Pathology Commons^™

Clonal Evolution Of Pancreatobiliary Neoplasms, Huamin Wang, Olca Basturk

Faculty, Staff and Student Publications

No abstract provided.

Initiation Of Metformin In Early Pregnancy Results In Fetal Bioaccumulation, Growth Restriction, And Renal Dysmorphology In A Primate Model, Erin Bolte, Tyler Dean, Brandon Garcia, Maxim D Seferovic, Kristin Sauter, Gwendolynn Hummel, Matthew Bucher, Feng Li, John Hicks, Xuan Qin, Melissa A Suter, Enrico R Barrozo, Michael Jochum, Cynthia Shope, Jacob E Friedman, Maureen Gannon, Stephanie R Wesolowski, Carrie E Mccurdy, Paul Kievit, Kjersti M Aagaard

Faculty, Staff and Students Publications

Background: In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and (most recently) preeclampsia. However, with its expanded use, concerns of unintended harm have been raised.

Objective: This study developed an experimental primate model and applied ultrahigh performance liquid chromatography coupled to triple-quadrupole mass spectrometry for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology.

Study design: Within 30 days of confirmed conception (defined as early pregnancy), 13 time-bred (timed-mated breeding) Rhesus dams with pregnancies designated for fetal necropsy were initiated on …

Determining Predictors Of Actual Living Kidney Donation Based On Potential Donor Characteristics, Andrea M Meinders, Edward A Graviss, Duc T Nguyen, Jonathan Daw, Krista L Lentine, John Devin Peipert, Ahmed Osama Gaber, David A Axelrod, Francis L Weng, Amy D Waterman

Faculty, Staff and Students Publications

Background: Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons.

Methods: At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing.

Results: Among 2184 …

A Machine Learning Model For Risk Stratification Of Postdiagnosis Diabetic Ketoacidosis Hospitalization In Pediatric Type 1 Diabetes: Retrospective Study, Devika Subramanian, Rona Sonabend, Ila Singh

Faculty, Staff and Students Publications

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes (T1D), occurring in approximately 20% of patients, with an economic cost of $5.1 billion/year in the United States. Despite multiple risk factors for postdiagnosis DKA, there is still a need for explainable, clinic-ready models that accurately predict DKA hospitalization in established patients with pediatric T1D.

OBJECTIVE: We aimed to develop an interpretable machine learning model to predict the risk of postdiagnosis DKA hospitalization in children with T1D using routinely collected time-series of electronic health record (EHR) data.

METHODS: We conducted a retrospective case-control …

T-Cell-Rich Hodgkin Lymphoma With Features Of Classic Hodgkin Lymphoma And Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Borderline Category With Overlapping Morphologic And Immunophenotypic Features, Siba El Hussein, Hong Fang, Fatima Zahra Jelloul, Wei Wang, Sanam Loghavi, Roberto N Miranda, Jonathan W Friedberg, W Richard Burack, Andrew G Evans, Jie Xu, L Jeffrey Medeiros

Faculty, Staff and Student Publications

Context.—: It is known that a subset of cases of classic Hodgkin lymphoma (CHL) with B-cell-rich nodules (lymphocyte-rich CHL) exhibits morphologic and immunophenotypic features that overlap with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), raising diagnostic difficulties that can be resolved in most cases by performing an adequate battery of immunohistochemical studies.

Objective.—: To fully characterize cases of T-cell-rich Hodgkin lymphoma where a specific diagnosis of NLPHL (ie, pattern D) or CHL could not be made even after complete immunophenotypic investigation.

Design.—: The clinical, immunomorphologic, and molecular (when applicable) presentation of 3 cases of T-cell-rich Hodgkin lymphoma was thoroughly investigated.

Results.—: These …

Promoting Resilience In Stress Management For Adolescents With Type 1 Diabetes: A Randomized Clinical Trial, Joyce P Yi-Frazier, Marisa E Hilliard, Maeve B O'Donnell, Chuan Zhou, Britney M Ellisor, Samantha Garcia Perez, Brenda Duran, Yuliana Rojas, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Miranda C Bradford, Samantha Scott, Sridevi Devaraj, Abby R Rosenberg

Faculty, Staff and Students Publications

IMPORTANCE: Type 1 diabetes (T1D) requires demanding self-management health behaviors, and adolescents with T1D are at risk for poor psychosocial and medical outcomes. Developing resilience skills may help adolescents with T1D and elevated distress navigate common stressors and achieve positive outcomes.

OBJECTIVE: To test the efficacy of the Promoting Resilience in Stress Management (PRISM) intervention on levels of hemoglobin A1c (HbA1c), diabetes distress, self-management behaviors, resilience, and quality of life among adolescents.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, parallel, 1:1 randomized clinical trial that followed up 172 participants for 12 months was conducted from January 1, 2020, to November …

Crohn's Disease-Associated Granulomatous Pancreatitis With Exocrine Pancreatic Insufficiency, Anthony A Xu, Sara Vincent, Samuel Ma, Vanessa Catania, Neda Zarrin-Khameh

Faculty, Staff and Students Publications

Extraintestinal manifestations of inflammatory bowel disease occur commonly and can lead to considerable morbidity. Pancreatic manifestations of inflammatory bowel disease have been reported to be more common in Crohn's disease (CD) than ulcerative colitis. We report a case of granulomatous inflammation in the body of the pancreas with exocrine pancreatic insufficiency, which prompted a diagnosis switch from ulcerative colitis to CD. This is of interest to readers to remind them that pancreatic manifestations can occur and are more common in CD.

Challenges Of Insulin-Like Growth Factor-1 Testing, Rongrong Huang, Junyan Shi, Ruhan Wei, Jieli Li

Faculty, Staff and Students Publications

Insulin-like growth factor 1 (IGF-1), primarily synthesized in the liver, was initially discovered due to its capacity to replicate the metabolic effects of insulin. Subsequently, it emerged as a key regulator of the actions of growth hormone (GH), managing critical processes like cell proliferation, differentiation, and apoptosis. Notably, IGF-1 displays a longer half-life compared to GH, making it less susceptible to factors that may affect GH concentrations. Consequently, the measurement of IGF-1 proves to be more specific and sensitive when diagnosing conditions such as acromegaly or GH deficiency. The recognition of the existence of IGFBPs and their potential to interfere …

Clinical Features And Outcomes Of Pediatric And Adult Patients Hospitalized For Coronavirus Disease 2019: A Comparison Across Age Strata, Grace X Li, Komal Gopchandani, Noah Brazer, Ashley Tippett, Chris Choi, Hui-Mien Hsiao, Miriam Oseguera, Abiodun Foresythe, Sanchita Bhattacharya, Venice Servellita, Alicia Sotomayor Gonzalez, Jennifer K Spinler, Mark D Gonzalez, Dalia Gulick, Colleen Kraft, Vyjayanti Kasinathan, Yun F Wayne Wang, Jennifer Dien Bard, Pei Ying Chen, Jessica Flores-Vazquez, Audrey R Odom John, Paul J Planet, Sridevi Devaraj, Ananth V Annapragada, Ruth Ann Luna, Charles Y Chiu, Christina A Rostad

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults.

METHODS: This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification. Adjusted odds ratios (aOR) of clinical outcomes were determined for children versus adults, for pediatric age …

If At First We Don't Succeed, Should We Try, Try Again?, Kriti Puri, Susan W Denfield

Faculty, Staff and Students Publications

No abstract provided.

Developing The Openflexure Microscope Towards Medical Use: Technical And Social Challenges Of Developing Globally Accessible Hardware For Healthcare, Joe Knapper, Freya Whiteford, Daniel Rosen, William Wadsworth, Julian Stirling, Catherine Mkindi, Joram Mduda, Valerian L Sanga, Paul T Nyakyi, Thomas Hervé Mboa Nkoudou, Elisée Jafsia, Stephane Fadanka, Kelsey Hummel, Sharmila Anandasabapathy, Richard Bowman

Faculty, Staff and Students Publications

The OpenFlexure Microscope is an accessible, three-dimensional-printed robotic microscope, with sufficient image quality to resolve diagnostic features including parasites and cancerous cells. As access to lab-grade microscopes is a major challenge in global healthcare, the OpenFlexure Microscope has been developed to be manufactured, maintained and used in remote environments, supporting point-of-care diagnosis. The steps taken in transforming the hardware and software from an academic prototype towards an accepted medical device include addressing technical and social challenges, and are key for any innovation targeting improved effectiveness in low-resource healthcare. This article is part of the Theo Murphy meeting issue 'Open, reproducible …

Utility Of Cystatin C-Based Equation For The Estimation Of Glomerular Filtration Rate In A Pediatric Population, Ridwan B Ibrahim, Poyyapakkam Srivaths, Estella Tam, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations …

Implementation, Evolution, And Laboratory Performance Of Methods-Based Proficiency Testing For Next-Generation Sequencing Detection Of Germline Sequence Variants, Karen D Tsuchiya, Birgit Funke, Madhuri Hegde, Avni Santani, Rhona J Souers, Szabolcs Szelinger, Jaimie Halley, Qin Zhao, Nicole Mot, Angshumoy Roy, Vanessa L Smith, Bing M Zhang, Karl Voelkerding, Ann M Moyer

Faculty, Staff and Students Publications

Context.—: Next-generation sequencing (NGS)-based assays are used for diagnosis of diverse inherited disorders. Limited data are available pertaining to interlaboratory analytical performance of these assays.

Objective.—: To report on the College of American Pathologists (CAP) NGS Germline Program, which is methods based, and explore the evolution in laboratory testing practices.

Design.—: Results from the NGS Germline Program from 2016-2020 were analyzed for interlaboratory analytical performance. Self-reported laboratory testing practices were also evaluated.

Results.—: From 2016-2020, a total of 297 laboratories participated in at least 1 program mailing. Of the 289 laboratories that provided information on tests offered, 138 (47.8%) offered …

Anticoagulant Medications: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Katherine Cashen, Arun Saini, Leonardo R Brandão, Jennifer Le, Paul Monagle, Katie M Moynihan, Lindsay M Ryerson, Alison Gehred, Elizabeth Lyman, Jennifer A Muszynski, Peta M A Alexander, Heidi J Dalton

Faculty, Staff and Students Publications

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the medications used for anticoagulation for pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE (PEACE).

DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION: Included studies assessed anticoagulation used in pediatric ECMO.

DATA EXTRACTION: Two authors reviewed all citations independently, with a third reviewer adjudicating any conflicts. Eighteen references were used for data extraction as well as for creation of recommendations. Evidence tables were constructed using a standardized data extraction form.

DATA SYNTHESIS: …

Management Of Extracorporeal Membrane Oxygenation Anticoagulation In The Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Ariane Willems, Marc M Anders, Alejandro V Garcia, Adam M Vogel, Andrew R Yates, Jennifer A Muszynski, Peta M A Alexander, Katherine Steffen, Sitaram Emani, Alison Gehred, Elizabeth Lyman, Lakshmi Raman

Faculty, Staff and Students Publications

OBJECTIVES: To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference.

DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION: ECMO anticoagulation and hemostasis management in the perioperative period and during procedures.

DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. Evidence tables were constructed …

Priorities For Clinical Research In Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Jennifer A Muszynski, Melania M Bembea, Alison Gehred, Elizabeth Lyman, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Peta M A Alexander

Faculty, Staff and Students Publications

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus.

DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children.

DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third …

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative (Peace) Consensus Conference, Peta M A Alexander, Melania M Bembea, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed S Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Christopher Almond, Marc M Anders, Gail M Annich, Leonardo R Brandão, Wayne Chandler, Megan Delaney, Robert Digeronimo, Sitaram Emani, Samir K Gadepalli, Alejandro V Garcia, Bereketeab Haileselassie, Robert Hyslop, Martin C J Kneyber, Lisa Baumann Kreuziger, Jennifer Le, Laura Loftis, Ali B V Mcmichael, D Michael Mcmullan, Paul Monagle, Kathleen Nicol, Matthew L Paden, Jason Patregnani, John Priest, Leslie Raffini, Lindsay M Ryerson, Steven R Sloan, Jun Teruya, Andrew R Yates, Alison Gehred, Elizabeth Lyman, Jennifer A Muszynski

Faculty, Staff and Students Publications

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.

DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill children.

DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any …

Impact Of Gut Health And Microbiome On Autism Spectrum Disorder, Sik Yu So, Tor C Savidge

Faculty, Staff and Students Publications

No abstract provided.

Individual Disruption Of 12 Testis-Enriched Genes Via The Crispr/Cas9 System Does Not Affect The Fertility Of Male Mice, Akira Suzuki, Norikazu Yabuta, Keisuke Shimada, Daisuke Mashiko, Keizo Tokuhiro, Yuki Oyama, Haruhiko Miyata, Thomas X Garcia, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

More than 1200 genes have been shown in the database to be expressed predominantly in the mouse testes. Advances in genome editing technologies such as the CRISPR/Cas9 system have made it possible to create genetically engineered mice more rapidly and efficiently than with conventional methods, which can be utilized to screen genes essential for male fertility by knocking out testis-enriched genes. Finding such genes related to male fertility would not only help us understand the etiology of human infertility but also lead to the development of male contraceptives. In this study, we generated knockout mice for 12 genes (Acrv1, Adgrf3, …

Comparison Of Cefiderocol In-Vitro Susceptibility Testing Modalities, Nicholas S Teran, Linh Vuong, Kady Phe, Todd M Lasco, William R Miller, Vincent H Tam

Faculty, Staff and Students Publications

No abstract provided.

Reversible Male Contraception By Targeted Inhibition Of Serine/Threonine Kinase 33, Angela F Ku, Kiran L Sharma, Hai Minh Ta, Courtney M Sutton, Kurt M Bohren, Yong Wang, Srinivas Chamakuri, Ruihong Chen, John M Hakenjos, Ravikumar Jimmidi, Katarzyna Kent, Feng Li, Jian-Yuan Li, Lang Ma, Chandrashekhar Madasu, Murugesan Palaniappan, Stephen S Palmer, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Yasmin M Vasquez, Jian Wang, Jennifer Wilkinson, Zhifeng Yu, Qiuji Ye, Damian W Young, Mingxing Teng, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that …

Rna Sequencing For Solid Tumor Fusion Gene Detection: Proficiency Testing Practice And Performance Comparison, Julia A Bridge, Kevin C Halling, Joel T Moncur, Rhona J Souers, Meera R Hameed, Helen Fernandes, Angshumoy Roy, Lea Surrey, Laura J Tafe, Patricia Vasalos, Dolores H Lopez-Terrada

Faculty, Staff and Students Publications

Context: Next-generation sequencing-based approaches using RNA have increasingly been used by clinical laboratories for the detection of fusion genes, intragenic rearrangements, and exon-skipping events. Correspondingly, the College of American Pathologists (CAP) has advanced RNA sequencing proficiency testing (PT) to ensure optimal performance of these assays.

Objective: To report on laboratory performance and practices of RNA sequencing for the detection of fusion genes, intragenic rearrangements, and exon-skipping events using CAP PT data from 8 mailings (2018-A through 2021-B).

Design: CAP PT RNA sequencing program results from 153 laboratories across 24 proficiency test specimens, interrogating 22 distinct engineered fusion transcripts, were analyzed …

The Dementia Care Study (D-Care): Recruitment Strategies And Demographic Characteristics Of Participants In A Pragmatic Randomized Trial Of Dementia Care, Mia Yang, Rafael Samper-Ternent, Elena Volpi, Aval-Na'ree Green, Maya Lichtenstein, Katy Araujo, Pamela Borek, Peter Charpentier, James Dziura, Thomas M Gill, Rebecca Galloway, Erich J Greene, Kristin Lenoir, Peter Peduzzi, Can Meng, Jordan Reese, Amy Shelton, Eleni A Skokos, Jenny Summapund, Erin Unger, David B Reuben, Jeff D Williamson, Alan B Stevens

Faculty, Staff and Student Publications

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.

METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients.

RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), …

Autophagy Is Required For Stem-Cell-Mediated Endometrial Programming And The Establishment Of Pregnancy, Pooja Popli, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Autophagy plays an important role in the normal growth and morphogenesis of a variety of tissues. Its role in uterine maturation, however, is not fully characterized. Recently, we reported that BECN1 (Beclin1)-dependent autophagy, but not apoptosis, is crucial for stem cell-mediated endometrial programming and the establishment of pregnancy in mice. Upon genetic and pharmacological inhibition of BECN1-mediated autophagy, female mice displayed severe endometrial structural and functional defects leading to infertility. Specifically, conditional loss of Becn1 in the uterus induces apoptosis and results in the gradual loss of endometrial progenitor stem cells. Importantly, the restoration of BECN1-driven autophagy, but not apoptosis …

Bringing Proteomics To Bear On Male Fertility: Key Lessons, Rachel Parkes, Thomas X Garcia

Faculty, Staff and Students Publications

Introduction: Male infertility is a major public health concern globally. Proteomics has revolutionized our comprehension of male fertility by identifying potential infertility biomarkers and reproductive defects. Studies comparing sperm proteome with other male reproductive tissues have the potential to refine fertility diagnostics and guide infertility treatment development.

Areas covered: This review encapsulates literature using proteomic approaches to progress male reproductive biology. Our search methodology included systematic searches of databases such as PubMed, Scopus, and Web of Science for articles up to 2023. Keywords used included 'male fertility proteomics,' 'spermatozoa proteome,' 'testis proteomics,' 'epididymal proteomics,' and 'non-hormonal male contraception.' Inclusion criteria …

Single-Center Outcomes After Liver Transplantation With Sars-Cov-2-Positive Donors: An Argument For Increased Utilization, Ashton A Connor, Max W Adelman, Constance M Mobley, Mozhgon Moaddab, Alexandra J Erhardt, David E Hsu, Elizabeth W Brombosz, Mansi Sanghvi, Yee Lee Cheah, Caroline J Simon, Mark J Hobeika, Ashish S Saharia, David W Victor, Sudha Kodali, Tamneet Basra, Edward A Graviss, Duc T Nguyen, Ahmed Elsaiey, Linda W Moore, Masayuki Nigo, Ashley L Drews, Kevin A Grimes, Cesar A Arias, Xian C Li, A Osama Gaber, R Mark Ghobrial

Faculty, Staff and Students Publications

Background: The COVID-19 pandemic has led to an increase in SARS-CoV-2-test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19-positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19-positive donors at a single center are presented here.

Methods: A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19-positive (n = 29 total; 25 index, 4 redo) and …

Effectiveness Of Cord Blood As A Strategy To Rule Out Conjugated Hyperbilirubinemia, Miray Kurtca, Sanjiv Harpavat, Sridevi Devaraj

Faculty, Staff and Students Publications

Early detection of biliary atresia is crucial for timely intervention and improved outcomes in infants with elevated conjugated bilirubin levels. This study aims to investigate the viability of cord blood gas analysis as a novel method for assessing conjugated bilirubin levels. Infants with high heel stick levels also showed elevated cord blood bilirubin levels, indicating that cord blood testing could replace the need for repeat heel stick tests, especially benefiting low birth weight infants. Ongoing research, including larger cohorts and alternative bilirubin measurement methods, will further validate this innovative screening approach. Infants with biliary atresia have high conjugated bilirubin levels …

Affinity-Tagged Smad1 And Smad5 Mouse Lines Reveal Transcriptional Reprogramming Mechanisms During Early Pregnancy, Zian Liao, Suni Tang, Kaori Nozawa, Keisuke Shimada, Masahito Ikawa, Diana Monsivais, Martin Matzuk

Faculty, Staff and Students Publications

Endometrial decidualization, a prerequisite for successful pregnancies, relies on transcriptional reprogramming driven by progesterone receptor (PR) and bone morphogenetic protein (BMP)-SMAD1/SMAD5 signaling pathways. Despite their critical roles in early pregnancy, how these pathways intersect in reprogramming the endometrium into a receptive state remains unclear. To define how SMAD1 and/or SMAD5 integrate BMP signaling in the uterus during early pregnancy, we generated two novel transgenic mouse lines with affinity tags inserted into the endogenous SMAD1 and SMAD5 loci (Smad1^HA/HA and Smad5^PA/PA). By profiling the genome-wide distribution of SMAD1, SMAD5, and PR in the mouse uterus, we demonstrated …

Network Of Epistatic Interactions In An Enzyme Active Site Revealed By Large-Scale Deep Mutational Scanning, Allison Judge, Banumathi Sankaran, Liya Hu, Murugesan Palaniappan, André Birgy, B V Venkataram Prasad, Timothy Palzkill

Faculty, Staff and Students Publications

Cooperative interactions between amino acids are critical for protein function. A genetic reflection of cooperativity is epistasis, which is when a change in the amino acid at one position changes the sequence requirements at another position. To assess epistasis within an enzyme active site, we utilized CTX-M β-lactamase as a model system. CTX-M hydrolyzes β-lactam antibiotics to provide antibiotic resistance, allowing a simple functional selection for rapid sorting of modified enzymes. We created all pairwise mutations across 17 active site positions in the β-lactamase enzyme and quantitated the function of variants against two β-lactam antibiotics using next-generation sequencing. Context-dependent sequence …

Trps1 Expression In Non-Melanocytic Cutaneous Neoplasms: An Immunohistochemical Analysis Of 200 Cases, Yi A Liu, Phyu P Aung, Yunyi Wang, Jing Ning, Priyadharsini Nagarajan, Jonathan L Curry, Carlos A Torres-Cabala, Doina Ivan, Victor G Prieto, Qingqing Ding, Woo Cheal Cho

Faculty, Staff and Student Publications

BACKGROUND: Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ.

METHODS: Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit …