bluuebunny/crossref_metadata_2025_split huggingface dataset:
ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human Cells
Authors: Liu Tiantian , Xie Aiguo , Xing Chao , He RuiZhe , Ni Wei , Peng Yinbo , Xu Peng , Fang Yong 
Published: January 2025

AbstractSilver nanoparticles (AgNPs) are recognized for their strong antibacterial properties, particularly in applications such as wound and burn treatment; however, the mechanisms of AgNP‐induced cytotoxicity remain inadequately defined. This study investigates the role of lysosomal dysfunction in AgNP‐induced cytotoxicity, focusing on lysosomal perinuclear clustering (LPC) and its relationship with cellular apoptosis. Human fibroblast HS27 cells are treated with 24 µg mL−1 AgNPs over 48 h, and lysosomal dynamics, cellular localization, and apoptosis rates are analyzed through confocal microscopy and flow cytometry. Protein expression levels of charged multivesicular body protein 4B(CHMP4B) and Kinesin 1, which are central to lysosomal transport and membrane repair, are examined via western blotting. The findings reveal that AgNP exposure leads to LPC and an increase in apoptosis in a time‐dependent manner, accompanied by reduced Kinesin 1 expression. Further, inhibition of CHMP4B and Kinesin 1 significantly promoted apoptosis, while their overexpression mitigated AgNP‐induced cytotoxic effects, underscoring their essential roles in lysosomal integrity. This study provides new insights into the cellular pathways of AgNP‐induced cytotoxicity, focusing on lysosomal transport disruption, and suggests potential molecular targets to reduce adverse effects in therapeutic applications. These results lay a foundation for optimizing AgNP efficacy and improving their safety profile in clinical settings.
New biofluid measures for TDP‐43
Authors: Esteve Aitana Sogorb 
Published: January 2025

AbstractTransactive response DNA‐binding protein 43 (TDP‐43) has emerged as a pivotal player in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and the recently described limbic‐predominant age‐related TDP‐43 encephalopathy (LATE).Detecting TDP‐43 pathology in a minimally invasive manner is crucial for early diagnosis, monitoring disease progression and the assessment of therapeutic interventions. This talk explores recent advancements in the discovery and validation of novel biofluid measures aimed at detecting and characterising TDP‐43 pathology.The era of proteomics has paved the way for the identification and validation of TDP‐43 biomarkers in biofluids. This presentation highlights the latest discoveries, encompassing both established and newly discovered candidates within cerebrospinal fluid (CSF) and blood.As the field progresses, the integration of these measures into clinical practice may revolutionise our approach to neurodegenerative diseases bringing us closer to effective treatments and improved patient care.
Discovery and preclinical development of [18F]ACI‐19626, a first‐in‐class TDP‐43 PET tracer
Authors: Seredenina Tamara 
Published: January 2025

AbstractBackgroundAggregated TDP‐43 is found as the main component of pathological inclusions in amyotrophic lateral sclerosis (ALS), limbic‐predominant age‐related TDP‐43 encephalopathy (LATE), in 50% of patients with frontotemporal dementia (FTD), and is present as co‐pathology in other neurodegenerative diseases, including Alzheimer’s disease (AD). Biofluid or imaging biomarkers of TDP‐43 pathology are currently unavailable. Direct detection of TDP‐43 aggregates holds promise for unraveling the pathobiology of disease and for enabling precision medicine approach via improved diagnosis, patient stratification and assessment of therapeutic efficacy in clinical trials in AD and related diseases.MethodsUsing our Morphomer® small molecule library of brain‐penetrant and beta sheet binding compounds, initial hits were identified using patients’ brain material. Radiobinding and autoradiography assays were used to assess binding affinity and target engagement on brain samples from cases with TDP‐43 proteinopathies, and selectivity over other aggregation‐prone proteins on AD and Parkinson’s disease (PD) tissue. The pharmacokinetics in the brain was studied in mice, followed by evaluation in cynomolgus monkeys to assess brain uptake, distribution and washout for selected 18F‐radiolabeled compounds.ResultsScreening of >500 compounds led to identification of several distinct chemical series that bound pathological TDP‐43 derived from FTLD‐TDP brain samples with nanomolar affinity. Rational drug design and medicinal chemistry optimization enabled the discovery of the TDP‐43 tracer, ACI‐19626. This compound has high affinity binding (low nM Kd) for human brain‐derived aggregated TDP‐43 and can differentiate FTLD‐TDP type A and B patient samples from age‐matched controls. ACI‐19626 displays selectivity for TDP‐43 over Abeta, Tau and alpha‐synuclein aggregates, and no binding to common off‐target proteins, including monoamine oxidase A and B. In monkeys, [18F]ACI‐19626 has a rapid brain uptake and fast and complete washout, a profile suitable for brain PET imaging.Conclusions[18F]ACI‐19626 was identified as a potential first‐in‐class TDP‐43 PET tracer and selected for evaluation in a First‐in‐Human study based on its excellent affinity, selectivity and pharmacokinetic properties. [18F]ACI‐19626 has the potential to detect and monitor the progression of TDP‐43 pathology in brains of living patients with TDP‐43 proteinopathies such as ALS, FTLD‐TDP, AD and LATE, enabling precision medicine approach and combination therapies.
Limbic predominant age‐related TDP‐43 encephalopathy neuropathological change (LATE‐NC) is associated with lower volume in gray and white matter of the temporal and frontal lobes and basal ganglia: A deformation‐based brain morphometry study
Authors: Tazwar Mahir , Evia Arnold M , Ridwan Abdur Raquib , Bennett David A. , Schneider Julie A. , Arfanakis Konstantinos 
Published: January 2025

AbstractBackgroundLimbic‐predominant age‐related TDP‐43 encephalopathy neuropathological change (LATE‐NC) is common in older adults and has been associated with substantial cognitive impairment. However, the association of LATE‐NC with brain morphometry has not been thoroughly investigated. In this work, we examined the association of LATE‐NC with brain morphometric anomalies using deformation‐based morphometry (DBM) in a large community cohort of older adults that came to autopsy (N=897).MethodCerebral hemispheres were acquired from 897 deceased older adults participating in Rush Memory and Aging Project, Religious Orders Study, Minority Aging Research Study, and Clinical Core. Hemispheres were imaged ex‐vivo on 3T MRI scanners, which was followed by detailed neuropathologic examination. The participant scans were non‐linearly registered to an ex‐vivo template, and the resulting deformation fields were used to calculate the logarithm of the Jacobian determinant in each voxel (LogJ maps).Voxel‐wise linear regression was used to test the association between deformations shown in the LogJ maps and LATE‐NC stages, controlling for other age‐related neuropathologies (Alzheimer’s disease, Lewy bodies, arteriolosclerosis, atherosclerosis, cerebral amyloid angiopathy, gross and microscopic infarcts), age at death, sex, education, postmortem intervals, and scanners. To identify the earliest LATE‐NC stage exhibiting morphometric abnormalities, LogJ values were compared between LATE‐NC stages 1–5 and stage 0. Statistical significance was set at p<0.05.ResultVoxel‐wise analysis revealed an independent association of LATE‐NC with significantly lower volume in both gray and white matter regions within the temporal and frontal lobes and basal ganglia (p<0.05), including amygdala, hippocampus, entorhinal, parahippocampal, temporal pole, inferior temporal, middle temporal, fusiform, medial orbitofrontal, lateral orbitofrontal, insula, accumbens, and putamen cortices. Groupwise comparison of LogJ values revealed significant morphometric anomalies in small temporal lobe areas in stages 1–2, more temporal lobe as well as basal ganglia tissue in stage 3, and finally also included frontal lobe areas in stages 4–5.ConclusionThe morphometric anomalies were detected as early as LATE‐NC stage 1, suggesting that MRI is sensitive to the early stages of the disease. This pattern is consistent with the known pathological distribution of LATE‐NC in the brain and may potentially be used in the development of a marker of this devastating neuropathology.
Understanding Family Caregiver Experience and Satisfaction with Nursing Home Care: A Conceptual Model
Authors: Piersol Catherine V , Martinez Jenny , Chew Felicia M , Leland Natalie E 
Published: January 2025

AbstractBackgroundFamily caregivers are challenged to manage the progressive cognitive decline and behavioral symptoms of Alzheimer’s disease and related dementias, which often trigger nursing home placement. Research has addressed the effect of nursing home placement on family caregivers; however, their perceptions about care are less understood. We sought to examine the experiences of family caregivers with the objective of developing a conceptual model to explain the complex nature of family caregiver experience.MethodsWe will describe our qualitative study that utilized the grounded theory method. Purposive sampling was used to recruit family caregivers from a sample of 23 nursing homes in the United States enrolled in a larger pragmatic trial. Caregivers participated in one‐on‐one, in‐depth interviews with trained research assistants. An iterative, three‐step data coding process was employed to analyze the interview transcripts.ResultsStudy participants (N = 30) were primarily female (90%), White (86.6%), and ranged from age 29 to 84. This presentation will characterize seven emerging themes that interrelate to create a conceptual model. One theme, “Family caregiver satisfaction with care” emerged as the core concept, with the other six themes serving as contributing intrinsic and extrinsic factors that interrelate and impact family caregiver perception of satisfaction. The contributing factors are (1) family caregiver interactions with nursing home staff, (2) staff management of resident behavioral symptoms; (3) nursing home context; (4) family caregiver knowledge of dementias; (5) family caregiver strain; and (6) the resident experience. Family caregivers experience each contributor simultaneously and in differing patterns, depending on the care situation. We will display our conceptual model and discuss how the interactions between contributing factors affect family caregiver satisfaction across a dynamic continuum from low to high satisfaction.ConclusionOur conceptual model offers a mechanism for understanding the factors important to family caregivers of nursing home residents with dementia, prompting their action and reaction to care situations and staff interactions. The model reflects the importance caregivers place on staff knowledge about dementia and their use of appropriate care approaches. Understanding how satisfaction with care is perceived by family caregivers may encourage collaboration between families and staff.
Digital Interventions in Neuro‐Rehabilitation: Gotcha! app‐based therapy for proper name anomia in people with dementia
Authors: Badalova Aygun 
Published: January 2025

AbstractBackgroundProper name anomia is a common experience that can become amplified in patients with a diagnosis of dementia (PWD). The Gotcha! app aims to provide practice‐based therapy for PWD to relearn the names of key people in their lives. It has been developed using the principles of errorless learning and spaced retrieval, which have previously been shown to improve the remembering the familiar people’s names and benefit the relationship between the PWD and their loved ones. (Clare et al, 1999, 2000, 2003).MethodsGotcha! is a digital confrontation naming therapy app which enables patients to train one face per day by using photos of the person whose name is to be trained. We employed a single‐case experimental design with weekly testing of free‐naming in both six‐week blocks (pre therapy and therapy). During the therapy, a novel speech verifier is used to provide real‐time feedback (Barbera et al. 2020). Two analyses method is used to investigate the behavioural data: 1) within‐subject non‐parametric analysis using Tau‐U metric (Parker et al. 2011); 2) a parametric group analysis using an ANOVA.ResultsThe trial is ongoing. Results from the first 20 subjects show:1) Tau‐U. 80% showed a positive trend with better naming during the training phase with 8/20 reaching statistical significance.2) ANOVA demonstrated a significant effect at the group level of training>baseline phase, F (1,19) = 13.18, p = 0.01ConclusionApp‐based proper name anomia retraining works for the majority of PWD in our trial thus far. Being able to freely recall and produce the name of a relative or loved one has a big impact on people’s lives.
Effects of technology‐based cognitive and exercise interventions on cognitive function in persons with mild cognitive impairment: A systematic review, network meta‐analysis, and meta regression
Authors: Ye Yifan , Zhang Lifeng 
Published: January 2025

AbstractBackgroundTechnology has been increasingly integrated into controlling the decline of cognitive function for persons with mild cognitive impairment (MCI). It is unclear whether technology‐based cognitive and exercise interventions could generate synergistic benefits and what components would optimize this effect.MethodsIn this study, we searched MEDLINE, Web of Science, Scopus, Embase and APA PsycInfo from inception to Nov 4, 2023. We included randomized controlled trails that evaluated the effects of technology‐based cognitive and exercise interventions on cognitive function for persons with MCI. Our primary outcome was global cognition. Outcomes were summarized in narrative synthesis and combined using meta‐analysis. Pairwise meta‐analysis and network meta‐analysis were sequentially performed to identify the effects of each category of interventions and their comparative intervention effectiveness, respectively. Meta‐regression was performed to examine any influence of study design and participants’ characteristics on the intervention effectiveness. This systematic review protocol was registered in PROSPERO (CRD 42023486359).FindingsA total of 28 studies with 1633 participants were included. The results of pairwise meta‐analyses indicated that technology‐based cognitive and exercise interventions were superior to active/passive controls in global cognition, cognitive shifting, proceeding speed, working memory, delayed recall, and category fluency (p<0.05). The results of network meta‐analyses indicated that the optimal components were cognitive stimulation combined with mind‐body exercise in improving global cognition (SUCRA: 77.0%, SMD 0.85, 95%CI ‐0.17 to 1.87) and cognitive shifting (SUCRA: 92.4%, SMD 1.57, 95%CI 0.88 to 2.25), while cognitive training combined with mind‐body exercise were the most beneficial in developing proceeding speed (SUCRA: 88.5%, SMD 0.68, 95%CI 0.14 to 1.22). Meta‐regression further suggested that the effects of the tested interventions were independent of the various factors relating to study design and participants’ characteristics.InterpretationTechnology‐based cognitive and exercise interventions can be effective in improving global cognition and core subdomains of cognition in persons with MCI. This review highlights the more superior effects of technology‐based cognitive stimulation combined with mind‐body exercise in improving global cognition.
Dual Perspectives
Authors: Ard Tyler , Pappas Ioannis 
Published: January 2025

Abstract“Dual Perspectives” integrates multiple MRI scans, creating a nuanced synthesis of grey matter and diffusion‐based regional connections. This rendering holds particular significance in the realm of Alzheimer’s and dementia research by offering a comprehensive examination of data crucial for understanding these complex neurodegenerative conditions.The inclusion of grey matter provides a detailed insight into the structural composition of the brain. Grey matter, comprised of neuronal cell bodies and dendrites, is fundamental to cognitive functions. High‐resolution grey matter imaging allows researchers to discern intricate structural alterations, contributing critical information about the anatomical changes associated with Alzheimer’s and dementia.Simultaneously, the image delves into the realm of diffusion‐based regional connections, derived from the movement of water molecules within the brain’s white matter pathways. Given the pivotal role these pathways play in transmitting signals between different brain regions, understanding diffusion‐based connections becomes essential in unraveling the intricacies of Alzheimer’s and dementia.The split harmonization of grey matter and diffusion‐based perspectives within this work offer a holistic view into the structural mediums of these neurodegenerative disorders. Overall, “Dual Perspectives” presents a lens into the intricacies of the brain, creating an artistic representation of neuroimaging‐derived data that is indispensable for advancing research in the field.
Bridging Academia and Community to Educate and Support Care Partners of People Living with Dementia
Authors: Webster Claire , Gauthier Serge , Rosa‐Neto Pedro , Morais José A 
Published: January 2025

AbstractBackgroundUniversities can play a very important role in providing post‐diagnosis dementia education and support to the community. The McGill University Dementia Education Program was founded in 2017 by Claire Webster, a former care partner and dementia care consultant with this aim. Mrs. Webster had no affiliation with the university prior to beginning the program other than being an annual guest lecturer on the topic of caregiving and dementia. Frustrated by the healthcare system, Mrs. Webster approached the university with an idea to introduce an innovative program centered on patient/care partner education using a multi‐disciplinary approach.MethodsThe program offers a comprehensive range of free resources and cutting‐edge teaching and learning techniques, including simulation to educate and support persons living with dementia, family and informal care partners, healthcare professionals, medical students and the public at large; a dementia companion guide available in 10 different languages with many more currently in translation; over 100 educational webinars and podcasts known as “McGill Cares”; virtual support groups for care partners; 14 bilingual video capsules demonstrating leisure and recreational activities and an online education program currently under development for care partners.McGill University has fully embraced the “person/patient centered care approach” into its medical curriculum by making in mandatory for all first‐year medical students to attend Claire Webster’s lecture on “Navigating the Journey of Caring for a Person Living with Dementia”.ResultsWithin only 5 years of its inception, the McGill University Dementia Education Program has received international recognition. The Academic and Medical Directors of the program (authors of this abstract) were selected by Alzheimer’s Disease International to write the 2021 and 2022 World Alzheimer’s Reports on the inter‐related topics of diagnosis and post‐diagnosis management. In 2023, Claire Webster was appointed to the Government of Canada’s Ministerial Advisory Board on Dementia.ConclusionUniversities can play a critical support role, bridging academia and community to provide service to society. They can institute community outreach programs that leverage the wealth of expertise within their institution, and they can integrate caregiver awareness and education into their medical school curriculum.
Young‐Onset Dementia and Career Development ♥ An Artsract
Authors: Allen Rachel Louise 
Published: January 2025

AbstractMy PhD research is about Young‐Onset Dementia and Career Development, focusing on women’s experiences.This artwork or abstract (‘artstract’) represents how the research has developed to date. Understanding of career is informed by Super’s (1980) Life‐Span, Life‐Space approach to career development, which can be understood flexibly to incorporate diverse experiences (including those of women and those living with a dementia diagnosis during working age).The sunshine, represented here as a ball of yarn (because yarn can be useful but can also unravel), represents the life stages of the approach, with the rainbow stripes below reflecting the Life Rainbow (Super, 1980). The woman’s face in silhouette (so the whole self cannot be seen) is decorated with painted flowers, building to a 3D representation around the brain and senses. This reflects the new beginnings and opportunities that can arise when living with dementia. However, several layers of paint, fabric and magazine collage are not visible because dementia can erode memories and abilities that the person can no longer utilise.The ’mess’ of collage and materials mixed with the simpler pencil lines represents the complexity of career. Whereas once this could be considered perhaps as linear, relating only to paid work and progression, this research conceptualises career more as life and work. When a woman is diagnosed with young‐onset dementia, this could impact several life stages and multiple roles in her life. She may be employed or retired, a carer for children, grandchildren or aging parents, and active in her community. Dementia is a condition with stigma, and this artstract challenges stereotypical assumptions and representations of dementia as something that only affects older people, or that those living with dementia do not have a career or that career cannot continue whilst living with a diagnosis. The bright colours were chosen to reflect the Life Rainbow (Super, 1980) and emphasise the experience of hope whilst living with a diagnosis.Super, Donald (1980) A Life‐Span, Life‐Space Approach to Career Development, Journal of Vocational Development 1980 Vol. 16 Pages 282‐298
Assessing the Influence of Modifiable and Non‐modifiable risk factors on Cognitive and Biomarker Trajectories in Preclinical Alzheimer's Disease: Establishing a Longitudinal Model for Brain Health
Authors: Maffei Luciana 
Published: January 2025

AbstractBackgroundThe pathogenesis of Alzheimer’s disease (AD) begins 15‐20 years before the onset of clinical symptoms, often referred to as the preclinical stage of AD. It is crucial to understand why some individuals develop AD and although biological, psychological, and social factors have been established, their influence in the very early stages of disease trajectories is somewhat unclear. Longitudinal studies are key to understanding how and when these risk factors determine brain health as well as the risk for developing AD later in life.MethodThis study will extract data from multiple DPUK and non‐DPUK longitudinal datasets containing lifestyle, psychological, environmental, social, and biological data from individuals as young as 18. The study will assess the relationship between a diverse range of biopsychosocial risk factors in the preclinical stage of AD and conduct machine learning statistical analyses to determine which and when these factors interact with biomarker activity contribute to disease risk.ResultsResults are expected to demonstrate a significant interaction between biopsychosocial risk factors and longitudinal biomarker activity in participants <55. Results are also expected to identify the age of biomarker change along with key predictors of initial disease trajectory.ConclusionResults from these longitudinal datasets may help with more accurate and earlier prediction tools across various populations and provide rationale to incorporate less understood psychosocial factors into these tools. The analysis will also inform the significance of modifiable factors so individuals can undertake their own preventative methods to reduce AD risk. The study may also have important implications for clinical trial design and promote healthy ageing.