Medical Specialties Commons^™

Generation Of Humanized Ldhc Knock-In Mice As A Tool To Assess Human Ldhc-Targeting Contraceptive Drugs, Rie Iida-Norita, Haruhiko Miyata, Yuki Kaneda, Chihiro Emori, Taichi Noda, Tatsuya Nakagawa, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Background: Lactate dehydrogenase C (LDHC) is specifically expressed in male germ cells and plays critical roles in glycolysis. Glycolysis is required to supply energy for sperm motility. Previous studies showed that Ldhc knock-out mice exhibit impaired sperm motility.

Objectives: We established human LDHC knock-in (hLDHC KI) mice and examined whether hLDHC KI mice can be used to assess LDHC-targeting drugs.

Material and methods: HLDHC was knocked-in to the mouse Ldhc (mLdhc) allele using the CRISPR/Cas9 system. Mating tests, sperm motility examinations with a computer-assisted sperm analysis (CASA) system, and in vitro fertilization (IVF) were performed. Furthermore, the effect of an …

Exploring The Role Of Vitamin D And The Gut Microbiome: A Cross-Sectional Study Of Individuals With Irritable Bowel Syndrome And Healthy Controls, Sarah W Matthews, Anna Plantinga, Robert Burr, Kevin C Cain, Tor Savidge, Kendra Kamp, Margaret M Heitkemper

Faculty, Staff and Students Publications

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with multifaceted pathophysiology. Prior studies have demonstrated higher rates of vitamin D deficiency in individuals with IBS compared to healthy controls (HC), as well as associations of vitamin D concentration with IBS symptoms. A systematic review of 10 mouse and 14 human studies reported a positive association between vitamin D (serum levels and supplementation) and beta diversity of gut microbiome in a variety of conditions. The present retrospective case-control study aimed to compare vitamin D (25(OH)D) plasma concentrations and gut microbiome composition in adult women with IBS (n=99) and …

Presentation Of External Ear Rosai-Dorfman Disease With Laryngeal Involvement, Kenji R Kobayashi, Yusif Hajiyev, Maren Y Fuller, Gunes Orman, Elton M Lambert

Faculty, Staff and Students Publications

Rosai-Dorfman disease (RDD) is a rare benign systemic histiocytic proliferation characterized by massive lymph node enlargement and sometimes associated with extranodal involvement. Even though it is considered to be benign, death can occur depending on the extent and location. Our case highlights a primary extranodal site of the right pinna with extension through the Eustachian tube to the subglottis. A previously healthy 15-year-old female presented with 1-year right pinna swelling, slowly enlarging and becoming more bothersome. An incisional biopsy was performed on the ear along with S100 staining yielding a diagnosis. After multidisciplinary case discussion, clofarabine monotherapy and systemic therapy …

Vincristine/Irinotecan/Temsirolimus Upfront Window Treatment Of High-Risk Hepatoblastoma: A Report From The Children’S Oncology Group Ahep0731 Study Committee, Patrick A Thompson, Marcio H Malogolowkin, Wayne L Furman, Jin Piao, Mark D Krailo, Nadia Chung, Lindsay Brock, Alexander J Towbin, Elizabeth B Mccarville, Milton J Finegold, Sarangarajan Ranganathan, Stephen P Dunn, Max R Langham, Eugene D Mcgahren, Gregory M Tiao, Christopher B Weldon, Allison F O'Neill, Carlos Rodriguez-Galindo, Rebecka L Meyers, Howard M Katzenstein

Faculty, Staff and Students Publications

Background: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB.

Procedures: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline …

Biallelic Variants In Cript Cause A Rothmund-Thomson-Like Syndrome With Increased Cellular Senescence, Luisa Averdunk, Maxim A Huetzen, Daniel Moreno-Andrés, Reinhard Kalb, Shane Mckee, Tzung-Chien Hsieh, Annette Seibt, Marten Schouwink, Seema Lalani, Eissa Ali Faqeih, Theresa Brunet, Peter Boor, Kornelia Neveling, Alexander Hoischen, Barbara Hildebrandt, Elisabeth Graf, Linchao Lu, Weidong Jin, Joerg Schaper, Jamal A Omer, Tanguy Demaret, Nicole Fleischer, Detlev Schindler, Peter Krawitz, Ertan Mayatepek, Dagmar Wieczorek, Lisa L Wang, Wolfram Antonin, Ron D Jachimowicz, Verena Von Felbert, Felix Distelmaier

Faculty, Staff and Students Publications

Purpose: Rothmund-Thomson syndrome (RTS) is characterized by poikiloderma, sparse hair, small stature, skeletal defects, cancer, and cataracts, resembling features of premature aging. RECQL4 and ANAPC1 are the 2 known disease genes associated with RTS in >70% of cases. We describe RTS-like features in 5 individuals with biallelic variants in CRIPT (OMIM 615789).

Methods: Two newly identified and 4 published individuals with CRIPT variants were systematically compared with those with RTS using clinical data, computational analysis of photographs, histologic analysis of skin, and cellular studies on fibroblasts.

Results: All CRIPT individuals fulfilled the diagnostic criteria for RTS and additionally had neurodevelopmental …

De Novo Variants In Cnot9 Cause A Neurodevelopmental Disorder With Or Without Epilepsy, Lydia Von Wintzingerode, Bruria Ben-Zeev, Claudia Cesario, Katie M Chan, Christel Depienne, Orly Elpeleg, Maria Iascone, Whitley V Kelley, Marie-Cécile Nassogne, Marcello Niceta, Lidia Pezzani, Nils Rahner, Nicole Revencu, Mir Reza Bekheirnia, Teresa Santiago-Sim, Marco Tartaglia, Michelle L Thompson, Marina Trivisano, Julia Hentschel, Heinrich Sticht, Rami Abou Jamra, Henry Oppermann

Faculty, Staff and Students Publications

Purpose: The study aimed to clinically and molecularly characterize the neurodevelopmental disorder associated with heterozygous de novo variants in CNOT9.

Methods: Individuals were clinically examined. Variants were identified using exome or genome sequencing. These variants were evaluated using in silico predictions, and their functional relevance was further assessed by molecular models and research in the literature. The variants have been classified according to the criteria of the American College of Medical Genetics.

Results: We report on 7 individuals carrying de novo missense variants in CNOT9, p.(Arg46Gly), p.(Pro131Leu), and p.(Arg227His), and, recurrent in 4 unrelated individuals, p.(Arg292Trp). All affected persons have …

Prevalence Of Ddc Genotypes In Patients With Aromatic L-Amino Acid Decarboxylase (Aadc) Deficiency And In Silico Prediction Of Structural Protein Changes, Nastassja Himmelreich, Mariarita Bertoldi, Majid Alfadhel, Malak Ali Alghamdi, Yair Anikster, Xinhua Bao, Fahad A Bashiri, Bruria Ben Zeev, Giovanni Bisello, Ahmet Cevdet Ceylan, Yin-Hsiu Chien, Yew Sing Choy, Sarah H Elsea, Lisa Flint, Àngels García-Cazorla, Charul Gijavanekar, Emel Yılmaz Gümüş, Muddathir H Hamad, Burcu Hişmi, Tomas Honzik, Oya Kuseyri Hübschmann, Wuh-Liang Hwu, Salvador Ibáñez-Micó, Kathrin Jeltsch, Natalia Juliá-Palacios, Çiğdem Seher Kasapkara, Manju A Kurian, Katarzyna Kusmierska, Ning Liu, Lock Hock Ngu, John D Odom, Winnie Peitee Ong, Thomas Opladen, Mari Oppeboen, Phillip L Pearl, Belén Pérez, Roser Pons, Agnieszka Magdalena Rygiel, Tan Ee Shien, Robert Spaull, Jolanta Sykut-Cegielska, Brahim Tabarki, Trine Tangeraas, Beat Thöny, Tessa Wassenberg, Yongxin Wen, Yusnita Yakob, Jasmine Goh Chew Yin, Jiri Zeman, Nenad Blau

Faculty, Staff and Students Publications

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive genetic disorder affecting the biosynthesis of dopamine, a precursor of both norepinephrine and epinephrine, and serotonin. Diagnosis is based on the analysis of CSF or plasma metabolites, AADC activity in plasma and genetic testing for variants in the DDC gene. The exact prevalence of AADC deficiency, the number of patients, and the variant and genotype prevalence are not known. Here, we present the DDC variant (n = 143) and genotype (n = 151) prevalence of 348 patients with AADC deficiency, 121 of whom were previously not reported. In addition, …

Obsessive-Compulsive Disorder In Youth And Young Adults With Depression: Clinical Characteristics Of Comorbid Presentations, David B Riddle, Andrew Guzick, Abu Minhajuddin, Orri Smárason, Gabrielle M Armstrong, Holli Slater, Taryn L Mayes, Lynnel C Goodman, Denise L Baughn, Sarah L Martin, Sarah M Wakefield, Joseph Blader, Ryan Brown, Wayne K Goodman, Madhukar H Trivedi, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD), anxiety disorders, and depressive disorders are highly comorbid, and each contribute to significant functional impairment for affected youth. Comorbid anxiety disorders in depressed youth have been associated with greater depressive symptom severity and impairment, but the impact of comorbid OCD in this population remains unclear. Accordingly, the present study examined the differential clinical characteristics of youth with depression and comorbid OCD relative to age/gender matched depressed youth with no such comorbidity and to those with depression and a comorbid (non-OCD) anxiety disorder. A sample of 797 youth and young adults ages 8-20 years who met diagnostic criteria …

Distinct Serum Immune Profiles Define The Spectrum Of Acute And Chronic Pancreatitis From The Multicenter Prospective Evaluation Of Chronic Pancreatitis For Epidemiologic And Translational Studies (Proceed) Study, Bomi Lee, Elaina K Jones, Murli Manohar, Liang Li, Dhiraj Yadav, Darwin L Conwell, Phil A Hart, Santhi Swaroop Vege, Evan L Fogel, Jose Serrano, Dana Andersen, Melena D Bellin, Mark D Topazian, Stephen K Van Den Eeden, Stephen J Pandol, Chris E Forsmark, William E Fisher, Walter G Park, Sohail Z Husain, Aida Habtezion, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis.

METHODS: Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic …

Radiologic-Pathologic Correlation Of Covid-19-Associated Acute Disseminated Encephalomyelitis, Amy Bezold, Huda Hussain, Julum Nwanze, James T Roberts, Kuang-Chun J Hsieh

Faculty, Staff and Students Publications

A 42-year-old woman presented with drooling, slurred speech, inability to walk and talk, and a recent positive COVID-19 test. She had two prior hospital admissions within the past week for similar symptoms with inconclusive evaluation. MRI of the brain demonstrated multifocal white matter hyperintense lesions on fluid-attenuated inversion recovery (FLAIR)/diffusion with variable enhancement. These imaging findings have been described in recent literature and are associated with inflammatory demyelinating disease, such as acute disseminated encephalomyelitis. The patient subsequently underwent a brain biopsy with a final diagnosis of inflammatory demyelinating lesion. To our knowledge, this is the first radiologic-pathologic correlation of COVID-19-associated …

Early Intraoperative Detection And Management Of Right Ventricular Failure After Left Ventricular Assist Device Implantation, Thomas R Powell

Faculty, Staff and Students Publications

No abstract provided.

The Association Of Academic Cosmetic Dermatology: Improving Cosmetic Dermatology Education Through Collaboration, Research, And Advocacy, Kira Minkis, Diana Bolotin, M Laurin Council, Anna Bar, Ronda S Farah, Nour Kibbi, Rachel Y N Miest, Jeffrey S Orringer, Arisa Ortiz, Kathleen C Suozzi, Neelam A Vashi, Simon S Yoo, Joerg Albrecht, Travis W Blalock, Alison J Bruce, Min Deng, Shraddha Desai, Milad Eshaq, Lori A Fiessinger, Erica Ghareeb, Tanya Greywal, Adelaide A Hebert, Deirdre Hooper, Maria Hordinsky, Jenny C Hu, Atieh Jibbe, Jayne Joo, Kristen M Kelly, Sonya Kenkare, Shilpi Khetarpal, Lauren C S Kole, A Shadi Kourosh, Helena Kuhn, Kachiu C Lee, Roberta Lucas, Janiene Luke, Mariam Mafee, Tiffany T Mayo, Zeena Y Nawas, Edit B Olasz Harken, Michelle V Pearlstein, Vesna Petronic-Rosic, Carolyn A Robinson, Megan N Rogge, Dana L Sachs, Sami K Saikaly, Olivia L Schenck, Cynthia A Schlick, Ladan Shahabi, Desmond M Shipp, Melissa Shive, Sirunya Silapunt, Amanda K Suggs, Leila Tolaymat, Kimberley H M Ward, Mara Weinstein Velez, Joshua Zeichner, Bianca Y Kang, Sarah A Ibrahim, Rachel E Christensen, Noor Anvery, Mckenzie A Dirr, Naomi Lawrence, Murad Alam

Faculty, Staff and Students Publications

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic …

Outcomes Of Temporary Ventricular Assist Device: A Pediatric Institutional Experience Over 25 Years, Junsang Cho, Andres A Fuentes-Baldemar, Hari P Tunuguntla, Joseph A Spinner, Sebastian C Tume, Athar M Qureshi, Jun Teruya, Jeffrey S Heinle, Iki Adachi

Faculty, Staff and Students Publications

Background: There are scarce data describing outcomes of pediatric temporary ventricular assist device support.

Methods: A retrospective single-center study was conducted to review clinical outcomes of all consecutive patients with temporary ventricular assist device between 1996 and 2021. Given the complex clinical course in some patients requiring multiple temporary ventricular assist device runs, outcome analysis was based on "encounters" (hospitalizations with temporary ventricular assist device, regardless of the number of devices used).

Results: In total, 126 temporary ventricular assist devices were implanted in 108 patients, resulting in a total of 114 encounters: 70 (61%) extracorporeal centrifugal pumps and 44 (39%) …

Mathematical Analysis Of Hemoglobin Target In Univentricular Parallel Circulation, Mubbasheer Ahmed, Sebastian I Acosta, George M Hoffman, James S Tweddell, Nancy S Ghanayem

Faculty, Staff and Students Publications

Objective: The hemoglobin threshold for a decision to transfuse red blood cells in univentricular patients with parallel circulation is unclear. A pediatric expertise initiative put forth a "weak recommendation" for avoiding reflexive transfusion beyond a hemoglobin of 9 g/dL. We have created a mathematical model to assess the impact of hemoglobin thresholds in patients with parallel circulation.

Methods: A univentricular circulation was mathematically modeled. We examined the impact on oxygen extraction ratios and systemic and venous oxygen saturations by varying hemoglobin levels, pulmonary to systemic blood flow ratios, and total cardiac output.

Results: Applying a total cardiac index of 6 …

The Systemic Availability Of Indispensable Amino Acids From Orally Ingested Algal And Legume Protein In Young Children At Risk Of Environmental Enteric Dysfunction, Nirupama Shivakumar, Sindhu Kashyap, Farook Jahoor, Sarita Devi, Thomas Preston, Tinku Thomas, Anura V Kurpad

Faculty, Staff and Students Publications

Background: The digestion and absorption of ingested protein may be reduced in children with environmental enteric dysfunction (EED), reducing systemic amino acid availability for protein synthesis with resultant growth faltering. This has not been directly measured in children with EED and associated growth faltering.

Objectives: To evaluate the systemic availability of algal (spirulina) and legume (mung bean) indispensable amino acids (IAAs) in children with EED.

Methods: Indian children (18-24 mo) from urban slums were assigned to EED (n = 24) or no-EED (control, n = 17) groups based on the lactulose rhamnose test, where the lactulose rhamnose ratio cutoff for …

It Is Time For A Paradigm Shift In Design, Execution, And Publishing Of Comparative Helicobacter Pylori Treatment Trials, David Y Graham

Faculty, Staff and Students Publications

No abstract provided.

Telehealth For Assessing And Managing Tardive Dyskinesia: Expert Insights From A Cross-Disciplinary Virtual Treatment Panel, Rif S El-Mallakh, Amy Belnap, Sanjay Iyer, Jeremy Schreiber, Desiree Matthews, Linda Lefler, Daniel Dees, Allen Bott, Nora Vanegas-Arroyave, Adam Wolff, Ulises Pesce, Khody Farahmand, Chirag Shah, Leslie Lundt

Faculty, Staff and Students Publications

Introduction: Publications on the integration of telehealth in the care of patients with movement disorders are increasing, but little has been presented regarding its use in tardive dyskinesia (TD), a drug-induced movement disorder associated with prolonged exposure to dopamine receptor blocking agents. This study was conducted to address that knowledge gap, based on insights from a panel of TD experts.

Methods: In 2020, six neurologists, three psychiatrists, and three psychiatric nurse practitioners participated in individual semistructured interviews about in-person and virtual TD assessment and management in their practices. Two virtual roundtables were then conducted to consolidate findings from these interviews. …

Measurement Of Fatigue In Patients Receiving Kidney Replacement Therapy, Melandrea L Worsley, Akshta Pai, L Parker Gregg

Faculty, Staff and Students Publications

No abstract provided.

Ceramide Compensation By Ceramide Synthases Preserves Retinal Function And Structure In A Retinal Dystrophy Mouse Model, Xinye Qian, Tanmay Srinivasan, Jessica He, Jiaxiong Lu, Yan Jin, Haiwei Gu, Rui Chen

Faculty, Staff and Students Publications

Increasing evidence has supported the role of ceramide as a mediator of photoreceptor dysfunction or cell death in ceramide accumulation and deficiency contexts. TLCD3B, a non-canonical ceramide synthase, was previously identified in addition to the six canonical ceramide synthases (CerSs), and the Tlcd3b-/- mouse model exhibited both retinal dysfunction and degeneration. As previous canonical CerS-deficient mouse models failed to display retinal degeneration, the mechanisms of how TLCD3B interacts with CerSs have not been investigated. Additionally, as the ceramide profile of each CerS is distinct, it is unclear whether the overall level or the homeostasis of different ceramide species plays a …

Outside Looking In, Alec B Rezigh, Austin Rezigh, Zahir Kanjee, Zaven Sargsyan, Stephanie Sherman, Ann M Kumfer

Faculty, Staff and Students Publications

No abstract provided.

Disseminating Child Abuse Clinical Decision Support Among Commercial Electronic Health Records: Effects On Clinical Practice, David A Feldstein, Isabel Barata, Thomas Mcginn, Emily Heineman, Joshua Ross, Dana Kaplan, Francesca Bullaro, Sundas Khan, Nicholas Kuehnel, Rachel P Berger

Faculty, Staff and Students Publications

Objectives: The use of electronic health record (EHR)-embedded child abuse clinical decision support (CA-CDS) may help decrease morbidity from child maltreatment. We previously reported on the development of CA-CDS in Epic and Allscripts. The objective of this study was to implement CA-CDS into Epic and Allscripts and determine its effects on identification, evaluation, and reporting of suspected child maltreatment.

Materials and methods: After a preimplementation period, CA-CDS was implemented at University of Wisconsin (Epic) and Northwell Health (Allscripts). Providers were surveyed before the go-live and 4 months later. Outcomes included the proportion of children who triggered the CA-CDS system, had …

Fkbp5 Inhibitors Modulate Alcohol Drinking And Trauma-Related Behaviors In A Model Of Comorbid Post-Traumatic Stress And Alcohol Use Disorder, Bryan Cruz, Valentina Vozella, Benjamin A Carper, Joy C Xu, Dean Kirson, Shawn Hirsch, Tracy Nolen, Lauren Bradley, Katie Fain, Meg Crawford, Thomas R Kosten, Eric P Zorrilla, Marisa Roberto

Faculty, Staff and Students Publications

Post-traumatic stress disorder (PTSD) leads to enhanced alcohol drinking and development of alcohol use disorder (AUD). Identifying shared neural mechanisms might help discover new therapies for PTSD/AUD. Here, we employed a rat model of comorbid PTSD/AUD to evaluate compounds that inhibit FK506-binding protein 51 (FKBP5), a co-chaperone modulator of glucocorticoid receptors implicated in stress-related disorders. Male and female rats received a familiar avoidance-based shock stress followed by voluntary alcohol drinking. We then assessed trauma-related behaviors through sleep bout cycles, hyperarousal, fear overgeneralization, and irritability. To evaluate the role of stress and alcohol history on the sensitivity to FKBP5 inhibitors, in …

Characterizing The Influence Of Exposure To Military Sexual Trauma And Intimate Partner Violence On Mental Health Outcomes Among Female Veterans, Carrie Esopenko, Nicola De Souza, Elisabeth A Wilde, Kristen Dams-O'Connor, Ellen Teng, Deleene S Menefee

Faculty, Staff and Students Publications

Military sexual trauma (MST) has deleterious long-term psychological consequences. Among female U.S. military members, MST is associated with increased risk for future interpersonal victimization, such as experiencing intimate partner violence (IPV). Few studies have investigated the implications of the cumulative effects of IPV and MST on psychological functioning. This study examined rates of co-exposure to MST, IPV, and their cumulative impact on psychological symptoms. Data were collected from 308 female Veterans (FVets; age:

Development Of Photo-Polymerization-Type 3d Printer For High-Viscosity Ceramic Resin Using Cnn-Based Surface Defect Detection, Jin-Kyo Chung, Jeong-Seon Im, Min-Soo Park

Faculty, Staff and Student Publications

Due to the high hardness and brittleness of ceramic materials, conventional cutting methods result in poor quality and machining difficulties. Additive manufacturing has also been tried in various ways, but it has many limitations. This study aims to propose a system to monitor surface defects that occur during the printing process based on high-viscosity composite resin that maximizes ceramic powder content in real time using image processing and convolutional neural network (CNN) algorithms. To do so, defects mainly observed on the surface were classified into four types by form: pore, minor, critical, and error, and the effect of each defect …

Innovations In Cell Therapy In Pediatric Diseases: A Narrative Review, Razan El Sayed, Karan Michael Shankar, Atharwa Rajan Mankame, Charles S Cox

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Stem cell therapy is a regenerative medicine modality that has the potential to decrease morbidity and mortality by promoting tissue regeneration or modulating the inflammatory response. An increase in the number of clinical trials investigating the efficacy and safety of stem cell therapy in pediatric diseases has led to advancements in this field. Currently, multiple sources and types of stem cells have been utilized in the treatment of pediatric diseases. This review aims to inform researchers and clinicians about preclinical and clinical stem cell therapy trials in pediatric patients. We discuss the different types of stem cells …

Stimulatory Effects Of Lycium Shawii On Human Melanocyte Proliferation, Migration, And Melanogenesis: In Vitro And In Silico Studies, Karen E Gerlach, Kanchan Ashok Phalak, Ethan O Cohen, Kiran N Chang, Roland Bassett, Gary J Whitman

Faculty, Staff and Student Publications

Rationale and objectives: Information evaluating the efficacy of 2D synthesized mammography (2Ds) reconstructions in microcalcification detection is limited. This study used stereotactic biopsy data for microcalcifications to evaluate the stepwise implementation of 2Ds in screening mammography. The study aim was to identify whether 2Ds + digital breast tomosynthesis (DBT) is non-inferior to 2D digital mammography (2DM) + 2Ds + DBT, 2DM + DBT, and 2DM in identifying microcalcifications undergoing further diagnostic imaging and stereotactic biopsy.

Materials and methods: Retrospective stereotactic biopsy data were extracted following 151,736 screening mammograms of healthy women (average age, 56.3 years; range, 30-89 years), performed between …

Co-Targeting Fasn And Mtor Suppresses Uveal Melanoma Growth, Anna Han, Dzmitry Mukha, Vivian Chua, Timothy J Purwin, Manoela Tiago, Bhavik Modasia, Usman Baqai, Jenna L Aumiller, Nelisa Bechtel, Emily Hunter, Meggie Danielson, Mizue Terai, Philip B Wedegaertner, Takami Sato, Solange Landreville, Michael A Davies, Stefan Kurtenbach, J William Harbour, Zachary T Schug, Andrew E Aplin

Faculty, Staff and Student Publications

Uveal melanoma (UM) displays a high frequency of metastasis; however, effective therapies for metastatic UM are limited. Identifying unique metabolic features of UM may provide a potential targeting strategy. A lipid metabolism protein expression signature was induced in a normal choroidal melanocyte (NCM) line transduced with GNAQ (Q209L), a driver in UM growth and development. Consistently, UM cells expressed elevated levels of fatty acid synthase (FASN) compared to NCMs. FASN upregulation was associated with increased mammalian target of rapamycin (mTOR) activation and sterol regulatory element-binding protein 1 (SREBP1) levels. FASN and mTOR inhibitors alone significantly reduced UM cell growth. Concurrent …

Twenty-Year Survival Following Lung Transplantation, John James Miggins, Ross M Reul, Spencer Barrett, Abbas Rana, Ahmed Alnajar, Jordan Dunson, Alexis Shafii, Puneet Garcha, John Goss, Gabriel Loor

Faculty, Staff and Students Publications

BACKGROUND: Lung transplantation median survival has seen improvements due to recognition of short-term survival factors but continues to trail behind other solid organs due to limited understanding of long-term survivorship. Given the creation of the United Network for Organ Sharing (UNOS) database in 1986, it was difficult to accrue data on long-term survivors until recently. This study characterizes factors impacting lung transplant survival beyond 20 years, conditional to 1-year survival.

METHODS: Lung transplant recipients listed in UNOS from 1987 to 2002 who survived to 1 post-transplant year were reviewed. Kaplan-Meier and adjusted Cox regression analyses were performed at 20 and …

Ndufs4 Regulates Cristae Remodeling In Diabetic Kidney Disease, Koki Mise, Jianyin Long, Daniel L Galvan, Zengchun Ye, Guizhen Fan, Irina I Serysheva, Travis I Moore, Jun Wada, Paul T Schumacker, Benny H Chang, Farhad R Danesh

Faculty, Staff and Student Publications

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generated diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model to investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that these conditional mice exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify …

Atoh1 Drives The Heterogeneity Of The Pontine Nuclei Neurons And Promotes Their Differentiation, Sih-Rong Wu, Jessica C Butts, Matthew S Caudill, Jean-Pierre Revelli, Ryan S Dhindsa, Mark A Durham, Huda Y Zoghbi

Faculty, Staff and Students Publications

Pontine nuclei (PN) neurons mediate the communication between the cerebral cortex andthe cerebellum to refine skilled motor functions. Prior studies showed that PN neurons fall into two subtypes based on their anatomic location and region-specific connectivity, but the extent of their heterogeneity and its molecular drivers remain unknown. Atoh1 encodes a transcription factor that is expressed in the PN precursors. We previously showed that partial loss of Atoh1 function in mice results in delayed PN development and impaired motor learning. In this study, we performed single-cell RNA sequencing to elucidate the cell state–specific functions of Atoh1 during PN development and …