Medicine and Health Sciences Commons^™

Omnidirectional Wireless Power Transfer For Millimetric Magnetoelectric Biomedical Implants, Wei Wang, Zhanghao Yu, Yiwei Zou, Joshua E Woods, Prahalad Chari, Yumin Su, Jacob T Robinson, Kaiyuan Yang

Faculty, Staff and Students Publications

Miniature bioelectronic implants promise revolutionary therapies for cardiovascular and neurological disorders. Wireless power transfer (WPT) is a significant method for miniaturization, eliminating the need for bulky batteries in today’s devices. Despite successful demonstrations of millimetric battery-free implants in animal models, the robustness and efficiency of WPT are known to degrade significantly under misalignment incurred by body movements, respiration, heart beating, and limited control of implant orientation during surgery. This paper presents an omnidirectional WPT platform for millimetric bioelectronic implants, employing the emerging magnetoelectric (ME) WPT modality, and “magnetic field steering” technique based on multiple transmitter (TX) coils. To accurately sense …

Car-Redirected Natural Killer T Cells Demonstrate Superior Antitumor Activity To Car-T Cells Through Multimodal Cd1d-Dependent Mechanisms, Xin Zhou, Ying Wang, Zhangqi Dou, Gloria Delfanti, Ourania Tsahouridis, Caroline Marnata Pellegry, Manuela Zingarelli, Gatphan Atassi, Mark G Woodcock, Giulia Casorati, Paolo Dellabona, William Y Kim, Linjie Guo, Barbara Savoldo, Ageliki Tsagaratou, J Justin Milner, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Human natural killer T (NKT) cells have been proposed as a promising cell platform for chimeric antigen receptor (CAR) therapy in solid tumors. Here we generated murine CAR-NKT cells and compared them with CAR-T cells in immune-competent mice. Both CAR-NKT cells and CAR-T cells showed similar antitumor effects in vitro, but CAR-NKT cells showed superior antitumor activity in vivo via CD1d-dependent immune responses in the tumor microenvironment. Specifically, we show that CAR-NKT cells eliminate CD1d-expressing M2-like macrophages. In addition, CAR-NKT cells promote epitope spreading and activation of endogenous T cell responses against tumor-associated neoantigens. Finally, we observed that CAR-NKT cells …

Genetic Risk Factors In Isolated Dystonia Escape Genome-Wide Association Studies, Björn-Hergen Laabs, Katja Lohmann, Eva-Juliane Vollstedt, Tobias Reinberger, Lisa-Marie Nuxoll, Gamze Kilic-Berkmen, Joel S Perlmutter, Sebastian Loens, Carlos Cruchaga, Andre Franke, Valerija Dobricic, Frauke Hinrichs, Anne Grözinger, Eckart Altenmüller, Steven Bellows, Sylvia Boesch, Susan B Bressman, Kevin R Duque, Alberto J Espay, Andreas Ferbert, Jeanne S Feuerstein, Samuel Frank, Thomas Gasser, Bernhard Haslinger, Robert Jech, Frank Kaiser, Christoph Kamm, Katja Kollewe, Andrea A Kühn, Mark S Ledoux, Ebba Lohmann, Abhimanyu Mahajan, Alexander Münchau, Trisha Multhaupt-Buell, Alexander Pantelyat, Sarah E Pirio Richardson, Deborah Raymond, Stephen G Reich, Rachel Saunders Pullman, Barbara Schormair, Nutan Sharma, Azadeh Hamzehei Sichani, Kristina Simonyan, Jens Volkmann, Aparna Wagle Shukla, Juliane Winkelmann, Laura J Wright, Michael Zech, Kirsten E Zeuner, Simone Zittel, Meike Kasten, Yan V Sun, Tobias Bäumer, Norbert Brüggemann, Laurie J Ozelius, Hyder A Jinnah, Christine Klein, Inke R König

Faculty, Staff and Students Publications

Background: Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia.

Objective: The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia.

Methods: Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation.

Results: This GWAS identified no common genome-wide significant …

Comparative Effectiveness Of Different Corticosteroid Regimens In Severe Alcohol-Associated Hepatitis, Alvi Husni Islam, Luis Antonio Díaz, Francisco Idalsoaga, Leonardo Guizzetti, Rokhsana Mortuza, Winston Dunn, Ashwani K Singal, Douglas Simonetto, Carolina Ramirez-Cadiz, Wei Zhang, Steve Qian, Joaquín Cabezas, Shiv K Sarin, Rakhi Maiwall, Prasun K Jalal, Fatima Higuera-De La Tijera, Lubomir Skladany, Natalia Bystrianska, Diego Rincon, Kristina R Chacko, Meritxell Ventura Cots, Guadalupe Garcia-Tsao, Juan G Abraldes, Patrick S Kamath, Marco Arrese, Vijay Shah, Ramon Bataller, Juan Pablo Arab

Faculty, Staff and Students Publications

No abstract provided.

To Manipulate Or Not? Management Of Pediatric Knee Arthrofibrosis Following Operative Fixation Of Tibial Spine Fractures, Matthew J Folkman, Neeraj M Patel, Alexandra C Stevens, Aristides I Cruz, R Jay Lee, Indranil Kushare, Theodore J Ganley, Henry Ellis, Peter Fabricant, Daniel Green, Benjamin Johnson, Scott Mckay, Gregory Schmale, Yi-Meng Yen, R Justin Mistovich

Faculty, Staff and Students Publications

Background: Knee arthrofibrosis is a common complication after surgical fixation of tibial spine fractures. However, there is no standardized treatment modality for resultant arthrofibrosis, with some surgeons electing for nonoperative management, while others prefer manipulation under anesthesia with a possible arthroscopic lysis of adhesions, if indicated. To better understand indications and outcomes from these treatment modalities for arthrofibrosis, we examined patients treated by both approaches.

Methods: We performed a multicenter retrospective case series of patients with arthrofibrosis after tibial spine fracture surgery. Arthrofibrosis was defined as loss of knee extension ≥10.0° and/or knee flexion ≥25.0° compared to the contralateral, uninjured …

Eyelid Reconstruction, Srinithya R Gillipelli, Diego M Quirarte, Winston R Owens, Matthew J Parham, Austin Y Jiang, Katherine J Williams, Amy S Xue

Faculty, Staff and Students Publications

Reconstruction of the eyelid is a complex process that requires an understanding of eyelid anatomy and various reconstructive techniques to restore function and appearance. The eyelids, essential for globe protection, moisture retention, and expression, contain the lacrimal system and intricate musculature that make reconstruction challenging. Tumor excision commonly results in defects in the eyelid that require careful reconstructive planning, with consideration for defect dimensions, location, and involvement of surrounding tissue. This review presents reconstructive techniques commonly used in the management of eyelid defects.

National Liver Cancer Screening Trial (Tracer) Study Protocol, Amit G Singal, Neehar D Parikh, Fasiha Kanwal, Jorge A Marrero, Sneha Deodhar, Stephanie Page-Lester, Camden Lopez, Ziding Feng, Nabihah Tayob

Faculty, Staff and Students Publications

BACKGROUND: Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice. …

Spinoplastic Reconstruction Using Iliac Crest Vascularized Bone Graft Following Sacral Ependymoma Resection, Edward M Reece, Nicole Van Spronsen, Calogero Velluto, Jonathan L Jeger, Christopher Fullmer, Isra Abdulwadood, Jenna Meyer, Alexander E Ropper, Sebastian Winocour, Michael A Bohl, Maziyar A Kalani

Faculty, Staff and Students Publications

Sacral reconstruction post tumor resection has historically been executed with the placement of hardware or free tissue transfer. Reconstruction using a vascularized bone graft is an alternative that avoids the complications associated with hardware placement or free tissue transfer. This article describes the first documented case of spinoplastic reconstruction using an iliac crest vascularized bone graft (IC-VBG) after the resection of a sacral ependymoma. This is a case of a 17-year-old boy with a history of a sacral myxopapillary ependymoma. He presented to a local emergency department complaining of 6 months of urinary incontinence and progressive paresthesias affecting the left …

Fetal Lower Urinary Tract Obstruction: International Delphi Consensus On Management And Core Outcome Set, H J Mustafa, A Khalil, S Johnson, 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 …

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, Stuart L Cramer, Alyssa Terry Reddy, Charles Gene Minard, 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 …

Blocking Il-17a Signaling Decreases Lung Inflammation And Improves Alveolarization In Experimental Bronchopulmonary Dysplasia, Meagan Goates, Amrit Shrestha, Shyam Thapa, Matthew Bettini, Roberto Barrios, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of preterm infants that is associated with life-long morbidities. Inflammatory insults contribute to BPD pathogenesis. Although the proinflammatory cytokine, IL-17a, plays a role in various neonatal inflammatory disorders, its role in BPD pathogenesis is unclear. To test the hypothesis that blocking IL-17a signaling decreases lipopolysaccharide (LPS)-mediated experimental BPD in neonatal mice, wild-type mice were injected intraperitoneally with phosphate-buffered saline or LPS during the saccular lung developmental phase. Pulmonary IL-17a expression was determined by enzyme-linked immunosorbent assay and by flow cytometry. LPS-injected mice had higher pulmonary IL-17a protein levels and IL-17a

Update On Pediatric Cancer Surveillance Recommendations For Patients With Neurofibromatosis Type 1, Noonan Syndrome, Cbl Syndrome, Costello Syndrome, And Related Rasopathies, Melissa R Perrino, Anirban Das, Sarah R Scollon, Sarah G Mitchell, Mary-Louise C Greer, Marielle E Yohe, Jordan R Hansford, Jennifer M Kalish, Kris Ann P Schultz, Suzanne P Macfarland, Wendy K Kohlmann, Philip J Lupo, Kara N Maxwell, Stefan M Pfister, Rosanna Weksberg, Orli Michaeli, Marjolijn C J Jongmans, Gail E Tomlinson, Jack Brzezinski, Uri Tabori, Gina M Ney, Karen W Gripp, Andrea M Gross, Brigitte C Widemann, Douglas R Stewart, Emma R Woodward, Christian P Kratz

Center for Medical Ethics and Health Policy Staff Publications

Neurofibromatosis type 1 (NF1), Noonan syndrome, and related syndromes, grouped as RASopathies, result from dysregulation of the RAS-MAPK pathway and demonstrate varied multisystemic clinical phenotypes. Together, RASopathies are among the more prevalent genetic cancer predisposition syndromes and require nuanced clinical management. When compared with the general population, children with RASopathies are at significantly increased risk of benign and malignant neoplasms. In the past decade, clinical trials have shown that targeted therapies can improve outcomes for low-grade and benign neoplastic lesions but have their own challenges, highlighting the multidisciplinary care needed for such individuals, specifically those with NF1. This perspective, which …

Transcriptomic And Epigenomic Signatures Distinguish High- And Low-Risk Endotypes For Liver Tumor Development, Sandra L Grimm, Tia Talley, Rahul K Jangid, Amrit Koirala, Micah B Castillo, Preethi H Gunaratne, Cristian Coarfa, Cheryl L Walker

Faculty, Staff and Students Publications

The epigenome is a target for environmental exposures and a potential determinant of inter-individual differences in response. In genetically identical C57Bl/6 mice exposed from gestation to weaning to the endocrine-disrupting chemical (EDC) tributyltin (TBT), hepatic tumor development later in life varied across multiple cohorts over time and depending on sex and diet. In one cohort where approximately half of TBT-exposed male mice developed liver tumors at 10 months (Katz et al. Hepatic tumor formation in adult mice developmentally exposed to organotin, Environmental Health Perspectives, 128 (1), 17010, 2020), transcriptomic (RNA-seq) and epigenomic (ChIP-seq) profiling was performed on blood and liver …

Automated Electronic Health Record Data Extraction And Curation Using Extractehr, Tamara P Miller, Kelly D Getz, Edward Krause, Yun Gun Jo, Sandhya Charapala, M Monica Gramatages, Karen Rabin, Michael E Scheurer, Jennifer J Wilkes, Brian T Fisher, Richard Aplenc

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Although the potential transformative effect of electronic health record (EHR) data on clinical research in adult patient populations has been very extensively discussed, the effect on pediatric oncology research has been limited. Multiple factors contribute to this more limited effect, including the paucity of pediatric cancer cases in commercial EHR-derived cancer data sets and phenotypic case identification challenges in pediatric federated EHR data.

Methods: The ExtractEHR software package was initially developed as a tool to improve clinical trial adverse event reporting but has expanded its use cases to include the development of multisite EHR data sets and the support …

Exploring Latent Clusters In Pediatric Ocd Based On Symptoms, Severity, Age, Gender, And Comorbidity, Orri Smárason, Robert R Selles, Davíð R M A Højgaard, John R Best, Karin Melin, Tord Ivarsson, Per Hove Thomsen, Bernhard Weidle, Nicole Michelle Mcbride, Eric A Storch, Daniel Geller, Sabine Wilhelm, Lara J Farrell, Allison M Waters, Sharna Mathieu, Noam Soreni, S Evelyn Stewart, Gudmundur Skarphedinsson

Center for Medical Ethics and Health Policy Staff Publications

Given diverse symptom expression and high rates of comorbid conditions, the present study explored underlying commonalities among OCD-affected children and adolescents to better conceptualize disorder presentation and associated features. Data from 830 OCD-affected participants presenting to OCD specialty centers was aggregated. Dependent mixture modeling was used to examine latent clusters based on their age- and gender adjusted symptom severity (as measured by the Children's Yale-Brown Obsessive-Compulsive Scale; CY-BOCS), symptom type (as measured by factor scores calculated from the CY-BOCS symptom checklist), and comorbid diagnoses (as assessed via diagnostic interviews). Fit statistics favored a four-cluster model with groups distinguished primarily by …

Loss-Of-Function In Rbbp5 Results In A Syndromic Neurodevelopmental Disorder Associated With Microcephaly, Yue Huang, Kristy L Jay, Alden Yen-Wen Huang, 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 …

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, Jennifer Decuir, Diya Surie, Yuwei Zhu, 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 …

Polygenic Risk Scores And Extreme Coronary Artery Calcium Phenotypes (Cac=0 And Cac≥1000) In Adults ≥75 Years Old: The Aric Study, Omar Dzaye, Alexander C Razavi, Zeina A Dardari, Frances M Wang, Yasuyuki Honda, Khurram Nasir, Josef Coresh, 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 …

Impact And Recovery Of Vha Epilepsy Care Services During The Covid-19 Pandemic, Zulfi Haneef, Erin Sullivan-Baca, Rizwana Rehman, Alan Towne, Ann C Van Cott, Aatif Husain

Faculty, Staff and Students Publications

BACKGROUND: The Epilepsy Centers of Excellence (ECoE) is a network of facilities within the Veterans Health Administration that evaluates and treats veterans with epilepsy and seizure disorders. This article outlines how the COVID-19 pandemic impacted ECoE services and recovery.

METHODS: Directors of 17 ECoEs were surveyed 4 times between May 2020 and July 2022 on 5 domains: functioning of outpatient epilepsy clinics, outpatient electroencephalogram, epilepsy monitoring unit, anticipated permanent operational changes, and utility of national and local recommendations. Data on the spread of COVID-19 and administrative workload data were compared with the availability of epilepsy services.

RESULTS: There was an …

Obturator Neurectomy For The Treatment Of Adductor Spasticity: A Novel Technique And Case Series, Maximillian S Feygin, Michael Larkin, Dan Curry, Scott B Rosenfeld, Aloysia Schwabe, Nisha Gadgil

Faculty, Staff and Students Publications

Background The management of adductor spasticity and long-term sequelae for cerebral palsy (CP) patients is complex. Hip displacement is a common consequence of CP, and obturator neurectomy (ON) is a potentially underutilized procedure to address the underlying adductor spasticity. The aim of this study is to describe the operational technique of ON and highlight the potential efficacy of ON in reducing spasticity, as well as pain, hip, and functional outcomes in these patients. Methods A total of eight patients from Texas Children's Hospital who underwent ON between 2008 and 2023 were included in this case series. Results ON led to …

An Ancient Ecospecies Of Helicobacter Pylori, Elise Tourrette, Roberto C Torres, Sarah L Svensson, Takashi Matsumoto, Muhammad Miftahussurur, Kartika Afrida Fauzia, Ricky Indra Alfaray, Ratha-Korn Vilaichone, Vo Phuoc Tuan, Helicobacter Genomics Consortium, Difei Wang, Abbas Yadegar, Lisa M Olsson, Zhemin Zhou, Yoshio Yamaoka, Kaisa Thorell, Daniel Falush

Faculty, Staff and Students Publications

Helicobacter pylori disturbs the stomach lining during long-term colonization of its human host, with sequelae including ulcers and gastric cancer1,2. Numerous H. pylori virulence factors have been identified, showing extensive geographic variation1. Here we identify a ‘Hardy’ ecospecies of H. pylori that shares the ancestry of ‘Ubiquitous’ H. pylori from the same region in most of the genome but has nearly fixed single-nucleotide polymorphism differences in 100 genes, many of which encode outer membrane proteins and host interaction factors. Most Hardy strains have a second urease, which uses iron as a cofactor rather than …

Revealing Patterns Of Sars-Cov-2 Variant Emergence And Evolution Using Rbd Amplicon Sequencing Of Wastewater, Xingwen Chen, John Balliew, Cici X Bauer, Jennifer Deegan, Anna Gitter, Blake M Hanson, Anthony W Maresso, Michael J Tisza, Catherine L Troisi, Janelle Rios, Kristina D Mena, Eric Boerwinkle, Fuqing Wu

Faculty, Staff and Student Publications

Objectives: Rapid evolution of SARS-CoV-2 has resulted in the emergence of numerous variants, posing significant challenges to public health surveillance. Clinical genome sequencing, while valuable, has limitations in capturing the full epidemiological dynamics of circulating variants in the general population. This study aimed to monitor the SARS-CoV-2 variant community dynamics and evolution using receptor-binding domain (RBD) amplicon sequencing of wastewater samples.

Methods: We sequenced wastewater from El Paso, Texas, over 17 months, compared the sequencing data with clinical genome data, and performed biodiversity analysis to reveal SARS-CoV-2 variant dynamics and evolution.

Results: We identified 91 variants and observed waves of …

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, Gabriela Matamoros, Ana Sanchez, Ruben Cimino, 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 …

Macrophage Iron Dyshomeostasis Promotes Aging-Related Renal Fibrosis, Lingzhi Wu, Hongchun Lin, Shaomin Li, Yuebo Huang, Yuxiang Sun, Shuangshuang Shu, Ting Luo, Tiantian Liang, Weiyan Lai, Jialing Rao, Zhaoyong Hu, Hui Peng

Faculty, Staff and Students Publications

Renal aging, marked by the accumulation of senescent cells and chronic low-grade inflammation, leads to renal interstitial fibrosis and impaired function. In this study, we investigate the role of macrophages, a key regulator of inflammation, in renal aging by analyzing kidney single-cell RNA sequencing data of C57BL/6J mice from 8 weeks to 24 months. Our findings elucidate the dynamic changes in the proportion of kidney cell types during renal aging and reveal that increased macrophage infiltration contributes to chronic low-grade inflammation, with these macrophages exhibiting senescence and activation of ferroptosis signaling. CellChat analysis indicates enhanced communications between macrophages and tubular …

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 …

Pharmacogenomic Insights In Psychiatric Care: Uncovering Novel Actionability, Allele-Specific Cyp2d6 Copy Number Variation, And Phenoconversion In 15,000 Patients, Jai N Patel, Sarah A Morris, Raul Torres, Brooke Rhead, Chris Vlangos, Daniel J Mueller, Lisa C Brown, Hailey Lefkofsky, Muneer Ali, Francisco M De La Vega, Kathleen C Barnes, Anthony Zoghbi, Joseph D Stanton, Marcus A Badgeley

Faculty, Staff and Students Publications

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and …

Experiences Of Midwestern Obstetric Clinicians During The Coronavirus Disease 2019 Pandemic, Drishti D Sinha, Megan Foeller, Abigail S Bell, Anthony J Nixon, Darrell Hudson, Aimee S James, Amy R Scheffer, Ana A Baumann, Emily Diveley, Ebony B Carter, Nandini Raghuraman, Indira U Mysorekar, Jeannie C Kelly

Faculty, Staff and Students Publications

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic led to healthcare system changes aimed at minimizing disease transmission that impacted experiences with obstetric healthcare.

OBJECTIVE: To explore experiences of clinicians providing obstetric care during the COVID-19 pandemic.

STUDY DESIGN: Qualitative, in-depth, semi-structured interviews were conducted with five nurse practitioners and 16 obstetrical physicians providing a mix of outpatient and inpatient obstetric care during the COVID-19 pandemic in a mid-sized, Midwestern city in the United States. Interviews elucidated challenges and facilitators of obstetric care provision and vaccination of pregnant patients against COVID-19 during the pandemic. Transcripts were coded inductively then deductively using …

Multidisciplinary Amputation Prevention At The Debakey Va Hospital: Our First Decade, Neal R Barshes, Aimee D Garcia, Cezarina Mindru, Maria Rodriguez-Barradas, Panos Kougias, David M Green, Samir S Awad

Faculty, Staff and Students Publications

BACKGROUND: In 2011, the Veterans Health Administration (VHA) undertook multidisciplinary efforts to improve care for patients with nonhealing foot ulcers and reduce leg amputation rates. This article examines the impact of interdisciplinary care for amputation prevention in the VHA.

METHODS: The VHA patient population was characterized using internal registries. Texas hospital admission data were used to identify sex and zip-code matched cohorts. VHA provided data on national and local frequencies of various amputations and the number of patients with diabetes.

RESULTS: Compared to matched nonveteran patients, veterans treated at VHA hospitals were older and more often self-identified as Black. They …

Attention-Based Cnn-Bilstm For Sleep State Classification Of Spatiotemporal Wide-Field Calcium Imaging Data, Xiaohui Zhang, Eric C Landsness, Hanyang Miao, Wei Chen, Michelle J Tang, Lindsey M Brier, Joseph P Culver, Jin-Moo Lee, Mark A Anastasio

2020-Current year OA Pubs

BACKGROUND: Wide-field calcium imaging (WFCI) with genetically encoded calcium indicators allows for spatiotemporal recordings of neuronal activity in mice. When applied to the study of sleep, WFCI data are manually scored into the sleep states of wakefulness, non-REM (NREM) and REM by use of adjunct EEG and EMG recordings. However, this process is time-consuming, invasive and often suffers from low inter- and intra-rater reliability. Therefore, an automated sleep state classification method that operates on spatiotemporal WFCI data is desired.

NEW METHOD: A hybrid network architecture consisting of a convolutional neural network (CNN) to extract spatial features of image frames and …

Current Best Practices And Future Opportunities For Reproducible Findings Using Large-Scale Neuroimaging In Psychiatry, Neda Jahanshad, Petra Lenzini, Janine Bijsterbosch

2020-Current year OA Pubs

Research into the brain basis of psychopathology is challenging due to the heterogeneity of psychiatric disorders, extensive comorbidities, underdiagnosis or overdiagnosis, multifaceted interactions with genetics and life experiences, and the highly multivariate nature of neural correlates. Therefore, increasingly larger datasets that measure more variables in larger cohorts are needed to gain insights. In this review, we present current "best practice" approaches for using existing databases, collecting and sharing new repositories for big data analyses, and future directions for big data in neuroimaging and psychiatry with an emphasis on contributing to collaborative efforts and the challenges of multi-study data analysis.