Digital Commons Network^™

Privacy-Aware Estimation Of Relatedness In Admixed Populations, Su Wang, Miran Kim, Wentao Li, Xiaoqian Jiang, Han Chen, Arif Harmanci

Faculty, Staff and Student Publications

BACKGROUND: Estimation of genetic relatedness, or kinship, is used occasionally for recreational purposes and in forensic applications. While numerous methods were developed to estimate kinship, they suffer from high computational requirements and often make an untenable assumption of homogeneous population ancestry of the samples. Moreover, genetic privacy is generally overlooked in the usage of kinship estimation methods. There can be ethical concerns about finding unknown familial relationships in third-party databases. Similar ethical concerns may arise while estimating and reporting sensitive population-level statistics such as inbreeding coefficients for the concerns around marginalization and stigmatization.

RESULTS: Here, we present SIGFRIED, which makes …

"Everything…Fell Apart Once Covid-19 Hit"-Leveraging The Covid-19 Response To Strengthen Public Health Activities Toward Ending The Hiv Epidemic: A Qualitative Study, Samantha A Devlin, Moctezuma Garcia, Kayo Fujimoto, Camden Hallmark, Marlene Mcneese, John Schneider, Moira C Mcnulty

Faculty, Staff and Student Publications

COVID-19 caused widespread disruption of activities for Ending the HIV Epidemic (EHE). In this study we assessed public health perspectives on leveraging the COVID-19 response to advance the goals of EHE. We conducted a qualitative study with 33 public health partners in the Midwestern and Southern United States from October 2020 to February 2022. Participants were asked how the strategies developed for COVID-19 could be applied to the HIV epidemic. Interviews were recorded, transcribed, and examined using rapid qualitative analysis. Four themes emerged: (1) Rebuilding teams and adapting culture for success in EHE activities; (2) Recognizing and modernizing the role …

Genome-Transcriptome-Functional Connectivity-Cognition Link Differentiates Schizophrenia From Bipolar Disorder, Jiayu Chen, Zening Fu, Juan R Bustillo, Nora I Perrone-Bizzozero, Dongdong Lin, Jose Canive, Godfrey D Pearlson, Julia M Stephen, Andrew R Mayer, Steven G Potkin, Theo G M Van Erp, Peter Kochunov, L Elliot Hong, Bhim M Adhikari, Ole A Andreassen, Ingrid Agartz, Lars T Westlye, Jing Sui, Yuhui Du, Fabio Macciardi, Faith M Hanlon, Rex E Jung, Jessica A Turner, Jingyu Liu, Vince D Calhoun

Faculty, Staff and Student Publications

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) and bipolar disorder (BD) share genetic risk factors, yet patients display differential levels of cognitive impairment. We hypothesized a genome-transcriptome-functional connectivity (frontoparietal)-cognition pathway linked to SZ-versus-BD differences, and conducted a multiscale study to delineate this pathway.

STUDY DESIGNS: Large genome-wide studies provided single nucleotide polymorphisms (SNPs) conferring more risk for SZ than BD, and we identified their regulated genes, namely SZ-biased SNPs and genes. We then (a) computed the polygenic risk score for SZ (PRSSZ) of SZ-biased SNPs and examined its associations with imaging-based frontoparietal functional connectivity (FC) and cognitive performances; (b) examined the spatial …

Policy Considerations That Support Equitable Access To Responsible, Accountable, Safe, And Ethical Uses Of Psychedelic Medicines, Sean J Belouin, Lynnette A Averill, Jack E Henningfield, Stephen N Xenakis, Ingrid Donato, Charles S Grob, Ann Berger, Veronica Magar, Alicia L Danforth, Brian T Anderson

Faculty, Staff and Students Publications

There is mounting evidence suggesting psychedelic and entactogen medicines (namely psilocybin and 3,4-methylenedioxymethamphetamine [MDMA]), in conjunction with proper psychosocial support, hold the potential to provide safe, rapid acting, and robust clinical improvements with durable effects. In the US, both psilocybin and MDMA have been granted Breakthrough Therapy designations by the US Food and Drug Administration and may potentially receive full FDA approval with similar regulatory considerations occurring in multiple countries. At the same time, regulatory changes are poised to increase access to legal or decriminalized psychedelic use in various non-medical settings. This review provides a brief discussion on the historical …

Serum Ctrp9 And High-Molecular Weight Adiponectin Are Associated With Ischemic Stroke., Yan-Qing Zhang, Yan-Wei Zhang, Jian-Li Dai, Chen Li, Wen-Qing Wang, Hai-Feng Zhang, Wayne Bond Lau, Xiao-Ming Wang, Xiao-Gang Liu, Rong Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke.

METHODS: There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured.

RESULTS: Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke …

Human Dectin-1 Deficiency Impairs Macrophage-Mediated Defense Against Phaeohyphomycosis, Rebecca A. Drummond, Jigar V. Desai, Amy P. Hsu, Vasileios Oikonomou, Donald C. Vinh, Joshua A. Acklin, Michael S. Abers, Magdalena A. Walkiewicz, Sarah L. Anzick, Muthulekha Swamydas, Simon Vautier, Mukil Natarajan, Andrew J. Oler, Daisuke Yamanaka, Katrin D. Mayer-Barber, Yoichiro Iwakura, David Bianchi, Brian Driscoll, Ken Hauck, Ahnika Kline, Nicholas S.P. Viall, Christa S. Zerbe, Elise M.N. Ferré, Monica M. Schmitt, Tom Dimaggio, Stefania Pittaluga, John A. Butman, Adrian M. Zelazny, Yvonne R. Shea, Cesar A. Arias, Cameron Ashbaugh, Maryam Mahmood, Zelalem Temesgen, Alexander G. Theofiles, Masayuki Nigo, Varsha Moudgal, Karen C. Bloch, Sean G. Kelly, M. Suzanne Whitworth, Ganesh Rao, Cindy J. Whitener, Neema Mafi, Juan Gea-Banacloche, Lawrence C. Kenyon, William R. Miller, Katia Boggian, Andrea Gilbert, Matthew Sincock, Alexandra F. Freeman, John E. Bennett, Rodrigo Hasbun, Constantinos M. Mikelis, Kyung J. Kwon-Chung, Yasmine Belkaid, Gordon D. Brown, Jean K. Lim, Douglas B. Kuhns, Steven M. Holland, Michail S. Lionakis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Subcutaneous phaeohyphomycosis typically affects immunocompetent individuals following traumatic inoculation. Severe or disseminated infection can occur in CARD9 deficiency or after transplantation, but the mechanisms protecting against phaeohyphomycosis remain unclear. We evaluated a patient with progressive, refractory Corynespora cassiicola phaeohyphomycosis and found that he carried biallelic deleterious mutations in CLEC7A encoding the CARD9-coupled, β-glucan-binding receptor, Dectin-1. The patient's PBMCs failed to produce TNF-α and IL-1β in response to β-glucan and/or C. cassiicola. To confirm the cellular and molecular requirements for immunity against C. cassiicola, we developed a mouse model of this infection. Mouse macrophages required Dectin-1 and CARD9 for IL-1β and …

Cerebral Blood Flow And Cardiovascular Risk Effects On Resting Brain Regional Homogeneity, Bhim M Adhikari, L Elliot Hong, Zhiwei Zhao, Danny J J Wang, Paul M Thompson, Neda Jahanshad, Alyssa H Zhu, Stefan Holiga, Jessica A Turner, Theo G M Van Erp, Vince D Calhoun, Kathryn S Hatch, Heather Bruce, Stephanie M Hare, Joshua Chiappelli, Eric L Goldwaser, Mark D Kvarta, Yizhou Ma, Xiaoming Du, Thomas E Nichols, Alan R Shuldiner, Braxton D Mitchell, Juergen Dukart, Shuo Chen, Peter Kochunov

Faculty, Staff and Student Publications

Regional homogeneity (ReHo) is a measure of local functional brain connectivity that has been reported to be altered in a wide range of neuropsychiatric disorders. Computed from brain resting-state functional MRI time series, ReHo is also sensitive to fluctuations in cerebral blood flow (CBF) that in turn may be influenced by cerebrovascular health. We accessed cerebrovascular health with Framingham cardiovascular risk score (FCVRS). We hypothesize that ReHo signal may be influenced by regional CBF; and that these associations can be summarized as FCVRS→CBF→ReHo. We used three independent samples to test this hypothesis. A test-retest sample of N = 30 healthy …

Anti-Diabetic Effects Of Glp1 Analogs Are Mediated By Thermogenic Interleukin-6 Signaling In Adipocytes, Absalon D Gutierrez, Zhanguo Gao, Vala Hamidi, Liang Zhu, Karla Bermudez Saint Andre, Kayla Riggs, Monika Ruscheinsky, Hongyu Wang, Yongmei Yu, Charles Miller, Hernan Vasquez, Heinrich Taegtmeyer, Mikhail G Kolonin

Faculty, Staff and Student Publications

Mechanisms underlying anti-diabetic effects of GLP1 analogs remain incompletely understood. We observed that in prediabetic humans exenatide treatment acutely induces interleukin-6 (IL-6) secretion by monocytes and IL-6 in systemic circulation. We hypothesized that GLP1 analogs signal through IL-6 in adipose tissue (AT) and used the mouse model to test if IL-6 receptor (IL-6R) signaling underlies the effects of the GLP1-IL-6 axis. We show that liraglutide transiently increases IL-6 in mouse circulation and IL-6R signaling in AT. Metronomic liraglutide treatment resulted in AT browning and thermogenesis linked with STAT3 activation. IL-6-blocking antibody treatment inhibited STAT3 activation in AT and suppressed liraglutide-induced …

Targeted Genome Sequencing Identifies Multiple Rare Variants In Caveolin-1 Associated With Obstructive Sleep Apnea, Jingjing Liang, Heming Wang, Brian E Cade, Nuzulul Kurniansyah, Karen Y He, Jiwon Lee, Scott A Sands, Jennifer A Brody, Han Chen, Daniel J Gottlieb, Daniel S Evans, Xiuqing Guo, Sina A Gharib, Lauren Hale, David R Hillman, Pamela L Lutsey, Sutapa Mukherjee, Heather M Ochs-Balcom, Lyle J Palmer, Shaun Purcell, Richa Saxena, Sanjay R Patel, Katie L Stone, Gregory J Tranah, Eric Boerwinkle, Xihong Lin, Yongmei Liu, Bruce M Psaty, Ramachandran S Vasan, Ani Manichaikul, Stephen S Rich, Jerome I Rotter, Tamar Sofer, Susan Redline, Xiaofeng Zhu

Faculty, Staff and Students Publications

Rationale: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA but limited data implicating specific genes.

Objectives: To search for rare variants contributing to OSA severity.

Methods: Leveraging high-depth genomic sequencing data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the CFS (Cleveland Family Study), followed by multistage gene-based association analyses in independent cohorts for apnea-hypopnea index (AHI) in a total …

A, B, C'S Of Trk Receptors And Their Ligands In Ocular Repair, Akash Gupta, Jeremias G Galletti, Zhiyuan Yu, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more selective to NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively. NGF is the most studied neurotrophin in the ocular surface and a human recombinant NGF has reached clinics, having been approved to treat neurotrophic keratitis. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are less studied neurotrophins in the ocular surface, even though brain-derived neurotrophic factor is well characterized in …

Increased Circulating Cortisol After Vaginal Birth Is Associated With Increased Fgf19 Secretion In Neonatal Pigs, Caitlin Vonderohe, Gregory Guthrie, Barbara Stoll, Valeria Melendez Hebib, Harry Dawson, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

The influence of birth modality (scheduled cesarean or spontaneous vaginal) on the development of the newborn has been a source of controversy in neonatology. The impact of cesarean vs vaginal birth on the development of bile acid and fibroblast growth factor 19 (FGF19) signaling is unknown. Our aim was to determine the effect of birth modality and gestational age (preterm vs term) on plasma hormone levels, bile acid pool distribution, expression of genes in the bile acid-FXR-FGF19 pathway, and plasma levels of FGF19 at birth and on day 3 of life in neonatal pigs. Four sows underwent cesarean delivery on …

Ontology-Based Feature Engineering In Machine Learning Workflows For Heterogeneous Epilepsy Patient Records, Satya S Sahoo, Katja Kobow, Jianzhe Zhang, Jeffrey Buchhalter, Mojtaba Dayyani, Dipak P Upadhyaya, Katrina Prantzalos, Meenakshi Bhattacharjee, Ingmar Blumcke, Samuel Wiebe, Samden D Lhatoo

Faculty, Staff and Student Publications

Biomedical ontologies are widely used to harmonize heterogeneous data and integrate large volumes of clinical data from multiple sources. This study analyzed the utility of ontologies beyond their traditional roles, that is, in addressing a challenging and currently underserved field of feature engineering in machine learning workflows. Machine learning workflows are being increasingly used to analyze medical records with heterogeneous phenotypic, genotypic, and related medical terms to improve patient care. We performed a retrospective study using neuropathology reports from the German Neuropathology Reference Center for Epilepsy Surgery at Erlangen, Germany. This cohort included 312 patients who underwent epilepsy surgery and …

Self-Guided Smartphone Application To Manage Chronic Musculoskeletal Pain: A Randomized, Controlled Pilot Trial, Chao Hsing Yeh, Jennifer Kawi, Lauren Grant, Xinran Huang, Hulin Wu, Robin L Hardwicke, Paul J Christo

Faculty, Staff and Student Publications

Objective: The goal of this study is to evaluate the feasibility and efficacy of an auricular point acupressure smartphone app (mAPA) to self-manage chronic musculoskeletal pain. Methods: A prospective, longitudinal, randomized, controlled pilot trial was conducted using a three-group design (self-guided mAPA (n = 14); in-person mAPA (n = 12); and control (n = 11)). The primary outcomes included physical function and pain intensity. Results: After a 4-week APA intervention, participants in the in-person mAPA group had improved physical function of 32% immediately post-intervention and 29% at the 1M follow-up. Participants in the self-guided mAPA group had …

Telerehabilitation: Future Of Phase Ii Cardiac Rehabilitation: Review Of Preliminary Outcomes, Mon S Bryant, Savitri E Fedson, Alexander Schutz, Lorraine D Cornwell, Amir Sharafkhaneh, Bandi Venkata

Center for Medical Ethics and Health Policy Staff Publications

In this brief communication, we reported Telehealth Home-Based Cardiac Rehabilitation (CR) program structure and preliminary outcomes from patients that completed a 12-week program after coronary artery bypass graft surgery (CABG). We aim to advocate the use of Telerehabilitation as a Phase II CR in patients immediately after the CABG. This approach was innovative and encouraging because the patients were still in subacute phase. The program can serve as a continuation of care for the patients after being discharged from a hospital while regaining their functional ability at home. Our preliminary outcomes demonstrated improvements in resting heart rate, activity level, nutrition …

Repeated Out-Of-Africa Expansions Of Helicobacter Pylori Driven By Replacement Of Deleterious Mutations, Harry A Thorpe, Elise Tourrette, Koji Yahara, Filipa F Vale, Siqi Liu, Mónica Oleastro, Teresa Alarcon, Tsachi-Tsadok Perets, Saeid Latifi-Navid, Yoshio Yamaoka, Beatriz Martinez-Gonzalez, Ioannis Karayiannis, Timokratis Karamitros, Dionyssios N Sgouras, Wael Elamin, Ben Pascoe, Samuel K Sheppard, Jukka Ronkainen, Pertti Aro, Lars Engstrand, Lars Agreus, Sebastian Suerbaum, Kaisa Thorell, Daniel Falush

Faculty, Staff and Students Publications

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying …

Clinical And In Vitro Evidence Favoring Immunoglobulin Treatment Of A Chronic Norovirus Infection In A Patient With Common Variable Immunodeficiency, Jeroen J A Van Kampen, Virgil A S H Dalm, Pieter L A Fraaij, Bas B Oude Munnink, Claudia M E Schapendonk, Ray W Izquierdo-Lara, Nele Villabruna, Khalil Ettayebi, Mary K Estes, Marion P G Koopmans, Miranda De Graaf

Faculty, Staff and Students Publications

BACKGROUND: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available.

METHODS: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced.

RESULTS: None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation …

Assessing The Contribution Of Rare Genetic Variants To Phenotypes Of Chronic Obstructive Pulmonary Disease Using Whole-Genome Sequence Data, Wonji Kim, Julian Hecker, R Graham Barr, Eric Boerwinkle, Brian Cade, Adolfo Correa, Josée Dupuis, Sina A Gharib, Leslie Lange, Stephanie J London, Alanna C Morrison, George T O'Connor, Elizabeth C Oelsner, Bruce M Psaty, Ramachandran S Vasan, Susan Redline, Stephen S Rich, Jerome I Rotter, Bing Yu, Christoph Lange, Ani Manichaikul, Jin J Zhou, Tamar Sofer, Edwin K Silverman, Dandi Qiao, Michael H Cho, Nhlbi Trans-Omics In Precision Medicine (Topmed) Consortium And Topmed Lung Working Group

Faculty, Staff and Students Publications

Rationale: Genetic variation has a substantial contribution to chronic obstructive pulmonary disease (COPD) and lung function measurements. Heritability estimates using genome-wide genotyping data can be biased if analyses do not appropriately account for the nonuniform distribution of genetic effects across the allele frequency and linkage disequilibrium (LD) spectrum. In addition, the contribution of rare variants has been unclear.

Objectives: We sought to assess the heritability of COPD and lung function using whole-genome sequence data from the Trans-Omics for Precision Medicine program.

Methods: Using the genome-based restricted maximum likelihood method, we partitioned the genome into bins based on minor allele frequency …

Reproducibility Efforts As A Teaching Tool: A Pilot Study, Nestoras Karathanasis, Daniel Hwang, Vibol Heng, Rimal Abhimannyu, Phillip Slogoff-Sevilla, Gina Buchel, Victoria Frisbie, Peiyao Li, Dafni Kryoneriti, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

The "replication crisis" is a methodological problem in which many scientific research findings have been difficult or impossible to replicate. Because the reproducibility of empirical results is an essential aspect of the scientific method, such failures endanger the credibility of theories based on them and possibly significant portions of scientific knowledge. An instance of the replication crisis, analytic replication, pertains to reproducing published results through computational reanalysis of the authors' original data. However, direct replications are costly, time-consuming, and unrewarded in today's publishing standards. We propose that bioinformatics and computational biology students replicate recent discoveries as part of their curriculum. …

Impact Of Molecular Sequence Data Completeness On Hiv Cluster Detection And A Network Science Approach To Enhance Detection, Sepideh Mazrouee, Camden J Hallmark, Ricardo Mora, Natascha Del Vecchio, Rocio Carrasco Hernandez, Michelle Carr, Marlene Mcneese, Kayo Fujimoto, Joel O Wertheim

Faculty, Staff and Student Publications

Detection of viral transmission clusters using molecular epidemiology is critical to the response pillar of the Ending the HIV Epidemic initiative. Here, we studied whether inference with an incomplete dataset would influence the accuracy of the reconstructed molecular transmission network. We analyzed viral sequence data available from ~ 13,000 individuals with diagnosed HIV (2012-2019) from Houston Health Department surveillance data with 53% completeness (n = 6852 individuals with sequences). We extracted random subsamples and compared the resulting reconstructed networks versus the full-size network. Increasing simulated completeness was associated with an increase in the number of detected clusters. We also subsampled …

De Novo Identification Of Microbial Contaminants In Low Microbial Biomass Microbiomes With Squeegee, Yunxi Liu, R A Leo Elworth, Michael D Jochum, Kjersti M Aagaard, Todd J Treangen

Faculty, Staff and Students Publications

Computational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low-biomass environments. Contamination from DNA extraction kits or sampling lab environments leaves taxonomic "bread crumbs" across multiple distinct sample types. Here we describe Squeegee, a de novo contamination detection tool that is based upon this principle, allowing the detection of microbial contaminants when negative controls are unavailable. On the low-biomass samples, we compare Squeegee predictions to experimental negative control data and show that …

A Comprehensive Artificial Intelligence Framework For Dental Diagnosis And Charting, Tanjida Kabir, Chun-Teh Lee, Luyao Chen, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

BACKGROUND: The aim of this study was to develop artificial intelligence (AI) guided framework to recognize tooth numbers in panoramic and intraoral radiographs (periapical and bitewing) without prior domain knowledge and arrange the intraoral radiographs into a full mouth series (FMS) arrangement template. This model can be integrated with different diseases diagnosis models, such as periodontitis or caries, to facilitate clinical examinations and diagnoses.

METHODS: The framework utilized image segmentation models to generate the masks of bone area, tooth, and cementoenamel junction (CEJ) lines from intraoral radiographs. These masks were used to detect and extract teeth bounding boxes utilizing several …

Conducting A Supportive Oncology Clinical Trial During The Covid-19 Pandemic: Challenges And Strategies, Jie Deng, John N. Lukens, Joy C. Cohn, Erin Mcmenamin, Barbara Murphy, Bryan A. Spinelli, Niya Murphy, Alicia K. Steinmetz, Megan A. Landriau, Alexander Lin

Department of Physical Therapy Faculty Papers

The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances.

Trial registration: ClinicalTrials.gov, a service of the US National Institute of …

Prevalence Of Sleep-Related Problems And Risks In A Community-Dwelling Older Adult Population: A Cross-Sectional Survey-Based Study, Nancy P Gordon, Jimmy H Yao, Leslea A Brickner, Joan C Lo

Faculty, Staff and Student Publications

BACKGROUND: Despite evidence of adverse health consequences of inadequate restorative sleep for older adults, assessment of sleep quantity, quality, and use of sleep aids is not routinely done. We aimed to characterize sleep problems, sleep risks, and advice received about sleep in a community-dwelling older adult population, overall and in subgroups with health conditions and functional difficulties.

METHODS: This cross-sectional study used weighted self-report data for 5074 Kaiser Permanente Northern California members aged 65-79y who responded to a 2017 or 2020 Member Health Survey. We estimated usual amount of sleep (< 6, 6 to < 7, ≥7 hours) and prevalence of sleep problems (frequent insomnia, frequent daytime fatigue, poor quality sleep, and potential sleep apnea (OSA) symptoms (frequent very loud snoring, apnea episodes)) for older adults overall, by self-rated health, and in subgroups reporting hypertension, diabetes, heart disease, frequent problems with balance/walking, and frequent memory problems. We also estimated percentages who regularly used sleep aids and had discussed sleep adequacy with a healthcare professional in the past year.

RESULTS: Approximately 30% of older adults usually got less …

A High-Resolution 3d Atlas Of The Spectrum Of Tuberculous Andcovid-19 Lung Lesions, Gordon Wells, Joel N Glasgow, Kievershen Nargan, Kapongo Lumamba, Rajhmun Madansein, Kameel Maharaj, Leon Y Perumal, Malcolm Matthew, Robert L Hunter, Hayden Pacl, Jacelyn E Peabody Lever, Denise D Stanford, Satinder P Singh, Prachi Bajpai, Upender Manne, Paul V Benson, Steven M Rowe, Stephan Le Roux, Alex Sigal, Muofhe Tshibalanganda, Carlyn Wells, Anton Du Plessis, Mpumelelo Msimang, Threnesan Naidoo, Adrie J C Steyn

Faculty, Staff and Student Publications

Our current understanding of the spectrum of TB and COVID-19 lesions in the human lung is limited by a reliance on low-resolution imaging platforms that cannot provide accurate 3D representations of lesion types within the context of the whole lung. To characterize TB and COVID-19 lesions in 3D, we applied micro/nanocomputed tomography to surgically resected, postmortem, and paraffin-embedded human lung tissue. We define a spectrum of TB pathologies, including cavitary lesions, calcium deposits outside and inside necrotic granulomas and mycetomas, and vascular rearrangement. We identified an unusual spatial arrangement of vasculature within an entire COVID-19 lobe, and 3D segmentation of …

Antibody-Drug Conjugates For The Treatment Of Her2-Positive Breast Cancer, Mariana K Najjar, Sara G Manore, Angelina T Regua, Hui-Wen Lo

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted …

Atomistic Measurement And Modeling Of Intrinsic Fracture Toughness Of Two-Dimensional Materials, Xu Zhang, Hoang Nguyen, Xiang Zhang, Pulickel M Ajayan, Jianguo Wen, Horacio D Espinosa

Faculty, Staff and Student Publications

Quantifying the intrinsic mechanical properties of two-dimensional (2D) materials is essential to predict the long-term reliability of materials and systems in emerging applications ranging from energy to health to next-generation sensors and electronics. Currently, measurements of fracture toughness and identification of associated atomistic mechanisms remain challenging. Herein, we report an integrated experimental-computational framework in which in-situ high-resolution transmission electron microscopy (HRTEM) measurements of the intrinsic fracture energy of monolayer MoS

Association Between Preoperative Hemodialysis Timing And Postoperative Mortality In Patients With End-Stage Kidney Disease, Vikram Fielding-Singh, Matthew W Vanneman, Tristan Grogan, Jacques P Neelankavil, Wolfgang C Winkelmayer, Tara I Chang, Vincent X Liu, Eugene Lin

Faculty, Staff and Students Publications

Importance: For patients with end-stage kidney disease treated with hemodialysis, the optimal timing of hemodialysis prior to elective surgical procedures is unknown.

Objective: To assess whether a longer interval between hemodialysis and subsequent surgery is associated with higher postoperative mortality in patients with end-stage kidney disease treated with hemodialysis.

Design, setting, and participants: Retrospective cohort study of 1 147 846 procedures among 346 828 Medicare beneficiaries with end-stage kidney disease treated with hemodialysis who underwent surgical procedures between January 1, 2011, and September 30, 2018. Follow-up ended on December 31, 2018.

Exposures: One-, two-, or three-day intervals between the most …

The Nogo Receptor Ngr2, A Novel Αvβ3 Integrin Effector, Induces Neuroendocrine Differentiation In Prostate Cancer, Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey-Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter Mccue, Andrew V. Kossenkov, Yanqing Wang, David W. Goodrich, Sheng-Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, …

High-Contrast Detection Of Somatostatin Receptor Subtype-2 For Fluorescence-Guided Surgery, Servando Hernandez Vargas, Solmaz Aghaamiri, Sukhen C Ghosh, Michael P Luciano, Luis C Borbon, Po Hien Ear, James R Howe, Jennifer M Bailey-Lundberg, Gregory D Simonek, Daniel M Halperin, Hop S Tran Cao, Naruhiko Ikoma, Martin J Schnermann, Ali Azhdarinia

Faculty, Staff and Student Publications

Dye design can influence the ability of fluorescently labeled imaging agents to generate tumor contrast and has become an area of significant interest in the field of fluorescence-guided surgery (FGS). Here, we show that the charge-balanced near-infrared fluorescent (NIRF) dye FNIR-Tag enhances the imaging properties of a fluorescently labeled somatostatin analogue.

Prognostic Performance Of Cystatin C In Covid-19: A Systematic Review And Meta-Analysis, Michal Matuszewski, Yurii Reznikov, Michal Pruc, Frank W Peacock, Alla Navolokina, Raúl Júarez-Vela, Lukasz Jankowski, Zubaid Rafique, Lukasz Szarpak

Faculty, Staff and Students Publications

Cystatin C is a specific biomarker of kidney function. We perform this meta-analysis to determine the association of Cystatin C with the COVID-19 severity. In this systematic review and meta-analysis, we searched PubMed, EMBASE, Cochrane library, and Web of Science for studies published until 2nd September 2022 that reported associations between Cystatin C levels and COVID-19 severity. The analysis was performed using a random-effects model to calculate pooled standard mean difference (SMD). Twenty-five studies were included in the meta-analysis. Pooled analysis showed statistically significant differences of Cystatin C levels among survive vs. decreased patients (0.998 ± 0.225 vs. 1.328 ± …