bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term Diesel Exhaust Exposure Results in Neuroinflammation and White Matter Injury
Authors: Lamorie-Foote Krista , Shkirkova Kristina , Liu Qinghai , Sioutas Constantinos , Morgan Todd , Finch Caleb , Mack William 
Published: December 2021

Abstract
Ambient air pollution (AAP) exposure is associated with white matter injury and cognitive decline in older adults(Chen et al. 2020,Erickson et al. 2020). Neuroinflammation and oxidative stress may contribute to this white matter injury. Diesel exhaust particulate matter (DEP) is a neurotoxic component of AAP.This study characterizes the time course by which neuroinflammation/oxidative stress occurs and results in white matter injury following DE exposure in a murine model. DEP (Sigma) was re-aerosolized for exposure. Mice were exposed to 100 µg/m3 DEP or filtered air (FA) for 5 hours (n=8/group), 100 hours (n=6/group), or 200 hours (n=6/group). Immunohistochemical analysis of degraded myelin basic protein (dMBP), a marker of myelin damage, was performed. Neuroinflammation and oxidative stress were assessed by histological analysis of complement C5a, an anaphylatoxin, and 4-Hydroxynonenal (4-HNE), a marker of lipid peroxidation.dMBP integrated density was increased in the corpus callosum of DEP mice at 5 (p&lt;0.01), 100 (p&lt;0.01), and 200 hours (p&lt;0.001) compared to FA mice.C5a integrated density was increased in the corpus callosum of DEP mice at 5 (p&lt;0.01), 100 (p&lt;0.01), and 200 hours (p&lt;0.01) compared to FA mice. 4-HNE integrated density was increased in the corpus callosum of DEP mice at 5 (p&lt;0.001), 100 (p=0.001), and 200 hours (p&lt;0.001) compared to FA mice. Neuroinflammation and oxidative stress are upregulated with associated white matter injury in the corpus callosum after 5 hours of DEP exposure.Short-term DEP exposure activates inflammatory/oxidative stress pathways, which may contribute to the pathogenesis of white matter injury.Erickson et al. 2020,PMID:32182984; Chen et al. 2020,PMID:32669395.
Collection of Data on Persons Living With Dementia Who Go Missing: First Responder Perspectives
Authors: Neubauer Noelannah , Philip Serrina , Marshall Samantha Dawn , Daum Christine , Perez Hector , Miguel-Cruz Antonio , Liu Lili 
Published: December 2021

Abstract
While it is commonly cited that 60% of persons living with dementia (PLWD) wander, it is unclear whether this number reflects global contexts. Population aging has created a pressing need for the development of programs to mitigate the risks of PLWD from getting lost and going missing. Such programs would require a national strategy for the collection and integration of data on missing incidents involving this population. This study is a first step to inform such a strategy. The purposes were to: 1) identify approaches to data collection on missing persons incidents involving PLWD among Canadian police and search and rescue (SAR) organizations; 2) describe the foreseeable challenges associated with developing a national data collection strategy. We used generic qualitative description to generate data with fifteen key informants. Virtual semi-structured interviews were completed and transcribed verbatim. Content analysis and trustworthiness strategies guided analysis and rigor. Our findings indicate that police and SAR organizations collect a multitude of data pertaining to missing incidents involving PLWD. However, there is a lack of standardization in data collection, entry and analysis. Privacy legislation, limited resources, and incompatible data management systems pose challenges to data sharing and interoperability. Underreporting of missing incidents to police results in an underestimation of missing incidents. An intersectoral, uniform approach to data collection would enable the storage, analysis and comparison of national data. Accurate data on critical wandering can inform prevention, search strategies, resource allocation and effectiveness of programs.
Findings From RAISE Act Research: Family Caregiver Priorities
Authors: Nadash Pamela , Tell Eileen , Regan Carol , Jansen Taylor , Alberth Andrew , Cohen Marc 
Published: December 2021

Abstract
To understand the needs and policy priorities of family caregivers, the Advisory Council commissioned research: first, through a request for information (RFI) in the Federal Register, which garnered roughly 1600 responses. Qualitative analysis revealed that family caregivers have diverse needs spanning their financial security as well as their needs for caregiver-focused supports; recommendations were similarly diverse, including requests for caregiver pay, improved access to respite, and other major policy changes. These findings fed into 12 focus groups focusing on diverse populations of caregivers, yielding more depth around caregiver priorities. Six stakeholder listening sessions built on these results, aiming to develop concrete suggestions for a national caregiver strategy – a key outcome of the Advisory Council. Such strategies ranged from a major publicity campaign creating awareness of family caregivers, to suggestions on implementing caregiver assessments, to more ambitious goals such as improved financing for long term services and supports more broadly.
Involving Persons with Dementia in Social Research: A Literature Review
Authors: Manley Pamela , Kemp Candace 
Published: December 2021

Abstract
Abstract Studies involving persons with dementia as research participants have increased over the years, due in part to an emphasis on patient and public involvement in health care and participatory action research. Recent studies indicate a growing trend toward engaging persons with dementia, not only as participants, but also as co-researchers. Further, studies involving persons with dementia as co-researchers and advisers have garnered increased attention due to the inclusion of this population’s unique perspectives and lived experiences. Theoretically, frameworks such as person-centered- and relationship-centered care, also influence and shape the research process. This literature review examines empirical research conducted over the past decade that reports the involvement of persons with dementia as research participants (“research on”) and co-researchers and advisers (“research with”). Among the 27 articles identified, 12 reported “research on,” and 15 reported “research with” persons with dementia. “Research on” targeted participants’ emotional expressions/responses, engagement in exercise/activities; social environment influences, and cognitive training; whereas “research with,” which was mostly qualitative, focused on co-researchers’ perspectives of and experiences with the research process; needs, priorities, and recommendations in research planning; partnering with persons with dementia on the design and development of research instruments, and the importance of critically evaluating the research process. Findings documenting research challenges, complexities, and ethical concerns are also discussed. Overall, findings demonstrate the feasibility of involving persons with dementia in a meaningful way and further affirms that including them as co-researchers is not only beneficial, but has the potential to enhance the entire research process.
Factors Driving the Transition of Alzheimer’s Disease Patients to Institutional Long-term Care
Authors: Davila Heather , Jasuja Guneet , Moo Lauren , Palnati Madhuri , Shao Qing , Zhang Quanwu , Monfared Amir Abbas Tahami , Miller Donald 
Published: December 2021

Abstract
Progression of Alzheimer’s disease (AD) may ultimately lead to costly institutional long term care (ILTC) so its avoidance is often a goal of care management. We studied predictors of AD patients transitioning to ILTC in the Veterans Affairs healthcare system (VA). We identified 30,017 Veterans at least 50 years old, with ≥2 ICD-9/10-CM diagnosis codes for AD on separate days, with first AD code in 2013-2018, at least 2 years of prior continuous VA service use, and no prior ILTC. Patients who subsequently transitioned to ILTC (cases) were matched to other AD patients with the same time since first AD code but no ILTC (controls) (median of 13 months; mean age of 80.2 years). The 8,261 matched sets were split randomly to a training sample, where logistic and random forest regressions were used to develop models, and a validation sample, where final models were evaluated. Predictors of ILTC initiation included measures of (1) poor health, such as high morbidity counts (Elixhauser score of 15+, odds ratio=1.31) and weight loss (1.29), (2) heavy service use, such as hospitalization (2.25) and home health care (1.54), and (3) dementia symptoms, such as a diagnosis code for dementia not-otherwise-specified recorded well before the AD code (1.93), functional/mobility difficulties (1.35), and lifestyle or psychosocial problems (1.53). The full model C statistic was 0.78. Transition to ILTC in AD patients is driven by many factors, including comorbidities, need for acute care, nonspecific symptoms of dementias, and functional challenges. Targeted interventions may delay transitions to ILTC.
Time-Varying Insomnia Symptoms and Incidence of Cognitive Impairment and Dementia among Older US Adults
Authors: Resciniti Nicholas , Kase Bezawit , Yelverton Valerie , C. Lohman Matthew 
Published: December 2021

Abstract
There is conflicting evidence regarding the association between insomnia and the onset of mild cognitive impairment (MCI) or dementia. This study aimed to evaluate if time-varying insomnia is associated with the development of MCI and dementia. Data from the Health and Retirement Study (n = 13,833) from 2002 to 2014 were used (59.4% female). The Brief Insomnia Questionnaire was used to identify insomnia symptoms compiled in an insomnia severity index, ranging from 0 to 4. In the analysis, participants’ symptoms could vary from wave-to-wave. Dementia was defined using results from the Health and Retirement Study (HRS) global cognitive assessment tool. Respondents were classified as either having dementia, MCI or being cognitively healthy. Cox proportional hazards models with time-dependent exposure using the counting process (start-stop time) were used for analysis. For each one-unit increase in the insomnia symptom index, there was a 5-percent greater hazard of MCI (HR = 1.05; 95% CI: 1.04–1.06) and dementia (HR = 1.05; 95% CI: 1.03–1.05), after fully adjusting. Using a nationally representative sample of adults aged 51 and older, this study found that time-varying insomnia symptoms are associated with the risk of MCI and dementia. This highlights the importance of identifying sleep disturbances and their change over time as potentially important risk factors for MCI and dementia.
In Their Own Words: A Study on COVID-19-Related Concerns and Perceptions of Risk Among Older University Employees
Authors: Sokan Amanda , Yuan Nicole , Felix Mariana , Wager Mark , O'Neill Lisa , Chen Zhao 
Published: December 2021

Abstract
The purpose of this qualitative study was to examine COVID-19-related concerns and risk perceptions among older employees aged 50+ related to reopening a large state university campus during the COVID-19 pandemic. Recruitment focused on older employees from diverse backgrounds and job classifications. Six focus group interviews, with a total of 24 participants, were conducted using Zoom video conferencing. Interviews were transcribed using Zoom and were double-checked for accuracy. Transcripts were coded and analyzed using ATLAS.ti 9 after establishing inter-rater reliability among two coders. During the campus reopening, older employees reported several concerns and perceptions of risk focused on COVID-19 exposure and transmission to others, individual health and health of other household members, mental health and stress, and job security. Findings were used to inform the development of intervention strategies and resources to promote the health and well-being among older employees during the pandemic.
Improving Care for Persons With Cognitive Impairment in Community-Based Long-Term Care and Acute Care Settings
Authors: Wang Jing , Wu Bei 
Published: December 2021

Abstract
The COVID-19 pandemic has highlighted the importance of providing person-centered care for our vulnerable populations across the globe. This symposium focuses on improving care for persons with cognitive impairment and dementia in various care settings. The first study explored dyadic experiences of living with early-onset dementia pre and during COVID-19 in China through a person-centered care lens. The second concept analysis presented four interrelated dimensions of Asian American caregiver support, including individual, family, community, and professional health system. The third study investigated undergraduate nursing students’ attitudes toward pursuing jobs of providing care for older adults with dementia in rapidly-aging urban areas in China and its associated factors. The fourth study examined the impact of social isolation on cognitive function and Quality of Life among acute ischemic stroke (AIS) patients in China. The last study explored an association between perceived control and cognitive function among acute ischemic stroke (AIS) patients in China. The last two studies suggested that perceived control and social isolation may be potential targets in cognitive interventions for AIS patients. This symposium presents the understanding of dementia caregiver support, the empirical evidence of living with dementia, the attitudes towards dementia care among the next generation of nursing workforce, and the impact of social factors on cognitive functions longitudinally. The presenters emphasize the importance of improving care in long-term care and acute care settings. There is a need to design person and family-centered care to improve health and wellbeing of persons with cognitive impairment.
Insertion of the protective APP A673T mutation by CRISPR/Cas9 base editing or PRIME editing.
Authors: Tremblay Jacques , Guyon Antoine , Rousseau Joël , Tremblay Guillaume , Begin Francis-Gabriel , Lamothe Gabriel 
Published: December 2021

Abstract
There is currently no treatment for Alzheimer disease (AD). However, the Icelandic mutation in the APP gene (A673T) has been shown to confer a protection against the onset and development of AD (Jonsson et al. Nature 2012). This single nucleotide mutation in APP exon 16 reduces the cleavage of the APP protein by the beta-secretase by 40% thus preventing the development of AD even in persons more than 95 years old. Our research group has initially shown that the presence of the A673T mutation in an APP gene reduced the secretion of beta-amyloid peptides even if there is also a FAD mutation in the gene. This is the case for 14 different FAD mutations. We have used CRISPR/Cas9 base editing and PRIME editing technologies to insert the A673T mutation in the APP gene. We have compared several different cytidine base editor complexes to achieve the most effective and accurate genome modification possible in HEK293T cells and in SH-SY5Y neuroblastomas. The insertion of the A673T mutation in cells containing the London mutation reduced the secretion of beta-amyloid peptides. We are currently using lentiviral vectors to infect neurons from a mouse model and human neurons induced from fibroblasts of a patient with the London mutation. The insertion of the protective Icelandic mutation in the APP gene using these editing technologies opens a new potential therapeutic avenue not only for Familial Alzheimer’s diseases but also for sporadic Alzheimer’s disease.
Exploring Health in the UK Biobank: Sociodemographic, Psychosocial, Lifestyle and Environmental Factors
Authors: Mutz Julian , Roscoe Charlotte , Lewis Cathryn 
Published: December 2021

Abstract
A greater understanding of factors associated with favourable health may help increase longevity and healthy life expectancy. We examined sociodemographic, psychosocial, lifestyle, and environmental exposures associated with multiple health indicators. The UK Biobank study recruited &gt;500,000 participants, aged 37-73, between 2006–2010. Health indicators examined were 81 cancer and 443 non-cancer illnesses used to classify participants by health status; long-standing illness; and self-rated health. Exposures were sociodemographic (age, sex, ethnicity, education, income and deprivation), psychosocial (loneliness and social isolation), lifestyle (smoking, alcohol intake, sleep duration, BMI, physical activity and stair climbing) and environmental (air pollution, noise and residential greenspace) factors. 307,378 participants (mean age = 56.1 years [SD = 8.07], 51.9% female) were selected for cross-sectional analyses. Low income, being male, neighbourhood deprivation, loneliness, social isolation, short or long sleep duration, low or high BMI and smoking was associated with poor health. Walking, vigorous-intensity physical activity and more frequent alcohol intake was associated with good health. There was some evidence that airborne pollutants (PM2.5, PM10, and NO2) and noise (Lden) were associated with poor health, though findings were not consistent across all models. Our findings highlight the multifactorial nature of health, the importance of non-medical factors, such as loneliness, healthy lifestyle behaviours and weight management, and the need to examine efforts to improve health outcomes of individuals with low income.
Urolithin A enhances muscle performance in elderly and positively impacts biomarkers linked to cellular health
Authors: Liu Sophia , Marcinek David 
Published: December 2021

Abstract
Background: Aging is associated with decline in mitochondrial function and reduced exercise capacity. Urolithin A (UA) is a natural gut metabolite shown to stimulate mitophagy and improve muscle function in aged animals, and induce mitochondrial gene expression in elderly. Purpose: Investigate if oral administration of UA improved walking distance (6MWT), muscle fatigue resistance in hand (FDI) and leg (TA) muscles, and had an impact on plasma biomarkers. Method: We conducted a randomized, double-blind, placebo-controlled study (NCT03283462) in elderly subjects (65-90 yrs.) supplemented daily with 1000mg UA or placebo for 4 months. 128 subjects were screened and 66 randomized. 6MWT and ATPmax via MRS were assessed at baseline and at 4 months. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 and 4 months. Results: UA significantly improved muscle endurance (i.e., change in number of muscle contractions from baseline) in two different muscles (hand: PL 11.6 ±147.5, UA 95.3 ± 115.5; and leg: PL 5.7± 127.1, UA 41.4 ±65.5) compared with placebo at 2-months. Plasma levels of several acylcarnitines, ceramides and C-reactive-protein were decreased by UA at the end-of study. 6MWT distance (PL 42.5 ± 73.3 m, UA 60.8± 67.2 m) and ATPmax increased in both groups from baseline (PL 13.7±31.4%, UA19.4± 56.8%) with UA supplemented group exhibiting greater improvements, although these were not statistically different between groups. Conclusion: UA supplementation improved muscle endurance, metabolic and inflammatory plasma biomarkers after 2-months, suggesting that UA can have a positive impact on muscle and cellular health in the elderly.
Analysis of DGAT2 mutations reveals potential links between cancer and lipid droplet deregulation
Authors: Graber Meghan , Barta Hayley 
Published: December 2021

Abstract
Diacylglycerol O-acyltransferase 2 is a transmembrane protein encoded by the DGAT2 gene that functions in lipid metabolism, triacylglycerol synthesis, and lipid droplet regulation. Since cancer cells exhibit altered lipid metabolism, it has been proposed that mutations in DGAT2 may contribute to this state. Using data from the Catalogue of Somatic Mutations in Cancer (COSMIC), we analyzed all reported DGAT2 mutations in human cancers. Bioinformatics analyses were performed to highlight the connections between age, pathogenicity, and cancer tissue type. Mutations are generally associated with samples from older individuals, except for those in glioblastomas which occur earlier. We also found that several DGAT2 mutations fall within the catalytic site of the enzyme and may affect enzyme function. Thus, these mutations may contribute to altered cancer metabolism. We identified D222V as a mutation hotspot neighboring a previously discovered Y223H mutation that causes Axonal Charcot-Marie-Tooth disease. Remarkably, Y223H has not been detected in cancers indicating it is inhibitory to cancer progression. Further analysis showed that most mutations do not affect DGAT2 gene expression suggesting this change is not a major contributor to cancer development. Intriguingly, although most cancers are characterized by low DGAT2 gene expression, some show high expression levels, indicating that, at least in certain cases, over-expression is not inhibitory to cellular proliferation. This work uncovers unknown roles of DGAT2 in cancers and suggests that its function may be more complex than previously appreciated.
In silico identification of anti-aging pharmaceutics from community knowledge
Authors: Beck Samuel , Lee Jun-Yeong , Rollins Jarod 
Published: December 2021

Abstract
In this era of Big Data, the volume of biological data is growing exponentially. Systematic profiling and analysis of these data will provide a new insight into biology and human health. Among diverse types of biological data, gene expression data closely mirror both the static phenotypes and the dynamic changes in biological systems. Drug-to-drug or drug-to-disease comparison of gene expression signature allows repurposing/repositioning of existing pharmaceutics to treat additional diseases that, in turn, provides a rapid and cost-effective approach for drug discovery. Thanks to technological advances, gene expression profiling by mRNA-seq became a routine tool to address all aspects of the problem in modern biological research. Here, we present how drug repositioning using published mRNA-seq data can provide unbiased and applicable pharmaco-chemical intervention strategies to human diseases and aging. In specifics, we profiled over a half-million gene expression profiling data generated from various contexts, and using this, we screened conditions that can suppress age-associated gene expression changes. As a result, our analysis identified various previously validated aging intervention strategies as positive hits. Furthermore, our analysis also predicted a novel group of chemicals that has not been studied from an aging context, and this indeed significantly extended the life span in model animals. Taken together, our data demonstrate that our community knowledge-guided in silico drug-discovery pipeline provides a useful and effective tool to identify the novel aging intervention strategy.
Interpretable Machine Learning of High-Dimensional Aging Health Trajectories
Authors: Farrell Spencer , Mitnitski Arnold , Rockwood Kenneth , Rutenberg Andrew 
Published: December 2021

Abstract
We have built a computational model of individual aging trajectories of health and survival, that contains physical, functional, and biological variables, and is conditioned on demographic, lifestyle, and medical background information. We combine techniques of modern machine learning with an interpretable network approach, where health variables are coupled by an explicit interaction network within a stochastic dynamical system. Our model is scalable to large longitudinal data sets, is predictive of individual high-dimensional health trajectories and survival from baseline health states, and infers an interpretable network of directed interactions between the health variables. The network identifies plausible physiological connections between health variables and clusters of strongly connected heath variables. We use English Longitudinal Study of Aging (ELSA) data to train our model and show that it performs better than traditional linear models for health outcomes and survival. Our model can also be used to generate synthetic individuals that age realistically, to impute missing data, and to simulate future aging outcomes given an arbitrary initial health state.