargeable aluminum-sulfur (Al-S) batteries are recognized as a promising option for large-scale energy storage due to high theoretical energy density and cost-effectiveness. However, the sulfur cathodes suffer from sluggish reaction kinetics and severe shuttle effect during cycling. Here we report robust two-dimensional covalent organic frameworks (COFs) as sulfur hosts that features accessible catalytic nitrogen sites and confined microporous channels. The fine regulation of different microporous sizes was achieved by controlling different-length organic ligands of various COFs, finally preparing two kinds of COFs. The sensitive comparation between both COFs demonstrates that smaller microporous channels in COFs possess higher confinement effect for polysulfides due to the stronger capillary forces, facilitating higher Coulombic efficiency and better cycling stability in Al-S batteries. Meanwhile, experimental characterizations and theoretical calculations reveal that accessible catalytic nitrogen sites in COFs promote the multistep conversion kinetics of the sulfur cathode during cycling. Consequently, the small-sized COF confined sulfur cathode exhibits a reversible capacity of 1120 mAh g[-1] at 0.2C and a 93.5% capacity retention after 100 cycles, supporting high capacity and exceptional cycling stability. This work provides a new avenue on rational design of emerging COF materials in Al-S batteries.},
}

@article {pmid42454435,
year = {2026},
author = {Walls, M and Claffey, A and Galvin, M},
title = {Moral distress in healthcare professionals working with motor neuron disease.},
journal = {Palliative & supportive care},
volume = {24},
number = {},
pages = {e196},
doi = {10.1017/S1478951526103058},
pmid = {42454435},
issn = {1478-9523},
mesh = {Humans ; *Motor Neuron Disease/psychology/complications/therapy ; *Health Personnel/psychology/statistics & numerical data ; Cross-Sectional Studies ; Female ; Male ; Adult ; Europe ; Surveys and Questionnaires ; Middle Aged ; Ethical Dilemmas ; Quality of Life/psychology ; },
abstract = {OBJECTIVES: To (1) identify clinical situations that may contribute to the experience of moral distress (MD) among professionals working with motor neuron disease (MND), (2) measure the occurrence and intensity of MD, and (3) explore associations with professional quality of life, turnover intention, and associated risk and/or protective factors.

METHODS: A cross-sectional online survey was distributed to healthcare professionals working in MND services across Europe. Data were analyzed using descriptive and inferential statistics.

RESULTS: In total, 230 responses from professionals across 17 European countries were analyzed from the international survey. And 67% of respondents indicated that MD resonated with their experience of working with MND. Those who considered leaving or changing their position due to the challenges associated with caring for this patient population were also more likely to report resonance with MD (χ[2] = 7.772, p = 0.020). The intensity of MD was associated with reduced professional quality of life (burnout [β = 0.106, p < 0.05], and secondary traumatic stress [β = 2.881, p < 0.001]). A total of 24 clinical scenarios were identified as potential contributors to experiences of MD in this population. Across all professional groups, service-/organization-level factors were the most common and distressing barriers to providing effective MND care.

SIGNIFICANCE OF RESULTS: This study demonstrates that MD is experienced by healthcare professionals working with MND across Europe. MD was associated with reduced professional quality of life and increased intentions to leave or change positions, underscoring its potential implications for workforce retention and sustainability. The findings show that system/organization, patient/condition and family-level causes are the primary drivers of MD in this population. Future research should focus on evaluating the effectiveness of interventions designed to address these key drivers and mitigate the impact of MD among healthcare professionals working with MND.},
}

Humans
*Motor Neuron Disease/psychology/complications/therapy
*Health Personnel/psychology/statistics & numerical data
Cross-Sectional Studies
Female
Male
Adult
Europe
Surveys and Questionnaires
Middle Aged
Ethical Dilemmas
Quality of Life/psychology

@article {pmid42454523,
year = {2026},
author = {Ahmed, RM and Tse, NY and Bocchetta, M and Dobson-Stone, C and Kwok, JB and Hodges, JR and Irish, M and Rohrer, JR and Piguet, O and Halliday, G},
title = {Changes in body composition in genetic C9orf72 carriers: The role of the hypothalamus and thalamus.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71669},
doi = {10.1002/alz.71669},
pmid = {42454523},
issn = {1552-5279},
support = {//National Health and Medical Research Council/ ; },
mesh = {Humans ; *C9orf72 Protein/genetics ; *Body Composition/genetics ; Magnetic Resonance Imaging ; Female ; Male ; *Thalamus/diagnostic imaging ; *Frontotemporal Dementia/genetics ; *Hypothalamus/diagnostic imaging ; Heterozygote ; Middle Aged ; Absorptiometry, Photon ; Aged ; },
abstract = {BACKGROUND: Patients with sporadic frontotemporal dementia (FTD) display changes in metabolism and body composition. No studies have examined body composition changes in pre-symptomatic C9orf72 mutation carriers METHODS: Asymptomatic C9orf72 expansion carriers between 2017 and 2022 (n = 28 non-carriers, 16 expansion-positive), underwent dual-energy X-ray absorptiometry (measurement of changes in body composition) and brain magnetic resonance imaging (MRI).

RESULTS: Changes in body composition were identified in the C9orf72 expansion carrier group compared to non-carrier group (average 11-12 years prior to onset): lower android-to-gynoid ratio (p = 0.009), and visceral adipose tissue area (p = 0.010). Lower android-to-gynoid ratio and lean mass were associated with lower volumes across the cortex, subcortex, and thalamus.

CONCLUSIONS: The current study highlights that genetically at-risk C9orf72 patients exhibit altered body composition. These findings align with the growing recognition that changes in genetic frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) extend beyond cognitive/motor symptoms and include early alterations in broader physiological function.},
}

Humans
*C9orf72 Protein/genetics
*Body Composition/genetics
Magnetic Resonance Imaging
Female
Male
*Thalamus/diagnostic imaging
*Frontotemporal Dementia/genetics
*Hypothalamus/diagnostic imaging
Heterozygote
Middle Aged
Absorptiometry, Photon
Aged

@article {pmid42455190,
year = {2026},
author = {Lei, Y and Huang, J and Li, M and Zhang, Y and Ye, Z and He, X and Tang, Z and Wei, J},
title = {Effects of respiratory muscle training on respiratory function in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42455190},
issn = {1432-1459},
support = {No. EWT201947//Department of Science and Technology of Hubei Province/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/complications/therapy ; *Breathing Exercises/methods ; *Respiratory Muscles/physiopathology ; },
abstract = {BACKGROUND: Respiratory decline is prognostically important in amyotrophic lateral sclerosis (ALS), but the efficacy of respiratory muscle training (RMT) remains uncertain. We synthesized randomized evidence on respiratory and related outcomes.

METHODS: We searched databases, specialized registers, and trial registries through June 19, 2025, for randomized RMT trials in ALS. Risk of bias was assessed with the Cochrane tool. Random-effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), and certainty was rated with GRADE.

RESULTS: Six studies were included; five concurrently randomized trials contributed quantitative data, whereas Pinto 2013 was retained for qualitative context. RMT improved maximal expiratory pressure (MEP; SMD 0.387, 95% CI 0.192-0.581; P = 0.008) and showed small favorable effects on maximal inspiratory pressure (MIP; SMD 0.156, 95% CI 0.089-0.224; P = 0.005), sniff nasal inspiratory pressure (SNIP; SMD 0.216, 95% CI 0.039-0.392; P = 0.034), peak expiratory flow (PEF; SMD 0.205, 95% CI 0.088-0.323; P = 0.017), and ALSFRS-R (SMD 0.214, 95% CI 0.039-0.388; P = 0.030). Forced vital capacity showed a borderline favorable trend (SMD 0.129, 95% CI - 0.003 to 0.262; P = 0.053). Low heterogeneity estimates were imprecise because most endpoints included only three to four small studies. Certainty was moderate for MIP, low for MEP, FVC, and PEF, and very low for SNIP and ALSFRS-R. Exploratory analyses identified no reliable effect modifiers.

CONCLUSIONS: RMT was associated with small, directionally consistent improvements mainly in pressure- and flow-based outcomes, whereas effects on FVC and longer-term clinical outcomes remain uncertain. RMT may be considered an individualized adjunct to ALS respiratory care, not a disease-modifying therapy. Larger, longer, standardized trials with patient-important endpoints are needed.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/complications/therapy
*Breathing Exercises/methods
*Respiratory Muscles/physiopathology

@article {pmid42455475,
year = {2026},
author = {Maity, D and Gowtham, A and Mishra, Y and Kaundal, RK},
title = {Exosome Biology at the Interface of Neurodegeneration and Therapeutic Innovation.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42455475},
issn = {1559-1182},
mesh = {Humans ; *Exosomes/metabolism ; Animals ; *Neurodegenerative Diseases/therapy/metabolism/pathology ; Biomarkers/metabolism ; },
abstract = {Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are defined by progressive neuronal loss, protein misfolding, and chronic neuroinflammation, yet effective disease-modifying therapies remain absent. Exosomes have emerged as key mediators of central nervous system communication and are increasingly central to the biology of neurodegeneration. These nanoscale vesicles transport proteins, lipids, and nucleic acids across cellular and anatomical barriers, influencing synaptic function, immune signaling, and metabolic homeostasis. Under pathological conditions, exosomes facilitate the spread of misfolded proteins such as amyloid-β, p-tau, α-synuclein, and TDP-43, thereby accelerating network-level degeneration. At the same time, their cargo exhibits disease-specific molecular signatures detectable in peripheral biofluids, supporting their development as minimally invasive biomarkers for early diagnosis and longitudinal monitoring. Advances in exosome engineering further underscore their potential as therapeutic delivery vehicles capable of crossing the blood-brain barrier and targeting pathogenic pathways with RNA-based therapeutics, proteins, or gene-editing systems. Together, these findings position exosomes as pivotal contributors to both the mechanistic progression and translational targeting of neurodegenerative diseases.},
}

Humans
*Exosomes/metabolism
Animals
*Neurodegenerative Diseases/therapy/metabolism/pathology
Biomarkers/metabolism

@article {pmid42456096,
year = {2026},
author = {Soliven, REMR and Igarashi, Y and Norii, T and Nakanishi, H and Suga, R and Takiguchi, T and Okada, I and Nakae, R and Yokobori, S},
title = {Performance of termination-of-resuscitation rules in foreign body airway obstruction-related out-of-hospital cardiac arrest: a prospective multicenter registry analysis.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/10903127.2026.2703842},
pmid = {42456096},
issn = {1545-0066},
abstract = {OBJECTIVES: Termination-of-resuscitation (TOR) rules were derived mainly from cardiac-origin out-of-hospital cardiac arrest (OHCA), but their interpretation in foreign body airway obstruction (FBAO)-related OHCA remains uncertain. This condition is a potentially reversible hypoxic arrest in which standard TOR criteria may perform differently. We evaluated the 2025 American Heart Association basic life support (BLS)-TOR and advanced life support (ALS)-TOR criteria in FBAO-related OHCA.

METHODS: This secondary analysis of the prospective multicenter MOCHI registry included patients with FBAO-related OHCA transported to 25 Japanese hospitals from April 2020 to March 2023. For the primary TOR analysis, we included patients who had not achieved return of spontaneous circulation (ROSC) before emergency medical services (EMS) arrival, because TOR rules are intended for patients who remain in cardiac arrest at the time of EMS assessment. Patients were retrospectively classified according to BLS-TOR and ALS-TOR criteria. Primary measures were the specificity of TOR-positive status for predicting unfavorable neurological outcome, defined as the proportion of patients with favorable neurological outcome (Cerebral Performance Category 1-2) who were classified as TOR-negative, and the proportion of TOR-positive patients who nevertheless achieved favorable neurological outcome.

RESULTS: Of 248 patients with FBAO-related OHCA (median age, 81.5 years; 83.1% witnessed), 49 (19.8%) survived to 30 days and 9 (3.6%) achieved favorable neurological outcome. The BLS-TOR rule classified 150/229 evaluable patients as TOR-positive; 2 achieved favorable neurological outcome (1.3%; 95% CI, 0.4-4.7%; specificity, 77.8% (95% CI, 45.3-93.7%)), and 20 survived to 30 days (13.3%; 95% CI, 8.8-19.7%). The ALS-TOR rule classified 12/242 patients as TOR-positive; none achieved favorable neurological outcome, but 4 survived to 30 days (33.3%; 95% CI, 13.8-60.9%).

CONCLUSIONS: In FBAO-related OHCA, BLS-TOR would have classified two patients with favorable neurological outcome as TOR-positive. The ALS-TOR rule was restrictive, but small numbers and 30-day survival among TOR-positive patients preclude firm safety conclusions. Termination-of-resuscitation criteria warrant cautious, etiology-aware interpretation when FBAO is suspected.},
}

@article {pmid42456270,
year = {2026},
author = {Martinez, D and Georgiou, GK and Inoue, T and Parrila, R and Protopapas, A},
title = {The genesis of reading fluency in beginning readers.},
journal = {Journal of experimental child psychology},
volume = {272},
number = {},
pages = {106593},
doi = {10.1016/j.jecp.2026.106593},
pmid = {42456270},
issn = {1096-0457},
abstract = {Although reading fluency plays a crucial role in reading comprehension, little is known about its early development. In this study, we first aimed to replicate Hudson et al.'s (2009, 2012) model of reading fluency development among beginning readers and, second, to expand it by incorporating components of articulation rate, sub-lexical orthographic knowledge, and reading accuracy, all of which are theoretically linked to reading fluency development. Three hundred and thirty English-speaking Grade 1 students (51.5% female; Mage = 74.82 months; SD = 3.60) were assessed at three time points (September [T1], January [T2], and May [T3]). At T1, we administered measures of rapid automatized naming (RAN), processing speed, phonemic blending fluency, and letter-sound fluency, at T2, measures of phonogram fluency and sub-lexical orthographic knowledge, and, finally, at T3, word reading fluency, nonword reading fluency, and text reading fluency. Using path analysis, we tested three models: a baseline model based on Hudson et al.'s model and two expanded models that included the additional measures. Our results replicated the core relations proposed by Hudson et al. and further demonstrated significant contributions from sub-lexical orthographic knowledge and reading accuracy to text reading fluency through word reading fluency. These findings are consistent with theoretical frameworks such as Ehri's (2014) orthographic mapping framework and the lexical quality hypothesis (Perfetti, 2007), showing the contributions but also limitations of the components of the reading fluency model.},
}

@article {pmid42456455,
year = {2026},
author = {Jung, MJ and Oh, WO},
title = {Strategic simulation-based management of triage clinical reasoning in novice emergency nurses: A randomized block design study.},
journal = {Nurse education in practice},
volume = {95},
number = {},
pages = {104928},
doi = {10.1016/j.nepr.2026.104928},
pmid = {42456455},
issn = {1873-5223},
abstract = {AIM: To develop and evaluate the effectiveness of the Triage Clinical Reasoning Simulation Program (Triage-CRSP).

BACKGROUND: Globally, emergency department (ED) triage is largely performed by general nurses, with increasing emphasis on clinical reasoning (CR) to assess care urgency; however, novice emergency nurses have limited triage-related competencies.

DESIGN: This study consisted of two phases: program development and effectiveness evaluation. The first phase involved developing Triage-CRSP. The second phase evaluated its effectiveness using a randomized block design, with the completion of KTAS (Korea Triage Acuracy Scale) training as the blocking factor.

METHODS: The theoretical framework of this program was based on O'Neill et al.'s clinical decision-making and novice clinical reasoning models. The simulation program was developed using a six-step approach to curriculum development. A total of 60 emergency nurses with less than three years of experience were stratified by completion of KTAS training and randomly allocated to either the intervention or control group; under a single-blind design, the intervention group received the developed Triage-CRSP, while the control group received the existing KTAS simulation.

RESULTS: The 'Triage-CR pattern' was identified as a structured multi-step clinical reasoning process. The intervention group demonstrated significantly greater improvements in triage clinical reasoning knowledge, recognition of critical clinical cues, emergency nursing performance and overall triage competence compared with the control group.

CONCLUSIONS: The simulation-based triage clinical reasoning program was effective in enhancing multiple dimensions of triage practice among novice emergency nurses.},
}

@article {pmid42456683,
year = {2026},
author = {Bouzigues, A and Grassi, M and Cantoni, V and Premi, E and Bellini, S and Binetti, G and Logroscino, G and Russell, LL and Ferry-Bolder, E and Foster, PH and van Swieten, JC and Jiskoot, LC and Seelaar, H and Sanchez-Valle, R and Laforce, R and Graff, C and Galimberti, D and Vandenberghe, R and de Mendonça, A and Di Fede, G and Santana, I and Gerhard, A and Langheinrich, T and Levin, J and Nacmias, B and Otto, M and Bertoux, M and Lebouvier, T and Ducharme, S and Butler, C and le Ber, I and Bruffaerts, R and Solje, E and Kinnunen, M and Krüger, J and Finger, E and Tartaglia, MC and Masellis, M and Rowe, JB and Synofzik, M and Moreno, F and Ghidoni, R and Migliaccio, R and Rohrer, JD and Borroni, B and , },
title = {Survival estimates and their predictors in genetic frontotemporal dementia: an international, retrospective, cohort study.},
journal = {The Lancet. Neurology},
volume = {25},
number = {8},
pages = {731-740},
doi = {10.1016/S1474-4422(26)00197-3},
pmid = {42456683},
issn = {1474-4465},
mesh = {Humans ; *Frontotemporal Dementia/genetics/mortality/diagnosis ; Retrospective Studies ; C9orf72 Protein/genetics ; tau Proteins/genetics ; Female ; Male ; Middle Aged ; Aged ; Cohort Studies ; Progranulins/genetics ; Mutation ; Kaplan-Meier Estimate ; },
abstract = {BACKGROUND: What drives the heterogeneity of survival estimates in genetic frontotemporal dementia is unknown. We sought to understand the natural history and predictors of disease trajectory, which are crucial not only for effective care but also for the design of therapeutic clinical trials and efficacy evaluation.

METHODS: In this international, cohort study, we used the Kaplan-Meier method to retrospectively assess survival estimates in patients enrolled in the GENFI cohort, which included 32 research sites located in Belgium, Canada, Finland, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and the UK, and comprised participants carrying a causal C9orf72 expansion or a causal mutation in GRN or MAPT genes. Survival was calculated as the time from symptom onset to time of death or censoring date; median survival estimate for all patients was the primary endpoint. Cox proportional hazards models were used to identify predictors of survival, which were subsequently externally validated in an independent cohort. We further designed a structural equation model to assess the relationships between predictors, applying a least absolute shrinkage and selection operator method.

FINDINGS: Of 278 participants of the GENFI cohort included in this study, 160 (58%) were men and 118 (42%) were women. 162 died during follow-up (58%) and 116 were still alive (42%) on June 1, 2024, the chosen censoring date. 138 participants carried a C9orf72 expansion, 94 carried a GRN mutation, and 46 a MAPT mutation. 179 participants were diagnosed with behavioural variant frontotemporal dementia, 46 with primary progressive aphasia, and 31 with frontotemporal dementia-amyotrophic lateral sclerosis. 22 participants had other diagnoses. The median survival estimate for all patients with genetic frontotemporal dementia was 6·94 years (95% CI 6·59-7·80) from symptom onset. The median survival estimate for patients with GRN mutations was 6·63 years (6·08-7·98), for patients with a C9orf72 expansion was 7·04 years (6·45-8·77), and for patients with MAPT mutations was 8·56 years (7·06-13·50). Older age at onset, shorter disease duration from onset to enrolment in the GENFI study, clinical presentation (ie, frontotemporal dementia-amyotrophic lateral sclerosis), domain of first symptom (ie, motor or language onset), and geographical area of residency (ie, central and southern Europe) were associated with poorer prognosis. Genetic group did not directly affect survival estimates; rather its effect was mediated by age at onset and clinical phenotype. We computed a genetic frontotemporal dementia survival risk index, which can be used at an individual patient level.

INTERPRETATION: Our results highlight that motor impairment in addition to cognitive and behavioural symptoms should be considered when estimating prognosis in genetic frontotemporal dementia. Individual risk scores might be of help for patient stratification in future therapeutic trials, although refinement and prospective validation are now needed.

FUNDING: Italian Ministry of Health (Ricerca Corrente), Fondation Philippe Chatrier, and Fondation Vaincre Alzheimer.},
}

Humans
*Frontotemporal Dementia/genetics/mortality/diagnosis
Retrospective Studies
C9orf72 Protein/genetics
tau Proteins/genetics
Female
Male
Middle Aged
Aged
Cohort Studies
Progranulins/genetics
Mutation
Kaplan-Meier Estimate

@article {pmid42457567,
year = {2026},
author = {Akiyama, T and Aoki, M},
title = {Cracking a New Era of Therapeutic Development in ALS.},
journal = {The Tohoku journal of experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1620/tjem.2026.J082},
pmid = {42457567},
issn = {1349-3329},
}

@article {pmid42458007,
year = {2026},
author = {Chen, W and Jiang, L and Duan, C and Kang, M and Ye, J and Wang, L and Pan, Y and Qu, H and Liao, X and Zhou, X and Li, Y and Gan, Z and Chen, J and Schacht, I and Place, RF and Li, LC and Wang, Y},
title = {Oligonucleotide-siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial.},
journal = {Nature medicine},
volume = {32},
number = {7},
pages = {2619-2628},
pmid = {42458007},
issn = {1546-170X},
support = {No.Z231100004823036//Beijing Municipal Science and Technology Commission/ ; 20230484245//Beijing Nova Program/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease partly caused by gain-of-function mutations in superoxide dismutase 1 (SOD1). Here we developed RAG-17, an siRNA-targeting SOD1, using an accessory oligonucleotide conjugate platform for enhanced central nervous system (CNS) delivery. Preclinically, RAG-17 rescued motor neuron degeneration, delayed disease progression, preserved motor function and extended survival in SOD1[G93A] ALS rodents, even with advanced-stage treatment. In cynomolgus monkeys, intrathecal RAG-17 led to dose-dependent, durable reductions in SOD1 mRNA (CNS) and protein (cerebrospinal fluid (CSF)). In a first-in-human trial in patients with SOD1-ALS (n = 6), participants were assigned to two cohorts-cohort 1 (n = 3) received an initial 60 mg dose (seven doses total) and cohort 2 (n = 3) received an initial 90 mg dose (six doses total). The dose was escalated in 30 mg steps to maintenance doses of 150 mg (n = 5) or 180 mg (n = 1). Thus, the primary safety endpoint was met, showing acceptable safety and tolerability. Treatment-emergent adverse events (TEAEs) occurred in 33% of participants (two of six). All TEAEs were mild to moderate, including muscle tremor (two patients) and elevated alanine aminotransferase (one patient), all of which resolved. No serious adverse events were reported. Furthermore, no other clinically meaningful changes were observed in laboratory parameters, vital signs, the ALS Functional Rating Scale-Revised score, physical or neurological examinations or ECG. The key secondary endpoints showed CSF SOD1 reductions of 69% (cohort 1, day 240) and 56% (cohort 2, day 210), and plasma neurofilament light chain reductions of 62% (cohort 1) and 52% (cohort 2), from baseline; no patient required invasive mechanical ventilation or died by the end of the study. These results demonstrate a favorable safety outcome, supporting the continued clinical evaluation of RAG-17 for SOD1-ALS. ClinicalTrials.gov registration: NCT05903690 .},
}

@article {pmid42458453,
year = {2026},
author = {Bolsinger, MM and Vivek, N and Singh, J and Challa, A and Zhu, A and Rothell, T and Wang, S and Zhang, T and Zhu, S and Robbins, N and Fenwick, L and Ruttenberg, G and Bogoniewski, A and Taha, HB},
title = {Extracellular vesicles as a liquid biopsy for amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08562-8},
pmid = {42458453},
issn = {1479-5876},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome diagnosed clinically using standardized criteria, with neuropathological confirmation of motor neuron loss and TDP-43 aggregates in postmortem brain tissue. Extracellular vesicles (EVs) have emerged as potential minimally invasive biomarkers for ALS, but studies vary widely in methodology and reproducibility. We conducted a systematic review and meta-analysis to evaluate the diagnostic potential of EV-associated proteins and RNAs in ALS. Following PRISMA guidelines, we searched PubMed and EMBASE from inception to May 21st, 2026. Forty-one studies met inclusion criteria. Where published summary statistics were available, these were used directly; where they were not, data were reconstructed from figures or obtained from authors and re-analyzed to derive standardized effect sizes and exploratory diagnostic accuracy estimates. Random-effects models were used for continuous outcomes, and diagnostic accuracy was assessed using hierarchical summary ROC and bivariate random-effects models. Publication bias was evaluated using Begg, Egger, and funnel plots. EV-associated TDP-43 was the most frequently studied protein. Meta-analysis of five studies showed a moderate but non-significant increase in EVs from ALS vs. controls (SMD = 1.30) with high heterogeneity (I = 97.8%). Sixteen studies assessing EV-RNA biomarkers showed minimal overlap and limited independent replication. Diagnostic accuracy meta-analysis across 11 studies yielded moderate performance (AUC = 0.839). No publication bias was found across both meta-analyses. EV biomarkers for ALS show biological promise but are limited by methodological variability and insufficient replication. This work highlights the need for standardized protocols, transparent data sharing, and independent validation.},
}

@article {pmid42458498,
year = {2026},
author = {Wang, H and Wen, R and Parker, E and Yang, L},
title = {TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-03083-9},
pmid = {42458498},
issn = {1478-811X},
support = {32300959//National Natural Science Foundation of China/ ; SL2024A04J00578//Guangzhou Scientific Research Grant/ ; 22KJ04//SCNU Young Faculty Development Program/ ; },
abstract = {Triggering receptor expressed on myeloid cells 2 (TREM2) is a critical myeloid receptor expressed on the surface of central nervous system microglia, capable of integrating signals from lipids, damage-associated molecular patterns, and abnormal protein aggregates to regulate phagocytosis, metabolic adaptation, inflammatory remodeling, and pathology-associated responses. Accumulating evidence indicates that TREM2 is neither uniformly protective nor uniformly pathogenic; rather, its biological effects are highly context-dependent, governed collectively by disease stage, pathological substrates, cellular compartments, and the local microenvironment. By coupling with TYROBP/DAP12 or DAP10, TREM2 actively drives the state remodeling of pathology-associated microglia. It profoundly influences the onset and progression of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), as well as acute central nervous system injuries, including ischemic stroke, spinal cord injury (SCI), and traumatic brain injury (TBI). Concurrently, soluble TREM2 (sTREM2) holds significant potential not only as a biomarker but also as a context-dependent effector molecule actively participating in pathological regulation. This review synthesizes current advancements by focusing on four core themes: the structural and signaling logic of the TREM2 axis; its regulation of disease-associated microglia (DAM) remodeling; the cross-disease significance of sTREM2; and the mechanistic basis for the divergent outcomes observed with TREM2-targeted therapies across different experimental models and disease stages. The objective is to elucidate the context-dependent roles of TREM2 by analyzing consensus mechanisms, sources of discrepancy, and translational implications, thereby providing a theoretical framework and strategic direction for more precise TREM2-targeted interventions.},
}

@article {pmid42458512,
year = {2026},
author = {Jo, M and Kim, S and Woo, J and Park, JS and Kim, SH and Nahm, M and Kim, SR and Lee, S and Kim, HJ},
title = {Targeting astrocyte-mediated neurotoxicity induced by ALS/FTD-associated RNA binding proteins.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-03082-w},
pmid = {42458512},
issn = {1478-811X},
support = {RS-2024-00454715//National Research Foundation of Korea/ ; RS-2024-00343239//National Research Foundation of Korea/ ; 26-BR-02-03//Korea Brain Research Institute/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders characterized by reactive astrocytes that contribute to neuronal injury through TAR DNA-binding protein 43 (TDP-43)-or fused in sarcoma (FUS)-driven neuroinflammatory signaling. Dehydrocostus lactone (DHE), a blood-brain barrier-permeable sesquiterpene lactone with established anti-inflammatory activity, represents a promising but unexplored therapeutic candidate for ALS/FTD.

METHODS: The therapeutic effects of DHE were evaluated in primary mouse and human astrocytes expressing ALS/FTD-associated RNA-binding protein pathology, ALS patient-derived fibroblasts, and primary cortical neurons exposed to astrocyte-conditioned medium. Drosophila models expressing mutant FUS or TDP-43 in glial cells were used to assess locomotor performance and survival. Molecular analyses examined nuclear factor kappa B (NF-κB) signaling, nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant responses, protein aggregation, mitochondrial function, and inflammatory mediator production. Plasma concentrations of inflammatory cytokines and chemokines were measured in patients with sporadic ALS.

RESULTS: DHE exerted neuroprotective effects through a dual mechanism involving suppression of NF-κB-dependent inflammatory signaling and activation of NRF2-mediated antioxidant pathways in astrocytes exhibiting FUS or TDP-43 proteinopathy. DHE attenuated astrocyte-mediated neurotoxicity and improved neuronal mitochondrial function in conditioned-medium assays. In addition, DHE reduced pathological FUS accumulation in FUS P525L-expressing astrocytes and in stress-challenged patient-derived fibroblasts. In Drosophila models, DHE significantly improved locomotor function and extended survival. Translationally, the chemokines CXCL10, CCL3, and CCL19 were elevated in plasma from patients with ALS, were induced by FUS or TDP-43 pathology in astrocytes, and were suppressed by DHE treatment, supporting the clinical relevance of the inflammatory pathways targeted by DHE.

CONCLUSION: DHE mitigates astrocyte-driven neurotoxicity associated with ALS/FTD-related RNA-binding protein pathology by suppressing inflammatory signaling and enhancing antioxidant defense mechanisms. The consistent therapeutic effects observed across mouse and human cellular models, patient-derived samples, and in vivo Drosophila models support further investigation of DHE as a potential therapeutic strategy for ALS/FTD and highlight astrocyte-mediated signaling pathways as actionable targets in neurodegenerative disease.},
}

@article {pmid42458576,
year = {2026},
author = {Akan, T and Aishwarya, R and Bhuiyan, MS and Conrad, SA and Vanchiere, JA and Bhuiyan, MAN},
title = {From unlabeled to labeled: self-supervised deep learning in computational pathology.},
journal = {BioData mining},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13040-026-00586-6},
pmid = {42458576},
issn = {1756-0381},
support = {R01HL172970, R01HL145753, R01HL145753-01S1, and R01HL145753-03S1//Foundation for the National Institutes of Health/ ; P20GM121307//Foundation for the National Institutes of Health/ ; },
abstract = {PURPOSE: The advancement of decision support systems for pathology and their implementation in clinical practice have been limited by the necessity for extensive, manually annotated datasets. Self-supervised learning (SSL) automates the extraction and interpretation of histopathological features from unannotated images, facilitating efficient model development without dependence on expert labeling. In this study, we introduce the SSL-HistoNet model that learns disease-relevant morphological representations from histopathological images through self-supervised learning.

MATERIALS AND METHODS: We applied it to WGA-stained skeletal muscle tissues from mouse models of amyotrophic lateral sclerosis (ALS) and Type I diabetes to explore its ability to capture pathological muscle phenotypes in an annotation-free setting. Following pretraining on unlabeled data, the SSL encoder was further integrated with an attention-guided classifier to evaluate its capacity to identify pathological muscle alterations.

RESULTS: SSL-HistoNet achieved a precision of 0.98, a recall of 0.98, and an AUC of 0.98, demonstrating performance comparable to or outperforming state-of-the-art supervised models. Alongside high discriminative performance, exploratory feature analyses demonstrated consistent class-level changes in morphology-related patterns identified through representation learning.

CONCLUSION: These findings highlight the capability of SSL-HistoNet as an annotation-free framework for outlining disease-specific tissue structures, reducing manual labeling demands and mitigating inter- and intra-observer variability in histological processes.

CLINICAL TRIAL NUMBER: Not applicable.},
}

@article {pmid42441689,
year = {2026},
author = {de Vienne, D and de Vienne, DM},
title = {Age-based risk estimates for C9orf72RE-related diseases: Theoretical developments and added value for genetic counseling.},
journal = {PLoS genetics},
volume = {22},
number = {7},
pages = {e1012230},
doi = {10.1371/journal.pgen.1012230},
pmid = {42441689},
issn = {1553-7404},
abstract = {The C9orf72 hexanucleotide repeat expansion is the most common genetic cause of amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). In genetic counseling, children of mutation carriers are often told that they have a 50% risk of carrying the mutation, but this figure does not take into account the fact that penetrance is age-related, with a unimodal distribution of disease onset around 58 years of age. Using a Bayesian approach, we developed a theory to calculate the probability of carrying the mutation for asymptomatic relatives (children/siblings and grandchildren/niblings) as well as the probability of developing ALS/FDT within a given time frame, based on their age. Using published data on age-related penetrance, we then calculated these probabilities and developed an online simulator that makes it easy to calculate them on a case-by-case basis. The conditional probabilities obtained can be very different from Mendelian values. For example, a 70-year-old asymptomatic child born to a carrier has approximately a 6% risk of being a carrier, which is far from 50%. For grandchildren, taking into account both their age and that of their parents also leads to figures that are much lower than those obtained if only their age were considered. For consultands, the decision to undergo testing is based in part on risk estimates. In this regard, the refined estimates and simulator we propose may prove to be valuable tools for genetic counseling for families affected by ALS/FTD linked to the C9orf72RE mutation. In addition, the formulas used in this study could also be used to calculate risk estimates for other diseases caused by autosomal dominant mutations with age-dependent penetrance.},
}

@article {pmid42441693,
year = {2026},
author = {Fisher, K and Ligay, A and Stratford, M and Hirani, R and Ober, DT and Al-Seykal, I and Frishman, WH and Etienne, M},
title = {Cardiac Autonomic Dysfunction and Sudden Cardiac Death in Amyotrophic Lateral Sclerosis: Clinical Implications and Considerations for Care.},
journal = {Cardiology in review},
volume = {},
number = {},
pages = {},
doi = {10.1097/CRD.0000000000001392},
pmid = {42441693},
issn = {1538-4683},
abstract = {Amyotrophic lateral sclerosis (ALS) is traditionally viewed as a motor neuron disease that progresses from muscular weakness to respiratory failure and death. Increasing evidence, however, demonstrates clinically meaningful involvement of the autonomic nervous system, particularly in cardiovascular regulation. This narrative review synthesizes current evidence on the mechanisms, clinical implications, and palliative considerations of cardiac autonomic dysfunction in ALS, with particular emphasis on its relationship to sudden cardiac death (SCD). Cardiac autonomic dysfunction is increasingly recognized as a significant contributor to disease burden in ALS, manifesting as abnormalities in heart rate variability, sympathetic overactivity, and corrected QT prolongation. These derangements may contribute to malignant arrhythmias, increasing susceptibility to SCD in combination with respiratory decline. Epidemiologic data suggest that SCD accounts for a meaningful proportion of ALS-related mortality, although it is likely underrecognized due to misclassification and lack of routine cardiac monitoring. Clinical implications include the need for improved risk stratification and earlier detection of autonomic dysfunction using accessible markers, such as electrocardiographic indices, orthostatic vital signs, and ambulatory monitoring. Emerging technologies, including wearable biosensors, may further enhance longitudinal assessment. These considerations also have direct relevance for advanced care planning, as ALS may involve unpredictable and abrupt cardiac death in addition to progressive respiratory decline. Recognizing ALS as a multisystem disorder with significant cardiac involvement supports the integration of structured cardiovascular monitoring into multidisciplinary care models and highlights the need for prospective studies to guide standardized management strategies.},
}

@article {pmid42442024,
year = {2026},
author = {Andreeva, T and Tuparev, N and Taneva, SG},
title = {Multimodal biophysical markers of neurodegeneration: Morphology, mechanics, and thermodynamics.},
journal = {Current opinion in structural biology},
volume = {100},
number = {},
pages = {103330},
doi = {10.1016/j.sbi.2026.103330},
pmid = {42442024},
issn = {1879-033X},
abstract = {The identification of novel noninvasive biomarkers remains a major challenge in the diagnosis of neurodegenerative diseases. Significant efforts focus on fluid biomarkers, including proteins, peptides, and miRNAs, detectable in blood plasma and peripheral blood cells. Here, we review recent findings on blood plasma and peripheral blood cells physical parameters in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis emphasizing atomic force microscopy and calorimetry assay. Alterations in morphology, nanostructure, and stiffness of red blood cells and platelets, together with thermodynamic signatures of red blood cells and plasma, provide sensitive indicators of disease-related changes. These integrated biophysical parameters not only distinguish neurodegeneration from healthy states but also enable discrimination among different neurodegenerative disorders, highlighting their potential as minimally invasive diagnostic markers.},
}

@article {pmid42442469,
year = {2026},
author = {Kerner, D and Carey, L and Hughes, J},
title = {Using CoI to Address Emerging Problems in Academic Pharmacy.},
journal = {American journal of pharmaceutical education},
volume = {},
number = {},
pages = {102051},
doi = {10.1016/j.ajpe.2026.102051},
pmid = {42442469},
issn = {1553-6467},
abstract = {Pharmacy education is currently facing numerous challenges, such as concerning first-time pass rates on licensure examinations, decreasing applicant pools, new accreditation standards, progression concerns, and changing financial and regulatory landscapes. These complex and shared issues require collaborative and innovative approaches across the academy. One potential strategy is the development of Communities of Inquiry (CoI), a collaborative model grounded in Garrison et al.'s theoretical framework of social, cognitive, and teaching presence. CoI emphasize active engagement, shared problem-solving, reflective discourse, and collective responsibility for learning and innovation. This manuscript describes the theoretical foundation of the CoI model and its application within pharmacy academia. Existing applications of CoI principles in pharmacy education literature, including faculty development initiatives and webinar-based learning experiences, are also reviewed. Additionally, a real-world example of a successful CoI is presented through the development of a NAPLEX Preparation CoI. Communities of Inquiry represent an effective framework for addressing new challenges in pharmacy education. Faculty, administrators, and professional organizations are encouraged to establish and participate in CoIs. As pharmacy education continues to evolve, the CoI approach presents a promising strategy for fostering innovation, meeting accreditation standards, and enhancing student outcomes through community-driven solutions.},
}

@article {pmid42442754,
year = {2026},
author = {Sonnenberg, A and Bakis, LK and Kohen, R},
title = {Gastrointestinal Diagnoses and Symptoms in Medicare Patients With Neuropsychiatric Diseases.},
journal = {Journal of clinical gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCG.0000000000002422},
pmid = {42442754},
issn = {1539-2031},
abstract = {BACKGROUND AND AIMS: Many patients with psychiatric and neurological diseases suffer from gastrointestinal symptoms. Our study aimed to analyze the frequency of gastrointestinal disease in patients with underlying neuropsychiatric diagnoses.

METHODS: The study utilized the 2018 Inpatient Standard Analytic File of the Centers for Medicare and Medicaid Services (CMS), which contains the electronic health records of 6,462,321 unique patients. The concurrence of 2 diagnoses was assessed by calculating odds ratios (OR) with their 95% CIs, adjusted for the confounding influences of demographic characteristics (age, sex, ethnicity).

RESULTS: Dementia was most strongly associated with dysphagia (2.85, 2.83 to 2.88). Schizophrenia was associated with functional GI disorders (1.62, 1.60 to 1.64), constipation (1.67, 1.65 to 1.69), and dyspepsia (2.02, 1.88 to 2.17). Bipolar disorder was most significantly associated with irritable bowel syndrome (1.83, 1.79 to 1.87) and dyspepsia (1.88, 1.77 to 2.01). Depression was significantly associated with all types of upper and lower GI symptoms with significant ORs ranging from 1.33 to 2.14. Amyotrophic lateral sclerosis was strongly associated with complaints of functional GI disorder (2.32, 2.18 to 2.46), constipation (2.37, 2.23 to 2.51), dysphagia (11.77, 11.19 to 12.39), flatulence and bloating (2.75, 2.14 to 3.54). Parkinson disease was mostly associated with constipation (1.79, 1.77 to 1.82) and dysphagia (2.96, 2.92 to 3.00). In Alzheimer disease, only symptoms of dysphagia (2.15, 2.12 to 2.17) stood out. Multiple sclerosis was associated with most GI diagnoses (OR ranging from 1.32 to 2.06), except for abdominal pain and reflux symptoms.

CONCLUSIONS: Concurrence of gastrointestinal and neuropsychiatric diagnoses is common. Caring for patients with neuropsychiatric diseases, physicians need to be aware of and proactively search for the presence of concurrent gastrointestinal disease.},
}

@article {pmid42442908,
year = {2026},
author = {Dongre, S and Soni, N and Bissa, B},
title = {Role of ESCRT pathway and autophagy in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {187},
number = {},
pages = {1-16},
doi = {10.1016/bs.irn.2026.05.022},
pmid = {42442908},
issn = {2162-5514},
mesh = {Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism ; *Autophagy/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; },
abstract = {Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss resulting from impaired proteostasis and vesicular trafficking. Neurons are particularly vulnerable to these processes due to their post-mitotic nature and complex architecture. Autophagy and the endolysosomal system constitute the primary degradative pathways responsible for maintaining neuronal homeostasis. However, increasing evidence indicates that their effective function critically depends on coordination with the endosomal sorting complexes required for transport (ESCRT). Beyond their canonical role in multivesicular body biogenesis and membrane scission, ESCRT components are now recognized as essential regulators of autophagosome closure, amphisome formation, autophagosome-lysosome fusion, and endolysosomal membrane repair. Disruption of this ESCRT-autophagy interface has emerged as a common pathological feature across major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia. This review synthesizes evidence from genetic, biochemical, and neuropathological studies to highlight shared molecular nodes, such as ESCRT-III components, the VPS4 ATPase, the adaptor protein ALIX, and late endosomal regulators, including Rab7, that couple membrane remodeling to autophagic flux. Failure of these regulatory checkpoints destabilizes endolysosomal integrity, arrests autophagic maturation, and promotes the accumulation of toxic protein species, thereby driving progressive neuronal degeneration. By framing neurodegeneration through the lens of ESCRT-autophagy coupling failure, this review provides a unified mechanistic perspective that links diverse pathogenic proteins to shared cellular vulnerabilities and identifies ESCRT-mediated membrane dynamics as a critical determinant of neuronal survival.},
}

Humans
*Endosomal Sorting Complexes Required for Transport/metabolism
*Autophagy/physiology
*Neurodegenerative Diseases/metabolism/pathology
Animals

@article {pmid42443201,
year = {2026},
author = {Wang, Y and Hu, W and Huang, R and Wu, F and Su, H and Zang, J and Huang, X and Liu, Y and Ren, H and Li, J and Zhang, M and Zhang, Y and Wang, G and Hao, Z},
title = {Nuclear condensates formed by truncated mutant NEK1s impede ribosomal RNA biogenesis and drive motor dysfunction.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-75500-z},
pmid = {42443201},
issn = {2041-1723},
support = {32000676//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {NIMA-related kinase 1 (NEK1), a serine/threonine kinase, is a risk variant for amyotrophic lateral sclerosis (ALS). While the full-length NEK1 is involved in diverse cellular processes, such as DNA damage response and microtubule stability, the pathogenic mechanism of NEK1 nonsense mutations in ALS remains elusive. Here, we demonstrate that three truncated forms of NEK1 derived from ALS-related NEK1 nonsense mutations translocate from the cytoplasm to the nucleus, exhibit nucleolar localization, and simultaneously form liquid-like nucleoplasmic foci. In contrast to the diffuse cytoplasmic distribution of wild-type NEK1, these nuclear-localized truncated mutants are prone to undergo liquid-liquid phase separation both in cells and in vitro. Mechanistically, the truncated NEK1s interact with the nucleolar protein FBL, thereby impairing ribosomal RNA biogenesis and translation. Transgenic flies expressing truncated mutant NEK1s display motor dysfunction and reduced survival length, and a knock-in transgenic mouse model expressing ALS-related NEK1 mutant similarly exhibits motor deficits accompanied by ribosomal RNA dysregulation. These findings suggest that ALS-related NEK1 mutants expressing truncated forms of NEK1 cause cell toxicity by interfering with ribosomal RNA metabolism and reveal a gain-of-function mechanism in ALS pathogenesis involving NEK1.},
}

@article {pmid42443387,
year = {2026},
author = {Kim, WS and Halliday, GM},
title = {Astrocytic lipid dysregulation as an early driver of neurodegeneration.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42443387},
issn = {1759-4766},
abstract = {Astrocytes have traditionally been cast as supportive glia, but they are increasingly recognized as metabolic hubs that regulate cholesterol synthesis, fatty acid detoxification, lipid droplet dynamics and redox homeostasis in the CNS. Neurons have a limited intrinsic capacity for lipid storage and detoxification and rely heavily on astrocytes to maintain a safe lipid environment. Emerging evidence indicates that dysregulation of astrocytic lipid homeostasis precedes overt neuronal degeneration in a range of neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, frontotemporal dementia and Huntington disease. Perturbations in astrocytic lipid handling can drive maladaptive reactive states, promote oxidative stress, impair lysosomal and mitochondrial function and disrupt neuron-glia lipid exchange, collectively creating an environment that leads to neurodegeneration. Therefore, lipid dysregulation within astrocytes could trigger or amplify neuronal vulnerability. In this Review, we assess evidence that astrocytic lipid metabolism is not solely protective or pathological but has instructive physiological roles and that astrocytic lipid dysregulation is an early driver of neurodegeneration. We critically evaluate disease-specific evidence, distinguishing correlative observations from causal mechanisms. We propose that targeting of astrocytic lipid homeostasis represents a promising strategy for preventing or minimizing neurodegeneration and opens new avenues for early detection and biomarker development.},
}

@article {pmid42444959,
year = {2026},
author = {Akpa, B},
title = {The role of radiologic assessment in evaluating and monitoring respiratory function in amyotrophic lateral sclerosis (ALS) patients: a narrative review.},
journal = {Journal of thoracic disease},
volume = {18},
number = {6},
pages = {672},
pmid = {42444959},
issn = {2072-1439},
abstract = {BACKGROUND AND OBJECTIVE: Respiratory failure is the primary cause of mortality in amyotrophic lateral sclerosis (ALS), usually caused by progressive neuromuscular respiratory weakness. Standard pulmonary function tests (PFTs) such as maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and both supine and upright forced vital capacity (FVC) are crucial for objective measurements of diaphragmatic weakness but have limitations, including dependence on the patient's performance and the inability to detect early, subclinical diaphragmatic impairment or be used effectively in patients with bulbar symptoms. Radiological assessments, particularly dynamic imaging, have emerged as potential objective tools for evaluating respiratory function. This review comprehensively summarizes findings on the use of diaphragmatic ultrasound (DUS), dynamic chest magnetic resonance imaging (MRI) and deep learning (DL)-based chest computed tomography (CT) for assessing lung function in ALS patients.

METHODS: Key radiological metrics include diaphragm thickness (DT), thickening fraction during inspiration, real-time diaphragmatic excursion, lung diameter changes and changes in pulmonary length and area. These measures have been compared with conventional PFTs in various studies to validate their use for diagnostic accuracy, particularly in early stages of disease.

KEY CONTENT AND FINDINGS: DUS is a non-invasive, widely available tool that strongly correlates with PFT measurements, especially FVC, MIP, and sniff nasal inspiratory pressure (SNIP). Dynamic measures, such as excursion and velocity, appear more sensitive to early dysfunction than thickness alone. Chest dynamic MRI has also shown significant correlations with spirometric parameters. Small cohort studies indicate that dynamic chest MRI is a superior, sensitive tool for detecting early respiratory impairment in asymptomatic patients with normal spirometry.

CONCLUSIONS: Radiological assessments, primarily DUS, DL-based chest CT and dynamic MRI, offer valuable, objective, and non-invasive methods for monitoring respiratory muscle strength in ALS. These techniques serve as complementary tools to traditional PFTs, particularly in selected clinical scenarios such ALS patients with early disease, bulbar involvement and unable to perform PFTs. Further longitudinal research with larger cohorts is needed to standardize protocols and validate their role as early parameters to guide the timely initiation of supportive interventions like non-invasive ventilation (NIV).},
}

@article {pmid42445484,
year = {2026},
author = {Ahmed, R and Kayande, A and Patil, R and Shelar, A and Zore, GB},
title = {Context-dependent reprogramming of ALS adhesin expression in Candida albicans: a multi-inducer analysis linking morphogenesis to virulence plasticity.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1848556},
pmid = {42445484},
issn = {1664-302X},
abstract = {Candida albicans employs the ALS (Agglutinin-Like Sequence) gene family to encode cell-surface adhesins that are central to host colonization, tissue invasion, and biofilm formation. Although individual ALS genes have been studied under specific conditions, no systematic, multi-inducer temporal analysis of the entire family has been reported to date. In this study, we present the first comprehensive temporal expression profiling of seven ALS genes (ALS1-ALS5, ALS7, and ALS9) under six host-relevant inducers, temperature (37 °C), neutral pH, serum, glucose, N-acetylglucosamine (NAG), and proline, across four time points (45 min, 90 min, 3 h, 6 h) in both yeast (30 °C) and hyphal (37 °C) growth phases. Morphological analysis confirmed that 37 °C and serum were the most potent hyphal inducers (94.13 ± 0.94% hyphae with serum at 37 °C). Quantitative PCR revealed a temporally stratified regulatory program: early-phase adhesins (ALS1, ALS2) showed transient induction during the first 90 min, whereas invasion-associated genes exhibited sustained late-phase activation. Notably, ALS3 displayed exceptional upregulation under glucose at 37 °C (25.17 ± 1.76-fold at 6 h; p < 0.001) and responded robustly to all inducers except serum. ALS7 reached 9.48-fold induction specifically under thermal stress, while ALS5 was preferentially expressed at 30 °C (6.70-fold under neutral pH), indicating niche-specific functional specialization. In silico promoter analysis linked these expression patterns to binding motifs for key transcription factors (Efg1, Cph1, Rim101, and Nrg1). Phylogenetic analysis revealed functional conservation of ALS2/ALS4 versus evolutionary divergence in ALS6/ALS7/ALS9. STRING-based protein interaction networks confirmed the central involvement of ALS proteins in adhesion and biofilm regulatory circuits. These findings establish a molecular framework for niche-specific virulence, identifying ALS3 as a prime therapeutic target for anti-adhesion strategies in invasive candidiasis. We hypothesize that C. albicans employs a temporally stratified and inducer-specific transcriptional program of the ALS family to adapt its surface architecture to diverse host microenvironments.},
}

@article {pmid42447123,
year = {2026},
author = {Wohnrade, C and Thau-Habermann, N and Gschwendtberger, T and Rückoldt, J and Huang, Z and Schreiber, S and Haastert-Talini, K and Petri, S},
title = {Neuromuscular ultrasound as a biomarker in the SOD1 mouse model of amyotrophic lateral sclerosis.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0353397},
pmid = {42447123},
issn = {1932-6203},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/genetics/physiopathology ; Mice ; *Superoxide Dismutase/genetics ; Disease Models, Animal ; Superoxide Dismutase-1 ; Biomarkers/metabolism ; Ultrasonography ; Mice, Transgenic ; Humans ; Sciatic Nerve/diagnostic imaging/pathology ; Muscle, Skeletal/diagnostic imaging/pathology ; Motor Neurons/pathology ; Disease Progression ; },
abstract = {A progression marker that indicates early disease-related changes and treatment responses in the to date incurable neurodegenerative disease amyotrophic lateral sclerosis (ALS) is highly desirable. Translation of therapeutics that have been successful in in vivo models into trials in human patients has proven difficult in recent decades. This failure can be attributed, at least in part, to the lack of specific biomarkers for ALS diagnosis and progression in human ALS patients as well as in in vivo models. Neuromuscular ultrasound is an easily accessible, non-invasive tool to support diagnosis of ALS in humans. Our current study shows for the first time that the disease can be detected in an ALS mouse model with the help of neuromuscular ultrasound. We characterized disease progression regarding changes in the peripheral nerves and muscles of the hind limb in the SOD1G93A mouse model of ALS using different techniques (neuromuscular ultrasound, electroneurography, motor function tests, phenotypic assessments and histology). By neuromuscular ultrasound, we measured the cross-sectional area and diameter of the sciatic nerve and analyzed hind limb muscle texture and thickness. Our results show that motor neuron loss and muscle atrophy - analogous to ALS in humans - can be measured by ultrasound in the SOD1G93A mouse model. Changes in nerve and muscle morphology appear at the same time or even before changes in the established tests (including electroneurographic measurements) performed in vivo in this model. Correlations with histologic features of disease progression make neuromuscular ultrasound a sensitive, non-invasive outcome marker for preclinical studies.},
}

Animals
*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/genetics/physiopathology
Mice
*Superoxide Dismutase/genetics
Disease Models, Animal
Superoxide Dismutase-1
Biomarkers/metabolism
Ultrasonography
Mice, Transgenic
Humans
Sciatic Nerve/diagnostic imaging/pathology
Muscle, Skeletal/diagnostic imaging/pathology
Motor Neurons/pathology
Disease Progression

@article {pmid42447443,
year = {2026},
author = {Hicks-Courant, K},
title = {Taking Responsibility.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502100},
doi = {10.1200/JCO-25-02100},
pmid = {42447443},
issn = {1527-7755},
abstract = {This essay is about how caring for my complicated father with amyotrophic lateral sclerosis (ALS) unexpectedly shaped how I approached my work as a gynecologic oncologist.},
}

@article {pmid42447895,
year = {2026},
author = {Arnolds, KB and Peinemann, F},
title = {[Infant-driven versus Practitioner-driven Feeding of Preterm Infants: A Systematic Review of Randomized Controlled Trials].},
journal = {Zeitschrift fur Geburtshilfe und Neonatologie},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2894-2931},
pmid = {42447895},
issn = {1439-1651},
abstract = {HINTERGRUND: Voraussetzung für eine erfolgreiche orale Ernährung ist die Berücksichtigung des individuellen Entwicklungsstands der Frühgeborenen. Pflegekräfte und Eltern sollten geschult sein, wie sie Verhaltenssignale des Säuglings während des Fütterns erkennen und darauf angemessen reagieren können. Diese Art der Ernährung wird in dieser Arbeit als "signalorientiertes und co-reguliertes" Füttern von Frühgeborenen bezeichnet. Im Unterschied zeichnet sich das "herkömmliche" Füttern dadurch aus, dass eine vorab festgelegte Flüssigkeitsmenge zu einer festgelegten Zeit verabreicht wird.

ZIELSETZUNG: Es soll untersucht werden, ob das "signalorientierte und co-regulierte" Füttern im Vergleich zum "herkömmlichen" Füttern zu einer früheren vollständigen oralen Ernährung führen kann.

METHODEN: Wir haben am 26. Juni 2024 in den elektronischen Datenbanken MEDLINE und Cochrane Library nach thematisch relevanten randomisierten Studien gesucht. Als primärer Endpunkt wurde die Anzahl der Tage bis zur vollständigen oralen Ernährung und als Effektmaß die mittlere Differenz gewählt. Die Metaanalyse wurde unter Verwendung der inversen Varianzmethode und des Random-Effects-Modells durchgeführt, und wir verwendeten den GRADE-Ansatz (Grading of Recommendations Assessment, Development, and Evaluation) für die Bewertung der Evidenz.

ERGEBNISSE: In der Studienauswahl fanden sich 12 randomisierte Studien, die den Einschlusskriterien entsprachen. Von diesen wurden 5 Studien in eine Metaanalyse einbezogen. Die geschätzte mittlere Differenz favorisierte die Gruppen mit signalorientiertem und co-reguliertem Füttern im Vergleich zu den Gruppen mit herkömmlicher Fütterung: -4,93 (95%-Konfidenzintervall -6,60 bis -3,26, p<0,00001, I[2] =66%). Die Qualität der Evidenz wurde als moderat eingestuft.

SCHLUSSFOLGERUNGEN: Die Daten der Studienteilnehmer sind mit einem leicht vorteilhaften Effekt für die signalorientierte und co-regulierte Ernährung von Frühgeborenen im Vergleich zur herkömmlichen Ernährung von Frühgeborenen vereinbar. Zukünftige Studien könnten weitere Daten zu unerwünschten Ereignissen während der Ernährung und Informationen zur häuslichen Nachsorge ergänzen.},
}

@article {pmid42448407,
year = {2026},
author = {Rangappa, N and Upadhyay, R and Lakshman, N and Ramasamy, S and Sevanan, M and Justin, A and Chinnathambi, S},
title = {Small molecular therapeutic targets for neurodegenerative diseases.},
journal = {Advances in protein chemistry and structural biology},
volume = {153},
number = {},
pages = {135-167},
doi = {10.1016/bs.apcsb.2025.10.012},
pmid = {42448407},
issn = {1876-1631},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology/genetics ; Animals ; *Molecular Targeted Therapy ; },
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis disease are characterized by progressive neuronal loss, protein aggregation, and synaptic dysfunction. These diseases share common pathological mechanisms including oxidative stress, mitochondrial impairment, chronic neuroinflammation, protein misfolding, and epigenetic dysregulation. Current therapies offer only symptomatic relief and fail to halt disease progression. Recent advances in transcriptomics and proteomics have enabled the identification of shared molecular pathways and druggable targets across multiple neurodegenerative diseases. The key targets, such as BDNF-TrkB, TREM2, SIRT1, PINK1-Parkin, GSK-3β, NLRP3, and mTOR have shown promise in preclinical models, offering opportunities for broad-spectrum therapeutic development. Importantly, blood-brain barrier disruption and neuroinflammatory crosstalk exacerbate disease pathology and hinder drug delivery. Innovative strategies involving nanocarriers, gene therapy, and epigenetic modulation are emerging to overcome these barriers. This review highlights the convergence of disease mechanisms, discusses common molecular signatures and therapeutic vulnerabilities, and explores novel small molecular interventions targeting shared pathways mainly in AD and PD. A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology/genetics
Animals
*Molecular Targeted Therapy

@article {pmid42449472,
year = {2026},
author = {de Albuquerque Bueno, MG and Dos Santos, DF and Rossor, AM and Laura, M and Horga, A and Frezatti, RSS and de Sousa Ferreira, EV and Blake, JC and Morrow, JM and Reilly, MM and Marques Júnior, W and Tomaselli, PJ},
title = {VRK1-Related Motor Neuropathy With Upper Motor Neuron Signs and Selective Muscle Involvement.},
journal = {Journal of the peripheral nervous system : JPNS},
volume = {31},
number = {3},
pages = {e70145},
doi = {10.1111/jns.70145},
pmid = {42449472},
issn = {1529-8027},
support = {MR/S005021/1//International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD)/ ; 25000.160.096/2014-07//Programa Nacional de Apoio à Atenção da Saúde da Pessoa com Deficiência (PRONAS)/ ; 465 458/20114-9//National Institute of Sciences and Technology (INCT)-Translational Medicine/ ; 310378/2021-4//Conselho Nacional de Pesquisa (CNPq)/ ; FE-CLI-24-0005-05//Biogen/ ; },
mesh = {Humans ; Female ; Male ; *Motor Neuron Disease/genetics/physiopathology/diagnostic imaging/pathology ; *Protein Serine-Threonine Kinases/genetics ; Adult ; Middle Aged ; Magnetic Resonance Imaging ; *Intracellular Signaling Peptides and Proteins/genetics ; *Muscle, Skeletal/physiopathology/diagnostic imaging/pathology ; Nerve Conduction Studies ; Young Adult ; Electromyography ; Neural Conduction/physiology ; Adolescent ; Child ; },
abstract = {INTRODUCTION: Hereditary motor neuropathies (HMN) represent a heterogeneous group of disorders with wide clinical and genetic variability. Despite advances in molecular diagnostics, approximately 50% of cases remain genetically unresolved, particularly those where distinguishing length-dependent motor neuropathy from motor neuron disorder with disproportionate segmental involvement is a challenge. Variants in the VRK1 gene, originally described in association with pontocerebellar hypoplasia, are now known to produce a broad clinical spectrum, including amyotrophic lateral sclerosis, dHMN, and less frequently, spastic paraplegia.

OBJECTIVES: This study's aim was to characterize the clinical presentation, electrophysiological findings, and muscle MRI patterns associated with VRK1-related motor neuron disease in a cohort of nine patients from five unrelated families.

METHODS: Five unrelated families with inherited motor neuropathy were investigated using next-generation sequencing techniques, including targeted gene panels or whole-exome sequencing, with subsequent confirmation by Sanger sequencing. A total of nine affected individuals underwent detailed clinical evaluation, nerve conduction studies (NCS), electromyography (EMG), and whole-body muscle MRI (wbMRI).

RESULTS: Nine affected individuals carrying biallelic VRK1 variants were evaluated. In most cases (66%), symptom onset occurred during the first decade of life. All patients presented with gradually progressive distal muscle weakness. Mean Medical Research Council (MRC) scores were 2.8 for ankle dorsiflexion and 1.9 for plantar flexion. Sensory nerve conduction studies were normal in all individuals evaluated (8/9), although mild sensory complaints were reported in four patients. Muscle cramps were observed in two-thirds of the cohort, while fasciculations were uncommon (11%). EMG findings consistently demonstrated a neurogenic pattern with predominant distal involvement, and evidence of both acute and chronic denervation was present in four patients. Whole-body muscle MRI, available for all patients, revealed a consistent pattern of fatty infiltration predominantly affecting posterior muscle compartments, with minimal STIR signal changes. Brain and spinal imaging, performed in all individuals, showed no abnormalities.

INTERPRETATIONS: Biallelic mutations in VRK1 are associated with a recognizable form of motor neuron disease characterized by features of dHMN combined with upper motor neuron involvement, along with a distinctive posterior-predominant pattern on muscle MRI. Identifying this phenotype, a known presentation of VRK1-related disorders, highlights the importance of targeted genetic testing in unresolved cases of hereditary motor neuropathy.},
}

Humans
Female
Male
*Motor Neuron Disease/genetics/physiopathology/diagnostic imaging/pathology
*Protein Serine-Threonine Kinases/genetics
Adult
Middle Aged
Magnetic Resonance Imaging
*Intracellular Signaling Peptides and Proteins/genetics
*Muscle, Skeletal/physiopathology/diagnostic imaging/pathology
Nerve Conduction Studies
Young Adult
Electromyography
Neural Conduction/physiology
Adolescent
Child

@article {pmid42450002,
year = {2026},
author = {Kim, Y and Jung, YK},
title = {Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.},
journal = {International journal of molecular sciences},
volume = {27},
number = {13},
pages = {},
doi = {10.3390/ijms27135730},
pmid = {42450002},
issn = {1422-0067},
support = {RS-2025-00519823//National Research Foundation of Korea/ ; RS-2024-00439842//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Proteasome Endopeptidase Complex/metabolism ; *Neurodegenerative Diseases/metabolism/therapy/pathology/drug therapy ; Animals ; Proteostasis ; *Protein Aggregation, Pathological/metabolism ; *Protein Aggregates ; Proteotoxic Stress ; Ubiquitin/metabolism ; Proteolysis ; Oxidative Stress ; },
abstract = {Neurodegenerative diseases are characterized by the accumulation of misfolded and aggregation-prone proteins, reflecting a failure of proteostasis. The ubiquitin-proteasome system (UPS), a major pathway for selective intracellular protein degradation, is essential for maintaining neuronal protein homeostasis. Proteasome dysfunction has been implicated in several major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), although its extent and mechanisms vary across disease contexts. In this review, we examine current evidence for proteasome dysfunction in neurodegeneration and discuss how disease-associated proteins impair proteasome function through direct inhibition, defective substrate processing, and sequestration into protein aggregates. We also address the contribution of oxidative stress, neuroinflammation, and aging to proteasome dysregulation. Finally, we highlight emerging therapeutic strategies aimed at restoring proteasome function, including pharmacological activation, modulation of proteasome assembly and stability, and targeted protein degradation approaches. Understanding the context-dependent nature of proteasome dysfunction will be important for developing effective proteostasis-based therapies.},
}

Humans
*Proteasome Endopeptidase Complex/metabolism
*Neurodegenerative Diseases/metabolism/therapy/pathology/drug therapy
Animals
Proteostasis
*Protein Aggregation, Pathological/metabolism
*Protein Aggregates
Proteotoxic Stress
Ubiquitin/metabolism
Proteolysis
Oxidative Stress

@article {pmid42450899,
year = {2026},
author = {Gerymski, R},
title = {Does Life Lose Its Meaning When the Heart Fails? Illness Perception, Perceived Stress and Meaning in Life in Polish Patients with Heart Failure.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {13},
pages = {},
doi = {10.3390/healthcare14131889},
pmid = {42450899},
issn = {2227-9032},
support = {Fifty percent of the study was conducted free of charge by the author (R.G.). The other half of the study was financed by the Institute of Psychology at the Opole University (no grant number provided)//University of Opole/ ; },
abstract = {Background/Objectives: Heart failure (HF) is a highly unpredictable disease that significantly impacts patients' well-being. One of the fundamental problems faced by cardiac patients is trying to answer the question of how to lead a meaningful life. Meaning in life is a crucial predictor of well-being, ill-being and quality of life for everyone, not just cardiac patients. Therefore, identifying its predictors is crucial. Based on Leventhal et al.'s common-sense model of self-regulation of health and illness, and Lipowski's disease perception concept, this study verified the role of illness perception and perceived stress in existential meaning in Polish HF patients. Methods: This manuscript presents the results of a cross-sectional study. Overall, 336 HF patients from Poland were examined. Four questionnaires were used: the Meaning in Life Questionnaire (MLQ), the Multidimensional Existential Meaning Scale (MEMS), the Perceived Stress Scale (PSS-10) and the Disease-Related Appraisals Scale (DRAS). Results: Negative illness perception and positive cognitive assessment of the illness were shown to be significant predictors of meaning in life in patients with HF. Furthermore, this relationship was mediated by perceived stress. Additionally, the positive correlation between negative illness assessment and positive illness perception was found. Conclusions: This study demonstrates that cognitive assessment of the disease can be associated with the existential resources of heart failure patients. It also highlights the importance of working on the existential sphere of cardiac patients and accurately verified theoretical assumptions regarding the relationship between illness perception and meaning in life, providing a basis for future longitudinal studies and meaning-oriented psychological help focused on individuals with HF.},
}

@article {pmid42451086,
year = {2026},
author = {Soni, N and Debnath, N and Rekapally, E and Jabbar, A and Tyagi, SC and Bissa, B and Tyagi, N},
title = {Vitamin D Signaling in Neurodegenerative Disorders: Mechanisms, Therapeutic Potential, and Clinical Implications.},
journal = {Nutrients},
volume = {18},
number = {13},
pages = {},
doi = {10.3390/nu18132082},
pmid = {42451086},
issn = {2072-6643},
support = {971566; 24 TPA1304527 and 25 TPA1481771 to Neetu Tyagi.//American Heart Association/ ; },
mesh = {Humans ; *Vitamin D/metabolism/therapeutic use ; *Neurodegenerative Diseases/metabolism/drug therapy/etiology ; *Signal Transduction ; Vitamin D Deficiency/complications ; Animals ; Oxidative Stress/drug effects ; Receptors, Calcitriol/metabolism ; Blood-Brain Barrier/metabolism ; Neuroprotective Agents ; },
abstract = {Vitamin D has long been recognized for its role in calcium homeostasis and bone metabolism; however, it is now emerging as an important regulator of central nervous system (CNS) function. Recent evidence suggests that vitamin D signaling contributes to the pathogenesis and progression of several neurodegenerative disorders. Vitamin D exerts neuroprotective effects through multiple mechanisms, including regulation of calcium homeostasis, modulation of immune responses, reduction in oxidative stress, stimulation of neurotrophic factors, and maintenance of blood-brain barrier (BBB) integrity. Vitamin D receptors and metabolizing enzymes are widely distributed across several brain regions, highlighting their direct involvement in neuronal function. This review summarizes the biosynthesis, metabolism, and signaling pathways of vitamin D. It explores its role in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury (TBI). Evidence from experimental and clinical studies indicates that vitamin D deficiency is associated with an increased risk and severity of these conditions, while supplementation may provide therapeutic benefits.},
}

Humans
*Vitamin D/metabolism/therapeutic use
*Neurodegenerative Diseases/metabolism/drug therapy/etiology
*Signal Transduction
Vitamin D Deficiency/complications
Animals
Oxidative Stress/drug effects
Receptors, Calcitriol/metabolism
Blood-Brain Barrier/metabolism
Neuroprotective Agents

@article {pmid42451691,
year = {2026},
author = {Singh, AA and Arukha, AP and Song, M},
title = {Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {13},
pages = {},
doi = {10.3390/molecules31132323},
pmid = {42451691},
issn = {1420-3049},
mesh = {Humans ; *Antioxidants/pharmacology/chemistry ; *Indoles/chemistry/pharmacology ; Animals ; *Neuroprotective Agents/pharmacology/chemistry ; Oxidation-Reduction/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neurons/drug effects/metabolism ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Reactive Oxygen Species/metabolism ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis, are distinguished by progressive neuronal dysfunction caused primarily by oxidative stress, mitochondrial impairment, neuroinflammation, and redox imbalance. Growing evidence suggests that indole-derived compounds have significant neuroprotective potential due to their antioxidant, anti-inflammatory, and redox-modulating properties. This review summarizes the structural and biological significance of indole scaffolds, focusing on the mechanisms by which natural, endogenous, microbiota-derived, and synthetic indole compounds protect neuronal networks. Indole-3-carbinol, 3,3'-diindolylmethane, indole-3-propionic acid, and melatonin are major indole derivatives that control important neuroprotective pathways like Nrf2/ARE signaling, mitochondrial bioenergetics, neurotrophic factor expression, apoptotic regulation, and suppression of proinflammatory mediators. These compounds also maintain synaptic plasticity, reduce reactive oxygen species production, and improve neuronal survival in neurodegenerative disease models. Additionally, updated information from translational and clinical research indicates that indole-based compounds may have promising therapeutic applications; however, obstacles like low bioavailability, metabolic instability, and blood-brain barrier penetration continue to be major obstacles to clinical application. Development in nanoparticle delivery systems, microbiome-targeted interventions, and rational structural optimization may improve therapeutic efficacy and translational potential. Overall, indole-derived compounds are a versatile class of redox modulators with potential applications in the prevention and treatment of neurodegenerative diseases via integrated antioxidant and neuroprotective mechanisms.},
}

Humans
*Antioxidants/pharmacology/chemistry
*Indoles/chemistry/pharmacology
Animals
*Neuroprotective Agents/pharmacology/chemistry
Oxidation-Reduction/drug effects
*Neurodegenerative Diseases/drug therapy/metabolism
*Neurons/drug effects/metabolism
Oxidative Stress/drug effects
Signal Transduction/drug effects
Reactive Oxygen Species/metabolism

@article {pmid42453524,
year = {2026},
author = {Yang, HI and Hsueh, KW and Ding, DC and Harn, HJ and Lin, YC and Chang, CY and Tsai, ST and Lin, SZ},
title = {Therapeutic potential of adipose-derived stem cell transplantation in amyotrophic lateral sclerosis: A combined clinical case and preclinical study.},
journal = {Tzu chi medical journal},
volume = {38},
number = {3},
pages = {332-339},
pmid = {42453524},
issn = {2223-8956},
abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal neurodegenerative disease with no adequate treatment. Transplantation of adipose-derived stem cells (ADSCs) may be an effective therapeutic strategy for delaying progression or restoring neurological function in ALS.

MATERIALS AND METHODS: We evaluated the safety and therapeutic efficacy of intravenous (i.v.) and intracerebral (i.c.) ADSC injection in a late-stage ALS patient and in a SOD1 transgenic (Tg) mouse model. Magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to examine potential cerebral hemorrhage and tumor generation in the treated patient. In addition, maximal inspiratory pressure, maximal expiratory pressure, tidal volume, and respiratory rate were measured as indices of respiratory function.

RESULTS: ADSC transplantation was safe, with MRI and CT showing no hemorrhage or tumorigenesis up to 12 months. The patient's Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score improved from 7 to 9 at 3 months and remained above baseline for 6 months. Respiratory function was preserved during this period. In SOD1 Tg mice, i.c. and i.v. ADSC infusion significantly prolonged survival (165.0 ± 10.4 and 147.3 ± 4.5 days vs. 129.7 ± 3.9 days) and improved motor scores (P < 0.01).

CONCLUSION: This preliminary finding suggests potential therapeutic feasibility, but further studies with larger cohorts are needed to confirm its safety and efficacy.},
}

@article {pmid42436608,
year = {2026},
author = {Teng, Z and Bushman, BJ},
title = {Rethinking Longitudinal Studies of Media Violence and Aggression: A Rejoinder to Lacko et al.'s (2026) Comment.},
journal = {Aggressive behavior},
volume = {52},
number = {4},
pages = {e70078},
pmid = {42436608},
issn = {1098-2337},
mesh = {*Aggression/psychology ; Humans ; *Violence/psychology ; Longitudinal Studies ; Media Exposure ; },
abstract = {Lacko et al. responded to the concerns raised in our commentary, providing an opportunity to reflect on broader methodological and theoretical issues in longitudinal research on media violence and aggression. This exchange highlights five lessons for future research: (1) longitudinal studies should place greater emphasis on developmental processes; (2) analytical approaches and the interpretation of findings are important; (3) examining the longitudinal effects of media violence on aggression requires high-quality longitudinal data; (4) greater transparency and openness in both data and analytical methods strengthen the field; and (5) future research should place greater emphasis on understanding when, how, and for whom media violence influences aggression. We hope these lessons will contribute to more rigorous longitudinal research and a deeper understanding of the developmental processes linking media violence and aggression.},
}

*Aggression/psychology
Humans
*Violence/psychology
Longitudinal Studies
Media Exposure

@article {pmid42436960,
year = {2026},
author = {Gromprasit, A and Thremthakanpon, W and Siripocaratana, K and Wanitcharoenporn, W and Jitprapaikulsarn, S and Sutthapakti, B and Laoruengthana, A},
title = {Accuracy and Reliability of Magnetic Resonance Imaging Measurement of Medial Femoral Condyle for Femoral Component Sizing in Oxford Unicompartmental Knee Arthroplasty.},
journal = {Arthroplasty today},
volume = {40},
number = {},
pages = {102088},
pmid = {42436960},
issn = {2352-3441},
abstract = {BACKGROUND: Accurate femoral component sizing is critical for Oxford unicompartmental knee arthroplasty (UKA) because inappropriate sizing can lead to early implant failure. Therefore, we developed a magnetic resonance imaging (MRI) measurement of medial femoral condyle (MRMFC) technique and compare its accuracy to existing methods.

METHODS: This study included 54 Oxford UKAs. Five sizing methods were assessed: radiographic templating, intraoperative sizing spoon, anthropometric estimation (based on patient height and gender), Yang et al.'s MRI method, and the MRMFC. The MRMFC determined 3 reference points of medial femoral condyle on the sagittal plane of MRI. The primary outcome was an overhang or underhang of femoral component over posterior femoral condyle as determined on postoperative lateral radiographs which ±2 mm are considered as ideal size.

RESULTS: The MRMFC method yielded the highest accuracy (50/54; 92.6%; 95% CI: 82.1-97.9), followed by the intraoperative sizing spoon (38/54; 70.4%, 56.4-82.0), Yang et al. MRI method (32/54; 59.3%, 45.0-72.4), anthropometric estimation (30/54; 55.6%, 41.4-69.1), and radiographic templating (25/54; 46.3%, 32.6-60.4). Pairwise testing demonstrated that MRMFC was better than the sizing spoon (P = .008), radiographic templating (P < .001), Yang et al. MRI method (P < .001), and anthropometric estimation (P < .001). The sizing spoon was superior to radiographic templating (P = .029). No significant differences were observed among radiographic templating, Yang et al. MRI method, and anthropometric estimation.

CONCLUSIONS: The MRMFC demonstrated the highest accuracy and reproducibility in preoperative planning for Oxford UKA. Intraoperative spoon sizing, however, remains a simple and practical method and performed moderately well with significantly better than radiographic templating.},
}

@article {pmid42437951,
year = {2026},
author = {Williams, KJ},
title = {Anti-inflammatory agents in atherosclerosis-and a need for reform: Extraordinary claims require extraordinary evidence.},
journal = {Journal of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/joim.70128},
pmid = {42437951},
issn = {1365-2796},
support = {//Ruth and Yonatan Ben-Avraham Fund/ ; },
abstract = {Since 1858, human atherosclerotic plaques have been shown to contain immune cells. But are these cells suitable therapeutic targets? Dozens of clinical trials of anti-inflammatory agents other than colchicine have been performed in patients with clinically evident atherosclerosis. None of these trials led any regulatory body in any jurisdiction to allow a cardiovascular indication for any of these agents. This discouraging work provides a background to evaluate new data on colchicine. In 2024-2025, new clinical trials of colchicine in patients with atherosclerosis showed benefit, no benefit, or harm. In 2025-2026, over a dozen meta-analyses so far have appeared, drawing on ∼34 trials, but do not agree with each other. One of these meta-analyses, Xie et al.'s in the Journal of Internal Medicine, provides a compelling graphical display of the pre-specified primary outcomes of six long-term clinical trials as they were published over time. The pattern of early positive trials, then newer negative (null) trials, suggests regression to the truth. Jeon and Cho et al.'s population-wide study in the Journal of Internal Medicine of patients with Type 2 diabetes and gout found no benefit from colchicine over nonsteroidal anti-inflammatory drugs on major adverse cardiovascular events. This information suggests several areas for reform of research on inflammation in atherosclerosis. Fully informed consent should require that clinical trials of anti-inflammatory agents in atherosclerotic arterial disease must disclose to trial participants the failures of this approach in over 50 clinical trials to date, spanning decades. Additionally, the field might reconsider its commitment to the Big Idea that inflammation must be a definitive therapeutic target in atherosclerosis. The track record so far for inflammation inhibition in atherosclerosis is extensive and disappointing-a fact that merits wider discussion. Therapeutic successes from targeting cholesterol-rich, apolipoprotein-B-containing lipoproteins-the proven causative agents of this disease-provide extraordinary evidence. Current data for colchicine and other anti-inflammatory therapies do not.},
}

@article {pmid42438447,
year = {2026},
author = {Jewett, G and Chan, E and Jagt, K and Petrillo Ballantyne, J and Wesolosky, J and Perera, T and Karnik, V and Hahn, C and Luk, C and Mobach, T},
title = {An intrathecal therapeutics clinic for administration of tofersen in amyotrophic lateral sclerosis: A Canadian nurse practitioner and neurologist collaborative model.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-10},
doi = {10.1017/cjn.2026.10647},
pmid = {42438447},
issn = {0317-1671},
}

@article {pmid42439979,
year = {2026},
author = {Langreen, S and Uecker, M and Juhl, S and Dingemann, J and Kiblawi, R},
title = {Is hypoalbuminemia a risk factor for small bowel anastomotic leaks in infants? A multivariate analysis.},
journal = {Pediatric surgery international},
volume = {42},
number = {1},
pages = {},
pmid = {42439979},
issn = {1437-9813},
mesh = {Humans ; *Hypoalbuminemia/complications ; Retrospective Studies ; *Anastomotic Leak/etiology/epidemiology ; Risk Factors ; Female ; *Intestine, Small/surgery ; Male ; Infant ; Multivariate Analysis ; Anastomosis, Surgical ; Infant, Newborn ; Incidence ; Serum Albumin ; },
abstract = {PURPOSE: Anastomotic leaks (AL) are critical complications following bowel anastomosis with an incidence of up to 10.5% in infants. Previous studies in animal models and adults have suggested a link between postoperative fluid overload and hypoalbuminemia with anastomotic leaks. In infants, the role of hypoalbuminemia on anastomotic integrity after small bowel anastomosis remains unclear.

METHODS: Retrospective study of infants < 1 year, undergoing elective small-bowel anastomosis between 2015 and 2024 (Ethics No.-11362-_BO_K_202). Data on demographics, weight gain, serum albumin levels and use of diuretic medication during the first five postoperative days were collected. Univariate and multivariate analysis were performed to detect risk factors for ALs in infants.

RESULTS: 13 of 219 patients (5.9%) developed ALs. Demographics were similar comparing patients with and without leaks. In univariate analysis, serum albumin levels were significantly lower (20.3 g/l vs. 26,3 g/l, p < 0.0001) in patients with AL compared to patients without AL and multivariate analysis confirmed a significant association between low serum albumin levels and AL occurrence, CONCLUSION: In infants, small bowel anastomotic leaks are associated with low postoperative serum albumin. Whether hypoalbuminemia should be regarded as an early warning sign of an undiagnosed, developing anastomotic leak or represents a causal risk factor can only be determined with further studies.},
}

Humans
*Hypoalbuminemia/complications
Retrospective Studies
*Anastomotic Leak/etiology/epidemiology
Risk Factors
Female
*Intestine, Small/surgery
Male
Infant
Multivariate Analysis
Anastomosis, Surgical
Infant, Newborn
Incidence
Serum Albumin

@article {pmid42432671,
year = {2026},
author = {Chen, F and Wang, L and Liu, H and Khan, Q and Tang, B and Bao, N},
title = {The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04551-7},
pmid = {42432671},
issn = {1477-3155},
abstract = {Neurological disorders refer to a diverse group of conditions that affect the brain, peripheral nerves, and spinal cord and impair socioemotional, cognitive, motor, and sensory functions. Alzheimer's disease (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are some of the well-known neurodegenerative diseases that affect millions of people worldwide. Despite the advanced technologies and nano-drug delivery systems, the success rate of developing drugs for neurological disorders is significantly low. Among several constraints, including gastrointestinal irritation, rapid metabolism, and low stability, the blood-brain barrier (BBB) emerges as one of the key challenges in the development and application of drugs against neurological disorders. These challenges necessitate innovative approaches to develop cost-effective therapeutic strategies. Drug repurposing, the discovery of new therapeutic benefits of existing drugs, is a promising drug discovery approach for discovering potential treatment options for complex neurological disorders. This review aims to explore the advanced and significant progress in drug repurposing for major neurological disorders, including MS, AD, PD, ALS, HD, stroke, and neuropsychiatric conditions. It places an explicit emphasis on discussing the potential role of artificial intelligence (AI)-assisted drug repurposing and understanding of the biological mechanisms in discovering new drugs for these neurological conditions. This also examines current challenges in drug repurposing and provides a critical review of the available opportunities and limitations in AI-assisted drug repurposing.},
}

@article {pmid42432783,
year = {2026},
author = {Choi, Y and Lee, S and Ashim, J and Yu, W and Cho, E and Lee, HW and Park, JS and Yoon, JH and Kim, HJ and Cheon, M},
title = {Cross-disease LC-MS/MS plasma proteomics identifies reproducible shared and disease-enriched biomarker signatures in neurodegenerative disorders.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02377-w},
pmid = {42432783},
issn = {2051-5960},
support = {RS-2024-00454715//the National Research Foundation of Korea (NRF) grant funded by the Korean government/ ; RS-2024-00343239//the National Research Foundation of Korea (NRF) grant funded by the Korean government/ ; RS-2023-00230402//the Ministry of Environment of Korea/ ; 26-BR-04-01//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; 26-BR-02-03, 26-BR-02-05, 26-BR-04-01//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; 26-BR-02-03, 26-BR-02-05, 26-BR-04-01, 26-BR-06-02//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; RS-2024-00512888//the Korea Technology and Information Promotion Agency for SMEs (TIPA) funded by the Ministry of SMEs and Startups/ ; },
abstract = {Neurodegenerative diseases (NDDs) exhibit considerable molecular heterogeneity, making it difficult to pinpoint robust, disease-specific biomarkers. Although proteomic studies have deepened our understanding of individual disorders, systematic cross-disease comparisons with cross-platform validation remain scarce, especially for rare conditions like spinal and bulbar muscular atrophy (SBMA). To address this gap, we conducted a comparative plasma proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 264 participants across major neurodegenerative and related diagnostic groups, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), SBMA, and cognitively healthy controls. This unified framework allowed us to capture both disease-specific and shared protein signatures across neurodegenerative conditions. Candidate proteins were then validated in the UK Biobank (Olink Explore) and the Global Neurodegeneration Proteomics Consortium (SomaScan). Of 23 proteins assessed in the UK Biobank, four unique proteins (yielding six disease-protein associations) showed nominally significant and directionally concordant changes; of 20 proteins represented by 27 probes tested in the Global Neurodegeneration Proteomics Consortium, seven proteins reached nominal significance, all with full directional concordance across both cohorts. Notably, IGFBP2 was consistently elevated in AD and PD across independent datasets, pointing to shared metabolic dysregulation, while ADIPOQ showed parallel increases in the same conditions, reinforcing convergent shifts in energy metabolism. By contrast, CRTAC1 and COMP were selectively reduced in motor neuron diseases, suggesting disease-enriched alterations in extracellular matrix composition. Taken together, our findings provide a cross-disease, cross-platform framework for uncovering reproducible proteomic biomarkers and shed light on both overlapping and distinct molecular pathways in neurodegeneration.},
}

@article {pmid42432887,
year = {2026},
author = {Ye, H and Wang, JL and Xu, QH and Gao, YL},
title = {Refining the link between REM sleep behavior disorder and neurodegeneration: Genetic correlation, Mendelian randomization, and colocalization evidence.},
journal = {Medicine},
volume = {105},
number = {28},
pages = {e48922},
doi = {10.1097/MD.0000000000048922},
pmid = {42432887},
issn = {1536-5964},
mesh = {Humans ; *REM Sleep Behavior Disorder/genetics/complications ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics ; Linkage Disequilibrium ; Genome-Wide Association Study ; Alzheimer Disease/genetics ; Parkinson Disease/genetics ; },
abstract = {Observational studies have proposed a link between isolated rapid eye movement sleep behavior disorder (iRBD) and several neurodegenerative diseases. We employed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analysis to assess the causal links between iRBD and these neurodegenerative conditions. iRBD demonstrated a positive causal association with Alzheimer disease (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.00-1.03, P = 1.10E-02), Parkinson disease (OR = 1.10, 95% CI: 1.03-1.16, P = 2.96E-03), and multiple sclerosis (OR = 1.09, 95% CI: 1.02-1.17, P = 1.61E-02). A strong positive genetic correlation with dementia with Lewy bodies was observed (rg = 1.6313, P = .0002), along with a causal association (OR = 1.45, 95% CI: 1.03-2.06, P = 3.53E-02), further supported by colocalization analysis. No significant causal relationship was identified between iRBD and amyotrophic lateral sclerosis (all P > .05). Additionally, reverse Mendelian randomization analyses did not reveal any causal relationships between the neurodegenerative diseases studied and iRBD. Our findings provide robust genetic evidence supporting a causal relationship between iRBD and the risk of multiple neurodegenerative diseases, highlighting the potential for shared pathophysiological mechanisms.},
}

Humans
*REM Sleep Behavior Disorder/genetics/complications
Mendelian Randomization Analysis
*Neurodegenerative Diseases/genetics
Linkage Disequilibrium
Genome-Wide Association Study
Alzheimer Disease/genetics
Parkinson Disease/genetics

@article {pmid42432946,
year = {2026},
author = {Jeong, J and Song, KJ and Lee, JC and Shin, SD and Kim, YJ},
title = {A simulation study on optimizing stationary camera locations for physician-directed telemedical supervision of prehospital advanced life support: Single-versus dual-camera setups.},
journal = {Medicine},
volume = {105},
number = {28},
pages = {e49685},
doi = {10.1097/MD.0000000000049685},
pmid = {42432946},
issn = {1536-5964},
support = {2020R1F1A1076561//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Telemedicine ; *Emergency Medical Services/methods ; Prospective Studies ; *Emergency Medical Technicians/education ; Smartphone ; *Video Recording/instrumentation/methods ; },
abstract = {Prehospital telemedicine, particularly real-time video conferencing, offers significant benefits in prehospital and disaster settings by enabling rapid data transmission. Using a smartphone mounted on a tripod as a stationary camera provides stable footage, comprehensive scene evaluation, and reduced technical complexity, thus complementing smart glasses and built-in cameras. However, the optimal camera location for visualizing key procedures remains unexplored. This study aims to compare the optimal stationary camera location and the effectiveness of single-camera versus dual-camera setups in visualizing key procedures for physician-directed telemedical supervision of prehospital advanced life support (ALS). This prospective, non-randomized simulation study involved 9 advanced emergency medical technicians performing ALS procedures in 20 simulations. Each simulation was recorded simultaneously from 4 stationary camera locations: right head, left head, right leg, and left leg. Reviewers evaluated the visibility of 6 key procedures (airway management, breathing support, chest compressions, intravenous access, electrocardiogram rhythm monitoring, and teamwork) using a 1 to 5 scale. Mixed models and generalized linear mixed models were applied to analyze the visibility scores and compare the effect sizes of the different camera setups. The median visibility scores and proportion of optimal visibility (scores of 4-5) varied significantly across the 4 camera locations for most procedures. However, the mixed model and generalized linear model analyses for overall visibility did not reveal significant differences in effect sizes between individual camera locations. Dual-camera setups showed significant improvement over single-camera setups, with an adjusted odds ratio of 4.89 (95% confidence interval: 1.92-12.4) for the right head + left head combination and 3.74 (95% confidence interval: 1.50-9.32) for the right head + left leg combination. Although no single-camera location provided optimal visualization for all procedures, dual-camera setups were more effective than single cameras in capturing field activity. These findings support the use of dual-camera setups to enhance physician-directed telemedical supervision of prehospital ALS, with potential applicability to disaster settings, and may inform the development of future protocols for prehospital telemedicine.},
}

Humans
*Telemedicine
*Emergency Medical Services/methods
Prospective Studies
*Emergency Medical Technicians/education
Smartphone
*Video Recording/instrumentation/methods

@article {pmid42434198,
year = {2026},
author = {Sleutjes, BTHM and Jacobsen, AB and Tankisi, H and Sirin, NG and Oge, AE and Henderson, RD and van Doorn, PA and van den Berg, LH and van Eijk, RPA},
title = {Quantifying motor unit loss prior to functional impairment in muscles affected by amyotrophic lateral sclerosis.},
journal = {Clinical neurophysiology practice},
volume = {11},
number = {},
pages = {538-542},
pmid = {42434198},
issn = {2467-981X},
abstract = {OBJECTIVES: The compound muscle action potential (CMAP) scan is a non-invasive method for deriving motor unit number estimates (MUNE) to track disease progression in muscles affected by amyotrophic lateral sclerosis (ALS). It remains to be established whether and how long motor unit loss precedes functional impairment.

METHODS: In 56 patients with ALS, we compared the longitudinal trajectories of MUNE derived from thenar CMAP scans, and fine motor function (FMF) using a functional rating scale. Linear and sigmoidal disease trajectories were modelled from which time differences were estimated between these measures to reach their half-maximum scores.

RESULTS: The normalized linear decline per month was 0.02 (95% CI 0.01 to 0.03) for FMF and 0.03 (95% CI 0.03 to 0.04) for MUNE. Half-maximum of FMF was reached after 26.3 months (95% CI 18.9 to 35.1) for the linear model, while MUNE had a shorter time required to reach 50% of its maximum with 13.0 months (95% CI 10.3 to 16.4). The head-to-head comparison between FMF and MUNE showed that MUNE values reached 50% of its maximum 13.1 months (95% CI 7.0-20.8) earlier. Results were similar for sigmoidal disease trajectories.

CONCLUSIONS: Simulated disease trajectories of MUNE values derived from CMAP scans in muscles affected by ALS indicated that MUNE may reach 50% of its maximum in approximately 60% of the time compared to functional impairment.

SIGNIFICANCE: These explorative findings underscore how neurophysiological measures may be of use for early disease monitoring, with relevance for both care and research settings.},
}

@article {pmid42434808,
year = {2026},
author = {Baker, B and Emerson, S and Tran, T and Mohapatra, N and Wang, D and Zaw, T and Doshi, A and Lopez, JM and Hassan, D and Kumar, P and Farmer, D and Wang, A},
title = {Brain targeting and trafficking of extracellular vesicles in central nervous system diseases: a therapeutic roadmap.},
journal = {Nanomedicine (London, England)},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/17435889.2026.2698782},
pmid = {42434808},
issn = {1748-6963},
abstract = {Extracellular vesicles (EVs) mediate intercellular signaling in the central nervous system (CNS) by transferring lipids, proteins, and nucleic acids among neurons, glia, endothelium, and immune cells. Brain targeting depends on a linked sequence: EV ligands and adsorbed protein coronas engage receptor modules, select endocytic routes, determine intracellular fate, and define the therapeutic readouts. These fates include lysosomal degradation, recycling, rare cytosolic delivery, or transport across the blood-brain barrier (BBB). In disease, the same pathways can disseminate proteopathic seeds and amplify neuroinflammation. Heparan sulfate proteoglycans (HSPGs) and LDL receptor family members, including low-density lipoprotein receptor-related protein 1 (LRP1), regulate tau, α-synuclein, and amyloid-β handling. Phosphatidylserine readers and complement shape myeloid sink capture and inflammatory output. Integrin, tetraspanin, and ICAM-1 nanoclusters influence avidity, organotropism, and immune suppression. At the BBB, endothelial HSPGs, LRP1, and transferrin receptor (TfR) support receptor-mediated uptake, motivating engineered ligands such as rabies virus glycoprotein-derived peptides, Angiopep-2, and TfR binders. However, endosomal escape remains a major kinetic barrier to nucleic acid delivery. We synthesize these principles across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, glioblastoma, and demyelinating disease, and outline design and assay standards needed to translate EV biology into safe, manufacturable CNS therapeutics.},
}

@article {pmid42435104,
year = {2026},
author = {Qiao, Y and Ma, ZS},
title = {Deterministic selection and compositional turnover in Parkinson's disease-associated gut dysbiosis.},
journal = {Antonie van Leeuwenhoek},
volume = {119},
number = {8},
pages = {},
pmid = {42435104},
issn = {1572-9699},
support = {NSFC Grant# 72274192//National Natural Science Foundation of China/ ; },
mesh = {*Parkinson Disease/microbiology/complications ; *Dysbiosis/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Bacteria/classification/genetics/isolation & purification ; },
abstract = {The scientific understanding of links between Parkinson's disease (PD) and gut microbiome dysbiosis has advanced significantly, yet the ecological mechanisms driving these microbial changes remain poorly understood. To address this gap, we postulated that PD-associated gut dysbiosis arises as harmful microbes outcompete beneficial bacteria, and consequently any therapeutic strategies must both suppress opportunistic pathogens and restore protective, fiber-degrading microbes to effectively rebalance the gut microbiome in PD. To evaluate ecological patterns consistent with this hypothesis, we apply Sloan's near-neutral model (SNM), Ning et al.'s stochasticity framework, and ecological network analysis to reanalyze six published gut microbiome datasets (1957 samples total: 804 healthy controls, 1153 PD cases). We first applied SNM to categorize bacterial species as neutral, positively selected, or negatively selected. While the overall proportions of these categories were similar between groups (neutral: ~ 40%, positively selected: ~ 47%, negatively selected: ~ 13%), stochasticity framework analysis revealed significantly stronger deterministic selection in PD microbiomes. Shared species analysis (SSA) resolved this apparent paradox by demonstrating substantial compositional shifts within each species category, indicating that while classification frequencies remained stable, the specific microbes occupying these ecological niches changed significantly in PD. This divergence between SNM category proportions and NSR values highlights a subtle yet critical aspect of community assembly dynamics. Ecological network analysis further revealed that neutral species had fewer antagonistic co-occurrence links, consistent with their ecological equivalence, while negatively selected species maintained higher relative abundances in both groups. Together, these findings indicate that PD-associated gut microbiomes are characterized by stronger deterministic assembly signatures and substantial compositional turnover within near-neutral ecological categories. These patterns are consistent with altered ecological assembly signatures in PD-associated dysbiosis.},
}

*Parkinson Disease/microbiology/complications
*Dysbiosis/microbiology
Humans
*Gastrointestinal Microbiome
*Bacteria/classification/genetics/isolation & purification

@article {pmid42435587,
year = {2026},
author = {Domínguez-García, A and Delgado-Uriarte, JC and Cervantes-Arriaga, A},
title = {Precision therapeutics and innovative clinical trial design in neurodegenerative diseases.},
journal = {Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion},
volume = {78},
number = {4},
pages = {100050},
doi = {10.1016/j.ric.2026.100050},
pmid = {42435587},
issn = {2564-8896},
abstract = {Neurodegenerative diseases are biologically heterogeneous disorders characterized by progressive neuronal dysfunction, overlapping molecular pathologies, and limited disease-modifying therapies. Advances in biomarker development, molecular staging, and precision medicine are reshaping therapeutic strategies and clinical trial design across Parkinson's disease, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington's disease, and related disorders. This review summarizes emerging therapeutic approaches, including monoclonal antibodies targeting protein aggregation, immune-modulating and metabolic interventions, antisense oligonucleotides, gene replacement and genome-editing strategies, stem cell-based therapies, and neurosurgical delivery platforms and neuromodulation technologies. It also examines evolving clinical trial methodologies such as biomarker-enriched recruitment, adaptive and delayed-start designs, platform trials, decentralized models, and master protocols. Additional emphasis is placed on diagnostic biomarkers, multimodal artificial-intelligence pipelines, systems-biology perspectives, network-based therapeutic strategies, and the reproducibility and interpretability requirements for computational tools. Despite recent progress, major challenges remain, including biological heterogeneity, limited translatability of preclinical models, delivery barriers, long-term safety concerns, and inequities in access to biomarker-based care and trial participation. Future directions will require combination therapies, integrated biomarker pipelines, preventive strategies, and pragmatic trial systems capable of translating biological advances into durable and equitable clinical benefit.},
}

@article {pmid42436372,
year = {2026},
author = {Roy, T and Ramesh, M and Nizam, NAA and Tandiono, S and Al-Jamal, KT and Al-Chalabi, A and Iacoangeli, A and Al Khleifat, A},
title = {Plasma exosomal HERV-K transcripts are increased in amyotrophic lateral sclerosis.},
journal = {BMC neuroscience},
volume = {27},
number = {1},
pages = {},
pmid = {42436372},
issn = {1471-2202},
support = {303476//National Institute for Health and Care Research/ ; MRC (MR/Z505705/1)//South London and Maudsley NHS Foundation Trust/ ; LS Association Milton Safenowitz Research Fellowship (RE19765)//NIHR Maudsley Biomedical Research Centre/ ; RE23378//LifeArc/ ; 1819242//Dementia Consortium/ ; 1122462/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/Z505705/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {Human endogenous retrovirus-K (HERV-K) reactivation is increasingly implicated in amyotrophic lateral sclerosis (ALS), with ongoing clinical trials investigating antiretroviral therapies. However, there is limited understanding of how HERV-K is trafficked in peripheral biofluids, and the role of exosomes, nano-sized extracellular vesicles, in this process remains largely unexplored. Exosomes offer a stable and cell-specific cargo reservoir that may reflect central pathogenic processes and serve as a minimally invasive biomarker source. In this study, we isolated plasma-derived exosomes from ALS patients (n = 21) and healthy controls (n = 16), and quantified exosomal HERV-K gag, env, and pol transcript levels using SYBR Green qPCR with RNase treatment and normalization to both traditional and exosome-enriched reference genes. HERV-K pol expression was significantly elevated in ALS, with fold-changes ranging from 1.59 to 1.85 (P = 0.037-0.051). env and gag also showed increased expression, though with greater variability. Normalization to the exosome-specific gene SOD2 provided the most consistent signal. These findings suggest that exosomal HERV-K transcripts, particularly pol, could serve as accessible biomarkers for patient stratification and treatment monitoring in HERV-K-targeted ALS trials. This work establishes proof-of-concept for using exosomal cargo to track endogenous retroviral activity in neurodegeneration and supports further investigation of liquid biopsy approaches in ALS precision medicine.},
}

@article {pmid42436431,
year = {2026},
author = {Parks, ASE and Conn, LG and Abrahao, A and Zinman, L and Sale, JEM},
title = {"Straddling two worlds": complexities of spousal caregiving in amyotrophic lateral sclerosis during younger middle age.},
journal = {BMC palliative care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12904-026-02230-w},
pmid = {42436431},
issn = {1472-684X},
abstract = {BACKGROUND: Family support is central to amyotrophic lateral sclerosis (ALS) care. Spouses often assume the role of primary caregiver, facing daily challenges as their partner's needs progressively increase. Younger ALS caregivers appear to have distinct experiences and needs, yet age- or life-stage variations and processes of caregiving are seldom considered in studies of ALS family caregiver experience.

METHODS: We undertook a qualitative study, guided by constructivist grounded theory methodology, to explore the dynamics of family caregiving following an ALS diagnosis in a younger middle-aged family member (≤55 years). Data were coded to identify psychosocial processes, including how family caregivers engage in caregiving.

RESULTS: In-depth interviews were conducted with ten spousal caregivers between August 2023 and August 2025. Overall, our theoretical understanding of spousal caregiving for younger middle-aged adults with ALS (YMAs) was captured by the core category 'straddling two worlds,' reflecting how caregivers navigated multiple interconnected dichotomies: present and future, familiar and new norms, current and anticipated losses, and the worlds of the living and the dying. To contend with an uncertain future, caregivers anchored themselves in the present as they navigated a shifting sense of normalcy. Middle age expectations and social norms shaped how caregivers engaged in caregiving and experienced losses that were often unending and ambiguous.

CONCLUSIONS: Caregiving for a spouse with ALS in younger middle age involves temporal, practical, emotional, and existential processes. Caregivers of YMAs may benefit from interventions that help them tolerate uncertainty, stay grounded in the present, maintain normalcy, and grieve losses throughout the caregiving trajectory.},
}

@article {pmid42436563,
year = {2026},
author = {Gregory, JM},
title = {Context of use matters: interpreting extracellular vesicle TDP-43 as a biomarker in ALS.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02376-x},
pmid = {42436563},
issn = {2051-5960},
}

@article {pmid42432003,
year = {2026},
author = {Chen, J and Xu, P and Chen, M and Lu, Z and Li, X and Stampas, A and Zong, Y and Zhou, P},
title = {Compound muscle action potential scan dataset in adults with spinal cord injury and healthy controls.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07864-2},
pmid = {42432003},
issn = {2052-4463},
support = {ZR2024QH582//Natural Science Foundation of Shandong Province/ ; ZR2024YQ077//Natural Science Foundation of Shandong Province/ ; tsqn202211226//Taishan Scholar of Shandong Province/ ; tstp20221144//Taishan Scholar of Shandong Province/ ; 25S11907200//Science and Technology Commission of Shanghai Municipality/ ; KFKT-2024-KF-013//Chinese Association of Rehabilitation Medicine/ ; 82572355//National Natural Science Foundation of China/ ; },
abstract = {Certain neurological conditions, such as amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI), result in motor unit loss in muscles. The stimulus-evoked compound muscle action potential (CMAP) scan captures comprehensive information on motor unit recruitment that enables rapid and non-invasive assessment of motor unit status. However, few publicly available CMAP scan datasets exist to support research on motor unit number estimation (MUNE). To address this gap, we collected CMAP scan data from the first dorsal interosseous (FDI) muscle of 13 individuals with SCI and 13 healthy participants, and established a dedicated CMAP scan dataset. The dataset includes CMAP waveforms evoked by each nerve stimulus from which CMAP scan curve and typical parameters were extracted for direct use. All SCI participants underwent multiple clinical assessments and exhibited a spectrum of impairment severity from mild to severe, resulting in diverse CMAP features. We anticipate that this dataset will facilitate the development of advanced CMAP scan-based assessment techniques and aid in the investigation of neuromuscular impairment.},
}

@article {pmid42432423,
year = {2026},
author = {Sugisawa, R and Sekiguchi, K and Noda, Y and Matoba, S and Suehiro, H and Kozuki, J and Tanaka, T and Chihara, N},
title = {Quantitative Spatiotemporal Analysis of Ultrasound Images of Fasciculations in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70338},
pmid = {42432423},
issn = {1097-4598},
support = {JP256f0137011//Japan Agency for Medical Research and Development/ ; 25K14534//Japan Society for the Promotion of Science/ ; 24K14297//Japan Society for the Promotion of Science/ ; },
abstract = {INTRODUCTION/AIMS: Fasciculations are a hallmark of amyotrophic lateral sclerosis (ALS), yet quantitative description of individual events on muscle ultrasound (MUS) is limited. We characterized the spatiotemporal kinematics of individual fasciculations to determine whether they differ between ALS and other neurogenic conditions.

METHODS: We retrospectively analyzed biceps brachii MUS recordings from 680 examinations (January 2020-June 2025), identifying 74 ALS and 40 non-ALS neurogenic recordings with fasciculations (167 and 62 segments). After propensity score matching for age and muscle strength, 62 matched pairs were analyzed. The Lucas-Kanade optical flow algorithm, which estimates frame-to-frame displacement vectors from local intensity gradients, was applied at 1-pixel intervals (57,600 points per 240 × 240 region; ≈60 μm) to quantify twitch durations, peak displacement velocity, and directional anisotropy as a measure of spatial movement coherence.

RESULTS: ALS fasciculations showed prolonged total duration (582.8 ± 112.8 ms vs. 489.2 ± 128.7 ms, p < 0.001), reduced directional anisotropy (0.534 ± 0.245 vs. 0.627 ± 0.215, p = 0.028), and lower peak displacement velocity (6.55 ± 6.56 vs. 9.53 ± 9.07 μm/ms, p = 0.039). MANOVA showed significant multivariate differences (Pillai's trace = 0.317 ± 0.030, p < 0.001) with moderate group separation (Mahalanobis distance = 1.10 ± 0.05).

DISCUSSION: ALS fasciculations showed spatially heterogeneous and temporally prolonged contraction patterns, suggesting motor units in a transitional state of incomplete reinnervation, distinct from the more stable architecture of chronic neurogenic disorders. This framework may complement existing ultrasound assessment and aid the study of motor unit pathology in ALS.},
}

@article {pmid42432439,
year = {2026},
author = {Kavale-Henderson, LA and Buckberry, J and Buckley, H and Cameron, C and King, C and Koon, H and Petchey, P and Snoddy, AME and Loch, C},
title = {"An Injurious and Utterly Unfit Environment": A Case Study Comparing Dental Evidence of Childhood Stress in Nineteenth Century Working-Class Peoples From British and Colonial New Zealand Contexts.},
journal = {American journal of biological anthropology},
volume = {190},
number = {3},
pages = {e70315},
pmid = {42432439},
issn = {2692-7691},
support = {21-UOO-01//Ministry of Business, Innovation and Employment/ ; //University of Otago/ ; },
mesh = {Humans ; New Zealand ; History, 19th Century ; United Kingdom ; Child ; Adult ; Male ; *Tooth/pathology ; *Stress, Psychological/pathology/history ; Female ; Child, Preschool ; Young Adult ; Infant ; Adolescent ; Transients and Migrants/history ; },
abstract = {OBJECTIVES: During the nineteenth century, the health and living conditions of many working-class European peoples declined in association with growing industrialization and urbanization. Emigration to British colonies grew as people sought to escape such hardships. This research presents the first direct comparison of dental markers of stress in a case study of migrants to a British colony (Otago, New Zealand) alongside a contemporaneous assemblage representing an origin population (London, United Kingdom).

MATERIALS AND METHODS: Dental markers of childhood stress, accentuated lines, were observed in thin-sections of archeological teeth from adults (n = 9) and children (n = 16) interred in London, United Kingdom (UK), and adult European migrants interred in Otago, New Zealand (NZ) (n = 24) using standard histological techniques.

RESULTS: All individuals interred in London, and 92% (22/24) of those in New Zealand exhibited evidence of accentuated line formation within the first 2.5 years of life. There was no difference in median accentuated line occurrence between adults and children interred in the UK. However, NZ adults had a lower median occurrence of accentuated lines over the first 2.5 years since birth (5 ALs/individual) than UK adults (13 ALs/individual). Accentuated lines most frequently occurred in infancy for all three groups examined. However, temporal trends in accentuated line occurrence differed between groups in association with age.

DISCUSSION: These results highlight the impact of childhood stresses on working-class people growing up during the nineteenth century, underlining potential differences in the childhood experiences of hardship in individuals that remained in Britain and those that departed for foreign soils.},
}

Humans
New Zealand
History, 19th Century
United Kingdom
Child
Adult
Male
*Tooth/pathology
*Stress, Psychological/pathology/history
Female
Child, Preschool
Young Adult
Infant
Adolescent
Transients and Migrants/history