Digital Commons Network^™

Understanding Rare Genetic Variants Within The Terminal Pathway Of Complement System In Preeclampsia, A Inkeri Lokki, Michael Triebwasser, Emma Daly, Finnpec Core Investigator Group, Mitja I Kurki, Markus Perola, Kirsi Auro, Jane E Salmon, Java Anuja, Mark Daly, John P Atkinson, Hannele Laivuori, Seppo Meri

2020-Current year OA Pubs

Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25-467.43), p value = 0.01 and rs147430470: I330T, OR (CI95) = 22.75 (1.17-440.78), p value = 0.01). In addition, one predisposing rare variant …

Correlation Of Genogroup I, Genotype 1 (Gi.1) Norovirus Neutralizing Antibody Levels With Gi.1 Histo-Blood Group Antigen-Blocking Antibody Levels, Robert L Atmar, Khalil Ettayebi, Frederick H Neill, Ralph P Braun, James Sherwood, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Background: The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histo-blood group antigen (HBGA)-blocking assays.

Methods: Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/genogroup I, genotype 1 (GI.1) (P1) virus strain. Results were compared with those previously determined using HBGA-blocking assays.

Results: Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.81; P < .001) with those measured by HBGA blocking.

Conclusions: Genogroup I, genotype 1 (GI.1)-specific HBGA-blocking antibodies are a surrogate …

First-In-Human Dose-Escalation Study Of Fianlimab, An Antilymphocyte Activation Gene-3 Antibody, With Cemiplimab In Patients With Advanced Malignancies, Nehal J Lakhani, Haeseong Park, Et Al.

2020-Current year OA Pubs

PURPOSE: Preclinical data indicate that fianlimab (antilymphocyte activation gene-3) plus cemiplimab (anti-PD-1) enhances antitumor activity. Here, we report prespecified final analyses of the dose-escalation part of a first-in-human, phase 1 study (NCT03005782) of fianlimab as monotherapy and in combination with cemiplimab in patients with advanced malignancies.

PATIENTS AND METHODS: Adult patients received 1 to 40 mg/kg of fianlimab plus 350 mg of cemiplimab every 3 weeks (Q3W) across various dose-escalation schedules. Primary objectives were the rate of dose-limiting toxicities, adverse events (including immune mediated), deaths, laboratory abnormalities, and pharmacokinetics. Secondary outcomes were objective response rate, best overall response, duration of …

Global Impact Of Aging On The Hemodynamic Response Function In The Gray Matter Of Human Cerebral Cortex, Nooshin J Fesharaki, Amanda Taylor, Keisjon Mosby, Ruosha Li, Jung Hwan Kim, David Ress

Faculty, Staff and Students Publications

In functional magnetic resonance imaging, the hemodynamic response function (HRF) is a stereotypical response to local changes in cerebral hemodynamics and oxygen metabolism due to briefly (< 4 s) evoked neural activity. Accordingly, the HRF is often used as an impulse response with the assumption of linearity in data analysis. In cognitive aging studies, it has been very common to interpret differences in brain activation as age-related changes in neural activity. Contrary to this assumption, however, evidence has accrued that normal aging may also significantly affect the vasculature, thereby affecting cerebral hemodynamics and metabolism, confounding interpretation of fMRI cognitive aging studies. In this study, use was made of a multisensory task to evoke the HRF in ~87% of cerebral cortex in cognitively intact adults with ages ranging from 22 to 75 years. This widespread activation enabled us to investigate age trends in the spatial distributions of HRF characteristics within the majority of cortical gray matter, which we termed as global age trends. The task evoked both positive and negative HRFs, which were characterized using model-free parameters in native-space coordinates. We found significant global age trends in the distributions of HRF parameters in terms of both amplitudes (e.g., peak amplitude and contrast-to-noise ratio) and temporal dynamics (e.g., full-width-at-half-maximum). Our findings offer insight into how age-dependent changes affect neurovascular coupling and show promise for use of HRF parameters as non-invasive indicators for age-related pathology.

Parent And Primary Care Clinician Perceptions About Pediatric Hypertension, Abbas H. Zaidi, Erica Sood, Sarah De Ferranti, Samuel Gidding, Varsha Zadokar, Jonathan Miller, Anne Kazak

Department of Pediatrics Faculty Papers

IMPORTANCE: Despite published guidelines and a prevalence of pediatric hypertension of approximately 3%, less than 25% of affected children are identified, with 60% not receiving any intervention despite detection. Understanding the knowledge and perceptions of parents or caregivers and health care teams is crucial to identify factors that may contribute to these unacceptably low detection rates.

OBJECTIVE: To examine the knowledge and perceptions of parents and health care teams regarding pediatric hypertension to identify common themes contributing to low hypertension detection.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study, interviewed parents of children diagnosed with hypertension who did not follow up …

Estimation Of Prevalence Of Autoimmune Diseases In The United States Using Electronic Health Record Data, Aaron H. Abend, Albert M. Lai, Et Al.

2020-Current year OA Pubs

BACKGROUNDPrevious epidemiologic studies of autoimmune diseases in the US have included a limited number of diseases or used metaanalyses that rely on different data collection methods and analyses for each disease.METHODSTo estimate the prevalence of autoimmune diseases in the US, we used electronic health record data from 6 large medical systems in the US. We developed a software program using common methodology to compute the estimated prevalence of autoimmune diseases alone and in aggregate that can be readily used by other investigators to replicate or modify the analysis over time.RESULTSOur findings indicate that over 15 million people, or 4.6% of …

Diversity And Characteristics Of The Oral Microbiome Associated With Self-Reported Ancestral/Ethnic Groups, Qingguo Wang, Bing-Yan Wang, She'neka Williams, Hua Xie

Faculty, Staff and Student Publications

Periodontitis disproportionately affects genetic ancestral/ethnic groups. To characterize the oral microbiome from different genetic ancestral/ethnic groups, we collected 161 dental plaque samples from self-identified African Americans (AAs), Caucasian Americans (CAs), and Hispanic Americans (HAs) with clinical gingival health or biofilm-induced gingivitis on an intact periodontium. DNA was extracted from these samples, and then DNA libraries were prepared and sequenced using an Illumina NovaSeq high-throughput sequencer. We found significant differences in the diversity and abundance of microbial taxa among dental plaque samples of the AA, CA, and HA groups. We also identified unique microbial species in a self-reported ancestral/ethnic group. Moreover, …

Defining Renal Recovery In Patients With Hepatorenal Syndrome-Acute Kidney Injury: Experience From North American Studies, Muhammad A. Mujtaba, Hussien Elsiesy, Sara Faiz, Syed A. Hussain, Ann Kathleen N. Gamilla-Crudo, Aftab Karim, Mohammad I. Khan, Muhammad W. Khattak, Zunaira Zafar, Michael Kueht, Khurram Jamil

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

INTRODUCTION: The degree of improvement in serum creatinine (SCr) has previously been suggested as a sensitive indicator of treatment response in patients with hepatorenal syndrome-acute kidney injury (HRS-AKI), while HRS reversal remains the primary endpoint in clinical trials.

METHODS: A total of ≥ 30% SCr improvement was analyzed as an exploratory prespecified endpoint in the CONFIRM trial. In this post hoc analysis, intent-to-treat population data from three Phase 3 studies (OT-0401, REVERSE, and CONFIRM) conducted in North America in patients with HRS-AKI were pooled to assess the incidence of > 30% improvement in SCr and its association with clinical outcomes.

RESULTS: …

Imlunestrant, An Oral Selective Estrogen Receptor Degrader, As Monotherapy And In Combination With Targeted Therapy In Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Phase Ia/Ib Ember Study, Komal L Jhaveri, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Imlunestrant is a next-generation oral selective estrogen receptor (ER) degrader designed to deliver continuous ER target inhibition, including in

METHODS: An i3+3 dose-escalation design was used, followed by dose expansions of imlunestrant as monotherapy or in combination with abemaciclib with or without aromatase inhibitor (AI), everolimus, or alpelisib. Imlunestrant was administered orally once daily and with the combination partner per label.

RESULTS: Overall, 262 patients with ER+/HER2- ABC were treated (phase Ia, n = 74; phase Ib, n = 188). Among patients who received imlunestrant monotherapy (n = 114), no dose-limiting toxicities or discontinuations occurred. At the RP2D (400 …

Impact Of Prior Inotuzumab Ozogamicin Treatment On Brexucabtagene Autoleucel Outcomes In Adults With B-Cell All, Ibrahim Aldoss, Gregory W Roloff, Rawan Faramand, Noam E Kopmar, Chenyu Lin, Anjali S Advani, Simone E Dekker, Vishal K Gupta, Timothy E O'Connor, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Amy Zhang, Katharine Miller, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Bhagirathbhai Dholaria, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Aaron C Logan, Abdullah Ladha, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Matthew Connor, Kristen M O'Dwyer, Laquisa C Hill, Stephanie B Tsai, Joshua Sasine, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu Veeraputhiran, Betsy Blunk, Caspian Oliai, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Vinod Pullarkat, Bijal D Shah, Lori S Muffly

Faculty, Staff and Students Publications

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). …

Clinical Use Of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging In Patients On Extracorporeal Membrane Oxygenation: Results From The Multicenter Safe Mri Ecmo Study, Sung-Min Cho, Shivalika Khanduja, Christopher Wilcox, Kha Dinh, Jiah Kim, Jin Kook Kang, Ifeanyi David Chinedozi, Zachary Darby, Matthew Acton, Hannah Rando, Jessica Briscoe, Errol L Bush, Haris I Sair, John Pitts, Lori R Arlinghaus, Audrey-Carelle N Wandji, Elena Moreno, Glenda Torres, Bindu Akkanti, Jose Gavito-Higuera, Steven Keller, Huimahn A Choi, Bo Soo Kim, Aaron Gusdon, Glenn J Whitman

Faculty, Staff and Student Publications

Background: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI.

Methods: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive …

Prenatal Social Disadvantage Is Associated With Alterations In Functional Networks At Birth, Ashley N Nielsen, Regina L Triplett, Lourdes M Bernardez, Ursula A Tooley, Max P Herzberg, Rachel E Lean, Sydney Kaplan, Dominique Meyer, Jeanette K Kenley, Dimitrios Alexopoulos, David Losielle, Aidan Latham, Tara A Smyser, Arpana Agrawal, Josh S Shimony, Joshua J Jackson, J Philip Miller, Marcus E Raichle, Barbara B Warner, Cynthia E Rogers, Chad M Sylvester, Deanna M Barch, Joan L Luby, Christopher D Smyser

2020-Current year OA Pubs

Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood-brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated …

Pre-Sleep Routines Affecting Sleep In Adults, Diana Navarro, Rebecca King, Cassandra Nelson

Fall 2024 OTD Capstone Symposium

This capstone project examines the impact of pre-sleep routines on adult sleep quality, emphasizing the role of consistent habits, reduced technology use, and stress management. A six-week intervention incorporating evidence-based strategies such as sleep hygiene education, environmental adjustments, and relaxation techniques was conducted. Results revealed significant improvements in sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), and enhanced physical and emotional well-being among participants. These findings highlight the importance of tailored pre-sleep routines in addressing sleep disorders and provide a foundation for broader implementation and future research.

Transplant-Associated Tma: The Conundrum Of Diagnosis And Treatment, Ang Li, Sarah E Sartain

Faculty, Staff and Students Publications

Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic cell transplantation is characterized by microangiopathic hemolytic anemia (MAHA) with persistent schistocytosis, elevated markers of hemolysis, thrombocytopenia, and microvascular thrombosis leading to ischemic injuries in the kidneys and other organs. The initial evaluation of the disease requires confirmation of non-immune MAHA and careful examination of known secondary causes of TMA. Due to increased likelihood of long-term renal failure and overall mortality, a rapid diagnosis and treatment of the underlying trigger is needed. However, the diagnostic criteria proposed to define TA-TMA remain insufficient. sC5b9, the soluble form of the membrane attack complex of the terminal …

Domain-Specific Representation Of Social Inference By Neurons In The Human Amygdala And Hippocampus, Runnan Cao, Julien Dubois, Adam N Mamelak, Ralph Adolphs, Shuo Wang, Ueli Rutishauser

2020-Current year OA Pubs

Inferring the intentions and emotions of others from behavior is crucial for social cognition. While neuroimaging studies have identified brain regions involved in social inference, it remains unknown whether performing social inference is an abstract computation that generalizes across different stimulus categories or is specific to certain stimulus domain. We recorded single-neuron activity from the medial temporal lobe (MTL) and the medial frontal cortex (MFC) in neurosurgical patients performing different types of inferences from images of faces, hands, and natural scenes. Our findings indicate distinct neuron populations in both regions encoding inference type for social (faces, hands) and nonsocial (scenes) …

Differential Relationship Between Meditation Methods And Psychotic-Like And Mystical Experiences, Timothy Palmer, Kenza Kadri, Eric Fakra, Jacqueline Scholl, Elsa Fouragnan

School of Psychology

Much work has investigated beneficial effects of mindfulness-based meditation methods, but less work has investigated potential risks and differences across meditation methods. We addressed this in a large pre-registered online survey including 613 mediators where we correlated participants' experience with fifty meditation techniques to psychotic-like experiences (PLEs) and mystical experiences. We found a positive correlation for both PLEs and mystical experiences with techniques aiming at reducing phenomenological content ('null-directed', NDM) or classified as non-dual or less embodied. In contrast, methods aiming at achieving an enhanced cognitive state (CDM), also described as 'attentional' or strongly embodied, showed negative correlations with PLEs. …

Integrative Multi-Omics Analysis Uncovers Tumor-Immune-Gut Axis Influencing Immunotherapy Outcomes In Ovarian Cancer, Spencer R Rosario, Mark D Long, Shanmuga Chilakapati, Eduardo Cortes Gomez, Sebastiano Battaglia, Prashant K Singh, Jianmin Wang, Katy Wang, Kristopher Attwood, Suzanne M Hess, A J Robert Mcgray, Kunle Odunsi, Brahm H Segal, Gyorgy Paragh, Song Liu, Jennifer A Wargo, Emese Zsiros

Faculty, Staff and Student Publications

Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We …

Clonal Landscape And Clinical Outcomes Of Telomere Biology Disorders: Somatic Rescue And Cancer Mutations, Fernanda Gutierrez-Rodrigues, Emma M Groarke, Natthakan Thongon, Juan Jose Rodriguez-Sevilla, Luiz Fernando B Catto, Marena R Niewisch, Ruba Shalhoub, Lisa J Mcreynolds, Diego V Clé, Bhavisha A Patel, Xiaoyang Ma, Dalton Hironaka, Flávia S Donaires, Nina Spitofsky, Barbara A Santana, Tsung-Po Lai, Lemlem Alemu, Sachiko Kajigaya, Ivana Darden, Weiyin Zhou, Paul V Browne, Subrata Paul, Justin Lack, David J Young, Courtney D Dinardo, Abraham Aviv, Feiyang Ma, Michel Michels De Oliveira, Ana Paula De Azambuja, Cynthia E Dunbar, Malgorzata Olszewska, Emmanuel Olivier, Eirini P Papapetrou, Neelam Giri, Blanche P Alter, Carmem Bonfim, Colin O Wu, Guillermo Garcia-Manero, Sharon A Savage, Neal S Young, Simona Colla, Rodrigo T Calado

Faculty, Staff and Student Publications

Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype. CH occurred predominantly in symptomatic patients and in signature genes typically associated with cancers: PPM1D, POT1, TERT promoter (TERTp), U2AF1S34, and/or TP53. Chromosome 1q gain (Chr1q+) was the commonest karyotypic abnormality. Clinically, multiorgan involvement and CH in TERTp, TP53, …

Diet And Immune Effects Trial (Diet)- A Randomized, Double-Blinded Dietary Intervention Study In Patients With Melanoma Receiving Immunotherapy, Rachel M Farias, Yan Jiang, Erma J Levy, Cindy Hwang, Jian Wang, Elizabeth M Burton, Lorenzo Cohen, Nadim Ajami, Jennifer A Wargo, Carrie R Daniel, Jennifer L Mcquade

Faculty, Staff and Student Publications

Background: Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and …

Trajectory, Interactions, And Predictors Of Higher Symptom Burden During Induction Therapy For Multiple Myeloma, Mona Kamal, Qiuling Shi, Shu-En Shen, Charles Cleeland, Xin Shelley Wang

Faculty, Staff and Student Publications

Background: Patients with multiple myeloma (MM) experience disabling symptoms that are difficult to manage and may persist after induction therapy. Monitoring disease-related and induction therapy-induced symptoms and identifying patients at greater risk for high symptom burden are unmet clinical needs. The objective of this study was to examine the trajectories of symptom severity over time and identify predictors of high symptom burden during MM induction therapy.

Methodology: Eligible patients with MM rated their symptoms by completing the MD Anderson Symptom Inventory MM module repeatedly during 16 weeks of induction therapy. Group-based trajectory modeling identified patient groups with persistently high-severity (versus …

Functional Connectivity Biomarker Extraction For Schizophrenia Based On Energy Landscape Machine Learning Techniques, Janerra D Allen, Sravani Varanasi, Fei Han, L Elliot Hong, Fow-Sen Choa

Faculty, Staff and Student Publications

Brain connectivity represents the functional organization of the brain, which is an important indicator for evaluating neuropsychiatric disorders and treatment effects. Schizophrenia is associated with impaired functional connectivity but characterizing the complex abnormality patterns has been challenging. In this work, we used resting-state functional magnetic resonance imaging (fMRI) data to measure functional connectivity between 55 schizophrenia patients and 63 healthy controls across 246 regions of interest (ROIs) and extracted the disease-related connectivity patterns using energy landscape (EL) analysis. EL analysis captures the complexity of brain function in schizophrenia by focusing on functional brain state stability and region-specific dynamics. Age, sex, …

A Latent Class Assessment Of Healthcare Access Factors And Disparities In Breast Cancer Care Timeliness, Matthew Dunn, Didong Li, Marc Emerson, Caroline Thompson, Hazel Nichols, Sarah Van Alsten, Mya Roberson, Stephanie Wheeler, Lisa Carey, Terry Hyslop, Jennifer Elston Lafata, Melissa Troester

Kimmel Cancer Center Faculty Papers

BACKGROUND: Delays in breast cancer diagnosis and treatment lead to worse survival and quality of life. Racial disparities in care timeliness have been reported, but few studies have examined access at multiple points along the care continuum (diagnosis, treatment initiation, treatment duration, and genomic testing).

METHODS AND FINDINGS: The Carolina Breast Cancer Study (CBCS) Phase 3 is a population-based, case-only cohort (n = 2,998, 50% black) of patients with invasive breast cancer diagnoses (2008 to 2013). We used latent class analysis (LCA) to group participants based on patterns of factors within 3 separate domains: socioeconomic status ("SES"), "care barriers," and …

Alcohol Use Disorder Polygenic Score Compared With Family History And Adh1b, Dongbing Lai, Michael Zhang, Marco Abreu, Tae-Hwi Schwantes-An, Grace Chan, Danielle M Dick, Chella Kamarajan, Weipeng Kuang, John I Nurnberger, Martin H Plawecki, John Rice, Marc Schuckit, Bernice Porjesz, Yunlong Liu, Tatiana Foroud

2020-Current year OA Pubs

IMPORTANCE: Identification of individuals at high risk of alcohol use disorder (AUD) and subsequent application of prevention and intervention programs has been reported to decrease the incidence of AUD. The polygenic score (PGS), which measures an individual's genetic liability to a disease, can potentially be used to evaluate AUD risk.

OBJECTIVE: To assess the estimability and generalizability of the PGS, compared with family history and ADH1B, in evaluating the risk of AUD among populations of European ancestry.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted between October 1, 2023, and May 21, 2024. A 2-stage design was used. …

Adiposity Throughout Adulthood And Risk Of Young-Onset Breast Cancer Tumor Subtypes In The Young Women's Health History Study, Lydia Marcus Post, Dorothy R. Pathak, Ann S. Hamilton, Kelly A. Hirko, Richard T. Houang, Emily H. Guseman, Dan Sanfelippo, Nicole Bohme Carnegie, L. Karl Olson, Hallgeir Rui, Ann G. Schwartz, Ellen M. Velie

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: The role of adult adiposity in young-onset breast cancer (YOBC) subtype risk is not well understood.

METHODS: In this population-based case (n = 1812)-control (n = 1,381) study of invasive YOBC (ages <50 >years), cases were identified from the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results registries, 2010 to 2015. Area-based, frequency-matched controls were sampled from the 2010 Census. General adiposity [body mass index (BMI)] and central adiposity (waist circumference and waist-to-height ratio) across adulthood and covariates were collected from in-person interviews and measurements. ORs and 95% confidence intervals (CI) for adiposity and YOBC tumor subtypes …

Individualized Functional Magnetic Resonance Imaging Neuromodulation Enhances Visuospatial Perception: A Proof-Of-Concept Study, Anthony Allam, Vincent Allam, Sandy Reddy, Eric M Rohren, Sameer A Sheth, Emmanouil Froudarakis, T Dorina Papageorgiou

Duncan NRI Faculty and Staff Publications

This proof-of-concept study uses individualized functional magnetic resonance imaging neuromodulation (iNM) to explore the mechanisms that enhance BOLD signals in visuospatial perception (VP) networks that are crucial for navigation. Healthy participants (n = 8) performed a VP up- and down-direction discrimination task at full and subthreshold coherence through peripheral vision, and superimposed direction through visual imagery (VI) at central space under iNM and control conditions. iNM targets individualized anatomical and functional middle- and medial-superior temporal (MST) networks that control VP. We found that iNM engaged selective exteroceptive and interoceptive attention (SEIA) and motor planning (MP) networks. Specifically, iNM increased …

Excess Mortality In Persons With Concurrent Hiv And Cancer Diagnoses: A Retrospective Cohort Study, Kamaria L Lee, Varada Sarovar, Jennifer O Lam, Wendy A Leyden, Stacey E Alexeeff, Alexandra N Lea, Rulin C Hechter, Haihong Hu, Julia L Marcus, Qing Yuan, Jennifer R Kramer, Lilie L Lin, Elizabeth Y Chiao, William J Towner, Michael A Horberg, Michael J Silverberg

Center for Medical Ethics and Health Policy Staff Publications

Background: With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality among PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population.

Methods: We identified 39,000 PWH and 387,767 demographically matched PWoH in three integrated healthcare systems from 2000 to 2016. We estimated excess mortality among PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus-, and …

A Preoperative Window-Of-Opportunity Study Of Oral Serd, Imlunestrant, In Newly Diagnosed Er-Positive, Her2-Negative Early Breast Cancer: Results From The Ember-2 Study, Patrick Neven, Rebecca Aft, Et Al.

2020-Current year OA Pubs

PURPOSE: Imlunestrant is an oral selective estrogen receptor degrader with favorable safety and preliminary efficacy in patients with advanced breast cancer. Pharmacodynamic (PD) biomarker data can optimize drug dosing; in this study, we present PD data from the EMBER-2 study.

PATIENTS AND METHODS: Postmenopausal women with untreated, operable estrogen receptor (ER)-positive, HER2-negative early breast cancer were randomized to 400 versus 800 mg of imlunestrant daily for ∼2 weeks before surgery. A single arm study tested a daily dose of 200 mg. PD biomarker changes (ER, progesterone receptor, Ki-67 by IHC, and mRNA expression of ER-related genes) were evaluated in paired …

Neurofeedback: New Territories And Neurocognitive Mechanisms Of Endogenous Neuromodulation, James Sulzer, T Dorina Papageorgiou, Rainer Goebel, Talma Hendler

Faculty, Staff and Students Publications

Neurofeedback (NF) is endogenous neuromodulation of circumscribed brain circuitry. While its use of real-time brain activity in a closed-loop system is similar to brain-computer interfaces, instead of controlling an external device like the latter, the goal of NF is to change a targeted brain function. In this special issue on NF, we present current and future methods for extracting and manipulating neural function, how these methods may reveal new insights about brain function, applications, and rarely discussed ethical considerations of guiding and interpreting the brain activity of others. Together, the articles in this issue outline the possibilities of NF use …

Secure Messaging Use And Wrong-Patient Ordering Errors Among Inpatient Clinicians, Sunny S Lou, Daphne Lew, Linlin Xia, Laura Baratta, Elise Eiden, Thomas Kannampallil

2020-Current year OA Pubs

IMPORTANCE: Use of secure messaging for clinician-to-clinician communication has increased exponentially over the past decade, but its association with clinician work is poorly understood.

OBJECTIVE: To investigate the association between secure messaging use and wrong-patient ordering errors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included inpatient attending physicians, trainee physicians, and advanced practice practitioners (APPs) from 14 academic and community hospitals. Secure messaging volume was assessed over a 3-month period (February 1 to April 30, 2023).

EXPOSURE: Secure messaging volume per clinician-day, measured as the count of secure messages sent and received by a clinician on a given clinician-day.

MAIN …

Redesigning The Hospital Environment To Improve Restfulness, Caellagh D Catley, Kayla Paynter, Kendall Jackson, Ashley Huggins, Jenny Ji, Sai Anusha Sanka, Michelle Simkins, Thomas M Maddox, Patrick G Lyons

2020-Current year OA Pubs

IMPORTANCE: Hospital wards are often not conducive to patient sleep, negatively affecting patient health and experience.

OBJECTIVES: To assess determinants of in-hospital restfulness and to design and test rest-promoting interventions on the wards in partnership with clinicians, staff, and patients.

DESIGN, SETTING, AND PARTICIPANTS: This rapid-sequential mixed-methods quality improvement study was performed at a large urban academic hospital in St Louis, Missouri, from May 1, 2021, to December 31, 2022, with follow-up through hospitalization. Mixed-methods activities involved purposively selected hospitalized adults on the wards, nurses, hospitalists, and hospital staff. Interventions included all adult hospitalizations on the study wards.

INTERVENTIONS: Sequential …