Medicine and Health Sciences Commons^™

Heterozygous Map3k20 Variants Cause Ectodermal Dysplasia, Craniosynostosis, Sensorineural Hearing Loss, And Limb Anomalies, Daniel Brooks, Elizabeth Burke, Sukyeong Lee, Tanya N Eble, Melanie O'Leary, Ikeoluwa Osei-Owusu, Heidi L Rehm, Shweta U Dhar, Lisa Emrick, David Bick, Michelle Nehrebecky, Ellen Macnamara, Dídac Casas-Alba, Judith Armstrong, Carolina Prat, Antonio F Martínez-Monseny, Francesc Palau, Pengfei Liu, David Adams, Undiagnosed Diseases Network, Seema Lalani, Jill A Rosenfeld, Lindsay C Burrage

Faculty, Staff and Students Publications

Biallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20. We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. …

Quantification And Visualization Of Cis-Regulatory Dynamics In Single-Cell Multi-Omics Data With Treasmo, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

Recent advances in single-cell multi-omics technologies have provided unprecedented insights into regulatory processes. We introduce TREASMO, a versatile Python package designed to quantify and visualize transcriptional regulatory dynamics in single-cell multi-omics datasets. TREASMO has four modules, spanning data preparation, correlation quantification, downstream analysis and visualization, enabling comprehensive dataset exploration. By introducing a novel single-cell gene-peak correlation strength index, TREASMO facilitates accurate identification of regulatory changes at single-cell resolution. Validation on a hematopoietic stem and progenitor cell dataset showcases TREASMO's capacity in quantifying the gene-peak correlation strength at the single-cell level, identifying regulatory markers and discovering temporal regulatory patterns along the …

Increased Plasma Branched Short-Chain Fatty Acids And Improved Glucose Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Arianne Aslamy, Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Patricia A Sheridan, Kari E Wong, Gautam Ramesh, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Faculty, Staff and Students Publications

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of …

A Surgical Collaborative To Empower Medical Student Research, Spoorthi Kamepalli, Joseph R Junkin, Syed S Bakhtiyar, Ashley Montgomery, Michael Dileo, Thao N Galván, John A Goss, Abbas A Rana

Faculty, Staff and Students Publications

Mini abstracts: Faculty at the Baylor College of Medicine have developed a flexible research collaborative through which students gain research skills and individualized mentorship. This division has produced 86 trainee first author publications, 64 manuscripts by 34 different medical students with an average Scimago Journal Rank of 1.293 (range: 1.035-1.551) since 2015.

Thiazide Diuretics Vs. Other Antihypertensive Drug Classes, Arindam Sarkar, Katelyn D Sarkar

Faculty, Staff and Students Publications

No abstract provided.

Cognitive, Emotional, And Other Non-Motor Symptoms Of Spinocerebellar Ataxias, Chi-Ying R Lin, Sheng-Han Kuo, Puneet Opal

Faculty, Staff and Students Publications

Purpose of review: Spinocerebellar ataxias (SCAs) are autosomal dominant degenerative syndromes that present with ataxia and brain stem abnormalities. This review describes the cognitive and behavioral symptoms of SCAs in the context of recent knowledge of the role of the cerebellum in higher intellectual function.

Recent findings: Recent studies suggest that patients with spinocerebellar ataxia can display cognitive deficits even early in the disease. These have been given the term cerebellar cognitive affective syndrome (CCAS). CCAS can be tracked using newly developed rating scales. In addition, patients with spinocerebellar ataxia also display impulsive and compulsive behavior, depression, anxiety, fatigue, and …

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Fetoscopic Endoluminal Tracheal Occlusion For Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience, Eric Bergh, Ahmet A Baschat, Magdalena Sanz Cortes, Holly L Hedrick, Greg Ryan, Foong-Yen Lim, Michael V Zaretsky, Mauro H Schenone, Timothy M Crombleholme, Rodrigo Ruano, Kristen A Gosnell, Anthony Johnson

Faculty, Staff and Students Publications

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed.

METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic …

Yap Induces A Neonatal-Like Pro-Renewal Niche In The Adult Heart, Rich Gang Li, Xiao Li, Yuka Morikawa, Francisco J Grisanti-Canozo, Fansen Meng, Chang-Ru Tsai, Yi Zhao, Lin Liu, Jong Kim, Bing Xie, Elzbieta Klysik, Shijie Liu, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

After myocardial infarction (MI), mammalian hearts do not regenerate, and the microenvironment is disrupted. Hippo signaling loss of function with activation of transcriptional co-factor YAP induces heart renewal and rebuilds the post-MI microenvironment. In this study, we investigated adult renewal-competent mouse hearts expressing an active version of YAP, called YAP5SA, in cardiomyocytes (CMs). Spatial transcriptomics and single-cell RNA sequencing revealed a conserved, renewal-competent CM cell state called adult (a)CM2 with high YAP activity. aCM2 co-localized with cardiac fibroblasts (CFs) expressing complement pathway component C3 and macrophages (MPs) expressing C3ar1 receptor to form a cellular triad in YAP5SA hearts and renewal-competent …

Genomic Data In The All Of Us Research Program, All Of Us Research Program Genomics Investigators

Faculty, Staff and Students Publications

Comprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for the field of human genetics1–4. The All of Us Research Program is a longitudinal cohort study aiming to enrol a diverse group of at least one million individuals across the USA to accelerate biomedical research and improve human health5,6. Here we describe the programme’s genomics data release of 245,388 clinical-grade genome sequences. This resource is unique in its diversity as 77% of participants are from communities that are historically under-represented in biomedical research and 46% are …

Centriole And Transition Zone Structures In Photoreceptor Cilia Revealed By Cryo-Electron Tomography, Zhixian Zhang, Abigail R Moye, Feng He, Muyuan Chen, Melina A Agosto, Theodore G Wensel

Faculty, Staff and Students Publications

Primary cilia mediate sensory signaling in multiple organisms and cell types but have structures adapted for specific roles. Structural defects in them lead to devastating diseases known as ciliopathies in humans. Key to their functions are structures at their base: the basal body, the transition zone, the "Y-shaped links," and the "ciliary necklace." We have used cryo-electron tomography with subtomogram averaging and conventional transmission electron microscopy to elucidate the structures associated with the basal region of the "connecting cilia" of rod outer segments in mouse retina. The longitudinal variations in microtubule (MT) structures and the lumenal scaffold complexes connecting them …

Fluid Assessment, Fluid Balance, And Fluid Overload In Sick Children: A Report From The Pediatric Acute Disease Quality Initiative (Adqi) Conference, David T Selewski, Matthew F Barhight, Erica C Bjornstad, Zaccaria Ricci, Marcelo De Sousa Tavares, Ayse Akcan-Arikan, Stuart L Goldstein, Rajit Basu, Sean M Bagshaw

Faculty, Staff and Students Publications

BACKGROUND: The impact of disorders of fluid balance, including the pathologic state of fluid overload in sick children has become increasingly apparent. With this understanding, there has been a shift from application of absolute thresholds of fluid accumulation to an appreciation of the intricacies of fluid balance, including the impact of timing, trajectory, and disease pathophysiology.

METHODS: The 26th Acute Disease Quality Initiative was the first to be exclusively dedicated to pediatric and neonatal acute kidney injury (pADQI). As part of the consensus panel, a multidisciplinary working group dedicated to fluid balance, fluid accumulation, and fluid overload was created. Through …

Programs And Processes For Advancing Pediatric Acute Kidney Support Therapy In Hospitalized And Critically Ill Children: A Report From The 26th Acute Disease Quality Initiative (Adqi) Consensus Conference, Tara M Neumayr, Benan Bayrakci, Rahul Chanchlani, Akash Deep, Jolyn Morgan, Ayse Akcan Arikan, Rajit K Basu, Stuart L Goldstein, David J Askenazi

Faculty, Staff and Students Publications

Pediatric acute kidney support therapy (paKST) programs aim to reliably provide safe, effective, and timely extracorporeal supportive care for acutely and critically ill pediatric patients with acute kidney injury (AKI), fluid and electrolyte derangements, and/or toxin accumulation with a goal of improving both hospital-based and lifelong outcomes. Little is known about optimal ways to configure paKST teams and programs, pediatric-specific aspects of delivering high-quality paKST, strategies for transitioning from acute continuous modes of paKST to facilitate rehabilitation, or providing effective short- and long-term follow-up. As part of the 26th Acute Disease Quality Initiative Conference, the first to focus on a …

Preoperative Hemodynamics Impact The Benefit Of Fenestration On Fontan Postoperative Length Of Stay, Garick D Hill, Danny T Y Wu, M Eric Ferguson, Saul Flores, Salil Ginde, Kevin D Hill, Michael Johansen, Jane W Newburger, Zhiqian Gao, James F Cnota

Faculty, Staff and Students Publications

BACKGROUND: Utilization of Fontan fenestration varies considerably by center.

OBJECTIVES: Using a multicenter Pediatric Heart Network dataset linking surgical and preoperative hemodynamic variables, the authors evaluated factors associated with use of Fontan fenestration and the impact of fenestration on post-Fontan length of stay (LOS).

METHODS: Patients 2 to 6 years old at Fontan surgery from 2010 to 2020 with catheterizationeffect.

RESULTS: Fenestration was used in 465 of 702 patients (66.2%). Placement of a fenestration was associated with center (range 27%-93% use,

CONCLUSIONS: There is wide center variability in use of Fontan fenestration that is not explained by preoperative hemodynamics. Fenestration …

A Case Of Diffuse Thyroid Lipomatosis With Amyloid Deposits Presenting With Thyrotoxicosis, Adrian M Gonzalez-Gil, Marco A Ruiz-Santillan, Bahar K Force, Ruchi Gaba

Faculty, Staff and Students Publications

Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL with amyloid deposits and concurrent thyrotoxicosis. A 64-year-old South-Asian woman with a several-year history of an enlarging goiter, unintentional weight loss, and work-up 10 months prior suggestive of thyroiditis presented with a viral syndrome in setting of several weeks of progressive fatigue. Her examination was notable for resting sinus tachycardia and massive painless goiter. Initial work-up revealed nephrotic range proteinuria with hypoalbuminemia, which progressed to end-stage-renal disease, elevated inflammatory markers, and elevated free …

Retinal Thickness In Essential Tremor And Early Parkinson Disease: Exploring Diagnostic Insights, Claudio Terravecchia, Giovanni Mostile, Clara G Chisari, Cristina Rascunà, Roberta Terranova, Calogero E Cicero, Loretta Giuliano, Giulia Donzuso, Giorgia Sciacca, Antonina Luca, Pierre-Marie Preux, Joseph Jankovic, Mario Zappia, Alessandra Nicoletti

Faculty, Staff and Students Publications

BACKGROUND: Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD.

METHODS: Macular layers and peripapillary retinal nerve fiber layer (RNFL) …

Endocrine-Sensitive Disease Rate In Postmenopausal Patients With Estrogen Receptor-Rich/Erbb2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, Or Their Combination: A Phase 3 Randomized Clinical Trial, Cynthia X Ma, Vera J Suman, Souzan Sanati, Kiran Vij, Meenakshi Anurag, A Marilyn Leitch, Gary W Unzeitig, Jeremy Hoog, Aranzazu Fernandez-Martinez, Cheng Fan, Richard A Gibbs, Mark A Watson, Travis J Dockter, Olwen Hahn, Joseph M Guenther, Abigail Caudle, Erika Crouch, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Mothaffar F Rimawi, Anna Weiss, Eric P Winer, Kelly K Hunt, Charles M Perou, Matthew J Ellis, Ann H Partridge, Lisa A Carey

Faculty, Staff and Students Publications

IMPORTANCE: Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast cancer. However, the combination has not been tested in early-stage disease.

OBJECTIVE: To determine whether neoadjuvant fulvestrant or A+F increases the rate of pathologic complete response or ypT1-2N0/N1mic/Ki67 2.7% or less residual disease (referred to as endocrine-sensitive disease) over anastrozole alone.

DESIGN, SETTING, AND PARTICIPANTS: A phase 3 randomized clinical trial assessing differences in clinical and correlative outcomes between each of the fulvestrant-containing arms and the anastrozole arm. Postmenopausal women with clinical stage II to III, ER-rich (Allred score 6-8 or …

Hepatic Encephalopathy Precipitated By Preeclampsia In The Setting Of Cirrhosis: A Case Report, Mary E Fang, Nicholas A Peoples, Alison N Goulding, Mary C Tolcher

Faculty, Staff and Students Publications

Preeclampsia and decompensated chronic liver disease are known triggers of acute hepatic dysfunction in pregnancy, rarely including hepatic encephalopathy. Differentiating the driver of acute hepatic dysfunction in patients with concomitant preeclampsia and preexisting liver disease presents a diagnostic challenge with important management implications.

A 42-year-old woman, gravida 3 para 0201, at 24 1/7 weeks of gestation presented with hepatic encephalopathy, transaminitis, and hyperbilirubinemia in the setting of cirrhosis and severe new-onset preeclampsia. The preeclampsia was thought to be the leading etiology of hepatic encephalopathy, prompting emergent Cesarean delivery at 24 2/7 weeks. Hepatic encephalopathy, blood pressure, and laboratory derangements improved …

Management Of Gunshot Wounds Near The Elbow: Experiences At A High-Volume Level I Trauma Center, Umar Ghilzai, Abdullah Ghali, Aaron Singh, Thomas Wesley Mitchell, Scott A Mitchell

Faculty, Staff and Students Publications

BACKGROUND: Gunshot-related fractures near the elbow are challenging, and available data to guide the practitioner are lacking. This report analyzes injury patterns and treatment strategies in a case series from a high-volume urban trauma center.

METHODS: All periarticular gunshot fractures near the elbow treated at a level 1 trauma center from 2014 to 2018 were retrospectively reviewed. Fracture location, patient demographics, concomitant injuries, treatment modalities, and complications were analyzed.

RESULTS: Twenty-four patients were identified. All patients received prophylactic antibiotics upon admission and underwent urgent surgical debridement. Open reduction and internal fixation (ORIF) was performed with initial debridement in 22 of …

Case Report: Contralateral Progression Of A Vestibular Schwannoma After Resection In A Patient With Neurofibromatosis Type 2, Ihika Rampalli, Collin William English, Tyler Lazaro, Benjamin Daniel Lovin, Sungho Lee, Andrew Tsao Huang, Ali Jalali, Kathleen Kelly Gallagher, Jacob J Mandel, Alex Daniel Sweeney, Akash J Patel

Faculty, Staff and Students Publications

BACKGROUND AND IMPORTANCE: Bilateral vestibular schwannomas (VS) are a distinctive feature of neurofibromatosis type 2 (NF2) that result in a serious reduction in the quality of life for patients. The growth rates of these schwannomas are variable, and the early detection of increased growth is fundamental for improving outcomes.

CLINICAL PRESENTATION: A 17-year-old man with NF2 and bilateral VS presented with complete right facial paralysis and sudden right hearing loss less than 1 month after resection of a left VS. Imaging revealed rapid growth of the right VS with intratumoral hemorrhage, and the patient underwent urgent surgical resection with some …

The Card8 Inflammasome Dictates Hiv/Siv Pathogenesis And Disease Progression, Qiankun Wang, Kolin M Clark, Ritudhwaj Tiwari, Nagarajan Raju, Gregory K Tharp, Jeffrey Rogers, R Alan Harris, Muthuswamy Raveendran, Steven E Bosinger, Tricia H Burdo, Guido Silvestri, Liang Shan

Faculty, Staff and Students Publications

While CD4+ T-cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of “natural” hosts such as sooty mangabeys do not cause CD4+ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T-cell activation abolishes CARD8 function and increases permissiveness …

Interim Estimates Of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States, Aaron M Frutos, Ashley M Price, Elizabeth Harker, Emily L Reeves, Haris M Ahmad, Vel Murugan, Emily T Martin, Stacey House, Elie A Saade, Richard K Zimmerman, Manjusha Gaglani, Karen J Wernli, Emmanuel B Walter, Marian G Michaels, Mary A Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Julie A Boom, Eileen J Klein, Natasha B Halasa, Adit A Ginde, Kevin W Gibbs, Yuwei Zhu, Wesley H Self, Sara Y Tartof, Nicola P Klein, Kristin Dascomb, Malini B Desilva, Zachary A Weber, Duck-Hye Yang, Sarah W Ball, Diya Surie, Jennifer Decuir, Fatimah S Dawood, Heidi L Moline, Ariana P Toepfer, Benjamin R Clopper, Ruth Link-Gelles, Amanda B Payne, Jessie R Chung, Brendan Flannery, Nathaniel M Lewis, Samantha M Olson, Katherine Adams, Mark W Tenforde, Shikha Garg, Lisa A Grohskopf, Carrie Reed, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Faculty, Staff and Students Publications

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE …

Postoperative Atrial Fibrillation (Poaf) After Cardiac Surgery: Clinical Practice Review, Orlando R Suero, Ahmed K Ali, Lauren R Barron, Matthew W Segar, Marc R Moon, Subhasis Chatterjee

Faculty, Staff and Students Publications

Postoperative atrial fibrillation (POAF) after cardiac surgery is associated with elevated morbidity and mortality. Although current prediction models have limited efficacy, several perioperative interventions can reduce patients' risk of POAF. These begin with preoperative medications, including beta-blockers and amiodarone. Moreover, patients should be screened for preexisting atrial fibrillation (AF) so that concomitant surgical ablation and left atrial appendage occlusion can be performed in appropriate candidates. Intraoperative interventions such as posterior pericardiectomy can reduce mediastinal fluid accumulation, which is a trigger for POAF. Furthermore, many preventive strategies for POAF are implemented in the immediate postoperative period. Initiating beta-blockers, amiodarone, or both …

Current And Emerging Antiviral Agents In The Prevention And Treatment Of Cytomegalovirus In Pediatric Transplant Recipients, Kristen G Valencia Deray, Lara A Danziger-Isakov, Kevin J Downes

Faculty, Staff and Students Publications

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients …

Circular Stag2 Rna Modulates Bladder Cancer Progression Via Mir-145-5p/Tagln2 And Is Considered As A Biomarker For Recurrence, Chris Du, Wayne C Waltzer, Jeremy E Wilusz, Massimiliano Spaliviero, Frank Darras, Victor Romanov

Faculty, Staff and Students Publications

Simple Summary

Bladder cancer (BCa) is a major urologic malignancy with a high potential for death-threatening complications. Successful treatment relies on timely diagnostics and prediction of clinical outcomes. Molecular markers can be helpful for earlier diagnosis and for making treatment decisions. The biomarker landscape for BCa is not satisfactory yet. The discovery of novel diagnostic indicators for making treatment decisions is critical. Biological fluids are the most convenient and reliable source of these molecules. Circular RNAs (CircRNAs), special non-coding RNAs with a stable structure that are formed by a unique backsplicing process, recently became popular candidates for biomarkers in cancer …

Hmzdupfinder: A Robust Computational Approach For Detecting Intragenic Homozygous Duplications From Exome Sequencing Data, Haowei Du, Zain Dardas, Angad Jolly, Christopher M Grochowski, Shalini N Jhangiani, He Li, Donna Muzny, Jawid M Fatih, Gozde Yesil, Nursel H Elçioglu, Alper Gezdirici, Dana Marafi, Davut Pehlivan, Daniel G Calame, Claudia M B Carvalho, Jennifer E Posey, Tomasz Gambin, Zeynep Coban-Akdemir, James R Lupski

Faculty, Staff and Students Publications

Homozygous duplications contribute to genetic disease by altering gene dosage or disrupting gene regulation and can be more deleterious to organismal biology than heterozygous duplications. Intragenic exonic duplications can result in loss-of-function (LoF) or gain-of-function (GoF) alleles that when homozygosed, i.e. brought to homozygous state at a locus by identity by descent or state, could potentially result in autosomal recessive (AR) rare disease traits. However, the detection and functional interpretation of homozygous duplications from exome sequencing data remains a challenge. We developed a framework algorithm, HMZDupFinder, that is designed to detect exonic homozygous duplications from exome sequencing (ES) data. The …

A Robust Quality Infrastructure Is Key To Safe And Effective Delivery Of Immune Effector Cells: How Fact-Finding Can Help, Kevin J Curran, Sarah Nikiforow, Carlos Bachier, Yen-Michael Hsu, David Maloney, Marcela V Maus, Philip Mccarthy, David Porter, Patricia Shi, Elizabeth J Shpall, Basem William, Kara Wacker, Phyllis Warkentin, Helen E Heslop

Faculty, Staff and Students Publications

Immune effector cells (IECs) include a broad range of immune cells capable of modulating several disease states, including malignant and nonmalignant conditions. The growth in the use of IECs as both investigational and commercially available products requires medical institutions to develop workflows/processes to safely implement and deliver transformative therapy. Adding to the complexity of this therapy are the variety of targets, diseases, sources, and unique toxicities that a patient experiences following IEC therapy. For over 25 years, the Foundation for the Accreditation of Cellular Therapy (FACT) has established a standard for the use of cellular therapy, initially with hematopoietic cell …

Loss Of The Endoplasmic Reticulum Protein Tmem208 Affects Cell Polarity, Development, And Viability, Debdeep Dutta, Oguz Kanca, Rishi V Shridharan, Paul C Marcogliese, Benjamin Steger, Marie Morimoto, F Graeme Frost, Ellen Macnamara, Michael F Wangler, Shinya Yamamoto, Andreas Jenny, David Adams, May C Malicdan, Hugo J Bellen

Faculty, Staff and Students Publications

Nascent proteins destined for the cell membrane and the secretory pathway are targeted to the endoplasmic reticulum (ER) either posttranslationally or cotranslationally. The signal-independent pathway, containing the protein TMEM208, is one of three pathways that facilitates the translocation of nascent proteins into the ER. The in vivo function of this protein is ill characterized in multicellular organisms. Here, we generated a CRISPR-induced null allele of the fruit fly ortholog

Estrogen Signaling In The Dorsal Raphe Regulates Binge-Like Drinking In Mice, Valeria C Torres Irizarry, Bing Feng, Xiaohua Yang, Nirali Patel, Sarah Schaul, Lucas Ibrahimi, Hui Ye, Pei Luo, Leslie Carrillo-Sáenz, Penghua Lai, Maya Kota, Devin Dixit, Chunmei Wang, Amy W Lasek, Yanlin He, Pingwen Xu

Faculty, Staff and Students Publications

Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had …

Efficacy And Safety Of Daxibotulinumtoxina For Injection In Cervical Dystonia: Aspen-1 Phase 3 Randomized Controlled Trial, Cynthia L Comella, Joseph Jankovic, Robert A Hauser, Atul T Patel, Marta D Banach, Edvard Ehler, Domenico Vitarella, Roman G Rubio, Todd M Gross, Aspen-1 Study Group

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: ASPEN-1 was a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, duration of response, and safety of 2 doses of DaxibotulinumtoxinA for Injection (DAXI), a novel botulinum toxin type A formulation in participants with cervical dystonia (CD).

METHODS: Adults (aged 18-80 years) with moderate-to-severe CD (Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] total score ≥20) were enrolled at 60 sites across 9 countries in Europe and North America. Participants were randomized (3:3:1) to single-dose intramuscular DAXI 125U, 250U, or placebo and followed for up to 36 weeks after injection. The primary end point was change …