Medicine and Health Sciences Commons^™

A Roadmap To Cysteine Specific Labeling Of Membrane Proteins For Single-Molecule Photobleaching Studies, Melanie Ernst, Robyn Mahoney-Kruszka, Nathan B Zelt, Janice L Robertson

2020-Current year OA Pubs

Single-molecule photobleaching analysis is a useful approach for quantifying reactive membrane protein oligomerization in membranes. It provides a binary readout of a fluorophore attached to a protein subunit at dilute conditions. However, quantification of protein stoichiometry from this data requires information about the subunit labeling yields and whether there is non-specific background labeling. Any increases in subunit-specific labeling improves the ability to determine oligomeric states with confidence. A common strategy for site-specific labeling is by conjugation of a fluorophore bearing a thiol-reactive maleimide group to a substituted cysteine. Yet, cysteine reactivity can be difficult to predict as it depends on …

Triacylglycerol Mobilization Underpins Mitochondrial Stress Recovery, Zakery N Baker, Yunyun Zhu, Rachel M Guerra, Andrew J Smith, Aline Arra, Lia R Serrano, Katherine A Overmyer, Shankar Mukherji, Elizabeth A Craig, Joshua J Coon, David J Pagliarini

2020-Current year OA Pubs

Mitochondria are central to myriad biochemical processes, and thus even their moderate impairment could have drastic cellular consequences if not rectified. Here, to explore cellular strategies for surmounting mitochondrial stress, we conducted a series of chemical and genetic perturbations to Saccharomyces cerevisiae and analysed the cellular responses using deep multiomic mass spectrometry profiling. We discovered that mobilization of lipid droplet triacylglycerol stores was necessary for strains to mount a successful recovery response. In particular, acyl chains from these stores were liberated by triacylglycerol lipases and used to fuel biosynthesis of the quintessential mitochondrial membrane lipid cardiolipin to support new mitochondrial …

Bowel Emergencies In Patients With Cancer, Hannah Hughes, Ankush Jajodia, Philippe Soyer, Vincent Mellnick, Michael N Patlas

2020-Current year OA Pubs

Cancer is the second most common cause of death worldwide. Bowel emergencies in patients with cancer are becoming increasingly more prevalent due to advances in cancer therapy and longer overall patient survival. When these patients present acutely, they are often frail and may have pre-existing co-morbidities. This article discusses the imaging features of bowel emergencies commonly encountered in oncological patients in clinical practice. These include chemotherapy related colitis, neutropenia enterocolitis and typhlitis, toxic megacolon, bowel perforation, malignant bowel obstruction and gastrointestinal haemorrhage. The radiologist plays a key role in identifying these oncological emergencies and guiding further management.

National Prescribing Practices For Pediatric Dystonia Among Providers In The United States., Sarah Paige Davis, Natalie J. Kane, Haley E. Botteron, Rose N. Gelineau-Morel

Manuscripts, Articles, Book Chapters and Other Papers

While multiple oral medications are used to treat dystonia, limited information exists on current prescribing practices. This study analyzes real-world prescribing practices for pediatric dystonia in the United States, evaluating prescription frequency, dosing, and the impact of comorbidities. Oracle electronic health record real-world data were queried from 2014 to 2019 for encounters of patients under age 18 with a dystonia diagnosis and available medication records. Information was extracted on prescriptions for dystonia medications (baclofen, clonidine, carbidopa-levodopa, gabapentin, tetrabenazine, trihexyphenidyl, and select benzodiazepines), dosing, and comorbid diagnoses of cerebral palsy (CP), epilepsy, or spasticity. A total of 4010 pediatric patients with …

Improvement On The Slopes: The Impact Of An Adaptive Snow Sports Program On Children And Young Adults With Disabilities., Stephanie M. Barton, Matthew J. Mclaughlin, Mark T. Fisher

Manuscripts, Articles, Book Chapters and Other Papers

PurposeThis retrospective cohort study sought to examine participant skill and functional progression in an adaptive snow sports program for children and young adults with disabilities.MethodsOne hundred twelve individuals, majority male, who participated in at least 2 adapted ski or snowboard sessions were evaluated by trained adaptive instructors. The primary outcome measure was standardized skill level ranging from 1-novice to 9-expert. Secondary outcome measures of cognitive, emotional, social, physical, and independence scores, were rated on a scale from 1-5, with 5 being the highest.ResultsThe median number of sessions per participant was 4 (range 2-65 sessions) and median participation duration was 2 …

Evaluating The World Health Organization's Hearts Model For Hypertension And Diabetes Management: A Pilot Implementation Study In Guatemala, Irmgardt Alicia Wellmann, Luis Fernando Ayala, Taryn M Valley, Vilma Irazola, Mark D Huffman, Michele Heisler, Peter Rohloff, Rocío Donis, Eduardo Palacios, Manuel Ramírez-Zea, David Flood

2020-Current year OA Pubs

BACKGROUND: The World Health Organization HEARTS Technical Package is a widely implemented global initiative to improve the primary care management of cardiovascular disease risk factors. The study's objective is to report outcomes from a pilot implementation trial of integrated hypertension and diabetes management based on the HEARTS model in Guatemala.

METHODS: We conducted a single-arm pilot implementation trial over six months from October 2023 to May 2024 in 11 Guatemalan Ministry of Health primary care facilities in two districts. The pilot evaluated a package of five HEARTS-aligned implementation strategies to improve the pharmacological treatment of hypertension and diabetes. The primary …

Mechanisms Of Uropathogenic E. Coli Mucosal Association In The Gastrointestinal Tract, Philippe N Azimzadeh, Nathaniel C Gualbuerto, Jerome S Pinkner, Kevin O Tamadonfar, Wandy Beatty, Thomas J Hannan, Karen W Dodson, Enid C Ibarra, Seonyoung Kim, Henry L Schreiber, James W Janetka, Andrew L Kau, Mark J Miller, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic

Emotional Ecosystems: Understanding The Relationship Between Family Interactions And Anxiety Among Cancer Caregivers, Keisha White Makinde, Jacquelyn J Benson, Kyle A Pitzer, Maysara Mitchell, Debra Parker Oliver, George Demiris, Karla T Washington

2020-Current year OA Pubs

OBJECTIVES: Recent studies have challenged the assumption that families are invariable sources of support for cancer caregivers, noting that relationships with family members can have both positive and negative effects on caregiver well-being. This study expands upon prior literature to examine the relationship between cancer caregivers' perceptions of the quality of their family interactions and their symptoms of anxiety.

METHODS: We employed secondary analysis of baseline data from a multisite randomized clinical trial of an intervention for cancer caregivers conducted at 3 large academic palliative care clinics. We performed linear regression analyses to analyze the relationship between caregivers' perceptions of …

The Impact Of Quantitative Platform On Candidacy For Bronchoscopic Lung Volume Reduction: A Multi-Center Retrospective Cohort Study, Max Wayne, Suchitra Pilli, Hee Jae Choi, Nathaniel Moulton, Praveen Chenna, Allen Cole Burks, Alexander Chen

2020-Current year OA Pubs

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) can be an effective treatment for highly selected patients with severe emphysema but only half of carefully selected patients derive clinical benefit. Two commercially available platforms exist to help determine candidacy for BLVR via quantitative analysis of computed tomography (CT) scans.

OBJECTIVES: To determine if the two commercially available quantitative platforms identified the same patient population that may benefit from BLVR.

DESIGN: A multicenter, retrospective cohort study.

METHODS: Consecutive patients referred for BLVR between January 1, 2022 and March 31, 2023 at three medical centers in the United States with the same CT scan …

Stroma-Derived Dickkopf-1 Contributes To The Suppression Of Nk Cell Cytotoxicity In Breast Cancer, Seunghyun Lee, Biancamaria Ricci, Jennifer Tran, Emily Eul, Jiayu Ye, Qihao Ren, David Clever, Julia Wang, Pamela Wong, Michael S Haas, Sheila A Stewart, Cynthia X Ma, Todd A Fehniger, Roberta Faccio

2020-Current year OA Pubs

Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone. By using genetic approaches, we find that bone-derived DKK1 contributes to the systemic DKK1 elevation in tumor-bearing female mice, while CAFs contribute to DKK1 at primary tumor site. Systemic and bone-specific DKK1 targeting reduce tumor growth. Intriguingly, deletion of CAF-derived DKK1 also limits breast cancer progression, without affecting its levels in circulation, …

Enhancing Immunotherapy Efficacy With Synergistic Low-Dose Radiation In Metastatic Melanoma: Current Insights And Prospects, Zahid Rafiq, Mingyo Kang, Hampartsoum B Barsoumian, Gohar S Manzar, Yun Hu, Carola Leuschner, Ailing Huang, Fatemeh Masrorpour, Weiqin Lu, Nahum Puebla-Osorio, James W Welsh

Faculty, Staff and Student Publications

Recent advances in oncology research have highlighted the promising synergy between low-dose radiation therapy (LDRT) and immunotherapies, with growing evidence highlighting the unique benefits of the combination. LDRT has emerged as a potent tool for stimulating the immune system, triggering systemic antitumor effects by remodeling the tumor microenvironment. Notably, LDRT demonstrates remarkable efficacy even in challenging metastatic sites such as the liver (uveal) and brain (cutaneous), particularly in advanced melanoma stages. The increasing interest in utilizing LDRT for secondary metastatic sites of uveal, mucosal, or cutaneous melanomas underscores its potential efficacy in combination with various immunotherapies. This comprehensive review traverses …

Hypoxia Signaling In The Adipose Tissue, Phu M Huynh, Fenfen Wang, Yu A An

Faculty, Staff and Student Publications

Obesity per se is rapidly emerging all over the planet and further accounts for many other life-threatening conditions, such as diabetes, cardiovascular diseases, and cancers. Decreased oxygen supply or increased relative oxygen consumption in the adipose tissue results in adipose tissue hypoxia, which is a hallmark of obesity. This review aims to provide an up-to-date overview of the hypoxia signaling in the adipose tissue. First, we summarize literature evidence to demonstrate that hypoxia is regularly observed during adipose tissue remodeling in humans and rodent models with obesity. Next, we discuss how hypoxia-inducible factors (HIFs) are regulated and how adipose tissues …

Propensity Score Matching: Should We Use It In Designing Observational Studies?, Fei Wan

2020-Current year OA Pubs

BACKGROUND: Propensity Score Matching (PSM) stands as a widely embraced method in comparative effectiveness research. PSM crafts matched datasets, mimicking some attributes of randomized designs, from observational data. In a valid PSM design where all baseline confounders are measured and matched, the confounders would be balanced, allowing the treatment status to be considered as if it were randomly assigned. Nevertheless, recent research has unveiled a different facet of PSM, termed "the PSM paradox". As PSM approaches exact matching by progressively pruning matched sets in order of decreasing propensity score distance, it can paradoxically lead to greater covariate imbalance, heightened model …

Examining Health Insurance And Non-Medical Challenges Among Vietnamese Americans In Texas During The Covid-19 Pandemic, Alexander Le, Saba Siddiqi, Celine Nguyen, Ben King, Paul Gerardo Yeh, Jannette Diep, Lauren Gilbert, Bich-May Nguyen

Faculty, Staff and Student Publications

When COVID-19 data on Asian Americans are available, they are frequently aggregated, concealing community-specific concerns. Consequently, there is limited COVID-19 literature on Vietnamese Americans. In this study, we investigated the association between health insurance coverage and non-medical challenges during the COVID-19 pandemic, in Vietnamese Americans in Texas. The NIH Community Engagement Alliance (CEAL) Common Survey 2 was administered electronically in English and Vietnamese and contained 23 questions about non-medical drivers of health, COVID-19 vaccination, and research participation. Vietnamese American adults in Texas were recruited between September 2021 and March 2022 via partnerships with community organizations. Responses were compared and analyzed …

Evaluation Of Fetal Growth And Birth Weight In Pregnancies With Placenta Previa With And Without Placenta Accreta Spectrum, Neha Agarwal, Ramesha Papanna, Baha M Sibai, Alexandra Garcia, Dejian Lai, Eleazar E Soto Torres, Farah H Amro, Sean C Blackwell, Edgar Hernandez-Andrade

Faculty, Staff and Student Publications

Objectives: We evaluated fetal growth and birthweight in pregnancies with placenta previa with and without placenta accreta spectrum (PAS).

Methods: We retrospectively studied pregnant patients with placenta previa with or without PAS diagnosed at 20-37 weeks' gestation. Estimated fetal weight (EFW) percentile and fetal growth rate were calculated based on ultrasound at two timepoints: 20-24 and 30-34-weeks' gestation. Fetuses were small (SGA) or large for gestational age (LGA) when EFW or abdominal circumference was < 10th or >90th percentile for gestational age, respectively. Fetal growth rate was estimated by subtracting EFW percentiles from the two ultrasounds. Birthweight in grams and percentiles were estimated …

Ligand Distances As Key Predictors Of Pathogenicity And Function In Nmda Receptors, Ludovica Montanucci, Tobias Brünger, Nisha Bhattarai, Christian M Boßelmann, Sukhan Kim, James P Allen, Jing Zhang, Chiara Klöckner, Ilona Krey, Piero Fariselli, Patrick May, Johannes R Lemke, Scott J Myers, Hongjie Yuan, Stephen F Traynelis, Dennis Lal

Faculty, Staff and Student Publications

Genetic variants in the genes GRIN1, GRIN2A, GRIN2B, and GRIN2D, which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic and neurodevelopmental disorders, including early onset epilepsy, developmental and epileptic encephalopathy, intellectual disability, and autism spectrum disorders. Missense variants in these genes can result in gain or loss of the NMDAR function, requiring opposite therapeutic treatments. Computational methods that predict pathogenicity and molecular functional effects of missense variants are therefore crucial for therapeutic applications. We assembled 223 missense variants from patients, 631 control variants from the general population, and 160 missense variants characterized by …

Species- And Strain-Specific Microbial Modulation Of Interferon, Innate Immunity, And Epithelial Barrier In 2d Air-Liquid Interface Respiratory Epithelial Cultures, Mian Horvath, Ruoyu Yang, Diana Cadena Castaneda, Megan Callender, Elizabeth S Aiken, Anita Y Voigt, Ryan Caldwell, José Fachi, Blanda Di Luccia, Zoe Scholar, Peter Yu, Andrew Salner, Marco Colonna, Karolina Palucka, Julia Oh

2020-Current year OA Pubs

BACKGROUND: The microbiome regulates the respiratory epithelium's immunomodulatory functions. To explore how the microbiome's biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on human primary bronchial air-liquid interface (ALI) cell cultures.

RESULTS: We found distinct species- and strain-level differences in host innate immunity and epithelial barrier response. Strikingly, we found that host interferon, an antiviral response, was one of the most variable host processes. This variability was not driven by microbial phylogenetic diversity, bioburden, nor by the microbe's ability to stimulate other innate immunity pathways.

CONCLUSIONS: Microbial colonization differentially stimulates host gene expression with …

Performance And Safety Of The Extravascular Implantable Cardioverter Defibrillator Through Long-Term Follow-Up: Final Results From The Pivotal Study., Paul Friedman, Francis Murgatroyd, Lucas V A Boersma, Jaimie Manlucu, Bradley P Knight, Nicolas Clémenty, Christophe Leclercq, Anish Amin, Béla Merkely, Ulrika Maria Birgersdotter-Green, Joseph Yat Sun Chan, Mauro Biffi, Reinoud Elwin Knops, Gregory Engel, Ignacio Muñoz Carvajal, Laurence M Epstein, Venkata Sagi, Jens Brock Johansen, Maciej Sterliński, Clemens Steinwender, Troy Hounshell, Richard Abben, Amy E Thompson, Yan Zhang, Christopher Wiggenhorn, Sarah Willey, Ian Crozier

Heart and Vascular Articles

BACKGROUND: Substernal lead placement of the extravascular implantable cardioverter defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous implantable cardioverter defibrillators and effective anti-tachycardia pacing (ATP) while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. Our aim was to report the performance and safety of the EV ICD system throughout the study.

METHODS: The EV ICD Pivotal study was a prospective, global, single-arm, premarket clinical study. Individuals with a Class I …

Deep Learning-Based Auto-Segmentation For Liver Yttrium-90 Selective Internal Radiation Therapy, Jun Li, Wookjin Choi, Rani Anne

Department of Radiation Oncology Faculty Papers

The aim was to evaluate a deep learning-based auto-segmentation method for liver delineation in Y-90 selective internal radiation therapy (SIRT). A deep learning (DL)-based liver segmentation model using the U-Net3D architecture was built. Auto-segmentation of the liver was tested in CT images of SIRT patients. DL auto-segmented liver contours were evaluated against physician manually-delineated contours. Dice similarity coefficient (DSC) and mean distance to agreement (MDA) were calculated. The DL-model-generated contours were compared with the contours generated using an Atlas-based method. Ratio of volume (RV, the ratio of DL-model auto-segmented liver volume to manually-delineated liver volume), and ratio of activity (RA, …

Acceptance And Commitment Therapy With Huntington's Disease: A Narrative Review And Case Report Of A Caregiver-Assisted Intervention, Simone H. Schriger, Chelsi N. Nurse, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

Acceptance and commitment therapy (ACT) is an experiential, action-oriented talk therapy that emphasizes acceptance of painful inner experience through increased psychological flexibility. In this narrative review and case report, we first review the extant literature on applications of ACT to patients with a variety of mental and physical health challenges, including neurodegenerative disorders, and their caregivers. We then discuss applications of ACT to Huntington's disease (HD). We provide a case report of a 52-year-old man living with HD who, accompanied by his caregiver, received a virtually-delivered 6-session ACT intervention. We measured the patient's self-reported symptoms of depression (PHQ-9) and anxiety …

Overcoming Cd226-Related Immune Evasion In Acute Myeloid Leukemia With Cd38 Car-Engineered Nk Cells, Luciana Melo Garcia, Achintyan Gangadharan, Pinaki Banerjee, Ye Li, Andy G X Zeng, Hind Rafei, Paul Lin, Bijender Kumar, Sunil Acharya, May Daher, Luis Muniz-Feliciano, Gary M Deyter, Gabriel Dominguez, Jeong Min Park, Francia Reyes Silva, Ana Karen Nunez Cortes, Rafet Basar, Nadima Uprety, Mayra Shanley, Mecit Kaplan, Enli Liu, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226. CRISPR-Cas9 deletion of CD226 led to reduced LFA-1 recruitment, poor synapse formation, and decreased NK cell anti-leukemic activity. Engineering NK cells to express a chimeric antigen receptor targeting the AML antigen CD38 (CAR38) could overcome the need for CD226 to establish strong immune synapses. LFA-1 …

Trmt1l-Catalyzed M22g27 On Tyrosine Trna Is Required For Efficient Mrna Translation And Cell Survival Under Oxidative Stress, Sseu-Pei Hwang, Han Liao, Katherine Barondeau, Xinyi Han, Cassandra Herbert, Hunter Mcconie, Amirtha Shekar, Dimitri G Pestov, Patrick A Limbach, Jeffrey T Chang, Catherine Denicourt

Faculty, Staff and Student Publications

tRNA modifications are critical for several aspects of their functions, including decoding, folding, and stability. Using a multifaceted approach encompassing eCLIP-seq and nanopore tRNA-seq, we show that the human tRNA methyltransferase TRMT1L interacts with the component of the Rix1 ribosome biogenesis complex and binds to the 28S rRNA as well as to a subset of tRNAs. Mechanistically, we demonstrate that TRMT1L is responsible for catalyzing N2,N2-dimethylguanosine (m22G) solely at position 27 of tRNA-Tyr-GUA. Surprisingly, TRMT1L depletion also impaired the deposition of 3-(3-amino-3-carboxypropyl) uridine (acp3U) and dihydrouridine on tRNA-Tyr-GUA, Cys-GCA, and Ala-CGC. TRMT1L knockout cells have a marked decrease in tRNA-Tyr-GUA …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds, Philipp E Scherer

Faculty, Staff and Students Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

The Golgi Complex Governs Natural Killer Cell Lytic Granule Positioning To Promote Directionality In Cytotoxicity, Luis A Pedroza, Frederique Van Den Haak, Alexander Frumovitz, Evelyn Hernandez, Everardo Hegewisch-Solloa, Tabitha K Orange, Keri B Sheehan, Susan Prockop, Aaron Bodansky, Ivan K Chinn, James R Lupski, Jennifer E Posey, Emily M Mace, Yu Li, Jordan S Orange

Faculty, Staff and Students Publications

Cytotoxic immune cells mediate precise attacks against diseased cells to maintain organismal health. Their operational unit of killing and host defense is lytic granules (LGs), which are specialized lysosomal-related organelles. Precision in cytotoxicity is achieved by converging the many LGs to the microtubule-organizing center (MTOC) and polarizing these to the diseased cell for secretion. We identify unappreciated intimate relationships between the Golgi, MTOC, and LGs after cytotoxic cell activation, as well as the trans-Golgin protein GCC2 on the LG surface. GCC2 serves to tether LGs to the Golgi following convergence, and both GCC2 and the Golgi are required for the …

Fate Erasure Logic Of Gene Networks Underlying Direct Neuronal Conversion Of Somatic Cells By Micrornas, Kitra Cates, Luorongxin Yuan, Yan Yang, Andrew S Yoo

2020-Current year OA Pubs

Neurogenic microRNAs 9/9

Safety And Efficacy Of Iv Onasemnogene Abeparvovec For Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b Smart Study, Hugh J. Mcmillan, Craig M. Zaidman, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing < 8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.5-21 kg.

METHODS: SMART was an open-label, multicenter, phase 3b study conducted across 13 sites in 9 countries (NCT04851873). Symptomatic pediatric participants with SMA (any type; treatment-naïve or had discontinued prior treatment) were stratified into 3 weight cohorts (≥8.5-13, >13-17, and >17-21 kg), administered onasemnogene abeparvovec, and followed for 52 weeks. Corticosteroids were initiated 24 hours before infusion with dose increases in response to adverse events (AEs) and subsequent tapering at investigator discretion. The primary objective was safety. Secondary objective was …

Development And Validation Of Natural Language Processing Algorithms In The Enact National Electronic Health Record Research Network, Yanshan Wang, Jordan Hilsman, Chenyu Li, Michele Morris, Paul M Heider, Sunyang Fu, Min Ji Kwak, Andrew Wen, Joseph R Applegate, Liwei Wang, Elmer Bernstam, Hongfang Liu, Jack Chang, Daniel R Harris, Alexandria Corbeau, Darren Henderson, John D Osborne, Richard E Kennedy, Nelly-Estefanie Garduno-Rapp, Justin F Rousseau, Chao Yan, You Chen, Mayur B Patel, Tyler J Murphy, Bradley A Malin, Chan Mi Park, Jungwei W Fan, Sunghwan Sohn, Sandeep Pagali, Yifan Peng, Aman Pathak, Yonghui Wu, Zongqi Xia, Salvatore Loguercio, Steven E Reis, Shyam Visweswaran

Faculty, Staff and Student Publications

Electronic health record (EHR) data are a rich and invaluable source of real-world clinical information, enabling detailed insights into patient populations, treatment outcomes, and healthcare practices. The availability of large volumes of EHR data are critical for advancing translational research and developing innovative technologies such as artificial intelligence. The Evolve to Next-Gen Accrual to Clinical Trials (ENACT) network, established in 2015 with funding from the National Center for Advancing Translational Sciences (NCATS), aims to accelerate translational research by democratizing access to EHR data for all Clinical and Translational Science Awards (CTSA) hub investigators. The present ENACT network provides access to …

Tfap2e Is Implicated In Central Nervous System, Orofacial And Maxillofacial Anomalies, Jeshurun C Kalanithy, Enrico Mingardo, Jil D Stegmann, Ramgopal Dhakar, Tikam Chand Dakal, Jill A Rosenfeld, Wen-Hann Tan, Stephanie A Coury, Audrey C Woerner, Jessica Sebastian, Paul A Levy, Leah R Fleming, Lea Waffenschmidt, Tobias T Lindenberg, Öznur Yilmaz, Khadija Channab, Bimaljeet K Babra, Andrea Christ, Britta Eiberger, Selina Hölzel, Clara Vidic, Felix Häberlein, Nina Ishorst, Juan E Rodriguez-Gatica, Behnaz Pezeshkpoor, Patrick A Kupczyk, Olivier M Vanakker, Sara Loddo, Antonio Novelli, Maria L Dentici, Albert Becker, Holger Thiele, Jennifer E Posey, James R Lupski, Alina C Hilger, Heiko M Reutter, Waltraut M Merz, Gabriel C Dworschak, Benjamin Odermatt

Faculty, Staff and Students Publications

Background: Previous studies in mouse, Xenopus and zebrafish embryos show strong tfap2e expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 (TFAP2E) in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.

Methods: Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies. Exome variant prioritisation prompted TFAP2E gene for functional analysis in zebrafish embryos. Embryonic morphology and development were assessed after antisense morpholino (MO) knockdown (KD), CRISPR/Cas9 knockout and overexpression …

Early-Onset Atherosclerotic Cardiovascular Disease, Idine Mousavi, John Suffredini, Salim S Virani, Christie M Ballantyne, Erin D Michos, Arunima Misra, Anum Saeed, Xiaoming Jia

Faculty, Staff and Students Publications

Recent trends indicate a concerning increase in early-onset atherosclerotic cardiovascular disease (ASCVD) among younger individuals (men aged < 55 years women aged < 65 years). These findings highlight the pathobiology of ASCVD as a disease process that begins early in life and underscores the need for more tailored screening methods and preventive strategies. Increasing attention has been placed on the growing burden of traditional cardiometabolic risk factors in young individuals while also recognizing unique factors that mediate risk of pre-mature atherosclerosis in this demographic such as substance use, socioeconomic disparities, adverse pregnancy outcomes, and chronic inflammatory states that contribute to the increasing incidence of early ASCVD. Additionally, mounting evidence has pointed out significant disparities in the diagnosis and management of early ASCVD and cardiovascular outcomes based on sex and race. Moving towards a more personalized approach, emerging data and technological developments using diverse tools such as polygenic risk scores and coronary artery calcium scans have shown potential in earlier detection of ASCVD risk. Thus, we review current evidence on causal risk factors that drive the increase in early ASCVD and highlight emerging tools to improve ASCVD risk assessment in young individuals.