Medicine and Health Sciences Commons^™

Bile Acid-Sensitive Human Norovirus Strains Are Susceptible To Sphingosine-1-Phosphate Receptor 2 Inhibition, Victoria Tenge, B Vijayalakshmi Ayyar, Khalil Ettayebi, Sue E Crawford, Nicole M Hayes, Yi-Ting Shen, Frederick H Neill, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are a diverse group of RNA viruses that cause endemic and pandemic acute viral gastroenteritis. Previously, we reported that many HuNoV strains require bile or bile acid (BA) to infect human jejunal intestinal enteroid cultures. BA was not essential for the replication of a pandemic-causing GII.4 HuNoV strain. We found the hydrophobic BA glycochenodeoxycholic acid (GCDCA) promotes the replication of the BA-dependent strain GII.3 in jejunal enteroids. Furthermore, we found that inhibition of the G-protein-coupled BA receptor, sphingosine-1-phosphate receptor 2 (S1PR2), by JTE-013, reduced GII.3 infection dose-dependently and inhibited GII.3 cellular uptake in enteroids. Herein, we sought …

First-In-Human Dose Escalation Trial To Evaluate The Clinical Safety And Efficacy Of An Anti-Magea1 Autologous Tcr-Transgenic T Cell Therapy In Relapsed And Refractory Solid Tumors, Martin Wermke, Tobias A W Holderried, Jason John Luke, Van K Morris, Winfried H Alsdorf, Katrin Wetzko, Borje S Andersson, Ignacio I Wistuba, Edwin R Parra, Mohammad B Hossain, Sandra Grund-Gröschke, Katrin Aslan, Arun Satelli, Anantha Marisetty, Swapna Satam, Mamta Kalra, Jens Hukelmann, M Alper Kursunel, Karine Pozo, Andreas Acs, Linus Backert, Melissa Baumeister, Sebastian Bunk, Claudia Wagner, Oliver Schoor, Ali S Mohamed, Andrea Mayer-Mokler, Norbert Hilf, Delfi Krishna, Steffen Walter, Apostolia M Tsimberidou, Cedrik M Britten

Faculty, Staff and Student Publications

RATIONALE OF THE TRIAL: Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors.

TRIAL DESIGN: The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of …

Onecut2 Acts As A Lineage Plasticity Driver In Adenocarcinoma As Well As Neuroendocrine Variants Of Prostate Cancer, Chen Qian, Qian Yang, Mirja Rotinen, Rongrong Huang, Hyoyoung Kim, Brad Gallent, Yiwu Yan, Radu M Cadaneanu, Baohui Zhang, Salma Kaochar, Stephen J Freedland, Edwin M Posadas, Leigh Ellis, Dolores Di Vizio, Colm Morrissey, Peter S Nelson, Lauren Brady, Ramachandran Murali, Moray J Campbell, Wei Yang, Beatrice S Knudsen, Elahe A Mostaghel, Huihui Ye, Isla P Garraway, Sungyong You, Michael R Freeman

Faculty, Staff and Students Publications

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic …

A Trivalent Protein-Based Pan-Betacoronavirus Vaccine Elicits Cross-Neutralizing Antibodies Against A Panel Of Coronavirus Pseudoviruses, Syamala Rani Thimmiraju, Rakesh Adhikari, Jeanna R Redd, Maria Jose Villar, Jungsoon Lee, Zhuyun Liu, Yi-Lin Chen, Suman Sharma, Amandeep Kaur, Nestor L Uzcategui, Shannon E Ronca, Wen-Hsiang Chen, Jason T Kimata, Bin Zhan, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.

Association Between Diabetes Mellitus And Total Hip Arthroplasty Outcomes: An Observational Study Using The Us National Inpatient Sample, Sumanth Chandrupatla, Kranti Rumalla, Jasvinder A Singh

Faculty, Staff and Students Publications

OBJECTIVES: To investigate the association of diabetes with postoperative outcomes in patients undergoing primary total hip arthroplasty (THA).

DESIGN: Retrospective cohort study using data from the US National Inpatient Sample (NIS).

SETTING: Study cohort was hospitalisations for primary THA in the USA, identified from the 2016-2020 NIS.

PARTICIPANTS: We identified 2 467 215 adults in the 2016-2020 NIS who underwent primary THA using International Classification of Diseases, 10th Revision codes. Primary THA hospitlizations were analysed as the overall group and also stratified by the underlying primary diagnosis for THA.

OUTCOME MEASURES: Outcome measures of interest were the length of hospital …

A Guide To Transcatheter Aortic Valve Design And Systematic Planning For A Redo-Tav (Tav-In-Tav) Procedure, Vinayak N Bapat, Miho Fukui, Syed Zaid, Atsushi Okada, Hasan Jilaihawi, Toby Rogers, Omar Khalique, João L Cavalcante, Uri Landes, Janarthanan Sathananthan, Giuseppe Tarantini, Gilbert H L Tang, Daniel J Blackman, Ole De Backer, Michael J Mack, Martin B Leon

Faculty, Staff and Students Publications

Transcatheter aortic valve replacement (TAVR) has become more common than surgical aortic valve replacement since 2016, with over 200,000 procedures globally each year. As patients increasingly outlive their TAVR devices, managing these cases is a growing concern. Treatment options include surgical removal of the old TAVR device (transcatheter aortic valve [TAV] explant) or implantation of a new transcatheter aortic valve (redo TAV). Redo TAV is complex because of the unique designs of TAV devices; compatibility issues; and the need for individualized planning based on factors such as implant depth, shape, and coronary artery relationships. This review serves as a comprehensive …

Radium-223 Treatment Produces Prolonged Suppression Of Resident Osteoblasts And Decreased Bone Mineral Density In Trabecular Bone In Osteoblast Reporter Mice, Song-Chang Lin, Guoyu Yu, Paul G Corn, Jossana Damasco, Yu-Chen Lee, Jian H Song, Nora M Navone, Christopher J Logothetis, Marites P Melancon, Theocharis Panaretakis, Sue-Hwa Lin

Faculty, Staff and Student Publications

Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as …

Transcatheter Heart Valve Explant With Infective Endocarditis-Associated Prosthesis Failure And Outcomes: The Explant-Tavr International Registry, Mateo Marin-Cuartas, Gilbert H L Tang, Philipp Kiefer, Shinichi Fukuhara, Rudiger Lange, Katherine B Harrington, Shekhar Saha, Christian Hagl, Neal S Kleiman, Sachin S Goel, Joerg Kempfert, Paul Werner, George A Petrossian, Arnar Geirsson, Nimesh D Desai, Michael W A Chu, Oliver D Bhadra, Christian Shults, Andrea Garatti, Flavien Vincent, Kendra J Grubb, Joshua B Goldberg, Michael J Mack, Thomas Modine, Paolo Denti, Tsuyoshi Kaneko, Vinayak N Bapat, Michael J Reardon, Michael A Borger, Syed Zaid

Faculty, Staff and Students Publications

Background and aims: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE.

Methods: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD).

Results: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant …

Low Skeletal Muscle Mass Is Associated With Inferior Preoperative And Postoperative Shoulder Function In Elderly Rotator Cuff Tear Patients, Yang Yang, Binbin Zheng, Xiaofang Lin, Mengqin Zhang, Yongzhi Ye, Haixiao Chen, Xiaobo Zhou

Faculty, Staff and Student Publications

BACKGROUND: The age-related loss of skeletal muscle mass is an important characteristic of sarcopenia, an increasingly recognized condition with systemic implications. However, its association with shoulder function in elderly patients with rotator cuff tears (RCT) remains unknown. This study aimed to investigate the relationship between low skeletal muscle mass and shoulder function in elderly RCT patients.

METHODS: A retrospective analysis was conducted on RCT patients who underwent chest computed tomography (CT) scans for clinical evaluation. Preoperative CT scan images of the chest were used to calculate the cross-sectional area (CSA) of thoracic muscle at the T4 level. The medical records …

Development And Implementation Of A Digital Quality Measure Of Emergency Cancer Diagnosis, Paarth Kapadia, Andrew J Zimolzak, Divvy K Upadhyay, Saritha Korukonda, Riyaa Murugaesh Rekha, Umair Mushtaq, Usman Mir, Daniel R Murphy, Alexis Offner, Gary A Abel, Georgios Lyratzopoulos, Luke T A Mounce, Hardeep Singh

Faculty, Staff and Students Publications

PURPOSE: Missed and delayed cancer diagnoses are common, harmful, and often preventable. Automated measures of quality of cancer diagnosis are lacking but could identify gaps and guide interventions. We developed and implemented a digital quality measure (dQM) of cancer emergency presentation (EP) using electronic health record databases of two health systems and characterized the measure's association with missed opportunities for diagnosis (MODs) and mortality.

METHODS: On the basis of literature and expert input, we defined EP as a new cancer diagnosis within 30 days after emergency department or inpatient visit. We identified EPs for lung cancer and colorectal cancer (CRC) …

Efficient Matrix Profile Computation With Euclidean Distance Using Eigen Transformation: Performance Evaluation Based On Beat-To-Beat Interval (Bbi) Data, James J Yang, Anne Buu

Faculty, Staff and Student Publications

The matrix profile serves as a fundamental tool to provide insights into similar patterns within time series. Existing matrix profile algorithms have been primarily developed for the normalized Euclidean distance, which may not be a proper distance measure in many settings. The methodology work of this paper was motivated by statistical analysis of beat-to-beat interval (BBI) data collected from smartwatches to monitor e-cigarette users’ heart rate change patterns for which the original Euclidean distance (L2-norm) would be a more suitable choice. Yet, incorporating the Euclidean distance into existing matrix profile algorithms turned out to be computationally challenging, especially …

Nasal Microbiome And The Effect Of Nasal Decolonization With A Novel Povidone-Iodine Antiseptic Solution: A Prospective And Randomized Clinical Trial, Diana Fernández-Rodríguez, Jeongeun Cho, Emanuele Chisari, Martin J Citardi, Javad Parvizi

Faculty, Staff and Student Publications

The aim of this study was to assess the profile of nasal microbiome and evaluate the effect of a specific nasal decolonization solution on the microbiome. We conducted a randomized, placebo-controlled, and parallel-group clinical study of 50 volunteers aged 18 years and older. The subjects were randomly assigned to receive a nasal antiseptic solution, containing povidone-iodine as the main ingredient, (n = 25) or a control solution (n = 25). Nasal swabs were obtained before application (baseline) and at 3 timepoints after application (5 min, 2 h, 24 h). Nasal swabs were subjected to next generation sequencing analysis and cultured …

Gestational Diabetes As A Risk Factor For Gbs Maternal Rectovaginal Colonization: A Systematic Review And Meta-Analysis, Vicki Mercado-Evans, Jacob J Zulk, Zainab A Hameed, Kathryn A Patras

Faculty, Staff and Students Publications

BACKGROUND: Maternal rectovaginal colonization by group B Streptococcus (GBS) increases the risk of perinatal GBS disease that can lead to death or long-term neurological impairment. Factors that increase the risk of rectovaginal GBS carriage are incompletely understood resulting in missed opportunities for detecting GBS in risk-based clinical approaches. There is a lacking consensus on whether gestational diabetes mellitus (GDM) is a risk factor for rectovaginal GBS. This systematic review and meta-analysis aims to address current conflicting findings and determine whether GDM should be clinically considered as a risk factor for maternal GBS colonization.

METHODS: Peer-reviewed studies that provided GDM prevalence …

Overcoming Challenges For Non-Us International Medical Graduates In Pediatric Infectious Diseases, Zheyi Teoh, Guliz Erdem, Cristina Tomatis-Souverbielle, Diego A Cruz-Vidal, Maria S Rueda, Roberto P Santos, Liset Olarte

Faculty, Staff and Students Publications

No abstract provided.

Safety And Effectiveness Of Using Disposable Ultrasonic Shears To Coagulate 5–7 Mm Blood Vessels: Protocol For A Prospective, Multicenter, Randomized, Parallel Controlled, Non-Inferiority Clinical Trial, Xipeng Wang, Chengqiang Li, Junqiang Fan, Jian Hu, Mingsong Wang, Hecheng Li

Faculty, Staff and Student Publications

BACKGROUND: The ultrasonic scalpel is widely used during surgery. It is safe and effective to close the pulmonary artery branch vessels of 7 mm or below with an ultrasonic energy device as reported. However, there have been no multicenter randomized clinical trial to assess the safety and effectiveness of using ultrasonic scalpel to coagulate 5-7 mm blood vessels in thoracic surgery.

METHODS: This is a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial. A total of 144 eligible patients planning to undergo lung or esophageal surgery will be randomly allocated to the experimental group and the control group. The investigational …

Artificial Chordae Implantation Vs Posterior Leaflet Preservation: A Comparison Of Midterm Results After Mitral Valve Replacement, Salih Salihi, Bilhan Özalp, Fatih Toptan, Ibrahim Kara

The Texas Heart Institute Journal

BACKGROUND: Various techniques have been proposed for the preservation of the subvalvular apparatus (SVA) in mitral valve replacement. This study aimed to compare the midterm results of posterior leaflet preservation with the results of selective preservation of the SVA involving artificial chordae implantation in terms of left ventricular performance in patients undergoing mitral valve replacement.

METHODS: In total, 127 patients were included in this study. Patients were allocated to 1 of 2 groups according to the techniques used to preserve the SVA. Patients in group 1 underwent posterior leaflet preservation: The anterior leaflet was completely resected, and the posterior leaflet …

Erratum: Hematologic Dnmt3a Reduction And High-Fat Diet Synergize To Promote Weight Gain And Tissue Inflammation, Jaime M Reyes, Ayala Tovy, Linda Zhang, Angelina S Bortoletto, Carina Rosas, Chun-Wei Chen, Sarah M Waldvogel, Anna G Guzman, Rogelio Aguilar, Sinjini Gupta, Ling Liu, Matthew T Buckley, Kalyani R Patel, Andrea N Marcogliese, Yumei Li, Choladda V Curry, Thomas A Rando, Anne Brunet, Ronald J Parchem, Rachel E Rau, Margaret A Goodell

Faculty, Staff and Students Publications

This corrects the article "Hematologic DNMT3A reduction and high-fat diet synergize to promote weight gain and tissue inflammation", 109122.

Bayesian Sequential Monitoring Strategies For Trials Of Digestive Cancer Therapeutics, Guillaume Mulier, Ruitao Lin, Thomas Aparicio, Lucie Biard

Faculty, Staff and Student Publications

Background: New therapeutics in oncology have presented challenges to existing paradigms and trial designs in all phases of drug development. As a motivating example, we considered an ongoing phase II trial planned to evaluate the combination of a MET inhibitor and an anti-PD-L1 immunotherapy to treat advanced oesogastric carcinoma. The objective of the paper was to exemplify the planning of an adaptive phase II trial with novel anti-cancer agents, including prolonged observation windows and joint sequential evaluation of efficacy and toxicity.

Methods: We considered various candidate designs and computed decision rules assuming correlations between efficacy and toxicity. Simulations were conducted …

Exploration Of A Potential Door Endpoint For Hospital-Acquired Bacterial Pneumonia And Ventilator-Associated Bacterial Pneumonia Using Six Registrational Trials For Antibacterial Drugs, Tori Kinamon, Ursula Waack, Mark Needles, Daniel Rubin, Deborah Collyar, Sarah B Doernberg, Scott R Evans, Toshimitsu Hamasaki, Thomas L Holland, Jessica Howard-Anderson, Henry Chambers, Vance G Fowler, Sumati Nambiar, Peter Kim, Helen W Boucher, Ramya Gopinath

Faculty, Staff and Student Publications

BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

METHODS: Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that …

Novel Mutation Leading To Splice Donor Loss In A Conserved Site Of Dmd Gene Causes Duchenne Muscular Dystrophy With Cryptorchidism, Jianhai Chen, Yangying Jia, Jie Zhong, Kun Zhang, Hongzheng Dai, Guanglin He, Fuping Li, Li Zeng, Chuanzhu Fan, Huayan Xu

Faculty, Staff and Students Publications

Background: As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic aetiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants.

Methods: In this study, a cohort of 115 Chinese probands with cryptorchidism was analysed using whole-genome sequencing, alongside 19 parental controls and 2136 unaffected men. Additionally, CRISPR-Cas9 editing of a conserved variant was performed in a mouse model, with MRI screening used to observe the phenotype.

Results: In …

Minimally Invasive Mitral Valve Surgery Using A Cold Fibrillatory Cardiac Arrest Technique In Patients With Prior Cardiac Surgery, Ahmed Ali, Zachary Gray, Gabriel Loor, Alexis E Shafii, Todd K Rosengart, Kenneth K Liao

The Texas Heart Institute Journal

OBJECTIVE: Minimally invasive mitral valve surgery (mini-MVS) is typically reserved for patients who have not undergone open cardiac surgery. In the reoperative setting, using intrapericardial dissection for crossclamping the aorta through a minimally invasive approach can be difficult and, at times, risky. Cold fibrillatory cardiac arrest (CFCA) with systemic cardiopulmonary bypass without cross-clamping is a well-described technique; however, data about its safety for patients who undergo reoperative mini-MVS are limited.

METHODS: Data for 34 patients who underwent reoperative mini-MVS with CFCA from March 2017 to March 2022 were reviewed retrospectively. A mini right thoracotomy (n = 30) or robotic (n …

Assessing Breast Disease With Deep Learning Model Using Bimodal Bi-View Ultrasound Images And Clinical Information, Fengping Liang, Yihua Song, Xiaoping Huang, Tong Ren, Qiao Ji, Yanan Guo, Xiang Li, Yajuan Sui, Xiaohui Xie, Lanqing Han, Yuanqing Li, Yong Ren, Zuofeng Xu

Faculty, Staff and Students Publications

Breast cancer is the second leading cause of carcinoma-linked death in women. We developed a multi-modal deep-learning model (BreNet) to differentiate breast cancer from benign lesions. BreNet was constructed and trained on 10,108 images from one center and tested on 3,762 images from two centers in three steps. The diagnostic ability of BreNet was first compared with that of six radiologists; a BreNet-aided scheme was constructed to improve the diagnostic ability of the radiologists; and the diagnosis of real-world radiologists' scheme was then compared with the BreNet-aided scheme. The diagnostic performance of BreNet was superior to that of the radiologists …

Membrane Vectorial Lipidomic Features Of Coral Host Cells’ Plasma Membrane And Lipid Profiles Of Their Endosymbionts Cladocopium, Tatyana V Sikorskaya, Ekaterina V Ermolenko, Taliya T Ginanova, Andrey V Boroda, Kseniya V Efimova, Mikhail Bogdanov

Faculty, Staff and Student Publications

The symbiotic relationships between coral animal host and autotrophic dinoflagellates are based on the mutual exchange and tight control of nutritional inputs supporting successful growth. The corals Sinularia heterospiculata and Acropora aspera were cultivated using a flow-through circulation system supplying seawater during cold and warm seasons of the year, then sorted into host cells and symbionts and subjected to phylogenetic, morphological, and advanced lipid analyses. Here we show, that the lipidomes of the dinoflagellates Cladocopium C1/C3 and acroporide-specific Cladocopium hosted by the corals, are determined by lipidomic features of different thermosensitivity and unique betaine- and phospholipid molecular species. Phosphatidylserines and …

Prediction Of Mild Cognitive Impairment Status: Pilot Study Of Machine Learning Models Based On Longitudinal Data From Fitness Trackers, Qidi Xu, Yejin Kim, Karen Chung, Paul Schulz, Assaf Gottlieb

Faculty, Staff and Student Publications

BACKGROUND: Early signs of Alzheimer disease (AD) are difficult to detect, causing diagnoses to be significantly delayed to time points when brain damage has already occurred and current experimental treatments have little effect on slowing disease progression. Tracking cognitive decline at early stages is critical for patients to make lifestyle changes and consider new and experimental therapies. Frequently studied biomarkers are invasive and costly and are limited for predicting conversion from normal to mild cognitive impairment (MCI).

OBJECTIVE: This study aimed to use data collected from fitness trackers to predict MCI status.

METHODS: In this pilot study, fitness trackers were …

Targeted Sequencing For Hereditary Breast And Ovarian Cancer In Brca1/2-Negative Families Reveals Complex Genetic Architecture And Phenocopies, Jocelyn N Plowman, Evanjalina J Matoy, Lavanya V Uppala, Samantha B Draves, Cynthia J Watson, Bridget A Sefranek, Mark L Stacey, Samuel P Anderson, Michael A Belshan, Elizabeth E Blue, Chad D Huff, Yusi Fu, Holly A F Stessman

Faculty, Staff and Student Publications

Approximately 20% of breast cancer cases are attributed to increased family risk, yet variation in BRCA1/2 can only explain 20%-25% of cases. Historically, only single gene or single variant testing were common in at-risk family members, and further sequencing studies were rarely offered after negative results. In this study, we applied an efficient and inexpensive targeted sequencing approach to provide molecular diagnoses in 245 human samples representing 134 BRCA mutation-negative (BRCAX) hereditary breast and ovarian cancer (HBOC) families recruited from 1973 to 2019 by Dr. Henry Lynch. Sequencing identified 391 variants, which were functionally annotated and ranked based on their …

In Vitro Data Suggest A Role For Pms2 Kozak Sequence Mutations In Lynch Syndrome Risk, Evanjalina J Matoy, Jocelyn N Plowman, Cynthia J Watson, Michael A Belshan, Elizabeth E Blue, Chad D Huff, Holly A F Stessman

Faculty, Staff and Student Publications

This study investigates the role of 5′ UTR PMS2 Kozak sequence genetic variation in cancer risk. It accomplishes this through the development of a mid-throughput reporter assay where variants can be tested for protein translation efficiency. The results highlight the importance of continued study of the Kozak sequence related to human disease.

Investigating Gene Functions And Single-Cell Expression Profiles Of De Novo Variants In Orofacial Clefts, Toshiyuki Itai, Fangfang Yan, Andi Liu, Yulin Dai, Chihiro Iwaya, Sarah W Curtis, Elizabeth J Leslie, Lukas M Simon, Peilin Jia, Xiangning Chen, Junichi Iwata, Zhongming Zhao

Faculty, Staff and Student Publications

Orofacial clefts (OFCs) are common congenital birth defects with various etiologies, including genetic variants. Online Mendelian Inheritance in Man (OMIM) annotated several hundred genes involving OFCs. Furthermore, several hundreds of de novo variants (DNVs) have been identified from individuals with OFCs. Some DNVs are related to known OFC genes or pathways, but there are still many DNVs whose relevance to OFC development is unknown. To explore novel gene functions and their cellular expression profiles, we focused on DNVs in genes that were not listed in OMIM. We collected 960 DNVs in 853 genes from published studies and curated these genes, …

Deepface: Deep-Learning-Based Framework To Contextualize Orofacial-Cleft-Related Variants During Human Embryonic Craniofacial Development, Yulin Dai, Toshiyuki Itai, Guangsheng Pei, Fangfang Yan, Yan Chu, Xiaoqian Jiang, Seth M Weinberg, Nandita Mukhopadhyay, Mary L Marazita, Lukas M Simon, Peilin Jia, Zhongming Zhao

Faculty, Staff and Student Publications

No abstract provided.

Deepface: Deep-Learning-Based Framework To Contextualize Orofacial-Cleft-Related Variants During Human Embryonic Craniofacial Development, Yulin Dai, Toshiyuki Itai, Guangsheng Pei, Fangfang Yan, Yan Chu, Xiaoqian Jiang, Seth M Weinberg, Nandita Mukhopadhyay, Mary L Marazita, Lukas M Simon, Peilin Jia, Zhongming Zhao

Faculty, Staff and Student Publications

Orofacial clefts (OFCs) are among the most common human congenital birth defects. Previous multiethnic studies have identified dozens of associated loci for both cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP). Although several nearby genes have been highlighted, the "casual" variants are largely unknown. Here, we developed DeepFace, a convolutional neural network model, to assess the functional impact of variants by SNP activity difference (SAD) scores. The DeepFace model is trained with 204 epigenomic assays from crucial human embryonic craniofacial developmental stages of post-conception week (pcw) 4 to pcw 10. The Pearson correlation coefficient between …

Crispr-Cas9 And Cas12a Target Site Richness Reflects Genomic Diversity In Natural Populations Of Anopheles Gambiae And Aedes Aegypti Mosquitoes, Travis C Collier, Yoosook Lee, Derrick K Mathias, Víctor López Del Amo

Faculty, Staff and Student Publications

Due to limitations in conventional disease vector control strategies including the rise of insecticide resistance in natural populations of mosquitoes, genetic control strategies using CRISPR gene drive systems have been under serious consideration. The identification of CRISPR target sites in mosquito populations is a key aspect for developing efficient genetic vector control strategies. While genome-wide Cas9 target sites have been explored in mosquitoes, a precise evaluation of target sites focused on coding sequence (CDS) is lacking. Additionally, target site polymorphisms have not been characterized for other nucleases such as Cas12a, which require a different DNA recognition site (PAM) and would …