Public Health Commons^™

A Large-Scale Genome-Wide Study Of Gene-Sleep Duration Interactions For Blood Pressure In 811,405 Individuals From Diverse Populations, Pavithra Nagarajan, Thomas W Winkler, Amy R Bentley, Clint L Miller, Aldi T Kraja, Karen Schwander, Songmi Lee, Wenyi Wang, Michael R Brown, John L Morrison, Ayush Giri, Jeffrey R O'Connell, Traci M Bartz, Lisa De Las Fuentes, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Zhijie Huang, Mart Kals, Minjung Kho, Christophe Lefevre, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Yuri Milaneschi, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Botong Shen, Stefan Stadler, Quan Sun, Jingxian Tang, Sébastien Thériault, Adriaan Van Der Graaf, Peter J Van Der Most, Yujie Wang, Stefan Weiss, Kenneth E Westerman, Qian Yang, Tabara Yasuharu, Wei Zhao, Wanying Zhu, Drew Altschul, Md Abu Yusuf Ansari, Pramod Anugu, Anna D Argoty-Pantoja, Michael Arzt, Hugues Aschard, John R Attia, Lydia Bazzanno, Max A Breyer, Jennifer A Brody, Brian E Cade, Hung-Hsin Chen, Yii-Der Ida Chen, Zekai Chen, Paul S De Vries, Latchezar M Dimitrov, Anh Do, Jiawen Du, Charles T Dupont, Todd L Edwards, Michele K Evans, Tariq Faquih, Stephan B Felix, Susan P Fisher-Hoch, James S Floyd, Mariaelisa Graff, Charles Gu, Dongfeng Gu, Kristen G Hairston, Anthony J Hanley, Iris M Heid, Sami Heikkinen, Heather M Highland, Michelle M Hood, Mika Kähönen, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Setoh Kazuya, Tanika N Kelly, Pirjo Komulainen, Daniel Levy, Henry J Lin, Peter Y Liu, Pedro Marques-Vidal, Joseph B Mccormick, Hao Mei, James B Meigs, Cristina Menni, Kisung Nam, Ilja M Nolte, Natasha L Pacheco, Lauren E Petty, Hannah G Polikowsky, Michael A Province, Bruce M Psaty, Laura M Raffield, Olli T Raitakari, Stephen S Rich, Renata L Riha, Lorenz Risch, Martin Risch, Edward A Ruiz-Narvaez, Rodney J Scott, Colleen M Sitlani, Jennifer A Smith, Tamar Sofer, Maris Teder-Laving, Uwe Völker, Peter Vollenweider, Guanchao Wang, Ko Willems Van Dijk, Otis D Wilson, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Xiaofeng Zhu, Jennifer E Below, Carsten A Böger, David Conen, Simon R Cox, Marcus Dörr, Mary F Feitosa, Ervin R Fox, Nora Franceschini, Sina A Gharib, Vilmundur Gudnason, Sioban D Harlow, Jiang He, Elizabeth G Holliday, Zoltan Kutalik, Timo A Lakka, Deborah A Lawlor, Seunggeun Lee, Terho Lehtimäki, Changwei Li, Ching-Ti Liu, Reedik Mägi, Fumihiko Matsuda, Alanna C Morrison, Brenda Wjh Penninx, Patricia A Peyser, Jerome I Rotter, Harold Snieder, Tim D Spector, Lynne E Wagenknecht, Nicholas J Wareham, Alan B Zonderman, Kari E North, Myriam Fornage, Million Veteran Program, Adriana M Hung, Alisa K Manning, James Gauderman, Han Chen, Patricia B Munroe, Dabeeru C Rao, Diana Van Heemst, Susan Redline, Raymond Noordam, Heming Wang

Faculty, Staff and Student Publications

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health …

Chance Or Strategy? Assessing The Unanticipated Policy Window For Active Transportation During The Covid-19 Pandemic: A Systematic Review, Katja Siefken, Michael Pratt, Juliana Mejía-Grueso, Adrian Bauman, Deborah Salvo, Catherine B Woods, Wanda Wendel-Vos, Justin Richards, J Jaime Miranda, Pedro C Hallal, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Physical activity (PA) policy is essential for promoting population-level PA by coordinating efforts across various sectors. Global crises like the COVID-19 pandemic can open policy windows, enabling rapid implementation of innovative policies. This study examined how policy windows shaped active transportation (AT) policies during the pandemic, resulting in infrastructural changes.

Methods: A systematic review using PubMed, Scopus, ProQuest-Coronavirus Research Database, Web of Science, WHO COVID-19 Research Database, PsycInfo, and SPORTDiscus conducted to characterize AT policy during the pandemic (2020-2023). Descriptive analyses were conducted in Stata. PROSPERO registration number: CRD42025644930.

Results: The search retrieved 3879 articles; 1162 were duplicates, leaving 2716 …

Accelerometer-Measured Chronoactivity And Type 2 Diabetes Risk: A Prospective Study In Uk Biobank Participants, Qiuyu Feng, Gali Albalak, Ko Willems Van Dijk, Jeroen H P M Van Der Velde, Qian Xiao, Raymond Noordam, Diana Van Heemst

Faculty, Staff and Student Publications

Objective: We assessed whether timing of physical activity, independent from the total activity amount, - which we refer to as chronoactivity - is associated with type 2 diabetes (T2D) risk.

Methods: We included UK Biobank participants with valid accelerometry data (UK, exposure measurement: 2013-2015, follow-up till November 2023) and without diabetes mellitus at baseline (N = 89,439; mean age: 61.7 [SD:7.9] years). Relative hourly physical activity was calculated by dividing the average hourly clock time physical activity by the average hourly physical activity in a week. Participants were categorized into different chronoactivity clusters using k-means cluster analysis on relative hourly …

Genome-Wide Approaches To Bacterial Strain Typing: A History And Review Of Recent Methodological Advances, William C Shropshire, Blake M Hanson, Samuel A Shelburne

Faculty, Staff and Student Publications

Purpose of review: Whole genome sequencing (WGS) has transformed bacterial strain typing, an essential tool for outbreak detection, antimicrobial resistance surveillance, and tracking clonal emergence across clinical, research, and public health settings. Herein, we will review recent advances in WGS-based bacterial strain typing methods for purposes of comparison and classification with a focus on improvements in variant identification, strain classification, and transmission assessment.

Recent findings: Advances in sequencing technologies as well as variant calling methodologies and parameter optimization have enhanced the precision and accuracy of single nucleotide variant identification. Hierarchical clustering of gene-by-gene strain typing, combined with novel data management …

Role And Use Of Race In Artificial Intelligence And Machine Learning Models Related To Health, Martin C Were, Ang Li, Bradley A Malin, Zhijun Yin, Joseph R Coco, Benjamin X Collins, Ellen Wright Clayton, Laurie L Novak, Rachele Hendricks-Sturrup, Abiodun O Oluyomi, Shilo Anders, Chao Yan

Faculty, Staff and Students Publications

The role and use of race within health-related artificial intelligence (AI) and machine learning (ML) models have sparked increasing attention and controversy. Despite the complexity and breadth of related issues, a robust and holistic framework to guide stakeholders in their examination and resolution remains lacking. This perspective provides a broad-based, systematic, and crosscutting landscape analysis of race-related challenges, structured around the AI and ML life cycle and framed through "points to consider" to support inquiry and decision-making.

Refinement Of Hyams Grading Criteria For Olfactory Neuroblastoma In An Endoscopic Sinus Surgery Predominant Cohort With Extended Follow-Up: Worth The Effort?, Stacey Gargano, Vincent Cracolici, Carl Snyderman, Eric Wang, Garret Choby, Aron Pollack, Paul Gardner, Diana Bell, Raja Seethala

Computational Medicine Center Faculty Papers

BACKGROUND: Hyams grading is considered prognostic in olfactory neuroblastoma (ONB), but grading criteria are subjective and predate modern classification and surgical approach. We evaluate the application of granular grading criteria to an endoscopic surgery predominant cohort with extended follow-up.

METHODS: 78 ONB patients were identified (1994-2019) with original diagnoses dating to 1979. Original Hyams grade, Modified Hyams grade incorporating more detailed criteria and other histologic features (i.e. divergent differentiation, clear cell/oncocytic change, and spindling) were assessed if feasible, evaluated for distribution by grade and correlated with outcomes.

RESULTS: Original Hyams grade (n = 43) distribution was: I: 4 (9%), II: …

Physician And Hospital Performance In Medicare’S Updated Bundled-Payment Model For Joint Replacement, Aidan P. Crowley, Austin S. Kilaru, Qian Erin Huang, Erkuan Wang, Jingsan Zhu, Ayush Arora, Torrey Shirk, Deborah S. Cousins, Kristin A. Linn, Said A. Ibrahim, Joshua M. Liao, Amol S. Navathe

Department of Medicine Faculty Papers

IMPORTANCE: Independent evaluations of Bundled Payments for Care Improvement Advanced (BPCI-A) have focused on hospitals and have not assessed the performance of physicians in participating physician group practices (PGPs). However, PGPs are accountable for a larger proportion of surgical procedures, including for lower-extremity joint replacement, in the BPCI-A model than are hospitals.

OBJECTIVE: To evaluate the association of treatment by BPCI-A-participating physicians and hospitals with health care spending, quality, and utilization for joint replacement procedures compared to nonparticipants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Medicare claims of beneficiaries receiving lower-extremity joint replacement between April 2016 and September 2019 …

A Multi-Modal Pelvic Mri Dataset For Deep Learning-Based Pelvic Organ Segmentation In Endometriosis, Xiaomin Liang, Linda A Alpuing Radilla, Kamand Khalaj, Haaniya Dawoodally, Chinmay Mokashi, Xiaoming Guan, Kirk E Roberts, Sunil A Sheth, Varaha S Tammisetti, Luca Giancardo

Faculty, Staff and Students Publications

Endometriosis affects approximately 190 million females of reproductive age worldwide. Magnetic Resonance Imaging (MRI) has been recommended as the primary non-invasive diagnostic method for endometriosis. This study presents new female pelvic MRI multicenter datasets for endometriosis and shows the baseline segmentation performance of two auto-segmentation pipelines: the self-configuring nnU-Net and RAovSeg, a custom network. The multi-sequence endometriosis MRI scans from two clinical institutions were collected. A multicenter dataset of 51 subjects with manual labels for multiple pelvic structures from three raters was used to assess interrater agreement. A second single-center dataset of 81 subjects with labels for multiple pelvic structures …

Experience Matters: An Application Of The Operative Value Index For Lumbar Fusions, Danyal Quraishi, Advith Sarikonda, D. Mitchell Self, Steven R. Glener, Arbaz A. Momin, Emily L. Isch, Ashmal K. Sami, Matthews Lan, Nicholas Clark, Ashwini Sharan, Srinivas Prasad, Jack Jallo, Joshua Pelta-Heller, Alex R. Vaccaro, James Harrop, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

INTRODUCTION: As healthcare systems transition to value-based care models, it is critical to understand factors influencing costs and outcomes in neurosurgery. This study utilizes Time-Driven Activity-Based Costing (TDABC) to assess the impact of surgeon experience and case volume on costs, clinical outcomes, and operative value in lumbar fusions. While TDABC has been applied in various surgical specialties, its use in neurosurgery, particularly in analyzing surgeon-specific factors, remains limited.

METHODS: A retrospective cohort study was conducted at a single center, analyzing lumbar instrumented arthrodesis procedures from 2017 to 2019. Primary variables included surgeon experience (years) and case volume (annual procedures). Confounding …

Stratifying The Population Based On Health Risk: Identification Of Patient Key Health Risk Factors Through Consensus Techniques, Carolina Castagna, Andrew Huff, Aaron Douglas, Phd, Matteo Garofano, Massimo Fabi, Richard W. Hass, Vittorio Maio

College of Population Health Faculty Papers

BACKGROUND: Risk stratification is a population health management approach that classifies patients according to their health risks and projected care needs. This strategy is especially valuable in primary care, where timely interventions for high-risk individuals can lead to better health outcomes, reduced healthcare expenditures, and a more sustainable healthcare system. The goal of this study was to establish expert consensus on the clinical and sociodemographic patient factors that should be incorporated into a primary care risk stratification tool.

METHODS: A multidisciplinary expert panel of 24 healthcare professionals, including primary care providers (PCPs), specialists, and allied health professionals, was convened in …

Sensing The Stiffness: Cellular Mechano-Sensing At The Implant Interface, Patricia S Pardo, Delia Danila, Raja Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

In this perspective, we highlight the relevance of the FA-Hippo signaling pathway and its regulation of the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ) as main players in the process of implants integration. The modulation and responses of YAP/TAZ triggered by substrate and ECM stiffness are of particular interest in the construction of materials used for medical implants. YAP/TAZ nuclear localization and activity respond to the substrate stiffness by several mechanisms that involve the canonical and non-canonical Hippo signaling and independently of the Hippo cascade. YAP/TAZ regulate the expression of genes involved in several mechanisms …

Engaging Trusted Messengers In Public Health Response: Key Strategies To Building Community Trust Among Cdc’S Prevention Research Center’S Vaccine Confidence Network, Emily Stiehl, Amy Borg, John P Cullen, Anaïs Mendiola, Olivia Dominguez, Danielle Pester, Shan Qiao, Pooja Gandhi, Nicole Kuiper, Princilla Minkah, Shekwonya Samuel, Stephen Flores, Richard Quartarone, Grace W Ryan, Paula Cuccaro, Maria E Fernández, Sage Kim

Faculty, Staff and Student Publications

As part of Centers for Disease Control and Prevention's (CDC) Prevention Research Center (PRC) Vaccine Confidence Network (PRC VCN), 26 academic institutions were funded to increase COVID-19 vaccine confidence and uptake in their communities. Six sites (in communities located in Alabama, Illinois, Massachusetts, New York, South Carolina, and Texas) formed a workgroup to identify emergent themes, and share challenges and opportunities across projects. This essay describes their efforts to engage trusted messengers in vaccine activities, and discusses strategies to develop and sustain these types of partnerships in the future. All sites recruited trusted messengers with strong community relationships to engage …

Sensory Neuron-Expressed Fgf13 Controls Nociceptive Signaling In Diabetic Neuropathy Models, Aditya K Singh, Matteo Bernabucci, Nolan M Dvorak, Zahra Haghighijoo, Jessica Di Re, Nana A Goode, Feni K Kadakia, Laura A Maile, Olumarotimi O Folorunso, Paul A Wadsworth, Cynthia M Tapia, Pingyuan Wang, Jigong Wang, Haiying Chen, Yu Xue, Jully Singh, Kali Hankerd, Isaac J Gamez, Makenna Kager, Vincent Truong, Patrick Walsh, Stephanie I Shiers, Nishka Kuttanna, Hanyue Liao, Margherita Marchi, Erika Salvi, Ilaria D'Amato, Daniela D'Amico, Parsa Arman, Catharina G Faber, Rayaz A Malik, Marina De Tommaso, Dan Ziegler, Krishna Rajarathnam, Thomas A Green, Peter M Grace, Matthew R Sapio, Michael J Iadarola, Gregory D Cuny, Diana S Chow, Giuseppe Lauria Pinter, Steve Davidson, Dustin P Green, Jun-Ho La, Jin Mo Chung, Jia Zhou, Theodore J Price, Elizabeth Salisbury, Subo Yuan, Fernanda Laezza

Faculty, Staff and Student Publications

Nociception involves complex signaling, yet intrinsic mechanisms bidirectionally regulating this process remain unexplored. Here, we show that the fibroblast growth factor 13 (FGF13)/Nav1.7 protein-protein interaction (PPI) complex bidirectionally modulates nociception, and that the FGF13/Nav1.7 ratio is upregulated in type 2 diabetic neuropathy (T2DN). PW164, an FGF13/Nav1.7 channel C-terminal tail domain (CTD) PPI interface inhibitor, which reduces complex assembly, selectively suppressed Na+ currents sensitized by capsaicin-induced activation of TRPV1 channels in human induced pluripotent stem cell-derived (hIPSC-derived) sensory neurons and inhibited mechanical and thermal hyperalgesia in mice. FGF13 silencing mimics PW164 activity in culture and in vivo. Conversely, ZL192, an FGF13 …

Impact Of Sanitation System Types On Residential And Environmental Presence Of Human Waste And Parasites In Alabama, Brandon Hunter, Catherine Coleman Flowers, Rojelio Mejia, Marc Arnold Deshusses

Faculty, Staff and Students Publications

Lowndes County is a predominantly Black rural county in Alabama, in the United States, which has a historical and current legacy of racial discrimination, creating inequitable infrastructure access and adverse health impacts. Over 80% rely on on-site sanitation infrastructure and most are failing. A community assessment of exposure to untreated sewage was conducted using samples from residential drinking water, surface swabs, and soil combined with environmental water and soil samples using culture-based and quantitative polymerase chain reaction (qPCR) methods. Testing varied slightly across samples, due to difficulty of access or availability. Of 43 households, 68% and 55% of houses had …

Rapid High-Sensitivity Detection Of Antibodies To Trypanosoma Cruzi With A Recombinant Tc24 Antigen-Based Magneto-Immunoassay: A Pilot Study, Kavya L Singampalli, Bin Zhan, Rojelio Mejia, Peter B Lillehoj

Faculty, Staff and Students Publications

The diagnosis of chronic Chagas disease is challenging due to the wide genetic diversity of Trypanosoma cruzi, the causative agent of Chagas disease, and low levels of parasitemia, resulting in low sensitivity and accuracy with existing diagnostics. We report a magneto-immunoassay that employs dually labeled magnetic beads incorporating a recombinant Tc24 antigen, which is homologous across multiple discrete typing units of T cruzi. In this pilot study, 102 serum samples from 7 endemic countries were tested by this magneto-immunoassay, revealing its ability to distinguish Chagas-positive from Chagas-negative cases more accurately and faster than a standard Tc24-based immunoassay.

Molecular Epidemiology And Clinical Characterization Of Carbapenemase-Producing Enterobacter Species From An International Cohort, Jianping Jiang, Lauren Komarow, Carol Hill, Angelique E Boutzoukas, Blake Hanson, Cesar A Arias, Robert A Bonomo, Scott Evans, Yohei Doi, Michael J Satlin, Gregory Weston, Eric Cober, Sandra Liliana Valderrama-Beltran, Soraya Salcedo Mendoza, Zhengyin Liu, Bettina C Fries, Paul Ananth Tambyah, Henry F Chambers, Vance G Fowler, David Van Duin, Barry N Kreiswirth, Liang Chen

Faculty, Staff and Student Publications

Background: Despite the global public health threat posed by carbapenem-resistant Enterobacter spp, clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp infections.

Methods: Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016 to 2018 with cultures positive for carbapenemase-producing Enterobacter spp were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed.

Results: We enrolled 136 hospitalized patients with carbapenemase-producing …

Oral Dosing Of The Nucleoside Analog Obeldesivir Is Efficacious Against Rsv Infection In African Green Monkeys, Jared Pitts, J Lizbeth Reyes Zamora, Savrina Manhas, Thomas Aeschbacher, Josolyn Chan, Vincent Cutillas, Varsha Nair, Nicholas C Riola, Arya Vijjapurapu, Meghan S Vermillion, Stacey Eng, Christopher Richards, Dong Han, Jason K Perry, Subhra Chaudhuri, Szu-Wen Liu, Clarissa Martinez, Nadine Peinovich, Kai-Hui Sun, Arthur Cai, Ross Martin, Jasmine Moshiri, Charlotte Hedskog, Darius Babusis, Dustin S Siegel, Rao Kalla, Vasanthi Avadhanula, Pedro A Piedra, Kim Stobbelaar, Peter L Delputte, Caleb Marceau, Roberto Mateo, Evguenia Maiorova, Hongmei Mo, Raju Subramanian, Richard L Mackman, Tomas Cihlar, Simon P Fletcher, John P Bilello

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC50: 0.20–0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identify a single amino acid substitution, I777L, in the L polymerase with …

Global Diversity Of Soil-Transmitted Helminths Reveals Population-Biased Genetic Variation That Impacts Diagnostic Targets, Marina Papaiakovou, Andrea Waeschenbach, Olumide Ajibola, Sitara Sr Ajjampur, Roy M Anderson, Robin Bailey, Jade Benjamin-Chung, Maria Cambra-Pellejà, Nicolas R Caro, David Chaima, Rubén O Cimino, Piet Cools, Anélsio Cossa, Julia Dunn, Sean Galagan, Javier Gandasegui, Berta Grau-Pujol, Emma L Houlder, Moudachirou Ibikounlé, Timothy P Jenkins, Khumbo Kalua, Eyrun F Kjetland, Alejandro J Krolewiecki, Bruno Levecke, Adrian Jf Luty, Andrew S Macdonald, Inácio Mandomando, Malathi Manuel, Maria Martínez-Valladares, Rojelio Mejia, Zeleke Mekonnen, Augusto Messa, Harriet Mpairwe, Osvaldo Muchisse, Jose Muñoz, Pauline Mwinzi, Valdemiro Novela, Maurice R Odiere, Charfudin Sacoor, Judd L Walson, Steven A Williams, Stefan Witek-Mcmanus, D Timothy J Littlewood, Cinzia Cantacessi, Stephen R Doyle

Faculty, Staff and Students Publications

Soil-transmitted helminths (STHs) are intestinal parasites that affect over a billion people worldwide. STH control relies on microscopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance; however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence settings. The genetic diversity of helminths and its potential impact on molecular diagnostics remain unclear. Using low-coverage genome sequencing, we assess the genetics of STHs within worm, faecal, and purified egg samples from 27 countries, identifying differences in the genetic connectivity and diversity of STH-positive samples across regions and cryptic diversity between closely related human- and pig-infective species. We …

Single-Cell Profiling Of Bone Metastasis Ecosystems From Multiple Cancer Types Reveals Convergent And Divergent Mechanisms Of Bone Colonization, Fengshuo Liu, Yunfeng Ding, Zhan Xu, Xiaoxin Hao, Tianhong Pan, George Miles, Siyue Wang, Yi-Hsuan Wu, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Liqun Yu, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Bone is a common site for metastasis of solid cancers. The diversity of histological and molecular characteristics of bone metastases (BMs) remains poorly studied. Here, we performed single-cell RNA sequencing on 42 BMs from eight cancer types, identifying three distinct ecosystem archetypes, each characterized by an enrichment of specific immune cells: macrophages/osteoclasts, regulatory/exhausted T cells, or monocytes. We validated these archetypes by immunostaining on tissue sections and bioinformatic analysis of bulk RNA sequencing/microarray data from 158 BMs across more than 10 cancer types. Interestingly, we found only a modest correlation between the BM archetypes and the tissues of origin; BMs …

High-Affinity Cd16a Polymorphism Associated With Reduced Risk Ofsevere Covid-19, Anita E Qualls, Tasha Tsao, Irene Lui, Shion A Lim, Yapeng Su, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Christian Bime, Carolyn S Calfee, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Impacc Network, Jason D Goldman, Daniel R Calabrese, James R Heath, James A Wells, Elaine F Reed, Lewis L Lanier, Harry Pickering, Oscar A Aguilar

Faculty, Staff and Students Publications

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 …

Exploring Sex-Specific Clinical Features In Chinese Patients With Takotsubo Syndrome, Hong-Yi Duan, Ling-Lin Wang, Ling-Chun Lyu, Zhen-Hua Shi, Xiao-Ping Lin, Zheng-Yang Yu, Guo-Hua Fan, Jing Chen, Xin-Hong Yang, Wei Deng, Chang-Wu Xu, Yan Huang, Qing Zhou, Jin-Ling Chen, Hong-Ning Song, Dong Hu, Jin-Qiu Liu, Hector Barajas-Martinez, Charles Antzelevitch, Kan Liu, Hong Jiang, Dan Hu

Department of Medicine Faculty Papers

BACKGROUND: Takotsubo syndrome (TTS) is considered as a transient acute heart failure syndrome predominant in females. However, data on Chinese TTS patients are limited. Therefore, this study aimed to investigate the clinical characteristics of Chinese TTS patients, identify prognostic markers.

METHODS: A total of 258 TTS patients were enrolled. Data on clinical characteristics and in-hospital major adverse cardiovascular events (MACE) were collected and analyzed. The latter included severe heart failure, shock, malignant arrhythmia, and death.

RESULTS: The average age of TTS patients was 59.3 ± 19.2 years. Female patients accounted for 68.9%. MACE occurred in 41.4% of patients during hospitalization. …

Assessment Of Functioning Using The Whodas 20 Among People With Myasthenia Gravis-Associated Disability: A Nationwide Follow-Up Study, Jia-Pei Hong, Chih-Hong Lee, Chien Tai Hong, Lung Chan, Chen-Chih Chung, Prangthip Charoenpong, Hou-Chang Chiu, Tsan-Hon Liou

Faculty, Staff and Students Publications

Background: Advancements in treatment have increased the life expectancy of patients with Myasthenia Gravis (MG), yet the understanding of functional changes in these individuals remains limited. In our study, we explored the functional abilities of individuals with MG using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

Methods: This observational study analyzed data from 286 patients with MG, acquired from the Data Bank of Persons with Disabilities (TDPD) in Taiwan between July 11, 2012, and December 31, 2021. Participants were diagnosed with MG after the acute phase. The functional disability outcome was assessed using the WHODAS 2.0. Due …

Systemic Exogenous Progestins With Or Without Estrogens Are Associated With Decreased Rates Of Venous Procedures For Varicose Veins, Paarth Jain, Adam M. Ostrovsky, Paul J Dimuzio, Luis H. Eraso, Michael Nooromid, Dawn Salvatore, Babak Abai

Department of Surgery Faculty Papers

OBJECTIVES: Risk factors for varicose veins (VVs) such as female sex, pregnancy, and obesity are high estrogen states, yet the role of systemic progestins with or without estrogens (SPEs) in VV management is not well characterized. This study investigates how SPE use affects rates of venous procedures for patients with VV.

METHODS: The TriNetX database was queried for subjects with International Classification of Diseases, 10th edition, diagnoses of asymptomatic VV, chronic venous insufficiency, and complicated VV (inflammation or ulceration). Patients were divided into a control cohort with no subsequent SPE use, a progestin-only cohort, and a combined estrogen-progestin (CEP) cohort. …

Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare

Faculty, Staff and Students Publications

Gamete donation has become a crucial part of Assisted Reproductive Technologies (ARTs), providing hope to individuals, including those who may have no other option for parenthood. This process comes with a wide range of ethical, medical, and legal challenges that need to be carefully addressed to protect the well-being and rights of all parties involved: donors, recipients, and offspring. Navigating these complexities requires strict ethical standards, robust regulatory frameworks, and international collaboration. By standardizing these, the field of gamete donation can continue to develop while ensuring that all parties are well informed and safeguarded. This paper explores the ethical concerns …

Unfolding The Mystery Of Autoimmunity: The Environmental Determinants Of Diabetes In The Young (Teddy) Study, Marian Rewers, Daniel Agardh, Suzanne Bennett Johnson, Ezio Bonifacio, Helena Elding Larsson, Patricia Gesualdo, William Hagopian, Michael J Haller, Heikki Hyöty, Randi Johnson, Richard Mcindoe, Eoin Mckinney, Jessica Melin, Åke Lernmark, Richard E Lloyd, Kristian F Lynch, Jill M Norris, Stephen S Rich, Roswith Roth, Desmond Schatz, Jorma Toppari, Eric Triplett, Kendra Vehik, Suvi M Virtanen, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Teddy Study Group

Faculty, Staff and Students Publications

In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune …

Cytokine Release Syndrome And Neurotoxicity Following Cd19 Car-T In B-Cell Lymphoma, Roni Shouval, Christopher Strouse, Soyoung Kim, Temitope Oloyede, Sairah Ahmed, Farrukh T Awan, Danny Luan, Veronika Bachanova, Talha Badar, Merav Bar, Pere Barba, Amer M Beitinjaneh, Amanda Cashen, Bhagirathbhai Dholaria, Mahmoud Elsawy, Siddhartha Ganguly, Praveen Ramakrishnan Geethakumari, Uri Greenbaum, Hamza Hashmi, Laquisa C Hill, Michael D Jain, Tania Jain, Partow Kebriaei, Adam S Kittai, Frederick L Locke, Premal D Lulla, Elena Mead, Joseph P Mcguirk, Alberto Mussetti, Taiga Nishihori, Amanda L Olson, Martina Pennisi, Miguel-Angel Perales, Peter A Riedell, Wael Saber, Abu-Sayeef Mirza, Margarida Magalhaes-Silverman, Elizabeth J Shpall, Mohamed Sorror, Kitsada Wudhikarn, Cameron J Turtle, Amy Moskop, Marcelo C Pasquini

Faculty, Staff and Students Publications

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns. Analyze temporal trends, risk factors, and associations between these toxicities and their severity. In this registry study by the Center for International Blood and Marrow Transplant Research, we studied CRS and ICANS in 1916 LBCL patients treated with commercial CAR-T therapies (axicabtagene ciloleucel 74.9%, tisagenlecleucel 25.1%) between 2018 and 2020. Outcomes include development of CRS/ICANS, timing and severity according to ASTC grading, overall survival (OS). Risk …

Performance Of Stool Xpert Mtb/Rif Ultra For Detection Of Mycobacterium Tuberculosis Among Adults Living With Hiv: A Multicentre, Prospective Diagnostic Study, George W Kasule, Sabine Hermans, Sozinho Acacio, Alexander Kay, Joachim Kikoyo Nsubuga, Carlos Fernández-Escobar, Nosisa Shiba, Lucia Carratalá-Castro, Derrick Semugenze, Patricia Mwachan, Shilzia Munguambe, Joanna Ehrlich, Elisa Lopez-Varela, Andrew R Dinardo, Frank Cobelens, Christoph Lange, Moses Joloba, Anna M Mandalakas, Willy Ssengooba, Alberto L García-Basteiro

Faculty, Staff and Students Publications

Background: When people living with HIV develop pulmonary tuberculosis, it often manifests without detectable acid-fast bacilli on sputum microscopy. We aimed to assess the diagnostic accuracy of stool Xpert MTB/RIF Ultra (hereafter, Ultra) for Mycobacterium tuberculosis detection among adults with HIV.

Methods: This multicentre, prospective diagnostic accuracy study was done in outpatient and inpatient health centres in Eswatini, Mozambique, and Uganda. We enrolled adults aged 15 years and older with HIV with presumptive tuberculosis. We evaluated the diagnostic accuracy of stool Ultra using the simple one-step processing method against a composite microbiological reference standard (CMRS) including three WHO-recommended tuberculosis diagnostic …

Military Inhalational Exposures Outside The Theater Of Conflict And Chronic Respiratory Symptoms, Reza Hosseini, Eric Garshick, Martin D Slade, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Ware Glenn Kuschner, Octavian C Ioachimescu, Michael Jerrett, Philippe R Montgrain, Susan P Proctor, Christine H Wendt, Cherry Wongtrakool, Emily S Wan, Paul D Blanc, Carrie A Redlich

Faculty, Staff and Students Publications

Importance: Deployment to Afghanistan and Southwest Asia has been associated with adverse respiratory health outcomes. However, the impact of inhalational exposures (eg, vapor, dust, gas, fumes), which are known correlates of reduced lung function and future chronic lung disease, during military service time outside this deployment period has not been assessed.

Objective: To assess military inhalational exposures during nonwartime routine activities and their associations with chronic respiratory symptoms.

Design, setting, and participants: This cross-sectional study used data from the US Department of Veterans Affairs Service and Health Among Deployed Veterans study. US veterans who served between October 7, 2001, and …

Decoding Metastatic Microenvironments Through Single-Cell Omics Reveals New Insights Into Niche Dynamics And Tumor Evolution, Fengshuo Liu, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastasis is the predominant cause of cancer mortality, primarily driven by complex tumor-host interactions within specialized metastatic niches. Recent advances in single-cell technologies have provided unprecedented insights into metastatic niche formation, evolution and function, including how primary tumors precondition distant organs for metastases and how disseminated tumor cells dynamically interact with host cells to modulate their environments. Integrated single-cell studies across multiple cancer types have also revealed divergent and convergent metastatic adaptation strategies. These findings collectively highlight metastasis as a dynamic, cooperative process shaped by intricate tumor-host interactions, and provide a foundation for novel therapeutic strategies targeting components of the …

Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja

Faculty, Staff and Students Publications

Purpose: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab).

Methods: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started …