Medical Specialties Commons^™

Failure Of Pavlik Harness Treatment In Infants Under 6 Months Old With Dislocated Hips: Short- And Intermediate-Term Results Of Subsequent Treatment Modalities, Ahmet Imerci, Mihir M. Thacker, James Richard Bowen

Jefferson Hospital Staff Papers and Presentations

OBJECTIVE: This study aimed to determine the short- and medium-term outcomes of hip dislocation in infants who failed Pavlik harness therapy and were subsequently treated with brace, closed reduction (CR) or open reduction (OR) before 6 months of age.

METHODS: Fifty infants (66 hip dislocations) who failed Pavlik harness therapy between 2000 and 2018 and were treated with a rigid abduction brace or undergoing a CR or OR/cast were evaluated. All demographic data obtained from the medical system, developments and complications during the follow-up and treatment process were recorded and evaluated.

RESULTS: Fifty infants (66 hips) with dislocated hips failed …

Pediatric Obesity In The United States: Age–Period–Cohort Analysis, Ashley W. Kranjac, Dinko Kranjac, Roxanne I. Aguilera

Sociology Faculty Articles and Research

The rates of obesity among American children aged 2–5 years has reached a historic high. It is crucial to identify the putative sources of population-level increases in obesity prevalence among preschool-aged children because early childhood is a critical window for obesity prevention and thus reduction of future incidence. We used the National Health and Nutrition Examination Survey data and hierarchical age–period–cohort analysis to examine lifecycle (i.e., age), historical (i.e., period), and generational (i.e., cohort) distribution of age- and sex-specific body mass index z-scores (zBMI) among 2–5-year-olds in the U.S. from 1999 to 2018. Our current findings indicate that period effects, …

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 …

Recurrent Upper Gastrointestinal Bleeding Due To Radiation-Induced Hemorrhagic Gastroduodenal Ectasia: A Review Of Current Treatment Options For Radiation-Induced Gastric Injury, Simone Jarrett, Rushi Kaushik Talati, Johann Hasbun, Wenqing Cao, Scott Smukalla

Einstein Health Papers

INTRODUCTION: Acute upper gastrointestinal bleeding is one of the most common medical emergencies that present to the hospital, and delineating the underlying etiology is essential to provide adequate definitive treatment. The purpose of this case report was to review the diagnosis and treatment of a rare complication known as radiation-induced hemorrhagic gastritis (RIHG) that can occur in patients with prior radiation exposure. The motivation for this study arose from the identification of a case within our institution.

CASE PRESENTATION: The study involved a review of the diagnosis and management of a patient who presented with anemia and recurrent episodes of …

Investigating The Association Between Metabolic Syndrome Conditions And Perinatal Mental Illness: A National Administrative Claims Study, Karishma Chhabria, Sudhakar Selvaraj, Jerrie Refuerzo, Chau Truong, Cecilia Ganduglia Cazaban

Faculty, Staff and Student Publications

BACKGROUND: Although the association between mental disorder and metabolic syndrome as a bidirectional relationship has been demonstrated, there is little knowledge of the cumulative and individual effect of these conditions on peripartum mental health. This study aims to investigate the association between metabolic syndrome conditions (MetS-C) and maternal mental illness in the perinatal period, while exploring time to incident mental disorder diagnosis in postpartum women.

METHODS: This observational study identified perinatal women continuously enrolled 1 year prior to and 1 year post-delivery using Optum's de-identified Clinformatics® Data Mart Database (CDM) from 2014 to 2019 with MetS-C i.e. obesity, diabetes, high …

Social Determinants Of Health And Other Predictors In Initiation Of Treatment With Cdk4/6 Inhibitors For Hr+/Her2- Metastatic Breast Cancer, Ravi K Goyal, Sean D Candrilli, Susan Abughosh, Hua Chen, Holly M Holmes, Michael L Johnson

Faculty, Staff and Student Publications

In hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC), cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) have replaced endocrine therapy alone as the standard of care; however, several barriers to treatment initiation still exist. We assessed social determinants of health (SDOH) and other factors associated with the initiation of CDK4/6i for HR+/HER2- MBC in the Medicare population. Using a retrospective cohort design, patients aged ≥65 years and diagnosed during 2015-2017 were selected from the SEER-Medicare database. Time from MBC diagnosis to first CDK4/6i initiation was the study outcome. The effect of SDOH measures and other predictors on 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. …

Association Of Differential Censoring With Survival And Suboptimal Control Arms Among Oncology Clinical Trials, Eric J Hsu, Timothy A Lin, Dor R Dabush, Zachary Mccaw, Alex Koong, Christine Lin, Joseph Abi Jaoude, Roshal Patel, Ramez Kouzy, Molly B El Alam, Sonal Noticewala, Yumeng Yang, Alexander D Sherry, Clifton D Fuller, Charles R Thomas, Chad Tang, Pavlos Msaouel, Prajnan Das, Bo Huang, Lu Tian, Ryan Sun, J Jack Lee, Tomer Meirson, Ethan B Ludmir

Faculty, Staff and Student Publications

Differential censoring, which refers to censoring imbalance between treatment arms, may bias the interpretation of survival outcomes in clinical trials. In 146 phase III oncology trials with statistically significant time-to-event surrogate primary endpoints, we evaluated the association between differential censoring in the surrogate primary endpoints, control arm adequacy, and the subsequent statistical significance of overall survival results. Twenty-four (16%) trials exhibited differential censoring that favored the control arm, whereas 15 (10%) exhibited differential censoring that favored the experimental arm. Positive overall survival was more common in control arm differential censoring trials (63%) than in trials without differential censoring (37%) or …

Defining The Kras- And Erk-Dependent Transcriptome In Kras-Mutant Cancers, Jeffrey A Klomp, Jennifer E Klomp, Clint A Stalnecker, Kirsten L Bryant, A Cole Edwards, Kristina Drizyte-Miller, Priya S Hibshman, J Nathaniel Diehl, Ye S Lee, Alexis J Morales, Khalilah E Taylor, Sen Peng, Nhan L Tran, Laura E Herring, Alex W Prevatte, Natalie K Barker, Laura D Hover, Jill Hallin, Alexey Sorokin, Preeti Marie Kanikarla, Saikat Chowdhury, Oluwadara Coker, Hey Min Lee, Craig M Goodwin, Prson Gautam, Peter Olson, James G Christensen, John P Shen, Scott Kopetz, Lee M Graves, Kian-Huat Lim, Andrea Wang-Gillam, Krister Wennerberg, Adrienne D Cox, Channing J Der

Faculty, Staff and Student Publications

How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and ERK-dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges significantly from the frequently cited Hallmark KRAS signaling gene signature, is driven predominantly through the ERK mitogen-activated protein kinase (MAPK) cascade, and accurately reflects KRAS- and ERK-regulated gene transcription in KRAS-mutant cancer patients. Integration with our ERK-regulated phospho- and total proteome highlights ERK deregulation of the anaphase promoting complex/cyclosome and other components of the cell cycle machinery as …

Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes, Heather M Sonnemann, Barbara Pazdrak, Barbara Nassif, Yimo Sun, Lama Elzohary, Amjad H Talukder, Arjun S Katailiha, Krishna Bhat, Gregory Lizée

Faculty, Staff and Student Publications

INTRODUCTION: Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain-containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists.

METHODS: The aim of this study was to …

Improved Liver Disease Prediction From Clinical Data Through An Evaluation Of Ensemble Learning Approaches, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

PURPOSE: Liver disease causes two million deaths annually, accounting for 4% of all deaths globally. Prediction or early detection of the disease via machine learning algorithms on large clinical data have become promising and potentially powerful, but such methods often have some limitations due to the complexity of the data. In this regard, ensemble learning has shown promising results. There is an urgent need to evaluate different algorithms and then suggest a robust ensemble algorithm in liver disease prediction.

METHOD: Three ensemble approaches with nine algorithms are evaluated on a large dataset of liver patients comprising 30,691 samples with 11 …

How Context Links To Best Practice Use In Long-Term Care Homes: A Mixed Methods Study, Yinfei Duan, Jing Wang, Holly J Lanham, Whitney Berta, Stephanie A Chamberlain, Matthias Hoben, Katharina Choroschun, Alba Iaconi, Yuting Song, Janelle Santos Perez, Shovana Shrestha, Anna Beeber, Ruth A Anderson, Leslie Hayduk, Greta G Cummings, Peter G Norton, Carole A Estabrooks

Faculty, Staff and Student Publications

Background: Context (work environment) plays a crucial role in implementing evidence-based best practices within health care settings. Context is multi-faceted and its complex relationship with best practice use by care aides in long-term care (LTC) homes are understudied. This study used an innovative approach to investigate how context elements interrelate and influence best practice use by LTC care aides.

Methods: In this secondary analysis study, we combined coincidence analysis (a configurational comparative method) and qualitative analysis to examine data collected through the Translating Research in Elder Care (TREC) program. Coincidence analysis of clinical microsystem (care unit)-level data aggregated from a …

Mri Measurement Of Cerebral Perfusion In Severe Congenital Heart Disease: Just The First Step, Kevin B. Kilgallon, Ira M. Cheifetz

Faculty Scholarship

Two questions on the mind of many parents of children with complex congenital heart disease (CHD) are: Will my child survive? And, how will their life be affected? As diagnostic procedures, along with medical and surgical treatments, for these infants have improved over the recent decades, more and more of these children are surviving into adolescence and adulthood. Despite these advances in care, children with complex CHD are at higher risk of neurodevelopmental disability (NDD) and decreased quality of life (QOL) compared to their peers without CHD.1,2

Seroprevalence Of Anti-Sars-Cov-2 Igg Antibodies In Healthcare Personnel In El Salvador Prior To Vaccination Campaigns, José Elías Aguilar Ramírez, Adrianna Maliga, Allison Stewart, Allison Lino, José Eduardo Oliva, Xochitl Sandoval, Emily Zielinski-Gutierrez, Rafael Chacon-Fuentes, Parminder S Suchdev, Susana Zelaya, Mario Sánchez, Delmy Lisseth Recinos, Beatriz López, Ella Hawes, Julie Liu, Shannon E Ronca, Sarah M Gunter, Kristy O Murray, Rhina Domínguez

Faculty, Staff and Students Publications

COVID-19, caused by the SARS-CoV-2 virus, is a highly pathogenic emerging infectious disease. Healthcare personnel (HCP) are presumably at higher risk of acquiring emerging infections because of occupational exposure. The prevalence of COVID-19 in HCP is unknown, particularly in low- to middle-income countries like El Salvador. The goal of this study was to determine the seroprevalence of anti-SARS-CoV-2 antibodies among HCP in El Salvador just prior to vaccine rollout in March 2021. We evaluated 2176 participants from a nationally representative sample of national healthcare institutions. We found 40.4% (n = 880) of the study participants were seropositive for anti-spike …

Cost-Effectiveness And Threshold Analysis Of Deep Brain Stimulation Vs Treatment-As-Usual For Treatment-Resistant Depression, Katherine E Kabotyanski, Ricardo A Najera, Garrett P Banks, Himanshu Sharma, Nicole R Provenza, Benjamin Y Hayden, Sanjay J Mathew, Sameer A Sheth

Faculty, Staff and Students Publications

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare …

Microvascular Reconstruction Of Midface Osteoradionecrosis, Larissa Sweeny, Neeraja Konuthula, Ryan Jackson, Mark K. Wax, Joseph M. Curry, Sara Yang, Dev Amin, Anne C. Kane, Steve B. Cannady, Kendall Tasche, Michael Dileo, Daniel Lander, Alexandra E. Kejner, Patrik Pipkorn

School of Medicine Faculty Publications

Background: Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes for this rare patient population. Methods: Retrospective multi-institutional review of FF reconstruction for midface ORN (2005–2022; n = 54). Results: The FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p …

A Modified Switching Procedure From Temporary To Tunneled Central Venous Dialysis Catheters, Johannes Eberhard, Constantin Bedau, Andrew Genius Chapple, Julia Klein, Christoph Reissfelder, Anna Isabelle Kaelsch, Andreas Lutz Heinrich Gerken, Sebastian Zach, Kay Schwenke

School of Medicine Faculty Publications

Background: Tunneled central venous catheters are commonly used for dialysis in patients without a functional permanent vascular access. In an emergent setting, a non-tunneled, temporary central venous catheter is often placed for immediate dialysis. The most critical step in the catheter insertion is venipuncture, which is often a major cause for longer intervention times and procedure-related adverse events. To avoid this critical step when placing a more permanent tunneled catheter, an exchange over a previously placed temporary one can be considered. In this paper, we present a modified switching approach with a separate access site. Methods: In this retrospective analysis …

Editorial: Management Of Pji/Ssi After Joint Arthroplasty, Li Cao, Javad Parvizi, Xiaogang Zhang, Xianzhe Liu, Wierd Zijlstra, Saad Tarabichi

Rothman Institute Papers

The management of periprosthetic joint infection (PJI) and surgical site infection (SSI) after joint arthroplasty poses a major challenge in orthopedic surgery. This Editorial provides an overview of the studies published in the special issue "Management of PJI/SSI after Joint Arthroplasty", summarizing the key findings from these studies, which cover a wide range of topics, including stringent preventive strategies, comprehensive diagnostic methods, and personalized treatment modalities. The authors concluded the editorial with their perspectives regarding the status quo of research in this field and future directions for research, such as the development of novel antibiotics, biofilm research, patient-specific risk factors, …

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 …

Management Of Fibromyalgia: An Update, Eric A Jones, Farrah Asaad, Nishil Patel, Esha Jain, Alaa Abd-Elsayed

Faculty, Staff and Student Publications

Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review, we aim to contribute to the evolving understanding and management of fibromyalgia, offering insights into the diverse tools available to improve the lives of those affected by this challenging condition. Management begins with educating patients to ultimately relieve them of unnecessary testing and provide reassurance. Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, …

Integrative Multi-Omics Analyses To Identify The Genetic And Functional Mechanisms Underlying Ovarian Cancer Risk Regions, Eileen O Dareng, Simon G Coetzee, Jonathan P Tyrer, Pei-Chen Peng, Will Rosenow, Stephanie Chen, Brian D Davis, Felipe Segato Dezem, Ji-Heui Seo, Robbin Nameki, Alberto L Reyes, Katja K H Aben, Hoda Anton-Culver, Natalia N Antonenkova, Gerasimos Aravantinos, Elisa V Bandera, Laura E Beane Freeman, Matthias W Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, Marcus Q Bernardini, Line Bjorge, Amanda Black, Natalia V Bogdanova, Kelly L Bolton, James D Brenton, Agnieszka Budzilowska, Ralf Butzow, Hui Cai, Ian Campbell, Rikki Cannioto, Jenny Chang-Claude, Stephen J Chanock, Kexin Chen, Georgia Chenevix-Trench, Aocs Group, Yoke-Eng Chiew, Linda S Cook, Anna Defazio, Joe Dennis, Jennifer A Doherty, Thilo Dörk, Andreas Du Bois, Matthias Dürst, Diana M Eccles, Gabrielle Ene, Peter A Fasching, James M Flanagan, Renée T Fortner, Florentia Fostira, Aleksandra Gentry-Maharaj, Graham G Giles, Marc T Goodman, Jacek Gronwald, Christopher A Haiman, Niclas Håkansson, Florian Heitz, Michelle A T Hildebrandt, Estrid Høgdall, Claus K Høgdall, Ruea-Yea Huang, Allan Jensen, Michael E Jones, Daehee Kang, Beth Y Karlan, Anthony N Karnezis, Linda E Kelemen, Catherine J Kennedy, Elza K Khusnutdinova, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Marilyne Labrie, Diether Lambrechts, Melissa C Larson, Nhu D Le, Jenny Lester, Lian Li, Jan Lubiński, Michael Lush, Jeffrey R Marks, Keitaro Matsuo, Taymaa May, John R Mclaughlin, Iain A Mcneish, Usha Menon, Stacey Missmer, Francesmary Modugno, Melissa Moffitt, Alvaro N Monteiro, Kirsten B Moysich, Steven A Narod, Tu Nguyen-Dumont, Kunle Odunsi, Håkan Olsson, N Charlotte Onland-Moret, Sue K Park, Tanja Pejovic, Jennifer B Permuth, Anna Piskorz, Darya Prokofyeva, Marjorie J Riggan, Harvey A Risch, Cristina Rodríguez-Antona, Mary Anne Rossing, Dale P Sandler, V Wendy Setiawan, Kang Shan, Honglin Song, Melissa C Southey, Helen Steed, Rebecca Sutphen, Anthony J Swerdlow, Soo Hwang Teo, Kathryn L Terry, Pamela J Thompson, Liv Cecilie Vestrheim Thomsen, Linda Titus, Britton Trabert, Ruth Travis, Shelley S Tworoger, Ellen Valen, Els Van Nieuwenhuysen, Digna Velez Edwards, Robert A Vierkant, Penelope M Webb, Opal Study Group, Clarice R Weinberg, Rayna Matsuno Weise, Nicolas Wentzensen, Emily White, Stacey J Winham, Alicja Wolk, Yin-Ling Woo, Anna H Wu, Li Yan, Drakoulis Yannoukakos, Nur Zeinomar, Wei Zheng, Argyrios Ziogas, Andrew Berchuck, Ellen L Goode, David G Huntsman, Celeste L Pearce, Susan J Ramus, Thomas A Sellers, Ovarian Cancer Association Consortium (Ocac), Matthew L Freedman, Kate Lawrenson, Joellen M Schildkraut, Dennis Hazelett, Jasmine T Plummer, Siddhartha Kar, Michelle R Jones, Paul D P Pharoah, Simon A Gayther

Faculty, Staff and Student Publications

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value < 5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value < 10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate < 0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.

A Phase 3b, Open-Label, Single-Arm, Multicenter, Expanded-Access Study Of The Safety And Clinical Outcomes Of Stratagraft® Treatment In Adults With Deep Partial-Thickness Thermal Burns, James H. Holmes Iv, Angela L.F. Gibson, Tracee Short, Victor C. Joe, Jeffrey Litt, Joshua Carson, Jeffrey E. Carter, Lucy Wibbenmeyer, Helen Hahn, Janice M. Smiell, Randi Rutan, Richard Wu, Jeffrey W. Shupp

School of Medicine Faculty Publications

Background: A phase 3b, open-label, multicenter, expanded-access study (NCT04123548) evaluated safety and clinical outcomes of StrataGraft treatment in adults with deep partial-thickness thermal burns with intact dermal elements. Methods: Adult patients with 3 % to < 50 % total body surface area burns were treated with a single application of ≤ 1:1 meshed StrataGraft and followed for 24 weeks. Primary endpoint was count and percentage of patients with treatment-emergent adverse events (TEAEs). Secondary endpoints included confirmed wound closure (WC) at Week 12, durable WC at Week 24, time to WC, scar evaluation, and wound infection-related events. Results: Fifty-two patients with 96 treatment sites were enrolled. Pruritus was the most common TEAE (22 patients [42.3 %]). Twenty serious TEAEs occurred in 10 patients (19.2 %); none were related to StrataGraft. There were 4 (7.7 %) deaths (aspiration, myocardial infarction, self-injury, Gram-negative rod sepsis); none were related to StrataGraft. Confirmed WC was achieved by Week 12 in 33 patients (63.5 %; 95 % CI: 50.4–76.5 %) and 69 treatment sites (71.9 %; 95 % CI: 62.9–80.9 %). Durable WC was achieved by Week 24 in 29 patients (55.8 %; 95 % CI: 42.3–69.3 %) and 58 treatment sites (60.4 %; 95 % CI: 50.6–70.2 %). Conclusions: StrataGraft demonstrated clinical benefit. Safety data were consistent with previously reported findings.

Hnrnpm Protects Against The Dsrna-Mediated Interferon Response By Repressing Line-Associated Cryptic Splicing, Rong Zheng, Mikayla Dunlap, Georg O M Bobkov, Carlos Gonzalez-Figueroa, Khushali J Patel, Jingyi Lyu, Samuel E Harvey, Tracey W Chan, Giovanni Quinones-Valdez, Mudra Choudhury, Charlotte A Le Roux, Mason D Bartels, Amy Vuong, Ryan A Flynn, Howard Y Chang, Eric L Van Nostrand, Xinshu Xiao, Chonghui Cheng

Faculty, Staff and Students Publications

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites. hnRNPM preferentially binds at intronic LINEs to repress pseudo splice site usage for cryptic splicing. Remarkably, cryptic exons can generate long dsRNAs through base-pairing of inverted ALU transposable elements interspersed among LINEs and consequently trigger an interferon response, a well-known antiviral defense mechanism. …

Metabolic Regulator Errγ Governs Gastric Stem Cell Differentiation Into Acid-Secreting Parietal Cells, Mahliyah Adkins-Threats, Sumimasa Arimura, Yang-Zhe Huang, Margarita Divenko, Sarah To, Heather Mao, Yongji Zeng, Jenie Y Hwang, Joseph R Burclaff, Shilpa Jain, Jason C Mills

Faculty, Staff and Students Publications

Parietal cells (PCs) produce gastric acid to kill pathogens and aid digestion. Dysregulated PC census is common in disease, yet how PCs differentiate is unclear. Here, we identify the PC progenitors arising from isthmal stem cells, using mouse models and human gastric cells, and show they preferentially express cell-metabolism regulator and orphan nuclear receptor Estrogen-related receptor gamma (Esrrg, encoding ERRγ). Esrrg expression facilitated the tracking of stepwise molecular, cellular, and ultrastructural stages of PC differentiation. Esrrg^P2ACreERT2 lineage tracing revealed Esrrg expression commits progenitors to differentiate into mature PCs. scRNA-seq indicated the earliest Esrrg+ PC progenitors preferentially …

Perturbations In Risk/Reward Decision Making And Frontal Cortical Catecholamine Regulation Induced By Mild Traumatic Brain Injury, Christopher P Knapp, Eleni Papadopoulos, Jessica A Loweth, Ramesh Raghupathi, Stan B Floresco, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and …

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 …

Blocking Oncostatin M Receptor Abrogates Stat3 Mediated Integrin Signaling And Overcomes Chemoresistance In Ovarian Cancer, Anjali Geethadevi, Zhiqiang Ku, Shirng-Wern Tsaih, Deepak Parashar, Ishaque P Kadamberi, Wei Xiong, Hui Deng, Jasmine George, Sudhir Kumar, Sonam Mittal, Ningyan Zhang, Sunila Pradeep, Zhiqiang An, Pradeep Chaluvally-Raghavan

The Brown Foundation: Institute of Molecular Medicine

Chemotherapy such as cisplatin is widely used to treat ovarian cancer either before or after surgical debulking. However, cancer relapse due to chemotherapy resistance is a major challenge in the treatment of ovarian cancer. The underlying mechanisms related to chemotherapy resistance remain largely unclear. Therefore, identification of effective therapeutic strategies is urgently needed to overcome therapy resistance. Transcriptome-based analysis, in vitro studies and functional assays identified that cisplatin-resistant ovarian cancer cells express high levels of OSMR compared to cisplatin sensitive cells. Furthermore, OSMR expression associated with a module of integrin family genes and predominantly linked with integrin αV (ITGAV) and …

Clinical Practice Guidelines For The Care Of Girls And Women With Turner Syndrome, Claus H Gravholt, Niels H Andersen, Sophie Christin-Maitre, Shanlee M Davis, Anthonie Duijnhouwer, Aneta Gawlik, Andrea T Maciel-Guerra, Iris Gutmark-Little, Kathrin Fleischer, David Hong, Karen O Klein, Siddharth K Prakash, Roopa Kanakatti Shankar, David E Sandberg, Theo C J Sas, Anne Skakkebæk, Kirstine Stochholm, Janielle A Van Der Velden, International Turner Syndrome Consensus Group, Philippe F Backeljauw

Faculty, Staff and Student Publications

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health …

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. …

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. …