Digital Commons Network^™

Racial And Sociodemographic Disparities In The Use Of Targeted Therapies In Advanced Ovarian Cancer Patients With Medicare, Anne Knisely, Chi-Fang Wu, Alexa Kanbergs, Nuria Agusti, Kirsten A Jorgensen, Sharon H Giordano, Roni Nitecki Wilke

Faculty, Staff and Student Publications

Objective: To describe sociodemographic and racial disparities in receipt of poly ADP-ribose polymerase inhibitors (PARPi) and bevacizumab among insured patients with ovarian cancer.

Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify patients with advanced stage, high grade serous ovarian cancer diagnosed between 2010 and 2019. The primary outcome of interest was receipt of PARPi or bevacizumab at any time after diagnosis. χ2 tests were used to compare categorical variables. Factors independently associated with the receipt of PARPi and/or bevacizumab were identified using a multivariable logistic regression.

Results: The cohort included 6242 patients; 276 …

Age-Related Decline In Blood-Brain Barrier Function Is More Pronounced In Males Than Females In Parietal And Temporal Regions, Xuejuan Jiang, Peter Kochunov, Elliot Hong, Ioannis Pappas, Meredith Braskie, Hosung Kim, Steven Cen, Kay Jann, Danny J J Wang

Faculty, Staff and Student Publications

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Sarmila Tandukar, Ahmed A Shibl, Jeevan Bahadur Sherchand, Aashish R Jha, Emily R Davenport

Faculty, Staff and Student Publications

Background: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation For Depression: A Randomized Clinical Trial, Dongsheng Zhou, Xingxing Li, Shuochi Wei, Chang Yu, Dongmei Wang, Yuchen Li, Jiaxin Li, Junyao Liu, Shen Li, Wenhao Zhuang, Yanli Li, Ruichenxi Luo, Zhiwang Liu, Jimeng Liu, Yongming Xu, Jialin Fan, Guidong Zhu, Weiqian Xu, Yiping Tang, Raymond Y Cho, Thomas R Kosten, Xiang-Yang Zhang

Staff and Researcher Publications

IMPORTANCE: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD).

OBJECTIVE: To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo …

Multicenter Validation Of An Rna-Based Assay To Predict Anti-Pd-1 Disease Control In Patients With Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma: The Predapt Study, Kevin C Flanagan, Jessica Ley, Douglas Adkins, Eric J Duncavage, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors.

METHODS: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from …

Protein Consumption And Risk Of Cvd Among Us Adults: The Multi-Ethnic Study Of Atherosclerosis (Mesa), Alexis C Wood, Nikhil S Padhye, Marcia C De Oliveira Otto

Faculty, Staff and Students Publications

BACKGROUND: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk.

OBJECTIVE: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke.

METHODS: In a multi-ethnic cohort of 5879 U.S. adults (45-84 years), who were free of CVD at baseline, protein intake was …

Distinct Escherichia Coli Transcriptional Profiles In The Guts Of Recurrent Uti Sufferers Revealed By Pangenome Hybrid Selection, Mark G Young, Jesús Bazan Villicana, Philippe Azimzadeh, Andrew Kau, Karen W Dodson, Henry L Schreiber 4th, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Low-abundance members of microbial communities are difficult to study in their native habitats, including Escherichia coli, a minor but common inhabitant of the gastrointestinal tract, and key opportunistic pathogen of the urinary tract. While multi-omic analyses have detailed interactions between uropathogenic Escherichia coli (UPEC) and the bladder mediating urinary tract infection (UTI), little is known about UPEC in its pre-infection reservoir, the gastrointestinal tract, partly due to its low relative abundance (<1%). To sensitively explore the genomes and transcriptomes of diverse gut E. coli, we develop E. coli PanSelect, which uses probes designed to specifically capture E. coli's broad pangenome. We demonstrate its ability to enrich diverse E. coli by orders of magnitude, in a mock community and in human stool from a study investigating recurrent UTI (rUTI). Comparisons of transcriptomes between gut E. coli of women with and without history of rUTI suggest rUTI gut E. coli are responding to increased oxygen and nitrate, suggestive of mucosal inflammation, which may have implications for recurrent disease. E. coli PanSelect is well suited for investigations of in vivo E. coli biology in other low-abundance environments, and the framework described here has broad applicability to other diverse, low-abundance organisms.

Act With Cf: A Randomized Trial Of Acceptance And Commitment Therapy Vs Supportive Psychotherapy For Adults With Cystic Fibrosis, C. Virginia O'Hayer, Patrick J. Smith, Christopher F. Drescher, Heather Bruschwein, Chelsi N. Nurse, Hallie M. Kushner, Krista Ingle, Michael J. Stephen, Jeffrey B. Hoag

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: Psychological distress, including anxiety and depression, is common among adults with CF, associating with poor quality of life, lung function, and healthcare utilization. This 3-year, multi-site, telehealth-delivered randomized trial sought to determine whether Acceptance and Commitment Therapy (ACT with CF) is superior to supportive psychotherapy (SP), in improving psychological functioning for adults with CF.

METHODS: One hundred twenty-four adults with CF and elevated anxiety and/or depressive symptoms were recruited coincident with the first COVID lockdown, from Thomas Jefferson University Hospitals, University of Virginia, Augusta University, Duke University Medical Center, and social media. Participants were randomized to 6 weeks of …

Sexual Dimorphism, Altered Hippocampal Glutamatergic Neurotransmission, And Cognitive Impairment In App Knock-In Mice., Caleigh A Findley, Samuel A Mcfadden, Tiarra Hill, Mackenzie R Peck, Kathleen Quinn, Kevin N Hascup, Erin R Hascup

Articles

BACKGROUND: It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes.

OBJECTIVE: In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP

METHODS: At 2-4 and 18+ months old, male and female APP

RESULTS: Glutamate recordings support elevated stimulus-evoked glutamate release in the DG and CA3 of young APP

CONCLUSIONS: These findings confirm a sex-dependent hyper-to-hypoactivation glutamatergic paradigm in APP

Genetic Alterations In Chromatin Regulatory Genes In Upper Tract Urothelial Carcinoma And Urothelial Bladder Cancer., Shuo Wang, Xuzhi Yan, Weihua Lan, Yapeng Wang, Ze Wang, Dali Tong, Yao Zhang, Qiang Ran, Haoyang Li, Junhao Jin, Haiyang Xiao, Jing Xu, Qian Yan, Dianzheng Zhang, Qiang Ma, Hualiang Xiao, Jun Qin, Luofu Wang, Jun Jiang, Qiuli Liu

PCOM Scholarly Works

PURPOSE: Upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) share histomorphological and therapeutic features but distinct epidemiologic and clinicopathologic characteristics. We examined alterations of chromatin regulatory genes in molecular subtypes, clonal relatedness, and T-cell receptor (TCR) diversity in UTUC and UCB.

MATERIALS AND METHODS: Targeted next-generation sequencing or whole-exome DNA sequencing and TCR sequencing were conducted with 34 UTUC and 49 UCB specimens from 63 patients. Tumors were subtyped based on the expression of CK5 and GATA3. Results of tissue microarray of 78 muscle-invasive bladder cancer (MIBC) samples were used as prognostic factors of different subtypes …

Association Between Glucagon-Like Peptide-1 Receptor Agonist Use And Progression Of Monoclonal Gammopathy Of Uncertain Significance To Multiple Myeloma Among Patients With Diabetes, Nikhil Grandhi, Lawrence Liu, Mei Wang, Theodore Thomas, Martin Schoen, Kristen Sanfilippo, Feng Gao, Graham A Colditz, Kenneth R Carson, Murali Janakiram, Su-Hsin Chang

2020-Current year OA Pubs

BACKGROUND: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes.

METHODS: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor …

Cohort Expansion And Genotype-Phenotype Analysis Of Rab11a-Associated Neurodevelopmental Disorder., Maria Carla Borroto, Heena Patel, Siddharth Srivastava, Lindsay C. Swanson, Boris Keren, Sandra Whalen, Cyril Mignot, Xiaodong Wang, Qian Chen, Jill A. Rosenfeld, Scott Mclean, Rebecca O. Littlejohn, Undiagnosed Diseases Network, Lisa Emrick, Lindsay C. Burrage, Ruben Attali, Gaetan Lesca, Cecile Acquaviva-Bourdain, Catherine Sarret, Laurie H. Seaver, Konrad Platzer, Tobias Bartolomaeus, Cornelia Wünsch, Susann Fischer, Ana Maria Rodriguez Barreto, Jorge L. Granadillo, Elisabeth Schreiner, Theresa Brunet, Ulrich A. Schatz, Isabelle Thiffault, Sureni V. Mullegama, Jacques L. Michaud, Fadi F. Hamdan, Elsa Rossignol, Philippe M. Campeau

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.

METHODS: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.

RESULTS: We reinforce the …

Seasons Of Kawasaki Disease During The Covid-19 Pandemic., Todd T. Nowlen, Ashraf S. Harahsheh, Geetha Raghuveer, Simon Lee, Anji T. Yetman, Nagib Dahdah, Michael A. Portman, Supriya S. Jain, Michael Khoury, Selemet Tierney, Cedric Manlhiot, Pedrom Farid, Brian W. Mccrindle

Manuscripts, Articles, Book Chapters and Other Papers

The incidence of Kawasaki Disease has a peak in the winter months with a trough in late summer/early fall. Environmental/exposure factors have been associated with a time-varying incidence. These factors were altered during the COVID-19 pandemic. The study was performed through the International Kawasaki Disease Registry. Data from patients diagnosed with acute Kawasaki Disease and Multiple Inflammatory Syndrome-Children were obtained. Guideline case definitions were used to confirm site diagnosis. Enrollment was from 1/2020 to 7/2023. The number of patients was plotted over time. The patients/month were tabulated for the anticipated peak Kawasaki Disease season (December-April) and non-peak season (May-November). Data …

Extrapolative Validity Evidence Of The Anastomosis Objective Structured Assessment Of Technical Skill (A-Osats) For Robotic Ileocolic Anastomosis, Tiffany K Brocke, Cory Fox, Julie M Clanahan, Coen L Klos, William C Chapman Jr, Paul E Wise, Michael M Awad, Kerri A Ohman

2020-Current year OA Pubs

OBJECTIVE: To collect validity evidence for the use of the Anastomosis Objective Structured Assessment of Technical Skills (A-OSATS) instrument, which has been developed to evaluate performance of a minimally invasive side-to-side bowel anastomosis with hand-sewn common enterotomy.

DESIGN: Residents performed a robotic ileocolic anastomosis simulation on an ex vivo porcine model. Faculty scored each resident with the A-OSATS and performed a provocative leak test on the completed anastomoses. Residents were reassessed on the sewing sub-score 1 month later. Data were compared with parametric and nonparametric analysis.

SETTING: Single academic general surgery residency PARTICIPANTS: PGY-4 and -5 general surgery residents (n …

Neighborhood Resources Associated With Psychological Trajectories And Neural Reactivity To Reward After Trauma, E Kate Webb, Stacey L House, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD).

OBJECTIVE: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward.

DESIGN, SETTING, AND PARTICIPANTS: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, …

Vagus Nerve Stimulation Recruits The Central Cholinergic System To Enhance Perceptual Learning, Kathleen A Martin, Eleni S Papadoyannis, Jennifer K Schiavo, Saba Shokat Fadaei, Habon A Issa, Soomin C Song, Sofia Orrey Valencia, Nesibe Z Temiz, Matthew J Mcginley, David A Mccormick, Robert C Froemke

Duncan NRI Faculty and Staff Publications

Perception can be refined by experience, up to certain limits. It is unclear whether perceptual limits are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies suggest that peripheral nerve stimulation, specifically vagus nerve stimulation (VNS), can alter neural activity and augment experience-dependent plasticity, although little is known about central mechanisms recruited by VNS. Here we developed an auditory discrimination task for mice implanted with a VNS electrode. VNS applied during behavior gradually improved discrimination abilities beyond the level achieved by training alone. Two-photon imaging revealed VNS induced changes to auditory cortical responses and activated cortically …

Systemic Effects Of Anti-Vegf Intravitreal Injection In Patients With Age-Related Macular Degeneration: A Multi-Institutional Real-World Study, Tzu-Yi Lin, Yi-Ting Hsieh, Sunir J. Garg, Lee-Jen Chen, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang, Eugene Yu-Chuan Kang

Wills Eye Hospital Papers

PURPOSE: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users.

METHODS: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among …

Fetal Sex Effects On Maternal Health Can Now Be Tested Via Randomization: A First-In-Class Illustration In Cows On Glucoregulatory Outcomes, Aridany Suarez-Trujillo, Colby J Vorland, Griffin T Nicholls, Daniella E Chusyd, Chelsie Parker, Lilian Golzarri-Arroyo, Sophia Swann, Bethany J Funnell, Kara R Stewart, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: The maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship.

Objective: To demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes.

Methods: Holstein dairy cows were stratified and randomized using sealed opaque envelopes to be artificially inseminated with either X- or Y-sorted bull semen until 40 cows became pregnant. Monthly body weight measurements were recorded, and an intravenous glucose …

Adverse Childhood Experiences And Psychological Correlates Of Substance Use Disorders Among Black Sexual Minority Women, Shemeka Thorpe, Kaylee A Palomino, Natalie Malone, Danelle Stevens-Watkins

Kinesiology and Health Promotion Faculty Publications

This study examined the influence of adverse childhood experiences (ACEs) on Black sexual minority women's mental health and substance use disorders in adulthood. Secondary data analysis was conducted using N = 149 Black sexual minority women's reports from the Generations Study. Study variables included psychological distress, chronic strains, stressful life events, ACEs, and substance use disorders, including alcohol use disorder and drug use disorder. Quantitative data analysis consisted of descriptives and bivariate correlations. Participants' total ACE scores were positively significantly correlated with increased alcohol misuse, chronic life strains, and stressful life events. Exposure to household interpersonal violence and household mental …

Feasibility, Acceptability, And Initial Efficacy Of A Wheelchair Exercise Training Program In Persons With Multiple Sclerosis: Study Protocol For A Parallel Group Randomized Controlled Trial

Faculty, Staff and Student Publications

Purpose: This study is a randomized controlled trial (RCT) that examines the feasibility, acceptability, and initial efficacy of a home-based, remotely supported and supervised exercise training program that was developed using a three-step community engaged research process for persons with multiple sclerosis (MS) who are wheelchair users.

Materials and methods: The study design is a parallel group RCT (NCT05888727). We aim to enroll 24 wheelchair users with MS who will be randomly assigned using REDCap randomization module into exercise training or attention/contact wellness control conditions. The conditions will be delivered remotely over 16 weeks and supported using online, …

Serum Metabolomic Markers Of Artificially Sweetened Beverage Consumption, Lyn M Steffen, Valerie K Sullivan, Casey M Rebholz

Faculty, Staff and Student Publications

BACKGROUND: The consumption of artificially sweetened beverages is on the rise. Use of artificial sweeteners has been associated with adverse health outcomes. There is a need to identify novel objective biomarkers of artificially sweetened beverages in order to improve dietary assessment and to provide insight into their metabolic impact.

OBJECTIVES: We aimed to identify serum metabolites that are associated with artificially sweetened beverage consumption.

METHODS: In the Atherosclerosis Risk in Communities (ARIC) study, consumption of artificially sweetened beverages was assessed using a food frequency questionnaire and fasting serum samples were collected during the first study visit (1987-1989). Participants were categorized …

Polygenic Risk Scores And Extreme Coronary Artery Calcium Phenotypes (Cac=0 And Cac≥1000) In Adults ≥75 Years Old: The Aric Study, Yasuyuki Honda, Candace M Howard-Claudio, Jin Jin, Bing Yu, Paul S De Vries, Lynne Wagenknecht, Aaron R Folsom, Ron Blankstein, Tanika N Kelly, Seamus P Whelton, Martin Bødtker Mortensen, Ziqiao Wang, Nilanjan Chatterjee, Kunihiro Matsushita, Michael J Blaha

Faculty, Staff and Student Publications

Background: Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age.

Methods: There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987-1989) and CAC scans …

Serum Levels Of Total Bile Acids Are Associated With An Increased Risk Of Hcc In Patients With Cirrhosis, Jing Ning, Saira Khaderi, Amit G Singal, Sumeet K Asrani, Jorge A Marrero, Hannah Powell, Kinza Rizwan, Omar Najjar, Christopher I Amos, Michelle Luster, Abeer Al-Sarraj, Emad Salem, Michael E Scheurer, Jagpreet Chhatwal, Salma Kaochar, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND: Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

METHODS: We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date. Competing risk proportional hazard-adjusted models were used to estimate the association between tertiles of serum TBA levels and the risk of developing HCC. We quantified the incremental predictive value of serum bile acid …

A Comparison Of The Diagnostic Capability Of Kato-Katz And Real-Time Pcr For The Assessment Of Treatment Efficacy Of Ivermectin And Albendazole Combination Against T Trichiura Infections, Alejandro Krolewiecki, Rojelio Mejia

Faculty, Staff and Students Publications

BACKGROUND: Trichuris trichiura is humans' second most prevalent soil-transmitted helminth (STH) infection after Ascaris lumbricoides, affecting approximately 460 million people worldwide. Despite its sub-optimal sensitivity, especially in low prevalence and infection intensity settings, the modified Kato-Katz (K-K) is still recommended as a diagnostic method by the World Health organization (WHO) guidelines.

METHODOLOGY/PRINCIPAL FINDINGS: Within a randomized clinical trial (RCT) comprising four treatment arms with two different anthelmintics, the present study reports an important secondary research objective to determine the diagnostic agreement between K-K and real-time PCR evaluating treatment efficacy against T. trichiura. The parasitological results were analyzed, including cure rates …

Loss-Of-Function In Rbbp5 Results In A Syndromic Neurodevelopmental Disorder Associated With Microcephaly, Jijun Wan, Sharayu V Jangam, Odelia Chorin, Annick Rothschild, Ortal Barel, Milena Mariani, Maria Iascone, Han Xue, Undiagnosed Diseases Network, Jing Huang, Cyril Mignot, Boris Keren, Virginie Saillour, Annelise Y Mah-Som, Stephanie Sacharow, Farrah Rajabi, Carrie Costin, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Jill A Rosenfeld, Christina G S Palmer, Stanley F Nelson, Michael F Wangler, Julian A Martinez-Agosto

Faculty, Staff and Students Publications

PURPOSE: Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 (HGNC:9888) encodes a core member of the protein complex that methylates histone 3 lysine-4 and has not been implicated in human disease.

METHODS: We identify 5 unrelated individuals with de novo heterozygous variants in RBBP5. Three nonsense/frameshift and 2 missense variants were identified in probands with neurodevelopmental symptoms, including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenic Drosophila models.

RESULTS: Both missense p.(T232I) and p.(E296D) variants affect evolutionarily conserved amino acids located at the …

A Phase 1 Study Of Abi-009 (Nab-Sirolimus) In Combination With Temozolomide And Irinotecan In Pediatric Patients With Recurrent Or Refractory Solid Tumors, Including Cns Tumors-A Children's Oncology Group Pediatric Early Phase Clinical Trial Network Study Advl1514, Stephan Voss, Elizabeth Fox, Xiaowei Liu, Kristina Denic, Joel M Reid, Brenda J Weigel

Faculty, Staff and Students Publications

BACKGROUND: Nab-sirolimus (ABI-009, nab-rapamycin; Aadi Bioscience Inc. [Aadi]) is a human albumin-bound form of sirolimus nanoparticles, a potent mTOR inhibitor. This phase I trial was conducted to define dose-limiting toxicities (DLT), maximum tolerated or recommended phase II dose (MTD/RP2D), and pharmacokinetics of Nab-sirolimus in combination with temozolomide and irinotecan.

METHODS: Using a rolling 6 design, Nab-sirolimus was administered intravenously (IV) on days (D) 1 and 8 of cycle (C) 1. In subsequent cycles, Nab-sirolimus was administered D1 and D8 in combination with temozolomide (125 mg/m

RESULTS: Thirty-three patients were enrolled, 32 were eligible. Dose determination included 17 evaluable patients, median …

Fetal Lower Urinary Tract Obstruction: International Delphi Consensus On Management And Core Outcome Set, S J Gordijn, W Ganzevoort, C Melling, C J Koh, G T Mandy, M D Kilby, A Johnson, R A Quintero, G Ryan, A A Shamshirsaz, A A Nassr, On Behalf Of The Luto Working Group

Faculty, Staff and Students Publications

OBJECTIVES: To reach an international expert consensus on the diagnosis, prognosis and management of fetal lower urinary tract obstruction (LUTO) by means of a Delphi procedure, and to use this to define a core outcome set (COS).

METHODS: A three-round Delphi procedure was conducted among an international panel of experts in fetal LUTO. The panel was provided with a list of literature-based parameters to consider for the diagnosis, prognosis, management and outcomes of LUTO. A parallel procedure was conducted with patient groups during the development of the COS.

RESULTS: A total of 168 experts were approached, of whom 99 completed …

Glp-1 Receptor Agonists And Risk For Cirrhosis And Related Complications In Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease, Yu-Xiao Yang, Yumei Cao, Xian Yu, Ronald Samuel, Basim Ali, Roxanne Desiderio, George Cholankeril, Mandeep Bajaj, Hashem B El-Serag, Steven M Asch

Faculty, Staff and Students Publications

IMPORTANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD.

OBJECTIVE: To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health …

Natural History Of Indeterminate Liver Nodules In Patients With Advanced Liver Disease: A Multicenter Retrospective Cohort Study, Steven-Huy Han, Cassie Xie, Jing Ning, Jo Ann Rinaudo, Ashwini Arvind, Anna S Lok, Fasiha Kanwal, Translational Liver Cancer Investigators

Faculty, Staff and Students Publications

Introduction: Indeterminate liver nodules (ILNs) are frequently encountered on diagnostic imaging after positive hepatocellular carcinoma (HCC) surveillance results, but their natural history remains unclear.

Methods: We conducted a multicenter retrospective cohort study among patients with ≥1 newly detected LI-RADS 3 (LR-3) lesion ≥1 cm or LI-RADS 4 (LR-4) lesion of any size (per LI-RADS v2018) between January 2018 and December 2019. Patients were followed with repeat imaging at each site per institutional standard of care. Multivariable Fine-Gray models were used to evaluate associations between potential risk factors and patient-level time-to-HCC diagnosis, with death and liver transplantation as competing risks.

Results: …

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Adam S Lauring, Manjusha Gaglani, Tresa Mcneal, Shekhar Ghamande, Ithan D Peltan, Samuel M Brown, Adit A Ginde, Aimee Steinwand, Nicholas M Mohr, Kevin W Gibbs, David N Hager, Harith Ali, Anne Frosch, Michelle N Gong, Amira Mohamed, Nicholas J Johnson, Vasisht Srinivasan, Jay S Steingrub, Akram Khan, Laurence W Busse, Abhijit Duggal, Jennifer G Wilson, Nida Qadir, Steven Y Chang, Christopher Mallow, Jennie H Kwon, Matthew C Exline, Nathan I Shapiro, Cristie Columbus, Ivana A Vaughn, Mayur Ramesh, Basmah Safdar, Jarrod M Mosier, Jonathan D Casey, H Keipp Talbot, Todd W Rice, Natasha Halasa, James D Chappell, Carlos G Grijalva, Adrienne Baughman, Kelsey N Womack, Jillian P Rhoads, Sydney A Swan, Cassandra Johnson, Nathaniel Lewis, Sascha Ellington, Fatimah S Dawood, Meredith Mcmorrow, Wesley H Self, Investigating Respiratory Viruses In The Acutely Ill (Ivy) Network

Faculty, Staff and Students Publications

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …