Digital Commons Network^™

Establishing A Peritoneal Dialysis Technique Survival Core Outcome Measure: A Standardised Outcomes In Nephrology-Peritoneal Dialysis Consensus Workshop Report, Emma H Elphick, Karine E Manera, Andrea K Viecelli, Jonathan C Craig, Yeoungjee Cho, Angela Ju, Jenny I Shen, Martin Wilkie, Samaya Anumudu, Neil Boudville, Josephine Sf Chow, Simon J Davies, Patricia Gooden, Tess Harris, Arsh K Jain, Adrian Liew, Andrea Matus-Gonzalez, Noa Amir, Annie-Claire Nadeau-Fredette, Thu Nguyen, Angela Yee-Moon Wang, Daniela Ponce, Rob Quinn, Alison Jaure, David W Johnson, Mark Lambie, Peritoneal Dialysis International

Faculty, Staff and Students Publications

Background

Methods

Results

Subclinical Atherosclerosis And Cardiovascular Events Among Patients With Colorectal Cancer, Julia A Levy, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Prior studies have documented that patients with colorectal cancer (CRC) are at an increased risk of cardiovascular disease (CVD).

OBJECTIVES: To examine coronary artery calcium (CAC) as a marker of subclinical atherosclerosis and its association with major adverse cardiovascular events (MACE) in patients with CRC across the cancer treatment trajectory.

METHODS: Adults with newly diagnosed CRC were enrolled in the prospective ColoCare study from 2017 to 2024. CAC was measured from routine diagnostic computed tomography (CT) and positron emission tomography-CT scans at CRC diagnosis until 5 years post-diagnosis. Atherosclerosis was defined as the presence of CAC. We used multivariable-adjusted …

A Cerebrospinal Fluid Synaptic Protein Biomarker For Prediction Of Cognitive Resilience Versus Decline In Alzheimer's Disease, Hamilton Se-Hwee Oh, Yuanyuan Shen, Jigyasha Timsina, Chengran Yang, Daniel Western, Muhammad Ali, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Rates of cognitive decline in Alzheimer's disease (AD) are extremely heterogeneous. Although biomarkers for amyloid-beta (Aβ) and tau proteins, the hallmark AD pathologies, have improved pathology-based diagnosis, they explain only 20-40% of the variance in AD-related cognitive impairment (CI). To discover novel biomarkers of CI in AD, we performed cerebrospinal fluid (CSF) proteomics on 3,397 individuals from six major prospective AD case-control cohorts. Synapse proteins emerged as the strongest correlates of CI, independent of Aβ and tau. Using machine learning, we derived the CSF YWHAG:NPTX2 synapse protein ratio, which explained 27% of the variance in CI beyond CSF pTau

Translational Genomics Of Osteoarthritis In 1,962,069 Individuals, Konstantinos Hatzikotoulas, Lorraine Southam, Lilja Stefansdottir, Cindy G Boer, Merry-Lynn Mcdonald, J Patrick Pett, Young-Chan Park, Margo Tuerlings, Rick Mulders, Andrei Barysenka, Ana Luiza Arruda, Vinicius Tragante, Alison Rocco, Norbert Bittner, Shibo Chen, Susanne Horn, Vinodh Srinivasasainagendra, Ken To, Georgia Katsoula, Peter Kreitmaier, Amabel M M Tenghe, Arthur Gilly, Liubov Arbeeva, Lane G Chen, Agathe M De Pins, Daniel Dochtermann, Cecilie Henkel, Jonas Höijer, Shuji Ito, Penelope A Lind, Bitota Lukusa-Sawalena, Aye Ko Ko Minn, Marina Mola-Caminal, Akira Narita, Chelsea Nguyen, Ene Reimann, Micah D Silberstein, Anne-Heidi Skogholt, Hemant K Tiwari, Michelle S Yau, Ming Yue, Wei Zhao, Jin J Zhou, George Alexiadis, Karina Banasik, Søren Brunak, Archie Campbell, Jackson T S Cheung, Joseph Dowsett, Tariq Faquih, Jessica D Faul, Lijiang Fei, Anne Marie Fenstad, Takamitsu Funayama, Maiken E Gabrielsen, Chinatsu Gocho, Kirill Gromov, Thomas Hansen, Georgi Hudjashov, Thorvaldur Ingvarsson, Jessica S Johnson, Helgi Jonsson, Saori Kakehi, Juha Karjalainen, Elisa Kasbohm, Susanna Lemmelä, Kuang Lin, Xiaoxi Liu, Marieke Loef, Massimo Mangino, Daniel Mccartney, Iona Y Millwood, Joshua Richman, Mary B Roberts, Kathleen A Ryan, Dino Samartzis, Manu Shivakumar, Søren T Skou, Sachiyo Sugimoto, Ken Suzuki, Hiroshi Takuwa, Maris Teder-Laving, Laurent Thomas, Kohei Tomizuka, Constance Turman, Stefan Weiss, Tian T Wu, Eleni Zengini, Yanfei Zhang, Arcogen Consortium, Argo Consortium, Dbds Genomic Consortium, Estonian Biobank Research Team, Finngen, Genes & Health Research Team, Hunt All-In Pain, Million Veteran Program, Regeneron Genetics Center, Manuel Allen Revez Ferreira, George Babis, Aris Baras, Tyler Barker, David J Carey, Kathryn S E Cheah, Zhengming Chen, Jason Pui-Yin Cheung, Mark Daly, Renée De Mutsert, Charles B Eaton, Christian Erikstrup, Ove Nord Furnes, Yvonne M Golightly, Daniel F Gudbjartsson, Nils P Hailer, Caroline Hayward, Marc C Hochberg, Georg Homuth, Laura M Huckins, Kristian Hveem, Shiro Ikegawa, Muneaki Ishijima, Minoru Isomura, Marcus Jones, Jae H Kang, Sharon L R Kardia, Margreet Kloppenburg, Peter Kraft, Nobuyuki Kumahashi, Suguru Kuwata, Ming Ta Michael Lee, Phil H Lee, Robin Lerner, Liming Li, Steve A Lietman, Luca Lotta, Michelle K Lupton, Reedik Mägi, Nicholas G Martin, Timothy E Mcalindon, Sarah E Medland, Karl Michaëlsson, Braxton D Mitchell, Dennis O Mook-Kanamori, Andrew P Morris, Toru Nabika, Fuji Nagami, Amanda E Nelson, Sisse Rye Ostrowski, Aarno Palotie, Ole Birger Pedersen, Frits R Rosendaal, Mika Sakurai-Yageta, Carsten Oliver Schmidt, Pak Chung Sham, Jasvinder A Singh, Diane T Smelser, Jennifer A Smith, You-Qiang Song, Erik Sørensen, Gen Tamiya, Yoshifumi Tamura, Chikashi Terao, Gudmar Thorleifsson, Anders Troelsen, Aspasia Tsezou, Yuji Uchio, A G Uitterlinden, Henrik Ullum, Ana M Valdes, David A Van Heel, Robin G Walters, David R Weir, J Mark Wilkinson, Bendik S Winsvold, Masayuki Yamamoto, John-Anker Zwart, Kari Stefansson, Ingrid Meulenbelt, Sarah A Teichmann, Joyce B J Van Meurs, Unnur Styrkarsdottir, Eleftheria Zeggini

Faculty, Staff and Students Publications

Osteoarthritis is the third most rapidly growing health condition associated with disability, after dementia and diabetes1. By 2050, the total number of patients with osteoarthritis is estimated to reach 1 billion worldwide2. As no disease-modifying treatments exist for osteoarthritis, a better understanding of disease aetiopathology is urgently needed. Here we perform a genome-wide association study meta-analyses across up to 489,975 cases and 1,472,094 controls, establishing 962 independent associations, 513 of which have not been previously reported. Using single-cell multiomics data, we identify signal enrichment in embryonic skeletal development pathways. We integrate orthogonal lines of evidence, including …

Feasibility And Acceptability Of The Team Pilot Trial With African American And Latino Families, Ashley M Butler, Marisa E Hilliard, Krystal Christopher, Marissa Baudino, Charles Minard, Lefkothea Karaviti

Faculty, Staff and Students Publications

Objective: We adapted the empirically supported Family Teamwork intervention protocol to support collaborative parent involvement in type 1 diabetes (T1D) management among African American and Latino parents of children with T1D. This randomized pilot study aimed to evaluate feasibility and acceptability of the Type 1 Diabetes Empowerment and Management (TEAM) intervention.

Methods: African American and Latino parents (n = 59; 65% recruitment rate) of youth (ages 5-10 years, M = 8.9 ± 1.6 years; 59% female, M hemoglobin A1c 9.0% ± 1.9%) with diabetes duration of ≥1 year and who were fluent in English and not planning to leave the …

Differentiating Pathology Of Acute Disseminated Encephalomyelitis From Multiple Sclerosis In Children Using Diffusion Magnetic Resonance Biomarkers, Esra Pehlivan, Martin Kinuthia Mwangi, Vihas Abraham, Urmi Mange, Sheng-Kwei Song, Peng Sun, Soe Soe Mar

2020-Current year OA Pubs

BACKGROUND: To investigate the pathologic differences in patients with pediatric-onset multiple sclerosis (POMS) and acute disseminated encephalomyelitis (ADEM) using diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI).

METHODS: Fifteen children with POMS and eight children with ADEM underwent DTI and DBSI. The comparison of DTI and DBSI diffusivity measures of POMS (31 scans) and ADEM (17 scans) was performed as group comparison and association over time.

RESULTS: In univariate analysis of average measures of DBSI and DTI over time, DBSI fractional anisotropy is lower in POMS than ADEM (P = 0.002), indicative of axonal injury of POMS. Higher …

Phase 1, First-In-Human, Single-/Multiple-Ascending Dose Study Of Iluzanebart In Healthy Volunteers, Andreas Meier, Spyros Papapetropoulos, Andrew Marsh, Kelly Neelon, David Stiles, Ryan O'Mara, Evan A Thackaberry, Marco Colonna, Raj Rajagovindan

2020-Current year OA Pubs

OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of iluzanebart, a fully human monoclonal antibody TREM2 (triggering receptor expressed on myeloid cells 2) agonist, after single- (SAD) and multiple-ascending-dose (MAD) administration.

METHODS: Healthy adult volunteers (N = 136) received intravenous placebo or iluzanebart 1-60 mg/kg (SAD) or 10-60 mg/kg (MAD) followed by serial pharmacokinetics and safety assessments. Safety assessments included adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory evaluations. Pharmacokinetics were assessed through noncompartmental analysis. The study also included open-label cohorts (3, 10, 20, 40, 60 mg/kg SAD; 10, 20, 40 mg/kg MAD) for cerebrospinal fluid (CSF) collection …

Functions Of Communication During Emergency Care Of Children With Medical Complexity: Caregiver Perspectives, Julia A Ciurria, Jennifer Reyes Lin, Cassandra M Pruitt, Bryan A Sisk

2020-Current year OA Pubs

OBJECTIVE: We investigated communication experiences of caregivers of children with medical complexity (CMC) during emergency care.

METHODS: Fifteen caregivers of CMC participated in semi-structured interviews regarding communication while seeking care for their child in the emergency department (ED). Thematic analysis was applied using a previously established functional communication model as an a priori framework.

RESULTS: Each of the previously established 8 core functions of communication were identified in this population. "Building relationships" manifested as clinicians soliciting caregiver input and responding to the needs of the caregiver. "Exchanging information" included clearly explaining next steps to caregivers. "Responding to emotions" acknowledged the …

Clinical Correlates Of A High Cardiorespiratory Risk Score For Very Low Birth Weight Infants, Sherry L Kausch, Claire C Slevin, Amanda Duncan, Karen D Fairchild, Douglas E Lake, Jessica Keim-Malpass, Zachary A Vesoulis, Brynne A Sullivan

2020-Current year OA Pubs

BACKGROUND: A pulse oximetry warning system (POWS) to analyze heart rate and oxygen saturation data and predict risk of sepsis was developed for very low birth weight (VLBW) infants.

METHODS: We determined the clinical correlates and positive predictive value (PPV) of a high POWS score in VLBW infants. In a two-NICU retrospective study, we identified times when POWS increased above 6 (POWS spike). We selected an equal number of control times, matched for gestational and chronologic age. We reviewed records for infection and non-infection events around POWS spikes and control times. We calculated the frequencies and PPV of a POWS …

Multi-Omic And Spatial Analysis Of Mouse Kidneys Highlights Sex-Specific Differences In Gene Regulation Across The Lifespan, Siqi Chen, Ruiyang Liu, Chia-Kuei Mo, Michael C Wendl, Andrew Houston, Preet Lal, Yanyan Zhao, Wagma Caravan, Andrew T Shinkle, Atieh Abedin-Do, Nataly Naser Al Deen, Kazuhito Sato, Xiang Li, André Luiz N Targino Da Costa, Yize Li, Alla Karpova, John M Herndon, Maxim N Artyomov, Joshua B Rubin, Sanjay Jain, Sheila A Stewart, Li Ding, Feng Chen, Et Al.

2020-Current year OA Pubs

There is a sex bias in the incidence and progression of many kidney diseases. To better understand such sexual dimorphism, we integrated data from six platforms, characterizing 76 kidney samples from 68 mice at six developmental and adult time points, creating a molecular atlas of the mouse kidney across the lifespan for both sexes. We show that proximal tubules have the most sex-biased differentially expressed genes emerging after 3 weeks of age and are associated with hormonal regulations. We reveal potential mechanisms involving both direct and indirect regulation by androgens and estrogens. Spatial profiling identifies distinct sex-biased spatial patterns in …

Wb5, A Novel Biomarker For Monitoring Efficacy And Success Of Mass Drug Administration Programs For Wuchereria Bancrofti Elimination, Rachel E. Pietrow, Catherine Bjerum, Benjamin G. Koudou, Taniawati Supali, Philip J Budge, Peter U. Fischer, Thomas B. Nutman, Sasisekhar Bennuru

2020-Current year OA Pubs

The success of mass drug administration at reducing the prevalence of lymphatic filariasis in endemic areas has led to an increased need for highly sensitive and specific diagnostic assays. To be useful in post-elimination surveillance in areas with low to zero prevalence, high test performance characteristics are required to enable the early detection of infection recrudescence. As current testing suffers from either sensitivity or specificity levels that fail to meet adopted target product profiles, additional targets that could be used as confirmatory tests or in multiplexed assays could overcome these issues. To this end, bioinformatic analyses coupled with stage-specific expression …

Treatment Patterns And Survival Among Veterans With De Novo Metastatic Hormone-Sensitive Prostate Cancer, Martin W Schoen, Saira Khan, Eric M Knoche, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Combination therapy for metastatic hormone-sensitive prostate cancer (mHSPC) has been widely adopted, yet clinical use and outcomes are unknown. Furthermore, optimal therapy is uncertain due to lack of direct comparison of androgen receptor pathway inhibitors (ARPIs) and docetaxel in high-volume disease.

OBJECTIVE: To evaluate the use of combination therapy and its association with overall survival among patients with mHSPC and to compare ARPIs vs docetaxel doublet therapy by volume of disease.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study was conducted in the US Veterans Health Administration among 6216 US veterans with de novo mHSPC from January 1, 2013, …

Early-Life Factors And Body Mass Index Trajectories Among Children In The Echo Cohort, Chang Liu, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Identifying atypical body mass index (BMI) trajectories in children and understanding associated, modifiable early-life factors may help prevent childhood obesity.

OBJECTIVE: To characterize multiphase BMI trajectories in children and identify associated modifiable early-life factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included longitudinal data obtained from January 1997 to June 2024, from the Environmental influences on Child Health Outcomes (ECHO) cohort, which included children aged 1 to 9 years with 4 or more weight and height assessments. Analyses were conducted from January to June 2024.

EXPOSURES: Prenatal exposure to substances and stress (smoking, alcohol, depression, anxiety), maternal characteristics (prepregnancy …

Multiregional Implementation Initiative's Impact On Guideline-Based Performance Measures For Patients Hospitalized With Heart Failure: Implement-Hf, Andrew J. Sauer, Nancy Sweitzer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite randomized data for survival benefit (with class 1 recommendations) for treating heart failure (HF) with reduced ejection fraction using quadruple medical therapy (QMT)-defined as evidence-based β-blockers, sodium-glucose cotransporter 2 inhibitor, preferably angiotensin receptor/neprilysin inhibitor, and mineralocorticoid receptor antagonist-it is underutilized. IMPLEMENT-HF is a multiregional HF quality improvement initiative to improve care and outcomes for patients with HF by enhancing the use of QMT in routine practice.

METHODS: This analysis of HF with reduced ejection fraction treatment in patients from hospitals participating in the American Heart Association's Get With The Guidelines-HF who volunteered to participate in IMPLEMENT-HF in 7 …

Using A Surgical Risk Predictor To Estimate Percutaneous Cryoablation Adverse Event Risk: A Single Center Comparative Analysis, Prisha Patel, Koustav Pal, Hadi Ahmed, Bill Tang, Iwan Paolucci, Mohammad Khavandi, Peiman Habibollahi, Ketan Shah, Steven Y Huang, Bruno C Odisio, Sanjay Gupta, Kamran Ahrar, Steven Yevich, Joshua D Kuban, Alda Tam, Rahul A Sheth

Faculty, Staff and Student Publications

Objective: To evaluate the relevance of established surgical risk calculators for predicting complications in patients undergoing percutaneous lung cryoablation (PLC).

Methods: The institution's database was queried for PLC procedures from March 2015 to May 2024, excluding those patients with concomitant local therapies or five or more lesions treated in a single setting. Demographics, frailty metrics as defined by the surgical literature, and procedural variables were collected. To evaluate the suitability of surgical risk estimate calculators, the requisite demographic data were input into the American College of Surgery surgical risk calculator; estimates for length of stay (LOS), serious complications, 30-day readmission, …

Sustained Improvement In Health-Related Quality Of Life In Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, And Dexamethasone: Maia Final Analysis Of Patient-Reported Outcomes, Aurore Perrot, Thierry Facon, Torben Plesner, Saad Z Usmani, Shaji Kumar, Nizar J Bahlis, Cyrille Hulin, Robert Z Orlowski, Hareth Nahi, Peter Mollee, Karthik Ramasamy, Murielle Roussel, Arnaud Jaccard, Michel Delforge, Lionel Karlin, Bertrand Arnulf, Ajai Chari, George Wang, Niodita Gupta-Werner, Shuchita Kaila, Huiling Pei, Kathryn Matt, Katharine S Gries, Robin Carson, Fredrik Borgsten, Katja Weisel

Faculty, Staff and Student Publications

Objectives: This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.

Methods: Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.

Results: The intent-to-treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D-Rd-treated patients showed improvements from baseline that were sustained over 5 years in the intent-to-treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D-Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16-2.91]), physical functioning (1.93 [1.18-3.14]), pain (1.41 [0.90-2.22]), and fatigue (2.00 [1.24-3.23]). Greater proportions of patients with bone lesions improved with D-Rd versus Rd on GHS and physical functioning.

Conclusions: In transplant-ineligible patients with NDMM, D-Rd improved health-related quality of …

T2-Weighted Imaging Of Rectal Cancer Using A 3d Fast Spin Echo Sequence With And Without Deep Learning Reconstruction: A Reader Study, Dan Nguyen, Sarah Palmquist, Ken-Pin Hwang, Jingfei Ma, Usama Salem, Jia Sun, Xinzeng Wang, Jong Bum Son, Randy Ernst, Peng Wei, Harmeet Kaur, Nir Stanietzky

Faculty, Staff and Student Publications

Purpose: To compare image quality and clinical utility of a T2-weighted (T2W) 3-dimensional (3D) fast spin echo (FSE) sequence using deep learning reconstruction (DLR) versus conventional reconstruction for rectal magnetic resonance imaging (MRI).

Methods: The study included 50 patients with rectal cancer who underwent rectal MRI consecutively between July 7, 2020 and January 20, 2021 using a T2W 3D FSE sequence with DLR and conventional reconstruction. Three radiologists reviewed the two sets of images, scoring overall SNR, motion artifacts, and overall image quality on a 3-point scale and indicating clinical preference for DLR or conventional reconstruction based on those three …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Temporal Trends Of Subsequent Central Nervous System Malignancies Among Survivors Of Childhood Cancer, Robert T Galvin, Yan Chen, Yan Yuan, Tabitha Cooney, Rebecca Howell, Susan Smith, Michael A Arnold, Miriam Conces, Wendy Leisenring, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970 and 1999 in the Childhood Cancer Survivor Study with CNS subsequent malignant neoplasms were identified. Cumulative incidence rates and standardized incidence ratios were compared among survivors diagnosed between 1970-1979 (n = 6223), 1980-1989 (n = 9680), and 1990-1999 (n = 8999). Multivariable models assessed risk factors for CNS subsequent malignant neoplasms.

Results: A total of 157 CNS …

Impact Of Comorbidities On The Mortality Benefits Of Lung Cancer Screening: A Post-Hoc Analysis Of The Plco And Nlst Trials, Sebastien Gendarme, Ehsan Irajizad, James P Long, Johannes F Fahrmann, Jennifer B Dennison, Seyyed Mahmood Ghasemi, Rongzhang Dou, Robert J Volk, Rafael Meza, Iakovos Toumazis, Florence Canoui-Poitrine, Samir M Hanash, Edwin J Ostrin

Faculty, Staff and Student Publications

Objectives: To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed tomography.

Methods: We developed a comorbidity index (Prostate, Lung, Colorectal, and Ovarian comorbidity index [PLCO-ci]) using LCS-eligible participants' data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts five-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated using the area under the receiver operating characteristics curve. In NLST, LC mortality (per original publication) was compared between low-dose computed tomography and chest radiograph arms across the PLCO-ci quintile …

Chd1 Loss Reprograms Srebp2-Driven Cholesterol Synthesis To Fuel Androgen-Responsive Growth And Castration Resistance In Spop-Mutated Prostate Tumors, Feiyu Chen, Haoyan Li, Yin Wang, Ximing Tang, Kevin Lin, Qidong Li, Chenling Meng, Wei Shi, Javier Leo, Xin Liang, Jie Zhang, Vivien Van, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Maria G Raso, Ana Aparicio, Yue Lu, Daniel E Frigo, Boyi Gan, Di Zhao

Faculty, Staff and Student Publications

Despite undergoing castration, most individuals with prostate cancer (PCa) experience progression to castration-resistant PCa (CRPC), in which the androgen receptor (AR) remains an important driver. Concurrent genetic alterations in SPOP and CHD1 define a unique subtype of PCa, but their interactions in tumor progression and therapy response remain unclear. Here, we provide genetic evidence supporting that CHD1 loss accelerates disease progression and confers resistance to castration in males with SPOP-mutated PCa. By leveraging genetic engineering and multiomics, we uncovered a noncanonical function of CHD1 in lipid metabolism reprogramming via repressing the SREBP2 transcriptome. Loss of CHD1 induces cholesterol production, supplies …

Defining The Optimal Radiation-Induced Lymphopenia Metric To Discern Its Survival Impact In Esophageal Cancer, Pim J J Damen, Max Peters, Brian Hobbs, Yiqing Chen, Uwe Titt, Remi Nout, Radhe Mohan, Steven H Lin, Peter S N Van Rossum

Faculty, Staff and Student Publications

Purpose: A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in patients with esophageal cancer has been established. However, an optimal metric for RIL remains undefined but is important for the application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.

Methods and materials: Patients with esophageal cancer treated with concurrent chemoradiation therapy (CRT; 2004-2022) were selected. Studied metrics included absolute lymphocyte counts (ALCs) and neutrophil counts-and calculated derivatives-at baseline and during CRT. Multivariable Cox regression models for progression-free survival (PFS) and overall survival (OS) …

Oral Microbiome Profile Of The Us Population, Anil K Chaturvedi, Emily Vogtmann, Jianxin Shi, Yukiko Yano, Martin J Blaser, Nicholas A Bokulich, J Gregory Caporaso, Maura L Gillison, Barry I Graubard, Xing Hua, Autumn G Hullings, Lisa Kahle, Rob Knight, Shilan Li, Jody Mclean, Vaishnavi Purandare, Yunhu Wan, Neal D Freedman, Christian C Abnet

Faculty, Staff and Student Publications

Importance: The oral microbiome likely plays key roles in human health. Yet, population-representative characterizations are lacking.

Objective: To characterize the composition, diversity, and correlates of the oral microbiome in US adults.

Design, setting, and participants: This cross-sectional study analyzed data from the population-representative National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012. Microbiome data were made publicly available in 2024. NHANES participants were aged 18 to 69 years and provided oral rinse samples in 1 of 2 consecutive NHANES cycles (2009-2010 and 2011-2012).

Exposures: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.

Main outcomes and measures: Oral microbiome …

Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G W Verhaak, Itay Tirosh, Mario L Suvà

Faculty, Staff and Student Publications

The evolution of isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) after standard-of-care therapy remains poorly understood. Here we analyzed matched primary and recurrent GBMs from 59 patients using single-nucleus RNA sequencing and bulk DNA sequencing, assessing the longitudinal evolution of the GBM ecosystem across layers of cellular and molecular heterogeneity. The most consistent change was a lower malignant cell fraction at recurrence and a reciprocal increase in glial and neuronal cell types in the tumor microenvironment (TME). The predominant malignant cell state differed between most matched pairs, but no states were exclusive or highly enriched in either time point, nor was there …

Enterovirus D68-Associated Respiratory Illness In Children., Benjamin R. Clopper, Adriana S. Lopez, Leah A. Goldstein, Terry Fei Fan Ng, Ariana P. Toepfer, Mary A. Staat, Elizabeth P. Schlaudecker, Leila C. Sahni, Julie A. Boom, Jennifer E. Schuster, Rangaraj Selvarangan, Natasha B. Halasa, Laura S. Stewart, John V. Williams, Marian G. Michaels, Geoffrey A. Weinberg, Peter G. Szilagyi, Eileen J. Klein, Janet A. Englund, Meredith L. Mcmorrow, Heidi L. Moline, Claire M. Midgley

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Enterovirus D68 (EV-D68) typically causes mild to severe acute respiratory illness (ARI). Testing and surveillance for EV-D68 in the US are limited, and important epidemiologic gaps remain.

OBJECTIVE: To characterize the epidemiology and clinical severity of EV-D68 among US children seeking care for ARI from 2017 to 2022, using a multisite, active, systematic surveillance network.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study collected data from the New Vaccine Surveillance Network, an active, prospective, population-based surveillance system of emergency departments (EDs) and hospitals at 7 US academic medical centers. Children with ARI and EV-D68-positive results were enrolled during platform-wide EV-D68 …

Phenotypic Spectrum Of Gna11 R183c Mosaicism., Donglin Zhang, Luis Fernando Sánchez-Espino, Marta Ivars, Elena Pope, Amy J. Nopper, Lisa M. Arkin, Megha M. Tollefson, Cinzia E. Lavarino, Maya Muldowney, Nagore Gené Olaciregui, Sonia Paco, Beth A. Drolet, Eulàlia Baselga

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Many vascular anomalies harbor postzygotic somatic variants in GNAQ and GNA11; however, the phenotype of specific G-protein variants has not been well described. We report the clinical characteristics of 17 patients with a GNA11 R183C variant.

METHODS: This case series is derived from a multinational cohort of vascular anomaly patients whose pathogenic mutations were identified using high-depth next generation sequencing. Data include vascular anomaly features, imaging reports, and extracutaneous manifestations of the GNA11 R183C variant.

RESULTS: We identified 17 subjects (median age 18 years [range 6-67]) with somatic GNA11 R183C variant. All patients had vascular lesions of the skin …

Exploring Trauma And African American Male Victims Of Intimate Partner Violence, Paige Shaunta Denigi Simon

Doctoral Dissertations and Projects

This qualitative phenomenological study aimed to examine the experiences of heterosexual African American men from Georgia who are victims of IPV. This study aims to identify barriers that hinder survivors from reporting their trauma and seeking mental health services and resources. The theoretical framework utilized for this research study is Intersectional Theory. Using Intersectionality as a theoretical lens for this research study allows for a greater understanding of the multiple components and experiences that shape the identity of the African American man. This qualitative phenomenological study answered the following central research questions: “In what ways do African American male victims …

Pelabresib Plus Ruxolitinib For Jak Inhibitor-Naive Myelofibrosis: A Randomized Phase 3 Trial, Raajit K Rampal, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Janus kinase (JAK) inhibitors provide limited depth and durability of response in myelofibrosis. We evaluated pelabresib-a bromodomain and extraterminal domain (BET) inhibitor-plus ruxolitinib (a JAK inhibitor) compared with placebo plus ruxolitinib as first-line therapy. In this phase 3 study (MANIFEST-2), JAK inhibitor-naive patients with myelofibrosis were randomized 1:1 to pelabresib 125 mg once daily (QD; 50-175 mg QD permitted) for 14 days followed by a 7-day break (21-day cycle), or to placebo in combination with ruxolitinib 10 or 15 mg twice daily (BID; 5 mg QD-25 mg BID permitted). Primary endpoint was reduction in spleen volume of ≥35% from baseline …

Social Anxiety Moderates The Association Between Adolescent Irritability And Bully Perpetration, Michael T Perino, Jennifer C Harper-Lednicky, Alecia C Vogel, Chad M Sylvester, Deanna M Barch, Joan L Luby

2020-Current year OA Pubs

BACKGROUND: Preliminary work suggests anxiety moderates the relationship between irritability and bullying. As anxiety increases, the link between irritability and perpetration decreases. We hypothesize that any moderation effect of anxiety is driven by social anxiety symptoms. We sought to explicate the moderating effect of anxiety, while clarifying relations to other aggressive behaviors.

METHODS: A sample of adolescents (

RESULTS: Irritability was significantly related to bullying (

CONCLUSIONS: Understanding how psychopathology interacts with social behaviors is of great importance. Higher social anxiety is linked to reduced relations between irritability and bullying; however, the link between irritability and other aggression remains positive. …

Research Participant Interest In Learning Results Of Biomarker Tests For Alzheimer Disease, Spondita Goswami, Sarah M Hartz, Amy Oliver, Sacha Jackson, Tomi Ogungbenle, Alissa Evans, Erin Linnenbringer, Krista L Moulder, John C Morris, Jessica Mozersky

2020-Current year OA Pubs

IMPORTANCE: While available evidence suggests there are not major psychosocial harms of return of research results, there are limited data on uptake of Alzheimer disease (AD) research results or reasons for declining to learn results among participants in AD research studies.

OBJECTIVES: To quantitatively and qualitatively evaluate who declines to learn individual AD biomarker research results and what factors are associated with the decision.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study was conducted between November 1, 2020, and April 15, 2024, among participants aged 65 years or older with unimpaired cognition and available biomarker data (apolipoprotein E genotype and …