Digital Commons Network^™

Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes With Regional Associated Biology And Patient Outcome, H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland

Faculty, Staff and Students Publications

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest …

Outcomes Of Subsequent Antilymphoma Therapies After Second-Line Axicabtagene Ciloleucel Or Standard Of Care In Zuma-7, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

The optimal management of patients with relapsed/refractory large B-cell lymphoma (LBCL) after disease progression or lack of response to second-line (2L) therapy remains unclear. Here, we report outcomes among patients who received subsequent antilymphoma therapy per investigator discretion separately by their randomized 2L arm in ZUMA-7, namely axicabtagene ciloleucel (axi-cel) vs standard of care (SOC). Progression-free survival (PFS) and overall survival (OS) were calculated from 3L therapy initiation. In the SOC arm, 127 of 179 randomized patients (71%) received 3L therapy. Median PFS among those who received 3L cellular immunotherapy (n = 68) vs those who did not (n = …

Limited Nerve Regeneration Across Acellular Nerve Allografts (Anas) Coincides With Changes In Blood Vessel Morphology And The Development Of A Pro-Inflammatory Microenvironment, Jesús A Acevedo Cintrón, Daniel A Hunter, Lauren Schellhardt, Deng Pan, Susan E Mackinnon, Matthew D Wood

2020-Current year OA Pubs

The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across …

Tenovin-1, A Selective Sirt1/2 Inhibitor, Attenuates High-Fat Diet-Induced Hepatic Fibrosis Via Inhibition Of Hsc Activation In Zdf Rats, Swati Sharma, Sreevarsha Gali, Amit Kundu, Jae Hyeon Park, Jae-Sung Kim, Hyung Sik Kim

2020-Current year OA Pubs

Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-β1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 …

Echocardiogram By Apical-Subcostal Protocol In Prone Position During Invasive Mechanical Ventilation In Cardiovascular Intensive Care Unit, César Del Castillo, Fernando Verdugo, Franco Appiani, Francisca Yáñez, Camila Bontá, Carlos Torres-Herrera, Angela Garcia, Zorba Blázquez-Bermejo, Javier Castrodeza, Daniel Requena, Andreina Rodríguez, Arquimedes Silvio, Agustín Gatica, Arnulfo Begazo, Mario Alfaro

Faculty, Staff and Students Publications

AIMS: To evaluate the feasibility of a transthoracic echocardiogram using an apical-subcostal protocol in invasive mechanical ventilation (IMV) and prone position.

METHODS: Prospective study of adults who required a prone position during IMV. A pillow was placed only under the left hemithorax in the prone position to elevate and ease the apical and subcostal windows. A critical care cardiologist (prone group) acquired and evaluated the images using the apical-subcostal protocol. Besides, we used ambulatory echocardiograms performed as a comparative group (supine group).

RESULTS: 86 patients were included, 43 in the prone and 43 in the supine. In the prone group, …

Folate As A Potential Treatment For Lethal Ventricular Arrhythmias In Tango2-Deficiency Disorder, Weiyi Xu, Yingqiong Cao, Sara B Stephens, Maria Jose Arredondo, Yifan Chen, William Perez, Liang Sun, Andy C Yu, Jean J Kim, Seema R Lalani, Na Li, Frank T Horrigan, Francisco Altamirano, Xander Ht Wehrens, Christina Y Miyake, Lilei Zhang

Faculty, Staff and Students Publications

TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac arrhythmias are recalcitrant to standard antiarrhythmic medications and constitute the leading cause of death. Disease modeling for TDD has been primarily carried out using human dermal fibroblast and, more recently, in Drosophila by multiple research groups. No human cardiomyocyte system has been reported, which greatly hinders the investigation and understanding of TDD-associated arrhythmias. Here, we established potentially novel patient-derived induced pluripotent stem cell differentiated cardiomyocyte (iPSC-CM) models that recapitulate key electrophysiological abnormalities in TDD. These electrophysiological abnormalities were rescued in iPSC-CMs …

Development Of Primary Osteoarthritis During Aging In Genetically Diverse Um-Het3 Mice., Sher Bahadur Poudel, Ryan R Ruff, Gozde Yildirim, Richard A Miller, David E Harrison, Randy Strong, Thorsten Kirsch, Shoshana Yakar

Faculty Research 2024

BACKGROUND: Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, including degeneration of the articular cartilage, alterations in subchondral bone (SCB) morphology, and inflammation of the synovium.

METHODS: We investigated the prevalence of primary OA in aged, genetically diverse UM-HET3 mice. Articular cartilage (AC) integrity and SCB morphology were assessed in 182 knee joints of 22-25 months old mice using the Osteoarthritis Research Society International (OARSI) scoring system and micro-CT, respectively. Additionally, we explored the …

Vertebral Hu Value And The Pectoral Muscle Index Based On Chest Ct Can Be Used To Opportunistically Screen For Osteoporosis, Xiong-Yi Wang, Sheng Pan, Wei-Feng Liu, Yi-Ke Wang, Si-Min Yun, You-Jia Xu

Faculty, Staff and Student Publications

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment.

METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The …

Impact Of Risk-Based Therapy On Late Morbidity And Mortality In Neuroblastoma Survivors: A Report From The Childhood Cancer Survivor Study, Danielle Novetsky Friedman, Pamela J Goodman, Wendy M Leisenring, Lisa R Diller, Susan L Cohn, Rebecca M Howell, Susan A Smith, Emily S Tonorezos, Suzanne L Wolden, Joseph P Neglia, Kirsten K Ness, Todd M Gibson, Paul C Nathan, Lucie M Turcotte, Brent R Weil, Leslie L Robison, Kevin C Oeffinger, Gregory T Armstrong, Charles A Sklar, Tara O Henderson

Faculty, Staff and Student Publications

Background: Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described.

Methods: Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. …

Relationship Between Sex Biases In Gene Expression And Sex Biases In Autism And Alzheimer's Disease, Stuart B Fass, Bernard Mulvey, Rebecca Chase, Wei Yang, Din Selmanovic, Sneha M Chaturvedi, Eric Tycksen, Lauren A Weiss, Joseph D Dougherty

2020-Current year OA Pubs

BACKGROUND: Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions.

METHODS: In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks.

RESULTS: We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune …

Long-Term Survival Follow-Up For Tebentafusp In Previously Treated Metastatic Uveal Melanoma, Joseph Sacco, Richard Carvajal, Marcus Butler, Alexander N Shoushtari, Jessica Hassel, Alexandra Ikeguchi, Leonel Hernandez-Aya, Paul Nathan, Omid Hamid, Josep Piulats, Matthew Rioth, Douglas B Johnson, Jason Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Chris Holland, Takami Sato

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.

PATIENTS AND METHODS: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. …

Relationship Between Youth Cardiometabolic Health And Physical Activity In Medical Records., Bethany Forseth, Janelle R. Noel-Macdonnell Phd, Sarah Hampl, Jordan A. Carlson, Kelsee Halpin, Ann M. Davis, Tarin Phillips, Robin P. Shook

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Thers is limited research examining modifiable cardiometabolic risk factors with a single-item health behavior question obtained during a clinic visit. Such information could support clinicians in identifying patients at risk for adverse cardiometabolic health. We investigated if children meeting physical activity or screen time recommendations, collected during clinic visits, have better cardiometabolic health than children not meeting recommendations. We hypothesized that children meeting either recommendation would have fewer cardiometabolic risk factors.

METHODS AND FINDINGS: This cross-sectional study used data from electronic medical records (EMRs) between January 1, 2013 through December 30, 2017 from children (2-18 years) with a well …

Phase 1, Randomized, Rater And Participant Blinded Placebo-Controlled Study Of The Safety, Reactogenicity, Tolerability And Immunogenicity Of H1n1 Influenza Vaccine Delivered By Vx-103 (A Mimix Microneedle Patch [Map] System) In Healthy Adult, Naveen Garg, Guy Tellier, Noah Vale, Jon Kluge, Jonathan L Portman, Anna Markowska, Lynda Tussey

Faculty, Staff and Student Publications

BACKGROUND: The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza.

METHODOLOGY: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 μg or 7.5 μg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a …

Etiological Involvement Of Kcnd1 Variants In An X-Linked Neurodevelopmental Disorder With Variable Expressivity., Tassja Kalm, Claudia Schob, Hanna Völler, Thatjana Gardeitchik, Christian Gilissen, Rolph Pfundt, Chiara Klöckner, Konrad Platzer, Annick Klabunde-Cherwon, Markus Ries, Steffen Syrbe, Francesca Beccaria, Francesca Madia, Marcello Scala, Federico Zara, Floris Hofstede, Marleen E H Simon, Richard H. Van Jaarsveld, Renske Oegema, Koen L I Van Gassen, Sjoerd J B Holwerda, Tahsin Stefan Barakat, Arjan Bouman, Marjon Van Slegtenhorst, Sara Álvarez, Alberto Fernández-Jaén, Javier Porta, Andrea Accogli, Margherita Maria Mancardi, Pasquale Striano, Michele Iacomino, Jong-Hee Chae, Sesong Jang, Soo Y. Kim, David Chitayat, Saadet Mercimek-Andrews, Christel Depienne, Antje Kampmeier, Alma Kuechler, Harald Surowy, Enrico Silvio Bertini, Francesca Clementina Radio, Cecilia Mancini, Simone Pizzi, Marco Tartaglia, Lucas Gauthier, David Genevieve, Mylène Tharreau, Noy Azoulay, Gal Zaks-Hoffer, Nesia K. Gilad, Naama Orenstein, Geneviève Bernard, Isabelle Thiffault, Jonas Denecke, Theresia Herget, Fanny Kortüm, Christian Kubisch, Robert Bähring, Stefan Kindler

Manuscripts, Articles, Book Chapters and Other Papers

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for …

Effects Of Protein-Enriched Nutritional Support On Skeletal Muscle Mass And Rehabilitative Outcomes In Brain Tumor Patients: A Randomized Controlled Trial, Kye Hee Cho, Eun Young Han, Min Kyu Jung, Chang Moo Kang, Ji Cheol Shin, Sang Hee Im

Faculty, Staff and Student Publications

Patients with brain tumors require extensive and prolonged rehabilitation efforts as they suffer from lesion-induced motor weakness as well as treatment-related side effects, often leading to a significant decline in function. Protein supplements have shown positive effects on promoting muscle strength and physical performance in various tumor etiologies. However, reports on their effects specifically in brain tumor patients remain scarce. This study aims to investigate the feasibility and efficacy of protein supplements in enhancing rehabilitative outcomes via muscle strengthening and functional gain in brain tumor patients with neurological demise. Sixty brain tumor patients were randomly assigned to either a protein …

A Multilevel Intervention To Promote Hpv Vaccination Among Young Adults In Texas: Protocol For A Randomized Controlled Trial, Qian Lu, Lenna Dawkins-Moultin, Dalnim Cho, Naomi Q P Tan, Suellen Hopfer, Yisheng Li, Lois Ramondetta, Yusi Xu, Di Lun, Minxing Chen

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.

METHODS: The study uses a two by three factorial design. …

Piga Mutations And Glycosylphosphatidylinositol Anchor Dysregulation In Polyposis-Associated Duodenal Tumorigenesis, Elena Meuser, Kyle Chang, Angharad Walters, Joanna J Hurley, Hannah D West, Iain Perry, Matthew Mort, Laura Reyes-Uribe, Rebekah Truscott, Nicholas Jones, Rachel Lawrence, Gareth Jenkins, Peter Giles, Sunil Dolwani, Bilal Al-Sarireh, Neil Hawkes, Emma Short, Geraint T Williams, Melissa W Taggart, Kim Luetchford, Patrick M Lynch, Diantha Terlouw, Maartje Nielsen, Sarah-Jane Walton, Andrew Latchford, Susan K Clark, Julian R Sampson, Eduardo Vilar, Laura E Thomas

Faculty, Staff and Student Publications

The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of …

Teen Pregnancy Involvement Among African, Caribbean And Black Adolescent Boys And Girls: A Scoping Review Protocol, Emmanuela Ojukwu, Eunice Bawafaa, Emily Mckay, Harsimran Grewal, Sara Afsah, Shivangi Singh, Elizabeth Saewyc

Faculty, Staff and Student Publications

OBJECTIVES: This study aims to investigate the incidence, associated factors and interventions to address teen pregnancy involvement (TPI) among African, Caribbean and Black (ACB) adolescents in North America.

DESIGN: We conducted a scoping review of the literature, guided by the social-ecological model.

DATA SOURCES: Studies were retrieved from databases such as Ovid Medline, Ovid Embase, CINAHL, CAB Direct and Google Scholar and imported into COVIDENCE for screening.

ELIGIBILITY CRITERIA: The Joanna Briggs Institute scoping reviews protocol guided the establishment of eligibility criteria. Included studies focused on rates, associated factors and interventions related to TPI among ACB boys and girls aged …

Secure Messaging And Telephone Use For Clinician-To-Clinician Communication, Sunny S Lou, Daphne Lew, Laura R Baratta, Elise Eiden, Christine A Sinsky, Thomas Kannampallil

2020-Current year OA Pubs

No abstract provided.

Delays To Antibiotics In The Emergency Department And Risk Of Mortality In Children With Sepsis., Roni D. Lane, Troy Richardson, Halden F. Scott, Raina M. Paul, Fran Balamuth, Matthew A. Eisenberg, Ruth Riggs, W Charles Huskins, Christopher M. Horvat, Grant E. Keeney, Leslie Hueschen, Justin M. Lockwood, Vishal Gunnala, Bryan P. Mckee, Nikhil Patankar, Venessa Lynn Pinto, Amanda M. Sebring, Matthew P. Sharron, Jennifer Treseler, Jennifer J. Wilkes, Jennifer K. Workman

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes.

OBJECTIVE: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour …

Development Of A Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration Of Imaging Features, Hop S Tran Cao, Russell G Witt, Khaled M Elsayes, Ali A Baiomy, Lianchun Xiao, Sarah Palmquist, Sunyoung S Lee, Yehia I Mohamed, Armeen Mahvash, Ching-Wei D Tzeng, Yun Shin Chun, Eugene Jon Koay, Asif Rashid, Manal M Hassan, James C Yao, Jean-Nicolas Vauthey, Ahmed O Kaseb

Faculty, Staff and Student Publications

Background: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems.

Methods: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of …

Methylthioadenosine Phosphorylase Genomic Loss In Advanced Gastrointestinal Cancers, Natalie Y L Ngoi, Tin-Yun Tang, Catia F Gaspar, Dean C Pavlick, Gregory M Buchold, Emma L Scholefield, Vamsi Parimi, Richard S P Huang, Tyler Janovitz, Natalie Danziger, Mia A Levy, Shubham Pant, Anaemy Danner De Armas, David Kumpula, Jeffrey S Ross, Milind Javle, Jordi Rodon Ahnert

Faculty, Staff and Student Publications

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.

MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI …

Delays To Antibiotics In The Emergency Department And Risk Of Mortality In Children With Sepsis, Roni D Lane, Troy Richardson, Halden F Scott, Raina M Paul, Fran Balamuth, Matthew A Eisenberg, Ruth Riggs, W Charles Huskins, Christopher M Horvat, Grant E Keeney, Leslie A Hueschen, Justin M Lockwood, Vishal Gunnala, Bryan P Mckee, Nikhil Patankar, Venessa Lynn Pinto, Amanda M Sebring, Matthew P Sharron, Jennifer Treseler, Jennifer J Wilkes, Jennifer K Workman

Faculty, Staff and Students Publications

IMPORTANCE: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes.

OBJECTIVE: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour …

Ketamine Vs Electroconvulsive Therapy For Treatment-Resistant Depression: A Secondary Analysis Of A Randomized Clinical Trial, Manish Kumar Jha, Samuel T Wilkinson, Kamini Krishnan, Katherine A Collins, Gerard Sanacora, James Murrough, Fernando Goes, Murat Altinay, Amy Aloysi, Ali Asghar-Ali, Brian Barnett, Lee Chang, Sara Costi, Donald Malone, Sina Nikayin, Steven E Nissen, Robert Ostroff, Irving Reti, Kathy Wolski, Dong Wang, Bo Hu, Sanjay J Mathew, Amit Anand

Staff and Researcher Publications

IMPORTANCE: The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD.

OBJECTIVE: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were …

Real-World Multiple Myeloma Risk Factors And Outcomes By Non-Hispanic Black/African American And Non- Hispanic White Race/Ethnicity In The United States., Tondre Buck, Monique A Hartley-Brown, Yvonne A Efebera, Carter P Milner, Jeffrey A Zonder, Paul G Richardson, Taylor Salinardi, Megan S Rice

Oncology Articles

Examination of the impact of race and ethnicity on multiple myeloma (MM) outcomes has yielded inconsistent results. This retrospective, real-world (RW) study describes patient, disease, and treatment characteristics (and associations with survival outcomes) among newly diagnosed MM patients of non-Hispanic (NH) Black/African American (AA) and NH White race/ethnicity in the US. We included patients from the nationwide Flatiron Health electronic health record-derived de-identified database who initiated first line of therapy (LOT) for MM between January 1, 2016 and March 31, 2022. Of 4,614 patients in our study cohort, 23.3% were NH Black/AA. Non-Hispanic Black/AA patients were younger than NH White …

Rewiring The Sex-Determination Pathway During The Evolution Of Self-Fertility., Yongquan Shen, Shin-Yi Lin, Jonathan Harbin, Richa Amin, Allison Vassalotti, Joseph Romanowski, Emily Schmidt, Alexis Tierney, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show …

Differential Expression Of Wnt5a Long And Short Isoforms In Non-Muscle-Invasive Bladder Urothelial Carcinoma., Amy M Strope, Cody Phillips, Sabin Khadgi, Scott A Jenkinson, Karen T Coschigano, Ramiro Malgor

Oncology Articles

Wnt ligands belong to a family of secreted glycoproteins in which binding to a range of receptors/co-receptors activates several intracellular pathways. WNT5A, a member of the Wnt family, is classified as a non-canonical Wnt whose activation triggers planar cell polarity (PCP) and Ca+2 downstream pathways. Aberrant expression of WNT5A has been shown to play both protective and harmful roles in an array of conditions, such as inflammatory disease and cancer. In the present study, using histological, immunohistochemical, and molecular methods, we investigated the expression of two isoforms of WNT5A, WNT5A-Short (WNT5A-S) and WNT5A-Long (WNT5A-L) in bladder urothelial carcinoma (UC). Three …

Post Hoc Analysis Of Daratumumab Plus Lenalidomide, Bortezomib And Dexamethasone In Black Patients From Final Data Of The Griffin Study., Ajay K Nooka, Jonathan L Kaufman, Cesar Rodriguez, Andrzej Jakubowiak, Yvonne Efebera, Brandi Reeves, Tanya M Wildes, Sarah A Holstein, Larry D Anderson, Ashraf Badros, Leyla Shune, Ajai Chari, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Oncology Articles

Due in part to racial disparities and underrepresentation in clinical studies, optimal therapies for Black patients with multiple myeloma remain undefined. This final analysis of GRIFFIN by race showed that the addition of daratumumab (D) to lenalidomide/bortezomib/dexamethasone (RVd) provides clinical benefit among both Black and White transplant-eligible newly diagnosed patients compared with RVd alone. However, Black patients were more likely to discontinue ≥1 drug due to treatment-emergent adverse events. In summary, these findings suggest a benefit of D-RVd front-line therapy among Black and White patients and underscore the importance of equitable treatment access for all patients.

Whamm Functions In Kidney Reabsorption And Polymerizes Actin To Promote Autophagosomal Membrane Closure And Cargo Sequestration., Alyssa M Coulter, Valerie Cortés, Corey J Theodore, Rachel E Cianciolo, Ron Korstanje, Kenneth G Campellone

Faculty Research 2024

The actin cytoskeleton is essential for many functions of eukaryotic cells, but the factors that nucleate actin assembly are not well understood at the organismal level or in the context of disease. To explore the function of the actin nucleation factor WHAMM in mice, we examined how Whamm inactivation impacts kidney physiology and cellular proteostasis. We show that male WHAMM knockout mice excrete elevated levels of albumin, glucose, phosphate, and amino acids, and display structural abnormalities of the kidney proximal tu- bule, suggesting that WHAMM activity is important for nutrient reabsorption. In kidney tis- sue, the loss of WHAMM results …

Metabolomics Profiling Reveals Distinct, Sex-Specific Signatures In Serum And Brain Metabolomes In Mouse Models Of Alzheimer's Disease., Ravi S Pandey, Mattias Arnold, Richa Batra, Jan Krumsiek, Kevin P Kotredes, Dylan Garceau, Harriet M. Jackson, Michael Sasner, Gareth R Howell, Rima Kaddurah-Daouk, Gregory W. Carter

Faculty Research 2024

INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation.

METHODS: We investigated differences in serum and brain metabolites between the early-onset 5XFAD and late-onset LOAD1 (APOE4.Trem2*R47H) mouse models of AD to C57BL/6J controls at 6 months of age.

RESULTS: We identified sex differences for several classes of metabolites, such as glycerophospholipids, sphingolipids, and amino acids. Metabolic signatures were notably different between brain and serum in both mouse models. The 5XFAD mice exhibited stronger differences in brain metabolites, whereas LOAD1 mice showed more …