bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Asian Americans’ awareness and interest in clinical research: Examining the role of culturally tailored messaging
Authors: McGowan Melissa , Jarvis‐Gibson Jeanne , Bui Elise , Rehberg Kathryn , Mitchell Alexandra , Manohar Rhea , Simoneau Elizabeth , Miscally Memi , Massett Holly A 
Published: June 2023

AbstractBackgroundAsian Americans and Pacific Islanders (AAPI) are one of the fastest‐growing populations in the United States, yet these communities comprise less than one percent of participants in NIH’s Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) clinical research. This underrepresentation is due to numerous barriers well‐documented in the literature, with a key deterrent being a lack of culturally and linguistically appropriate outreach materials. This abstract presents findings from focus groups conducted by the National Institute on Aging (NIA) to identify culturally and linguistically appropriate message concepts that raise awareness, address barriers and motivate Asian American and Pacific Islanders to consider participation in AD/ADRD research studies.MethodEighteen virtual focus groups (N = 103 individuals) were conducted with Chinese Americans, Filipino Americans, and Indian Americans who are at‐risk for AD/ADRD or are caregivers to people living with dementia. Focus groups were conducted in Chinese, Hindi, Tagalog and English. The sessions tested multiple audience‐tailored message concepts designed to increase interest and encourage participation in AD/ADRD clinical research. These discussions also examined participants’ preferred language, terminology and communication approaches.ResultOverall, message concepts that 1) emphasized the value of caring for family members; 2) offered a sense of hope; 3) communicated a clear call to action; and 4) provided opportunities to learn more information about clinical research resonated across all groups. Between participant audiences, there were some important differences, including around terminology preferences. For example, Chinese‐American participants expressed concern about the term “caregiver” as it implied that taking care of a loved one was a burden or a professional job, rather than a familial responsibility. Concept visuals will be presented.ConclusionThis research conducted by NIA improves our understanding of messaging concepts that do and do not resonate with AAPI, providing valuable insight into themes that should be leveraged to effectively promote awareness about AD/ADRD clinical research with these communities. The finding from this study were used to develop, finalize and make available to the research community a suite of culturally and linguistically appropriate materials to increase awareness and interest in AD/ADRD clinical research among AAPI communities.
Understanding counseling challenges of dementia risk prediction through discourse‐linguistic approaches – the media perspective of the PreTAD study
Authors: Schwegler Carolin , Werken Katrin , Snijders Katharina Elisabeth , Stümpel Johanne , Rostamzadeh Ayda , Ribaldi Federica , Marquié Marta , Schmitz‐Luhn Björn , Boada Mercè , Frisoni Giovanni B , Jessen Frank , Woopen Christiane 
Published: June 2023

AbstractBackgroundDiagnostics for early detection of Alzheimer’s disease (AD), using biomarkers, and dementia risk prediction are constantly evolving which will eventually lead to an extended availability even for symptom‐free individuals. These developments of predictive medicine are changing medical procedures and ways of thinking as well as opportunities for patients. Furthermore, they are slowly exerting influence on public attitudes towards medicine. The PreTAD project aims at providing insights on people’s perspectives towards prediction as well as the effect of predictive medicine on individuals and society from a clinical, ethical, legal and linguistic point of view.MethodIn the linguistic part of the PreTAD study, we address the fact that patients and their relatives bring common knowledge, discursive arguments and attitudes – and thereby certain expectations – into the doctor‐patient‐interaction, for example into a counseling visit for predictive interventions. Among personal sources, the origin and distribution of that knowledge can be the public media discourse (online and offline). On the basis of an empirical linguistic media analysis (German, English), we seek to determine public knowledge about AD and dementia risk prediction before we aim to elaborate communicative patterns and influential arguments of the public discourse on this topic.ResultThe findings of the linguistic approach of the PreTAD study contribute to the understanding of people’s perspectives, preconceptions, stereotypes, expectations and hopes regarding dementia risk prediction. To ensure good clinical practice regarding predictive interventions, especially in pre‐symptomatic at‐risk stages, the latter have to be acknowledged and carefully negotiated in doctor‐patient‐interaction.ConclusionA closer look at public knowledge, influential communicative patterns and attitudes towards AD, early detection diagnostics, and dementia risk prediction can shed light on the broader context of present counseling challenges.
Extended insight into selective vulnerability of neurons in AD using machine learning approach
Authors: Srivastava Gyan P 
Published: June 2023

AbstractBackgroundAlzheimer’s disease is characterized by the spread of tau pathology and loss of neurons with a specific spatio‐temporal pattern. Recent publications have attempted to uncover the identity of the selectively vulnerable neurons using single‐nucleus transcriptomic data derived from affected brain regions from patients with Alzheimer’s disease. Correlating advancing tau pathology as measured by Braak staging with neuronal loss, one of the major markers reported for the susceptible excitatory neurons was RORB, which was also validated using quantitative neuropathological methods. However, the heterogeneity of RORB expression in the highlighted clusters suggested that not all RORB expressing neurons may be susceptible. Besides, further classifying neuronal population into sub‐populations shows population specific RORB expression.MethodTherefore, we further extended our insight into selective vulnerability of neuronal sub‐populations using a machine learning (ML) approach. We identified a transcriptionally homogeneous population using ML‐based classifiers with high accuracy and AUC > 0.90.ResultOur analysis shows that fine mapping of transcriptionally similar neurons is key to pinpoint sub‐populations that are selectively lost during later Braak stages. For instance, refined sub‐population analysis revealed that neuronal populations with moderate RORB expression were lost while those with higher RORB expression do not show significant change with advancing Braak stage.ConclusionOur analysis provides a reference of neuronal sub‐populations and associated markers that could be further interrogated to uncover potential mechanisms that underlie selective degeneration in Alzheimer’s Disease.
G protein‐biased GPR3 signaling induces glial activation and ameliorates amyloid pathology in a preclinical Alzheimer’s disease mouse model
Authors: Thathiah Amantha , Huang Yunhong , Huang Yunhong , Guimaraes Thais Rafael , Todd Nicholas , Ferguson Carolyn , Weiss Kathryn , Stauffer Fiona , McDermott Breanne , Hurtle Bryan T. , Saito Takashi , Saido Takaomi , MacDonald Matthew L , Farris Sean P. , Homanics Gregg E. 
Published: June 2023

AbstractBackgroundBiased G protein‐coupled receptor (GPCR) ligands preferentially activate G protein‐ or β‐arrestin signaling pathways and are leading to the development of drugs with superior efficacy and reduced side‐effects in heart disease, pain management, and neuropsychiatric disorders. Although GPCRs are implicated in the pathophysiology of Alzheimer’s disease (AD), biased GPCR signaling is an unexplored area of investigation in AD. Previous work demonstrated that Gpr3 deficiency ameliorates amyloid‐β (Aβ) pathology. However, Gpr3‐deficient mice display several adverse phenotypes, including elevated anxiety‐like behavior, reduced fertility, and memory impairment, which are potentially associated with impaired G protein‐signaling. We hypothesized that generation of a G protein‐biased GPR3 mouse model, which maintains G protein‐signaling while eliminating β‐arrestin signaling, would attenuate AD‐associated phenotypes while preserving the beneficial effects of GPR3‐mediated G protein‐signaling.MethodsWe used a CRISPR/Cas9 genome‐editing strategy to develop two novel G protein‐biased GPR3 mouse models. We utilized a broad range of molecular, cellular, and biochemical methodologies, including mass spectrometry, immunoblot and immunohistochemical analyses, RNA profiling, and behavioral testing to determine the physiological relevance of G protein‐biased GPR3 signaling in naïve mice and in the preclinical AppNL‐G‐F AD mouse model.ResultsWe determine that, in contrast to Gpr3‐deficient mice, G protein‐biased GPR3 mice do not display elevated anxiety levels, reduced fertility, or cognitive impairment. We then established that GPR3 is expressed in neurons, microglia, and astrocytes and is associated with cell‐type‐specific effects on AD pathogenesis. Accordingly, we determine that G protein‐biased signaling leads to a reduction in Aβ generation in neurons, the activation and hypertrophy of disease‐associated‐microglia (DAM) and pan‐reactive astrocytes, and to an increase in amyloid plaque compaction in AppNL‐G‐F mice.ConclusionsThese studies provide the first demonstration of G protein‐biased signaling in neuronal regulation of Aβ generation and microglial and astrocytic regulation of neuroinflammation in a preclinical AD mouse model and open an exciting area of investigation on biased agonism as a therapeutic intervention strategy for AD.
Care management needs of family caregivers at different stages of dementia
Authors: Huang Huei‐Ling , Shyu Yea‐Ing L , Hsu Wen Chuin 
Published: June 2023

AbstractBackgroundIn Taiwan, more than 90% of persons with dementia who live at home are cared for by family caregivers. According to previous researches, family caregivers of dementia have a higher level of burden than almost all other diseases of old age. In addition, due to the different courses of dementia in each stage, coupled with the complexity of its problems, persons with different stages of dementia have different care demands. Therefore, this study aimed to explore the care management needs of family caregivers caring for persons with dementia at different stages.MethodA cross‐sectional study was conducted. Of the 250 family caregivers of persons with dementia were included. The Care Management Needs Scale (CMNS) was used to measure the care management needs of family caregivers, which is divided into six dimensions of needs (care service, psychological support, immediate information, anticipated information, referral and tracking of long‐term care resources, and individual case management service). The severity of dementia was determined by a neurologist using the Clinical Dementia Rating (CDR) scale.ResultFrom very mild dementia to severe dementia, the dimension with the highest needs at each stage are individual case management service, immediate information, referral and tracking of long‐term care resources, and care service, respectively. The overall needs, care service and psychological support in moderate dementia are significantly higher than very mild dementia. According to the needs of each item, the three highest needs are related to the dimension of immediate information and individual case management service in very mild dementia and mild dementia; in the case of moderate to severe dementia, care service began to appear in the three highest needs.ConclusionThe study concluded that different stages of dementia have different care management needs. When moderate dementia (CDR = 2.0), the need for care services will begin to increase. The findings suggest that care management should be provided for different stages of dementia. This study’s results provide a knowledge base for designing dementia stage‐specific care management in clinical practice and developing community‐based, long‐term care systems for family caregivers of persons with dementia.
Dietary pattern and brain structure among young adults
Authors: Thomas Aline , Labache Loïc , Tsuchida Ami , Arsandaux Julie , Zago Laure , Tzourio Christophe , Crivello Fabrice , Samieri Cécilia 
Published: June 2023

AbstractBackgroundEnvironmental factors, such as nutrition, influence brain physiology and health throughout the life course. While research has focused on the extremes of the age spectrum, less is known about early adulthood, yet a critical period for the consolidation of brain maturation and the building of adult behaviors. Nutrition may impact late maturational changes in the post‐adolescent brain and contribute to the degree of brain reserve that minimizes the risk to develop dementia. We took advantage of a large sample of young adults to evaluate the association of dietary behavior with brain structure characteristics.MethodThis cross‐sectional study included 1721 university students (18‐35 years‐old) from the French i‐Share cohort, who underwent brain MRI. A 12‐item online Food Frequency Questionnaire was used to evaluate consumption in major food groups and to determine dietary patterns from Principal Component Analysis (PCA). Multivariable‐adjusted linear regressions were used to estimate the association of PCA scores with brain structure (cortical thickness and surface area, grey matter and white matter volumes, diffusion parameters).ResultThe first PCA component (explained variance, 17%) contrasted a healthy diet (higher fruit and vegetable intakes) to a poor diet (higher fast food, sugary drink and snack consumptions). In models adjusted for total intracranial volume, age, sex, physical activity, body mass index, alcohol and tobacco consumptions, a higher PCA score (reflecting healthier diet) was associated with lower total gray matter volume (β for 1 point score = –0.17 [95%CI, –0.31; –0.03] cm3), in various brain areas (Figure). Healthy diet was also associated with lower global white matter volume (β = –0.18 [–0.32; –0.03] cm3). No association was found with diffusion tensor imaging, and neurite orientation dispersion and density imaging metrics in the white matter.ConclusionIn this large sample of young adults, healthier diet was associated with lower brain volumes, independent of multiple potential confounders. Gray matter volume loss during post‐adolescence is a marker of brain maturation; thus, environmental factors emphasizing this loss may benefit maturation. Our results raise the hypothesis that a healthy diet may favor and a poor diet may hamper brain maturation; an assumption which deserves further investigation in other populations.
Alpha‐secretase ADAM10 as a blood‐based biomarker in Alzheimer’s disease and type 2 diabetes mellitus
Authors: de Oliveira Danielle dos Santos Maia Salheb , Grigoli Marina Mantellatto , Cominetti Marcia Regina 
Published: June 2023

AbstractBackgroundAD (Alzheimer’s disease) is a progressive neurodegenerative disease characterized by extensive neuronal losses and deposits of neurofibrillary tangles and senile plaques. Patients with T2DM (type 2 diabetes mellitus) have structural brain changes and cognitive impairment, with a high risk of developing AD. These data suggest that insulin may play a key role in brain activity and memory formation. Based on these findings, AD has been called by some researchers T3DM (type 3 diabetes mellitus) or cerebral diabetes. Our group has been studying peripheral biomarkers for AD since 2010. Among them, our focus is the study of ADAM10 (A Disintegrin And Metalloprotease), an α‐secretase that inhibits the formation of senile plaques and, therefore, is protective against AD. We observed that this protein is decreased in platelets and increased in plasma of elderly people with this dementia compared to cognitively healthy elderly people.MethodThe participants of this research were people aged 60 or over, divided into 4 groups: participants with AD, participants with T2DM, participants with AD and concomitant presence of T2DM and cognitively unimpaired (CU) controls with regular plasma glucose levels. In this work, due to the COVID‐19 pandemic, we are presenting the results of a pilot trial carried out with data collected from 9 participants in each group. Patients’ blood was collected and plasma was used in assays to determine ADAM10 levels using an ADAM10‐specific Enzyme‐Linked Immunosorbent Assay (ELISA) kit (Life Sciences, catalog number LS‐F23768). Results were confirmed using SDS‐PAGE followed by western blotting analyses with the primary antibody anti‐ADAM10 (Ab39180 rabbit, Abcam). A “young control” performed with plasma samples from a young donnor and soroalbumin bands were used as endogen controls to avoid interassay biases in the densitometry analyses.ResultPlasma ADAM10 was elevated in persons with AD and T2DM and these levels were even higher when plasma from patients with both diseases was analysed.ConclusionThis study shows a clinical impact related to a new approach that could be used in the treatment of AD, also observing the metabolic and inflammatory states of the patients. Study also contributes to a better understanding of the biology of the disease itself.
Dementia increases medical costs and length of hospital stay of motorcycle crash‐related hospitalizations: A nationwide population‐based cohort study in Taiwan
Authors: Liu Chih‐Ching 
Published: June 2023

AbstractBackgroundPrior studies showed dementia had a higher risk of hospitalization for a motor vehicle accident injury than the general population. However, the effect of dementia on the medical cost and length of inpatient days of motorcycle crash‐related hospitalizations still unknown. This study describes the total amount of medial cost and length of inpatient days for motorcycle crash‐related hospitalizations among patients with and without dementia and assesses whether dementia is related to a higher medical cost and length of inpatient days for motorcycle crash‐related hospitalizations.MethodThis was a population‐based, retrospective cohort study. Dementia aged 40‐64 and its age‐ and sex‐ matched participants without dementia were identified when they had the first hospitalization for MVAI. Data were obtained from the Taiwan National Health Insurance Research Database entries and Taiwan Police‐reported Traffic Accident Registry between 2006 and 2015. Linear regression with generalized estimating equations were applied to compare the medical cost and length of inpatient days of people with and without dementia.ResultOver the 10‐year follow‐up periods, the mean medical expenses related to the first hospitalization for MVAI among patient with and without dementia was NTD $ 81207±136647 and NTD $ 58947±135543, respectively, with a difference in log10 average inpatient costs of NTD $ 0.082 (95%CI 0.054‐0.110). Additionally, compared to patients without dementia, patients with dementia were significantly related to a longer inpatient stay due to the first hospitalization for MVAI (11.6±15.9 vs. 9.0±32.3 days), with a difference in log10 average inpatient days of 0.054 days (95%CI 0.029‐0.078).ConclusionIn motorcycle crash‐related hospitalizations, dementia was associated with higher medical cost and longer length of inpatient stay than those for patients without dementia.
Combining data and mathematical models for the design of personalised light interventions to improve sleep timing in aging
Authors: Rodriguez Thalia , Cleator Sean F , Monica Ciro Della , Revell Victoria Louise , Dijk Derk‐Jan , Skeldon Anne C 
Published: June 2023

AbstractBackgroundMore than 70% of people living with dementia (PLWD) experience sleep disturbances (e.g., early bedtime, long time in bed) even in the early stages of cognitive decline. Light interventions have been proposed as a promising non‐pharmacological approach to improve sleep timing, but current implementations are burdensome and not personalised. Quantitative tools for designing pragmatic light interventions for the home‐setting could benefit PLWD and their carers.Here, we report on a quantitative computational tool which combines readily collectable data with a new mathematical model to provide personalised advice on light interventions. Our focus is on designing low‐burden interventions requiring minimal changes to lifestyle or sleep‐wake routines.MethodEighteen older adults (65‐80 y) monitored their light exposure and sleep for a period of 7‐10 days at home using a wristworn monitor (Actiwatch Spectrum) and a sleep diary from which we calculated daily sleep timing and duration.We constructed a new mechanistic mathematical model for sleep timing that incorporates sleep homeostasis, circadian rhythmicity and light data (HCL). For each participant, we fitted the model to their sleep timing and duration data. We then used simulations to predict the effect of different light interventions on sleep timing and used optimisation to determine light exposure patterns that promote a target sleep onset time.ResultIndividuals varied in their sleep duration (07:18 ± 0:56 hh:mm; mean ± SD) and mid‐sleep timing (03:22 ± 01:00 hh:mm). We successfully retrieved ‘personal’ model parameters that accurately captured sleep duration and timing for 17 of the 18 participants. Our simulations indicated that the effect of a given light exposure pattern on sleep timing depends on the personalised model parameters, suggesting that an intervention that works for one person may not work for someone else. We were able to propose light exposure patterns requiring minimal behavioural change, facilitating adherence.ConclusionIt is possible to extract individual physiological parameters for sleep‐wake regulation from data collected in the field. These individual parameters can be used to design personalised light interventions. Our fully‐documented code could be combined with passive sleep monitors and environmental light sensors to unobtrusively recommend personalised light exposure patterns in close‐to real time.