Medicine and Health Sciences Commons^™

Impact Of Academic Golden Weekend Initiative On Academic Success For An Internal Medicine Clerkship, Elif S. Duran, Maria A. Alvarenga, Stephanie Onyechi, Jose E. Campo Maldonado

Research Colloquium

Background: COVID-19 precautions led to a change in the number of protected weekends for the UTRGV Internal Medicine Clerkship, going from 2 protected weekends to none. The aim of Academic Golden Weekends during a fully inpatient clerkship has been to maximize the student experience by providing enough time to balance all the necessary components of the student experience. Starting April 26, 2021, all cohorts completing their Internal Medicine Clerkship as third-year medical students had 3 protected weekends.

Methods: Two surveys were created to compare the pre-intervention and post-intervention cohorts. The surveys focused on student satisfaction regarding the time they had …

Redox-Responsive Nano-Self Assemblies For Targeted Cancer Therapeutics, Partha Laskar, Sudhir Kotnala, Elian Martin, Anupam Dhasmana, Vivek K. Kashyap, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

Research Colloquium

Background: Despite significant advances in cancer therapeutics, it remains one of the leading causes of deaths due to poor response to available treatment modalities and drug resistance. Combination therapy has shown the potential to provide a synergistic therapeutic effect and to overcome drug resistance. However, smart delivery systems that can improve the bioavailability and the delivery of multiple hydrophobic anti-cancer drugs simultaneously at the tumor site without normal organ toxicity could be an effective strategy for cancer treatment.

Methods: Here, a PEGylated drug-drug conjugate (CUR-PEG-S-S-CPT) have been successfully synthesized by conjugating two hydrophobic anti-cancer molecules, curcumin and camptothecin through …

Case Report: Congenital Myasthenia Gravis- A Case For Newborn Screening?, Dakota Bigham, Barbara Stewart

Research Colloquium

Background: Myasthenia gravis is an autoimmune neuromuscular junction disorder which can result in involuntary muscle weakness. It commonly affects various muscular groups involving the eyes, face, arms, legs, and even muscles used for breathing. Most often Myasthenia Gravis affects adults, but it can occur in the pediatric population. Congenital Myasthenia Gravis (CMG) has a broad and variable presentation with many potential differential diagnoses. In rare cases, CMG can present in the first years of life with a fatigable weakness and a severe respiratory failure. In the more common, benign cases, presentation can occur later in life. Here, we present an …

Case Report: Covid-19 Pneumothorax, Dakota Bigham, Barbara Stewart

Research Colloquium

Background: As cases of Covid-19 continue to rise, more population subtypes become at risk. Although rare in past years, COVID-19 is becoming more prevalent in children. Last counts obtained show that there are 8,992 cases per 100,000 in children, state hospitalizations rates ranging from 1.7%- 4.0% of their total cumulated hospitalizations with 0.1%-1.9% of all their pediatric COVID-19 cases resulting in hospitalization. As these cases rise, we are still unsure of the immediate or long-term effects in children, and continual observation and documentation of all clinical courses is of the utmost importance. Here, we present an interesting case of a …

Interrupting The Axis: A Case Of Igg-4 Related Hypophysitis In A Young Hispanic Male, Christine E. Loftis, Emilia C. Dulgheru, Lina Pedraza Sanchez, Josenny L. Rodriguez-Paez

Research Colloquium

Background: Hypophysitis refers to inflammation of the pituitary gland that can lead to the disruption of the hypothalamic-pituitary-adrenal axis. Primary hypophysitis has five variants differentiated by histologic findings: lymphocytic, granulomatous, xanthomatous, IgG4-related, and necrotizing. IgG4-related hypophysitis is very rare and is commonly a manifestation of a multi-organ systemic disorder. We present a case of a 43-year-old man presenting with severe headache and symptomatic hyponatremia in the setting of isolated IgG-4 related hypophysitis.

Case Presentation: A 43-year-old male presented with a two-day history of severe posterior headache associated with several episodes of vomiting, photophobia, generalized weakness and fatigue. Patient had no …

Appropriateness Of Inpatient Transthoracic Echocardiography In A Community Hospital With A New Cardiology Fellowship Program, Christian D. Avalos, Y. Wady Aude

Research Colloquium

Background: The 2011 Appropriate Use Criteria (AUC) for echocardiography was developed to guide in the rational use of high quality cardiovascular imaging. Transthoracic echocardiography (TTE) orders with seemingly inappropriate indications were repeatedly identified at our hospital. Our goals were to identify the percentage of inappropriate TTEs, find a correlation between ordering physicians and appropriateness of TTEs, and reduce the inappropriate use of TTEs in the inpatient setting.

Methods: After implementing a required free-text indication for TTE orders, the indications of 100 random TTEs were retrospectively categorized as appropriate, inappropriate, and uncertain based on the AUC. TTEs for cardiac evaluation prior …

A Case Report On Autoimmune Encephalitis After Head Trauma, Chioma V. Uche, Ashley Ikwuezunma

Research Colloquium

Background: Autoimmune inflammatory encephalitis is an inflammation of the brain characterized by prominent neuropsychiatric symptoms and are associated with antibodies against neuronal cell-surface proteins, ion channels, or receptors. Most common causes of autoimmune encephalitis include Anti-NMDA antibodies, paraneoplastic syndromes, and in rare cases, seroconversion from an HSV infection. This report discusses a rare case of autoimmune encephalitis after a head trauma obtained from a ground level fall.

Case Presentation: Patient was a 55-year-old Hispanic man who presented to the emergency department with worsening confusion. Two months prior, the patient presented to an urgent care with a head laceration after a …

Developing A Chlorophyll-Based Near-Infrared Fluorescent Probe For Cancer Cell Imaging, Benilde E. Adriano, Nycol M. Cotto, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

Research Colloquium

Introduction: Near-Infrared (NIR) fluorescence-based imaging is a noteworthy and safer strategy for cancer cells/tissues imaging compared to radiological imaging. NIR fluorescence offers deep tissue penetration and have minimal obstruction by autofluorescence and photon scattering [1]. There are several NIR dyes including indocyanine green (ICG) [2] and IR-1061 [3] that allow high-resolution tissue imaging. However, these dyes possess some low-quality characteristics which limit their use, namely photo instability, toxicity, poor water solubility, and short half-lives [4]. Therefore, more efficient and effective alternatives are urgently required to provide the desired clinical outcomes. Chlorophyll (Chl) is a natural dietary NIR fluorescence emitting …

Dieulafoy's Lesion As A Cause Of Upper Gastrointestinal Bleeding In A Hispanic Male With Alcoholic Liver Cirrhosis, Baron S. Ekeledo, Semenawit Burka, Fatimah Bello, Jose Rodriguez

Research Colloquium

Introduction: Dieulafoy's lesion is a rare and potentially life-threatening condition. It accounts for 1.5 to 2% of reported acute gastrointestinal (GI) bleeding and has been linked to alcoholism and antiplatelet drug use. Unfortunately, the exact prevalence in the Hispanic population is unknown.

Case report: A 40-year-old man with a history of alcohol abuse and liver cirrhosis presented to the emergency room with complaints of frank hematemesis of 1 day duration. He was found to be diaphoretic, tachycardic (118), hypotensive (BP: 77/49), Hb - 6.2g/dl and with an INR of 1.92 (N: 0.8-1.2). Initial working diagnosis of esophageal varices …

Subacute Stroke In Young Hispanic Male With Vertebrobasilar Dolichoectasia, Ashika A. Chacko, Nevin A. Varghese

Research Colloquium

Background: Vertebrobasilar dolichoectasia (VBD) is a rare clinical entity characterized by dilatation, elongation, and tortuosity of the vertebrobasilar arteries. Patients with VBD can present varying symptoms from ischemia, compression of blood vessels, or rarely subarachnoid hemorrhage.

Case presentation: A 29-year-old Hispanic man with history of hypertension presented to emergency department with progressive left upper extremity weakness, dizziness, slurry speech, and diplopia of one-week duration. On arrival, the patient was afebrile, heart rate 75 bpm and blood pressure 193/107 mmHg. He was alert and oriented x3. Neurological exam demonstrated decreased strength (4/5) on left upper extremity and left arm pronator drift. …

Severe Hypercalcemia: Unusual Life-Threatening Presentation Of Addison’S Disease, Aramide Mikhail Tijani, Jonathan Yaw Gyebi-Agyepong, Nestor Gerardo Astorga, Niral G. Patel

Research Colloquium

Background: Addison’s Disease, also known as primary adrenal insufficiency, is a rare disorder of the adrenal gland typically characterized by the combination of cortisol and mineralocorticoid deficiencies in addition to electrolyte abnormalities including hyponatremia and hyperkalemia. Addison's disease is an uncommon cause of hypercalcemia. We present a rare case of hypercalcemia in the setting of primary adrenal insufficiency.

Case Presentation: Our patient is 43-year-old Hispanic lady with no reported medical history who presented to the Emergency Room for evaluation of intractable nausea and vomiting of about a month duration. Clinical examination revealed a lethargic, dehydrated, and hypotensive lady. Initial laboratory …

Igf-1 Reduce Protein O-Glcnacylation Via Ampk Activation In H9c2 Cardiomyoblast Cultured In High Glucose Media, Andres Medina, Lizbeth Trevino, Alejandra Salinas, Yadira Chaires, Erick Rodriguez, Genaro Antonio Ramirez-Correa

Research Colloquium

Background: Diabetes is a disease characterized by the increase in the serum glucose concentration. Therefore, this glucose excess shunts into the hexosamine biosynthetic pathway producing UDP-GlcNAc, which can be transfer to serine residues and modify the activity of different proteins, including contractile proteins in cardiomyocytes, decreasing their function. Here we show the effect of IGF-1 treatment on this posttranslational modification.

Methods: H9c2 cell line were cultured in DMEM media, 10% FBS, at 80% of confluence. Cells were incubated in high-glucose (30 mM) in the presence or absence of 10 µmol/L of IGF-1 (HG and HG+IGF-1). As control groups, we used …

Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Poornima Devi Shaji, Swathi Holla, Nirnoy Dan, Shabnam Malik, Murali M. Yallapu, Meena Jaggi, Stephen W. Behrman, Subhash C. Chauhan, Sheema Khan

Research Colloquium

Introduction: In pancreatic ductal adenocarcinoma (PDAC), low patient survival rate remains a problem. The activating point mutation of KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRAS^G12D regulates cell proliferation, differentiation, apoptosis; recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both PDAC and stromal cells, which modulate tumor microenvironment and metastasis. Therefore, we have developed a novel combination therapy for PDAC by targeting mutated KRAS^G12D and Gal-1 to target both proliferation and metastasis in PDAC. This includes the delivery of KRAS^{G12D …}

Spinal Cord Injury: Tissue Bridge Influence On Neurophysiology And Functional Recovery, Alyssa I. Canales, Marylu Cabello

Research Colloquium

Introduction: Spinal cord injuries affect about 300,000 individuals in the United States and cause varying degrees of motor and sensory impairment. The standard of care for those with a spinal cord injury typically involves traditional rehabilitation. Unfortunately, over a year of rehabilitation is often required to achieve meaningful improvements in motor or sensory function. In order to improve rehabilitative efforts for those with spinal cord injury, it is critical to identify biomarkers that could serve as indicators for those who would respond to standard rehabilitation efforts.

Objective: Following spinal cord injury, edema forms around the area of injury in the …

Medical School Watercooler Newsletter - October 5, 2023, Lindsey Lyle

Watercooler Newsletter

This is the October 5, 2023 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents Include:

• Meet a Med Student: Alexander Polski
• Simpkins selected as AAFP emerging leader institute scholar
• Bauer named assistant dean for admissions at Whiddon college of medicine

Clinical Presentation Of Patients With Lower Limb Spasticity Undergoing Routine Treatment With Botulinum Toxin: Baseline Findings From An International Observational Study, Alberto Esquenazi, Richard D. Zorowitz, Stephen Ashford, Pascal Maisonobe, Simon Page, Jorge Jacinto

Moss-Magee Rehabilitation Papers

OBJECTIVE: Describe how people with lower limb spasticity present for treatment in routine clinical practice.

METHODS: Prospective, observational study (Clinicaltrials.gov: NCT04050527) of ambulatory adult patients (≥ 18 years) with unilateral lower limb spasticity (able to take ≥ 5 steps with or without assistance) presenting for routine spasticity management, including treatment with abobotulinumtoxinA.

RESULTS: The study population included 430 adults with lower limb spasticity. Despite their relatively young age (mean ± standard deviation 53.7 ± 13.9 years), only 20% of patients were employed. Most patients had an acquired brain injury due to cerebrovascular disease; 84.1% reported having concomitant upper limb spasticity. …

Severe Pediatric Open Skull Fracture With Exposed Brain Matter: A Case Report, Sophia Mirkin, Michael Wu, Jessica Colon, Jose J. Burgos, Fernando Perez

HPD Articles

Head trauma in the pediatric population carries a high rate of morbidity and mortality. The major causes of head trauma are related to falls, recreational activities, motor vehicle accidents, and gunshot wounds. Traumatic brain injury (TBI) can occur after severe head trauma and is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force. Intracranial edema and herniation are common consequences of a TBI in pediatric patients and are commonly relieved via decompressive craniectomy. This case study describes a 13-year-old male presenting to the trauma center after an unhelmeted all-terrain vehicle (ATV) …

Évaluation De L’Impact De La Coexposition Sur Les Biomarqueurs D’Exposition Aux Pesticides Pyréthrinoïdes Chez Les Travailleurs Agricoles, Michèle Bouchard, Marc Bossou, Jonathan Côté

Rapports de recherche scientifique

Il existe peu de données publiées sur l'impact de la coexposition sur la toxicocinétique des pesticides chez les travailleurs agricoles, nécessaires pour une interprétation adéquate des données de biosurveillance de l’exposition. La présente recherche a visé à évaluer l’impact de la coexposition sur les niveaux de biomarqueurs d’exposition aux pesticides pyréthrinoïdes chez les travailleurs agricoles. Le pyréthrinoïde lambda-cyhalothrine (LCT) et le fongicide captane ont été utilisés comme pesticides sentinelles, puisqu’ils sont largement employés en culture agricole.

Dans le volet 1, les profils temporels individuels des biomarqueurs d'exposition à la lambda-cyhalothrine ont été comparés chez des opérateurs après un épisode …

Greater Number Of Weekly Stairs Climbed Is Associated With Lower Low Back Pain Prevalence Among Female But Not Male Physical Therapists, Amy H. Amabile, Sharon L. Larson, Lisa T. Hoglund, John P. Guarnieri, Maureen Mcdonald, Madeline R. Reich

Department of Physical Therapy Faculty Papers

INTRODUCTION: Certain cardiovascular health benefits of stair climbing are now widely accepted, but no prior studies have as yet been found linking the quantity of stairs climbed to low back pain (LBP) morbidity. Low back pain is a common musculoskeletal impairment, and research has begun to show an association between LBP and gluteus maximus (GM) weakness. With stair climbing being the activity which most activates GM, the aim of the present research was to assess the relationship between stair ambulation and LBP prevalence. The hypothesis of this cross-sectional study was that individuals with LBP would report a significantly lower numbers …

Immune Cell Deconvolution Reveals Possible Association Of Γδ T Cells With Poor Survival In Head And Neck Squamous Cell Carcinoma, Anuraag S Parikh, Yize Li, Angela Mazul, Wade Thorstad, Jason Rich, Randal C Paniello, Ryan S Jackson, Patrik Pipkorn, Paul Zolkind, Zongtai Qi, Douglas Adkins, Li Ding, Sidharth V Puram, Et Al.

2020-Current year OA Pubs

(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating …

Greater Number Of Weekly Stairs Climbed Is Associated With Lower Low Back Pain Prevalence Among Female But Not Male Physical Therapists, Amy H. Amabile, Sharon L. Larson, Lisa T. Hoglund, John P. Guarnieri, Maureen Mcdonald, Madeline R. Reich

Department of Physical Therapy Faculty Papers

INTRODUCTION: Certain cardiovascular health benefits of stair climbing are now widely accepted, but no prior studies have as yet been found linking the quantity of stairs climbed to low back pain (LBP) morbidity. Low back pain is a common musculoskeletal impairment, and research has begun to show an association between LBP and gluteus maximus (GM) weakness. With stair climbing being the activity which most activates GM, the aim of the present research was to assess the relationship between stair ambulation and LBP prevalence. The hypothesis of this cross-sectional study was that individuals with LBP would report a significantly lower numbers …

Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel

Faculty, Staff and Student Publications

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem …

Sparx: Elucidate Single-Cell Spatial Heterogeneity Of Drug Responses For Personalized Treatment, Ziyang Tang, Xiang Liu, Zuotian Li, Tonglin Zhang, Baijian Yang, Jing Su, Qianqian Song

Publications

Spatial cellular authors heterogeneity contributes to differential drug responses in a tumor lesion and potential therapeutic resistance. Recent emerging spatial technologies such as CosMx, MERSCOPE and Xenium delineate the spatial gene expression patterns at the single cell resolution. This provides unprecedented opportunities to identify spatially localized cellular resistance and to optimize the treatment for individual patients. In this work, we present a graph-based domain adaptation model, SpaRx, to reveal the heterogeneity of spatial cellular response to drugs. SpaRx transfers the knowledge from pharmacogenomics profiles to single-cell spatial transcriptomics data, through hybrid learning with dynamic adversarial adaption. Comprehensive benchmarking demonstrates the …

In-Utero Exposure To Antibiotics And Risk Of Colorectal Cancer In A Prospective Cohort Of 18 000 Adult Offspring, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Dean P Jones, Timothy Zaki, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring.

METHODS: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides …

An Intrinsically Disordered Region Controlling Condensation Of A Circadian Clock Component And Rhythmic Transcription In The Liver, Kun Zhu, Isaac J Celwyn, Dongyin Guan, Yang Xiao, Xiang Wang, Wenxiang Hu, Chunjie Jiang, Lan Cheng, Rafael Casellas, Mitchell A Lazar

Faculty, Staff and Students Publications

Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBα, a repressive component of the molecular clock, forms circadian condensates in the nuclei of mouse liver. These condensates are dictated by an intrinsically disordered region (IDR) located in the protein's hinge region which specifically concentrates nuclear receptor corepressor 1 (NCOR1) at the genome. IDR deletion diminishes the recruitment of NCOR1 and disrupts rhythmic gene transcription in vivo. REV-ERBα condensates are located at high-order transcriptional repressive hubs in the liver genome that are highly correlated with circadian gene repression. Deletion of the IDR disrupts transcriptional …

Global Effect Of Modifiable Risk Factors On Cardiovascular Disease And Mortality, Global Cardiovascular Risk Consortium, Christina Magnussen, Francisco M Ojeda, Darryl P Leong, Jesus Alegre-Diaz, Philippe Amouyel, Larissa Aviles-Santa, Dirk De Bacquer, Christie M Ballantyne, Antonio Bernabé-Ortiz, Martin Bobak, Hermann Brenner, Rodrigo M Carrillo-Larco, James De Lemos, Annette Dobson, Marcus Dörr, Chiara Donfrancesco, Wojciech Drygas, Robin P Dullaart, Gunnar Engström, Marco M Ferrario, Jean Ferrières, Giovanni De Gaetano, Uri Goldbourt, Clicerio Gonzalez, Guido Grassi, Allison M Hodge, Kristian Hveem, Licia Iacoviello, M Kamran Ikram, Vilma Irazola, Modou Jobe, Pekka Jousilahti, Pontiano Kaleebu, Maryam Kavousi, Frank Kee, Davood Khalili, Wolfgang Koenig, Anna Kontsevaya, Kari Kuulasmaa, Karl J Lackner, David M Leistner, Lars Lind, Allan Linneberg, Thiess Lorenz, Magnus Nakrem Lyngbakken, Reza Malekzadeh, Sofia Malyutina, Ellisiv B Mathiesen, Olle Melander, Andres Metspalu, J Jaime Miranda, Marie Moitry, Joseph Mugisha, Mahdi Nalini, Vijay Nambi, Toshiharu Ninomiya, Karen Oppermann, Eleonora D'Orsi, Andrzej Pająk, Luigi Palmieri, Demosthenes Panagiotakos, Arokiasamy Perianayagam, Annette Peters, Hossein Poustchi, Andrew M Prentice, Eva Prescott, Ulf Risérus, Veikko Salomaa, Susana Sans, Satoko Sakata, Ben Schöttker, Aletta E Schutte, Sadaf G Sepanlou, Sanjib Kumar Sharma, Jonathan E Shaw, Leon A Simons, Stefan Söderberg, Abdonas Tamosiunas, Barbara Thorand, Hugh Tunstall-Pedoe, Raphael Twerenbold, Diego Vanuzzo, Giovanni Veronesi, Julia Waibel, S Goya Wannamethee, Masafumi Watanabe, Philipp S Wild, Yao Yao, Yi Zeng, Andreas Ziegler, Stefan Blankenberg

Faculty, Staff and Students Publications

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease (CVD) and all-cause mortality. The regional and sex-specific prevalence of these modifiable risk factors and their impact on CVD and all-cause mortality have not been evaluated using individual-level data.

METHODS: The Global Cardiovascular Risk Consortium harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions. Associations between body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, smoking, and diabetes with incident CVD and all-cause mortality were examined using Cox regression analyses and stratified by geographic region, age and sex. Population-attributable fractions were estimated for 10-year incident …

Pls3 Missense Variants Affecting The Actin-Binding Domains Cause X-Linked Congenital Diaphragmatic Hernia And Body-Wall Defects, Florence Petit, Mauro Longoni, Julie Wells, Richard S Maser, Eric L Bogenschutz, Matthew J Dysart, Hannah T M Contreras, Frederic Frénois, Barbara R Pober, Robin D Clark, Philip F Giampietro, Hilger H Ropers, Hao Hu, Maria Loscertales, Richard Wagner, Xingbin Ai, Harrison Brand, Anne-Sophie Jourdain, Marie-Ange Delrue, Brigitte Gilbert-Dussardier, Louise Devisme, Boris Keren, David J Mcculley, Lu Qiao, Rebecca Hernan, Julia Wynn, Tiana M Scott, Daniel G Calame, Zeynep Coban-Akdemir, Patricia Hernandez, Andres Hernandez-Garcia, Hagith Yonath, James R Lupski, Yufeng Shen, Wendy K Chung, Daryl A Scott, Carol J Bult, Patricia K Donahoe, Frances A High

Faculty, Staff and Student Publications

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical …

Utility And Precision Evidence Of Technology In The Treatment Of Type 1 Diabetes: A Systematic Review, Laura M Jacobsen, Jennifer L Sherr, Elizabeth Considine, Angela Chen, Sarah M Peeling, Margo Hulsmans, Sara Charleer, Marzhan Urazbayeva, Mustafa Tosur, Selma Alamarie, Maria J Redondo, Korey K Hood, Peter A Gottlieb, Pieter Gillard, Jessie J Wong, Irl B Hirsch, Richard E Pratley, Lori M Laffel, Chantal Mathieu

Faculty, Staff and Students Publications

BACKGROUND: The greatest change in the treatment of people living with type 1 diabetes in the last decade has been the explosion of technology assisting in all aspects of diabetes therapy, from glucose monitoring to insulin delivery and decision making. As such, the aim of our systematic review was to assess the utility of these technologies as well as identify any precision medicine-directed findings to personalize care.

METHODS: Screening of 835 peer-reviewed articles was followed by systematic review of 70 of them (focusing on randomized trials and extension studies with ≥50 participants from the past 10 years).

RESULTS: We find …

Disease-Modifying Therapies And Features Linked To Treatment Response In Type 1 Diabetes Prevention: A Systematic Review, Jamie L Felton, Kurt J Griffin, Richard A Oram, Cate Speake, S Alice Long, Suna Onengut-Gumuscu, Stephen S Rich, Gabriela S F Monaco, Carmella Evans-Molina, Linda A Dimeglio, Heba M Ismail, Andrea K Steck, Dana Dabelea, Randi K Johnson, Marzhan Urazbayeva, Stephen Gitelman, John M Wentworth, Maria J Redondo, Emily K Sims, Ada/Easd Pmdi

Faculty, Staff and Students Publications

BACKGROUND: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification.

METHODS: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a …

Rare Variants In Long Non-Coding Rnas Are Associated With Blood Lipid Levels In The Topmed Whole-Genome Sequencing Study, Yuxuan Wang, Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Jacob A Holdcraft, Donna K Arnett, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Brian E Cade, Jenna C Carlson, April P Carson, Yii-Der Ida Chen, Joanne E Curran, Paul S De Vries, Susan K Dutcher, Patrick T Ellinor, James S Floyd, Myriam Fornage, Barry I Freedman, Stacey Gabriel, Soren Germer, Richard A Gibbs, Xiuqing Guo, Jiang He, Nancy Heard-Costa, Bertha Hildalgo, Lifang Hou, Marguerite R Irvin, Roby Joehanes, Robert C Kaplan, Sharon Lr Kardia, Tanika N Kelly, Ryan Kim, Charles Kooperberg, Brian G Kral, Daniel Levy, Changwei Li, Chunyu Liu, Don Lloyd-Jone, Ruth Jf Loos, Michael C Mahaney, Lisa W Martin, Rasika A Mathias, Ryan L Minster, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Joanne M Murabito, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Dabeeru C Rao, Susan Redline, Alexander P Reiner, Stephen S Rich, Muagututi'a Sefuiva Ruepena, Wayne H-H Sheu, Jennifer A Smith, Albert Smith, Hemant K Tiwari, Michael Y Tsai, Karine A Viaud-Martinez, Zhe Wang, Lisa R Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Jerome I Rotter, Xihong Lin, Pradeep Natarajan, Gina M Peloso

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants …