Sophia Miryam Schüssler-Fiorenza Rose

All Publications

• Dynamic lipidome alterations associated with human health, disease and ageing. Nature metabolism Hornburg, D., Wu, S., Moqri, M., Zhou, X., Contrepois, K., Bararpour, N., Traber, G. M., Su, B., Metwally, A. A., Avina, M., Zhou, W., Ubellacker, J. M., Mishra, T., Schüssler-Fiorenza Rose, S. M., Kavathas, P. B., Williams, K. J., Snyder, M. P. 2023

  Abstract

  Lipids can be of endogenous or exogenous origin and affect diverse biological functions, including cell membrane maintenance, energy management and cellular signalling. Here, we report >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation, as well as cytokine-lipidome networks. We performed comprehensive longitudinal lipidomic profiling and analysed >1,500 plasma samples from 112 participants followed for up to 9 years (average 3.2 years) to define the distinct physiological roles of complex lipid subclasses, including large and small triacylglycerols, ester- and ether-linked phosphatidylethanolamines, lysophosphatidylcholines, lysophosphatidylethanolamines, cholesterol esters and ceramides. Our findings reveal dynamic changes in the plasma lipidome during respiratory viral infection, insulin resistance and ageing, suggesting that lipids may have roles in immune homoeostasis and inflammation regulation. Individuals with insulin resistance exhibit disturbed immune homoeostasis, altered associations between lipids and clinical markers, and accelerated changes in specific lipid subclasses during ageing. Our dataset based on longitudinal deep lipidome profiling offers insights into personalized ageing, metabolic health and inflammation, potentially guiding future monitoring and intervention strategies.

  View details for DOI 10.1038/s42255-023-00880-1

  View details for PubMedID 37697054

  View details for PubMedCentralID 7736650

• Multi-omics approaches in psychoneuroimmunology and health research: Conceptual considerations and methodological recommendations. Brain, behavior, and immunity Mengelkoch, S., Lautman, Z., Alley, J. C., Roos, L. G., Ehlert, B., Moriarity, D. P., Lancaster, S., Miryam Schussler-Fiorenza Rose, S., Snyder, M. P., Slavich, G. M. 2023

  Abstract

  The field of psychoneuroimmunology (PNI) has grown substantially in both relevance and prominence over the past 40 years. Notwithstanding its impressive trajectory, a majority of PNI studies are still based on a relatively small number of analytes. To advance this work, we suggest that PNI, and health research in general, can benefit greatly from adopting a multi-omics approach, which involves integrating data across multiple biological levels (e.g., the genome, proteome, transcriptome, metabolome, lipidome, and microbiome/metagenome) to more comprehensively profile biological functions and relate these profiles to clinical and behavioral outcomes. To assist investigators in this endeavor, we provide an overview of multi-omics research, highlight recent landmark multi-omics studies investigating human health and disease risk, and discuss how multi-omics can be applied to better elucidate links between psychological, nervous system, and immune system activity. In doing so, we describe how to design high-quality multi-omics PNI studies, decide which biological samples (e.g., blood, stool, urine, saliva, solid tissue) are most relevant, incorporate behavioral and wearable sensing data into multi-omics research, and understand key data quality, integration, analysis, and interpretation issues. PNI researchers are addressing some of the most interesting and important questions at the intersection of psychology, neuroscience, and immunology. Applying a multi-omics approach to this work will greatly expand the horizon of what is possible in PNI and has the potential to revolutionize our understanding of mind-body medicine.

  View details for DOI 10.1016/j.bbi.2023.07.022

  View details for PubMedID 37543247

• Precision environmental health monitoring by longitudinal exposome and multi-omics profiling. Genome research Gao, P., Shen, X., Zhang, X., Jiang, C., Zhang, S., Zhou, X., Schüssler-Fiorenza Rose, S. M., Snyder, M. 2022

  Abstract

  Conventional environmental health studies have primarily focused on limited environmental stressors at the population level, which lacks the power to dissect the complexity and heterogeneity of individualized environmental exposures. Here, as a pilot case study, we integrated deep-profiled longitudinal personal exposome and internal multi-omics to systematically investigate how the exposome shapes a single individual's phenome. We annotated thousands of chemical and biological components in the personal exposome cloud and found they were significantly correlated with thousands of internal biomolecules, which was further cross-validated using corresponding clinical data. Our results showed that agrochemicals and fungi predominated in the highly diverse and dynamic personal exposome, and the biomolecules and pathways related to the individual's immune system, kidney, and liver were highly associated with the personal external exposome. Overall, this data-driven longitudinal monitoring study shows the potential dynamic interactions between the personal exposome and internal multi-omics, as well as the impact of the exposome on precision health by producing abundant testable hypotheses.

  View details for DOI 10.1101/gr.276521.121

  View details for PubMedID 35667843

• Adverse childhood experiences, diabetes and associated conditions, preventive care practices and healthcare access: A population-based study. Preventive medicine Rose, S. M., Slavich, G. M., Snyder, M. P. 2022: 107044

  Abstract

  Our objective was to examine associations between Adverse Childhood Experiences (ACEs) and diabetes mellitus, including related conditions and preventive care practices. We used data from the Behavioral Risk Factor Surveillance System (BRFSS) 2009-2012, a cross-sectional, population-based survey, to assess ACEs, diabetes, and healthcare access in 179,375 adults. In those with diabetes (n = 21,007), we assessed the association of ACEs with myocardial infarction, stroke, and five Healthy People 2020 (HP2020) diabetes-related preventive-care objectives (n = 13,152). Healthcare access indicators included lack of a regular healthcare provider, insurance, and difficulty affording healthcare. Regression analyses adjusted for age, sex, and race. The adjusted odds ratio (AOR) of diabetes increased in a stepwise fashion by ACE exposure, ranging from 1.2 (95% CI 1.1-1.3) for 1 ACE to 1.7 (95% CI 1.6-1.9) for ≥4 ACEs, versus having no ACEs. In persons with diabetes, those with ≥4 ACEs had an elevated adjusted odds of myocardial infarction (AOR = 1.6, 95% CI 1.2-2.0) and stroke (AOR = 1.8, 95% CI 1.3-2.4), versus having no ACEs. ACEs were also associated with a reduction in the adjusted percent of HP2020 diabetes objectives met: 72.9% (95% CI 71.3-74.5) for those with no ACEs versus only 66.5% (95% CI 63.8-69.3%) for those with ≥4 ACEs (p = 0.0002). Finally, ACEs predicted worse healthcare access in a stepwise fashion for all indicators. In conclusion, ACEs are associated with greater prevalence of diabetes and associated conditions, and with meeting fewer HP2020 prevention goals. ACEs screening and trauma-informed care practices are thus recommended.

  View details for DOI 10.1016/j.ypmed.2022.107044

  View details for PubMedID 35398366

• Wearable sensors enable personalized predictions of clinical laboratory measurements. Nature medicine Dunn, J., Kidzinski, L., Runge, R., Witt, D., Hicks, J. L., Schussler-Fiorenza Rose, S. M., Li, X., Bahmani, A., Delp, S. L., Hastie, T., Snyder, M. P. 2021

  Abstract

  Vital signs, including heart rate and body temperature, are useful in detecting or monitoring medical conditions, but are typically measured in the clinic and require follow-up laboratory testing for more definitive diagnoses. Here we examined whether vital signs as measured by consumer wearable devices (that is, continuously monitored heart rate, body temperature, electrodermal activity and movement) can predict clinical laboratory test results using machine learning models, including random forest and Lasso models. Our results demonstrate that vital sign data collected from wearables give a more consistent and precise depiction of resting heart rate than do measurements taken in the clinic. Vital sign data collected from wearables can also predict several clinical laboratory measurements with lower prediction error than predictions made using clinically obtained vital sign measurements. The length of time over which vital signs are monitored and the proximity of the monitoring period to the date of prediction play a critical role in the performance of the machine learning models. These results demonstrate the value of commercial wearable devices for continuous and longitudinal assessment of physiological measurements that today can be measured only with clinical laboratory tests.

  View details for DOI 10.1038/s41591-021-01339-0

  View details for PubMedID 34031607

• Depression, health comorbidities, cognitive symptoms and their functional impact: Not just a geriatric problem. Journal of psychiatric research Schüssler-Fiorenza Rose, S. M., Bott, N. T., Heinemeyer, E. E., Hantke, N. C., Gould, C. E., Hirst, R. B., Jordan, J. T., Beaudreau, S. A., O'Hara, R. 2021; 139: 185-192

  Abstract

  To compare the prevalence of cognitive symptoms and their functional impact by age group accounting for depression and number of other health conditions.We analyzed data from the 2011 Behavioral Risk Factor Surveillance System, a population-based, cross-sectional telephone survey of US adults. Twenty-one US states asked participants (n = 131, 273) about cognitive symptoms (worsening confusion or memory loss in the past year) and their functional impact (interference with activities and need for assistance). We analyzed the association between age, depression history and cognitive symptoms and their functional impact using logistic regression and adjusted for demographic characteristics and other health condition count.There was a significant interaction between age and depression (p < 0.0001). In adults reporting depression, the adjusted odds of cognitive symptoms in younger age groups (<75 years) were comparable or greater to those in the oldest age group (≥75 years) with a peak in the middle age (45-54 years) group (OR 1.9 (95% Confidence Interval: 1.4-2.5). In adults without depression, adults <75 years had a significantly lower adjusted odds of cognitive symptoms compared to the oldest age group with the exception of the middle-aged group where the difference was not statistically significant. Over half of adults under age 65 with depression reported that cognitive symptoms interfered with life activities compared to 35.7% of adults ≥65 years.Cognitive symptoms are not universally higher in older adults; middle-aged adults are also particularly vulnerable. Given the adverse functional impact associated with cognitive symptoms in younger adults, clinicians should assess cognitive symptoms and their functional impact in adults of all ages and consider treatments that impact both cognition and functional domains.

  View details for DOI 10.1016/j.jpsychires.2021.05.013

  View details for PubMedID 34087515

• The 5-HTTLPR Long, not Short, Allele Predicts Two-year Longitudinal Increases in Cortisol and Declines in Verbal Memory in Older Adults. International journal of geriatric psychiatry Hirst, R. B., Jordan, J. T., Miryam Schussler-Fiorenza Rose, S., Schneider, L., Kawai, M., Gould, C., Anker, L., Chick, C. F., Beaudreau, S., Hallmayer, J., O'Hara, R. 2020

  Abstract

  OBJECTIVES: The short form or s-allele variant of the serotonin transporter polymorphism (5-HTTLPR), as compared with the long form or l-allele variant, has been associated with the presence of cognitive dysfunction, and particularly memory impairment in older adults. This body of cross-sectional work has culminated in the hypothesis that presence of the s-allele predicts greater memory decline in older adults (1). Yet, to date, there are no longitudinal studies which have investigated this issue.METHODS/DESIGN: Here we examine 109 community-dwelling older adults (mean and SD of age=70.7±8.7years) who underwent blood draw for genotyping, cognitive, and psychological testing at baseline, 12-month, and 24-month follow-up.RESULTS: Multilevel modeling found that s-allele carriers (ss or ls) performed worse than ll homozygotes at baseline on delayed verbal recall. Yet, s-allele carriers' memory performance was stable over the two-year follow-up period, while l-allele homozygotes experienced significant memory decline. l-allele homozygote status was associated with both increased cortisol and decreased memory over time, resulting in attenuated verbal memory performance differences compared to s-allele carriers with age.CONCLUSIONS: Overall, our findings do not support the hypothesis that presence of the 5-HTTLPR s-allele is a marker for memory decline in older adults. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/gps.5319

  View details for PubMedID 32400901

• Molecular Choreography of Acute Exercise. Cell Contrepois, K. n., Wu, S. n., Moneghetti, K. J., Hornburg, D. n., Ahadi, S. n., Tsai, M. S., Metwally, A. A., Wei, E. n., Lee-McMullen, B. n., Quijada, J. V., Chen, S. n., Christle, J. W., Ellenberger, M. n., Balliu, B. n., Taylor, S. n., Durrant, M. G., Knowles, D. A., Choudhry, H. n., Ashland, M. n., Bahmani, A. n., Enslen, B. n., Amsallem, M. n., Kobayashi, Y. n., Avina, M. n., Perelman, D. n., Schüssler-Fiorenza Rose, S. M., Zhou, W. n., Ashley, E. A., Montgomery, S. B., Chaib, H. n., Haddad, F. n., Snyder, M. P. 2020; 181 (5): 1112–30.e16

  Abstract

  Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

  View details for DOI 10.1016/j.cell.2020.04.043

  View details for PubMedID 32470399

• Personal aging markers and ageotypes revealed by deep longitudinal profiling. Nature medicine Ahadi, S., Zhou, W., Schussler-Fiorenza Rose, S. M., Sailani, M. R., Contrepois, K., Avina, M., Ashland, M., Brunet, A., Snyder, M. 2020; 26 (1): 83–90

  Abstract

  The molecular changes that occur with aging are not well understood1-4. Here, we performed longitudinal and deep multiomics profiling of 106 healthy individuals from 29 to 75 years of age and examined how different types of 'omic' measurements, including transcripts, proteins, metabolites, cytokines, microbes and clinical laboratory values, correlate with age. We identified both known and new markers that associated with age, as well as distinct molecular patterns of aging in insulin-resistant as compared to insulin-sensitive individuals. In a longitudinal setting, we identified personal aging markers whose levels changed over a short time frame of 2-3 years. Further, we defined different types of aging patterns in different individuals, termed 'ageotypes', on the basis of the types of molecular pathways that changed over time in a given individual. Ageotypes may provide a molecular assessment of personal aging, reflective of personal lifestyle and medical history, that may ultimately be useful in monitoring and intervening in the aging process.

  View details for DOI 10.1038/s41591-019-0719-5

  View details for PubMedID 31932806

• Deep longitudinal multiomics profiling reveals two biological seasonal patterns in California. Nature communications Sailani, M. R., Metwally, A. A., Zhou, W. n., Rose, S. M., Ahadi, S. n., Contrepois, K. n., Mishra, T. n., Zhang, M. J., Kidziński, Ł. n., Chu, T. J., Snyder, M. P. 2020; 11 (1): 4933

  Abstract

  The influence of seasons on biological processes is poorly understood. In order to identify biological seasonal patterns based on diverse molecular data, rather than calendar dates, we performed a deep longitudinal multiomics profiling of 105 individuals over 4 years. Here, we report more than 1000 seasonal variations in omics analytes and clinical measures. The different molecules group into two major seasonal patterns which correlate with peaks in late spring and late fall/early winter in California. The two patterns are enriched for molecules involved in human biological processes such as inflammation, immunity, cardiovascular health, as well as neurological and psychiatric conditions. Lastly, we identify molecules and microbes that demonstrate different seasonal patterns in insulin sensitive and insulin resistant individuals. The results of our study have important implications in healthcare and highlight the value of considering seasonality when assessing population wide health risk and management.

  View details for DOI 10.1038/s41467-020-18758-1

  View details for PubMedID 33004787

• Longitudinal multi-omics of host-microbe dynamics in prediabetes. Nature Zhou, W., Sailani, M. R., Contrepois, K., Zhou, Y., Ahadi, S., Leopold, S. R., Zhang, M. J., Rao, V., Avina, M., Mishra, T., Johnson, J., Lee-McMullen, B., Chen, S., Metwally, A. A., Tran, T. D., Nguyen, H., Zhou, X., Albright, B., Hong, B., Petersen, L., Bautista, E., Hanson, B., Chen, L., Spakowicz, D., Bahmani, A., Salins, D., Leopold, B., Ashland, M., Dagan-Rosenfeld, O., Rego, S., Limcaoco, P., Colbert, E., Allister, C., Perelman, D., Craig, C., Wei, E., Chaib, H., Hornburg, D., Dunn, J., Liang, L., Rose, S. M., Kukurba, K., Piening, B., Rost, H., Tse, D., McLaughlin, T., Sodergren, E., Weinstock, G. M., Snyder, M. 2019; 569 (7758): 663–71

  Abstract

  Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2Dbetter, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.

  View details for DOI 10.1038/s41586-019-1236-x

  View details for PubMedID 31142858

• MULTIOMICS PROFILING OF LIFE COURSE STRESS AND ADVERSITY Rose, S., Contrepois, K., Slavich, G. M., Snyder, M. P. LIPPINCOTT WILLIAMS & WILKINS. 2019: A70–A71

  View details for Web of Science ID 000467560700201

• A longitudinal big data approach for precision health. Nature medicine Schüssler-Fiorenza Rose, S. M., Contrepois, K. n., Moneghetti, K. J., Zhou, W. n., Mishra, T. n., Mataraso, S. n., Dagan-Rosenfeld, O. n., Ganz, A. B., Dunn, J. n., Hornburg, D. n., Rego, S. n., Perelman, D. n., Ahadi, S. n., Sailani, M. R., Zhou, Y. n., Leopold, S. R., Chen, J. n., Ashland, M. n., Christle, J. W., Avina, M. n., Limcaoco, P. n., Ruiz, C. n., Tan, M. n., Butte, A. J., Weinstock, G. M., Slavich, G. M., Sodergren, E. n., McLaughlin, T. L., Haddad, F. n., Snyder, M. P. 2019; 25 (5): 792–804

  Abstract

  Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability of deep longitudinal profiling to make health-related discoveries, identify clinically relevant molecular pathways and affect behavior in a prospective longitudinal cohort (n = 109) enriched for risk of type 2 diabetes mellitus. The cohort underwent integrative personalized omics profiling from samples collected quarterly for up to 8 years (median, 2.8 years) using clinical measures and emerging technologies including genome, immunome, transcriptome, proteome, metabolome, microbiome and wearable monitoring. We discovered more than 67 clinically actionable health discoveries and identified multiple molecular pathways associated with metabolic, cardiovascular and oncologic pathophysiology. We developed prediction models for insulin resistance by using omics measurements, illustrating their potential to replace burdensome tests. Finally, study participation led the majority of participants to implement diet and exercise changes. Altogether, we conclude that deep longitudinal profiling can lead to actionable health discoveries and provide relevant information for precision health.

  View details for PubMedID 31068711

• Factors Associated with Supportive Care Service Use Among California Alzheimer's Disease Patients and Their Caregivers. Journal of Alzheimer's disease : JAD Newkirk, L. A., Dao, V. L., Jordan, J. T., Alving, L. I., Davies, H. D., Hewett, L. n., Beaudreau, S. A., Schneider, L. D., Gould, C. E., Chick, C. F., Hirst, R. B., Rose, S. M., Anker, L. A., Tinklenberg, J. R., O'Hara, R. n. 2019

  Abstract

  Existing literature on factors associated with supportive care service (SCS) use is limited. A better understanding of these factors could help tailor SCS to the needs of frequent users, as well as facilitate targeted outreach to populations that underutilize available services.To investigate the prevalence of SCS use and to identify factors associated with, and barriers to, service use.California Alzheimer's Disease Center patients with AD (n = 220) participated in the study from 2006-2009. Patients and their caregivers completed assessments to determine SCS use. Cognitive, functional, and behavioral status of the patients were also assessed. A two-part hurdle analysis identified 1) factors associated with any service use and 2) service use frequency among users.Forty percent of participants reported using at least one SCS. Patients with more impaired cognition and activities of daily living and more of the following: total number of medications, comorbid medical conditions, and years of education were more likely to use any SCS (p < 0.05). Factors associated with more frequent SCS use included younger age, more years of education, older age of AD onset, female gender, and having a spouse or relative for a caregiver (p < 0.05). Caregivers frequently indicated insufficient time as a reason for not receiving enough services.Factors associated with any SCS use mostly differed from those associated with SCS frequency, suggesting different characteristics between those who initiate versus those who continue SCS use. Our findings highlight the importance of targeted education on services and identifying barriers to long-term SCS use.

  View details for DOI 10.3233/JAD-190438

  View details for PubMedID 31743997

• Subjective but Not Objective Sleep is Associated with Subsyndromal Anxiety and Depression in Community-Dwelling Older Adults. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Gould, C. E., Karna, R., Jordan, J., Kawai, M., Hirst, R., Hantke, N., Pirog, S., Cotto, I., Schussler-Fiorenza Rose, S. M., Beaudreau, S. A., O'Hara, R. 2018

  Abstract

  OBJECTIVE: To examine the relationship between subclinical anxiety and depressive symptoms and objective sleep architecture measures and subjective sleep reports in older adults.METHODS: Community-dwelling older adults (N=167) self-rated their current severity of anxiety symptoms, depressive symptoms, daytime sleepiness, and global sleep quality. Participants received overnight ambulatory polysomnography to assess sleep architecture. Multivariate linear regression models examined associations between anxiety and depressive symptoms and objective and subjective sleep measures.RESULTS: Significant findings emerged for subjective sleep, with higher depression and anxiety scores associated with worse global sleep quality and greater anxiety scores associated with greater daytime sleepiness. No significant associations were observed between subclinical levels of anxiety or depressive symptoms with sleep architecture.CONCLUSION: Subclinical levels of late-life anxiety and depression have distinct associations with subjective sleep disturbance. Findings implicate subjective measures of sleep quality and daytime sleepiness as stronger trait markers for subthreshold psychiatric symptoms than objective sleep biomarkers.

  View details for PubMedID 29709510

• Potentially Avoidable Hospitalizations among People at Different Activity of Daily Living Limitation Stages HEALTH SERVICES RESEARCH Schussler-Fiorenza Rose, S. M., Stineman, M. G., Pan, Q., Bogner, H., Kurichi, J. E., Streim, J. E., Xie, D. 2017; 52 (1): 132-155

  Abstract

  To determine whether higher activity of daily living (ADL) limitation stages are associated with increased risk of hospitalization, particularly for ambulatory care sensitive (ACS) conditions.Secondary data analysis, including 8,815 beneficiaries from 2005 to 2006 Medicare Current Beneficiary Survey (MCBS).ADL limitation stages (0-IV) were determined at the end of 2005. Hospitalization rates were calculated for 2006 and age adjusted using direct standardization. Multivariate negative binomial regression, adjusting for baseline demographic and health characteristics, with the outcome hospitalization count was performed to estimate the adjusted rate ratio of ACS and non-ACS hospitalizations for beneficiaries with ADL stages > 0 compared to beneficiaries without limitations.Baseline ADL stage and health conditions were assessed using 2005 MCBS data and count of hospitalization determined using 2006 MCBS data.Referenced to stage 0, the adjusted rate ratios (95 percent confidence interval) for stage I to stage IV ranged from 1.9 (1.4-2.5) to 4.1 (2.2-7.8) for ACS hospitalizations compared with from 1.6 (1.3-1.9) to 1.8 (1.4-2.5) for non-ACS hospitalizations.Hospitalization rates for ACS conditions increased more dramatically with ADL limitation stage than did rates for non-ACS conditions. Adults with ADL limitations appear particularly vulnerable to potentially preventable hospitalizations for conditions typically manageable in ambulatory settings.

  View details for DOI 10.1111/1475-6773.12484

  View details for Web of Science ID 000393579500008

• Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information. PLoS biology Li, X., Dunn, J., Salins, D., Zhou, G., Zhou, W., Schüssler-Fiorenza Rose, S. M., Perelman, D., Colbert, E., Runge, R., Rego, S., Sonecha, R., Datta, S., McLaughlin, T., Snyder, M. P. 2017; 15 (1)

  Abstract

  A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography.

  View details for DOI 10.1371/journal.pbio.2001402

  View details for PubMedID 28081144

• Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd NATURE COMMUNICATIONS Wang, Z., Monteiro, C. D., Jagodnik, K. M., Fernandez, N. F., Gundersen, G. W., Rouillard, A. D., Jenkins, S. L., Feldmann, A. S., Hu, K. S., McDermott, M. G., Duan, Q., Clark, N. R., Jones, M. R., Kou, Y., Goff, T., Woodland, H., Amaral, F. M., Szeto, G. L., Fuchs, O., Rose, S. M., Sharma, S., Schwartz, U., Bengoetxea Bausela, X., Szymkiewicz, M., Maroulis, V., Salykin, A., Barra, C. M., Kruth, C. D., Bongio, N. J., Mathur, V., Todoric, R. D., Rubin, U. E., Malatras, A., Fulp, C. T., Galindo, J. A., Motiejunaite, R., Jueschke, C., Dishuck, P. C., Lahl, K., Jafari, M., Aibar, S., Zaravinos, A., Steenhuizen, L. H., Allison, L. R., Gamallo, P., de Andres Segura, F., Devlin, T. D., Perez-Garcia, V., Ma'ayan, A. 2016; 7

  Abstract

  Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization.

  View details for DOI 10.1038/ncomms12846

  View details for Web of Science ID 000385363000014

  View details for PubMedID 27667448

• Adverse Childhood Experiences, Support, and the Perception of Ability to Work in Adults with Disability. PloS one Schüssler-Fiorenza Rose, S. M., Eslinger, J. G., Zimmerman, L., Scaccia, J., Lai, B. S., Lewis, C., Alisic, E. 2016; 11 (7): e0157726

  Abstract

  To examine the impact of adverse childhood experiences (ACEs) and support on self-reported work inability of adults reporting disability.Adults (ages 18-64) who participated in the Behavioral Risk Factor Surveillance System in 2009 or 2010 and who reported having a disability (n = 13,009).The study used a retrospective cohort design with work inability as the main outcome. ACE categories included abuse (sexual, physical, emotional) and family dysfunction (domestic violence, incarceration, mental illness, substance abuse, divorce). Support included functional (perceived emotional/social support) and structural (living with another adult) support. Logistic regression was used to adjust for potential confounders (age, sex and race) and to evaluate whether there was an independent effect of ACEs on work inability after adding other important predictors (support, education, health) to the model.ACEs were highly prevalent with almost 75% of the sample reporting at least one ACE category and over 25% having a high ACE burden (4 or more categories). ACEs were strongly associated with functional support. Participants experiencing a high ACE burden had a higher adjusted odds ratio (OR) [95% confidence interval] of 1.9 [1.5-2.4] of work inability (reference: zero ACEs). Good functional support (adjusted OR 0.52 [0.42-0.63]) and structural support (adjusted OR 0.48 [0.41-0.56]) were protective against work inability. After adding education and health to the model, ACEs no longer appeared to have an independent effect. Structural support remained highly protective, but functional support only appeared to be protective in those with good physical health.ACEs are highly prevalent in working-age US adults with a disability, particularly young adults. ACEs are associated with decreased support, lower educational attainment and worse adult health. Health care providers are encouraged to screen for ACEs. Addressing the effects of ACEs on health and support, in addition to education and retraining, may increase ability to work in those with a disability.

  View details for DOI 10.1371/journal.pone.0157726

  View details for PubMedID 27379796

  View details for PubMedCentralID PMC4933396

• Understanding non-performance reports for instrumental activity of daily living items in population analyses: a cross sectional study BMC GERIATRICS Stineman, M. G., Xie, D., Pan, Q., Kurichi, J. E., Saliba, D., Rose, S. M., Streim, J. E. 2016; 16

  Abstract

  Concerns about using Instrumental Activities of Daily Living (IADLs) in national surveys come up frequently in geriatric and rehabilitation medicine due to high rates of non-performance for reasons other than health. We aim to evaluate the effect of different strategies of classifying "does not do" responses to IADL questions when estimating prevalence of IADL limitations in a national survey.Cross-sectional analysis of a nationally representative sample of 13,879 non-institutionalized adult Medicare beneficiaries included in the 2010 Medicare Current Beneficiary Survey (MCBS). Sample persons or proxies were asked about difficulties performing six IADLs. Tested strategies to classify non-performance of IADL(s) for reasons other than health were to 1) derive through multiple imputation, 2) exclude (for incomplete data), 3) classify as "no difficulty," or 4) classify as "difficulty." IADL stage prevalence estimates were compared across these four strategies.In the sample, 1853 sample persons (12.4 % weighted) did not do one or more IADLs for reasons other than physical problems or health. Yet, IADL stage prevalence estimates differed little across the four alternative strategies. Classification as "no difficulty" led to slightly lower, while classification as "difficulty" raised the estimated population prevalence of disability.These analyses encourage clinicians, researchers, and policy end-users of IADL survey data to be cognizant of possible small differences that can result from alternative ways of handling unrated IADL information. At the population-level, the resulting differences appear trivial when applying MCBS data, providing reassurance that IADL items can be used to estimate the prevalence of activity limitation despite high rates of non-performance.

  View details for DOI 10.1186/s12877-016-0235-0

  View details for PubMedID 26956616

• Adverse Childhood Experiences, Support, and the Perception of Ability to Work in Adults with Disability PLOS ONE Schüssler-Fiorenza Rose , S. M., Eslinger, J. G., Zimmerman, L., Scaccia, J., Lai, B. S., Lewis, C., Alisic, E. 2016

  View details for DOI 10.1371/journal.pone.0157726

• Identifying neuropsychiatric disorders in the Medicare Current Beneficiary Survey: the benefits of combining health survey and claims data BMC Health Services Research Schussler-Fiorenza Rose, S. M., Xie, D., Streim, J. E., Pan, Q., Kwong, P. L., Stineman, M. G. 2016; 16 (537)

  View details for DOI 10.1186/s12913-016-1774-y

• Increasing Discussion Rates of Incontinence in Primary Care: A Randomized Controlled Trial. Journal of women's health (2002) Schüssler-Fiorenza Rose, S. M., Gangnon, R. E., Chewning, B., Wald, A. 2015; 24 (11): 940-9

  Abstract

  A minority of women with urinary incontinence (UI) and even fewer with fecal incontinence (FI) report having discussed it with a health care provider in the past year. Thus our aim was to evaluate whether the use of an electronic pelvic floor assessment questionnaire (ePAQ-PF) improves communication about incontinence in primary care.Women 40 years and older who were scheduled for an annual wellness physical at an internal medicine clinic between August 2007 and August 2008 were randomized to complete the ePAQ-PF prior to (n = 145) or after (n = 139) their visit. Clinicians of women in the intervention group received the ePAQ-PF report prior to the visit. Outcome measures from clinic note abstraction included mention of UI (primary) and FI. Participant-reported outcome measures included discussion of UI and FI and initiator of discussion.Discussions of UI was more common in the intervention group than the control group: (27% vs. 19%; odds ratio [OR], 1.6 95% confidence interval [95%CI] 0.9-2.8, particularly for women over 60 (33% vs. 12%; OR 3.8, 95%CI 1.2-11.8) and for women with UI (42% vs. 25%; OR 2.2, 95%CI 1.1-4.1). The intervention primarily led to an increase in clinician-initiated UI discussions which were more common in the intervention group (18% vs. 4%, OR 4.8, 95%CI 1.9-12.0) Participants in the intervention group more frequently reported discussion of FI (14% vs. 6%; OR 2.5, 95%CI 1.1-6.0) which was clinician initiated in over half the cases (9% vs. 3%; OR 3.5, 95%CI 1.1-11.0).Use of the ePAQ-PF prior to clinic visits increases discussion of UI and FI, particularly clinician-initiated discussion. These findings suggest that such instruments may increase the detection and treatment of this often "silent" affliction.

  View details for DOI 10.1089/jwh.2015.5230

  View details for PubMedID 26555779

  View details for PubMedCentralID PMC4649726

• Traumatic brain injury in US Veterans with traumatic spinal cord injury Journal of Rehabilitation Research and Development Creasey, G. H., Latev, Z. C., Schüssler-Fiorenza Rose, S. M., Rose, J. 2015; 52 (6): 669-676

  View details for DOI 10.1682/JRRD.2014.11.0291

• Increasing Discussion Rates of Incontinence in Primary Care: A Randomized Controlled Trial Journal of Women's Health Schüssler-Fiorenza Rose, S. M., Gangnon, R. F., Chewning, B., Wald, A. 2015; 24 (11): 940-949
• Activity Limitation Stages Empirically Derived for Activities of Daily Living (ADL) and Instrumental ADL in the U.S. Adult Community-Dwelling Medicare Population. PM & R : the journal of injury, function, and rehabilitation Stineman, M. G., Streim, J. E., Pan, Q., Kurichi, J. E., Schüssler-Fiorenza Rose, S. M., Xie, D. 2014; 6 (11): 976-87

  Abstract

  Stages quantify severity like conventional measures but further specify the activities that people are still able to perform without difficulty.To develop Activity Limitation Stages for defining and monitoring groups of adult community-dwelling Medicare beneficiaries.Cross-sectional.Community.There were 14,670 respondents to the 2006 Medicare Current Beneficiary Survey.Stages were empirically derived for the Activities of Daily Living (ADLs) and the Instrumental Activities of Daily Living (IADLs) by profiling the distribution of performance difficulties as reported by beneficiaries or their proxies. Stage prevalence estimates were determined, and associations with demographic and health variables were examined for all community-dwelling Medicare beneficiaries.ADL and IADL stage prevalence.Stages (0-IV) define 5 groups across the separate ADL and IADL domains according to hierarchically organized profiles of retained abilities and difficulties. For example, at ADL-I, people are guaranteed to be able to eat, toilet, dress, and bathe/shower without difficulty, whereas they experience limitations getting in and out of bed or chairs and/or difficulties walking. In 2006, an estimated 6.0, 2.9, 2.2, and 0.5 million beneficiaries had mild (ADL-I), moderate (ADL-II), severe (ADL-III), and complete (ADL-IV) difficulties, respectively, with estimates for IADL stages even higher. ADL and IADL stages showed expected associations with age and health-related concepts, supporting construct validity. Stages showed the strongest associations with conditions that impair cognition.Stages as aggregate measures reveal the ADLs and IADLs that people are still able to do without difficulty, along with those activities in which they report having difficulty, consequently emphasizing how groups of people with difficulties can still participate in their own lives. Over the coming decades, stages applied to populations served by vertically integrated clinical practices could facilitate large-scale planning, with the goal of maximizing personal autonomy among groups of community-dwelling people with disabilities.

  View details for DOI 10.1016/j.pmrj.2014.05.001

  View details for PubMedID 24798263

  View details for PubMedCentralID PMC4216780

• Adverse childhood experiences and disability in u.s. Adults. PM & R : the journal of injury, function, and rehabilitation Schüssler-Fiorenza Rose, S. M., Xie, D., Stineman, M. 2014; 6 (8): 670-680

  Abstract

  To assess relationships between adverse childhood experiences and self-reported disabilities in adult life.Cross-sectional, random-digit-dialed, state-population-based survey (Behavioral Risk Factor Surveillance System).Fourteen states and the District of Columbia.Noninstitutionalized adults ages ≥18 years surveyed in 2009 and/or in 2010 (n = 81,184).The Behavioral Risk Factor Surveillance System Adverse Childhood Experience (ACE) Module asks about abuse (physical, sexual, emotional), family dysfunction (exposures to domestic violence, living with mentally ill, substance abusing, or incarcerated family member(s), and/or parental separation and/or divorce) that occurred before age 18 years. The ACE score sums affirmed ACE categories (range, 0-8). We controlled for demographic characteristics (age, race, education, income, and marital status) and self-reported physical health conditions (stroke, myocardial infarction, diabetes, coronary heart disease, asthma). Five states asked participants about mental health conditions (anxiety, depression). A subset analysis of participants in these states evaluated the effect of adjusting for these conditions.The primary outcome was disability (self-reported activity limitation and/or assistive device use).More than half of participants (57%) reported at least 1 adverse childhood experience category, and 23.2% reported disability. The odds ratio (95% confidence interval) of disability increased in a graded fashion from odds ratio 1.3 (95% confidence interval, 1.2-1.4) among those who experienced 1 adverse experience to odds ratio 5.8 (95% confidence interval, 4.6-7.5) among those with 7-8 adverse experiences compared with those with no such experiences when adjusting for demographic factors. The relationship between adverse experiences and disability remained strong after adjusting for physical and mental health conditions.There is a strong graded relationship between childhood exposure to abuse and household dysfunction and self-reported disability in adulthood, even after adjusting for potentially mediating health conditions. Greater clinician, researcher, and policymaker awareness of the impact of childhood adversity on disability is crucial to help those affected by childhood adversity lead more functional lives.

  View details for DOI 10.1016/j.pmrj.2014.01.013

  View details for PubMedID 24486921

• Comparison of complex versus simple activity of daily living staging: validation of simple stages. Archives of physical medicine and rehabilitation Schüssler-Fiorenza, C. M., Xie, D., Pan, Q., Stineman, M. G. 2013; 94 (7): 1320-1327

  Abstract

  To compare activities of daily living (ADL) staging based on 2-level responses to ADL difficulty questions (simple ADL stages) with ADL staging based on 4-level ADL question responses (complex ADL stages).Analysis of the Second Longitudinal Study of Aging, a prospective cohort study, using descriptive statistics and logistic regression.Participants' homes.Community-dwelling persons (N=9447) aged ≥70 years in 1994.Not applicable.(1) Agreement and face validity: baseline simple ADL stage; (2) construct validity: baseline health, difficulty, and need characteristics; (3) prognostic comparison (determined at the Wave 2 interview): primary-nursing home use and/or death; secondary-death.The systems showed good agreement (κ=.75). The simple ADL stages stratified people into distinct groups and reflected the expected stepwise increases from stage 0 to stage IV in health and need characteristics, such as the prevalence of home-related challenges (2.9%-84.5%) and perceived need for home modifications (2.1%-33.6%). In comparing the prognostic ability using the primary outcome, the complex system model demonstrated slightly increased discrimination between milder stages and a slightly higher C statistic (.666 vs .664).Although complex staging appears slightly better at classifying people into distinct prognostic strata with respect to nursing home use and/or death at Wave 2, simple ADL stages demonstrate strong, clinically relevant associations with health and need characteristics.

  View details for DOI 10.1016/j.apmr.2012.11.046

  View details for PubMedID 23313353

• Adverse Childhood Experiences, Disability and Health-Risk Behaviors Population Health Matters (Formerly Health Policy Newsletter) Schüssler-Fiorenza Rose, S. 2013; 26 (3): Available at: http://jdc.jefferson.edu/hpn/vol26/iss3/12
• Current perspectives: fecal incontinence in older adults Aging Health Schüssler-Fiorenza, C., Wald, A. 2007; 3 (6): 751-765

  View details for DOI 10.2217/1745509X.3.6.751

• The surgical management of Graves' disease JOURNAL OF SURGICAL RESEARCH Schussler-Fiorenza, C. M., Bruns, C. M., Chen, H. 2006; 133 (2): 207-214

  Abstract

  The historical aspects of the pathophysiology and treatment of Graves' disease are briefly discussed in this paper.The three treatment modalities of Graves' disease are anti-thyroid drug therapy, radioactive iodine therapy, and surgery. Although the majority of patients with Graves' disease in the U.S. are treated with radioactive iodine, surgery still plays an important role when patients cannot tolerate anti-thyroid drug therapy, when medical treatment is rejected by patients, or when surgery is deemed the fastest and safest route in managing the patient.The indications for surgical management of Graves' disease are discussed with emphasis on available data supporting the extent of thyroid resection based on the incidences of hypothyroidism, recurrence of hyperthyroidism, recurrent laryngeal nerve injury and hypoparathyroidism.

  View details for DOI 10.1016/j.jss.2005.12.014

  View details for Web of Science ID 000238243000021

  View details for PubMedID 16458922

• Satisfaction with Care Understanding Health Outcomes Research Smith, M., Schüssler-Fiorenza , C. M., Rockwood, T. Jones and Bartlett. 2006; 2nd: 185–216
• Clinical risk score correlates with yield of PET scan in patients with colorectal hepatic metastases - Discussion JOURNAL OF GASTROINTESTINAL SURGERY Fischer, J., Schussler-Fiorenza, C., Eagon, J., Schmidt, C. 2004; 8 (2): 157-158

  View details for Web of Science ID 000220024200003

• Clinical risk score correlates with yield of PET scan in patients with colorectal hepatic metastases 44th Annual Meeting of the Society-of-the-Alimentary-Tract Schussler-Fiorenza, C. M., Mahvi, D. M., Niederhuber, J., Rikkers, L. F., Weber, S. M. SPRINGER. 2004: 150–57

  Abstract

  Although positron emission tomography (PET) detects occult metastatic disease in approximately 20% of patients with isolated hepatic colorectal metastases, it is associated with false negative results in up to 16%. We hypothesized that patients with a poorer prognosis (as defined by clinical risk score [CRS]) would have a higher yield from PET. All patients with colorectal liver metastases who were imaged by means of PET between 1998 and 2002 were identified from a prospective PET database. All patients were assigned a CRS, with one point added for each of five preoperative factors (disease-free interval <1 year, tumor size >5 cm, tumor number >1, carcinoembryonic antigen >200, and node-positive primary lesion). A total of 85 PET scans were reviewed. In half the patients (53%), PET provided no additional information over conventional imaging. Occult extrahepatic disease was detected or questionable findings seen on conventional imaging were confirmed in 20% of PET scans, whereas PET readings were inaccurate in 27%. PET findings were correlated with CRS in a subset of 63 patients presenting with a first occurrence of hepatic colorectal metastases. Among patients with a CRS of 0, no patient had extrahepatic disease detected by PET and 57% had false positive readings, whereas among patients with a CRS of 1 or more, 14% were found to have additional disease that was detected only by PET, and there were no false positive readings (P<0.001, Fisher's exact test). Patients with isolated hepatic colorectal metastases and a CRS of 0 should undergo conventional imaging alone prior to surgical exploration.

  View details for DOI 10.1016/j.gassur.2003.11.009

  View details for Web of Science ID 000220024200002

  View details for PubMedID 15036190