Medical Specialties Commons^™

Sphingosine-1-Phosphate Inhibition Increases Endoplasmic Reticulum Stress To Enhance Oxaliplatin Sensitivity In Pancreatic Cancer, Zachary Gao, Harinarayanan Janakiraman, Yang Xiao, Sung Wook Kang, Jiangling Dong, Jasmine Choi, Besim Ogretmen, Hyun-Sung Lee, Ernest Ramsay Camp

Faculty, Staff and Students Publications

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer resistant to current therapies, including oxaliplatin (Oxa). Growing evidence supports the ability of cancers to harness sphingolipid metabolism for survival. Sphingosine-1-phosphate (S1P) is an anti-apoptotic, pro-survival mediator that can influence cellular functions such as endoplasmic reticulum (ER) stress. We hypothesize that PDAC drives dysregulated sphingolipid metabolism and that S1P inhibition can enhance ER stress to improve therapeutic response to Oxa in PDAC.

METHODS: RNA sequencing data of sphingolipid mediators from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) datasets were analyzed. Murine and human PDAC cell lines were treated …

An Oocyte-Specific Cas9-Expressing Mouse For Germline Crispr/Cas9-Mediated Genome Editing, Denise G Lanza, Jianqiang Mao, Isabel Lorenzo, Lan Liao, John R Seavitt, M Cecilia Ljungberg, Elizabeth M Simpson, Francesco J Demayo, Jason D Heaney

Faculty, Staff and Students Publications

Cas9 transgenes can be employed for genome editing in mouse zygotes. However, using transgenic instead of exogenous Cas9 to produce gene-edited animals creates unique issues including ill-defined transgene integration sites, the potential for prolonged Cas9 expression in transgenic embryos, and increased genotyping burden. To overcome these issues, we generated mice harboring an oocyte-specific, Gdf9 promoter driven, Cas9 transgene (Gdf9-Cas9) targeted as a single copy into the Hprt1 locus. The X-linked Hprt1 locus was selected because it is a defined integration site that does not influence transgene expression, and breeding of transgenic males generates obligate transgenic females to serve as embryo …

Development And Publication Of Clinical Practice Parameters, Reviews, And Meta-Analyses: A Report From The Society Of Cardiovascular Anesthesiologists Presidential Task Force, Miklos D Kertai, Benu Makkad, Bruce A Bollen, Hilary P Grocott, Bessie Kachulis, Michael L Boisen, Jacob Raphael, Tjorvi E Perry, Hong Liu, Michael C Grant, Jacob Gutsche, Wanda M Popescu, Nadia B Hensley, Michael A Mazzeffi, Roman M Sniecinski, Emily Teeter, Nirvik Pal, Jennie Y Ngai, Alexander Mittnacht, Yianni G T Augoustides, Stephanie O Ibekwe, Archer Kilbourne Martin, Amanda J Rhee, Rachel L Walden, Kathryn Glas, Andrew D Shaw, Linda Shore-Lesserson

Faculty, Staff and Students Publications

The Society of Cardiovascular Anesthesiologists (SCA) is committed to improving the quality, safety, and value that cardiothoracic anesthesiologists bring to patient care. To fulfill this mission, the SCA supports the creation of peer-reviewed manuscripts that establish standards, produce guidelines, critically analyze the literature, interpret preexisting guidelines, and allow experts to engage in consensus opinion. The aim of this report, commissioned by the SCA President, is to summarize the distinctions among these publications and describe a novel SCA-supported framework that provides guidance to SCA members for the creation of these publications. The ultimate goal is that through a standardized and transparent …

Alveolar Epithelial Cell Dysfunction In Idiopathic Pulmonary Fibrosis Linked To Lipid Alterations: Therapeutic Implications, Francesca Polverino, Ana Mora

Faculty, Staff and Students Publications

No abstract provided.

Improved Postoperative Speech Recognition And Processor Use With Early Cochlear Implant Activation, Ankita Patro, Nathan R Lindquist, Jourdan T Holder, Michael H Freeman, René H Gifford, Kareem O Tawfik, Matthew R O'Malley, Marc L Bennett, David S Haynes, Elizabeth L Perkins

Faculty, Staff and Students Publications

Objective: To report speech recognition outcomes and processor use based on timing of cochlear implant (CI) activation.

Study design: Retrospective cohort.

Setting: Tertiary referral center.

Patients: A total of 604 adult CI recipients from October 2011 to March 2022, stratified by timing of CI activation (group 1: ≤10 d, n = 47; group 2: >10 d, n = 557).

Main outcome measures: Average daily processor use; Consonant-Nucleus-Consonant (CNC) and Arizona Biomedical (AzBio) in quiet at 1-, 3-, 6-, and 12-month visits; time to peak performance.

Results: The groups did not differ in sex ( p = 0.887), age at CI …

Re-Evaluation Of The Methodology For Estimating The Us Specialty Physician Workforce, W Stephen Black-Schaffer, David J Gross, Zakia Nouri, Aidan Delisle, Michael Dill, Jason Y Park, James M Crawford, Michael B Cohen, Rebecca L Johnson, Donald S Karcher, Thomas M Wheeler, Stanley J Robboy

Faculty, Staff and Students Publications

Increasing pursuit of subspecialized training has quietly revolutionized physician training, but the potential impact on physician workforce estimates has not previously been recognized. The Physicians Specialty Data Reports of the Association of American Medical Colleges, derived from specialty designations in the American Medical Association (AMA) Physician Professional Data (PPD), are the reference source for US physician workforce estimates; by 2020, the report for pathologists was an undercount of 39% when compared with the PPD. Most of the difference was due to the omission of pathology subspecialty designations. The rest resulted from reliance on only the first of the AMA PPD's …

Neurocritical Care And Neuromonitoring Considerations In Acute Pediatric Spinal Cord Injury, Ajay X Thomas, Jennifer C Erklauer

Faculty, Staff and Students Publications

Management of pediatric spinal cord injury (SCI) is an essential skill for all pediatric neurocritical care physicians. In this review, we focus on the evaluation and management of pediatric SCI, highlight a novel framework for the monitoring of such patients in the intensive care unit (ICU), and introduce advancements in critical care techniques in monitoring and management. The initial evaluation and characterization of SCI is crucial for improving outcomes as well as prognostication. While physical examination and imaging are the main stays of the work-up, we propose the use of somatosensory evoked potentials (SSEPs) and transcranial magnetic stimulation (TMS) for …

Total Syntheses Of Hosieines A-C, Jiayang Zhang, Xu Yan, Qing-Bao Zhang, Fang Wang, Bin Yang, Yang Yang

Children’s Nutrition Research Center Staff Publications

The collective total syntheses of (±)-hosieines A-C with a cage-like tetracyclic framework have been realized, which includes the first syntheses of hosieines B-C. The key strategy of the synthesis employs a one-pot domino reaction that involves Cu-catalyzed [3+2] cycloaddition, 1,6-enone formation, and 1,6-aza-Michael addition forming the 5/6/6-aza-tricyclic skeleton. Other salient synthetic tactics comprise a challenging double bond migration and a 1,4-aza-Michael addition reaction to afford the tetracyclic framework.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations In Chronic Pancreatitis: A Multicenter, Cross-Sectional Study, Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear …

Innominate Artery Pseudoaneurysm From A Salter-Harris Fracture Of The Sternoclavicular Joint, Emily Y Fan, Santiago Abrill Zegarra, Jennifer Walker, Errol Mortimer, Jessica P Simons

Faculty, Staff and Student Publications

Fractures and dislocations of the sternoclavicular joint (SCJ) are uncommon, accounting for <5% of all shoulder girdle injuries. They are relatively more common in the pediatric population than in the adult population and can often present concurrently as a posteriorly displaced medial clavicular dislocation with a fracture through the unfused physis. It is especially important to recognize this injury, because its management and potential sequelae are very different from those for fractures of the clavicle shaft. This type of injury frequently requires closed or open operative management because fracture-dislocation of the SCJ can be associated with potentially serious complications such as pneumothorax, brachial plexus injury, vagus nerve injury, tracheal injury, and vascular compromise. Few case reports describe fracture-dislocation of the SCJ resulting in vascular injuries. We describe the case of a 17-year-old boy who sustained a blunt hockey injury resulting in a right physeal fracture-dislocation of the SCJ causing an innominate artery pseudoaneurysm. This was treated with excision of the pseudoaneurysm, bovine pericardial patch angioplasty repair of the innominate artery, and open reduction and internal fixation of the medial clavicular physeal fracture.

Does A Reduction In Receiving Assistance With Daily Activities Among Older Adults In Mexico Indicate An Increase In Unmet Needs Or A Decrease In Needs For Care?, Brian Downer, Rafael Samper-Ternent, Philip Cantu, Matthew Miller, Rebeca Wong

Faculty, Staff and Student Publications

OBJECTIVES: The percentage of older adults in Mexico with difficulty completing activities of daily living (ADL) who receive assistance from family appears to be decreasing. We compared 2 birth cohorts of older adults in Mexico to investigate whether this trend reflects an increase in unmet caregiving needs or a decrease in the need for care.

METHODS: We selected Mexican Health and Aging Study participants aged 60-76 in 2001 (n = 4,805) and 2018 (n = 6,494). ADL tasks were dressing, walking, bathing, getting in and out of bed, and toileting. Participants who reported difficulty with an ADL were asked if …

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), …

Transitioning From An In-Person Intervention To Augmented Text Messaging During Covid-19 In Mexican Americans With Prediabetes: The Starr County Diabetes Prevention Randomized Clinical Trial, Sharon A Brown, Mary A Winter, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

PURPOSE: The purpose of the study was to explore the feasibility of using commonly available technology, such as text messaging, for diabetes prevention in rural Mexican American communities during COVID-19.

METHODS: Participants were selected from a diabetes prevention study funded by the National Institutes of Health that, prior to COVID-19, involved in-person group intervention sessions. Participants were predominantly female adults born in Mexico and Spanish-speaking. A subsample (n = 140) was divided into 3 cohorts: (1) 50 who completed the initial in-person intervention prior to the COVID-19 research pause, (2) 60 who needed additional support sessions to complete the intervention …

Samhd1 Compound Heterozygous Rare Variants Associated With Moyamoya And Mitral Valve Disease In The Absence Of Other Features Of Aicardi-Goutières Syndrome, Aamuktha R Karla, Amélie Pinard, Maura L Boerio, Dimitri Hemelsoet, Simon J Tavernier, Michel De Pauw, Elke Vereecke, Stuart Fraser, Michael J Bamshad, Dongchuan Guo, Bert Callewaert, Dianna M Milewicz

Faculty, Staff and Student Publications

Aicardi-Goutières syndrome (AGS) is an autosomal recessive inflammatory syndrome that manifests as an early-onset encephalopathy with both neurologic and extraneurologic clinical findings. AGS has been associated with pathogenic variants in nine genes: TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1, ADAR, IFIH1, LSM11, and RNU7-1. Diagnosis is established by clinical findings (encephalopathy and acquired microcephaly, intellectual and physical impairments, dystonia, hepatosplenomegaly, sterile pyrexia, and/or chilblains), characteristic abnormalities on cranial CT (calcification of the basal ganglia and white matter) and MRI (leukodystrophic changes), or the identification of pathogenic/likely pathogenic variants in the known genes. One of the genes associated with AGS, SAMHD1, has also …

Premastectomy Radiotherapy And Immediate Breast Reconstruction: A Randomized Clinical Trial, Mark V Schaverien, Puneet Singh, Benjamin D Smith, Wei Qiao, Catherine L Akay, Elizabeth S Bloom, Mariana Chavez-Macgregor, Carrie K Chu, Mark W Clemens, Jessica S Colen, Richard A Ehlers, Rosa F Hwang, Melissa M Joyner, Rene D Largo, Alexander F Mericli, Melissa P Mitchell, John W Shuck, Nina Tamirisa, Debasish Tripathy, Mark T Villa, Wendy A Woodward, Rensi Zacharia, Henry M Kuerer, Karen E Hoffman

Faculty, Staff and Student Publications

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR).

Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR.

Design, setting, and participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible.

Intervention: This …

Serum Metabolomic Markers Of Protein-Rich Foods And Incident Ckd: Results From The Atherosclerosis Risk In Communities Study, Lauren Bernard, Jingsha Chen, Hyunju Kim, Kari E Wong, Lyn M Steffen, Bing Yu, Eric Boerwinkle, Andrew S Levey, Morgan E Grams, Eugene P Rhee, Casey M Rebholz

Faculty, Staff and Student Publications

RATIONALE & OBJECTIVE: While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD).

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: A total of 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline.

EXPOSURES: Dietary intake of 6 protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry), serum metabolites.

OUTCOMES: Incident CKD (estimated …

Final Report Of The Phase Ii Next/Cns-Gct-4 Trial: Gempox Followed By Marrow-Ablative Chemotherapy For Recurrent Intracranial Germ Cell Tumors, Margaret Shatara, Megan Blue, Joseph Stanek, Yin A Liu, Daniel M Prevedello, Pierre Giglio, Vinay K Puduvalli, Sharon L Gardner, Jeffrey C Allen, Kenneth K Wong, Marvin D Nelson, Floyd H Gilles, Roberta H Adams, Jasmine Pauly, Katrina O'Halloran, Ashley S Margol, Girish Dhall, Jonathan L Finlay

Faculty, Staff and Student Publications

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Methods: A total of 9 patients with confirmed …

The Tudor-Knot Domain Of Kat5 Regulates Nucleosomal Substrate Acetylation, Fan Xuan, Hongwen Xuan, Mengying Huang, Wei He, Han Xu, Xiaobing Shi, Hong Wen

Faculty, Staff and Student Publications

The lysine acetyltransferase KAT5 is a pivotal enzyme responsible for catalyzing histone H4 acetylation in cells. In addition to its indispensable HAT domain, KAT5 also encompasses a conserved Tudor-knot domain at its N-terminus. However, the function of this domain remains elusive, with conflicting findings regarding its role as a histone reader. In our study, we have employed a CRISPR tiling array approach and unveiled the Tudor-knot motif as an essential domain for cell survival. The Tudor-knot domain does not bind to histone tails and is not required for KAT5's chromatin occupancy. However, its absence leads to a global reduction in …

Analytical Challenges In Omics Research On Asthma And Allergy: A National Institute Of Allergy And Infectious Diseases Workshop, Supinda Bunyavanich, Patrice M Becker, Matthew C Altman, Jessica Lasky-Su, Carole Ober, Karsten Zengler, Evgeny Berdyshev, Richard Bonneau, Talal Chatila, Nilanjan Chatterjee, Kian Fan Chung, Colleen Cutcliffe, Wendy Davidson, Gang Dong, Gang Fang, Patricia Fulkerson, Blanca E Himes, Liming Liang, Rasika A Mathias, Shuji Ogino, Joseph Petrosino, Nathan D Price, Eric Schadt, James Schofield, Max A Seibold, Hanno Steen, Lisa Wheatley, Hongmei Zhang, Alkis Togias, Kohei Hasegawa

Center for Medical Ethics and Health Policy Staff Publications

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes …

Glial Lipid Droplets Resolve Ros During Sleep, Lindsey D Goodman, Matthew J Moulton, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The Sehgal lab presents data showing that the non-cell autonomous pathway of glial lipid droplet formation occurs during sleep and helps to resolve neuronal reactive oxygen species (ROS). This promotes neuronal function after an active day. Hence, this pathway has an important physiological function beyond its previously described role in ROS-associated diseases, including Alzheimer’s disease.

Lac-Phe Mediates The Effects Of Metformin On Food Intake And Body Weight, Shuke Xiao, Veronica L Li, Xuchao Lyu, Xudong Chen, Wei Wei, Fahim Abbasi, Joshua W Knowles, Alan Sheng-Hwa Tung, Shuliang Deng, Gaurav Tiwari, Xu Shi, Shuning Zheng, Laurie Farrell, Zsu-Zsu Chen, Kent D Taylor, Xiuqing Guo, Mark O Goodarzi, Alexis C Wood, Yii-Der Ida Chen, Leslie A Lange, Stephen S Rich, Jerome I Rotter, Clary B Clish, Usman A Tahir, Robert E Gerszten, Mark D Benson, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin’s effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2+ cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the …

European Society Of Coloproctology Guideline On Training In Robotic Colorectal Surgery (2024), Samson Tou, Stephanie Au, Cillian Clancy, Steven Clarke, Danielle Collins, Frances Dixon, Elizabeth Dreher, Christina Fleming, Anthony G Gallagher, Marcos Gomez-Ruiz, Jos Kleijnen, Yasuko Maeda, Katie Rollins, Klaus E Matzel

Staff and Researcher Publications

No abstract provided.

Signaling Mechanisms Underlying Activity-Dependent Integration Of Adult-Born Neurons In The Mouse Olfactory Bulb, Suyang Bao, Juan M Romero, Benjamin D W Belfort, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Adult neurogenesis has fascinated the field of neuroscience for decades given the prospects of harnessing mechanisms that facilitate the rewiring and/or replacement of adult brain tissue. The subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle are the two main areas in the brain that exhibit ongoing neurogenesis. Of these, adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and continued circuit integration within adult brain tissue. This review focuses on some of the recognized molecular and signaling …

Flexible Bayesian Product Mixture Models For Vector Autoregressions, Suprateek Kundu, Joshua Lukemire

Faculty, Staff and Student Publications

Bayesian non-parametric methods based on Dirichlet process mixtures have seen tremendous success in various domains and are appealing in being able to borrow information by clustering samples that share identical parameters. However, such methods can face hurdles in heterogeneous settings where objects are expected to cluster only along a subset of axes or where clusters of samples share only a subset of identical parameters. We overcome such limitations by developing a novel class of product of Dirichlet process location-scale mixtures that enables independent clustering at multiple scales, which results in varying levels of information sharing across samples. First, we develop …

Fear Antiviral Response Pathway Is Independent Of Interferons And Countered By Poxvirus Proteins, Emily A Rex, Dahee Seo, Sruthi Chappidi, Chelsea Pinkham, Sabrynna Brito Oliveira, Aaron Embry, David Heisler, Yang Liu, Moiz Munir, Karolin Luger, Neal M Alto, Flávio Guimarães Da Fonseca, Robert Orchard, Dustin C Hancks, Don B Gammon

Faculty, Staff and Student Publications

The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 …

Delta Radiomic Features Predict Resection Margin Status And Overall Survival In Neoadjuvant-Treated Pancreatic Cancer Patients, Kai Wang, John D Karalis, Ahmed Elamir, Alessandro Bifolco, Megan Wachsmann, Giovanni Capretti, Paola Spaggiari, Sebastian Enrico, Kishore Balasubramanian, Nafeesah Fatimah, Giada Pontecorvi, Martina Nebbia, Adam Yopp, Ravi Kaza, Ivan Pedrosa, Herbert Zeh, Patricio Polanco, Alessandro Zerbi, Jing Wang, Todd Aguilera, Matteo Ligorio

Faculty, Staff and Student Publications

Background: Neoadjuvant therapy (NAT) emerged as the standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgery; however, surgery is morbid, and tools to predict resection margin status (RMS) and prognosis in the preoperative setting are needed. Radiomic models, specifically delta radiomic features (DRFs), may provide insight into treatment dynamics to improve preoperative predictions.

Methods: We retrospectively collected clinical, pathological, and surgical data (patients with resectable, borderline, locally advanced, and metastatic disease), and pre/post-NAT contrast-enhanced computed tomography (CT) scans from PDAC patients at the University of Texas Southwestern Medical Center (UTSW; discovery) and Humanitas Hospital (validation cohort). …

Recurrent Lymphoid And Myeloid Relapses Due To Treatment Cessations Reveal Natural History Of Ph-Positive B-All And Pose A Diagnostic Challenge, Shimin Hu, Elias J Jabbour, Collin Y Hu, Guilin Tang, Wei Wang, L Jeffrey Medeiros, Carlos Bueso-Ramos

Faculty, Staff and Student Publications

No abstract provided.

Bone Marrow-Restricted Aberrant Myeloperoxidase Expression In B-Acute Lymphoblastic Leukemia: A Diagnostic Dilemma And Mimicry Of Mixed Phenotype Acute Leukemia, Wei J Wang, Brandon T Gehris, Daniel Rivera, Sibel Ak, David Feng, Wei Wang, Zhihong Hu

Faculty, Staff and Student Publications

Myeloperoxidase (MPO) is the most specific marker of the myeloid lineage, essential for diagnosing acute myeloid leukemia and mixed phenotype acute leukemia with myeloid components. In this regard, we present a unique case of B-acute lymphoblastic leukemia (B-ALL) with isolated MPO expression in bone marrow blasts detected by flow cytometry and immunohistochemistry, while peripheral blood blasts were negative for MPO expression. In this report, our discussion encompasses diagnostic pitfalls from a laboratory testing perspective in similar cases and includes a literature review. Furthermore, we emphasize the necessity of conducting a comprehensive analysis for the accurate diagnosis of MPO-positive B-ALL cases.

Diagnostic Utility Of Immunohistochemistry In Detection Of Npm1 Mutations In Acute Myeloid Leukemia With A Patchy Distribution, Qing Wei, Sa A Wang, Sanam Loghavi, Hong Fang, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

Nucleophosmin 1 (NPM1) mutations occur in approximately one‐third cases of adult de novo acute myeloid leukemia (AML). Identification of NPM1 mutations is important for classification, risk stratification, tailored therapy, and monitoring minimal residual disease. Mutational analysis is widely used for detecting NPM1 mutations. Immunochemistry assessing abnormal cytoplasmic localization of NPM1 protein has been used as a surrogate marker for NPM1 mutations. We present a case of AML with mutated NPM1 that was missed by sequencing analysis but detected by immunohistochemistry. This case highlights the value of immunohistochemistry in identifying NPM1 mutations in a subset of AML cases.

Alk-Positive Histiocytosis Of External Auditory Canal In A 3-Year-Old Boy, Shu-Hsien Wang, Hsuan-Ying Huang, L Jeffrey Medeiros, Kung-Chao Chang

Faculty, Staff and Student Publications

No abstract provided.