Digital Commons Network^™

Exploring Individual Differences In Amygdala-Mediated Memory Modulation, Martina K Hollearn, Joseph R Manns, Lou T Blanpain, Stephan B Hamann, Kelly Bijanki, Robert E Gross, Daniel L Drane, Justin M Campbell, Krista L Wahlstrom, Griffin F Light, Aydin Tasevac, Phillip Demarest, Peter Brunner, Jon T Willie, Cory S Inman

Faculty, Staff and Students Publications

Amygdala activation by emotional arousal during memory formation can prioritize events for long-term memory. Building upon our prior demonstration that brief electrical stimulation to the human amygdala reliably improved long-term recognition memory for images of neutral objects without eliciting an emotional response, our study aims to explore and describe individual differences and stimulation-related factors in amygdala-mediated memory modulation. Thirty-one patients undergoing intracranial monitoring for intractable epilepsy were shown neutral object images paired with direct amygdala stimulation during encoding with recognition memory tested immediately and one day later. Adding to our prior sample, we found an overall memory enhancement effect without …

Implementation Of Electronic Triggers To Identify Diagnostic Errors In Emergency Departments, Viralkumar Vaghani, Ashish Gupta, Usman Mir, Li Wei, Daniel R Murphy, Umair Mushtaq, Dean F Sittig, Andrew J Zimolzak, Hardeep Singh

Faculty, Staff and Students Publications

Importance: Missed diagnosis can lead to preventable patient harm.

Objective: To develop and implement a portfolio of electronic triggers (e-triggers) and examine their performance for identifying missed opportunities in diagnosis (MODs) in emergency departments (EDs).

Design, setting, and participants: In this retrospective medical record review study of ED visits at 1321 Veterans Affairs health care sites, rules-based e-triggers were developed and implemented using a national electronic health record repository. These e-triggers targeted 6 high-risk presentations for MODs in treat-and-release ED visits. A high-risk stroke e-trigger was applied to treat-and-release ED visits from January 1, 2016, to December 31, 2020. A …

Spock2 Controls The Proliferation And Function Of Immature Pancreatic Β-Cells Through Mmp2, Katarzyna Blaszczyk, Anna P Jedrzejak, Natalia Ziojla, Ekaterina Shcheglova, Karolina Szarafin, Artur Jankowski, Christine A Beamish, Jolanta Chmielowiec, Omaima M Sabek, Ashok Balasubramanyam, Sanjeet Patel, Malgorzata Borowiak

Faculty, Staff and Students Publications

Human pluripotent stem cell-derived β-cells (SC-β-cells) represent an alternative cell source for transplantation in diabetic patients. Although mitogens could in theory be used to expand β-cells, adult β-cells very rarely replicate. In contrast, newly formed β-cells, including SC-β-cells, display higher proliferative capacity and distinct transcriptional and functional profiles. Through bidirectional expression modulation and single-cell RNA-seq, we identified SPOCK2, an ECM protein, as an inhibitor of immature β-cell proliferation. Human β-cells lacking SPOCK2 presented elevated MMP2 expression and activity, leading to β-integrin-FAK-c-JUN pathway activation. Treatment with the MMP2 protein resulted in pronounced short- and long-term SC-β-cell expansion, significantly increasing glucose-stimulated insulin …

Testosterone Modulation Of Muscle Transcriptomic Profile During Lifestyle Therapy In Older Men With Obesity And Hypogonadism, Viola Viola, Tagari Samanta, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Ngoc Ho Lam Nguyen, Georgia Colleluori, Yoann Barnouin, Nicola Napoli, Clifford Qualls, Benny Abraham Kaipparettu, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Testosterone replacement therapy (TRT) added to lifestyle therapy can mitigate weight-loss-induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism.

Objective: To investigate the molecular mechanisms underlying the attenuation of muscle and BMD loss in response to TRT during intensive lifestyle intervention in this high-risk older population.

Methods: Among 83 older (≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently < 300 ng/dL) associated with frailty (Modified Physical Performance Test score ≤ 31) randomized into 26-week lifestyle therapy plus testosterone (LT+TRT) or placebo (LT+Pbo) in the LITROS trial, 38 underwent serial muscle biopsies for the muscle transcriptomics substudy.

Results: Despite similar ~10% weight loss, lean body mass and thigh muscle volume decreased less in LT+TRT than LT+Pbo (-2% vs. -4%, respectively; p = …

Polygenic Score For Clinicopathologic Features And Survival Outcomes In Papillary Thyroid Carcinoma, Sophie Li, Guibin Zheng, Li Xu, Maitrayee Goswami, Mark E Zafereo, Steven I Sherman, Guojun Li, Erich M Sturgis, Jennifer R Wang

Faculty, Staff and Students Publications

Importance: Genome-wide association studies have identified germline variants associated with the development of papillary thyroid carcinoma (PTC) that can be used to construct a polygenic score (PGS). It is important to determine whether patients with higher germline genetic risk, as summarized using PGS, present with more aggressive disease and/or develop worse clinical outcomes.

Objective: To assess whether germline risk defined by PGS is associated with clinicopathologic features and survival outcomes for patients with PTC.

Design, setting, and participants: This retrospective cohort study included patients with newly diagnosed PTC who presented to The University of Texas MD Anderson Cancer Center for …

Acute-On-Chronic Liver Failure (Aclf): The ‘Kyoto Consensus’-Steps From Asia, Ashok Choudhury, Anand V Kulkarni, Vinod Arora, A S Soin, Abdul Kadir Dokmeci, Abhijeet Chowdhury, Abraham Koshy, Ajay Duseja, Ajay Kumar, Ajay Kumar Mishra, Ajay Kumar Patwa, Ajit Sood, Akash Roy, Akash Shukla, Albert Chan, Aleksander Krag, Amar Mukund, Ameet Mandot, Amit Goel, Amna Subhan Butt, Amrish Sahney, Ananta Shrestha, Andrés Cárdenas, Angelo Di Giorgio, Anil Arora, Anil Chandra Anand, Anil Dhawan, Ankur Jindal, Anoop Saraya, Anshu Srivastava, Anupam Kumar, Apichat Kaewdech, Apurva Pande, Archana Rastogi, Arun Valsan, Ashish Goel, Ashish Kumar, Ashwani K Singal, Atsushi Tanaka, Audrey Coilly, Ayaskanta Singh, Babu Lal Meena, Barath Jagadisan, Barjesh Chander Sharma, Bikrant Bihari Lal, C E Eapen, Cesar Yaghi, Chandan Kumar Kedarisetty, Chang Wook Kim, Charles Panackel, Chen Yu, Chetan R Kalal, Chhagan Bihari, Chien Hao Huang, Chitranshu Vasishtha, Christian Jansen, Christian Strassburg, Chun Yen Lin, Constantine J Karvellas, Cosmas Rinaldi Adithya Lesmana, Cyriac Abby Philips, Debbie Shawcross, Dharmesh Kapoor, Dhiraj Agrawal, Diana Alcantara Payawal, Dibya Lochan Praharaj, Dinesh Jothimani, Do Seon Song, Dong Joon Kim, Dong-Sik Kim, Duan Zhongping, Fazal Karim, Francois Durand, Gamal E Shiha, Gennaro D'Amico, George K Lau, Girish Kumar Pati, Graciela Elia Castro Narro, Guan-Huei Lee, Gupse Adali, Guru Prasad Dhakal, Gyongyi Szabo, H C Lin, Hai Li, Hari Kumar Nair, Harshad Devarbhavi, Harshvardhan Tevethia, Hasmik Ghazinian, Hemamala Ilango, Hong Ling Yu, Irsan Hasan, J Fernandez, Jacob George, Jaideep Behari, James Fung, Jasmohan Bajaj, Jaya Benjamin, Jennifer C Lai, Jidong Jia, Jin Hua Hu, Jin Jun Chen, Jin Lin Hou, Jin Mo Yang, Johannes Chang, Jonel Trebicka, Jörg C Kalf, Jose D Sollano, Joy Varghese, Juan Pablo Arab, Jun Li, K Rajender Reddy, Kaiser Raja, Kalpana Panda, Kamal Kajal, Karan Kumar, Kaushal Madan, Kemal Fariz Kalista, Kessarin Thanapirom, Khin Maung Win, Ki Tae Suk, Krishnadas Devadas, Laurentius A Lesmana, Lubna Kamani, Madhumita Premkumar, Madunil A Niriella, Mamun Al Mahtab, Man Fung Yuen, Manal Hel Sayed, Manasa Alla, Manav Wadhawan, Manoj Kumar Sharma, Manoj Sahu, Manya Prasad, Mark Dhinesh Muthiah, Martin Schulz, Meenu Bajpai, Mettu Srinivas Reddy, Michael Praktiknjo, Ming Lung Yu, Mithra Prasad, Mithun Sharma, Mohamed Elbasiony, Mohammed Eslam, Mohd Golam Azam, Mohd Rela, Moreshwar S Desai, Mukul Vij, Nadim Mahmud, Narendra Singh Choudhary, Navin Kumar Marannan, Necati Ormeci, Neeraj Saraf, Nipun Verma, Nobuaki Nakayama, Norifumi Kawada, Oidov Baatarkhuu, Omesh Goyal, Osamu Yokosuka, P N Rao, Paolo Angeli, Pathik Parikh, Patrick S Kamath, Paul J Thuluvath, Philipp Lingohr, Piyush Ranjan, Prashant Bhangui, Pravin Rathi, Puja Sakhuja, Puneet Puri, Qin Ning, R K Dhiman, Rahul Kumar, Rajan Vijayaraghavan, Rajeev Khanna, Rakhi Maiwall, Ravi Mohanka, Richard Moreau, Rino Alvani Gani, Rohit Loomba, Rohit Mehtani, Ruveena Bhavani Rajaram, S S Hamid, Sachin Palnitkar, Sadhna Lal, Sagnik Biswas, Sakkarin Chirapongsathorn, Samagra Agarwal, Sanjeev Sachdeva, Sanjiv Saigal, Santhosh E Kumar, Sargsyan Violeta, Satender Pal Singh, Satoshi Mochida, Saurabh Mukewar, Seema Alam, Seng Gee Lim, Shahinul Alam, Shalimar, Shantan Venishetty, Shikha S Sundaram, Shiran Shetty, Shobna Bhatia, Shweta A Singh, Shyam Kottilil, Simone Strasser, S M Shasthry, Soe Thiha Maung, Soek Siam Tan, Sombat Treeprasertsuk, Sonal Asthana, Steffen Manekeller, Subhash Gupta, Subrat Kumar Acharya, Sudhamshu K C, Sudhir Maharshi, Sumeet Asrani, Sunil Dadhich, Sunil Taneja, Suprabhat Giri, Surender Singh, Tao Chen, Tarana Gupta, Tatsuo Kanda, Tawesak Tanwandee, Teerha Piratvishuth, Ulrich Spengler, V G Mohan Prasad, Vandana Midha, Venera Rakhmetova, Vicente Arroyo, Vikrant Sood, Vinay Kumar Br, Vincent Wai-Sun Wong, Viniyendra Pamecha, Virendra Singh, Vishwa Mohan Dayal, Vivek A Saraswat, Wray Kim, Wasim Jafri, Wenyi Gu, Wong Yu Jun, Xiaolong Qi, Yogesh K Chawla, Yoon Jun Kim, Yu Shi, Zaigham Abbas, Guresh Kumar, Shuichiro Shiina, Lai Wei, Masao Omata, Shiv Kumar Sarin, Apasl-Aclf Research Consortium (Aarc) For Apasl-Aclf Working Party

Faculty, Staff and Students Publications

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the …

Hes V20 Outperforms Galad For Detection Of Hcc: A Phase 3 Biomarker Study In The United States, Hashem B El-Serag, Qingchun Jin, Nabihah Tayob, Emad Salem, Michelle Luster, Abeer Alsarraj, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis.

APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and …

Gheard: An Open-Access Modular Curriculum To Incorporate Equity, Anti-Racism, And Decolonization Training Into Global Health Education, Amy R L Rule, Heather A Haq, Adelaide Barnes, Demarco Bowen, Msandeni Chiume-Kayuni, Whitney Cameron, S Aya Fanny, Elizabeth Groothuis, Bethany Hodge, Cindy Howard, James C Hudspeth, Sheridan Langford, Megan S Mchenry, Ijeoma Nnodim Opara, Beena D Kamath-Rayne, Parminder S Suchdev, Reena P Tam, Franci Taylor, Victor Musiime

Faculty, Staff and Students Publications

Background Global health (GH) interest is rising among graduate medical education (GME) trainees, yet GH engagement is marred by the impact of colonization or racism, and there remains a lack of training to confront these challenges.

Objective To develop a modular, open-access curriculum that provides training in decolonization for GH GME and evaluate its feasibility and impact on learners’ critical reflection on decolonization.

Methods From 2019 to 2022, 40 GH educators, including international and indigenous scholars from diverse organizations, created the Global Health Education for Equity, Anti-Racism, and Decolonization (GHEARD) curriculum. Using Kern’s 6 steps of curriculum development, critical gaps …

Comprehensive Assessment Reveals Numerous Clinical And Neurophysiological Differences Between Mecp2-Allelic Disorders, Davut Pehlivan, Chengjun Huang, Holly K Harris, Christine Coquery, Aditya Mahat, Mirjana Maletic-Savatic, Laurence Mignon, Sukru Aras, Daniel G Glaze, Charles S Layne, Leonardo Sahelijo, Huda Y Zoghbi, Matthew J Mcginley, Bernhard Suter

Faculty, Staff and Students Publications

OBJECTIVE: Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) result from under- and overexpression of MECP2, respectively. Preclinical studies using genetic-based treatment showed robust phenotype recovery for both MDS and RTT. However, there is a risk of converting MDS to RTT, or vice versa, if accurate MeCP2 levels are not achieved. The aim of this study was to identify biomarkers distinguishing RTT from MDS.

MATERIALS AND METHODS: We prospectively enrolled 11 MDS and 6 male RTT like (MRL) individuals for a panel of clinical and neurophysiological assessments over two visits, 8-10 months apart.

RESULTS: We identified numerous clinical and physiological …

Association Between Maternal Stress And Child Sleep Quality: A Nationwide Echo Prospective Cohort Study, Sarah Dee Geiger, Aruna Chandran, Marie L Churchill, Maxwell Mansolf, Cai Zhang, Salma Musaad, Courtney K Blackwell, Stephanie M Eick, Dana E Goin, Susan Korrick, Akram Alshawabkeh, Patricia A Brennan, Carrie V Breton, Jose F Cordero, Sean Deoni, Viren D'Sa, Anne L Dunlop, Amy J Elliott, Assiamira Ferrara, Arlene Keddie, Monique Lebourgeois, Kaja Z Lewinn, Daphne Koinis-Mitchell, Maristella Lucchini, Sara S Nozadi, Thomas O'Connor, Yeyi Zhu, Emily Zimmerman, Susan L Schantz

Children’s Nutrition Research Center Staff Publications

Background: Childhood sleep quality is associated with physical, cognitive, and behavioral health and predicts later sleep quality; it has many determinants, including developmental exposures.

Objectives: To examine associations between maternal stress during pregnancy and childhood sleep quality and determine whether postnatal stress mediates the association.

Method: Data from the Environmental Influences on Child Health Outcomes cohort were used. Perceived Stress Scale (PSS) T-scores were the exposure measure. Outcome measures were preschool Child Behavior Checklist (CBCL) sleep syndrome scale and Patient-Reported Outcomes Measurement Information System Sleep Disturbance Parent Proxy short form 4a (PSD4a) T-scores at ages 4-8 years. Linear mixed-effects regression …

Mid-Life Anti-Inflammatory Metabolites Are Inversely Associated With Long-Term Cardiovascular Disease Events, Anum Saeed, Chris Mckennan, Jiaxuan Duan, Yueh-Ning Yang, Kevin E Kip, David Finegold, Michael Vu, Justin Swanson, Oscar L Lopez, Ann Cohen, Mark Mapstone, Bing Yu, Christie M Ballantyne, Steven E Reis

Faculty, Staff and Student Publications

BACKGROUND: Preclinical data have shown that low levels of metabolites with anti-inflammatory properties may impact metabolic disease processes. However, the association between mid-life levels of such metabolites and long-term ASCVD risk is not known.

METHODS: We characterised the plasma metabolomic profile (1228 metabolites) of 1852 participants (58.1 ± 7.5 years old, 69.6% female, 43.6% self-identified as Black) enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Logistic regression was used to assess the impact of metabolite levels on ASCVD risk (nonfatal MI, revascularisation, and cardiac mortality). We additionally explored the effect of genetic variants neighbouring ASCVD-related genes …

Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers, Mark Zobeck, Javed Khan, Rajkumar Venkatramani, M Fatih Okcu, Michael E Scheurer, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Molecular markers increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.

Methods: Clinical variables and somatic mutation data for 20 genes from 641 patients with RMS in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The Baseline Clinical (BC) model included treatment location, age, fusion status, and risk group. The Gene Enhanced 2 (GE2) model added TP53 and MYOD1 mutations to the BC predictors. The Gene …

Revisiting What Constitutes A Neglected Tropical Disease?, Paul J Brindley, Peter J Hotez, Shaden Kamhawi

Center for Medical Ethics and Health Policy Staff Publications

PLOS Neglected Tropical Diseases (PLOS NTDs) publishes research devoted to pathogenesis and other clinical aspects, epidemiology, prevention, diagnosis, treatment, and control of the neglected tropical diseases (NTDs), as well as work relevant to public health policy. We define NTDs as poverty-promoting infectious diseases that can negatively impact the quality of life in rural areas and poor urban areas of low- and middle-income countries but which can also affect specific communities within high-income countries. The poverty-inducing effects of the NTDs operate by impairing child health and development, pregnancy outcomes for both mother and child, worker productivity, and quality of life. The …

Longitudinal Phage-Bacteria Dynamics In The Early Life Gut Microbiome, Michael J Tisza, Richard E Lloyd, Kristi Hoffman, Daniel P Smith, Marian Rewers, Sara J Javornik Cregeen, Joseph F Petrosino

Center for Medical Ethics and Health Policy Staff Publications

Microbial colonization of the human gut occurs soon after birth, proceeds through well-studied phases and is affected by lifestyle and other factors. Less is known about phage community dynamics during infant gut colonization due to small study sizes, an inability to leverage large databases and a lack of appropriate bioinformatics tools. Here we reanalysed whole microbial community shotgun sequencing data of 12,262 longitudinal samples from 887 children from four countries across four years of life as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We developed an extensive metagenome-assembled genome catalogue using the Marker-MAGu pipeline, …

Resilience And Coping: A Qualitative Analysis Of Cognitive And Behavioral Factors In Adults With Osteogenesis Imperfecta, Hannah E Cho, Whitney S Shepherd, Gianna M Colombo, Andrew D Wiese, W Conor Rork, Kristin M Kostick, Dianne Nguyen, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Justin H Qian, Brendan Lee, V Reid Sutton, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The aim of this qualitative study was to investigate resilience among adults with Osteogenesis Imperfecta (OI).

Materials and methods: Semi-structured interviews were conducted with 15 adults with OI. Transcripts were coded and subsequently abstracted, yielding themes specific to resilience and coping. Interview guides covered broad topics including pain challenges specific to OI, mental health issues related to OI, and priorities for future interventions for individuals with OI.

Results: Participants described resilience in the context of OI as the ability to grow from adversity, adapt to challenges resulting from OI-related injuries, and find identities apart from their condition. Psychological coping …

Association Of Serum Endocannabinoid Levels With Pancreatitis And Pancreatitis-Related Pain, Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli

Faculty, Staff and Student Publications

No abstract provided.

American Cochlear Implant Alliance Position Statement On Newborn Congenital Cytomegalovirus Screening, Megan Honor Pesch, Kevin David Brown, Amy L Birath, Gail J Demmler-Harrison, Cailtin Sapp, Anne Morgan Selleck, Alex D Sweeney

Faculty, Staff and Students Publications

It is estimated that 1 in every 200 US newborns has congenital cytomegalovirus (cCMV). Delayed identification of cCMV in newborns precludes timely intervention to mitigate sequelae of the infection such as hearing loss and other neurological complications. Newborn testing for cCMV enables appropriate diagnosis and intervention by multidisciplinary teams to properly manage the immediate sequelae of cCMV, avoid unnecessary additional testing that can result from delayed diagnosis, and monitor for future complications. It is the position of the American Cochlear Implant Alliance, the National CMV Foundation, and the American Academy of Otolaryngology-Head and Neck Surgery that universal newborn cCMV screening …

Prediction Models Of Basal Energy Expenditure In Children And Adolescents Across The Bmi Spectrum Based On Room Calorimetry: A Cross-Sectional Cohort Study, Maurice Puyau, Roman Shypailo, Nancy F Butte, Salma Musaad, Fida Bacha

Children’s Nutrition Research Center Staff Publications

Background: Existing equations for prediction of basal energy expenditure (BEE) may not be accurate in children with overweight or obesity (OW/OB).

Objectives: We aimed to develop BEE prediction equations applicable to children and adolescents across a wide BMI spectrum using gold standard room calorimetry.

Methods: We measured weight, height, waist and hip circumferences, body composition (DXA), and BEE (whole room calorimetry) in a cross-sectional cohort of 1155 healthy children, 5-19 years of age. 67% of the males and 51% of the females were classified as OW/OB. We applied multiple linear regression analyses to develop BEE prediction models for each sex. …

Figg At 5: An Update On Us Public Perspectives On Forensic Investigative Genetic Genealogy Five Years After Its Introduction To Criminal Investigations, Christi J Guerrini, Jill O Robinson, Mohamed I Elsaid, Whitney Bash Brooks, Ariel Levchenko, Stephanie M Fullerton, Sara Huston, Norah L Crossnohere, John F P Bridges, Jacklyn M Dahlquist, Louiza Kalokairinou, Diana Madden, Cece Moore, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

In 2018, after law enforcement announced it had used a technique called forensic investigative genetic genealogy (FIGG) to identify the Golden State Killer, we conducted a U.S. general population survey and found most respondents supported using FIGG to solve violent crimes. Since then, FIGG has helped close hundreds of criminal cases, but it also has weathered controversies. On FIGG's fifth anniversary, we conducted an expanded, follow-up survey with U.S.-based participants to determine if public opinion had changed and found continued support for FIGG across most applications. The same proportion (91 %) of respondents in the 2018 and 2023 surveys endorsed …

Diagnostic Performance Of Contrast-Enhanced Ultrasound In Traumatic Solid Organ Injuries In Children: A Systematic Review And Meta-Analysis, Payam Jannatdoust, Parya Valizadeh, Amir Hassankhani, Melika Amoukhteh, Delaram J Ghadimi, Mahsa Heidari-Foroozan, Paniz Sabeghi, Paniz Adli, Jennifer H Johnston, Pauravi S Vasavada, Ali Gholamrezanezhad

Faculty, Staff and Student Publications

Background: Blunt abdominal trauma (BAT) is a significant contributor to pediatric mortality, often causing liver and spleen injuries. Contrast-enhanced computed tomography (CT), the gold standard for diagnosing solid organ injury, poses radiation risks to children. Contrast-enhanced ultrasound (CEUS) may be a promising alternative imaging modality.

Objectives: To evaluate the diagnostic utility of CEUS for detecting solid organ injuries following BAT in the pediatric population.

Methods: A systematic review and meta-analysis were conducted through a thorough literature search in PubMed, Scopus, Web of Science, and Embase databases up to October 1, 2023. Diagnostic accuracy metrics were aggregated using a bivariate model, …

A Statistical Framework For Multi-Trait Rare Variant Analysis In Large-Scale Whole-Genome Sequencing Studies, Xihao Li, Han Chen, Margaret Sunitha Selvaraj, Eric Van Buren, Hufeng Zhou, Yuxuan Wang, Ryan Sun, Zachary R Mccaw, Zhi Yu, Min-Zhi Jiang, Daniel Dicorpo, Sheila M Gaynor, Rounak Dey, Donna K Arnett, Emelia J Benjamin, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, April P Carson, Jenna C Carlson, Nathalie Chami, Yii-Der Ida Chen, Joanne E Curran, Paul S De Vries, Myriam Fornage, Nora Franceschini, Barry I Freedman, Charles Gu, Nancy L Heard-Costa, Jiang He, Lifang Hou, Yi-Jen Hung, Marguerite R Irvin, Robert C Kaplan, Sharon L R Kardia, Tanika N Kelly, Iain Konigsberg, Charles Kooperberg, Brian G Kral, Changwei Li, Yun Li, Honghuang Lin, Ching-Ti Liu, Ruth J F Loos, Michael C Mahaney, Lisa W Martin, Rasika A Mathias, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Kari E North, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Susan Redline, Alexander P Reiner, Stephen S Rich, Colleen M Sitlani, Jennifer A Smith, Kent D Taylor, Hemant K Tiwari, Ramachandran S Vasan, Satupa'itea Viali, Zhe Wang, Jennifer Wessel, Lisa R Yanek, Bing Yu, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Josée Dupuis, James B Meigs, Paul L Auer, Laura M Raffield, Alisa K Manning, Kenneth M Rice, Jerome I Rotter, Gina M Peloso, Pradeep Natarajan, Zilin Li, Zhonghua Liu, Xihong Lin

Faculty, Staff and Student Publications

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple …

Incidence And Survival Of Children And Adolescents With Wilms Tumor, United States, 2001-2020, Andres F Espinoza, Ekene Onwuka, David A Siegel, Shifan Dai, Sanjeev A Vasudevan, Michael E Scheurer, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Background: Wilms tumor (WT) is the most common pediatric malignancy of the kidney. Past studies describing WT incidence and survival used surveillance data with < 30% of the US population. We evaluated differences in WT incidence and survival comparing demographic groups and tumor characteristics.

Methods: We analyzed new cases of WT among patients aged < 20 years at diagnosis by using incidence data from US Cancer Statistics (USCS) for 2003-2020 and 5-year relative survival (RS) data from the National Program of Cancer Registries (NPCR) for 2001-2019. To assess incidence trends, average annual percent change (AAPC) was calculated by using joinpoint regression. Relative survival (RS) and all-cause survival were calculated overall and by demographic and clinical variables.

Results: During 2003-2020, 8218 cases of WT were reported in USCS, which represented an age-adjusted incidence rate of 5.7 cases per million. Rates were the highest among females (6.3), children aged 0-4 years (17.2), and non-Hispanic Black patients (7.1). Overall, trends remained stable (AAPC = -0.4, 95% CI: -1.4 to 0.4). Among 7567 cases of WT in NPCR, 5-year RS was 92.6%. Patients with the lowest …

Cross-Sectional Comparison Of Structural Mri Markers Of Impairment In A Diverse Cohort Of Older Adults, Julie K Wisch, Kalen Petersen, Peter R Millar, Omar Abdelmoity, Ganesh M Babulal, Karin L Meeker, Meredith N Braskie, Kristine Yaffe, Arthur W Toga, Sid O'Bryant, Beau M Ances, Habs‐Hd Study Team

2020-Current year OA Pubs

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented. The purpose of this study was to identify which commonly used structural MRI measure (hippocampal volume, cortical thickness in AD signature regions, or brain age gap [BAG]) had the best correspondence with the Clinical Dementia Rating (CDR) in an ethno-racially diverse sample. 2870 individuals recruited by the Healthy and Aging …

Synthesis And In Vitro Evaluation Of Novel Compounds And Discovery Of A Promising Iodine-125 Radioligand For Purinergic P2x7 Receptor (P2x7r), Lin Qiu, Jinzhi Wang, Manju Tewari, Derek T Rensing, Terrance M Egan, Joel S Perlmutter, Zhude Tu

2020-Current year OA Pubs

The purinergic P2X ligand-gated ion channel 7 receptor (P2X7R) plays a critical role in various inflammatory processes and other diseases. Fast determination of compounds P2X7R binding potency and discovery of a promise PET radiotracer for imaging P2X7R require a P2X7R suitable radioligand for radioactive competitive binding assay. Herein, we designed and synthesized thirteen new P2X7R ligands and determined the in vitro binding potency. The fluorescence screening assay identified the iodide compound 1c with high potency and specificity toward P2X7R with an IC

Nrf2/Cyclooxygenase 2 Signaling In Cr(Vi)-Induced Carcinogenesis, Lei Zhao, Yi-Fang Wang, Andrea Adamcakova-Dodd, Peter Thorne, Ranakul Islam, Ke Jian Liu, Fei Chen, Jia Luo, Ling-Zhi Liu

Kimmel Cancer Center Faculty Papers

Long-term exposure to hexavalent chromium [Cr(VI)] has been linked to lung cancer, and cyclooxygenase-2 (COX-2) is a well-known inflammatory factor. However, the role and mechanism of COX-2 in Cr(VI)-induced carcinogenesis are not clear yet. To address this question, we employed a mouse model exposed to Cr(VI) through intranasal instillation of particulate zinc chromate (ZnCrO4) for 12 weeks. Metabolomics and RNA-seq assays revealed enhanced activity of the arachidonic acid (AA)/eicosanoid metabolism pathway in lung tissues from mice exposed to Cr(VI). COX-2, the key enzyme of the AA/eicosanoid pathway, was significantly upre- gulated in Cr(VI)-exposed lung tissues, as well as in the …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Wf-Ppg: A Wrist-Finger Dual-Channel Dataset For Studying The Impact Of Contact Pressure On Ppg Morphology, Matthew Yiwen Ho, Hung Manh Pham, Aaqib Saeed, Dong Ma

Research Collection School Of Computing and Information Systems

Photoplethysmography (PPG) is a simple optical technique widely used in wearable devices for continuous cardiac health monitoring. However, the quality of PPG signals, particularly their morphology, is influenced by the contact pressure between the skin and the sensor. This variability in signal quality complicates complex tasks that rely on high-quality signals, such as blood pressure and heart rate variability estimation, making them less reliable or even impossible. To address this issue, we present a novel dataset (termed WF-PPG) comprising PPG signals from the wrist measured under varying contact pressures, along with high-quality PPG signals from the fingertip captured simultaneously. Data …

Multi-Cancer Early Detection Tests: Attributes For Clinical Implementation, Jon O. Ebbert, Ernest T. Hawk, Christopher V. Chambers, Margaret A. Tempero, Elliot K. Fishman, Jospeh E. Ravenell, Tomasz M. Beer, Seema P. Rego

Department of Family & Community Medicine Faculty Papers

Guideline-recommended screening programs exist for only a few single-cancer types, and these cancers represent less than one-half of all new cancer cases diagnosed each year in the U.S. In addition, these "single-cancer" standard of care (SoC) screening tests vary in accuracy, adherence, and effectiveness, though all are generally understood to lead to reductions in cancer-related mortality. Recent advances in high-throughput technologies and machine learning have facilitated the development of blood-based multi-cancer early detection (MCED) tests. The opportunity for early detection of multiple cancers with a single blood test holds promise in addressing the current unmet need in cancer screening. By …

Notch3 Deletion Regulates Hiv-1 Gene Expression And Systemic Inflammation To Ameliorate Chronic Kidney Disease, Mackenzie Thornton, Nicole Sommer, Mercedes Mcgonigle, Anil Kumar Ram, Sireesha Yerrathota, Henrietta Ehirim, Aakriti Chaturvedi, Johnny Dinh Phan, Anubhav Chakraborty, V. Praveen Chakravarthi, Sumedha Gunewardena, Mudit Tyagi, Jaya Talreja, Tao Wang, Pravin Singhal, Pamela V. Tran, Timothy A. Fields, Patricio E. Ray, Navneet K. Dhillon, Madhulika Sharma

Center for Translational Medicine Faculty Papers

Anti-retroviral therapy (ART) has decreased human immunodeficiency virus (HIV)-1-associated morbidity. However, despite ART, immune cells remain latently infected, leading to chronic inflammation and HIV-1-associated comorbidities. New strategies are needed to target viral proteins and inflammation. We found activation of Notch3 in renal cells of the HIV-1 transgenic mouse model (HIV-Tg26) and in patients with HIV-associated nephropathy. We hypothesized that targeting NOTCH3 activation constitutes an effective therapy for HIV-related chronic kidney disease. We generated HIV-Tg26 mice with Notch3 knocked out (Tg-N3KO). Compared to HIV-Tg26 mice at 3 months, Tg-N3KO mice showed a marked reduction in renal injury, skin lesions and mortality …

Tracking Community Outreach And Engagement Activities Among National Cancer Institute-Designated Cancer Centers, Todd Burus, Caree Mcafee, Pamela Hull, Amy Leader, Christopher Mcnair

Kimmel Cancer Center Faculty Papers

The National Cancer Institute's (NCI) Cancer Center Support Grant mandates that NCI-designated cancer centers establish a Community Outreach and Engagement (COE) component to help direct efforts at reducing cancer burden within their catchment areas. Despite the critical role of COE offices, little is known about how they track and evaluate outreach activities and outcomes. We gathered information on current practices from representatives of 40 out of 65 COE offices using an online survey. Although nearly all responding centers (97.5%) tracked COE activities, no consensus existed on resources used, and satisfaction with current solutions was mixed (51.0% not satisfied). Respondents expressed …