Medical Specialties Commons^™

Antioxidant Responses And Phytochemical Accumulation In Raphanus Species Sprouts Through Elicitors And Predictive Models Under High Temperature Stress, María-Trinidad Toro, Roberto Fustos-Toribio, Jaime Ortiz, José Becerra, Nelson Zapata, María Dolores López-Belchí

Faculty, Staff and Students Publications

Crop production is being impacted by higher temperatures, which can decrease food yield and pose a threat to human nutrition. In the current study, edible and wild radish sprouts were exposed to elevated growth temperatures along with the exogenous application of various elicitors to activate defense mechanisms. Developmental traits, oxidative damage, glucosinolate and anthocyanin content, and antioxidant capacity were evaluated alongside the development of a predictive model. A combination of four elicitors (citric acid, methyl jasmonate—MeJa, chitosan, and K2SO4) and high temperatures were applied. The accumulation of bioactives was significantly enhanced through the application of two elicitors, K2SO4 and methyl …

Haploinsufficiency Of Zfhx3, Encoding A Key Player In Neuronal Development, Causes Syndromic Intellectual Disability, María Del Rocío Pérez Baca, Eva Z Jacobs, Lies Vantomme, Pontus Leblanc, Elke Bogaert, Annelies Dheedene, Laurenz De Cock, Sadegheh Haghshenas, Aidin Foroutan, Michael A Levy, Jennifer Kerkhof, Haley Mcconkey, Chun-An Chen, Nurit Assia Batzir, Xia Wang, María Palomares, Marieke Carels, Zfhx3 Consortium, Bart Dermaut, Bekim Sadikovic, Björn Menten, Bo Yuan, Sarah Vergult, Bert Callewaert

Faculty, Staff and Students Publications

Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function (LoF) variation in ZFHX3 as a cause for syndromic intellectual disability (ID). ZFHX3 is a zinc-finger homeodomain transcription factor involved in various biological processes, including cell differentiation and tumorigenesis. We describe 42 individuals with protein-truncating variants (PTVs) or (partial) deletions of ZFHX3, exhibiting variable intellectual disability and autism spectrum disorder, recurrent facial features, relative short stature, brachydactyly, and, rarely, cleft palate. ZFHX3 LoF associates with a specific methylation profile in whole blood extracted DNA. Nuclear abundance of ZFHX3 increases during human brain development and …

De Novo Variants In Dennd5b Cause A Neurodevelopmental Disorder, Marcello Scala, Valeria Tomati, Matteo Ferla, Mariateresa Lena, Julie S Cohen, Ali Fatemi, Elly Brokamp, Anna Bican, John A Phillips, Mary E Koziura, Michael Nicouleau, Marlene Rio, Karine Siquier, Nathalie Boddaert, Ilaria Musante, Serena Tamburro, Simona Baldassari, Michele Iacomino, Paolo Scudieri, Undiagnosed Diseases Network, Jill A Rosenfeld, Gary Bellus, Sara Reed, Hind Al Saif, Rossana Sanchez Russo, Matthew B Walsh, Vincent Cantagrel, Amy Crunk, Stefano Gustincich, Sarah M Ruggiero, Mark P Fitzgerald, Ingo Helbig, Pasquale Striano, Mariasavina Severino, Vincenzo Salpietro, Nicoletta Pedemonte, Federico Zara

Faculty, Staff and Students Publications

The Rab family of guanosine triphosphatases (GTPases) includes key regulators of intracellular transport and membrane trafficking targeting specific steps in exocytic, endocytic, and recycling pathways. DENND5B (Rab6-interacting Protein 1B-like protein, R6IP1B) is the longest isoform of DENND5, an evolutionarily conserved DENN domain-containing guanine nucleotide exchange factor (GEF) that is highly expressed in the brain. Through exome sequencing and international matchmaking platforms, we identified five de novo variants in DENND5B in a cohort of five unrelated individuals with neurodevelopmental phenotypes featuring cognitive impairment, dysmorphism, abnormal behavior, variable epilepsy, white matter abnormalities, and cortical gyration defects. We used biochemical assays and confocal …

Early Estimate Of Nirsevimab Effectiveness For Prevention Of Respiratory Syncytial Virus-Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season - New Vaccine Surveillance Network, October 2023-February 2024, Heidi L Moline, Ayzsa Tannis, Ariana P Toepfer, John V Williams, Julie A Boom, Janet A Englund, Natasha B Halasa, Mary Allen Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Marian G Michaels, Leila C Sahni, Eileen J Klein, Laura S Stewart, Elizabeth P Schlaudecker, Peter G Szilagyi, Jennifer E Schuster, Leah Goldstein, Samar Musa, Pedro A Piedra, Danielle M Zerr, Kristina A Betters, Chelsea Rohlfs, Christina Albertin, Dithi Banerjee, Erin R Mckeever, Casey Kalman, Benjamin R Clopper, Meredith L Mcmorrow, Fatimah S Dawood

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants agedtrials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%-90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023-February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, …

Maternal And Perinatal Health Research During Emerging And Ongoing Epidemic Threats: A Landscape Analysis And Expert Consultation, Mercedes Bonet, Magdalena Babinska, Pierre Buekens, Shivaprasad S Goudar, Beate Kampmann, Marian Knight, Dana Meaney-Delman, Smaragda Lamprianou, Flor Muñoz Rivas, Andy Stergachis, Cristiana M Toscano, Joycelyn Bhatia, Sarah Chamberlain, Usman Chaudhry, Jacqueline Mills, Emily Serazin, Hannah Short, Asher Steene, Michael Wahlen, Olufemi T Oladapo

Faculty, Staff and Students Publications

INTRODUCTION: Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner.

METHODS: Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of …

Correction To: Using Phosphoproteomics Data To Understand Cellular Signaling: A Comprehensive Guide To Bioinformatics Resources, Sara R Savage, Bing Zhang

Faculty, Staff and Students Publications

No abstract provided.

Heterogeneity And Overlap In The Continuum Of Linguistic Profile Of Logopenic And Semantic Variants Of Primary Progressive Aphasia: A Profile Analysis Based On Multidimensional Scaling Study, Gaia Chiara Santi, Francesca Conca, Valentina Esposito, Cristina Polito, Silvia Paola Caminiti, Cecilia Boccalini, Carmen Morinelli, Valentina Berti, Salvatore Mazzeo, Valentina Bessi, Alessandra Marcone, Sandro Iannaccone, Se-Kang Kim, Sandro Sorbi, Daniela Perani, Stefano F Cappa, Eleonora Catricalà

Faculty, Staff and Students Publications

BACKGROUND: Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce.

METHODS: Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients' linguistic performance in a shared space. Patients had been studied with [

RESULTS: Patients' profiles were distributed across a …

Geographic Distribution Of Human Infections With Zoonotic Ancylostoma Ceylanicum And Anthropophilic Hookworms In Ecuador: A Retrospective Analysis Of Archived Stool Samples, Dayana Aguilar-Rodríguez, Victor Seco-Hidalgo, Andrea Lopez, Natalia Romero-Sandoval, Manuel Calvopiña, Angel Guevara, Lucy Baldeón, Alejandro Rodríguez, Rojelio Mejia, Thomas B Nutman, William J Sears, Philip J Cooper

Faculty, Staff and Students Publications

Zoonotic human infections with Ancylostoma ceylanicum have recently been reported in the Americas. We used archived human stool samples to study the geographic distribution of human infections with A. ceylanicum and anthropophilic hookworms in different geoclimatic regions (coastal, Andean, and Amazon) of Ecuador. We analyzed retrospectively archived human stool samples from five studies previously screened for hookworm infection by microscopy, of which four included hookworm-positive samples only and one involved hookworm-negative samples to increase geographic distribution of sampling. Stools were analyzed using multi-parallel quantitative polymerase chain reaction (qPCR) assays to detect Necator americanus, Ancylostoma duodenale, A. ceylanicum, Ascaris lumbricoides, Trichuris …

Inactivation Of Adenosine Receptor 2a Suppresses Endothelial-To-Mesenchymal Transition And Inhibits Subretinal Fibrosis In Mice, Qiuhua Yang, Yongfeng Cai, Qian Ma, Albert Xiong, Peishan Xu, Zhidan Zhang, Jiean Xu, Yaqi Zhou, Zhiping Liu, Dingwei Zhao, John Asara, Wei Li, Huidong Shi, Ruth B Caldwell, Akrit Sodhi, Yuqing Huo

Faculty, Staff and Students Publications

Anti–vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A (Adora2a), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury–induced CNV or mice with a deficiency in the …

Correction: Jiménez-Ortigosa Et Al Cryo-Electron Tomography Of Candida Glabrata Plasma Membrane Proteins J Fungi 2021, 7, 120, Cristina Jiménez-Ortigosa, Jennifer Jiang, Muyuan Chen, Xuyuan Kuang, Kelley R Healey, Paul Castellano, Nikpreet Boparai, Steven J Ludtke, David S Perlin, Wei Dai

Faculty, Staff and Students Publications

The authors wish to update the article title to "Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins" [...].

Enhancing Prognostic Power In Multiple Myeloma Using A Plasma Cell Signature Derived From Single-Cell Rna Sequencing, Jian-Rong Li, Shahram Arsang-Jang, Yan Cheng, Fumou Sun, Anita D'Souza, Binod Dhakal, Parameswaran Hari, Quillan Huang, Paul Auer, Yong Li, Raul Urrutia, Fenghuang Zhan, John D Shaughnessy, Siegfried Janz, Jing Dong, Chao Cheng

Faculty, Staff and Students Publications

Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum …

Hippo Cooperates With P53 To Maintain Foregut Homeostasis And Suppress The Malignant Transformation Of Foregut Basal Progenitor Cells, Yu Jiang, Haidi Huang, Jiangying Liu, Dan Luo, Rongzi Mu, Jianghong Yuan, Jihong Lin, Qiyue Chen, Wufan Tao, Ling Yang, Man Zhang, Pingping Zhang, Fengqin Fang, Jianming Xu, Qingqiu Gong, Zhiping Xie, Yongchun Zhang

Faculty, Staff and Students Publications

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of

Consensus-Based Development Of A Pediatric Echocardiography Complexity Score: Design, Rationale, And Results Of A Quality Improvement Collaborative, Sowmya Balasubramanian, Sunkyung Yu, Sarina K Behera, Aarti H Bhat, Joseph A Camarda, Nadine F Choueiter, Pei-Ni Jone, Leo Lopez, Shobha S Natarajan, David A Parra, Anitha Parthiban, Ritu Sachdeva, Shubhika Srivastava, Elif Seda Selamet Tierney

Faculty, Staff and Students Publications

BACKGROUND: The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score.

METHODS AND RESULTS: The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. …

Kidney Function Trajectories And Right Heart Failure Following Lvad Implantation, Carl P Walther, Andrew B Civitello, Harveen K Lamba, Nandan K Mondal, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: Preoperative kidney dysfunction is a risk factor for right heart failure (RHF) after implantation of a left ventricular assist device (LVAD). However, characteristic kidney function trajectories before and after post-LVAD RHF are uncertain, so we investigated this.

METHODS AND RESULTS: We identified individuals who received primary continuous-flow LVAD implantation from July 1, 2014 to December 31, 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data set. Incident RHF was ascertained using the INTERMACS definition at 1 and 3 months and classified as transient or persistent. Kidney function trajectories before and after RHF onset, and relationships of …

Germline Genetic Testing And Survival Outcomes Among Children With Rhabdomyosarcoma: A Report From The Children's Oncology Group, Bailey A Martin-Giacalone, He Li, Michael E Scheurer, Dana L Casey, Shannon Dugan-Perez, Deborah A Marquez-Do, Donna Muzny, Richard A Gibbs, Donald A Barkauskas, David Hall, Douglas R Stewart, Joshua D Schiffman, Matthew T Mcevoy, Javed Khan, David Malkin, Corinne M Linardic, Brian D Crompton, Jack F Shern, Stephen X Skapek, Rajkumar Venkatramani, Douglas S Hawkins, Aniko Sabo, Sharon E Plon, Philip J Lupo

Faculty, Staff and Students Publications

IMPORTANCE: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma.

OBJECTIVE: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed with rhabdomyosarcoma who were treated across 171 Children's Oncology Group sites from March 15, 1999, to December 8, 2017. Data analysis was performed from June 16, 2021, to May 15, 2023.

EXPOSURE: The presence of a CPV in 24 rhabdomyosarcoma-associated cancer-predisposition genes (CPGs) or an expanded set …

Congenital Tooth Agenesis And Risk Of Early-Onset Cancer, Saga Elise Eiset, Jeremy Schraw, Gitte Vrelits Sørensen, Pernille Axél Gregersen, Sonja A Rasmussen, Cecilia H Ramlau-Hansen, Philip J Lupo, Henrik Hasle

Faculty, Staff and Students Publications

IMPORTANCE: There is some evidence that tooth agenesis (congenital absence of 1 or more teeth) is associated with cancer risk, especially carcinomas of the colon and ovaries, but results of previous studies are conflicting, and associations have not yet been evaluated in a population-based setting.

OBJECTIVE: To examine the association between tooth agenesis and specific cancer types before 40 years of age.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used linking data from nationwide registries in Denmark to assess all Danish live-born singletons born from January 1, 1977, to December 31, 2018, and followed up for up to 40 …

Adipose Triglyceride Lipase Is A Therapeutic Target In Advanced Prostate Cancer That Promotes Metabolic Plasticity, Dominik Awad, Pham Hong Anh Cao, Thomas L Pulliam, Meredith Spradlin, Elavarasan Subramani, Tristen V Tellman, Caroline F Ribeiro, Riccardo Muzzioli, Brittany E Jewell, Hubert Pakula, Jeffrey J Ackroyd, Mollianne M Murray, Jenny J Han, Mei Leng, Antrix Jain, Badrajee Piyarathna, Jingjing Liu, Xingzhi Song, Jianhua Zhang, Albert R Klekers, Justin M Drake, Michael M Ittmann, Cristian Coarfa, David Piwnica-Worms, Mary C Farach-Carson, Massimo Loda, Livia S Eberlin, Daniel E Frigo

Faculty, Staff and Students Publications

UNLABELLED: Lipid metabolism plays a central role in prostate cancer. To date, the major focus has centered on de novo lipogenesis and lipid uptake in prostate cancer, but inhibitors of these processes have not benefited patients. A better understanding of how cancer cells access lipids once they are created or taken up and stored could uncover more effective strategies to perturb lipid metabolism and treat patients. Here, we identified that expression of adipose triglyceride lipase (ATGL), an enzyme that controls lipid droplet homeostasis and a previously suspected tumor suppressor, correlates with worse overall survival in men with advanced, castration-resistant prostate …

Intraoperative Evaluation Of Breast Tissues During Breast Cancer Operations Using The Masspec Pen, Kyana Y Garza, Mary E King, Chandandeep Nagi, Rachel J Dehoog, Jialing Zhang, Marta Sans, Anna Krieger, Clara L Feider, Alena V Bensussan, Michael F Keating, John Q Lin, Min Woo Sun, Robert Tibshirani, Christopher Pirko, Kirtan A Brahmbhatt, Ahmed R Al-Fartosi, Alastair M Thompson, Elizabeth Bonefas, James Suliburk, Stacey A Carter, Livia S Eberlin

Faculty, Staff and Students Publications

IMPORTANCE: Surgery with complete tumor resection remains the main treatment option for patients with breast cancer. Yet, current technologies are limited in providing accurate assessment of breast tissue in vivo, warranting development of new technologies for surgical guidance.

OBJECTIVE: To evaluate the performance of the MasSpec Pen for accurate intraoperative assessment of breast tissues and surgical margins based on metabolic and lipid information.

DESIGN, SETTING, AND PARTICIPANTS: In this diagnostic study conducted between February 23, 2017, and August 19, 2021, the mass spectrometry-based device was used to analyze healthy breast and invasive ductal carcinoma (IDC) banked tissue samples from adult …

Adipose Tissue Dysfunction And Energy Balance Paradigms In People Living With Hiv, Claudia E Ramirez Bustamante, Neeti Agarwal, Aaron R Cox, Sean M Hartig, Jordan E Lake, Ashok Balasubramanyam

Faculty, Staff and Students Publications

Over the past 4 decades, the clinical care of people living with HIV (PLWH) evolved from treatment of acute opportunistic infections to the management of chronic, noncommunicable comorbidities. Concurrently, our understanding of adipose tissue function matured to acknowledge its important endocrine contributions to energy balance. PLWH experience changes in the mass and composition of adipose tissue depots before and after initiating antiretroviral therapy, including regional loss (lipoatrophy), gain (lipohypertrophy), or mixed lipodystrophy. These conditions may coexist with generalized obesity in PLWH and reflect disturbances of energy balance regulation caused by HIV persistence and antiretroviral therapy drugs. Adipocyte hypertrophy characterizes visceral …

Expanded Clinical Phenotype And Untargeted Metabolomics Analysis In Rars2-Related Mitochondrial Disorder: A Case Report, Ameya S Walimbe, Keren Machol, Stephen F Kralik, Elizabeth A Mizerik, Yoel Gofin, Mir Reza Bekheirnia, Charul Gijavanekar, Sarah H Elsea, Lisa T Emrick, Fernando Scaglia

Faculty, Staff and Students Publications

Background

RARS2-related mitochondrial disorder is an autosomal recessive mitochondrial encephalopathy caused by biallelic pathogenic variants in the gene encoding the mitochondrial arginyl-transfer RNA synthetase 2 (RARS2, MIM *611524, NM_020320.5). RARS2 catalyzes the transfer of L-arginine to its cognate tRNA during the translation of mitochondrially-encoded proteins. The classical presentation of RARS2-related mitochondrial disorder includes pontocerebellar hypoplasia (PCH), progressive microcephaly, profound developmental delay, feeding difficulties, and hypotonia. Most patients also develop severe epilepsy by three months of age, which consists of focal or generalized seizures that frequently become pharmacoresistant and lead to developmental and epileptic encephalopathy (DEE). …

Integrating Genome Sequencing And Untargeted Metabolomics In Monozygotic Twins With A Rare Complex Neurological Disorder, Rulan Shaath, Aljazi Al-Maraghi, Haytham Ali, Jehan Alrayahi, Adam D Kennedy, Karen L Debalsi, Sura Hussein, Najwa Elbashir, Sujitha S Padmajeya, Sasirekha Palaniswamy, Sarah H Elsea, Ammira A Akil, Noha A Yousri, Khalid A Fakhro

Faculty, Staff and Students Publications

Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We used untargeted metabolomics and whole-genome sequencing (WGS) to gain a more comprehensive understanding of a rare disease with a complex presentation affecting female twins from a consanguineous family. The sisters presented with polymicrogyria, a Dandy–Walker malformation, respiratory distress, and multiorgan dysfunctions. Through WGS, we identified two rare homozygous variants in both subjects, a pathogenic variant in ADGRG1(p.Arg565Trp) and a novel variant in CNTNAP1(p.Glu910Val). These genes have been previously associated with autosomal recessive polymicrogyria and hypomyelinating neuropathy with/without …

Genetic Sex Validation For Sample Tracking In Next-Generation Sequencing Clinical Testing, Jianhong Hu, Viktoriya Korchina, Hana Zouk, Maegan V Harden, David Murdock, Alyssa Macbeth, Steven M Harrison, Niall Lennon, Christie Kovar, Adithya Balasubramanian, Lan Zhang, Gauthami Chandanavelli, Divya Pasham, Robb Rowley, Ken Wiley, Maureen E Smith, Adam Gordon, Gail P Jarvik, Patrick Sleiman, Melissa A Kelly, Harris T Bland, Mullai Murugan, Eric Venner, Eric Boerwinkle, Emerge Iii Consortium, Cynthia Prows, Lisa Mahanta, Heidi L Rehm, Richard A Gibbs, Donna M Muzny

Faculty, Staff and Students Publications

OBJECTIVE: Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups.

RESULTS: Precise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that …

A Greb1-Steroid Receptor Feedforward Mechanism Governs Differential Greb1 Action In Endometrial Function And Endometriosis, Sangappa B Chadchan, Pooja Popli, Zian Liao, Eryk Andreas, Michelle Dias, Tianyuan Wang, Stephanie J Gunderson, Patricia T Jimenez, Denise G Lanza, Rainer B Lanz, Charles E Foulds, Diana Monsivais, Francesco J Demayo, Hari Krishna Yalamanchili, Emily S Jungheim, Jason D Heaney, John P Lydon, Kelle H Moley, Bert W O'Malley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor's transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback …

Best Practices For Helicobacter Pylori Management, David Y Graham

Faculty, Staff and Students Publications

For decades, antimicrobial therapy for Helicobacter pylori infection has been given empirically, and the results of therapy (success or failure) have either not been confirmed or when confirmed have not been used to modify prescribing behavior. These practices coupled with increasing antibiotic resistance have resulted in low cure rates overall. Susceptibility testing for H pylori has increasingly become available, especially in the United States. Availability of susceptibility-based therapy has encouraged adoption of the principles of antimicrobial stewardship for H pylori infection (eg, limiting antibiotic choice to antibiotics for which the infection is susceptible given at optimal doses, formulations, frequency of …

Prognostic Significance Of Acute Kidney Injury Stage 1b In Hospitalized Patients With Cirrhosis: A Us Nationwide Study, Kavish R Patidar, Giuseppe Cullaro, Mobasshir A Naved, Shaowli Kabir, Ananth Grama, Eric S Orman, Salvatore Piano, Andrew S Allegretti

Faculty, Staff and Students Publications

Understanding the prognostic significance of acute kidney injury (AKI) stage 1B [serum creatinine (sCr) ≥1.5 mg/dL] compared with stage 1A (sCr < 1.5 mg/dL) in a US population is important as it can impact initial management decisions for AKI in hospitalized cirrhosis patients. Therefore, we aimed to define outcomes associated with stage 1B in a nationwide US cohort of hospitalized cirrhosis patients with AKI. Hospitalized cirrhosis patients with AKI in the Cerner-Health-Facts database from January 2009 to September 2017 (n = 6250) were assessed for AKI stage 1 (≥1.5-2-fold increase in sCr from baseline) and were followed for 90 days for outcomes. The primary outcome was 90-day mortality; secondary outcomes were in-hospital AKI progression and AKI recovery. Competing-risk multivariable analysis was performed to determine the independent association between stage 1B, 90-day mortality (liver transplant as a competing risk), and AKI recovery (death/liver transplant as a competing risk). Multivariable logistic regression analysis was performed to determine the independent association between stage 1B and AKI progression. In all, 4654 patients with stage 1 were analyzed: 1A (44.3%) and 1B (55.7%). Stage 1B patients had a significantly higher cumulative incidence of 90-day mortality compared with stage 1A patients, 27.2% versus 19.7% ( p < 0.001). In multivariable competing-risk analysis, patients with stage 1B (vs. 1A) had a higher risk for mortality at 90 days [sHR 1.52 (95% CI 1.20-1.92), p = 0.001] and decreased probability for AKI recovery [sHR 0.76 (95% CI 0.69-0.83), p < 0.001]. Furthermore, in multivariable logistic regression analysis, AKI stage 1B (vs. 1A) was independently associated with AKI progression, OR 1.42 (95% CI 1.14-1.72) ( p < 0.001). AKI stage 1B patients have a significantly higher risk for 90-day mortality, AKI progression, and reduced probability of AKI recovery compared with AKI stage 1A patients. These results could guide initial management decisions for AKI in hospitalized patients with cirrhosis.

Systemic Lupus Erythematosus And Lupus Nephritis Presenting As Severe Constitutional Symptoms, Ton La, Sahifah Ansari, Ethan Ha, Matthew Novakovic

Faculty, Staff and Students Publications

Systemic lupus erythematosus (SLE) is a remitting-relapsing systemic autoantibody and immune complex disease with a similar clinical presentation to that of malignancy and infection. The authors report a case of newly diagnosed SLE and lupus nephritis in a 48-year-old woman with constitutional symptoms and unintentional weight loss. Her presentation was further complicated by pericardial effusion and methicillin-resistant Staphylococcus aureus (MRSA) facial cellulitis and bacteremia. In the context of nonspecific symptoms and a wide initial differential diagnosis, the early consideration of rheumatologic etiologies and the involvement of consultant services led to appropriate diagnostic testing and a timely diagnosis.

Discontinuation Of Contact Precautions In Patients With Hospital-Acquired Mrsa And Vre Infections During The Covid-19 Pandemic: A Multi-Center Experience, Gillean Kelly, Marisa Hudson, Bridget Apple, Debora Bundage, Bradley Lembcke, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

Variations in the literature support the benefit of contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) infections in the hospital setting. During personal protective equipment shortages throughout the COVID-19 pandemic, contact precautions were discontinued for MRSA and VRE-infected patients. Rates of hospital-acquired MRSA and VRE infections were compared before and after this intervention, along with hand hygiene proportions. Contact precaution discontinuation did not lead to an increase in hospital-acquired MRSA or VRE infections.

The Pug Flap: Conjoined Profunda Artery Perforator And Upper Gracilis Flap For Breast Reconstruction, Isra Abdulwadood, Lacey R Pflibsen, Nicholas R Jarvis, Sebastian Winocour, Alanna M Rebecca, William J Casey, Edward M Reece

Faculty, Staff and Students Publications

Abdominal-based free flaps are the mainstay of autologous breast reconstruction; however, the region may not be ideal for patients with inadequate soft tissue or history of abdominal surgery. This case describes the use of a novel conjoined flap based on the profunda artery perforator and upper gracilis pedicles, named the perforator and upper gracilis (PUG) flap. This flap design aims to maximize medial thigh flap volume while ensuring robust tissue perforation. Here, we present our experience with the PUG flap in a breast cancer patient undergoing autologous reconstruction. The patient was a 41-year-old woman seeking nipple-sparing mastectomy and immediate autologous …

Environmental Justice: A Missing Core Tenet Of Global Health, Redeat Workneh, Merhawit Abadi, Krystle Perez, Sharla Rent, Elliott Mark Weiss, Stephanie Kukora, Olivia Brandon, Gal Barbut, Sahar Rahiem, Shaphil Wallie, Joseph Mhango, Benjamin C Shayo, Friday Saidi, Gesit Metaferia, Mahlet Abayneh, Gregory C Valentine

Faculty, Staff and Students Publications

No abstract provided.

Echocardiographic Image Collection And Evaluation In Infants With Chd: Lessons Learned From The Imaging Core Lab For The Residual Lesion Score Study, Jami C Levine, Steven Colan, Felicia Trachtenberg, Edward Marcus, Matthew Ferguson, Anitha Parthiban, Carolyn Taylor, Andreea Dragulescu, Benjamin Goot, Ronald V Lacro, Carol Mcfarland, Shanthi Narasimhan, Matthew O'Connor, Marcus Schamberger, Shubhika Srivistava, Michael Taylor, Meena Nathan

Faculty, Staff and Students Publications

Many factors affect patient outcome after congenital heart surgery, including the complexity of the heart disease, pre-operative status, patient specific factors (prematurity, nutritional status and/or presence of comorbid conditions or genetic syndromes), and post-operative residual lesions. The Residual Lesion Score is a novel tool for assessing whether specific residual cardiac lesions after surgery have a measurable impact on outcome. The goal is to understand which residual lesions can be tolerated and which should be addressed prior to leaving the operating room. The Residual Lesion Score study is a large multicentre prospective study designed to evaluate the association of Residual Lesion …