@article {pmid41796799,
year = {2026},
author = {Zhao, DY and Nabeel-Shah, S and Ni, Z and Pu, S and Zhong, G and Schmitges, FW and Braunschweig, U and Blencowe, BJ and Greenblatt, JF},
title = {RNA-Binding Proteins TDP-43 and FUS Promote R-Loop Resolution and Regulate Transcription Termination.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111348},
doi = {10.1016/j.jbc.2026.111348},
pmid = {41796799},
issn = {1083-351X},
abstract = {TDP-43 and FUS are RNA-binding proteins involved in the regulation of diverse RNA processing events and have been strongly implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We have previously demonstrated the role of symmetrical dimethylation (me2s) of a conserved arginine residue (R1810 in human POLR2A) in the C-terminal domain (CTD) of RNA polymerase II (RNAPII), which facilitates the recruitment of the Tudor domain-containing protein SMN to resolve R-loops at transcriptional termination sites. Here, we demonstrate that TDP-43 and FUS contribute to transcription termination through the R1810me2s-SMN pathway. Our data show that TDP-43-and to a lesser extent, FUS-are recruited to chromatin via this pathway, and that disruption of their recruitment leads to defective RNAPII termination. This impairment results in the accumulation of R-loops and elevated DNA damage at gene terminators. Using transcriptome-wide analyses, we further show that TDP-43 RNA-binding sites are highly correlated with regions of R-loop formation. Importantly, we find that the RNA-binding activity of TDP-43 is essential for its role in resolving R-loops and promoting efficient transcription termination. These findings establish a mechanistic link between TDP-43/FUS, R-loop resolution, and transcription termination, providing new insights into how their dysfunction may drive genome instability and contribute to the pathogenesis of ALS and FTD.},
}

@article {pmid41796748,
year = {2026},
author = {Stopyra, W and Voytsekhivskyy, O and Grzybowski, A},
title = {Accuracy of sixteen axial length adjusted intraocular lens power calculation formulas in long Caucasian eyes.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100301},
doi = {10.1016/j.apjo.2026.100301},
pmid = {41796748},
issn = {2162-0989},
abstract = {OBJECTIVE: To compare the accuracy of sixteen intraocular lens (IOL) power calculation formulas incorporating targeted adjustments or regression-based modifications of axial length (AL) in eyes longer than 26.00mm.

DESIGN: Retrospective observational study.

METHODS: The data of myopic patients with cataract who underwent uneventful phacoemulsification with in-the-bag implantation of a PARTIAL-RoF narrow IOL between January 2020 and June 2025 were reviewed. Preoperative IOL power was calculated using the IOLMaster 700 with six formulas: Barrett Universal II (BU II), Haigis, Hoffer Q, Holladay 1, Holladay 2, and SRK/T. The implanted IOL power was selected from BU II or SRK/T recommendations. Refraction was measured three months postoperatively. Postoperative IOL power predictions were generated using the following formulas or formula variants: K6, PEARL-DGS, Castrop, Eom, VRF CMAL; Holladay 1 with Wang-Koch 2 center optimization (WK2), modified Wang-Koch (MWK), non-linear regression (NLR), and Fam-adjusted method (F2); SRK/T WK2, SRK/T MWK, SRK/T F2; Holladay 2 NLR; Hoffer Q WK2; Haigis WK2; and Barrett True AL. The primary outcome measures were root mean square absolute error (RMSAE) and the percentage of eyes with prediction error (PE) within ± 0.25 D, ± 0.50 D, ± 0.75 D, and ± 1.00 D.

RESULTS: One hundred sixty-four eyes with ALs ranging from 26.04mm to 29.72mm were included. RMSAE values across the sixteen formulas ranged from 0.393 (Holladay 1 NLR and SRK/T WK2) to 0.803 (Haigis WK2). The percentage of eyes with PE within ±0.50 D ranged from 35.98% (Haigis WK2) to 81.1% (Holladay 1 NLR). Holladay 1 NLR-followed by SRK/T WK2, Holladay 1 MWK, VRF CMAL, PEARL-DGS, and Eom-demonstrated significantly higher accuracy than most other formulas. Haigis WK2 and Hoffer Q WK2 were the least accurate.

CONCLUSIONS: Certain modified third-generation formulas (Holladay 1 NLR, SRK/T WK2) achieve accuracy comparable to that of new-generation formulas (PEARL-DGS, K6, VRF CMAL) in IOL power calculations for long eyes. However, some third- and fourth-generation formulas-even after AL-based modification (Hoffer Q WK2, Haigis WK2)-continue to yield suboptimal results in this anatomical range.},
}

@article {pmid41796411,
year = {2026},
author = {Manyem, M and Gomathy, SB and Subramanian, VK and Sugan, S and Sugumaran, R and Narayan, SK},
title = {Unraveling amyotrophic lateral sclerosis: a novel peripherin mutation in a young male with sporadic onset.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {4},
pages = {},
pmid = {41796411},
issn = {1590-3478},
}

@article {pmid41795667,
year = {2026},
author = {Burgess, A and Allen, O and Barkhaus, P and Barnes, B and Benatar, M and Bertorini, T and Bowser, R and Mascias Cadavid, J and Carter, GT and Cudkowicz, M and Denson, K and Dyckman, K and Elsharif, B and Feldman, E and Foucher, J and Fullum, T and Glass, J and Helmold, B and Jackson, C and Jhooty, S and Leday, A and Mallon, E and Mcdermott, C and Olby, N and Ostrow, L and Pattee, G and Pioro, E and Ratner, D and Sang, H and Tito, E and Vieira, F and Wicks, P and Bedlack, R and Gelevski, D},
title = {ALS untangled #83: clenbuterol.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2638588},
pmid = {41795667},
issn = {2167-9223},
abstract = {ALS Untangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review clenbuterol, a β-2 adrenergic agonist, as a potential treatment for amyotrophic lateral sclerosis (ALS). Clenbuterol has biological effects that could be relevant to the pathophysiology of ALS such as inducing muscle hypertrophy, improving mitochondrial function, and reducing neuroinflammation. Two studies in mouse models of motor neuron disease and two open label trials suggest possible benefits. However these have methodological flaws which limit interpretation. Clenbuterol can have an array of side effects, some severe. Drop-outs due to side effects were very common in one of the ALS trials and in a separate expanded access program. Based on this information, we cannot currently endorse clenbuterol as an ALS treatment, but we do hope to see further studies of it, or another long acting β-2 adrenergic agonist in people with ALS.},
}

@article {pmid41795629,
year = {2026},
author = {Shafie, M and Tamba, C and Bhinder, H and , and Kalra, S and Pizzagalli, F},
title = {Brain Folding Trajectories in Amyotrophic Lateral Sclerosis.},
journal = {Human brain mapping},
volume = {47},
number = {4},
pages = {e70449},
pmid = {41795629},
issn = {1097-0193},
support = {MOP-123534/CAPMC/CIHR/Canada ; //ALS Society of Canada/ ; //Brain Canada Foundation/ ; 202292PHR2//Italian Ministry of University and Research (MUR), PRIN 2022/ ; //Shelly Mrkonjic ALS Research Fund/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology ; Male ; Female ; Middle Aged ; Magnetic Resonance Imaging ; Aged ; Disease Progression ; *Cerebral Cortex/diagnostic imaging/pathology ; Longitudinal Studies ; Adult ; Neuroimaging ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease, and neuroimaging markers offer a promising avenue to capture this variability. Cortical folding alterations in ALS remain largely unexplored despite growing interest in neuroimaging markers of the disease. This study is the first whole-brain investigation of sulcal morphometry in ALS. A total of 222 individuals diagnosed with ALS and 194 healthy controls (HC) were recruited through the Canadian ALS Neuroimaging Consortium (CALSNIC) for a longitudinal investigation. Using T1-weighted MRI processed with FreeSurfer and BrainVISA, we extracted cortical thickness and four sulcal features: width, mean depth, surface area, and length, across 123 sulci. We identified widespread alterations in ALS, with 19 sulci showing increased width and length alongside reduced depth and surface area, primarily in frontal and parietal regions surrounding the motor strip. The central sulcus (CS) emerged as the most consistently affected region, displaying bilateral widening and reduced depth, changes that closely tracked motor decline. Longitudinal analyses revealed progressive widening and reduced depth and surface area of the CS. These alterations closely tracked the progression of motor symptoms over the course of the disease and aligned with regional cortical thickness alterations. Our findings demonstrate that brain folding patterns, and in particular CS, are altered in ALS and correlate with clinical progression, resembling the neurodegenerative pattern of the disease. By revealing complementary and sensitive changes, sulcal-based metrics may offer promising neuroimaging biomarkers for early detection, prognosis, and patient stratification in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology
Male
Female
Middle Aged
Magnetic Resonance Imaging
Aged
Disease Progression
*Cerebral Cortex/diagnostic imaging/pathology
Longitudinal Studies
Adult
Neuroimaging

@article {pmid41794640,
year = {2026},
author = {Chen, X and Zhu, B},
title = {Decoding the functions of nuclear speckles in neurodegeneration.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2026.01.010},
pmid = {41794640},
issn = {1878-108X},
support = {DP2 GM140924/GM/NIGMS NIH HHS/United States ; R35 GM157978/GM/NIGMS NIH HHS/United States ; },
abstract = {Nuclear speckles, traditionally considered mainly as reservoirs of splicing factors, are increasingly recognized as dynamic biomolecular condensates essential for RNA metabolism, transcriptional regulation, and chromatin organization. Recent advances reveal their phase separation properties, compositional complexity, and stress-responsive remodeling, positioning nuclear speckles as key regulators of proteostasis and stress adaptation. Here, we synthesize emerging evidence linking nuclear speckle dysfunction to neurodegenerative proteinopathies, particularly amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) and tauopathies. We highlight how disease-associated repeat RNAs, dipeptide repeat proteins, and hyperphosphorylated tau disrupt nuclear speckle integrity, driving transcriptional and splicing defects. Finally, we discuss therapeutic strategies to rejuvenate nuclear speckles, emphasizing their potential as novel targets for restoring proteostasis and mitigating neurodegeneration. This review underscores nuclear speckles as critical yet underexplored regulators of neuronal resilience.},
}

@article {pmid41778709,
year = {2026},
author = {La Cognata, V and Guarnaccia, M and Morello, G and Gentile, G and Cavallaro, S},
title = {Unlocking amyotrophic lateral sclerosis diagnosis: How artificial intelligence is transforming early prediction.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01318},
pmid = {41778709},
issn = {1673-5374},
}

@article {pmid41752224,
year = {2026},
author = {Oriol, NE and Lin, J and Bennet, J and DeLorenzo, D and Fallon, MK and Gracy, D and Hill, C and Vasquez, M and Vavasis, A and Williams, M and Honoré, P},
title = {Developing a Public Health Quality Tool for Mobile Health Clinics to Assess and Improve Care.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {2},
pages = {},
pmid = {41752224},
issn = {1660-4601},
support = {unknown//Association of American Medical Colleges/ ; unknown/CC/CDC HHS/United States ; unknown//U.S. Department of Health and Human Services/ ; unknown//Family Health Council of Central Pennsylvania/ ; unknown//Aetna Foundation/ ; unknown//The Leon Lowenstein Foundation/ ; unknown//Northeastern University, Knox County Maine Mobile/ ; },
mesh = {Humans ; *Mobile Health Units/standards ; *Public Health ; *Quality Improvement ; Telemedicine ; },
abstract = {This report describes the development and deployment of the Public Health Quality Tool (PHQTool), an online resource designed to help mobile health clinics (MHCs) assess and improve the quality of their public health services. MHCs provide essential clinical and public health services to underserved populations but have historically lacked tools to assess and improve the quality of their work. To address this gap, the PHQTool was developed as an online, evidence-based, self-assessment resource for MHCs, hosted on the Mobile Health Map (MHMap) platform. This report documents the collaborative development process of the PHQTool and presents preliminary evaluation findings related to usability and relevance among mobile health clinics. Drawing from national public health frameworks and Honore et al.'s established public health quality aims, the PHQTool focuses on six aims most relevant to mobile care: Equitable, Health Promoting, Proactive, Transparent, Effective, and Efficient. Selection of the six quality aims was guided by explicit criteria developed through pilot testing and stakeholder feedback. The six aims were those that could be directly implemented through mobile clinic practices and were feasible to assess within diverse mobile clinic contexts. The remaining three aims ("population-centered," "risk-reducing," and "vigilant") were determined to be less directly actionable at the program level or required system-wide or data infrastructure beyond the scope of individual mobile clinics. Development included expert consultation, pilot testing, and iterative refinement informed by user feedback. The tool allows clinics to evaluate practices, identify improvement goals, and track progress over time. Since implementation, 82 MHCs representing diverse organizational types have used the PHQTool, reporting high usability and identifying common improvement areas such as outreach, efficiency, and equity-driven service delivery. Across pilot and post-pilot implementation phases, a majority of respondents agreed or strongly agreed that the tool was user-friendly, relevant to their work, and appropriately scoped for mobile clinic practice. Usability and acceptance were assessed using descriptive statistics, including percentage agreement across Likert-scale items as well as qualitative feedback collected during structured debriefs. Reported findings reflect self-reported perceptions of feasibility, clarity, and relevance rather than inferential statistical comparisons. The PHQTool facilitates systematic quality assessment within the mobile clinic sector and supports consistent documentation of public health efforts. By providing a standardized, accessible framework for evaluation, it contributes to broader efforts to strengthen evidence-based quality improvement and promote accountability in MHCs.},
}

Humans
*Mobile Health Units/standards
*Public Health
*Quality Improvement
Telemedicine

@article {pmid41748268,
year = {2026},
author = {Challa, S and Griffith, M and Jegede, A and Tijani, A and Himes, E and Idiodi, I and Okoli, C and Dimowo, S and Omoluabi, E and Liu, JX},
title = {Understanding clients' and providers' perspectives on the implementation of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) for self-injection programming in Nigeria.},
journal = {BMJ global health},
volume = {10},
number = {Suppl 6},
pages = {},
pmid = {41748268},
issn = {2059-7908},
mesh = {Humans ; *Medroxyprogesterone Acetate/administration & dosage ; Nigeria ; Female ; *Contraceptive Agents, Female/administration & dosage ; Injections, Subcutaneous ; Adult ; Male ; Interviews as Topic ; Self Administration ; Qualitative Research ; *Attitude of Health Personnel ; Middle Aged ; Young Adult ; },
abstract = {Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is an injectable contraceptive method with a small needle and prefilled syringe system that has been approved for self-injection (SI) by clients. As DMPA-SC for SI programmes are being scaled, employing an implementation science lens is critical to understanding what works. This study explored providers' and clients' experiences with providing and receiving services, respectively, for DMPA-SC for SI in Nigeria, using an implementation science framework.Between 2021 and 2023, we conducted N=141 interviews with providers offering DMPA-SC for SI, and N=129 interviews with their clients using DMPA-SC for SI in Lagos, Enugu and Plateau States. Using Proctor et al's implementation science framework, we noted observations for each interview question, extracted related quotes, and coded observations and quotes by implementation outcome (acceptability, appropriateness, feasibility, fidelity, cost, efficiency, safety, client-centredness and adoption).Among clients, learning about DMPA-SC and SI from social network members facilitated acceptability and adoption of the method. Clients reported that provider outreach was appropriate for contraceptive information. However, providers desired support to mitigate their own out-of-pocket costs and enhance the feasibility of outreach. Occasionally, providers used clients' age or education to decide whether they could self-inject independently, rather than clients' ability to perform SI procedures, limiting client-centredness Many providers felt their fidelity to SI provision protocols could improve with refresher trainings on the latest guidelines around offering SI. Clients indicated that proactive follow-up support from providers for continued SI and side effect management was appropriate and desired; providers concurred with offering such support.Findings suggest that programme scale-up efforts should prioritise: (1) leveraging peer support or social networks to facilitate acceptability of DMPA-SC for SI among clients, (2) improving access to training aids to ensure fidelity to protocols and facilitate adoption among clients and providers, (3) emphasising shared decision-making in judgement-free client trainings to encourage client-centredness, and (4) investing in models for proactive follow-up support to improve feasibility of continuation for clients' desired length of time.},
}

Humans
*Medroxyprogesterone Acetate/administration & dosage
Nigeria
Female
*Contraceptive Agents, Female/administration & dosage
Injections, Subcutaneous
Adult
Male
Interviews as Topic
Self Administration
Qualitative Research
*Attitude of Health Personnel
Middle Aged
Young Adult

@article {pmid41746390,
year = {2026},
author = {Kural, I and M Mombeek, LM and Wilson, DM},
title = {Role of mitochondria in neuronal function and survival in the enteric and central nervous systems.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {83},
number = {1},
pages = {},
pmid = {41746390},
issn = {1420-9071},
support = {11P4G24N//Fonds Wetenschappelijk Onderzoek/ ; G0A9625FWO//Fonds Wetenschappelijk Onderzoek/ ; },
abstract = {UNLABELLED: Mitochondria are indispensable organelles that not only generate cellular energy through oxidative phosphorylation but also regulate calcium homeostasis, redox balance, and apoptotic signaling. Given the high metabolic demands of neurons, mitochondrial function and resilience mechanisms are essential for neuronal development, maturation, and survival; when these systems fail, pathological outcomes can arise. This review highlights the critical role of mitochondria in maintaining neuronal function, with discussion related to both the central (CNS) and enteric (ENS) nervous systems. We present how mitochondrial dysfunction, through impaired bioenergetics, oxidative stress, defective quality control, and altered dynamics, can drive neuronal cell loss. Furthermore, we highlight the link between mitochondrial defects and nervous system pathological outcomes in both primary mitochondrial disorders, such as mitochondrial neurogastrointestinal encephalomyopathy, and secondary mitochondrial disorders, such as Alzheimer, Parkinson, and Huntington disease, as well as amyotrophic lateral sclerosis. By integrating evidence from the CNS and ENS, this review highlights the central role of mitochondria in supporting and preserving neuronal health, as well as the potential of mitochondria as therapeutic targets in neurodegenerative disease.

GRAPHICAL ABSTRACT: [Image: see text]},
}

@article {pmid41692368,
year = {2026},
author = {Dehury, S and Tiwari, S and Los Rios, P},
title = {Refolding-assisted purification of native full-length TDP-43 compatible with BSL-2 safety regulations.},
journal = {Methods (San Diego, Calif.)},
volume = {248},
number = {},
pages = {83-91},
doi = {10.1016/j.ymeth.2026.02.009},
pmid = {41692368},
issn = {1095-9130},
mesh = {*DNA-Binding Proteins/isolation & purification/chemistry/genetics ; Escherichia coli/genetics/metabolism ; Humans ; Protein Refolding ; *Containment of Biohazards/methods ; Recombinant Proteins/isolation & purification/chemistry/genetics ; Chromatography, Affinity/methods ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) is a prion-like RNA-binding protein that plays a key role in amyotrophic lateral sclerosis and frontotemporal dementia. Producing full-length TDP-43 consistently is thus relevant for its in vitro studies and yet it remains challenging, especially with the current requirement to work under biosafety level-2 (BSL-2) containment due to new safety regulations for Prion-like and amyloidogenic proteins. Here we describe a refolding-assisted purification protocol for TDP-43 from soluble fraction that can be implemented with basic equipment in standard BSL-2 laboratories. Expression in Escherichia coli is followed by IMAC-capture on an EDTA/DTT-tolerant Ni[2+]-NTA resin under 4 M urea, then on-column refolding via a gradient urea wash using resin-limiting conditions that favour the binding to high-affinity His-tagged protein. After removal of the SUMO solubility tag, the preparation is monitored by a robust quality-control pipeline: SDS-PAGE and immunoblotting for integrity and purity, mass photometry for oligomeric state, far-UV circular dichroism for secondary structure, fluorescence anisotropy for native functional assays, and light-scattering for stability and aggregation propensity measurements. A concise BSL-2 standard operating procedure specifies containment, decontamination, and waste handling for prion-like proteins. This protocol enables safe, cost-effective, and reproducible access to native-like full-length TDP-43 and is readily adaptable to other prion-like aggregation-prone proteins.},
}

*DNA-Binding Proteins/isolation & purification/chemistry/genetics
Escherichia coli/genetics/metabolism
Humans
Protein Refolding
*Containment of Biohazards/methods
Recombinant Proteins/isolation & purification/chemistry/genetics
Chromatography, Affinity/methods

@article {pmid41633321,
year = {2026},
author = {Di Gennaro, G and Grammaldo, LG and Tomasini, A},
title = {Toward a multidimensional understanding of internalized epilepsy stigma.},
journal = {Epilepsy & behavior : E&B},
volume = {177},
number = {},
pages = {110899},
doi = {10.1016/j.yebeh.2026.110899},
pmid = {41633321},
issn = {1525-5069},
mesh = {Humans ; *Epilepsy/psychology ; *Social Stigma ; Emotions ; },
abstract = {This letter responds to Prieto et al.'s discussion of our article Rethinking epilepsy stigma: the uncanny, the emotional, and the structural. We clarify that our original framework was primarily theoretical, aiming to illuminate the multifaceted mechanisms sustaining internalized epilepsy stigma, including the "uncanny" experience of seizures, ambivalent emotional responses, and structural inequities. We highlight how third-generation psychotherapeutic approaches, emphasizing psychological flexibility, mindfulness, and emotional acceptance, complement cognitive-behavioral strategies by enhancing individuals' capacity to relate adaptively to stigma-related distress. We propose that integrating behavioural, emotional, and structural perspectives offers a multidimensional framework to better understand and address internalized epilepsy stigma, guiding interventions that promote psychological well-being, social inclusion, and empowerment for people living with epilepsy.},
}

Humans
*Epilepsy/psychology
*Social Stigma
Emotions

@article {pmid41408351,
year = {2025},
author = {Ibragimov, U and Giordano, NA and Amaresh, S and Getz, T and Matuszewski, T and Steck, AR and Li, Y and Blum, EH and Tuttle, J and Pipalia, H and Cooper, HLF and Carpenter, JE},
title = {Implementation outcomes and strategies of a peer recovery coach program: findings from a qualitative assessment in the U.S. South, 2024-2025.},
journal = {Addiction science & clinical practice},
volume = {20},
number = {1},
pages = {95},
pmid = {41408351},
issn = {1940-0640},
support = {R01 CE003509/CE/NCIPC CDC HHS/United States ; R01CE003509/ACL/ACL HHS/United States ; R01CE003509/CC/CDC HHS/United States ; },
mesh = {Humans ; *Peer Group ; *Substance-Related Disorders/rehabilitation/therapy ; Qualitative Research ; *Emergency Service, Hospital ; Male ; Female ; Georgia ; Adult ; Program Evaluation ; Middle Aged ; *Mentoring ; Interviews as Topic ; },
abstract = {INTRODUCTION: Successful implementation of peer recovery coach (PRC) programs may help improve linkage to services and clinical outcomes for emergency department (ED) patients with substance use disorder (SUD). However, literature on implementation outcomes and strategies of PRC programs is limited. We conducted a qualitative assessment of implementation outcomes and strategies for an ED-based PRC program in Atlanta, Georgia.

METHODS: We conducted qualitative interviews with 27 program participants (ED patients with SUD served by PRC program) and 29 service providers and partners (peer recovery coaches, ED physicians and staff, SUD treatment and other service providers) in October 2023 - March 2025. We transcribed audio-recordings and analyzed data using rapid qualitative analysis approach mapping emerging themes to Proctor's model of implementation outcomes and Leeman et al.'s implementation strategies framework.

RESULTS: We identified two major themes related to implementation outcomes: (1) PRC program acceptability (patients' positive interactions with PRCs) and (2) appropriateness (sub-themes include: successful linkage to community services; PRC program as an important resource for patients; added value of PRC team; no negative impact on ED workflow). Themes related to implementation strategies include (1) streamlined communication between PRC and ED teams (direct communication via electronic medical records system, single contact phone number, informing ED service providers of clinical and program outcomes), (2) addressing barriers to community-based services (preparing patient's medical documentation, insurance, transportation to community services); (3) supportive supervision of PRCs (addressing daily and long-term issues through regular meetings; limiting caseload; and providing orientation, on-job training and mental health support) and (4) addressing telehealth implementation challenges (ensuring access to electronic medical records system).

CONCLUSION: This study outlines key implementation outcomes and strategies for PRC programs, offering practical guidance for successful ED-based PRC program implementation.},
}

Humans
*Peer Group
*Substance-Related Disorders/rehabilitation/therapy
Qualitative Research
*Emergency Service, Hospital
Male
Female
Georgia
Adult
Program Evaluation
Middle Aged
*Mentoring
Interviews as Topic

@article {pmid40772650,
year = {2025},
author = {Zhang, Y and Guo, Z and Qiu, R and Ren, Z and Huo, J and Yang, Y and Qiao, B and Jiang, Z and Liu, T},
title = {The ConPET Mechanism Remains Veiled: Reply to "Unlocking the ConPeT Mechanism".},
journal = {Angewandte Chemie (International ed. in English)},
volume = {64},
number = {36},
pages = {e202514007},
doi = {10.1002/anie.202514007},
pmid = {40772650},
issn = {1521-3773},
support = {22171141//National Natural Science Foundation of China/ ; 22193010//National Natural Science Foundation of China/ ; 22193014//National Natural Science Foundation of China/ ; 21925103//National Natural Science Foundation of China/ ; 22271077//National Natural Science Foundation of China/ ; 020-63233022//Fundamental Research Funds for the Central Universities/ ; 24HASTIT001//Program for Science & Technology Innovation Talents in Universities of Henan Province/ ; },
abstract = {In this journal, a Correspondence by Ventura, Cozzi, and Ceroni reported time-resolved absorption spectroscopy studies in the electron transfer process from cyanoarene photocatalyst 3,4,5,6-tetrakis(diphenyl amino)phthalonitrile (4DPAPN) in the presence of tetrabutylammonium oxalate (TBAOx). This was used as a model reaction to investigate the mechanism of consecutive photoinduced electron transfer (ConPET) in our previously reported asymmetric [3+2] photocycloaddition. They proposed a new electron transfer pathway in which the electron from the excited state of the radical anion 4DPAPN*[•-] solvated in acetonitrile. This article replies to their Correspondence, including: the experimental and theoretical analysis on the driving force of electron transfer and a series of new experiments conducted with purer reagents under more stringent conditions, which suggest that the process of proton-coupled electron transfer (PCET) followed by ConPET cannot be excluded, as proposed in our previous publication. Yet, Ceroni et al.'s efforts to study organic photochemical reactions using time-resolved spectroscopy remain worthwhile, and their proposed mechanism also led us to consider other possible pathways for the reaction. This article concludes with a series of constructive suggestions for further studying the ConPET mechanism using time-resolved absorption spectroscopy and other techniques.},
}

@article {pmid40654711,
year = {2025},
author = {Major, AJ and Abdaltawab, A and Phillips, JM and Wang, T and Lee, EK and Lichtenfeld, MJ and Chandrasekaran, C and Saalmann, YB and Maier, A and Desimone, R and Miller, EK and Bastos, AM and Mendoza-Halliday, D},
title = {A ubiquitous spectrolaminar motif across independent studies, including Mackey et al.'s own data.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40654711},
issn = {2692-8205},
support = {R00 MH116100/MH/NIMH NIH HHS/United States ; },
abstract = {Our study (Mendoza-Halliday et al., 2024) made two contributions: (1) discovery of a ubiquitous cortical motif and (2) a tool derived from it-the Frequency-based Layer Identification Procedure (FLIP and vFLIP). Mackey et al. critique the tool, questioning its advantage over classic current source density (CSD) analysis, and reason backwards to challenge the motif's ubiquity. In our rebuttal, we confirm the spectrolaminar motif in diverse cortical areas using data from multiple research groups (who joined us in this rebuttal) as well as Mackey et al.'s own dataset. Additionally, we introduce vFLIP2, an improved version of our tool that addresses their comments. It reliably identified and localized the motif in our data and Mackey et al.'s data. Our findings reaffirm the motif's ubiquity. We value Mackey et al.'s comments, which helped refine our tool.},
}

@article {pmid40543562,
year = {2025},
author = {Pope, E and Ameral, V and Falcón, A and Smith, J and Shoemaker-Hunt, SJ and Bounthavong, M and McCullough, M and Kim, B},
title = {Knowledge and attitudes regarding substance use disorder treatment and harm reduction practices among US pharmacists: A scoping review.},
journal = {Journal of the American Pharmacists Association : JAPhA},
volume = {65},
number = {5},
pages = {102462},
doi = {10.1016/j.japh.2025.102462},
pmid = {40543562},
issn = {1544-3450},
mesh = {Humans ; Attitude of Health Personnel ; *Harm Reduction ; *Health Knowledge, Attitudes, Practice ; Opioid-Related Disorders/drug therapy ; *Pharmacists/psychology/statistics & numerical data ; Professional Role ; *Substance-Related Disorders/therapy/drug therapy ; United States ; },
abstract = {BACKGROUND: Pharmacists are uniquely positioned to address substance use disorders (SUDs) and expand harm reduction services due to their accessibility and expertise in medication management. However, attitudinal and structural barriers may limit their full potential in this role.

OBJECTIVE: This scoping review examines pharmacists' knowledge, attitudes, and engagement in SUD treatment and harm reduction.

METHODS: A scoping review was conducted using Levac et al.'s enhancement of Arksey and O'Malley's framework. A systematic search of MEDLINE (PubMed), PsycInfo, Embase, ProQuest Health & Medical, and ProQuest Psychology was performed on August 3, 2024, yielding 87 articles addressing pharmacists' knowledge, attitudes, and practices related to SUD and harm reduction.

RESULTS: Pharmacists generally acknowledge the efficacy of medications for opioid use disorder (MOUDs) in reducing opioid-related mortality but often hold stigmatizing beliefs about individuals with SUDs. While supportive of harm reduction strategies, such as naloxone distribution and needle and syringe programs, engagement varies widely. Significant gaps in education and training persist, leaving pharmacists with limited confidence and practical experience in SUD care, despite their reported familiarity with MOUDs and naloxone pharmacology.

CONCLUSION: This review highlights a complex interplay of support, barriers, and knowledge gaps shaping pharmacists' roles in SUD treatment and harm reduction. Targeted education, supportive policies, and interprofessional collaboration are crucial to enabling pharmacists to provide stigma-free, comprehensive care for individuals with SUDs.},
}

Humans
Attitude of Health Personnel
*Harm Reduction
*Health Knowledge, Attitudes, Practice
Opioid-Related Disorders/drug therapy
*Pharmacists/psychology/statistics & numerical data
Professional Role
*Substance-Related Disorders/therapy/drug therapy
United States

@article {pmid40457309,
year = {2025},
author = {Gupta, A and Wyatt, LC and Mammen, S and Zanowiak, JM and Lim, S and Islam, NS and Kumar, R and Beane, S and Gold, HT},
title = {Cost analysis of implementing a community health worker-led weight reduction randomized-controlled trial among prediabetic south asian patients at primary care sites in NYC.},
journal = {Implementation science : IS},
volume = {20},
number = {1},
pages = {26},
pmid = {40457309},
issn = {1748-5908},
support = {U48 DP001904/DP/NCCDPHP CDC HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1TR0001445/TR/NCATS NIH HHS/United States ; 1UG3HL15310/HL/NHLBI NIH HHS/United States ; U2C DK137135/DK/NIDDK NIH HHS/United States ; U48DP001904/CC/CDC HHS/United States ; UG3 HL154302/HL/NHLBI NIH HHS/United States ; U54 MD000538/MD/NIMHD NIH HHS/United States ; 1U2CDK137135/DK/NIDDK NIH HHS/United States ; R01 MD018528/MD/NIMHD NIH HHS/United States ; R01DK110048-01A1/DK/NIDDK NIH HHS/United States ; R18DK110740/DK/NIDDK NIH HHS/United States ; R18 DK110740/DK/NIDDK NIH HHS/United States ; R01MD018528/MD/NIMHD NIH HHS/United States ; R01 DK110048/DK/NIDDK NIH HHS/United States ; U54MD000538/MD/NIMHD NIH HHS/United States ; },
mesh = {Humans ; *Community Health Workers/economics ; *Primary Health Care/economics ; *Prediabetic State/therapy/ethnology ; New York City ; *Weight Reduction Programs/economics/methods ; COVID-19/epidemiology ; Male ; Costs and Cost Analysis ; Female ; Middle Aged ; Weight Loss ; Cost-Benefit Analysis ; SARS-CoV-2 ; },
abstract = {BACKGROUND: We conducted a cost analysis of implementing a randomized controlled trial that proved the effectiveness of a community health worker (CHW) facilitated weight loss intervention among South Asian patients with prediabetes receiving care at primary care practices in New York City. South Asians have a high prevalence of diabetes, but no study to date has evaluated the cost of implementing an evidence-based lifestyle intervention in this population. Cost estimates are necessary for an intervention's adoption and scale-up.

METHODS: The first wave of the intervention was implemented in-person, followed by two waves implemented remotely during the COVID-19 pandemic. We estimated the implementation, intervention, and adaptation costs and the costs by each wave of implementation, by applying the Gold et al.'s economic framework and ERIC discrete implementation strategy compilation Costs were calculated from the perspective of a health care payer, public health agency, or health care system. The CHW intervention included group education sessions over six months. For each wave, we separately estimated the total cost, cost per practice, and cost when implemented at only one practice. Using the Bureau of Labor Statistics salary estimates, we calculated the national average (mean salary) and lower (25th percentile salary) and upper (75th percentile salary) bounds.

RESULTS: The average total 6-month implementation costs over 3 waves, each targeting seven practices was $215,420 (range: $158,620-$257,020). Program staff salaries comprised > 93% of total costs. Adaptation cost was nearly 1/3 of start-up costs. On average, implementation at one practice would cost twice as much as the per-practice costs when implemented simultaneously at seven practices in a wave, due to spread of start-up costs across multiple sites.

CONCLUSIONS: Staff salaries comprise most of the budget to implement such an intervention. It is most efficient for an agency to implement this intervention across several practices simultaneously. Decision-makers will need to evaluate relative costs and effectiveness of other options to achieve weight loss in a minority community with constrained resources.

CLINICALTRIALS: GOV: This study was registered on June 15, 2017 at  https://www.

CLINICALTRIALS: gov as NCT03188094. https://clinicaltrials.gov/ct2/show/NCT03188094 .},
}

Humans
*Community Health Workers/economics
*Primary Health Care/economics
*Prediabetic State/therapy/ethnology
New York City
*Weight Reduction Programs/economics/methods
COVID-19/epidemiology
Male
Costs and Cost Analysis
Female
Middle Aged
Weight Loss
Cost-Benefit Analysis
SARS-CoV-2

@article {pmid40138021,
year = {2025},
author = {Vaughan, DP and Real, R and Jensen, MT and Fumi, RG and Hodgson, M and Jabbari, E and Lux, D and Wu, L and , and , and Warner, TT and Jaunmuktane, Z and Revesz, T and Rowe, JB and Rohrer, J and Morris, HR},
title = {Analysis of C9orf72 repeat length in progressive supranuclear palsy, corticobasal syndrome, corticobasal degeneration, and atypical parkinsonism.},
journal = {Journal of neurology},
volume = {272},
number = {4},
pages = {293},
pmid = {40138021},
issn = {1432-1459},
support = {220258/WT_/Wellcome Trust/United Kingdom ; T033371/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00030/14//Cambridge Centre for Parkinson-Plus/ ; /WT_/Wellcome Trust/United Kingdom ; NIHR203312//NIHR Cambridge Biomedical Research Centre/ ; PROSPECT2//Progressive Supranuclear Palsy Association/ ; },
mesh = {Humans ; C9orf72 Protein/genetics ; *Supranuclear Palsy, Progressive/genetics ; Male ; Female ; Aged ; *DNA Repeat Expansion/genetics ; *Parkinsonian Disorders/genetics ; Middle Aged ; *Corticobasal Degeneration/genetics ; Aged, 80 and over ; Cohort Studies ; },
abstract = {BACKGROUND: Pathogenic hexanucleotide repeat expansions in C9orf72 are the commonest genetic cause of frontotemporal dementia and/or amyotrophic lateral sclerosis. There is growing interest in intermediate repeat expansions in C9orf72 and their relationship to a wide range of neurological presentations, including Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, and corticobasal syndromes.

AIMS: To assess the prevalence of intermediate C9orf72 repeat expansions in a large cohort of prospectively-recruited patients clinically diagnosed with progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and atypical parkinsonism (APS), compared with healthy controls. We also sought to replicate the association between C9orf72 repeat length and CBD in neuropathologically confirmed cases.

METHODS: 626 cases, including PSP (n = 366), CBS (n = 130), and APS (n = 53) from the PROSPECT study, and 77 cases with pathologically confirmed CBD were screened for intermediate repeat expansions in C9orf72 using repeat-primed PCR. These were compared to controls from the PROSPECT-M-UK study and from the 1958 Birth Cohort.

RESULTS: There was no difference in the mean or largest allele size in any affected patient group compared with controls. A higher proportion of our affected cohort had large C9orf72 repeat expansions compared to controls, but there was no difference when comparing the frequency of intermediate expansions between affected patients and controls. There was no relationship between repeat length and age at onset, level of disability, or survival.

CONCLUSIONS: Intermediate expansions in C9orf72 do not appear to be a genetic risk factor for PSP, CBS, CBD, or atypical parkinsonism. They are not associated with age at onset, disability, or survival in our study.},
}

Humans
C9orf72 Protein/genetics
*Supranuclear Palsy, Progressive/genetics
Male
Female
Aged
*DNA Repeat Expansion/genetics
*Parkinsonian Disorders/genetics
Middle Aged
*Corticobasal Degeneration/genetics
Aged, 80 and over
Cohort Studies

@article {pmid39972510,
year = {2025},
author = {Endres-Dighe, S and Sucaldito, AD and McDowell, R and Wright, A and LoVette, A and Miller, WC and Go, V and Gottfredson O'Shea, N and Lancaster, KE},
title = {Mechanisms of resilience and coping to intersectional HIV prevention and drug-use stigma among people who inject drugs in rural Appalachian Ohio.},
journal = {Harm reduction journal},
volume = {22},
number = {1},
pages = {18},
pmid = {39972510},
issn = {1477-7517},
support = {UG3DA044822//National Institute of Drug Abuse/ ; K01 DA048174/DA/NIDA NIH HHS/United States ; K01DA048174//National Institute of Drug Abuse/ ; R36 DA060059/DA/NIDA NIH HHS/United States ; R36DA060059//National Institute of Drug Abuse/ ; R21 DA053708/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; *Social Stigma ; *HIV Infections/prevention & control/psychology ; *Resilience, Psychological ; Male ; *Adaptation, Psychological ; *Substance Abuse, Intravenous/psychology ; Female ; Rural Population ; Adult ; Social Support ; Ohio ; Middle Aged ; Appalachian Region ; },
abstract = {BACKGROUND: Intersectional stigma of drug-use and HIV hinders provision and utilization of HIV prevention services for people who inject drugs (PWID), particularly within rural US communities. Resilience and coping may be critical for PWID to counter pervasive stigma.

METHODS: Between October 2021 and July 2022, 35 in-depth interviews were conducted in Appalachian Ohio to understand the intersection of drug-use and HIV prevention stigma and how resilience and coping processes are displayed, shared, and enacted. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted, guided by Harper et al.'s four key resilience processes: (a) engaging in health-promoting cognitive processes, (b) enacting in health behavioral practices, (c) exchanging social support, and (d) empowering other PWID to engage in health behavior practices.

RESULTS: Resilience processes aligned with the Harper framework with additional coping processes identified, including anticipation strategies and maladaptive coping. Empowering other PWID emerged as a prominent resiliency process, often supported by systems of support like syringe service programs (SSPs), which provided resources and helped reduce stigma. However, bidirectional social support was constrained, as PWID frequently acted as providers of resources and referrals for peers despite limited knowledge of HIV prevention strategies and feeling unsupported themselves. Anticipation strategies were employed to manage anticipated stigma, including accessing support or, conversely, avoiding healthcare and refraining from disclosing drug use. Maladaptive coping included behaviors such as social isolation and self-administered medical care, highlighting critical gaps in opportunities to foster resilience.

CONCLUSIONS: Findings highlight that empowering peers and anticipation strategies can be key resilience processes, while maladaptive coping and limited bidirectional social support underscore the need for resilience-building and stigma-reduction interventions. Tailored systems of support for PWID in rural communities are critical to fostering adaptive coping and enhancing engagement with HIV prevention services.},
}

Humans
*Social Stigma
*HIV Infections/prevention & control/psychology
*Resilience, Psychological
Male
*Adaptation, Psychological
*Substance Abuse, Intravenous/psychology
Female
Rural Population
Adult
Social Support
Ohio
Middle Aged
Appalachian Region

@article {pmid38865034,
year = {2024},
author = {Rashed, HR and Staff, NP and Milone, M and Mauermann, ML and Berini, S and Cheshire, WP and Coon, EA and Fealey, RD and Sorenson, E and Cutsforth-Gregory, J and Benarroch, EE and Sandroni, P and Low, PA and Singer, W and Shouman, K},
title = {Autonomic impairment in primary lateral sclerosis.},
journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society},
volume = {34},
number = {4},
pages = {421-425},
pmid = {38865034},
issn = {1619-1560},
mesh = {Humans ; Male ; Middle Aged ; Female ; *Autonomic Nervous System Diseases/physiopathology/diagnosis/etiology ; Adult ; Retrospective Studies ; Aged ; Sweating/physiology ; Motor Neuron Disease/physiopathology/diagnosis/complications ; Autonomic Nervous System/physiopathology ; },
abstract = {PURPOSE: Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis.

METHODS: Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded.

RESULTS: A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns.

CONCLUSION: We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.},
}

Humans
Male
Middle Aged
Female
*Autonomic Nervous System Diseases/physiopathology/diagnosis/etiology
Adult
Retrospective Studies
Aged
Sweating/physiology
Motor Neuron Disease/physiopathology/diagnosis/complications
Autonomic Nervous System/physiopathology

@article {pmid37100111,
year = {2023},
author = {Enders, J and Jack, J and Thomas, S and Lynch, P and Lasnier, S and Cao, X and Swanson, MT and Ryals, JM and Thyfault, JP and Puchalska, P and Crawford, PA and Wright, DE},
title = {Ketolysis is required for the proper development and function of the somatosensory nervous system.},
journal = {Experimental neurology},
volume = {365},
number = {},
pages = {114428},
pmid = {37100111},
issn = {1090-2430},
support = {R01 DK091538/DK/NIDDK NIH HHS/United States ; T32 HD057850/HD/NICHD NIH HHS/United States ; P20 GM103418/GM/NIGMS NIH HHS/United States ; R01 AG069781/AG/NIA NIH HHS/United States ; T32 DK128770/DK/NIDDK NIH HHS/United States ; R01 NS043314/NS/NINDS NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; P20 GM144269/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Friedreich Ataxia/pathology ; Mice, Knockout ; Ketones ; Oxidation-Reduction ; Sensory Receptor Cells/pathology ; },
abstract = {Ketogenic diets are emerging as protective interventions in preclinical and clinical models of somatosensory nervous system disorders. Additionally, dysregulation of succinyl-CoA 3-oxoacid CoA-transferase 1 (SCOT, encoded by Oxct1), the fate-committing enzyme in mitochondrial ketolysis, has recently been described in Friedreich's ataxia and amyotrophic lateral sclerosis. However, the contribution of ketone metabolism in the normal development and function of the somatosensory nervous system remains poorly characterized. We generated sensory neuron-specific, Advillin-Cre knockout of SCOT (Adv-KO-SCOT) mice and characterized the structure and function of their somatosensory system. We used histological techniques to assess sensory neuronal populations, myelination, and skin and spinal dorsal horn innervation. We also examined cutaneous and proprioceptive sensory behaviors with the von Frey test, radiant heat assay, rotarod, and grid-walk tests. Adv-KO-SCOT mice exhibited myelination deficits, altered morphology of putative Aδ soma from the dorsal root ganglion, reduced cutaneous innervation, and abnormal innervation of the spinal dorsal horn compared to wildtype mice. Synapsin 1-Cre-driven knockout of Oxct1 confirmed deficits in epidermal innervation following a loss of ketone oxidation. Loss of peripheral axonal ketolysis was further associated with proprioceptive deficits, yet Adv-KO-SCOT mice did not exhibit drastically altered cutaneous mechanical and thermal thresholds. Knockout of Oxct1 in peripheral sensory neurons resulted in histological abnormalities and severe proprioceptive deficits in mice. We conclude that ketone metabolism is essential for the development of the somatosensory nervous system. These findings also suggest that decreased ketone oxidation in the somatosensory nervous system may explain the neurological symptoms of Friedreich's ataxia.},
}

Animals
Mice
*Friedreich Ataxia/pathology
Mice, Knockout
Ketones
Oxidation-Reduction
Sensory Receptor Cells/pathology

@article {pmid36884103,
year = {2023},
author = {Miki, Y and Shibuya, E and Yoshizawa, T and Tomiyama, M and Wakabayashi, K},
title = {Is amyotrophic lateral sclerosis a prion-like disorder? A case report.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {44},
number = {7},
pages = {2587-2589},
pmid = {36884103},
issn = {1590-3478},
support = {21K07452//JSPS KAKENHI/ ; 22H02948//JSPS KAKENHI/ ; Not provided//Hirosaki University Priority Research Grant for Future Innovation/ ; },
mesh = {Humans ; *Prions ; *Amyotrophic Lateral Sclerosis/diagnosis ; DNA-Binding Proteins ; },
}

Humans
*Prions
*Amyotrophic Lateral Sclerosis/diagnosis
DNA-Binding Proteins

@article {pmid32238767,
year = {2020},
author = {Kalimuthu, K and Kim, JM and Subburaman, C and Kwon, WY and Hwang, SH and Jeong, S and Cho, MG and Kim, HJ and Park, KS},
title = {Characterization of Rajath Bhasma and Evaluation of Its Toxicity in Zebrafish Embryos and Its Antimicrobial Activity.},
journal = {Journal of microbiology and biotechnology},
volume = {30},
number = {6},
pages = {920-925},
pmid = {32238767},
issn = {1738-8872},
mesh = {Animals ; *Anti-Infective Agents/chemistry/pharmacology/toxicity ; Bacteria/drug effects ; Embryo, Nonmammalian/drug effects ; India ; *Medicine, Ayurvedic ; *Metal Nanoparticles/chemistry/toxicity ; Microbial Sensitivity Tests ; Particle Size ; *Silver/chemistry/pharmacology/toxicity ; Zebrafish ; },
abstract = {In India, nanotechnology has been used in therapeutic applications for several millennia. One example of a traditional nanomedicine is Rajath Bhasma (als°Called calcined silver ash), which is used as an antimicrobial and for the treatment of various ailments and conditions such as memory loss, eye diseases, and dehydration. In this study, we aimed t°Characterize the physical composition and morphology of Rajath Bhasma and its suitability for use as a non-toxic antimicrobial agent. First, Rajath Bhasma was physically characterized via i) Fourier-transform infrared spectroscopy to analyze the surface functional groups, ii) scanning electron microscopy coupled with energydispersive X-ray spectroscopy to observe the morphology and elemental composition, and iii) X-ray diffraction to determine the crystalline phases. Thereafter, functional characterization was performed through toxicity screening using zebrafish embryos and through antimicrobial activity assessment against gram-positive (Staphylococcus epidermidis) and gram-negative (Escherichia coli) bacteria. Rajath Bhasma was found to harbor alkene, hydroxyl, aldehyde, and amide functional groups originating from biological components on its surface. The main component of Rajath Bhasma is silver, with particle size of 170-210 nm, and existing in the form of spherical aggregates with pure crystalline silver structures. Furthermore, Rajath Bhasma did not exert toxic effects on zebrafish embryos at concentrations below 5 μg/ml and exhibited effective antimicrobial activity against both gram-positive and gram-negative bacteria. The present results indicate that Rajath Bhasma is a potentially effective antimicrobial agent without toxicity when used at concentrations below 5 μg/ml.},
}

Animals
*Anti-Infective Agents/chemistry/pharmacology/toxicity
Bacteria/drug effects
Embryo, Nonmammalian/drug effects
India
*Medicine, Ayurvedic
*Metal Nanoparticles/chemistry/toxicity
Microbial Sensitivity Tests
Particle Size
*Silver/chemistry/pharmacology/toxicity
Zebrafish

@article {pmid27376163,
year = {2016},
author = {Petit, MD and Fernández, J},
title = {28th Annual DIA EuroMeeting (April 6-8, 2016 - Hamburg, Germany).},
journal = {Drugs of today (Barcelona, Spain : 1998)},
volume = {52},
number = {5},
pages = {305-308},
doi = {10.1358/dot.2016.52.5.2510259},
pmid = {27376163},
issn = {1699-3993},
abstract = {The 28(th) Drug Information Association (DIA) Annual EuroMeeting took place in Hamburg, Germany, gathering together participants from different industries, organizations, academic research centers, regulatory agencies and health ministries, mainly from the E.U. The conference began with a regulatory Town Hall meeting focusing on the E.U. Medicines Agencies Network strategy to 2020. This was followed by an opening plenary session where the diverse roles of innovation in drug development were discussed. Areas for discussion over the meeting were classified into 14 main themes, and for each session, profession¬als from the pharmaceutical industry, regulatory agencies and health ministries, as well as delegates from patient organizations, presented their considerations for debate. This report covers some regulatory sessions presented at the meeting.},
}

@article {pmid27800222,
year = {2015},
author = {Elbay, AE and Topalkara, A and Elbay, A and Erdoğan, H and Vural, A and Bahadır Çetin, A},
title = {Evaluation of Serum Homocysteine and Leptin Levels in Patients with Uveitis.},
journal = {Turkish journal of ophthalmology},
volume = {45},
number = {4},
pages = {146-151},
pmid = {27800222},
issn = {2149-8695},
abstract = {OBJECTIVES: To evaluate the serum homocysteine (Hcy) and leptin levels in patients with uveitis.

The 70 cases included in the study comprised 3 groups: patients with Behçet's uveitis (BU), patients with non-Behçet's uveitis (NBU) and healthy controls. Body mass index was calculated for each subject. Serum Hcy and leptin levels were measured. Furthermore, acute-phase reactants including erythrocyte sedimentation rate (ESR), C-reactive protein and neutrophil count were measured.

RE­SULTS: Serum Hcy levels were 15.04±4.59 µmol/L in the BU group, 15.4±6.87 µmol/L in the NBU group and 13.64±4.72 µmol/L in the control group (p>0.05). The serum leptin levels of male patients in the BU group, NBU group and control group were 4.76±3.54 ng/ml, 6.33±3.74 ng/ml and 5.47±6.33 ng/ml, respectively (p>0.05). When we compared serum leptin levels in female patients and controls, the mean serum leptin concentrations were significantly higher in female BU and NBU patients (24.83±17.62 ng/ml and 28.46±13.90 ng/ml, respectively) than in healthy control volunteers (9.62±6.36 ng/ml, p<0.05). In addition, the ESR value differences between groups were statistically significant (p<0.05).

CONCLUSION: A larger case series is necessary to investigate serum Hcy and leptin concentrations in uveitis patients.},
}

@article {pmid41606993,
year = {2026},
author = {Lindström, L and Ahlsson, F and Axelsson, O and Granfors, M and Lampa, E and Nelander, M and Wikström, AK},
title = {Differences in prediction of adverse perinatal outcome in term pregnancies by choice of fetal growth reference: A validation study.},
journal = {Acta obstetricia et gynecologica Scandinavica},
volume = {105},
number = {3},
pages = {466-478},
pmid = {41606993},
issn = {1600-0412},
support = {LUL-964880//Region Uppsala/ ; //Födelsefonden/ ; },
mesh = {Humans ; Female ; Pregnancy ; Sweden/epidemiology ; Infant, Newborn ; *Infant, Small for Gestational Age ; *Fetal Development ; Adult ; *Pregnancy Outcome ; Perinatal Mortality ; *Fetal Growth Retardation/diagnosis ; Birth Weight ; Reference Values ; Cohort Studies ; Growth Charts ; Registries ; },
abstract = {INTRODUCTION: Our objectives were to evaluate the association between fetal growth abnormalities and adverse perinatal outcomes in term pregnancies using four different fetal growth references: the recently published Swedish references by Lindström et al., the currently used Swedish references by Maršál et al., and the international standards by the WHO and INTERGROWTH-21st (IG21st). The study aimed to evaluate the performance of each reference and determine which reference most accurately identifies small for gestational age (SGA) infants at risk of perinatal mortality and morbidity.

MATERIAL AND METHODS: This population-based cohort study included 1 126 059 singleton term births in Sweden from 2010 to 2020. Data were obtained from national registers, including the Swedish Medical Birth Register and the Swedish Neonatal Quality Register. Birthweight centiles were calculated using each growth reference. Adverse perinatal outcomes were categorized by severity and included stillbirth, neonatal death, and serious neonatal morbidity. Logistic regression models were used to assess predictive performance, and sensitivity and false positive rates (FPR) were calculated for SGA thresholds (<3rd and <10th centiles).

RESULTS: The distribution of birthweight centiles varied significantly across references. For SGA <3rd centile, the rate ranged from 9.6% for Lindström, 2.5% for Maršál, 1.9% for WHO, to 0.7% for IG21st. All references showed similar overall predictive performance (C-index ≈ 0.67) but with different discriminatory ability. The predicted risk of perinatal death increased at lower centiles for the Lindström reference than for the Maršál and WHO references, and at higher centiles for the IG21st reference. The Lindström reference identified the highest proportion of infants as SGA and had the highest sensitivity but also the highest FPR for detecting adverse outcomes. The IG21st reference classified the smallest proportion as SGA, resulting in the lowest sensitivity and FPR.

CONCLUSIONS: While all fetal growth references showed comparable predictive ability for adverse perinatal outcomes, they differed substantially in sensitivity and FPR. When the top priority is to identify as many at-risk fetuses as possible, Lindström et al.'s reference seems to be the best choice. However, when the top priority is a balanced sensitivity versus FPR, the WHO reference seems most suitable for clinical practice in this population of term births.},
}

Humans
Female
Pregnancy
Sweden/epidemiology
Infant, Newborn
*Infant, Small for Gestational Age
*Fetal Development
Adult
*Pregnancy Outcome
Perinatal Mortality
*Fetal Growth Retardation/diagnosis
Birth Weight
Reference Values
Cohort Studies
Growth Charts
Registries

@article {pmid41502663,
year = {2025},
author = {Ma, Y and Tian, H and Xiao, W and Ma, Y and Su, H and Zhu, L and Jiang, Y and Ge, L and Li, Y and Yuan, M and Liu, X},
title = {Machine Learning Approaches for Optimizing Drug Combinations in Neurodegenerative Diseases: A Brief Review.},
journal = {ACS omega},
volume = {10},
number = {48},
pages = {57950-57973},
pmid = {41502663},
issn = {2470-1343},
abstract = {As the global population ages, the prevalence of neurodegenerative diseases (NDDs)(?)including Alzheimer's disease, Parkinson's disease, Huntington's disease, Multisystem Atrophy (multiple system atrophy), and amyotrophic lateral sclerosis(?)continues to rise, largely driven by environmental, metabolic, and lifestyle risk factors. Advances in computational technologies, particularly machine learning (ML) and deep learning, are reshaping research in this field. This review summarizes the major features of these diseases and emphasizes the role of ML in drug discovery, virtual screening, drug repurposing, and drug combination optimization. Representative approaches include support vector machines for classification, convolutional neural networks|convolutional neural network for imaging analysis, recurrent neural networks for temporal biomedical data, and transformers for multimodal integration. These methods highlight the potential of computational strategies to improve therapeutic development. In addition, the review underscores the substantial incidence rates and socioeconomic burden of these conditions, which have made them focal points for algorithmic innovation. With research evolving rapidly, the development of AI-driven approaches is expected to enable more effective, targeted interventions and improve patient outcomes. This Perspective provides a concise overview of current progress and identifies promising future directions in the fight against NDDs.},
}

@article {pmid40971256,
year = {2026},
author = {Dmuchowska, DA and Godzien, J and Mojsak, P and Godlewski, A and Gosk, W and Pietrowska, K and Konopinska, J and Kretowski, A and Ciborowski, M},
title = {Comment on: Changes in Aqueous Humor Cytokines and Metabolomics in Contralateral Eye After Unilateral Cataract Surgery.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {42},
number = {1},
pages = {9-11},
doi = {10.1177/10807683251380991},
pmid = {40971256},
issn = {1557-7732},
mesh = {Humans ; *Aqueous Humor/metabolism ; *Metabolomics/methods ; *Cataract Extraction/methods ; *Cytokines/metabolism ; *Cataract/metabolism ; Aged ; Male ; },
abstract = {UNLABELLED: We extend Li et al.'s investigation of aqueous humor (AH) metabolomics in sequential cataract surgery by referencing our prior study on interocular symmetry/asymmetry in AH metabolomic profiles from simultaneous bilateral cataract surgery in emmetropic patients, which demonstrated similar AH compositions in fellow eyes. We also illustrate variability with 2 sequential-surgery cases and highlight the most and least variable metabolites across 6 biochemical classes. Taken together with Li et al., these observations support careful attribution of second-eye changes to surgery versus biology.

PURPOSE: To extend the findings of Li et al. on AH metabolomics in sequential cataract surgery by incorporating reference data on interocular symmetry/asymmetry in AH metabolomic profiles and illustrating variability in sequential cases.

METHODS: We drew on our prior study of simultaneous bilateral cataract surgery in emmetropic patients, which demonstrated high interocular similarity, and examined AH metabolomic variability in 2 patients undergoing sequential cataract surgery.

RESULTS: Baseline interocular comparisons highlight metabolic symmetry in the AH among patients undergoing simultaneous cataract surgery. In 2 additional cases, we identified the most and least variable metabolites across 6 biochemical classes among patients undergoing sequential cataract surgery, complementing the observations of Li et al.Conclusion:Our reference data help contextualize Li et al.'s results. Although based on limited cases, our findings emphasize the need for caution when interpreting AH metabolomics in sequential surgery to distinguish true intra- and inter-individual biological variability from potential surgical effects on the second eye. Multimodal approaches integrating metabolomic and vascular metrics may improve biomarker selection and inform surgical timing.},
}

Humans
*Aqueous Humor/metabolism
*Metabolomics/methods
*Cataract Extraction/methods
*Cytokines/metabolism
*Cataract/metabolism
Aged
Male

@article {pmid30950445,
year = {2019},
author = {Bahcaci, U and Demirbuken, I},
title = {Effects of chemotherapy process on postural balance control in patients with breast cancer.},
journal = {Indian journal of cancer},
volume = {56},
number = {1},
pages = {50-54},
doi = {10.4103/ijc.IJC_47_18},
pmid = {30950445},
issn = {1998-4774},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Postural Balance/drug effects/*physiology ; Prognosis ; Prospective Studies ; Survivors/*statistics & numerical data ; },
abstract = {BACKGROUND: Breast cancer (BC) is the most common type of cancer among women in the world. Patients can face musculoskeletal disorders due to treatment side effects that result in failure to walk, falling, or fractures associated with balance problems.

PURPOSE: The aim of this study was to determine whether postural balance would be affected during chemotherapy (CT) in people with BC.

MATERİALS AND METHODS: A total of 32 women who consulted the medical oncology department, between 31 and 63 years of age, were admitted to the study. For fear of falling, fall efficiacy scale; for static balance, double-leg, single-leg, and tandem stance tests with eyes opened and eyes closed; Romberg test; for dinamic balance, Sit To Stand (STS) test, and Time Up and Go (TUG) tests were performed in the patients.

RESULTS: Reduced fear of falling between CT cycles (P < 0.0125), no change in postural sway in double-leg stance test with eyes opened (P = 0.734) and eyes closed (P = 0.127), significantly increased postural instability in single-leg and tandem stance test with eyes opened and eyes closed (P = 0.000), no change in postural stability in Romberg test (P > 0.05), significantly increased postural instability in STS (P = 0.000) and TUG tests (P = 0.000), and significantly increased time of finishing the STS (P = 0.021) and TUG tests (P = 0.010) were noted.

CONCLUSİON: Patients demonstrated postural instability which can ruin the daily life activities in many parameters of measurements. Postural balance exercises should be performed by BC survivors undergoing CT.},
}

Adult
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Breast Neoplasms/*drug therapy/pathology
Female
Follow-Up Studies
Humans
Middle Aged
Postural Balance/drug effects/*physiology
Prognosis
Prospective Studies
Survivors/*statistics & numerical data

@article {pmid29902001,
year = {2018},
author = {Ding, H and Wu, X and Pan, J and Hu, X and Gong, D and Zhang, G},
title = {New Insights into the Inhibition Mechanism of Betulinic Acid on α-Glucosidase.},
journal = {Journal of agricultural and food chemistry},
volume = {66},
number = {27},
pages = {7065-7075},
doi = {10.1021/acs.jafc.8b02992},
pmid = {29902001},
issn = {1520-5118},
mesh = {Acarbose/pharmacology ; Binding Sites ; Circular Dichroism ; Glycoside Hydrolase Inhibitors/*pharmacology ; Inhibitory Concentration 50 ; Kinetics ; Molecular Docking Simulation ; Pentacyclic Triterpenes ; Spectrometry, Fluorescence/methods ; Triterpenes/chemistry/metabolism/*pharmacology ; alpha-Glucosidases/chemistry/genetics/*metabolism ; Betulinic Acid ; },
abstract = {Betulinic acid (BA), an important pentacyclic triterpene widely distributed in many foods, possesses high antidiabetic activity. In this study, BA was found to exhibit stronger inhibition of α-glucosidase than acarbose with an IC50 value of (1.06 ± 0.02) × 10[-5] mol L[-1] in a mixed-type manner. BA bound with α-glucosidase to form a BA-α-glucosidase complex, resulting in a more compact structure of the enzyme. The obtained concentrations and spectra profiles of the components resolved by the multivariate-curve resolution-alternating least-squares confirmed the formation of the BA-α-glucosidase complex. Molecular docking showed that BA tightly bound to the active cavity of α-glucosidase, which might hinder the entrance of the substrate leading to a decline in enzyme activity. The chemical modification of α-glucosidase verified the results of the computer simulation that the order of importance of the four amino acid residues in the binding process was His > Tyr > Lys > Arg.},
}

Acarbose/pharmacology
Binding Sites
Circular Dichroism
Glycoside Hydrolase Inhibitors/*pharmacology
Inhibitory Concentration 50
Kinetics
Molecular Docking Simulation
Pentacyclic Triterpenes
Spectrometry, Fluorescence/methods
Triterpenes/chemistry/metabolism/*pharmacology
alpha-Glucosidases/chemistry/genetics/*metabolism
Betulinic Acid

@article {pmid27800224,
year = {2015},
author = {Savku, E and Gündüz, K},
title = {Diagnosis, Follow-Up and Treatment Results in Thyroid Ophthalmopathy.},
journal = {Turkish journal of ophthalmology},
volume = {45},
number = {4},
pages = {156-163},
pmid = {27800224},
issn = {2149-8695},
abstract = {OBJECTIVES: To discuss our follow-up and treatment results in thyroid-associated ophthalmopathy (TAO).

The records of 168 TAO cases who were followed at our clinic between October 1998 and October 2013 were reviewed retrospectively. The severity and activity of the disease were evaluated according to the criteria of the European Group on Graves' Ophthalmopathy (EUGOGO) and Clinical Activity Score (CAS).

RE­SULTS: Sixty-three men and 105 women participated in the study. The mean age of the patients was 42.3±12.4 years. Smoking habit was noted in 54.2% of the cases. Graves' disease was the most common (80.4%) thyroid pathology accompanying TAO. TAO was mild in 64.4%, moderate-to-severe in 33.6% and severe in 2% of the eyes. Male gender was found as an independent risk factor for severity of the disease (p=0.040). TAO was in the active phase in 32.6% of the eyes. Older age and high thyroid receptor antibody titer were correlated with disease activity (P=0.031 and P<0.001, respectively). Thirty-four patients (20%) were treated for ocular findings. The most common treatment was systemic steroid therapy (12%); others included orbital decompression (5%), orbital radiotherapy (2%), and topical application of guanethidine (1%).

CONCLUSION: Non-infiltrative phase and mild ocular findings were generally seen in TAO. Therefore, treatment is not recommended for many cases. Systemic steroid therapy is the most commonly used treatment modality in the active phase. However, orbital decompression surgery is necessary in a small number of cases with sight-threatening ocular findings.},
}

@article {pmid27800223,
year = {2015},
author = {Altıntaş, AG and Arifoğlu, HB and Köklü, ŞG},
title = {Modified Y-splitting Procedure for the Treatment of Duane Retraction Syndrome.},
journal = {Turkish journal of ophthalmology},
volume = {45},
number = {4},
pages = {152-155},
pmid = {27800223},
issn = {2149-8695},
abstract = {OBJECTIVES: To present the outcomes of modified lateral rectus Y-splitting combined with either unilateral or bilateral horizontal rectus recession in Duane Retraction Syndrome (DRS) with significant upshoot or downshoot.

A total of 12 patients including 10 patients with Type I DRS and 2 with Type III DRS underwent modified Y-splitting surgery. Amount of additional recessions varied with the degree of preoperative deviation by intraoperative adjustable suture technique. Preoperatively 3 patients had esotropia (ET), 6 had exotropia (XT), and 3 patients had orthotropia. The mean preoperative deviation was 19.3 prism diopters (PD) (range, 18-20 PD) in ET patients and 19.2 PD (range, 16-20 PD) in XT patients.

RE­SULTS: Postoperatively, all patients had significant correction in horizontal deviation and aligned within 4 PD of orthotropia, and no patients exhibited abnormal head posture. Co-contraction and globe retraction were markedly reduced and abnormal ocular vertical movement disappeared or significantly decreased in all cases. No patients experienced recurrence of ocular motility disorders in the mean 26-month (range, 13-66 months) follow-up period.

CONCLUSION: Modified Y-splitting surgery combined with co-contracting horizontal muscle recession technique seems to be a safe and effective treatment in DRS.},
}

@article {pmid27800221,
year = {2015},
author = {Söğütlü Sarı, E and Koç, R and Yazıcı, A and Şahin, G and Çakmak, H and Kocatürk, T and Ermiş, SS},
title = {Tear Osmolarity, Break-up Time and Schirmer's Scores in Parkinson's Disease.},
journal = {Turkish journal of ophthalmology},
volume = {45},
number = {4},
pages = {142-145},
pmid = {27800221},
issn = {2149-8695},
abstract = {OBJECTIVES: Dry eye is an important problem in Parkinson's disease (PD) with a potential to affect life quality. Tear osmolarity, accepted as the gold standard in dry eye diagnosis, has not been studied in this subset of patients so far. Therefore, in this study we aimed to evaluate tear osmolarity, Schirmer's test scores and tear film break-up time (TBUT) in PD patients.

PD patients with a minimum follow-up of 1 year and healthy controls who admitted for refractive abnormalities were enrolled to the study. Subjects using any systemic medication with a possibility to affect tear tests were not included in the study. The presence of any ocular surface disorder, previous ocular surgery, previous dry eye diagnosis, any topical ophthalmic medication or contact lens use were other exclusion criteria. Age, gender, disease duration, and Hoehn and Yahr (H&Y) score for disease severity were noted, and blink rate (BR), Schirmer's test score, TBUT and tear osmolarity of the right eye were measured in both groups.

RE­SULTS: Thirty-seven PD patients and 37 controls were enrolled to the study. The groups were age and gender matched. The mean disease duration and H&Y score were 5.70±2.64 years and 1.70±0.93, respectively. H&Y staging and disease duration were not correlated to BR, Schirmer's scores, TBUT, or tear osmolarity (p>0.05). The mean BR was 8.54±4.99 blinks/minute in PD patients and 11.97±6.36 blinks/minute in the control group. Mean Schirmer's scores, TBUT and osmolarity values were 9.08±4.46 mm, 11.38±4.05 seconds and 306.43±12.63 mOsm/L in the PD group and 17.16±9.57 mm, 12.81±3.66 seconds and 303.81±16.13 mOsm/L in the control group. The differences were significant only in BR and Schirmer's scores.

CONCLUSION: BR and Schirmer's scores decreased significantly in PD patients. Although not significant, the demonstrated tear osmolarity increment might be important to document the dry eye and inflammatory process of the ocular surface in PD patients.},
}

@article {pmid27800220,
year = {2015},
author = {Betül Türkoğlu, E and Tuna, S and Alan, S and İhsan Arman, M and Tuna, Y and Ünal, M},
title = {Effect of Systemic Infliximab Therapy in Patients with Sjögren's Syndrome.},
journal = {Turkish journal of ophthalmology},
volume = {45},
number = {4},
pages = {138-141},
pmid = {27800220},
issn = {2149-8695},
abstract = {OBJECTIVES: To investigate the effect of systemic infliximab therapy on tear function tests and the ocular surface in patients with Sjögren's syndrome secondary to various autoimmune diseases.

This prospective study included 22 eyes of 22 patients with Sjögren's syndrome who began treatment with systemic infliximab. Tear film break-up time (TBUT), anesthetized Schirmer's 1 test, fluorescein staining test, and Ocular Surface Disease Index (OSDI) scores were recorded before treatment and in the 3rd and 6th months of treatment.

RE­SULTS: In the 3rd month of infliximab therapy, no significant changes were observed in Schirmer's values, TBUT, fluorescein staining, or OSDI scores (p=0.260, p=0.357, p=0.190 and p=0.07, respectively). In the 6th month of infliximab therapy, no significant changes were observed in TBUT, fluorescein staining, Schirmer's value or OSDI scores (p=0.510, p=0.320, p=0.220 and p=0.344, respectively).

CONCLUSION: Infliximab therapy, which is commonly used in systemic autoimmune diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, and ankylosing spondylitis, did not show a positive effect on ocular surface and tear function tests.},
}

@article {pmid41793822,
year = {2026},
author = {Li, P and Wang, Y and Bao, Z and He, X and Wang, S and Su, X and Nie, W and Xu, F and Zhou, H and Li, H and Xu, B},
title = {Metagenomics-based insights into the microbial community composition and quality characteristics development potentiality in traditional dry-cured ham.},
journal = {International journal of food microbiology},
volume = {453},
number = {},
pages = {111705},
doi = {10.1016/j.ijfoodmicro.2026.111705},
pmid = {41793822},
issn = {1879-3460},
abstract = {The objective of this study was to elucidate the formation mechanisms of quality characteristics in traditional dry-cured ham. The microbial community composition in three types of dry-cured ham was analyzed using metagenomics technology. Volatile flavor profiles were characterized via gas chromatography-mass spectrometry (GC-MS) and gas chromatography-ion mobility spectrometry (GC-IMS), while peptide profiles were determined using liquid chromatography-mass spectrometry (LC-MS). Based on metagenomic data, biosynthetic pathways of volatile flavor compounds and bioactive peptides in dry-cured hams were reconstructed. Key microorganisms identified include Staphylococcus equorum, Staphylococcus saprophyticus, Aspergillus glaucus, Aspergillus ruber, Debaryomyces hansenii, and Debaryomyces fabryi. Using GC-MS and GC-IMS, 25 volatile compounds were identified in dry-cured ham, with branched-chain compounds exhibiting higher odor activity values (OAVs). LC-MS analysis identified 203 microbial-derived peptide fragments, predominantly possessing angiotensin-converting enzyme (ACE) inhibitory, dipeptidyl peptidase-IV (DPP-IV) inhibitory, and antioxidant activities. Further investigation into the contribution of microbial communities to the characteristic quality attributes revealed that Staphylococcus species promote the formation of 3-methyl-butanal via branched-chain amino acid transaminase (BCAT) and 3-hydroxy-2-butanone via acetolactate synthase (ALS). With regard to functional bioactive peptides, Staphylococcus indirectly contributes to the synthesis of NPPKFD, DLEE, and KRQKYD via glutamyl endopeptidase activity. Additionally, proteins derived from Aspergillus glaucus (actin-related protein 5) and Staphylococcus equorum (chromosome segregation protein) serve as direct precursors for bioactive peptides, yielding potential sequences such as KNSKDPVSI and LEDDI. This study provides evidence indicating the role of microbial communities in shaping the quality characteristics of dry-cured ham.},
}

@article {pmid41490046,
year = {2026},
author = {Maheswari Jawahar, V and Zeng, Y and Armour, EM and Yue, M and Citrano, K and Lovchykova, A and Reeves, MM and Rawlinson, B and DeTure, M and Dunmore, JA and Song, Y and Ball, SK and Wszolek, ZK and Graff-Radford, NR and Boeve, BF and Knopman, DS and Day, GS and Small, SA and Dickson, DW and Ward, ME and Gendron, TF and Zhang, Y and Prudencio, M and Gitler, AD and Petrucelli, L},
title = {TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia.},
journal = {PLoS biology},
volume = {24},
number = {1},
pages = {e3003573},
pmid = {41490046},
issn = {1545-7885},
support = {R35 NS097273/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; R01 NS120992/NS/NINDS NIH HHS/United States ; R35 NS137159/NS/NINDS NIH HHS/United States ; R01 AG064690/AG/NIA NIH HHS/United States ; R01 NS117461/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *DNA-Binding Proteins/metabolism/genetics ; *Polyadenylation/genetics ; Female ; *Vesicular Transport Proteins/genetics/metabolism ; Male ; Aged ; 3' Untranslated Regions/genetics ; Middle Aged ; Aged, 80 and over ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) dysfunction is a hallmark of several neurodegenerative diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer's disease. Although cryptic exon inclusion is a well-characterized consequence of TDP-43 loss of function, emerging evidence reveals broader roles in RNA metabolism, notably in the regulation of alternative polyadenylation (APA) of disease-relevant transcripts. In the present study, we examined 3' untranslated region lengthening events in the brains of individuals with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), focusing on the functional impact of APA dysregulation. To investigate whether TDP-43-mediated APA events occur in the postmortem brain, we measured the 3' untranslated region length of the retromer component vacuolar protein sorting 35 (VPS35) and the ETS transcription factor (ELK1) in the frontal cortex of a large cohort of FTLD-TDP patients and of healthy controls, and evaluated if these APA events are associated with FTLD-TDP clinical characteristic, markers of TDP-43 pathology [e.g., hyperphosphorylated TDP-43 and cryptic stathmin-2 RNA], or the expression of VPS35 and VPS29 proteins, the latter being essential to the retromer complex. We identified robust 3' untranslated region lengthening of VPS35 and ELK1 in FTLD-TDP, which strongly associated with markers of TDP-43 pathology, and ELK1 APA also associated with an earlier age of disease onset. Functionally, VPS35 APA was associated with reduced VPS35 and VPS29 protein expression, and lower VPS35 levels were associated with increased hyperphosphorylated TDP-43 and cryptic stathmin-2 RNA. Together, these data implicate APA dysregulation as a critical downstream consequence of TDP-43 dysfunction and suggest that TDP-43 loss may contribute to retromer impairment through APA-mediated repression of retromer subunits.},
}

Humans
*Frontotemporal Dementia/genetics/metabolism/pathology
*DNA-Binding Proteins/metabolism/genetics
*Polyadenylation/genetics
Female
*Vesicular Transport Proteins/genetics/metabolism
Male
Aged
3' Untranslated Regions/genetics
Middle Aged
Aged, 80 and over

@article {pmid39809899,
year = {2025},
author = {Cui, Y and Arnold, FJ and Li, JS and Wu, J and Wang, D and Philippe, J and Colwin, MR and Michels, S and Chen, C and Sallam, T and Thompson, LM and La Spada, AR and Li, W},
title = {Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain.},
journal = {Nature genetics},
volume = {57},
number = {2},
pages = {369-378},
pmid = {39809899},
issn = {1546-1718},
support = {R01 CA193466/CA/NCI NIH HHS/United States ; R01 CA228140/CA/NCI NIH HHS/United States ; R01 HG007538/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; *Quantitative Trait Loci/genetics ; *Brain/metabolism ; *Gene Expression Regulation/genetics ; *Tandem Repeat Sequences/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Phenotype ; Alzheimer Disease/genetics ; Genetic Variation ; Male ; C9orf72 Protein/genetics ; Female ; Multiomics ; },
abstract = {Tandem repeat (TR) size variation is implicated in ~50 neurological disorders, yet its impact on gene regulation in the human brain remains largely unknown. In the present study, we quantified the impact of TR size variation on brain gene regulation across distinct molecular phenotypes, based on 4,412 multi-omics samples from 1,597 donors, including 1,586 newly sequenced ones. We identified ~2.2 million TR molecular quantitative trait loci (TR-xQTLs), linking ~139,000 unique TRs to nearby molecular phenotypes, including many known disease-risk TRs, such as the G2C4 expansion in C9orf72 associated with amyotrophic lateral sclerosis. Fine-mapping revealed ~18,700 TRs as potential causal variants. Our in vitro experiments further confirmed the causal and independent regulatory effects of three TRs. Additional colocalization analysis indicated the potential causal role of TR variation in brain-related phenotypes, highlighted by a 3'-UTR TR in NUDT14 linked to cortical surface area and a TG repeat in PLEKHA1, associated with Alzheimer's disease.},
}

Humans
*Quantitative Trait Loci/genetics
*Brain/metabolism
*Gene Expression Regulation/genetics
*Tandem Repeat Sequences/genetics
Amyotrophic Lateral Sclerosis/genetics
Phenotype
Alzheimer Disease/genetics
Genetic Variation
Male
C9orf72 Protein/genetics
Female
Multiomics

@article {pmid41793180,
year = {2026},
author = {Smith, SE and Miller, TM and Atkinson, A and Pestronk, A and Bucelli, RC},
title = {Integrating Serum Neurofilament Light Chain Into Amyotrophic Lateral Sclerosis Diagnostic Criteria.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70212},
pmid = {41793180},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Serum neurofilament light chain (NfL) is a promising diagnostic biomarker for differentiating amyotrophic lateral sclerosis (ALS) from clinical mimics. This study assessed the utility of integrating serum NfL into current diagnostic criteria to enhance diagnostic certainty in patients with a provisional ALS diagnosis who were confirmed as having ALS at follow-up.

METHODS: We conducted a single-center, retrospective study of consecutive patients with a provisional ALS diagnosis at their initial visit at the WashU Medicine ALS Center. All underwent electrodiagnostic testing and serum NfL measurement via SIMOA using an HD-X analyzer (Quanterix). Elevated serum NfL was defined with a cutoff of 38 pg/mL.

RESULTS: The study included 43 patients with a provisional ALS diagnosis (29 men [67.4%]; median age, 63 years [range, 36-80 years]). At follow-up, 27/43 (62.8%) patients progressed to definite ALS. Serum NfL was elevated in 34/43 (79.1%) of the total cohort and 24/27 (88.9%) of those who progressed to definite ALS. Integrating serum NfL with Gold Coast Criteria (GCC) was associated with a tenfold increase in the odds of identifying patients likely to progress to definite ALS (OR 10 [1.39, 71.87], p = 0.02).

DISCUSSION: Our results suggest that serum NfL is a robust complement to current ALS diagnostic criteria and shows potential to improve early identification and diagnostic certainty of patients likely to progress to definite ALS. Integrating serum NfL with GCC provided the strongest predictive model. These findings warrant larger multicenter, prospective studies to confirm results.},
}

@article {pmid41792996,
year = {2026},
author = {Magen, I and Kaneb, HM and Masnata, M and Pulimood, N and Emde, A and Genge, A and Hornstein, E},
title = {Cell free miRNAs are pharmacodynamic biomarkers for enhanced Dicer activity by Enoxacin in human patients with Amyotrophic lateral sclerosis.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.03.002},
pmid = {41792996},
issn = {1525-0024},
abstract = {The activity of the RNase III enzyme DICER is downregulated in both sporadic and genetic forms of Amyotrophic Lateral Sclerosis (ALS). Accordingly, hundreds of microRNAs (miRNAs) are broadly downregulated, leading to de-repression of their mRNA targets. Enoxacin is a fluoroquinolone that enhances DICER activity and miRNA biogenesis. Here, we tested for the first time the molecular effect of Enoxacin on miRNA biogenesis in ALS patients and demonstrated that Enoxacin's engagement with DICER can be pharmacodynamically monitored via miRNA levels in human subjects. In an investigator-initiated, first-in-human study (REALS1), we explored miRNAs as pharmacodynamic biomarkers of DICER activation. Patients with sporadic ALS received oral Enoxacin twice daily for 30 days in a double-blind, randomized clinical trial. The study demonstrated comparable Enoxacin levels in plasma and cerebrospinal fluid (CSF). Furthermore, an increase in cell-free miRNA levels in both plasma and CSF at all time points following Enoxacin treatment (400 mg or 800 mg/day), was measured relative to baseline. Additionally, no serious adverse events were reported. In conclusion, pharmacological enhancement of DICER activity by Enoxacin increases miRNA biogenesis in patients with ALS. These results support further investigation of Enoxacin efficacy in larger clinical trials.},
}

@article {pmid41792976,
year = {2026},
author = {Shah, JS and Oskarsson, B and Zhou, X and Heckman, MG and Sledge, HJ and Virador, G and Parizadeh, D and Middlebrooks, EH},
title = {Expanding the Motor Band Sign in Motor Neuron Disease Using 7T MRI: Visualization of Cortical Layer-Dependent Iron Deposition in the Primary Motor Cortex.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70179},
pmid = {41792976},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: There are no established biomarkers of upper motor neuron degeneration to aid in the diagnosis of motor neuron disease (MND). This study examines the diagnostic value of the motor band sign as a marker of upper motor neuron degeneration and its relationship to clinical findings in MND.

METHODS: Records of consecutive patients who underwent 7T magnetic resonance imaging (MRI) between October 2021 and April 2025 for evaluation of MND or other neurologic indications were retrospectively reviewed. Clinical variables and plasma neurofilament light chain (pNfL) levels were recorded. An upper motor neuron score (Mayo UMNS) was derived from reflex scores. Blinded MRI review assessed the degree of susceptibility-weighted imaging (SWI) hypointensity in the hand, foot, and bulbar motor cortex regions.

RESULTS: An MBS was observed in 100 of 117 (85.5%) MND patients and in 16 (15.5%) patients with non-MND diagnoses, corresponding to a sensitivity of 85.5% (78.0%-90.7%) and 84.5% (76.2%-90.2%) specificity. The MBS in 78 MND patients (70.9%) preferentially involved the middle and deep cortical layers, giving a trilaminar appearance, while only one non-MND patient had this finding. Mayo UMNS (β = 0.89, p < 0.001), pNfL (β = 0.63, p = 0.033), and age at evaluation (β = 0.68, p = 0.027) were independently associated with the summed SWI score.

DISCUSSION: The 7T MRI MBS is a sensitive and specific marker for MND that complements established clinical evaluation. Using 7T, a trilaminar appearance of the motor cortex, reflecting known histopathological changes, can be visualized and may be specific to MND.},
}

@article {pmid41792723,
year = {2026},
author = {Huang, NX and Cai, ZW and Zhuang, SP and Lin, HY and Chen, S and Zou, ZY and Wu, Y and Chen, HJ},
title = {Impairment of brain short association fibers across clinical stages in amyotrophic lateral sclerosis: a new biomarker mirroring disease progression.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04770-7},
pmid = {41792723},
issn = {1741-7015},
support = {2024J01625//Natural Science Foundation of Fujian Province/ ; 2024Y9256//Fujian Province Joint Funds for the Innovation of Science and Technology/ ; 2024Y9253//Fujian Province Joint Funds for the Innovation of Science and Technology/ ; 82572160//National Natural Science Foundation of China/ ; 2023CXA009//Fujian Provincial Health Technology Project/ ; },
abstract = {BACKGROUND: A quantitative biomarker for clinical staging is essential for amyotrophic lateral sclerosis (ALS) stratification. This study evaluated microstructural impairment in brain short association fibers (SAFs) across ALS stages via neurite orientation dispersion and density imaging (NODDI) and assessed correlations with disease severity.

METHODS: Diffusion-weighted imaging data were collected from 87 ALS patients (categorized into four groups King's stages) and 37 healthy controls. Whole-brain SAF mapping was performed via a spherical deconvolution-driven probabilistic tractography approach. Diffusion tensor imaging (DTI) and NODDI parameters (neurite density index, NDI; orientation dispersion index, ODI; isotropic volume fraction, ISO) were estimated for each SAF.

RESULTS: Seven SAFs connecting the left postcentral-precentral gyrus, left precentral-precentral gyrus, right postcentral-precentral gyrus, right paracentral-posterior cingulate gyrus, left paracentral-posterior cingulate gyrus, left precentral-superior parietal gyrus, and left precentral-superior frontal gyrus exhibited significant NDI differences across the five groups. Additionally, one fiber connecting the left medial orbitofrontal-rostral anterior cingulate gyrus demonstrated an ISO difference [false discovery rate (FDR)-corrected p < 0.05]. Progressive trends of NDI reduction and ISO increase were observed at higher ALS stages. No intergroup differences were found in the ODI or DTI parameters. The NDI values of these seven SAFs were positively correlated with disease severity scores (FDR-corrected p < 0.05). Combining NDI and ISO revealed moderate classification potential for ALS (area under the curve = 0.780).

CONCLUSIONS: Neurite injury in SAFs involving primary motor and extramotor areas worsened alongside clinical staging and motor disability in ALS. NODDI provides quantitative SAF-related biomarkers for assessing ALS disease severity.},
}

@article {pmid41792545,
year = {2026},
author = {Færge, S and Muldtofte, L and Ustrup, M and Mikkelsen, AKK and Speyer, H},
title = {Recognizing epistemic injustice in healthcare: a case for methodological pluralism.},
journal = {Medicine, health care, and philosophy},
volume = {},
number = {},
pages = {},
pmid = {41792545},
issn = {1572-8633},
abstract = {Nielsen et al. (2025) recently presented a critique of the current scholarship on epistemic injustice in healthcare, emphasizing the absence of robust empirical evidence, the conceptual difficulty of establishing criteria for identification, and the risk of theoretical misapplication of Miranda Fricker's original framework. While the call for nuance and careful theoretical articulation might be worthwhile, the framing of their critique risks reinforcing precisely the patterns of epistemic exclusion that the concept of epistemic injustice is meant to expose. The implication that epistemic injustice must be operationalized and empirically validated in large-scale quantitative studies before it can be acknowledged as clinically and ethically significant may inadvertently replicate a longstanding hierarchy of knowledge in which certain forms of suffering become "real" only once translated into quantifiable data. In this response, we aim to advance the scholarly debate by questioning the argumentative basis of Nielsen et al.'s claim that fundamental scientific, conceptual, and theoretical flaws undermine the field of epistemic injustice in healthcare. We propose instead approaching epistemic injustice with social objectivity and methodological pluralism; the concept should not be dismissed for lacking quantification or standardization, but rather recognized for its complexity and significance in improving equity, care, and clinical encounters.},
}

@article {pmid41791963,
year = {2026},
author = {Mendon, A and Jain, S and Mishra, N and Bagwe Parab, S},
title = {Calprotectin as an immune-dysregulation biomarker in amyotrophic lateral sclerosis: Insights for diagnosis and therapy.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2026.02.148},
pmid = {41791963},
issn = {0035-3787},
abstract = {Motor neuron degeneration is a defining feature of amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disorder. Early diagnosis remains challenging due to the absence of reliable and validated biomarkers. Calprotectin, a well-established inflammatory marker in various neuroinflammatory conditions, has paradoxically been found at reduced levels in the blood of ALS patients in a limited number of studies, raising the hypothesis of immune dysregulation rather than classical neuroinflammation. However, these findings are primarily derived from small patient cohorts and have yet to be independently replicated. This review critically assesses the emerging role of calprotectin in ALS by comparing it with other candidate biomarkers, including vascular endothelial growth factor (VEGF), apolipoprotein A1 (ApoA1), interleukin-8 (IL-8), interleukin-7 (IL-7), and interleukin-10 (IL-10). While calprotectin may reflect a distinct immunological profile, its standalone diagnostic value remains unclear. Nonetheless, its integration into a multi-analyte biomarker panel could enhance diagnostic precision and biological insight. The review also explores underlying immunological mechanisms, including receptor interactions (RAGE, TLR4, CD33), cellular mediators (microglia, lymphocytes, monocytes), and therapeutic implications. Future research should prioritize mechanistic investigation of calprotectin modulation in ALS, longitudinal validation in larger cohorts, and integration within multimodal biomarker frameworks. A better understanding of disease-specific immune alterations may contribute to earlier diagnosis, stratified patient monitoring, and targeted therapeutic development.},
}

@article {pmid41791528,
year = {2026},
author = {Tolkachjov, SN},
title = {Response to Li et al.'s "Comment on 'Gene Expression Profiling (GEP) in Dermatology, Part 2: Clinical Applications'-toward safe, patient-centered implementation.".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.02.108},
pmid = {41791528},
issn = {1097-6787},
}

@article {pmid41791354,
year = {2026},
author = {Gan, Y and Ju, R and Peng, Y and Xiao, S and Qiu, R and Wang, S and Zhang, Y and Guo, L and Gu, W},
title = {A multi-platform analytical strategy for Atractylodes lancea authentication: Fusion of stable isotope, elemental, chromatographic, and spectroscopic profiles.},
journal = {Talanta},
volume = {305},
number = {},
pages = {129603},
doi = {10.1016/j.talanta.2026.129603},
pmid = {41791354},
issn = {1873-3573},
abstract = {BACKGROUND & AIMS: The quality and market value of the medicinal herb Atractylodes lancea (AL) are critically dependent on its variety, geographical origin, and production mode. To combat adulteration and ensure efficacy, we developed a novel multi-platform analytical strategy integrated with machine learning to establish a robust traceability model for variety discrimination, geographical origin determination, and production mode identification of AL and identify the key chemical indicators responsible for its authentication.

RESULTS: Significant differences were found in trace element concentrations and isotopic ratios among samples. AL's main flavors were spicy, sweet, and fruity, with terpenoids as key aroma contributors. OPLS-DA identified key indicators for tracing AL's variety, including eleven trace elements (e.g., V, Al) and eight volatile compounds (e.g., β-Sesquiphellandrene, 2-Pinen-10-ol). For tracing AL origins, ten trace elements (e.g., Sr, Cr), two stable isotopes (δ[13]C, δ[15]N), five flavor components (e.g., 2-ethyl-3,6-dimethylpyrazine, 2-Pentadecanone), and twenty-six volatile components (e.g., γ-Gurjunene, β-Bisabolene) were identified. Furthermore, three trace elements (Mg, Li and Pb), two isotopes (δ[13]C and δ[15]N), two flavor components (α-Pinene and n-Nonylcyclohexane), and two volatile components (α-Copaene and α-Curcumene) were identified as key indicators for tracing AL's production modes. Finally, among the nine machine learning algorithms evaluated, LightGBM demonstrated superior performance, achieving a traceability accuracy of 95.28 ± 3.01%.

CONCLUSION: The multi-platform data fusion strategy presents a thorough and dependable approach to quality control for Atractylodes lancea. This method establishes a precise, efficient, and adaptable framework, demonstrating substantial potential for application to other high-value botanicals and complex natural products.},
}

@article {pmid41791136,
year = {2026},
author = {Gültekin, M and İlikhan, BA and Baydemir, R and Değirmenci, Y and Başak, AN},
title = {Pathogenic VCP (p.Arg453Trp) variant in three siblings with frontotemporal dementia-amyotrophic lateral sclerosis spectrum: A Turkish family.},
journal = {Clinical neurology and neurosurgery},
volume = {265},
number = {},
pages = {109381},
doi = {10.1016/j.clineuro.2026.109381},
pmid = {41791136},
issn = {1872-6968},
}

@article {pmid41789885,
year = {2026},
author = {Coronas, LE and Timr, S and Sterpone, F and Franzese, G},
title = {Unveiling the entropic role of hydration water in SOD1 partitioning within FUS condensate.},
journal = {The Journal of chemical physics},
volume = {164},
number = {9},
pages = {},
doi = {10.1063/5.0300133},
pmid = {41789885},
issn = {1089-7690},
abstract = {Biological processes such as the sequestration of superoxide dismutase 1 (SOD1) into biomolecular condensates, including fused in sarcoma and stress granules, are vital for understanding disease mechanisms, including amyotrophic lateral sclerosis. Moreover, protein-crowder interactions within these condensates are recognized as fundamental to cellular phase separation and disease-related processes. However, the specific role of the hydration environment in governing SOD1's behavior and transition dynamics within these condensates remains poorly understood, limiting our ability to accurately model these critical biological systems. Therefore, we incorporate explicit water into an implicit solvent model (OPEP) to investigate how water influences SOD1's behavior, residence times, and transition rates among associative states. We employ the advanced CVF (Coronas, Vilanova, Franzese) water model, which accurately captures hydrogen-bond networks at the molecular level. While the OPEP model indicates that bovine serum albumin (BSA) crowders reduce SOD1's partition coefficient (PC) primarily through non-specific interactions, our explicit-water approach points to hydration entropy in BSA as a key contributor to the observed PC reduction. This result offers a new perspective on the system's free-energy landscape, complementing those obtained from OPEP alone. Our research supports the notion that explicitly modeling water can enhance our understanding of protein-crowder interactions and their biological implications, further emphasizing the potential role of water in cellular phase separation and disease-related processes.},
}

@article {pmid41789796,
year = {2026},
author = {Creer, S and Griffiths, AW and Hobson, E and Davies, S and Massey, C and Stokes, L and Waters-Harvey, B and Bamber, R and Hastings, S and Bedford, J and Gould, RL and McDermott, C and Mayberry, E},
title = {"What about me? I'm supposed to be … superhuman?": exploring staff perspectives on how to deliver high quality psychological care for people living with amyotrophic lateral sclerosis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17582024.2026.2637420},
pmid = {41789796},
issn = {1758-2032},
abstract = {OBJECTIVES: To explore healthcare professionals' experiences of providing informal psychological care in Amyotrophic Lateral Sclerosis (ALS) services.

METHODS: A qualitative focus group and interview study with 28 UK-based, ALS healthcare professionals. Data was analyzed using reflexive thematic analysis.

RESULTS: Healthcare professionals reported psychological distress in their roles arising from the intrinsic nature of ALS, alongside system factors and their needs as staff members. Participants identified critical needs for themselves to improve psychological care including: psychological skills training, clear role definition, understanding of specialist psychology and structured staff support. Participants identified patient needs as: support for informal carers, access to specialist psychology, clear and inclusive referral pathways, and having person-centered, tiered approaches to care delivery.

CONCLUSIONS: The psychological impact of ALS extends beyond patients and families to healthcare professionals, creating systemic challenges in care delivery. Effective psychological care in ALS requires a comprehensive approach that addresses not only the needs of individual patients but also staff and systemic issues. A distress loop exists where inadequate psychological services affect both staff wellbeing and care quality for patients and their families. Without addressing patient, staff, and service-level issues, people living with ALS and healthcare professionals will continue to experience preventable psychological distress.},
}

@article {pmid41789732,
year = {2026},
author = {Scarpa, E and D'Amora, U and De Cesare, N and Bonadies, I and Dubbioso, R and Nolano, M and Dardano, P and De Stefano, L and Fasolino, A and Zeppetelli, S and Silvestri, A and Zanardi, C and Milella, E and Fasolino, I},
title = {3D Artificial Skin Model As a Novel Strategy for the Detection of Pyroptosis-Cascade Activation in Amyotrophic Lateral Sclerosis.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.5c23366},
pmid = {41789732},
issn = {1944-8252},
abstract = {Amyotrophic lateral sclerosis (ALS) is a severe adult-onset neurodegenerative disease with limited treatment approaches. Evidence has shown that degeneration of cutaneous nerves may reflect neurodegenerative processes occurring within the central nervous system. Although skin biopsy is widely adopted in clinical practice, the procedure is invasive and requires multiple patients' tissue removals. Therefore, we developed a 3D innervated skin model by combining 3D printing of methacrylated hyaluronic acid as an innovative tool for better reproducing the dermis and epidermis and electrospinning of polylactic acid for mimicking skin innervation. Later, 3D artificial skin was colonized with a preneuronal cell line (SH-SY5Y) and fibroblasts isolated from skin biopsy of ALS patients at different disease stages. 3D skin possesses a porosity suitable for cell colonization and a high stability. Importantly, biological results reveal an increase of TAR DNA-binding protein 43 aggregates, NOD-like receptor pyrin domain containing protein 3, interleukin (IL)-18, IL-6, and nitrites in 3D skin of ALS patients, thus indicating pyroptosis activation linked to neurodegeneration. This physiologically relevant 3D skin model reduces the need for repeated biopsies, allows standardized experimental conditions, and supports biomarker research and preclinical drug testing in ALS.},
}

@article {pmid41789116,
year = {2026},
author = {Bublitz, SK and Lorenzl, S and Klima, A and Schmidt, S and Schäffer, B and Gleich, S},
title = {Mapping end-of-life care for patients with neurological conditions in German hospices: a point prevalence survey.},
journal = {BMJ neurology open},
volume = {8},
number = {1},
pages = {e001404},
pmid = {41789116},
issn = {2632-6140},
abstract = {BACKGROUND: Access to palliative care for patients with neurological diseases remains limited. Contributing factors include difficulties in predicting disease trajectories, resource constraints in long-term care and challenges in identifying the end-of-life phase-often compounded by communication and cognitive impairments.

METHODS: We conducted a national point-prevalence survey among German inpatient hospices using an online questionnaire.

RESULTS: The response rate was 44%, with 83% of participating hospices providing complete datasets. Most patients in hospices suffered from oncological diseases (n=785; 77.3%), including primary brain tumours (n=102; 10.0%). At the time of the survey, neurological diagnoses accounted for approximately 5% of hospice admissions. While 51% of hospices reported having access to neurological consultation, this was usually informal or ad hoc. 19% reported no current access to a neurologist but considered such collaboration desirable.

CONCLUSIONS: This survey provides an overview of the current representation of patients with neurological conditions in German inpatient hospices. The findings reveal limited structured collaboration between neurology and palliative care, alongside structural and societal barriers that complicate timely hospice referral and end-of-life planning. Strengthening interdisciplinary cooperation, enhancing neurologists' engagement in palliative care and expanding specialised outpatient support for patients and families are essential to improving equitable and needs-based end-of-life care for individuals with neurological conditions.},
}

@article {pmid41788548,
year = {2026},
author = {Zheng, Y and Zhou, W and Chang, H and Zheng, K},
title = {Brain organoids as precision models for neurodegenerative diseases: from disease modeling to drug discovery.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1764964},
pmid = {41788548},
issn = {1662-4548},
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have become major global causes of disability and mortality. Their complex pathogenic mechanisms remain incompletely understood, and effective disease-modifying therapies are still lacking. Traditional animal models and two-dimensional (2D) cell culture systems exhibit notable limitations in structural complexity, human relevance, and translational validity, making it difficult to faithfully recapitulate human-specific neuropathology. In recent years, brain organoid technology derived from induced pluripotent stem cells (iPSCs) has advanced rapidly, enabling the self-organization of diverse neuronal and glial cell types within a three-dimensional (3D) architecture that partially mimics human brain development and disease-related pathological events. When integrated with CRISPR-Cas9-based genome editing and multi-omics profiling, organoids support causal mechanism studies, target validation, and individualized drug-response prediction, highlighting their growing value in early-stage drug discovery. Despite current challenges-including insufficient maturation, lack of vascularization and immune components, and batch variability-the continuous progress in bioengineering, microfluidic systems, and artificial intelligence (AI)-driven multimodal data analysis is steadily expanding the translational potential of organoids as human-relevant preclinical models. Overall, brain organoids provide an essential foundation for constructing physiologically relevant and predictive research platforms for neurodegenerative diseases, offering new opportunities for therapeutic development and precision medicine.},
}

@article {pmid41787388,
year = {2026},
author = {Alhathli, E and Cooper-Knock, J and Girach, ZU and Julian, TH and Bauer, C and Timmons, HO and Ward, BD and Walker, H and Azzouz, M and Elrayess, MA and Al-Khelaifi, F and Yousri, NA and Gul, A and Kelsall, A and Moll, T and Harvey, C and Gornall, S and Wong, K and Allen, SP and Strange, A and Shaw, PJ},
title = {Hypothesis-free evaluation of circulating metabolome provides cell-specific insights regarding the role of energy substrate availability in amyotrophic lateral sclerosis.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04727-w},
pmid = {41787388},
issn = {1741-7015},
support = {894-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; 956-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/Z504105/1//UK Research and Innovation/ ; SBF005\1064/AMS_/Academy of Medical Sciences/United Kingdom ; DOD/14/43//My Name'5 Doddie Foundation/ ; NF-SI-0617-10077//National Institute for Health and Care Research/ ; NIHR 203321//NIHR Sheffield Biomedical Research Centre/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with limited therapeutic options. The circulating metabolome comprises small molecules present in plasma/serum which are the intermediates and end-products of cellular metabolism, and is linked to ALS pathogenesis.

METHODS: We conducted hypothesis-free two-sample Mendelian randomisation (MR) analysis of the concentration of 575 plasma/serum metabolites, to determine which are causally linked to risk of ALS. Significant metabolites were validated in an independent GWAS of plasma/serum metabolite concentrations and evaluated for sex-specific effects. Correlations between directly measured patient biofluid metabolite concentrations and ALS risk/severity were examined in 94 ALS patients and 40 controls. We experimentally assessed metabolic function in a murine neurons and human astrocytes carrying an ALS-associated G4C2-repeat expansion within C9orf72.

RESULTS: MR causally associated five metabolites with ALS risk after multiple-testing correction. Higher serum concentration of glycoprotein acetyls (P = 9.7e - 9, β = 0.21) and the peptide DSGEGDFXAEGGGVR (P = 8.0e - 6, β = 0.22) was associated with increased ALS risk, whereas higher plasma concentration of phenylalanylserine, isobutyrylcarnitine, and acetylcarnitine was protective (P < 5e - 5, β = - 0.29 to - 0.72). DSGEGDFXAEGGGVR has been linked to glucose metabolism but we have used genetic fine-mapping to link DSGEGDFXAEGGGVR, neuronal glucose uptake through GLUT3, and ALS risk. Direct measurement of metabolite concentrations in patient biofluids revealed elevated acetylcarnitine levels in patients with ALS, which were associated with delayed symptom onset (Cox regression, P = 0.02, HR = 0.4). Similarly, lactate is elevated in ALS patient CSF (ANOVA, P = 1.3e - 3) and in patients with longer survival time (Cox regression, P = 0.03, HR = 0.3). Plasma fructose is elevated in ALS patients with shorter survival time (Cox regression, P = 0.02, HR = 1.1). In vitro, neurons and astrocytes carrying an ALS-associated G4C2-repeat expansion within C9orf72 demonstrated reduced metabolic flexibility.

CONCLUSIONS: We provide evidence that impaired energy substrate availability contributes to ALS risk and severity. CNS cell types differ in their use of energy substrates and therefore we postulate the relative importance of different cell types for different stages of disease. Our findings support further investigation of metabolic interventions to treat or prevent ALS.},
}

@article {pmid41785987,
year = {2026},
author = {Feo, A and Popovic, MM and Faghihi, S and Eshkoly-Lior, T and Tailor, PD and Marin, AI and Santina, A and Choi, WT and Sarraf, D},
title = {Spectrum of Colopathy and Severe Polyposis Associated with Pentosan Polysulfate Sodium Maculopathy: A Retrospective Case Series.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.02.050},
pmid = {41785987},
issn = {1879-1891},
abstract = {OBJECTIVE: To expand the spectrum of gastrointestinal (GI) manifestations associated with pentosan polysulfate sodium (PPS) maculopathy.

DESIGN: Retrospective case series.

SUBJECTS: Eight patients (16 eyes) diagnosed with PPS maculopathy who also underwent GI evaluation between 2019 and 2025.

METHODS: Electronic medical records were reviewed for demographics, PPS dosage and duration, ocular findings, GI history, diagnostic presentation, and histopathology. Multimodal imaging included fundus photography, fundus autofluorescence, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Colonoscopy was performed in all patients with histopathologic analysis in selected cases. PPS maculopathy was staged according to Wang et al.'s classification system. Genetic testing was obtained in selected cases to exclude any form of inherited maculopathy or familial adenomatous polyposis.

MAIN OUTCOME MEASURES: Clinical and imaging features of PPS maculopathy and GI pathological diagnosis, including polyposis, dysplasia, and inflammatory bowel disease.

RESULTS: The cohort included 6 women and 2 men (median age: 68.5 years). Median PPS exposure was 25.4 years with a median cumulative dose of 2899 grams. At presentation, 62.5% of eyes were stage 1, 31.3% stage 2, and 6.3% stage 3. At final follow-up, 25% of eyes were stage 1, 50% stage 2, and 25% stage 3. Overall, 37.5% of eyes showed progression of maculopathy stage, and cRORA was present in 75% of eyes at last follow-up. Additional findings included acquired vitelliform lesions, outer retinal tubulations, epiretinal membranes, and type 2 macular neovascularization. Colonoscopy revealed severe adenomatous polyposis in 6 of the 8 patients (75%), with 3 requiring partial or total colectomy and 2 undergoing endoscopic resection. One patient developed ulcerative colitis, and 2 additional patients were diagnosed with Crohn's disease or microscopic colitis. The median latency to GI diagnosis was 10 years after PPS initiation.

CONCLUSIONS: This study expands the recognized systemic toxicity of PPS, demonstrating that PPS maculopathy patients are at risk of concomitant colonic disease, including severe polyposis and dysplasia. The frequent detection of asymptomatic polyposis underscores the importance of colonoscopy screening in exposed patients, even in the absence of GI symptoms. Heightened interdisciplinary awareness and long-term surveillance are warranted to mitigate the vision- and life-threatening consequences of PPS toxicity.},
}

@article {pmid41785403,
year = {2026},
author = {Oh, J and Oh, SI},
title = {Subjective sleep quality in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/21678421.2026.2614597},
pmid = {41785403},
issn = {2167-9223},
abstract = {OBJECTIVE: Sleep disturbances are common and clinically significant non-motor symptoms in amyotrophic lateral sclerosis (ALS), arising from motor, respiratory, and psychological factors. This study aimed to synthesize available evidence on subjective sleep quality in ALS, estimate the prevalence of poor sleep quality, examine associated factors, and compare patients with healthy controls.

METHODS: : PubMed, EMBASE, Cochrane Central, and CINAHL were searched for studies published between January 2000 and August 2025 that assessed subjective sleep quality in ALS using validated patient-reported outcome measures, such as Pittsburgh Sleep Quality Index (PSQI). Pooled analyses were performed using random-effects models. Meta-regression was applied to explore associations with demographic and clinical variables.

RESULTS: : A total of 23 studies comprising 1899 ALS patients were included, of which 20 were eligible for meta-analysis. All included studies assessed subjective sleep quality using the PSQI, and the pooled mean PSQI score was 6.94, exceeding the clinical cutoff for poor sleep quality. The pooled prevalence of poor sleepers was 56.7%. Nine studies including healthy controls showed significantly higher PSQI scores in ALS patients compared with controls (mean difference 2.69). Several factors, including functional status, depression, anxiety, fatigue, daytime sleepiness, constipation, and cognitive impairment, were associated with poorer sleep, however, meta-regression did not identify significant associations with age, sex, disease duration, or ALSFRS-R.

CONCLUSIONS: : Sleep disturbances are highly prevalent and clinically significant in ALS. These findings highlight the need for systematic screening and proactive management across all stages of the disease. Future research should evaluate a wider range of interventions to improve sleep quality and patient outcomes.},
}

@article {pmid41785396,
year = {2026},
author = {Scirocco, E and Pogemiller Bulat, A and Carey, JR and Giacomelli, E and Boyce, D and Paganoni, S and Berry, JD},
title = {Bridging the gap: understanding participation barriers in ALS clinical trials through on-the-ground insights.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2640126},
pmid = {41785396},
issn = {2167-9223},
abstract = {OBJECTIVE: This study explores the experiences and perceptions of people living with amyotrophic lateral sclerosis (pALS), their caregivers, and healthcare providers regarding participation in clinical trials. The study tested the hypothesis, based on existing literature, that geographic distance from multidisciplinary ALS clinics is the primary barrier to awareness and participation in clinical trials.

METHODS: A road trip was conducted to engage individuals, particularly those residing more than 90 miles from specialized clinics. Qualitative and semi-quantitative methods were used to collect data from in-person interviews conducted with pALS, their caregivers, and healthcare providers in urban (high population density), suburban (residential areas on the outskirts of urban centers), and rural (sparsely populated) settings across the East Coast of the US. Thematic analysis was employed to interpret the data.

RESULTS: Based on the interviews, a trusted, supportive, and knowledgeable medical team knowledgeable about ALS research emerged as a critical factor influencing patient participation decisions. Geographic distance alone did not meaningfully impact research interest or awareness. Healthcare providers faced challenges, including time constraints and limited access to updated information about studies, which hindered their ability to promote participation. Healthcare providers cited informal partnerships with advocacy organizations and research centers as crucial for facilitating research participation.

CONCLUSIONS: Tailored communication strategies that leverage established relationships between pALS and their trusted healthcare providers may enhance research participation. As decentralized research models evolve, improving trial education and access and fostering knowledge and trust could significantly boost enrollment in ALS clinical research.},
}

@article {pmid41785390,
year = {2026},
author = {Nomizo, S and Komatsu, J and Shima, A and Muramatsu, D and Matsubara, K and Nozaki, I and Noguchi-Shinohara, M and Nishiyama, A and Suzuki, N and Aoki, M and Ono, K},
title = {Gadolinium enhancement of the cauda equina in a case of familial ALS with p.S135G SOD1 mutation.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2638591},
pmid = {41785390},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Gadolinium enhancement of the cauda equina is typically associated with inflammatory diseases. We report a case of familial ALS with a Cu/Zn superoxide dismutase (SOD1) gene mutation showing marked gadolinium enhancement of the lumbar nerve roots. To date, only a few cases of ALS with gadolinium enhancement of the nerve roots have been reported. To our knowledge, this is the first reported case of ALS with an p.S135G SOD1 mutation exhibiting gadolinium enhancement in the cauda equina.},
}

@article {pmid41785113,
year = {2026},
author = {Rzeszutek, MJ and Regnier, SD and Kaplan, BA and Traxler, HK and Stein, JS and Tomlinson, DC and Koffarnus, MN},
title = {Identification and management of nonsystematic cross-commodity data: Toward best practice.},
journal = {Experimental and clinical psychopharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1037/pha0000836},
pmid = {41785113},
issn = {1936-2293},
support = {//National Institutes of Health; National Institute on Alcohol Abuse and Alcoholism/ ; //National Institutes of Health; National Institute on Drug Abuse/ ; /NH/NIH HHS/United States ; //Food and Drug Administration; Center for Tobacco Products/ ; },
abstract = {Data systematicity has been an important area of consideration for behavioral economic demand. Stein et al. (2015) introduced criteria and an accompanying algorithm to aid researchers in identifying data series that may be considered "nonsystematic"-that is, data that may not follow empirically based assumptions such as an overall decrease in consumption as the cost of a commodity increases and consistency in decreases in consumption. However, those criteria and algorithm are only directly applicable to own-price demand, or demand for a commodity that is increasing in price. Cross-price demand, or demand for a second commodity that changes as a function of some other commodity, does not have a similar set of criteria or algorithm for assessing cross-commodity demand systematicity. Cross-price or cross-commodity demand is useful in understanding how changes in one substance or commodity may change the consumption of another substance or commodity. Thus, we extend Stein et al.'s criteria and algorithm to classify if a cross-commodity can be considered a substitute, complement, or independent, and then assess its systematicity based on its classification. We demonstrate this algorithm on three different cross-commodity demand data sets and describe important considerations regarding data exclusions to prevent biasing results from own-price and cross-price demand. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid41784486,
year = {2026},
author = {Calix Kannaley, K},
title = {Exploring the use of narrative-based approaches in individuals with amyotrophic lateral sclerosis: A narrative review.},
journal = {Palliative & supportive care},
volume = {24},
number = {},
pages = {e81},
doi = {10.1017/S1478951526101965},
pmid = {41784486},
issn = {1478-9523},
abstract = {OBJECTIVES: Narrative-based approaches have been utilized in medicine to better understand the illness experiences of individuals living with chronic conditions. In particular, people with amyotrophic lateral sclerosis (pALS) may benefit from use of narrative-based approaches, given the potential impact of progressive decline on identity of self. This review explores the use of narrative-based approaches in studies involving pALS to provide further insight to the experiences and psychosocial needs of this population.

METHODS: A search was conducted utilizing EMBASE, CINAHL, PsycInfo, and Google Scholar with several terms related to amyotrophic lateral sclerosis (ALS) and narrative-based approaches. Studies were included if they were written in English, incorporated methods that promoted the production of narratives, and reported data that could be clearly isolated to pALS.

RESULTS: The search revealed a total of 154 articles for title and abstract screening. Fifty-two articles were selected for full-text review. Thirty-two articles met the criteria for data extraction. Four descriptive categories emerged upon examination of the narrative-based approaches implemented across the studies: psychosocial intervention, illness experience, intervention targeting specific needs, and secondary analysis of data. Some of the common themes identified across studies included: loss of physical and communicative function, adaptation to life changes, shifts in identity, and tension with the healthcare system.

SIGNIFICANCE OF RESULTS: Despite the communication challenges that often coincide with disease progression, narrative-based approaches can be utilized in pALS. These approaches should be implemented to gain insight on the disease experiences of pALS, providing opportunity for patient-centered interventions to address the psychosocial needs of this population.},
}

@article {pmid41783572,
year = {2026},
author = {Liu, W and Xue, Y and Cao, C and Yang, L and Zhang, L},
title = {Copper Homeostasis and Cuproptosis in Neurological Disorders.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {580005},
pmid = {41783572},
issn = {1177-8881},
mesh = {*Copper/metabolism ; Humans ; *Homeostasis ; *Nervous System Diseases/metabolism/drug therapy ; Animals ; },
abstract = {Neurological disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) pose a serious global public health threat, with complex etiologies involving genetic, environmental, and metabolic factors. Current data indicate that the prevalence of these disorders is rapidly increasing with the aging population, resulting in a growing economic and healthcare burden worldwide. In recent years, the imbalance of copper homeostasis has been increasingly implicated in the pathogenesis of neurological diseases. Copper overload can aggravate neuronal injury by inducing oxidative stress (OS), mitochondrial dysfunction, and protein misfolding, while copper deficiency disrupts the function of copper-dependent enzymes and leads to metabolic abnormalities. The mechanism of cuproptosis, proposed in 2022, describes a novel form of programmed cell death characterized by lipoylated protein aggregation and the loss of Fe-S cluster proteins, offering new insights into copper-related diseases. Multiple studies have demonstrated the crucial role of copper homeostasis and cuproptosis in the onset, progression, and treatment of neurological diseases. This narrative review summarizes the molecular mechanisms involved in copper homeostasis regulation and, on that basis, discusses the role of copper metabolism abnormalities in AD, PD, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Wilson's disease (WD), Menkes disease (MD), and stroke. Additionally, we highlight the mechanisms of existing copper-regulating drugs and their therapeutic potential in neurological disorders, while pointing out the limitations of current drug development.},
}

*Copper/metabolism
Humans
*Homeostasis
*Nervous System Diseases/metabolism/drug therapy
Animals

@article {pmid41783158,
year = {2025},
author = {Uemura, K and Hiro, S and Attachaipanich, S and Du, R and Yusof, NISM and Kinoshita, M and Hikosaka, M and Ohtsuki, G},
title = {Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1669272},
pmid = {41783158},
issn = {1662-5102},
abstract = {In this review, we synthesize recent conceptual and experimental advances in neuroscience, highlighting selected studies that delineate the roles of reactive microglia and astrocytes in the contexts of developmental inflammatory stress, neurodegenerative diseases, and cellular senescence. Since the characterization of disease-associated glial phenotypes in 2017, building on earlier pioneering discoveries, we focus here on disease-associated microglia (DAM) and disease-associated astrocyte (DAA) to reassess their contributions to glio-inflammation. It is now recognized that the stress-induced glial states are far from uniform; however, the ontogeny, molecular determinants, and functional consequences of this heterogeneity remain incompletely understood, particularly in psychiatric disorders, Alzheimer's disease, and amyotrophic lateral sclerosis. Accordingly, we compare the glial heterogeneity and its underlying mechanisms across translational mouse models and human neuropathology, considering their evolutionary and physiological contexts. While this review does not aim to be exhaustive, we propose an integrative framework that redefines glial stress responses through the combined lenses of inflammation, transcriptomics, mitochondrial dynamics, lipid metabolism, epigenomic regulation, and cellular senescence. Finally, we outline emerging frontiers for AI-enabled multi-omic physiological and pathological approaches, emphasizing their potential to illuminate glial state transitions and accelerate therapeutic discovery in the near future.},
}

@article {pmid41782322,
year = {2026},
author = {Kaya, Y and Kırboğa, KK},
title = {Brain Organoids as Emerging Platforms for Modeling Neurodegenerative Diseases: Progress, Challenges, and Future Directions.},
journal = {Journal of neurochemistry},
volume = {170},
number = {3},
pages = {e70395},
doi = {10.1111/jnc.70395},
pmid = {41782322},
issn = {1471-4159},
abstract = {Neurodegenerative diseases are a group of disorders (such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis) characterized by loss of function and death of neurons in different parts of the nervous system. These pathologies constitute a global burden, especially for aging populations. This circumstance leads to an increasing demand for understanding the fundamental mechanisms and development of therapeutic strategies. Conventional models, including two-dimensional cell culture and animal models, postmortem brain tissue provide an overview about neurodegenerative disorders but do not completely recapitulate cellular and molecular mechanisms of the human brain. Although three-dimensional (3D) brain organoids exhibit similar properties with physiological and pathological conditions of human brain, including interaction of neuronal, glial cells and self-organizing structure, protein aggregation, neuroinflammation, and neuronal degeneration. The integration of reprogrammed human induced pluripotent stem cells (iPSCs) with 3D brain organoid systems provides a clinical platform as a bridge between bench to bedside. Brain organoids have been used to elucidate novel insights into the molecular and genetic mechanisms underlying neurodegenerative diseases. Furthermore, brain organoids serve as a tool for in vitro disease modeling, drug screening and emergence of new treatments. Despite these clinical benefits, there are various limitations such as incomplete tissue maturation, lack of vascularization and incomplete cellular diversity in this 3D culture system. This review describes in detail the advantages and disadvantages of brain organoids usage in modeling neurodegenerative diseases from a contemporary perspective.},
}

@article {pmid41781412,
year = {2026},
author = {Mortimer, AJ and Sander, CF and Parmar, AR and Williams, AJ and Azzouz, M and Hautbergue, GM and Shaw, PJ and Ferraiuolo, L and Mead, RJ},
title = {Comparison of AAV9-driven motor neuron transduction following different CNS-directed delivery methods in mice.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-38039-z},
pmid = {41781412},
issn = {2045-2322},
support = {2023/MNDS/6501/791MEA/MNDA_/Motor Neurone Disease Association/United Kingdom ; 2023/MNDS/6501/791MEA//MND Scotland/ ; },
abstract = {Gene therapies are promising for diseases previously considered incurable. Adeno-associated virus serotype 9 (AAV9) demonstrates remarkable tropism for motor neurons (MNs) and represents an exciting candidate to target genetic causes of motor neuron diseases like amyotrophic lateral sclerosis (ALS). However, systemic delivery risks immunogenicity and off-target effects, therefore localised delivery to the CNS is advantageous. We assessed MN transduction in wild-type post-natal mice using AAV9-controlled, cytomegalovirus-promoter driven, enhanced GFP expression. Intra-cisterna magna (ICM) and intra-cerebroventricular (ICV) methods were compared. Four weeks post-delivery, GFP positivity in MN and astrocytes were quantified via immunohistochemical approaches and viral genome copy number determined by qPCR. All delivery methods achieved high MN transduction in lumbar spinal cord (> 68%). Unilateral ICV delivery provided the highest and most consistent levels (89 ± 3%), and minimal peripheral viral copies. ICV delivery resulted in higher astrocytic transduction, most notably in the cortex. Brainstem MN transduction was high with all methods (> 55%). We failed to find evidence of neuronal transduction in motor cortex. Viral genome copies trended higher in spinal cord and brainstem with ICV approaches, however further work is required to understand how bilateral repeated dose delivery leads to more profound increases. Whilst several routes of administration into cerebrospinal fluid exist, direct comparisons for targeting MNs in vivo remain limited. Overall, all methods of CNS-directed delivery result in high levels of motor neuron transduction in the lumbar spinal cord and brainstem, but not in motor cortex. Unilateral ICV appears to provide the best balance between consistent, high levels of transduction and low off-target effects. However, ICM might be the better option if seeking to avoid astrocytic transduction.},
}

@article {pmid41781384,
year = {2026},
author = {Gunn, AP and Hilton, JBW and Mukherjee, S and Liddell, JR and Mercer, SW and McLean, CA and Masters, CL and Crouch, PJ and Roberts, BR},
title = {Decreased metallothionein-3 expression in the human spinal cord is a common feature of amyotrophic lateral sclerosis and multiple sclerosis.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-31283-9},
pmid = {41781384},
issn = {2045-2322},
}

@article {pmid41781371,
year = {2026},
author = {Zhang, L and Huang, Y and Huang, W and Huang, Q and Lin, Y and Gu, J},
title = {TDP-43 phosphorylation: Exploring kinases, phosphatases, and therapeutic potential in neurodegeneration.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424284},
doi = {10.1177/13872877261424284},
pmid = {41781371},
issn = {1875-8908},
abstract = {TAR DNA-binding protein 43 (TDP-43) is a multifunctional DNA/RNA-binding protein whose abnormal phosphorylation and aggregation are central to the pathogenesis of several neurodegenerative diseases. TDP-43 proteinopathy, characterized by hyperphosphorylation and cytoplasmic accumulation, is a defining pathological feature of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and is frequently observed in Alzheimer's disease. The phosphorylation state of TDP-43 is dynamically regulated by a network of protein kinases-including CK1, GSK3β, CDC7, and PKA-and counterbalanced by phosphatases such as PP2A and PP1; however, the precise molecular mechanisms governing this equilibrium in disease remain incompletely understood. Notably, phosphorylated TDP-43 acquires prion-like properties, enabling self-templated aggregation and cell-to-cell propagation, which amplifies pathology and drives disease progression. These insights have catalyzed the development of therapeutic strategies aimed at modulating TDP-43 phosphorylation, with kinase inhibitors and phosphatase enhancers emerging as promising candidates for targeting TDP-43 proteinopathies. This review integrates current knowledge on the regulatory networks controlling TDP-43 phosphorylation, examines its role in prion-like spread, and evaluates emerging therapeutic approaches aimed at mitigating TDP-43-mediated neurodegeneration.},
}

@article {pmid41778725,
year = {2026},
author = {Rizvi, FAS and Jimoh, Y and Allouh, MZ and Rahmon, D and Chaudhry, GR},
title = {Mesenchymal stem cell therapies for neurodegenerative diseases: Advancements, challenges, and opportunities.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01147},
pmid = {41778725},
issn = {1673-5374},
abstract = {Neurodegenerative diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, retinal degenerative diseases, Alzheimer's disease, and Parkinson's disease, continue to pose a significant clinical challenge due to the progressive loss of neural tissue structure and function. Stem cell-based therapies are gaining attention for the treatment of neurodegenerative diseases. Mesenchymal stem cells, particularly those derived from perinatal tissues, exhibit remarkable plasticity, along with immunomodulatory, neurotrophic, and regenerative capabilities. Mesenchymal stem cells primarily influence their environment through paracrine signaling and can also differentiate into neural lineages, aiding in neuronal repair. Tissue-specific progenitor cells, such as neural stem cells and retinal progenitor cells, offer greater therapeutic precision. This review examines advancements in mesenchymal stem cell-based therapies for neurodegenerative diseases, discusses relevant clinical trials, and highlights the challenges, while proposing that personalized regenerative treatments utilizing lineage-restricted progenitors may improve patient outcomes in these complex disorders.},
}

@article {pmid41778604,
year = {2026},
author = {Ahn, GJ and Cha, KC and Lee, J and Son, YJ and Roh, YI and Jung, WJ and Lee, Y and Im, HY and Hwang, SO},
title = {Comparison of the Hemodynamic Effects of Epinephrine on Blood Pressure Augmentation at 1-, 3-, and 5-Minute Dosing Intervals.},
journal = {Journal of the American Heart Association},
volume = {},
number = {},
pages = {e046743},
doi = {10.1161/JAHA.125.046743},
pmid = {41778604},
issn = {2047-9980},
abstract = {BACKGROUND: Although current cardiopulmonary resuscitation guidelines recommend administering epinephrine at 3- to 5-minute intervals during advanced life support (ALS), scientific evidence for the optimal dosing interval for enhancing hemodynamic parameters remains limited. Therefore, we compared the hemodynamic effects of 1-, 3-, and 5-minute epinephrine dosing intervals on blood pressure augmentation in a porcine ventricular fibrillation cardiac arrest model.

METHODS: Forty-two pigs were randomly assigned to 1-, 3-, and 5-minute epinephrine dosing-interval groups. After ventricular fibrillation induction and a 2-minute downtime, basic life support was initiated with a 30:2 compression-to-ventilation ratio for 8 minutes, followed by 30 minutes of ALS, including asynchronous ventilation at a rate of a single ventilation every 6 seconds, with oxygen delivered at 15 L/min. Epinephrine (0.02 mg/kg) was administered at predetermined intervals of 1, 3, or 5 minutes. We compared the pressure-time integrals for mean blood pressure, coronary perfusion pressure, and diastolic blood pressure among the groups over the 30-minute ALS period.

RESULTS: The mean blood pressure (P<0.001), coronary perfusion pressure (P=0.001), and diastolic blood pressure pressure-time integrals (P=0.005) were significantly higher in the 1-minute group than in the 3- and 5-minute groups. Crucially, mean blood pressure and coronary perfusion pressure pressure-time integrals remained positive in the 1-minute group but became negative in the 3- and 5-minute groups during ALS. The diastolic blood pressure pressure-time integral also remained positive for a longer duration in the 1-minute group.

CONCLUSIONS: A 1-minute epinephrine dosing interval may be significantly more effective in augmenting blood pressure and critical hemodynamic parameters during ALS than are the currently recommended 3- or 5-minute intervals.},
}

@article {pmid41777380,
year = {2026},
author = {, },
title = {Retraction: Enhancing ALS disease management: exploring integrated user value through online communities evidence.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1793079},
doi = {10.3389/fneur.2026.1793079},
pmid = {41777380},
issn = {1664-2295},
abstract = {[This retracts the article DOI: 10.3389/fneur.2024.1393261.].},
}

@article {pmid41777232,
year = {2026},
author = {Yerraguntla, S and Bakshi, B and Chandran, K and Foucher, J and Benatar, M and Wicks, P and Bedlack, R and Shirilla, D and Sun, Y and Maragakis, N and Greenstein, E and Mascias Cadavid, J and Rao, A and Allen, O and Dyckman, K and Wang, O and Beauchamp, M and Chang, V and Brown, A and Carbunar, O and Paganoni, S and Bertorini, T and Pioro, E and Elsharif, B and Jiang, N and Pattee, G and Carter, G and Breevoort, S and Tito, E and Nathaniel, G and Jackson, C and Olby, N and McDermott, C and Ratner, D and Li, X},
title = {ALSUntangled #82: N-acetylcysteine.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2026.2638590},
pmid = {41777232},
issn = {2167-9223},
abstract = {N-acetylcysteine is a thiol-containing compound and a precursor of glutathione, with mechanistic plausibility for ALS, including reducing oxidative stress, regulating neuroinflammation, and mitigating mitochondrial dysfunction. Preclinical studies have yielded conflicting results on whether N-acetylcysteine can delay the onset of motor impairment and prolong survival in ALS mouse models. Several case studies of oral or subcutaneous administration of N-acetylcysteine in patients with ALS did not demonstrate convincing benefits. Clinical trials to date have also failed to demonstrate efficacy in slowing ALS progression. While N-acetylcysteine shows theoretical promise, further research is needed to clarify its therapeutic role in ALS. At present, ALSUntangled does not support the use of N-acetylcysteine as a treatment to slow ALS progression.},
}

@article {pmid41776751,
year = {2026},
author = {Roca-Pereira, S and López-Sampere, Y and Mengod-Soler, P and Peña-Fonteboa, M and Marco, C and Caravaca-Puchades, A and Domínguez, R and Vázquez-Costa, JF and Santamaría, E and Fernández-Irigoyen, J and Colomina, MJ and León Moreno, I and Martínez Yélamos, A and Martínez Yélamos, S and Santpere, G and Obis, E and Portero-Otín, M and Piñol-Ripoll, G and Povedano, M and Andrés-Benito, P},
title = {Proteomic profile of CSF obtained at the time of diagnosis determines amyotrophic lateral sclerosis progression and survival: CXCL7 levels in disease prognosis and survival.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70089},
doi = {10.1111/bpa.70089},
pmid = {41776751},
issn = {1750-3639},
support = {PI20/000155//Instituto de Salud Carlos III/ ; PI23/00176//Instituto de Salud Carlos III/ ; PI24/01516//Instituto de Salud Carlos III/ ; CD23/00097//Instituto de Salud Carlos III/ ; //Fundació Catalana d'Esclerosi Lateral Amiotròfica (ELA) Miquel Valls/ ; //Elles contra l'Esclerosi Lateral Amiotròfica (ELA)/ ; //Swim for Esclerosi Lateral Amiotròfica (ELA)/ ; //Mà amiga/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily affecting motor neurons. Neurofilament light chain (NfL) is the most established prognostic biomarker; however, its diagnostic resolution is limited, particularly within intermediate concentration ranges, and it does not capture the molecular heterogeneity of ALS. This study aimed to identify complementary cerebrospinal fluid (CSF) biomarkers and pathway-specific signatures through a non-targeted multiomic approach. We performed SWATH-MS-based proteomics and LC-MS/MS lipidomics on CSF from ALS patients stratified by survival (ALS-SS and ALS-LS) and healthy controls. Weighted protein co-expression network analysis (WPCNA) was applied to identify biologically coherent protein modules associated with disease phenotype and progression. Top biomarker candidates were further evaluated using immunoassays in an independent cohort. Post-mortem ALS spinal cord tissues were analyzed to explore the pathophysiological relevance of identified proteins. CSF proteomic profiles robustly distinguished ALS patients from controls and stratified patient subgroups by survival, revealing a molecular signature characterized by inflammation, downregulation of detoxification mechanisms, and synaptic dysregulation in aggressive disease forms. In contrast, lipidomic profiles showed limited discriminatory power. WPCNA identified modular proteomic signatures capturing ALS heterogeneity, and machine learning models based on these profiles yielded optimal biomarker panels for diagnosis and prognosis. CXCL7 emerged as a promising complementary biomarker, and shed light in disease physiopathology. Immunoassay validation supported the diagnostic and prognostic potential of CXCL7 and its association with survival time. Histopathological analysis further confirmed CXCL7 localization in anterior horn motor neurons, despite no detectable changes in whole spinal cord lysates at late disease stages. Comprehensive CSF proteomic profiling, combined with network-based analysis, enhances our understanding of ALS molecular heterogeneity and provides a framework for precision biomarker discovery. CXCL7 complements NfL as a diagnostic and prognostic biomarker, supporting improved patient stratification and advancing the development of personalized therapeutic strategies in ALS.},
}

@article {pmid41776545,
year = {2026},
author = {Krishnamurthy, SS and Buzatto, AZ and Campkin, C and Müller, HP and Wiesner, D and Weishaupt, J and Klose, V and Wiesenfarth, M and Elmas, Z and Herrmann, C and Parlak, Ö and Günther, K and Saad, R and Weiland, U and Dupuis, L and Ludolph, A and Li, L and Kassubek, J and Dorst, J and Roselli, F},
title = {Disruption of the angiopoietin-like system connects lipid homeostasis and hypothalamic dysfunction in ALS.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04749-4},
pmid = {41776545},
issn = {1741-7015},
abstract = {BACKGROUND: Alterations in lipid metabolism are manifestations of amyotrophic lateral sclerosis (ALS) that contribute to the risk and rate of progression. Blood levels of triglycerides and cholesterol are altered in ALS patients and pre-symptomatic gene carriers, but mechanistic insights into these changes are lacking.

METHODS: Serum samples from sporadic ALS patients (n = 118), mutated SOD1 and FUS/TARDBP (n = 20, 40, 17, respectively) with age and gender-matched controls (n = 96) were analysed for alterations in the angiopoietin-like protein (ANGPTL) system using enzyme-linked immunosorbent assays. SOD1[G93A] murine model was studied at pre-symptomatic (P50), early symptomatic (P90), and fully symptomatic (P110) stages, along with their wild-type (WT) littermates for ANGPTLs. Untargeted lipidomics on serum was performed using high-resolution liquid chromatography-mass spectrometry. Further, the involvement of the hypothalamus was studied using hypothalamic volumetry in patients and an antibody array spanning 308 proteins in mice.

RESULTS: We show that mutation-specific patterns of systemic lipid abnormalities appear in ALS and that they correlate with reduced levels of angiopoietin-like proteins 3 and 4. ANGPTL-3/4, in turn, correlates with hypothalamic atrophy but not with corticospinal involvement, as determined by MRI volumetry and diffusion tensor imaging. Lipid phenotype and decreased ANGPTL in humans are recapitulated in two SOD1 murine ALS models, in which ANGPTL-3, -4, and -8 expression patterns are consistent with the repartitioning of lipid utilisation from muscles to the brown adipose tissue; systemic levels of ANGPTL-3 correlate with hypothalamic neuroinflammation and vascular permeability and with hypothalamic levels of agouti-related protein and neuropeptide Y.

CONCLUSIONS: These data provide a molecular mechanism linking peripheral lipid metabolism to the dysfunction of a specific hypothalamic circuit through the mediation of systemic ANGPTL-3 and -4. This finding constitutes a molecularly defined entry point to manipulate lipid metabolism in ALS.},
}

@article {pmid41776544,
year = {2026},
author = {Hirota, R and Lankford, KL and Nakazaki, M and Toyoshima, M and Kocsis, JD},
title = {Intranasal administration of human mesenchymal stromal cell-derived small extracellular vesicles delays disease progression in the SOD1(G93A) mouse model.},
journal = {Molecular brain},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13041-026-01288-0},
pmid = {41776544},
issn = {1756-6606},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, with no established disease-modifying therapy. Mesenchymal stem/stromal cells (MSCs) have been reported to exert neuroprotective effects in models of injury and disease, acting primarily through release of small extracellular vesicles (sEVs). MSC-derived sEVs (MSC-sEVs) have therefore attracted attention as a potential cell-free therapeutic approach for treating neurological conditions such as ALS. Because MSC-sEVs can cross both the nasal epithelial barrier and blood-brain barrier to reach the central nervous system (CNS), intranasal administration represents an attractive approach for repeated delivery of MSC-sEVs for long-term administration. In this study, we administered bone marrow-derived MSC-sEVs or vehicle intranasally to a SOD1(G93A) transgenic mouse model of ALS; the large majority of the sEVs had surface markers for exosomes. Dosing was for three consecutive days per week beginning one day after onset of neurological symptoms and continuing until a moribund state. Neurological score and body weight were recorded daily. Although total survival time and post-onset survival duration were not significantly prolonged by MSC-sEV treatment, MSC-sEV treatment significantly delayed progression from a mild symptom phase (NeuroScore 1) to more severe symptoms (NeuroScore 2) compared with vehicle-treated controls and showed a trend toward slower weight loss. These findings indicate that intranasal administration of MSC-sEVs can delay functional deterioration and prolong the mild impairment stage in an ALS mouse model. If translatable to human patients, such preservation of neurological function could represent a clinically meaningful outcome.},
}

@article {pmid41776147,
year = {2026},
author = {Nowell, WB and McGale, N and Levy, O and Wilding, S and Heinrich, P and Patel, NC and Andrews, JA and Rofail, D},
title = {Exploring the Lived Experiences of Individuals with Amyotrophic Lateral Sclerosis (ALS): A Qualitative Study and Conceptual Model of Signs, Symptoms, and Functional Impacts.},
journal = {Neurology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41776147},
issn = {2193-8253},
abstract = {INTRODUCTION: This study aimed to explore the experience of living with amyotrophic lateral sclerosis (ALS) and to develop a conceptual model for this rare disease.

METHODS: Concept elicitation interviews were conducted (January-September 2024) with people living with ALS (PLwALS; n = 31), caregivers (n = 20), and clinicians (n = 10). Qualitative data were analyzed separately to develop a conceptualization of the experience of living with ALS. Concept saturation was assessed every 5-6 interviews, and a conceptual model was developed.

RESULTS: The mean age of PLwALS was 42.4 years (standard deviation [SD] 11.5), 81% were female, 84% were white, and 23% had SOD1-ALS. The mean time since diagnosis was 4.6 years (SD 4.2); mean normed Rasch Overall ALS Disability Scale score was 76 (SD 17.16). Signs, symptoms, and functions reported during PLwALS interviews included neuromuscular, bulbar, speech, neurocognitive (e.g., memory issues), and a range of physical functioning issues (e.g., motor coordination). PLwALS also reported impacts on a range of activities and psychosocial interactions (e.g., eating, depressed mood, and relationships), alongside management strategies they employed. Interviews with caregivers and clinicians supported findings from the PLwALS interviews. Caregivers also identified signs such as drooling/excess salivation, and impacts related to ALS management (e.g., need for writing aids). Clinicians additionally considered loss of speech and neurocognitive signs (e.g., behavior/personality change) as ALS clinical manifestations. Concept saturation was reached, and a consolidated, comprehensive conceptual model was developed.

CONCLUSION: This research provides a holistic understanding of the experience of living with ALS and is the first conceptual model based on in-depth concept elicitation interviews. The findings highlight the range of signs, symptoms, and impacts that PLwALS experience, emphasizing its serious humanistic impact and high unmet need, and will help to guide patient-centric evaluation of clinical outcome assessments in future ALS studies.},
}

@article {pmid41775600,
year = {2026},
author = {Ding, JY and Li, WX and Wang, J and Huang, CY and Xu, XW and Yang, Q and Liu, XL and Yu, L and Hao, SR and Zhang, HF and Chen, JJ},
title = {Effectiveness of multimodal artificial liver support for acute-on-chronic liver failure: A single-center cohort study.},
journal = {Hepatobiliary & pancreatic diseases international : HBPD INT},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.hbpd.2026.02.001},
pmid = {41775600},
issn = {1499-3872},
abstract = {BACKGROUND: Multimodal artificial liver support (ALS) has been proven to be effective in a porcine model of acute liver failure. This study aimed to evaluate the curative effect in patients with acute-on-chronic liver failure (ACLF).

METHODS: Data from ACLF patients receiving multimodal ALS between January 2014 and August 2019 were collected. Patients were divided into two groups according to the patterns of ALS: a trimodal ALS group (trimodal group) and a bimodal ALS group (bimodal group). A propensity score matching was performed to control for baseline bias between the groups. Survival rates and laboratory parameters were compared after single session and after completion of all the sessions of treatments.

RESULTS: A total of 182 patients undergoing multimodal ALS were screened. Propensity score matching generated 47 pairs. The short-term (28/90 days) survival rates were significantly higher in the trimodal group than those in the bimodal group (28-day survival rate: 91.5% vs. 76.6%, P = 0.049; 90-day survival rate: 91.5% vs. 74.5%, P = 0.027). The model for end-stage liver disease score was improved both after single session and after completion of all the sessions of treatments. Single session of trimodal ALS significantly reduced bilirubin (P < 0.001) and bile acid (P = 0.003) levels compared with bimodal ALS. Compared with baseline, gamma-glutamyltransferase (P = 0.001) and alkaline phosphatase (P = 0.021) levels were significantly decreased after completion of all the sessions of treatments in the trimodal group. However, no significant differences were observed in these two parameters within the bimodal group. Trimodal ALS was associated with increased clearance rates of interleukin-8 (P = 0.009) and macrophage migration inhibitory factor (P = 0.012). Multivariate Cox regression revealed that trimodal ALS was an independent predictor of lower 28- and 90-day mortality (both P < 0.05).

CONCLUSIONS: Trimodal ALS may provide a greater survival benefit for patients with ACLF, likely because of its superior ability to clear toxic substances and suppress inflammation.},
}

@article {pmid41775321,
year = {2026},
author = {Lu, YH and Zhu, XP and Li, S and Zhang, FN and Cai, CB and Tian, M and Zhu, YH and Zeng, LH and Tan, J and Yu, CY and Chen, J},
title = {From scaffold to effector: reframing GFAP in neurodegeneration.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.02.051},
pmid = {41775321},
issn = {2090-1224},
abstract = {BACKGROUND: Neurodegenerative disorders impose a growing global burden, yet disease-modifying therapies remain limited. Glial fibrillary acidic protein (GFAP) has shifted from a passive astrocytic marker to an active effector that shapes neurodegenerative pathology.

AIM: of Review: This review synthesizes mechanistic and translational evidence that defines GFAP as a proteoform-governed hub and highlights its value for biomarker-guided precision intervention. Key Scientific Concepts of Review: An extensive literature search across major databases was conducted using predefined keywords and strict inclusion criteria, covering mechanistic, pathological, and clinical studies. Evidence supports a GFAP proteoform code in which alternative splicing generates functionally distinct isoforms, and PTMs encode context-dependent assembly dynamics and signaling outputs. We summarize how GFAP proteoforms integrate cytoskeletal remodeling with inflammatory transcriptional programs (notably STAT3 and NF-κB), proteostasis stress, and mitochondrial dysfunction, thereby coupling astrocyte state transitions to neuronal vulnerability and synaptic impairment. Disease trajectories are context-specific: GFAP dysfunction drives primary toxicity in Alexander disease (AxD); in Alzheimer's disease (AD), isoform-specific mechanisms intersect with amyloidogenic machinery and track early preclinical astrocyte activation; and in frontotemporal dementia (FTD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), GFAP reflects inflammatory-metabolic coupling during progression. Translationally, ultrasensitive plasma assays reveal GFAP elevation years to decades before symptom onset, complementing NfL and amyloid/tau within AT(N)-oriented diagnostic frameworks. Therapeutically, we evaluate precision strategies beyond global suppression, including ASO-based modulation, targeting STAT3/NF-κB-driven reactive programs, and restoring proteostasis via chaperone/autophagy pathways. Future progress hinges on isoform-/PTM-specific probes, conformational sensors, and spatial proteomic atlases validated in prospective longitudinal cohorts. In conclusion, GFAP represents both a mechanistic driver and a scalable biomarker, offering a translationally actionable axis to advance precision medicine in neurodegeneration.},
}

@article {pmid41775065,
year = {2026},
author = {Esmaeili, A and Dashtian, K and Zare-Dorabei, R and Kerman, K and Mahdavi, M},
title = {A tri-responsive sensor based on co-encapsulated organic probes and multifunctional bimetallic V/Ce-MOF nanozyme in a hydrogel for the detection of l-Serine in saliva.},
journal = {Talanta},
volume = {305},
number = {},
pages = {129594},
doi = {10.1016/j.talanta.2026.129594},
pmid = {41775065},
issn = {1873-3573},
abstract = {Rapid and accurate detection of l-Serine, a key potential biomarker of neurological diseases such as Alzheimer, Parkinson and Amyotrophic lateral sclerosis (ALS) disease, is crucial for public health. Herein, we prepared a tri-responsive sensor capable of colorimetric, fluorimetric, and electrochemical detection. This portable sensor integrates co-encapsulated organic probes with a multifunctional bimetallic cerium/vanadium metal-organic framework (UiO-66-NH2(Ce/V)) nanozyme activity, all embedded within a biocompatible agarose-based hydrogel for detection of l-serine in a saliva sample. Physicochemical and electrochemical analyzes confirmed that the UiO-66-NH2(Ce/V) nanozyme, with peroxidase-like activity, facilitated the oxidation of tetramethylbenzidine (TMB) in the colorimetric assay, ortho-phenylenediamine (OPD) in the fluorometric assay and TMB in the electrochemical assay. The oxidation of these probes resulted in the formation of colored compounds in the colorimetric and fluorometric sensors, as well as created sharp anodic peaks in the electrochemical sensors via Vmax of 3.99 M[-1], 5.85 M[-1] and 0.002 M[-1], respectively. The results prove that increasing the concentration of l-serine inhibited the oxidation-reduction reactions, causing a reduction in the intensity of both the colors and the sensor peaks. It demonstrated a wide linear detection range of 5 to 250 μM for the colorimetric sensor, 1-250 μM for the fluorometric sensor, and 0.3-250 μM for the electrochemical sensor with a detection limit of 0.27 μM, 0.26 μM, and 0.076 μM, respectively. These sensors were applied to the detection of l-serine in human saliva samples, achieving recovery rates between 92.20% and 107.50% with RSD of <5%, and excellent reproducibility. The findings suggest that these sensors have significant potential for use in hospitalized healthcare systems to monitor disease biomarkers and represent a promising approach for early diagnosis of disease.},
}

@article {pmid41773017,
year = {2026},
author = {Liang, X and Zhao, T and Dai, X and Sun, Y and Yuan, J and Afzalpurkar, S and Duong, C and Yu, A and Tang, F and He, X and Liu, X and Chen, X and Cao, Z and Wang, Y},
title = {FUS is an N1- and N6-methyladenosine-binding protein.},
journal = {Nucleic acids research},
volume = {54},
number = {5},
pages = {},
pmid = {41773017},
issn = {1362-4962},
support = {R35 ES031707/NH/NIH HHS/United States ; T32 ES018827/NH/NIH HHS/United States ; R35 ES031707/NH/NIH HHS/United States ; },
mesh = {*RNA-Binding Protein FUS/metabolism/genetics ; Humans ; *Adenosine/analogs & derivatives/metabolism ; Methyltransferases/metabolism/genetics/antagonists & inhibitors ; Methylation ; Cell Line, Tumor ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism/genetics ; Protein Binding ; },
abstract = {Nucleotide repeat expansions contribute to a number of neurological disorders. Mutations and augmented expression in fused in sarcoma (FUS) can result in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we reveal that FUS is an N1- and N6-methyladenosine (m1A- and m6A)-binding protein, where the protein interacts with the methylated adenosines in CAG repeat expansion RNA, thereby leading to the protein's cytoplasmic redistribution in SH-SY5Y cells. We also found that ectopically expressed FUS co-localizes with CAG repeat RNA in the cytosol. This co-localization is diminished upon genetic depletion of m6A and m1A writer proteins (i.e. METTL3 and TRMT61A), pharmacological inhibition of METTL3, and ectopic overexpression of m1A and m6A eraser proteins (i.e. ALKBH3 and FTO). Moreover, binding to methylated CAG repeat RNA renders the ectopically expressed FUS protein less dynamic in cells. Together, our study underscores a critical role for m1A and m6A in enhancing FUS-RNA interaction, which results in aberrant subcellular distribution and attenuated mobility of the protein in cells. These findings unveil a novel mechanism underlying neurodegenerative disorders emanating from elevated expression of FUS and suggest targeting FUS-methylated adenosine interactions as a potential therapeutic strategy for FUS proteinopathy.},
}

*RNA-Binding Protein FUS/metabolism/genetics
Humans
*Adenosine/analogs & derivatives/metabolism
Methyltransferases/metabolism/genetics/antagonists & inhibitors
Methylation
Cell Line, Tumor
Amyotrophic Lateral Sclerosis/genetics/metabolism
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism/genetics
Protein Binding

@article {pmid41772759,
year = {2026},
author = {Donega, S and Gorospe, M and Harries, LW and Ferrucci, L},
title = {Loss of Splicing Homeostasis as a Hallmark of Aging.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/10985549.2026.2627235},
pmid = {41772759},
issn = {1098-5549},
abstract = {Alternative splicing is a fundamental mechanism that ensures accurate gene expression, supports cellular adaptability, and expands protein diversity beyond the limits of a fixed gene pool. With aging, splicing fidelity weakens, contributing to decline in RNA homeostasis and disrupting essential cellular functions, including mitochondrial oxidative phosphorylation, genome stability, and immune regulation, and in turn accelerating tissue and organ dysfunction. Evidence from senescent cells, aged tissues, and model organisms shows that altered levels of splicing factors and increased RNA polymerase II elongation rates impair co-transcriptional splicing and promote mis-spliced isoforms that reinforce senescence and drive pathology. Dysfunction of RNA-binding proteins further contributes to aberrant splicing, linking splicing defects to age-related diseases such as atherosclerosis, osteoarthritis, sarcopenia, and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Therapeutic strategies to correct splicing defects, such as antisense oligonucleotides, RNA interference, CRISPR-Cas systems, ADAR-mediated editing, and RNA aptamers, can restore a homeostatic balance of mRNA isoforms. However, major challenges remain, including distinguishing adaptive physiological from pathological splicing 'noise' and achieving targeted delivery to tissues. Despite these obstacles, RNA splicing dysregulation represents a promising avenue to extend health span by reestablishing homeostatic RNA programs, and reinforces the idea that "transcriptomic instability" is a hallmark of aging.},
}

@article {pmid41772409,
year = {2026},
author = {Sorenson, E and Heitzman, D and Lee, I and Jang, G and Elman, L and Habib, AA and Wymer, J and Hayat, G and Goutman, SA and Fernandes, JAM and Floeter, MK and Ajroud-Driss, S and Gwathmey, K and Kasarskis, E and Kisanuki, YY and Lomen-Hoerth, C and Walk, D and Johnston, WS and Diaz, F and Maragakis, NJ and Paganoni, S and Shah, J and Oskarsson, B and Zinman, L and Heiman-Patterson, T and Jawdat, O and Fournier, CN and Pulley, MT and Scelsa, SN and Shoesmith, C and Simmons, Z and Sherman, AV and Hoover, BN and Yun, RY and Cheung, K and Mitsumoto, H and , },
title = {Prospective Validation of the New PLS Diagnostic Criteria From PLS Natural History Study: EMG and Neurofilament Analyses.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70192},
pmid = {41772409},
issn = {1097-4598},
support = {//Mr. David Marren and family/ ; //Spastic Paraplegia Foundation/ ; //ALS Association/ ; //Mitsubishi Tanabe Pharma Corporation/ ; //Muscular Dystrophy Association/ ; //Wings over wall street/ ; //Sean M. Healey and AMG center for ALS research/ ; },
abstract = {BACKGROUND: Primary lateral sclerosis (PLS) is an ultrarare upper motor neuron syndrome with a prognosis unique from classical ALS. The study of PLS is complicated by its rarity and the difficulty distinguishing PLS from ALS. We present data from a 1-year prospective follow-up study on PLS and efforts to distinguish it from ALS.

METHODS: Seventy-six PLS participants enrolled in this prospective natural history study. EMG studies, blood neurofilament light chain levels (NfLs), and demographic characteristics were obtained at baseline. At 1-year follow-up, repeat EMG studies were conducted to determine which participants fulfilled criteria for ALS. Baseline characteristics were then compared to determine features that predict reclassification.

RESULTS: Seventy participants completed 1-year follow-up. Five of the 70 were reclassified to ALS (7.1%). Those reclassified had higher trends in baseline blood NfL levels (91.4 vs. 34.0 pg/mL, p = 0.13) and shorter symptom duration (39 vs. 69 months in the PLS group, p = 0.15). Reclassification was noted in both probable and definite PLS participants. All cases with a symptomatic duration of less than 2 years retained the PLS phenotype (5 of 5). NfL levels over 90 pg/mL predicted reclassification with 94% specificity and 60% sensitivity. No other features predicted reclassification to ALS.

CONCLUSIONS: In our population, reclassification of PLS to ALS occurred at a low frequency at 1 year follow-up (7.1%). Baseline NfL was the strongest predictor in differentiating UMN dominant ALS from PLS at 1-year follow-up. Based on our data, we propose EMG and NfL criteria for enrollment in future PLS trials.},
}

@article {pmid41772347,
year = {2026},
author = {Ahuja, V and Sahu, B and Khurana, S and Kumari, K and Ganguly, NK and Gourie-Devi, M and Verma, S and Dastidar, SG and Taneja, V},
title = {Granules Gone Rogue: Nuclear and Cytoplasmic Ribonucleoprotein Structures in Amyotrophic Lateral Sclerosis-Fused in Sarcoma (ALS-FUS) Pathology.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41772347},
issn = {1559-1182},
support = {211610027970//University Grants Commission/ ; EMDR/IG/9/2024-01739//Indian Council of Medical Research/ ; 3/1/2/151/Neuro/2021-NCD-I//Indian Council of Medical Research/ ; IIRPIG-2023-0001508//Indian Council of Medical Research,India/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; Humans ; *RNA-Binding Protein FUS/metabolism/genetics ; *Cytoplasmic Granules/metabolism/pathology ; Animals ; *Ribonucleoproteins/metabolism ; *Cell Nucleus/metabolism ; *Cytoplasm/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. Among its genetic subtypes, mutations in the fused in sarcoma (FUS) gene represent an aggressive form, often associated with early onset and rapid progression. FUS is a ubiquitously expressed DNA/RNA-binding nuclear protein involved in maintaining DNA damage repair and RNA metabolism. It also plays a crucial role in the formation of ribonucleoprotein (RNP) granules such as cytoplasmic stress granules and nuclear paraspeckles under stress. In ALS, pathogenic FUS mutations frequently disrupt the subcellular distribution of FUS, leading to cytoplasmic mislocalization and aggregation. Mutant FUS further disrupts granular dynamics by its aberrant incorporation into stress granules and altering their biophysical properties. The loss of nuclear FUS function leads to elevated levels of the long non-coding RNA NEAT1 and enhanced paraspeckle assembly with disrupted structural integrity. The impaired nucleocytoplasmic granular dynamics compromise the cellular resilience, thereby increasing motor neuron vulnerability. The interaction of FUS with other ALS-associated proteins causes pathological alterations in the cellular milieu, suggesting a common underlying disease mechanism. This comprehensive review emphasizes the FUS-mediated RNP granule regulation under physiological and pathological conditions. Further, clinically approved and emerging therapeutic strategies aimed at attenuating FUS pathology and RNP granule dynamics have been described.},
}

*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics
Humans
*RNA-Binding Protein FUS/metabolism/genetics
*Cytoplasmic Granules/metabolism/pathology
Animals
*Ribonucleoproteins/metabolism
*Cell Nucleus/metabolism
*Cytoplasm/metabolism

@article {pmid41772317,
year = {2026},
author = {Weller, B and Lin, CW and Rothballer, S and Calderwood, MA and Falter-Braun, P and Falter, C},
title = {NeuroViOme: a viral orfeome collection for studies of neurodegenerative disease.},
journal = {Journal of neurovirology},
volume = {32},
number = {2},
pages = {},
pmid = {41772317},
issn = {1538-2443},
mesh = {Humans ; *Neurodegenerative Diseases/virology/genetics/pathology ; *Host-Pathogen Interactions/genetics ; *Viral Proteins/genetics/metabolism ; *Open Reading Frames/genetics ; Animals ; Virus Replication/genetics ; },
abstract = {Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS) pose a global health challenge due to their progressive course and lack of curative therapies. These conditions lead to severe neurological decline, significantly impacting patient independence and quality of life, and ultimately result in lethal outcome. Emerging evidence suggests that viral infections contribute to the onset and progression of these neurological diseases, Leblanc and Vorberg (PLoS Pathog 18:e1010670, 2022), either by directly inducing neurological symptoms or by triggering immune responses resulting in neuropathology. Nevertheless, systematic studies of the direct interplay between viral and host proteins in neurodegeneration remain scarce. A key aspect of viral pathogenesis is direct interaction between viral and host proteins (protein-protein interactions, PPIs), which are essential for viral replication and can disrupt or redirect host cell function Kim et al. (Nat Biotechnol, 2022); Zhou et al. (Res Sq, 2022), potentially contributing to the development of diseases traditionally considered non-communicable. Understanding these molecular mechanisms is crucial for advancing diagnostic and therapeutic strategies in neurodegenerative conditions, particularly ALS and MS. To enable systematic studies of these interactions, we introduce NeuroViOme as ORFeome resource encompassing nearly all protein-coding sequences from nine viruses selected based on their prevalence, neurotropism, and mechanistic or epidemiological links to neurodegenerative processes. NeuroViOme includes ORFs from Enteroviruses (EV-A71, EV-D68, CVB3, Echovirus E30), Herpesviruses (HSV-1, EBV, HHV3/Varicella Zoster), the endogenous retrovirus HERV-K, and Polyomavirus JCPyV. To our knowledge, this represents the most comprehensive viral ORF set assembled for neurodegeneration research to date. The collection builds the foundation for interactome mapping and functional genomics analyses and provides a valuable basis for systematic studies of viral perturbations of host pathways.},
}

Humans
*Neurodegenerative Diseases/virology/genetics/pathology
*Host-Pathogen Interactions/genetics
*Viral Proteins/genetics/metabolism
*Open Reading Frames/genetics
Animals
Virus Replication/genetics

@article {pmid41772227,
year = {2026},
author = {Rizzo, GEM and Vanella, G and Fuccio, L and Facciorusso, A and Mazza, S and Catena, F and Fabbri, C and Anderloni, A and Tarantino, I},
title = {Endoscopic ultrasound-guided gastrointestinal anastomoses for the treatment of afferent limb syndrome: a systematic review and meta-analysis.},
journal = {Surgical endoscopy},
volume = {},
number = {},
pages = {},
pmid = {41772227},
issn = {1432-2218},
abstract = {BACKGROUND AND STUDY AIMS: Afferent limb syndrome (ALS) is a rare condition resulting in a mechanical obstruction in the afferent loop after surgical gastrointestinal (GI) reconstruction. Endoscopic ultrasound (EUS)-guided gastrojejunostomy (GJ) or jejunojejunostomy (JJ) is increasing in clinical practice. Therefore, the aim of this systematic review with meta-analysis is to evaluate the efficacy and safety of EUS-GJ or EUS-JJ for ALS.

PATIENTS AND METHODS: The most important medical databases were systematically searched through May 2025. The primary outcome was technical success of EUS-GJ/JJ for ALS. Secondary outcomes were clinical success, safety, and recurrence rate. A random-effects model was used to pool the results. Heterogeneity was expressed as inconsistency index (I[2]) and explored through subgroup analyses.

RESULTS: 9 studies (all retrospective) involving 188 patients were included in the analysis. The weighted mean age was 65.38(± 10.57) years and the etiology of the ALS was mostly malignant. Technical success was 96.3% (CI95% 93.2-99.4%, I[2] = 0%). Clinical success was 95% (CI95% 91.2-98.7%, I[2] = 0%) and adverse events (AEs) rate was 6.9% (CI95% 2.9-11.1%, I[2] = 0%). Recurrence rate was 16.6% (CI95% 7.7-25.4%, I[2] = 43.79%). Subgroup analyses showed differences in the recurrence rate between the use of a fully covered self-expandable metal stent (FCSEMS) (35.9% [CI95% 20.3-51.6%, I[2] = 0%]) and a lumen-apposing metal stent (LAMS)(10.4% [CI95% 4-16.8%, I[2] = 0%], p = 0.003). Follow-up ranged from a median of 96.5 to 185 days.

CONCLUSIONS: EUS-guided GI anastomosis is an effective treatment for ALS, showing high technical and clinical success rates and a low incidence of AEs. The use of LAMS over FCSEMS seems to reduce the recurrence rate, suggesting the routine use of LAMS in the case of EUS-guided GI anastomosis for treating ALS.},
}

@article {pmid41769387,
year = {2026},
author = {Scirocco, E and Scalia, J and Ugolini, B and Casagrande, G and Ho, D and Hagar, JL and Kingsley, K and Hoffman, R and Cooley, C and Cudkowicz, ME and Paganoni, S and Berry, JD},
title = {The Amyotrophic Lateral Sclerosis House Call Program: A Single-Center Experience in the United States.},
journal = {Neurology research international},
volume = {2026},
number = {},
pages = {6629960},
pmid = {41769387},
issn = {2090-1852},
abstract = {BACKGROUND: Accessing multidisciplinary care poses challenges for people living with amyotrophic lateral sclerosis (ALS) due to mobility issues. As ALS care rarely requires hospital-based technology, most care is available through home visits. The Daniella Lipper ALS House Call Program (HCP) at Massachusetts General Hospital (MGH), launched in 2017 in collaboration with Compassionate Care ALS, has pioneered home-based ALS care in Eastern Massachusetts.

METHODS: A retrospective chart review of ALS and primary lateral sclerosis (PLS) patients enrolled in the HCP at MGH was conducted. Data on demographics, visit details, and procedures performed during home visits were collected from electronic health records for patients seen from January 2024 to December 2024.

RESULTS: In 2024, the ALS HCP conducted 959 visits for 142 patients (average age: 68 years, range: 36-93; 47.9% female). Of these patients, 137 (96.5%) were diagnosed with ALS and 5 (3.5%) with PLS. Notably, 61 patients (43%) received care exclusively at home. Key interventions included 44 gastrostomy tube exchanges and 59 respiratory assessments, both of which significantly reduced hospital visits. The average distance traveled by the care team was 30.32 miles per visit.

CONCLUSIONS: The Daniella Lipper ALS HCP at MGH brings ALS expertise into the patient's home, minimizing travel burdens and ensuring continuity of care. The program illustrates the feasibility and impact of home-based ALS care, suggesting potential for broader implementation across the nation. Development will focus on expanding services, such as tracheostomy changes in the homes, and on creating sustainable models for similar initiatives.},
}

@article {pmid41768770,
year = {2026},
author = {Perlatti, B and Vellanki, S and Zhang, Y and Chiang, YM and Hu, Y and Yuan, M and Dunbar, K and Fine, A and Grau, MF and Li, S and O'Donnell, T and Shenoy, R and Li, H and Shi, H and Xu, X and Chen, Z and Arvedson, T and Tang, Y and Cramer, RA and Cee, V and Harvey, CJB},
title = {An Antifungal with a Novel Mechanism of Action Discovered via Resistance Gene-Guided Genome Mining.},
journal = {ACS central science},
volume = {12},
number = {2},
pages = {197-207},
pmid = {41768770},
issn = {2374-7943},
abstract = {Invasive fungal infections claim over two million lives annually, a problem exacerbated by rising resistance to current antifungal treatments and an increasing population of immunocompromised individuals. Despite this, antifungal drug development has stagnated, with few novel agents and fewer novel targets explored in recent decades. Here, we validate acetolactate synthase (ALS), an enzyme critical for branched-chain amino acid biosynthesis and absent in humans, as a promising target for new therapeutics. Using resistance gene-guided genome mining, we discovered a biosynthetic gene cluster in Aspergillus terreus encoding HB-35018 (1), a novel spiro-cis-decalin tetramic acid that potently inhibits ALS. Biochemical and antifungal assays demonstrate that 1 surpasses existing ALS inhibitors in efficacy against Aspergillus fumigatus and other pathogenic fungi. Structural studies via cryo-electron microscopy reveal a unique covalent binding interaction between compound 1 and ALS, distinct from known inhibitors, and finally, we demonstrate that ALS is essential for virulence in a mouse model of invasive aspergillosis. These findings position ALS as a promising target for antifungal development and demonstrate the potential of resistance gene-guided genome mining for antifungal discovery.},
}

@article {pmid41768173,
year = {2026},
author = {Capitani, G and Lozzi, D and Curcio, G and Migliore, S},
title = {Moral decision-making in patients with neurodegenerative diseases: a systematic review.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1745923},
pmid = {41768173},
issn = {1664-1078},
abstract = {INTRODUCTION: Moral decision-making, a core component of social cognition, relies on integrating affective and cognitive processes supported by distributed neural networks. Neurodegenerative diseases disrupt these systems to varying degrees, offering unique models to investigate the neural bases of moral cognition. This review aimed to systematically examine moral decision-making deficits across neurodegenerative diseases, delineate disease-specific patterns of moral cognition impairment, and highlight conceptual and methodological gaps to inform future research and clinical assessment.

METHODS: A systematic search of PubMed, Web of Science, and Scopus was conducted for studies published up to January 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.

RESULTS: Seventeen studies met inclusion criteria. Convergent evidence indicates that behavioral variant frontotemporal dementia (bvFTD) produces a distinctive utilitarian bias characterized by diminished empathy, emotional blunting, and impaired integration of intention and outcome, reflecting degeneration of the ventromedial prefrontal cortex, anterior insula, and amygdala within the salience and default mode networks. In contrast, Alzheimer's disease (AD) patients typically preserve affective aversion to harm, suggesting relative sparing of limbic-ventromedial circuits despite conceptual and executive decline. Moral reasoning in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) remains largely intact unless frontotemporal involvement occurs, while dementia with Lewy bodies (DLB) manifests intermediate profiles marked by reduced cognitive theory of mind and aberrant moral affect.

DISCUSSION: These findings delineate disease-specific patterns of moral dysfunction linked to network-level degeneration rather than global cognitive decline. Understanding these mechanisms holds translational relevance for early diagnosis, ethical capacity assessment, and the development of ecologically valid tools to monitor socio-emotional deterioration in neurodegenerative disorders.},
}

@article {pmid41768026,
year = {2026},
author = {Porges, SW},
title = {When A Critique Becomes Untenable: A Scholarly Response To Grossman Et Al.'S Evaluation Of Polyvagal Theory.},
journal = {Clinical neuropsychiatry},
volume = {23},
number = {1},
pages = {113-128},
pmid = {41768026},
issn = {2385-0787},
abstract = {A recent critique advanced by Grossman et al. (2026, this issue) argues that Polyvagal Theory is scientifically untenable, asserting that its core claims regarding autonomic organization, respiratory sinus arrhythmia (RSA), and evolutionary framing are inconsistent with established neurophysiology. The present paper evaluates these assertions not by disputing individual claims in isolation, but by examining whether the critique engages Polyvagal Theory as it is articulated in the peer-reviewed literature and whether it meets the epistemic standards required for scientific refutation. Rather than responding sequentially to individual objections, the analysis clarifies the theory's conceptual foundations, scope, and explicit conditions of falsifiability as a systems-level, pathway-specific framework of autonomic state regulation. It demonstrates that the critique repeatedly evaluates a reconstructed proxy of the theory shaped by persistent category errors, including conflation of neuroanatomy with neurophysiology, reduction of theory to measurement, and substitution of phylogenetic continuity for functional organization. These structural misrepresentations propagate across methodological, neurophysiological, evolutionary, and developmental domains, precluding meaningful empirical adjudication. Across these domains, the paper shows that disagreements concerning RSA metrics, comparative anatomy, or evolutionary framing do not engage the theory's specified mechanisms or demonstrate conditions under which its predictions would fail. Where disagreement exists, it reflects differences in measurement preference, level of analysis, or theoretical framing rather than evidence against the theory's organizing principles. An appendix presents a historical audit showing that several central claims reiterated in the critique were identified in the literature nearly two decades earlier as mischaracterizations of Polyvagal Theory. Their continued repetition without substantive modification reflects a persistent failure of representational uptake rather than unresolved empirical controversy. It is concluded that the charge of scientific untenability does not apply to Polyvagal Theory as formulated, but instead reflects a critique that fails to engage the theory on its own terms. Productive scientific discourse requires representational fidelity, appropriate alignment of levels of analysis, and responsiveness to theoretical and empirical clarification ‒ criteria essential to theory evaluation but not met in the critique under review.},
}

@article {pmid41767843,
year = {2026},
author = {Ben Khalaf, N},
title = {Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1711422},
pmid = {41767843},
issn = {1663-4365},
abstract = {The maintenance of protein homeostasis is essential for neuronal survival and function; however, it progressively declines with age, predisposing the brain to neurodegenerative diseases. Molecular chaperones Hsp70 and Hsp90 are key guardians of proteostasis, pivotally regulating protein folding, refolding, and degradation under both physiological and stress conditions. This review integrates an overview of the structural features, isoforms, and mechanistic interactions of Hsp70 and Hsp90. It highlights how their dysfunction contributes to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. We first examine the architecture and ATP-driven chaperone cycles of Hsp70 and Hsp90, their co-chaperone networks, and the feedback regulation by the Heat Shock Factor-1 pathway. We then discuss evidence linking age-related declines in chaperone expression and HSF-1 activity to proteostasis collapse and neuronal vulnerability. The review particularly examines how Hsp70 and Hsp90 differentially influence pathogenic protein aggregation (e.g., tau, α-synuclein, TDP-43, and mutant huntingtin) and how this balance is altered in the aging brain. Regarding therapeutic approaches, we summarize current strategies targeting these chaperones, including small-molecule modulators of Hsp70 and Hsp90, co-chaperone inhibitors, and recombinant chaperone therapy, which has shown to restore proteostasis and cognitive function in experimental models. These emerging interventions underscore the dual nature of Hsp70/Hsp90 systems, acting as both protectors and potential contributors to neurodegeneration, depending on their regulation and interaction context. By linking molecular chaperone biology to aging and translational therapeutics, this review establishes a framework for developing precision approaches that enhance proteostasis capacity, delay age-associated neurodegeneration, and promote healthy brain aging.},
}

@article {pmid41767786,
year = {2026},
author = {Stirn, YJ and Lee, WC},
title = {Estimation of Conditional Standard Errors of Measurement for MLE Scores in MST.},
journal = {Educational and psychological measurement},
volume = {},
number = {},
pages = {00131644261420391},
pmid = {41767786},
issn = {1552-3888},
abstract = {This paper proposes an information-based analytic method for calculating the conditional standard error of measurement (CSEM) in multistage testing (MST) using maximum likelihood estimation. The accuracy of the proposed method was evaluated by comparing CSEMs computed using the analytic method with those obtained from simulation across the same four MST designs. The results show that analytic and simulation-based CSEMs converge as test length increases, indicating that the proposed method provides a reliable approximation for longer tests. However, shorter tests and more complex MST designs require additional items to achieve comparable accuracy. The study also compared the proposed method with Park et al.'s analytic approach. Practical implications of the proposed method are discussed.},
}

@article {pmid41767168,
year = {2026},
author = {Bakare, AB and Lee, Y and Hong, J and Richter, CP and Kuriakose, JP},
title = {Assessing Large Language Models for Early Article Identification in Otolaryngology-Head and Neck Surgery Systematic Reviews.},
journal = {Health care science},
volume = {5},
number = {1},
pages = {19-28},
pmid = {41767168},
issn = {2771-1757},
abstract = {BACKGROUND: Assess ChatGPT and Bard's effectiveness in the initial identification of articles for Otolaryngology-Head and Neck Surgery systematic literature reviews.

METHODS: Three PRISMA-based systematic reviews (Jabbour et al. 2017, Wong et al. 2018, and Wu et al. 2021) were replicated using ChatGPTv3.5 and Bard. Outputs (author, title, publication year, and journal) were compared to the original references and cross-referenced with medical databases for authenticity and recall.

RESULTS: Several themes emerged when comparing Bard and ChatGPT across the three reviews. Bard generated more outputs and had greater recall in Wong et al.'s review, with a broader date range in Jabbour et al.'s review. In Wu et al.'s review, ChatGPT-2 had higher recall and identified more authentic outputs than Bard-2.

CONCLUSION: Large language models (LLMs) failed to fully replicate peer-reviewed methodologies, producing outputs with inaccuracies but identifying relevant, especially recent, articles missed by the references. While human-led PRISMA-based reviews remain the gold standard, refining LLMs for literature reviews shows potential.},
}

@article {pmid41766085,
year = {2026},
author = {Seco, M and Moreira, I and Oliveira, J and Moreira, S},
title = {Amyotrophic Lateral Sclerosis Caused by a Pathogenic Variant in SOD1 Gene: An Atypical Rapidly Progressive Phenotype.},
journal = {Journal of clinical neuromuscular disease},
volume = {27},
number = {3},
pages = {122-123},
doi = {10.1097/CND.0000000000000548},
pmid = {41766085},
issn = {1537-1611},
}

@article {pmid41766077,
year = {2026},
author = {Hass, RM and Reiter-Campeau, S and Laughlin, RS and Liewluck, T},
title = {Respiratory Onset Amyotrophic Lateral Sclerosis in a Patient With C9orf72 Expansion.},
journal = {Journal of clinical neuromuscular disease},
volume = {27},
number = {3},
pages = {96-98},
doi = {10.1097/CND.0000000000000556},
pmid = {41766077},
issn = {1537-1611},
mesh = {Humans ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology ; *DNA Repeat Expansion/genetics ; Male ; Middle Aged ; Female ; },
abstract = {Respiratory-onset amyotrophic lateral sclerosis (ALS) is uncommon, accounting for less than 5% of all patients with ALS. Familial ALS is also uncommon, with the most common variant being related to a C9orf72 hexanucleotide repeat expansion. Respiratory-onset ALS in familial ALS is rare, with few cases discussed in the literature related to ERBB4, SOD1, and FUS variants. Here we present a case of respiratory-onset ALS related to a C9orf72 repeat expansion, expanding the spectrum of associated phenotypes associated with C9orf72 expansions and highlighting the importance of genetic testing in patients living with ALS.},
}

Humans
*C9orf72 Protein/genetics
*Amyotrophic Lateral Sclerosis/genetics/physiopathology
*DNA Repeat Expansion/genetics
Male
Middle Aged
Female

@article {pmid41766075,
year = {2026},
author = {Kuhn, C and Bromberg, M and Margolis, A and Hayes, H},
title = {Exploring Intimacy in Amyotrophic Lateral Sclerosis: A Pilot Study of Educational Support in a Multidisciplinary Clinic.},
journal = {Journal of clinical neuromuscular disease},
volume = {27},
number = {3},
pages = {82-88},
doi = {10.1097/CND.0000000000000546},
pmid = {41766075},
issn = {1537-1611},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Pilot Projects ; Male ; Female ; Middle Aged ; Aged ; *Patient Education as Topic/methods ; Adult ; *Sexual Partners/psychology ; *Interpersonal Relations ; Surveys and Questionnaires ; },
abstract = {OBJECTIVE: This pilot study explored the feasibility and perceived usefulness of an educational intervention on intimacy delivered within a multidisciplinary ALS clinic.

METHODS: Individuals with ALS and their partners (if applicable) received the publicly available "Sexuality, Intimacy & Chronic Illness" fact sheet during routine clinic visits. A follow-up survey was conducted 4-6 weeks later to assess whether the information was informative, sufficient, and helpful. Demographic and clinical data were collected, and open-ended responses were analyzed descriptively.

RESULTS: Forty-two individuals received the fact sheet; 6 individuals and their partners (N = 12) completed follow-up surveys. Most respondents (83%) reported that ALS had impacted their intimate relationships, and 75% had discussed these changes with their partner. Half found the fact sheet informative, and 58% felt the information was sufficient. Open-ended responses revealed diverse needs, including interest in tailored content (eg, erectile dysfunction) and a desire for providers to ask permission before discussing intimacy. Caregivers described shifting roles and emotional strain, indicating that written materials alone may not fully address intimacy-related challenges.

CONCLUSIONS: Integrating discussions of intimacy into ALS care is feasible and appreciated by some patients and partners. Although written educational materials may offer a useful starting point, a more personalized, consent-based approach-potentially modeled on frameworks like Ex-PLISSIT-may better address the relational needs of individuals with ALS and their caregivers. These findings support incorporating intimacy into holistic ALS care and developing guidelines to facilitate such discussions in multidisciplinary settings.},
}

Humans
*Amyotrophic Lateral Sclerosis/psychology/complications
Pilot Projects
Male
Female
Middle Aged
Aged
*Patient Education as Topic/methods
Adult
*Sexual Partners/psychology
*Interpersonal Relations
Surveys and Questionnaires

@article {pmid41765997,
year = {2026},
author = {Wu, J and Xu, Y and Yin, T and Zhang, N and Ge, J and Fan, D and Ye, S},
title = {Voxel-mirrored homotopic connectivity in upper motor neuron-dominant amyotrophic lateral sclerosis is associated with different spread directions.},
journal = {Brain imaging and behavior},
volume = {20},
number = {2},
pages = {},
pmid = {41765997},
issn = {1931-7565},
support = {82071426//National Natural Science Foundation of China/ ; 82001350//National Natural Science Foundation of China/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; YJXJ-JZ-2021-0014//Beijing E-Town Cooperation & Development Foundation/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *Corpus Callosum/physiopathology/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Aged ; Gray Matter/physiopathology/diagnostic imaging ; Neural Pathways/physiopathology/diagnostic imaging ; *Brain/physiopathology/diagnostic imaging ; Brain Mapping/methods ; Diffusion Tensor Imaging ; Adult ; Motor Neurons ; },
abstract = {By adopting the method of voxel-mirrored homotopic connectivity (VMHC), the correlation of the synchrony of spontaneous neural functional activities between symmetrical regions is determined to be mediated by the corpus callosum (CC). This study investigated differences in homotopic functional connectivity (FC) across distinct symptom spread directions in individuals with upper motor neuron-dominant amyotrophic lateral sclerosis (UMN-D ALS). The UMN-D ALS patients were categorized into two groups on the basis of the direction of symptom spread-horizontal spread (group H) and vertical spread (group V). Indices of interhemispheric functional and structural changes are derived via analyses of VMHC and probabilistic fiber tracking. The VMHC analysis of grey matter revealed that the intergroup differences in the superior frontal gyrus (SFG) were greater in group H than in groups V and HC (voxel P < 0.05, cluster P < 0.05, GRF corrected). According to CC-based VMHC analysis, group H had greater VMHC values than did group V (45 mm[3] vs. 18 mm[3] at a voxel-level threshold of P < 0.05, uncorrected). In UMN-D ALS, the results of VMHC analysis vary with different spread directions. In group H, homotopic FC significantly increased, possibly associated with early bilateral limb involvement and subsequent compensatory increases in the SFG. These results contribute to the understanding of the relationship between brain function and symptom evolution in individuals with ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/pathology
Male
Female
Middle Aged
*Corpus Callosum/physiopathology/diagnostic imaging
Magnetic Resonance Imaging/methods
Aged
Gray Matter/physiopathology/diagnostic imaging
Neural Pathways/physiopathology/diagnostic imaging
*Brain/physiopathology/diagnostic imaging
Brain Mapping/methods
Diffusion Tensor Imaging
Adult
Motor Neurons

@article {pmid41765421,
year = {2026},
author = {Niidome, T and Ishida, T},
title = {[Mechanism of action and clinical trial results of a new drug for amyotrophic lateral sclerosis (ALS), Mecobalamin (Rozebalamin[®]) for intramuscular injection, 25 mg].},
journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica},
volume = {161},
number = {2},
pages = {115-122},
doi = {10.1254/fpj.25066},
pmid = {41765421},
issn = {0015-5691},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Vitamin B 12/administration & dosage/analogs & derivatives/therapeutic use/pharmacology ; Injections, Intramuscular ; Animals ; Clinical Trials as Topic ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive, intractable neurodegenerative disease characterized by generalized muscle atrophy and weakness, dysarthria, dysphagia, and respiratory muscle paralysis. Respiratory dysfunction due to muscle weakness is the primary cause of death; without mechanical ventilation, death typically occurs within 2 to 5 years after onset. Mecobalamin, an active form of vitamin B12, is thought to suppress homocysteine-induced neuronal cell death in ALS by acting as a coenzyme for methionine synthase, which catalyzes the conversion of homocysteine to methionine. Since the 1990s, research on neurodegenerative diseases supported by Japan's Ministry of Health, Labour and Welfare has suggested that high-dose mecobalamin may confer clinical benefits in ALS. This led to the initiation of clinical development. A Phase II/III double-blind, placebo-controlled comparative trial was conducted, but did not meet its primary endpoint. Based on these trial findings, an investigator-initiated Phase III placebo-controlled, double-blind comparative trial was conducted primarily at Tokushima University Hospital, targeting patients who developed ALS within one year before starting the trial. The trial demonstrated the efficacy of high-dose mecobalamin in slowing the decline in the Revised ALS Functional Rating Scale total score, which was the primary endpoint. Safety was also confirmed. Based on these results, mecobalamin received regulatory approval in September 2024 for the indication "slowing the progression of functional impairment in ALS." It is expected to offer a new treatment option for patients with ALS.},
}

*Amyotrophic Lateral Sclerosis/drug therapy
Humans
*Vitamin B 12/administration & dosage/analogs & derivatives/therapeutic use/pharmacology
Injections, Intramuscular
Animals
Clinical Trials as Topic

@article {pmid41765206,
year = {2026},
author = {Kotapati, C and Van Tran, LT and Cardoso, FC},
title = {Voltage-gating and neuronal signalling in neurodegeneration: From neuropathology to therapeutic opportunities in motor neuron disease.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107336},
doi = {10.1016/j.nbd.2026.107336},
pmid = {41765206},
issn = {1095-953X},
abstract = {Voltage-gated ion channels (VGICs) are central to motor neuron excitability, governing the initiation and propagation of action potentials and synaptic transmission. Disruption of their finely tuned gating properties contributes to pathology-associated hyperexcitability, a hallmark of several neurodegenerative conditions, including motor neuron disease (MND). In this review, we examine the physiological roles of voltage-gated sodium, calcium and potassium channels in motor neurons, and evaluate how mutations, altered expression, aberrant biophysics, and maladaptive signalling impair the voltage signalling processes that drive and underlie neuronal dysfunction and degeneration. We synthesise evidence linking ion channel dysfunction to altered excitability, excitotoxicity, impaired neurotransmission, motor system instability and progressive motor neuron loss in MND. We discuss current therapies that offer modest benefit and may act directly or indirectly on neuronal excitability but with limited target specificity. Motivated by the the urgent need for effective treatments for MND, we discuss emerging strategies that leverage highly selective VGIC modulators, particularly gating-modifier peptides inhibitors, to counteract hyperexcitability in MND. We further highlight that understanding how voltage-sensing and channel gating are altered in MND offers new avenues for selective targeted intervention. Together, the evidence supports VGICs as critical yet poorly explored therapeutic targets for halting motor neurodegeneration.},
}

@article {pmid41764146,
year = {2026},
author = {Ciuro, M and Sangiorgio, M and Leanza, G and Gulino, R},
title = {Neuroinflammation and Oxidative Stress in SOD1 Animal Models of ALS: A Meta-analysis Study of Their Effects on Disease Onset and Progression.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41764146},
issn = {1559-1182},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Oxidative Stress/physiology ; Disease Models, Animal ; *Disease Progression ; *Superoxide Dismutase-1/metabolism ; *Neuroinflammatory Diseases/pathology ; Humans ; Mice ; *Inflammation/pathology ; Male ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disorder characterized by progressive motor neuron degeneration. Among the key mechanisms implicated in ALS pathogenesis, neuroinflammation and oxidative stress have emerged as prominent contributors to disease progression. This systematic review with meta-analysis involved 344 preclinical studies conducted on SOD1 animal models of ALS, to quantitatively evaluate the effects of treatments targeting neuroinflammation and oxidative stress on functional outcomes such as disease onset, survival, motor neuron degeneration, and locomotion. Data extraction and validation were performed using a combination of a large language model and human review. Results show that while most interventions led to reduced astrogliosis, M1 microgliosis, and oxidative stress, and increased M2 microgliosis, these effects were more strongly associated with improved survival and motor outcomes than with delayed disease onset. The analysis also revealed that treatment timing significantly influences outcomes, with interventions initiated during the late pre-onset window showing the highest efficacy. Furthermore, sex differences were noted, with male mice displaying better outcomes in progression metrics but worse in the age at onset. Overall, this meta-analysis indicates that inflammation and oxidative stress are important contributors to ALS progression in SOD1 animal models, identifies potentially critical therapeutic windows, and supports the consideration of sex-balanced and stage-specific treatment strategies at the preclinical level.},
}

Animals
*Amyotrophic Lateral Sclerosis/pathology/metabolism
*Oxidative Stress/physiology
Disease Models, Animal
*Disease Progression
*Superoxide Dismutase-1/metabolism
*Neuroinflammatory Diseases/pathology
Humans
Mice
*Inflammation/pathology
Male

@article {pmid41763528,
year = {2026},
author = {Kuznetsov, AV},
title = {Modeling the growth of cytosolic TDP-43 inclusion bodies and accumulated neurotoxicity of misfolded oligomers in neurons.},
journal = {Computer methods in biomechanics and biomedical engineering},
volume = {},
number = {},
pages = {1-28},
doi = {10.1080/10255842.2026.2618583},
pmid = {41763528},
issn = {1476-8259},
abstract = {This paper introduces a mathematical model for the growth of transactive response DNA binding protein of 43 kDa (TDP-43) inclusion bodies in neuron soma. The parameter representing the accumulated neurotoxicity caused by misfolded TDP-43 oligomers is also introduced. The model's equations enable the numerical calculation of the concentrations of TDP-43 monomers, dimers, free oligomers, and oligomers deposited in inclusion bodies. By simulating the deposition of free oligomers into inclusion bodies, the model predicts the size of TDP-43 inclusion bodies. An approximate solution to the model equations is derived for the scenario where protein degradation machinery is dysfunctional, leading to infinite half-lives for TDP-43 dimers, monomers, and both free and deposited oligomers. This solution, valid at large times, predicts that the radius of the inclusion body increases proportionally to the cube root of time, whereas the accumulated neurotoxicity increases linearly with time. To the best of the author's knowledge, this study is the first to model the relationship between the size of TDP-43 inclusion bodies and time, and the first to introduce the concept of accumulated neurotoxicity caused by misfolded TDP-43 oligomers. Sensitivity analysis of the approximate solution indicates that the inclusion body radius and accumulated neurotoxicity become independent of the kinetic constants at large timescales. Unlike the case of infinite half-lives, the numerical solution for physiologically relevant (finite) half-lives demonstrates that the long-term behavior of the inclusion body radius and accumulated neurotoxicity remains dependent on the kinetic constants, converging to distinct curves over time.},
}

@article {pmid41763443,
year = {2026},
author = {Zafarjonovna, AZ and Aysulu, E and Matlyuba, S and Rashid, H and Azamatovich, JB and Ahmadjon, A and Barno, A and Kurbanovna, AM and Ugli, MRM and Shaxodat, I and Rustam, T and Jumaniyazovna, MG and Ishankulov, A},
title = {Small extracellular vesicles as emerging biomarkers and therapeutic targets in neurodegenerative diseases.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {},
number = {},
pages = {120932},
doi = {10.1016/j.cca.2026.120932},
pmid = {41763443},
issn = {1873-3492},
abstract = {Small extracellular vesicles (sEVs) have rapidly emerged as versatile mediators of intercellular communication with significant potential to transform the diagnosis and treatment of neurodegenerative diseases (NDDs). Increasing evidence shows that sEVs not only participate in the propagation of pathogenic proteins but also serve as accessible, CNS-informative carriers of molecular signatures that reflect neuronal, glial, and systemic disease processes. This dual role positions sEVs at the intersection of biomarker discovery and therapeutic innovation. In the diagnostic domain, advances in immunoaffinity capture, single-vesicle analysis, and multi-omics profiling have enabled increasingly precise characterization of neuron-, astrocyte-, and microglia-derived sEVs, revealing candidate markers for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and related disorders. However, translation remains limited by methodological heterogeneity, a lack of large-scale validation, and the need for standardized pre-analytical and analytical pipelines aligned with the ISEV/MISEV guidelines. On the therapeutic front, native and engineered sEVs, particularly those derived from mesenchymal and neural stem cells, demonstrate promising neuroprotective effects, including the modulation of neuroinflammation; the enhancement of synaptic resilience; and the delivery of antioxidant, anti-amyloid, or gene-modifying cargo across the blood-brain barrier. Scalable GMP manufacturing, cargo-loading strategies, targeting specificity, and long-term safety remain key challenges for clinical translation. This narrative review synthesizes current advances in sEV-based biomarkers and therapeutics, outlines technological and regulatory barriers, and proposes a translational roadmap spanning mechanistic discovery, platform standardization, and integration into precision-medicine frameworks. Collectively, emerging data position sEVs as powerful tools capable of reshaping the diagnostic and therapeutic landscape of NDDs, provided that coordinated multidisciplinary efforts address the remaining gaps in validation, scalability, and regulatory readiness.},
}

@article {pmid41763422,
year = {2026},
author = {Li, Y and Liu, S and Cao, L and Zhu, M and Lin, S and Wang, X and Qiu, Z and Teng, Y},
title = {Ginsenoside compound K inhibited the gelation of GGGGCC repeats and regulated co-aggregation with arginine-rich poly-dipeptides in C9orf72-related ALS.},
journal = {International journal of biological macromolecules},
volume = {351},
number = {},
pages = {151138},
doi = {10.1016/j.ijbiomac.2026.151138},
pmid = {41763422},
issn = {1879-0003},
abstract = {GGGGCC repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It produces toxic RNA repeats and poly-dipeptides, leading to abnormal phase separation and deposition in nerve cells. In particular, repeat RNAs form gels that induce cellular toxicity. Thus, they are potential therapeutic targets. Ginsenoside compound K (CK) is the major metabolite of Panax ginseng, a traditional Chinese medicine commonly used for the treatment of neurodegenerative diseases. In this study, CK significantly inhibited the gelation of GGGGCC repeats both in vitro and in vivo. Moreover, it reduced the co-aggregation of RNA and arginine-rich poly-dipeptides via electrostatic interactions. Further investigation suggested that CK preferentially interacts with G-quadruplex monomers formed by GGGGCC repeats rather than with complex multimers, thereby inhibiting the formation of toxic RNA foci. These results elucidate the mechanism of action of CK in C9orf72-related ALS/FTD. Thus, this study provides new avenues for the potential application of ginsenoside in the treatment of neurodegeneration.},
}

@article {pmid41763275,
year = {2026},
author = {Shi, B and Liu, M and Wang, Y},
title = {ATCRN: Attention-guided Temporal Convolutional Remix Network for P300 speller.},
journal = {Journal of neuroscience methods},
volume = {430},
number = {},
pages = {110727},
doi = {10.1016/j.jneumeth.2026.110727},
pmid = {41763275},
issn = {1872-678X},
abstract = {BACKGROUND: The P300 speller is a prominent brain-computer interface (BCI) that facilitates communication by detecting P300 event-related potentials. However, its performance is substantially constrained by the low signal-to-noise ratio of EEG signals and the inherent temporal variability of the P300 response.

NEW METHOD: We propose the Attention-guided Temporal Convolutional Remix Network (ATCRN), an end-to-end model that synergistically integrates a novel Temporal Convolutional Remix Network (TCRN) with a dual-attention framework. The TCRN employs multi-level skip connections to enable dynamic, cross-hierarchical fusion of local and global temporal features, addressing the variable latency of P300. Externally, the Convolutional Block Attention Module (CBAM) suppresses noise in spatial and channel dimensions. Internally, Efficient Channel Attention (ECA) modules within TCRN block perform dynamic channel recalibration.

RESULTS: On BCI Competition III Dataset II, ATCRN achieved character recognition rates of 99% and 98% for two subjects at the 15th repetition, and yielded superior information transfer rates. Evaluation across eight ALS patients showed robust P300 detection (average AUC-ROC 0.882).

ATCRN outperforms both established CNN/TCN benchmarks and recent Transformer-based models across two public datasets, achieving state-of-the-art results in P300 detection and character spelling.

CONCLUSION: The proposed ATCRN provides a novel, robust, and effective decoding framework for the P300 speller. The integration of TCRN for temporal feature fusion and the dual-attention mechanism for feature refinement offers a practical solution for advancing BCI applications.},
}

@article {pmid41762823,
year = {2026},
author = {Nissinen, P and Silén-Lipponen, M and Kähkönen, O and Saaranen, T},
title = {Nursing students' learning experiences, outcomes, and methods in distance education: An integrative literature review.},
journal = {Nurse education today},
volume = {162},
number = {},
pages = {107051},
doi = {10.1016/j.nedt.2026.107051},
pmid = {41762823},
issn = {1532-2793},
abstract = {BACKGROUND: The transformation of nursing education has emphasized the role of distance education as a permanent component. Nursing students' learning experiences and outcomes in this format show considerable variation and raise questions about the most effective distance learning methods.

AIMS: The aim of this integrative review was to explore nursing students' experiences with distance learning, identify the learning outcomes it produces, and examine the distance learning methods used in nursing education.

DESIGN: Integrative literature review.

METHODS: A systematic literature search was conducted in the CINAHL (EBSCO, PubMed/Medline, Education database (ProQuest), Scopus and ERIC (EBSCO) databases, including peer-reviewed studies published in English between 2018 and 2024. The review followed the PRISMA 2020 guidelines. Quality appraisal was performed using Hawker et al.'s evaluation tool. Data was analyzed using inductive content analysis.

RESULTS: A total of 43 studies were included in the review. Five main themes were identified describing students' experiences: the accessibility of digital learning platforms, the quality and structure of learning materials, the acquisition of practical and clinical skills, social interaction and peer support, motivation, self-regulation, and emotional well-being. Learning outcomes were categorized into cognitive, psychomotor, and affective domains. The most common learning methods included synchronous, asynchronous, and blended approaches, with blended learning showing particularly positive results.

CONCLUSION: Distance education can support nursing students' learning when it is well-structured and combines pedagogical planning with interactive and practical elements. Not all competencies, particularly clinical skills, can be taught remotely. The learning experience is shaped by individual abilities, guidance, and technical conditions, and distance education may not suit all students equally well. Effective methods, especially blended learning, support engagement and learning when aligned with student needs and pedagogical goals.},
}