bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIFFERENCES OF RANKINGS IN DEATH CERTIFICATES AMONG PERSONS WITH ALZHEIMER’S DISEASE
Authors: Brown Candace , Pan Yinghao , Miller Maggi , Lohman Matthew 
Published: January 2025

Abstract
A 2021 report indicates that 19.1% of people ages 76-84 and 34.6% of people aged 85 and older have Alzheimer’s disease (AD). Data provided on death certificates using the International Statistical Classification of Diseases is guided by the WHO for coding cause and contributing comorbidities of death. Death rankings assist in monitoring which diseases need attention for better informed decision making in healthcare. However, classifying immediate cause of death presents challenges when the likelihood of polymorbidity occurs with advancing age in patients with presenting AD but inconclusive diagnoses of the disease. We used the Alzheimer’s Disease and Related Dementia South Carolina (SCADR) registry and linked it with state death certificates to examine sociodemographic variables and survival probabilities of decedents between the years 2014-2019. Cox proportional hazards models were fitted and hazard ratios (HRs) computed, adjusting age at diagnosis and race. Turnbull’s method estimated the survival probabilities or curves for subgroups as the time from AD diagnosis to death. Of the 78,534 patients in the study 94% were diagnosed with AD at age 61 or older. AD was listed as the immediate cause of death among all racial groups, except for Native American/American Indian, contrasting from previous research of underreporting of the disease by factor of 2.7 with underestimations more likely for people identifying as Black and Latino. However, only 1.4% had a conclusive diagnosis of the disease by autopsy. Survival probabilities drop precipitously in the first few years after diagnosis with only 25% of the cohort surviving beyond 5 years.
CHARACTERIZING PROTEIN STRUCTURES IN BETA-AMYLOID TREATED NEURONS WITH LIMITED PROTEOLYSIS-MASS SPECTROMETRY
Authors: Anderson-Steward Kuren , Hao Ying , Guha Deyaan , Li Ziyi , Jin Benjamin , Singleton Andrew , Qi Andy 
Published: January 2025

Abstract
Limited Proteolysis by Mass Spectrometry (LiP-MS) is a technique used to observe the structural changes of proteins on a proteome-wide scale. Limited proteolysis consists of a specific, or limited, number of proteases performing hydrolyzation on a large portion of proteins. This causes the protease to detect the weak portion of the hydrolyzed protein and cut it out. The technique of limited proteolysis coupled mass spectrometry aims to alleviate the limitations of classic proteomic analysis, such as being unable to detect protein structural alterations on a wide scale and at high throughput. In this experiment, we used iPSC-derived neurons treated with beta-amyloid and performed classic proteomics and LiP-MS in parallel to observe the proteome scale of structural changes caused by beta-amyloid. Through experimentation, it was found that the control group consisted of 180 protein profiles that the beta-amyloid treated group did not possess using the limited proteolysis-mass spectrometry technique. Additionally, various cleavage sites by proteinase K in the beta-amyloid treated neurons compared to the control neurons, as well as multiple molecular pathways, such as neuron projection cytoplasm, were identified.
CROSSTALK BETWEEN HYALURONAN AND ITS REGULATORS AFFECTS AGING
Authors: Basu Kaustuv , Heldin Paraskevi 
Published: January 2025

Abstract
The regulation of extracellular matrix (ECM) turnover is crucial in aging. Hyaluronan (HA) is a large, viscoelastic polysaccharide and a major component of ECM. It lubricates and organizes tissue structure in different body parts (e.g. skin) and orchestrates multiple cellular functions through its receptors CD44 and RHAMM and binding proteins. HA is synthesized by HA synthase (HAS). The synthesis of HA in the longest-lived rodent naked mole rat (NMR) and the extended lifespan of a transgenic mouse overexpressing the NMR-HAS2 gene illustrates the importance of HA in longevity. HA level is significantly modulated with increasing age. Thus, understanding the complex crosstalk between HA and its regulators is crucial to regulating aging. Here, we revealed a vital connection between the function of p53 and its paralogue p63 and HA biosynthesis and CD44 signaling. Previously, it was reported that p53 suppressed the expressions of CD44 and RHAMM. We identified that CD44 interacted with the apoptosis-stimulating protein of p53 (iASPP) and affected p53-mediated apoptosis. We also revealed that the mutant p53 suppressed HAS2 and -3 mRNA expression. The mutation status of endogenous p53 and the balance between p53 and p63 levels affected HAS2 and HAS3 expression differently after TGF-β1 stimulation. We noticed that the activation of p63 and Ras was essential for regulating HAS and CD44 without TGF-β1 stimulation. We observed the importance of the HA receptor in regulating aging and aging-related disease. Our study unveiled the significance of the interplay between HA and its regulators, vital in understanding the complex aging process.
DEVELOPMENT OF SCAFFOLD FOR A ISCHEMIC STROKE MICROFLUIDIC CHIP PLATFORM
Authors: Agbomi Lidadi , Nathaniel Thomas , Goodwin Richard , Gao Bruce 
Published: January 2025

Abstract
Age-related brain diseases are rising, with strokes, especially ischemic strokes (IS), being a leading cause of death. Accurate modeling of IS is crucial for diagnosis, but animal models have limitations. When creating a new, human, cell-based microfluidic chip platform for modeling IS, a suitable 3D scaffold for cell growth is essential. For this, we chose to generate a 3D scaffold using a hydrogel platform that contains microchannels that will model the cerebral vasculature. 3D Agarose hydrogels were fabricated for testing. Hydrogels of 0.5%, 1%, and 2% agarose were polymerized according to the manufacturer’s protocol. Hydrogels were placed in a 60mm Petri dish. Testing was done on each hydrogel to determine the best agarose concentration after frozen for 10, 15, and 20 hours, then lyophilized for 8 hours. This method helped make the hydrogel more porous. The carbohydrate glass was fabricated by combining 53g of sucrose, 25g of glucose, 10g of Dextran, and 50 ml of Reverse Osmosis water and heated to 165°C. This solution was then poured into a heated 50mL glass syringe to be extruded into the hydrogel later. The 2% agarose hydrogel yielded the best results after lyophilization with the agarose maintaining some of its gel-like characteristics, while being more porous to help with fluid flow later. Preliminary tests were successful. Further tests will determine the best method for extruding carbohydrate glass into the hydrogel. Once it is extruded, the scaffold will be integrated into a microfluidic chip platform, and flow experiments will be initiated.
FEASIBILITY OF RECRUITING PEOPLE WITH MILD COGNITIVE IMPAIRMENT IN THE CONTEXT OF HEART FAILURE
Authors: Jung Miyeon , Pressler Susan , Hammers Dustin , Apostolova Liana 
Published: January 2025

Abstract
Recruiting people with mild cognitive impairment (MCI) with another chronic condition such as heart failure (HF) can be arduous. Our investigative group will discuss the challenges encountered while recruiting older adults with both MCI and HF using data from a pilot study testing the efficacy of cognitive interventions to improve cognitive function and the strategies to overcome them. Initially, eligibility criteria included age ≥65 years, HF confirmed by echocardiography, and MCI defined using a 2-step process: (1) Montreal Cognitive Assessment (MoCA) ≤23; and (2) diagnostic consensus of MCI based on the presence of cognitive impairment in the absence of functional decline. Enrollment began on 4/3/2023 by screening Cardiology and Neurology clinics patients. Only 12 participants were enrolled over the next 7 months (rate=1.5 participants/month) due to high screen failure rates (59%) owing to MoCA performances above the eligibility threshold and low recruitment rate (5%). To meet recruitment goals (8 participants/month), eligibility criteria were modified by lowering the age cutoff from 65 to 55 years and removing the MoCA screen and the MCI requirements, while adding the requirement of subjective cognitive concern allowing both those with normal cognition and MCI but not dementia. Phone recruitment was added by screening electronic health records of people who diagnosed with HF. 7 months after implementing the modifications, additional 58 participants were consented exceeding our recruitment goals (69% of those consented=MCI, 26%=normal cognition, 5%=dementia/excluded from the study). In conclusion, feasibility of our original strategies recruiting older adults with both MCI and HF was not supported.
FECAL TRANSPLANT FROM LONG LIVING AMES DWARF MICE ALTERS THE MICROBIOME AND BIOMARKERS OF LIVER HEALTH IN CONTROL MICE
Authors: Ashiqueali Sarah , Hayslip Natalie , Chaudhari Diptaraj , Schneider Augusto , Zhu Xiang , Noureddine Sarah , Yadav Hariom , Masternak Michal 
Published: January 2025

Abstract
Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions and accelerates mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their normal littermates, and vice versa, on the recipient gut microbiota and liver transcriptome. Importantly, our previous studies highlight differences between the microbiomes of Ames dwarf relative to their normal siblings, potentially contributing to their extended lifespan and healthspan. Our findings demonstrate that FMT from Ames dwarf mice to normal mice significantly alters the recipient’s gut microbiota, reprograms bacterial metabolic functions related to healthy aging, and changes the liver transcriptome, indicating improved metabolic health. Our liver mRNA sequencing and RT-PCR validation reveals that FMT in normal recipient animals administered dwarf donor stool may contribute to the significant downregulation of p21, Elovl3, and Insig2, genes involved with cellular senescence and liver metabolic pathways. Our data suggest a regulatory axis exists between the gut and liver, highlighting the potential of microbiome-targeted therapies in promoting healthy aging. Future research should validate these findings and study the underlying mechanisms that confer geroprotection.
FROM GEROSCIENCE TO GEROTHERAPEUTICS: KUAKINI CENTER OF RESEARCH EXCELLENCE FOR TRANSLATIONAL RESEARCH ON AGING
Authors: Willcox Bradley , Nakagawa Kazuma , Lee Yeonjung , Masaki Kamal , Allsopp Richard 
Published: January 2025

Abstract
The primary aim of the Kuakini HHP Center of Excellence for Translational Research on Aging is to utilize geroscientific principles to improve human healthspan, including pharmacology-based gerotherapeutics. This research leverages an exceptional cohort of 8,006 American men of Japanese and Okinawan ancestry, aged 45-68 years at the baseline exam in 1965. Fourteen comprehensive clinical exams have been conducted. Over 500,000 biological samples and over 900 brains have been collected over six decades. The primary aim of our Center is to translate these largely NIH-funded resources into therapeutic innovations that modify aging’s biological pathways, potentially preventing or alleviating multiple age-related diseases and optimizing human healthspan. Our early-stage investigators have novel, recent data on risk factors for premature cognitive aging. Our research approach, with our biotech collaborators, has also contributed to a data science ecosystem with AI and ML-enabled insights on healthy aging from novel multi-omic studies and aging-related health outcomes from our human aging cohort. Key findings are consistent with the geroscience hypothesis and have identified specific pathways for targeted gerotherapeutic interventions, now in Phase 2 human trials, that may contribute to healthier human aging. This presentation will present the latest findings regarding the specific pathways, the molecular targets, and the gerotherapeutic agents that hold promise to mitigate major aging-related diseases, including sarcopenia and cognitive impairment.
FUNCTIONAL CHARACTERIZATION OF ENDOCANNABINOID RELATED 2-AG SYNTHASES IN DOPAMINERGIC NEURONS
Authors: Price Quentin , Basu Disa , Cai Huaibin 
Published: January 2025

Abstract
We previously linked several loss of function mutations of the enzyme diglycerol lipase beta (DAGLB) to early onset Parkinsonism. Parkinson’s disease is defined as the loss of dopaminergic neruons (DANs) in the substantia nigra compacta (SNC). DAGLB is the main synthase of 2-arachidonyl glycerol (2-AG) in nigral DANs. 2-AG from the nigral DANs disinhibits presynaptic inputs such as the GABAergic inputs from the direct spiny projection neurons (dSPNs) of the striatum. However, DAGLA is expressed in nigral DANs as well. We asked ourselves if decreasing the expression fo both DAGLA and DAGLB in the nigral DANs of mice induce motor phenotypes of Parkinson’s disease.
LOSARTAN REJUVENATES SERUM AND HEART METABOLOME OF AGED MICE BY ANGIOTENSIN DEPENDENT AND INDEPENDENT MECHANISMS
Authors: Bene Michael , Marx Ruth , Powell Laura , Ferrucci Luigi , Khadeer Mohammed , Moaddel Ruin , Rudek Michelle , Walston Jeremy 
Published: January 2025

Abstract
Emerging evidence suggests losartan, a selective angiotensin II receptor type 1 (AT1) antagonist, may reduce frailty risk and improve physical function in older adults. Losartan is metabolized to EXP3174 (a potent AT1 antagonist) and EXP3179 (a PPARγ agonist). To elucidate mechanisms through which losartan may reduce frailty and improve physical function we performed targeted metabolomics in serum and heart samples from young (4 months) and aged (24-28 months) mice. Aged mice treated with losartan displayed a global shift towards a more “youthful” serum metabolome (ρ=-0.22, p=0.01) and a stronger “youthful” shift in the heart metabolome (ρ= -0.49, p =3.6e-8), with 71/120 and 74/115 measured metabolites shifting in abundance opposite to age respectively. Serum of AT1KO mice showed no significant metabolomic change but displayed a similar “youthful” shift when treated with losartan, indicating losartan’s effect is AT1 independent. Supporting this, a mediation analysis of serum levels of losartan and EXP3174 revealed serum losartan had a significant correlation to the metabolomic aging signature that was not mediated by EXP3174. In contrast to serum, AT1KO alone shifted the heart metabolome to a more ‘youthful” state suggesting losartan’s effect on the heart may be partially AT1 dependent. Interestingly, AT2KO mice also displayed more “youthful” serum and heart metabolomes, but when treated with losartan produced an interference effect blocking the “youthful” shift seen with either AT2KO or losartan alone. Losartan’s “rejuvenating” effect on serum and heart metabolome was associated with improved survival in WT mice (log-rank, p =0.015) further supporting improvement in aging trajectory.
NO PHONE, MORE STRESS: EXPLORING ANXIETY AS THE MEDIATOR BETWEEN NOMOPHOBIA AND STRESS
Authors: Shaleha Rinanda , Roque Nelson 
Published: January 2025

Abstract
This study (N=567) examines how nomophobia, the fear of being without one’s mobile phone, affects mental health by influencing anxiety and stress. Through regression and mediation analyses with nonparametric bootstrap, we found that anxiety mediates 69.24% of the impact of nomophobia on stress (ACME =.0724, 95% CI [.0568,.09], p &lt;.00001). This substantial mediation underscores the central role of anxiety in the relationship between nomophobia and stress. Analysis by age and gender revealed variable mediation strengths: Young adults of both genders exhibited robust effects, with males showing a mediation proportion of 73.3% (ACME = 0.07424, p &lt;.0001) and females 66.9% (ACME = 0.06940, p &lt;.0001). Middle-aged females demonstrated a particularly high proportion at 88% (ACME = 0.05532, p =.002), contrasted by less pronounced effects in middle-aged males (ACME = 0.02218, p =.196). Older females also displayed significant effects, with a mediation proportion of 82.8% (ACME = 0.09425, p =.004). The observed demographic variations highlight the role of contextual factors such as age and gender in the psychological impacts of nomophobia. These insights are crucial for developing tailored interventions that more effectively counteract the adverse effects of mobile device dependency. Notably, the consistent mediation of stress by anxiety across most groups suggests that strategies focused on reducing anxiety could be particularly effective in managing nomophobia-related stress.
PANDEMIC HARDSHIP AMONG SENIOR LIVING RESIDENTS: WHO WAS MOST VULNERABLE?
Authors: George Mollie , Wilkinson Lindsay , Masters Julie , Boron Julie Blaskewicz 
Published: January 2025

Abstract
The COVID-19 pandemic presented unprecedented challenges for older adults. While there has been an abundance of research on the pandemic-related experiences of community-dwelling older adults, little research has examined those in senior living communities (SLCs). This is significant given the restrictions enforced in SLCs to reduce the risk of infection and potential hospitalization or death. The current research aimed to investigate the pandemic-related experiences and correlates of pandemic hardship among those residing in SLCs. Survey data were collected during the pandemic from adults age 60 or older living in a group of SLCs in Nebraska. Most respondents in the analytic sample (n=726; Mage=84, SD=7, range: 60-100; 73% female) resided in independent living (86%). Drawing on descriptive statistics and linear regression analysis, the results revealed a moderate to high amount of pandemic hardship (M=4, scale: 1-6). The most prevalent negative pandemic-related experiences included difficulty visiting family and friends (91% of respondents agreed), missing out on important events (83%), and perceiving little control over their lives (68%). In models accounting for sociodemographic and health characteristics, residents most vulnerable to the hardship of the pandemic were less likely to be never married (ps&lt; 0.05), had lower perceived health (p&lt; 0.05), and scored lower on resilience (p&lt; 0.001). This research reveals the pandemic-related experiences of an understudied population of independent and assisted living residents, including areas of their lives they perceived to be most impacted by social distancing. This can be helpful in identifying vulnerable groups in need of support during times of crisis.
PHYSICAL ACTIVITY, PURPOSE, AND COGNITION: TESTING POSSIBLE MEDIATION PATHWAYS WITH CROSS-LAGGED PANEL ANALYSIS
Authors: Sadeqi Farima , Best Ryan 
Published: January 2025

Abstract
Numerous studies have emphasized the cognitive benefits older adults experience from engaging in regular physical activity. Previous research has largely highlighted the physiological mechanisms of this relationship, like improvements in cardiovascular health and brain structure, but recent work has begun investigating possible psychological pathways. Prior work from the authors supported the hypothesis that purpose in life acts as a mediator between physical activity and cognitive function, though research suggests a bidirectional relationship between physical activity and purpose in life. Given the bidirectional nature of the relationship between these two variables, the current work tests the possibility that physical activity could also act as the mediator in a single model using a structural equation modeling framework. In a sample of 2960 adults aged 33 to 92 collected through two waves of the Midlife in the United States (MIDUS) study, we examined two potential mediation pathways in a cross-lagged panel model where purpose in life mediates the effect of physical activity on cognition and vice versa. Two separate models test mediation pathways on executive functioning and episodic memory. Results show that purpose in life acted as a significant mediator between physical activity and both cognitive abilities (p &lt;.021), while the indirect effects of physical activity between purpose in life and both cognitive abilities were not significant (p &gt;.67). Findings from this study suggest that among physical activities with similar cardiovascular benefits, the one that also nurtures individuals’ purpose in life and boosts psychological well-being should be prioritized.
REDEFINING SUCCESSFUL AGING: INTEGRATING DISABILITY AND THE ROLE OF MODIFIABLE FACTORS
Authors: Khamzina Madina , Mejia Shannon , Rogers Wendy 
Published: January 2025

Abstract
Disability is a common experience in older adulthood, yet traditional models often neglect its role in successful aging. This study integrates disability into the successful aging framework, utilizing subjective well-being and self-rated health as key indicators. We aim to link disability and successful aging and examine modifiable factors that could foster successful aging among individuals with disabilities over time. We conducted cross-sectional analyses using data from two year periods, the 2011 (N=6,440) and 2020 (N=3,220) waves of the National Health and Aging Trends Study. Disabilities related to mobility, hearing, and vision were self-reported. Indicators of successful aging included subjective well-being and self-rated health. Physical activity and social engagement were examined as modifiable protective factors. Moderation analyses tested whether these factors had stronger effects among individuals with disabilities. The prevalence of successful aging among those with disabilities was 40% in 2011 and 38% in 2020. Regression analyses showed that each type of disability was negatively associated with successful aging indicators. Social engagement and physical activity consistently supported successful aging across both time periods. Social engagement was especially beneficial in 2011 for those with mobility, hearing, and multiple disabilities. Findings underscore the importance of recognizing successful aging with disability and highlight the role of modifiable factors like physical activity and social engagement in promoting successful aging. This study supports the inclusion of disability in aging paradigms, emphasizing adaptive strategies for older adults with disabilities.