Geriatrics Commons^™

The Causal Pivot: A Structural Approach To Genetic Heterogeneity And Variant Discovery In Complex Diseases, Chad A Shaw, C J Williams, Taotao Tan, Daniel Illera, Nicholas Di, Joshua M Shulman, John W Belmont

Center on Aging Staff Publications

We present the Causal Pivot (CP) as a structural causal model (SCM) for analyzing genetic heterogeneity in complex diseases. The CP leverages an established causal factor or factors to detect the contribution of additional suspected causes. Specifically, polygenic risk scores (PRSs) serve as known causes, while rare variants (RVs) or RV ensembles are evaluated as candidate causes. The CP incorporates outcome-induced association by conditioning on disease status. We derive a conditional maximum-likelihood procedure for binary and quantitative traits and develop the Causal Pivot likelihood ratio test (CP-LRT) to detect causal signals. Through simulations, we demonstrate the CP-LRT’s robust power and …

Deepmvp: Deep Learning Models Trained On High-Quality Data Accurately Predict Ptm Sites And Variant-Induced Alterations, Bo Wen, Chenwei Wang, Kai Li, Ping Han, Matthew V Holt, Sara R Savage, Jonathan T Lei, Yongchao Dou, Zhiao Shi, Yi Li, Bing Zhang

Center on Aging Staff Publications

Post-translational modifications (PTMs) are critical regulators of protein function, and their disruption is a key mechanism by which missense variants contribute to disease. Accurate PTM site prediction using deep learning can help identify PTM-altering variants, but progress has been limited by the lack of large, high-quality training datasets. Here, we introduce PTMAtlas, a curated compendium of 397,524 PTM sites generated through systematic reprocessing of 241 public mass-spectrometry datasets, and DeepMVP, a deep learning framework trained on PTMAtlas to predict PTM sites for phosphorylation, acetylation, methylation, sumoylation, ubiquitination and N-glycosylation. DeepMVP substantially outperforms existing tools across all six PTM types. Its …

Developing Deep Learning Methods For Cognitive Impairment Detection Based On Non-Invasive Data, Muath Alsuhaibani

Electronic Theses and Dissertations

Cognitive impairment detection is on the rise to help reduce the burden of healthcare costs on institutions and individuals. Mild Cognitive Impairment (MCI) is an early stage of cognitive decline progressing to Alzheimer’s disease (AD) or AD-related Dementia (ADRD). Detecting the early stages of AD/ADRD is crucial for early interventions among older adults to mitigate cognitive decline over time. However, the current diagnostic methods are often costly and/or invasive, such as MRI and PET scans. Thus, the search for non-invasive and cost-effective screening tools for the early detection of cognitive impairment using speech, language, visual, and motor data is growing. …

Implementation Of A Triage System For The Residents At A Residential Facility To Improve Triage Assessment Skills Of The Staff As Well As Improve The Level And Timeliness Of Care, Andrew J. Choi Rn, Neha Gopal Rn, Andres N. Padilla Rn, Dana Son

Master's Projects and Capstones

Triage is an integral part of the clinical process which involves assessing patients and determining their level of care in order to get them appropriate, timely treatment. Several countries utilize a standardized triage system with established criteria to aid staff in their decision-making during assessments (Peta et al., 2023). The Nursing and Residential Triage (NaRT) tool, from the Manchester Triage System (MTS), was shown to enhance staff clinical assessment skills and help avoid inappropriate ED transfers during a study among older adults in a residential facility (Markey et al., 2024). For this project, the main issue identified at the residential …

Lessons In Longevity From Blood Stem Cells Under Protein Stress, André Catic

Center on Aging Staff Publications

Blood stem cells are among the body's longest-living cells despite being highly vulnerable to proteotoxic damage, which accelerates their aging. To maintain protein homeostasis (proteostasis), hematopoietic stem cells (HSCs) employ mechanisms such as reduced translation rates, high chaperone activity, autophagy, and selective protein degradation. These strategies mitigate protein misfolding, maintain quiescence, and preserve regenerative potential. Disruptions in proteostasis can lead to the elimination of impaired HSCs through differentiation or apoptosis, ensuring the integrity of the stem cell pool. Due to the systemic impact of the blood on aging and its experimental and clinical accessibility, investigating HSC proteostasis provides insights into …

Responding To The Needs Of Dementia Care Partners: Recommendations For Policy Change At The State And Federal Levels., Walter D. Dawson, Jenn Reed, Allison Lindauer, Sherril B. Gelmon

Institute on Aging Publications

The need to optimize supports of Alzheimer's disease and related dementias (ADRD) care partners through policy innovation is high. This study sought to frame the care and support needs of multiple historically underrepresented populations who may be underserved and/or have difficulty accessing culturally specific services and determine specific policies that may reduce ADRD care partner burden and improve wellbeing. Qualitative data were gathered through interviews ( = 24) with leaders of organizations that support people living with ADRD and focus groups ( = 5) with dementia care partners from four communities historically underserved in the United States (Asian, Black, Indigenous, …

Smartboot: Real-Time Monitoring Of Patient Activity Via Remote Edge Computing Technologies, Gozde Cay, Myeounggon Lee, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system-a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch-for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and …

Integrative Spatial Omics Reveals Distinct Tumor-Promoting Multicellular Niches And Immunosuppressive Mechanisms In Black American And White American Patients With Tnbc, Qian Zhu, Akhila Balasubramanian, Jaya Ruth Asirvatham, Megha Chatterjee, Badrajee Piyarathna, Jaspreet Kaur, Nada Mohamed, Ling Wu, Stacy Wang, Niloufar Pourfarrokh, Paula Danika Binsol, Mahak Bhargava, Uttam Rasaily, Yitian Xu, Junjun Zheng, Deborah Jebakumar, Arundhati Rao, Carolina Gutierrez, Angela R Omilian, Carl Morrison, Gokul M Das, Christine Ambrosone, Erin H Seeley, Shu-Hsia Chen, Yi Li, Eric Chang, Xiaoxian Li, Elizabeth Baker, Ritu Aneja, Xiang H-F Zhang, Arun Sreekumar

Center on Aging Staff Publications

Racial disparities in the clinical outcomes of triple-negative breast cancer (TNBC) have been well-documented, but the underlying biological mechanisms remain poorly understood. To investigate these disparities, we employed a multi-omic approach integrating imaging mass cytometry and spatial transcriptomics to characterize the tumor microenvironment (TME) in self-identified Black American (BA) and White American (WA) TNBC patients. Our analysis revealed that the TME in BA patients is marked by a network of endothelial cells, macrophages, and mesenchymal-like cells, which correlates with reduced patient survival. In contrast, the WA TNBC microenvironment is enriched in T-cells and neutrophils, indicative of T-cell exhaustion and suppressed …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

Enzyme-Independent Functions Of Hdac3 In The Adult Hear, Sichong Qian, Chen Zhang, Wenbo Li, Shiyang Song, Guanqiao Lin, Zixiu Cheng, Wenjun Zhou, Huiqi Yin, Yueli Wang, Haiyang Li, Ying H Shen, Zheng Sun

Center on Aging Staff Publications

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes …

Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun

Center on Aging Staff Publications

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal …

The Somatic Mosaicism Across Human Tissues Network, Tim H H Coorens, Ji Won Oh, Yujin Angelina Choi, Nam Seop Lim, Boxun Zhao, Adam Voshall, Alexej Abyzov, Lucinda Antonacci-Fulton, Samuel Aparicio, Kristin G Ardlie, Thomas J Bell, James T Bennett, Bradley E Bernstein, Thomas G Blanchard, Alan P Boyle, Jason D Buenrostro, Kathleen H Burns, Fei Chen, Rui Chen, Sangita Choudhury, Harsha V Doddapaneni, Evan E Eichler, Gilad D Evrony, Melissa A Faith, Thomas G Fazzio, Robert S Fulton, Manuel Garber, Nils Gehlenborg, Soren Germer, Gad Getz, Richard A Gibbs, Raquel G Hernandez, Fulai Jin, Jan O Korbel, Dan A Landau, Heather A Lawson, Niall J Lennon, Heng Li, Yan Li, Po-Ru Loh, Gabor Marth, Michael J Mcconnell, Ryan E Mills, Stephen B Montgomery, Pradeep Natarajan, Peter J Park, Rahul Satija, Fritz J Sedlazeck, Diane D Shao, Hui Shen, Andrew B Stergachis, Hunter R Underhill, Alexander E Urban, Melissa W Vondran, Christopher A Walsh, Ting Wang, Tao P Wu, Chenghang Zong, Eunjung Alice Lee, Flora M Vaccarino

Center on Aging Staff Publications

From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues …

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

Correlation Between Drug-Related Problems And The Treatment Cost For Geriatric Ischemic Stroke Patients In Tulungagung, Dhanang Prawira Nugraha, Martanty Aditya

Jurnal Ekonomi Kesehatan Indonesia

Ischemic stroke was one of the diseases that frequently occurred in geriatric patients, while hemorrhagic stroke had a higher prevalence. Geriatric patients who experienced a stroke were not exempt from drug-related problems (DRP) due to the complexity of treatment and comorbid factors they encountered. This study aimed to determine the correlation between DRP and the cost of care for ischemic stroke patients, particularly in the geriatric population. The study design was cross-sectional, with data collected retrospectively, and the sample comprised 53 geriatric stroke patients who met the inclusion and exclusion criteria. DRP was assessed using the PCNE 6.2 criteria, and …

Tata Laksana Fraktur Panggul Pada Geriatri: Sudut Pandang Internis, Laila M. Jannah, Noto Dwimartutie

Jurnal Penyakit Dalam Indonesia

Hip fracture are a common issue in geriatric patients, associated with increased risk of morbidity and mortality. The complex and multimorbid characteristics of geriatric patients presents significant challenge in their management. Optimal outcomes require a comprehensive interdisciplinary approach to care, aiming to restore functional status and reduce postoperative complications. A holistic strategy, grounded in thorough Comprehensive Geriatric Assessment (CGA), is essential to guide individualized treatment and ensure effective, patient-centered management.

Senior Health (Age 65+) In The Mountain West, 2024, Taylor Volk, Kristian Thymianos, Caitlin J. Saladino, William E. Brown Jr.

Health

This fact sheet presents senior health care statistics for the Mountain West states of Arizona, Colorado, Nevada, New Mexico, and Utah. The “2024 Senior Report – State Summaries,” study from America’s Health Rankings, United Foundation provided the data for all fifty states and Washington, D.C.

Interprofessional Education: A Geriatric Immersion Experiential, Emily J. Balog, Jennifer Degennaro, Lisa Bodenheimer, Stephanie Berdugo-Hernandez, Isabella Berdugo-Hernandez, Matthew Mclaughlin, Kevin Overbeck, Elyse Perweiler

Rowan-Virtua SOM Faculty Teaching & Learning Seminar

The Geriatric Interprofessional Education Immersion (GIPEI) course was developed using a mixed methods design guided by the Knowledge-to-Action (KTA) Framework and embedded data-driven decision-making (DDDM). The eight-week, tri-weekly immersion integrates Experiential and Adult Learning Theories, the 4Ms Framework, IPEC competencies, and TeamSTEPPS to foster age-friendly clinical decision-making. Quantitative and qualitative data, including pre/post-tests, rubrics, observations, and student interviews, inform iterative improvement. The somato-psycho-socio-semiotic model of health further anchors student reflection and care planning. Findings aim to demonstrate improved learner ability to recognize and apply age-friendly care, while supporting evidence-informed curriculum refinement. The course is funded by the geriatric workforce enhancement …

Assessing Older Adult Behavioral Health Diagnoses In Oregon By Geographical Area, Physical Disability Status, And Age., N F. Parsons, Allyson Stodola, Ellis Hews, Nirmala Dhar, Sheryl Elliott, Sarah Dys, Walter D. Dawson

Institute on Aging Publications

This repeated cross-sectional study aims to assess potential differences among behavioral health (BH) diagnoses for older adults. Differences in services across urban versus rural/remote areas may contribute to deeply entrenched barriers to improved BH for this population.

Association Of The G8 Screening Tool With Neoadjuvant Chemotherapy Outcomes In Older Adults With Urothelial Carcinoma, Kendall Ozorowski, Umma Fatema, Amman Bhasin, Julia Palecki, Michael Zimmerman, Kristine Swartz, Kevin Zarrabi, Kuang-Yi Wen

Health Equity and Quality Improvement (HEQI) Summit

Intro

• Urothelial carcinoma (UC) predominately affects older adults who often face increased adverse outcomes and reduced survival.
• Standard of care treatment entails neoadjuvant cisplatin- based chemotherapy followed by cystectomy with urinary diversion.
• The American Society of Clinical Oncology recommends older patients with cancer undergo Comprehensive Geriatric Assessment (CGA) prior to cancer treatment.
• The G8, a geriatric assessment tool, is a validated screening tool for identifying frailty requiring CG

Incorporation Of The 4ms, With A Focus On Mentation, Into The H&P For Older Adults Hospitalized With A Hip Fracture And Its Effect On Delirium Documentation, Emily Custer, Do, Kristine Swartz, Md, Lily Ackermann, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

Delirium affects 15% to over 50% of patients with hip fractures during their hospital stay (1) and is associated with increased mortality, increased length of hospital stay, poorer functional outcomes, and higher risk of nursing home placement (1,2). However, at Thomas Jefferson University Hospital, the prevalence of documented delirium post-hip fracture is only 5.22%, suggesting potential under recognition. Additionally, at the end of 2025, a new CMS inpatient quality metric will require public reporting on a hospital's capability to provide age-appropriate care for older adults, which can be done by utilizing the 4M framework of age-friendly health care. The …