Digital Commons Network^™

Advancing Academic Capacity In Physical And Rehabilitation Medicine To Strengthen Rehabilitation In Health Systems Worldwide: A Joint Effort By The European Academy Of Rehabilitation Medicine, The Association Of Academic Physiatrists, And The International Society Of Physical And Rehabilitation Medicine, Walter R Frontera, Gerold Stucki, Julia P Engkasan, Gerard E Francisco, Christoph Gutenbrunner, Nazirah Hasnan, Jorge Lains, Yusniza Mohd Yusof, Stefano Negrini, Zaliha Omar, Linamara Rizzo Battistella, Gwen Sowa, Henk Stam, Jerome Bickenbach, European Academy Of Rehabilitation Medicine, Association Of Academic Physiatrists, International Society Of Physical And Rehabilitation Medicine

Faculty, Staff and Student Publications

No abstract provided.

Macrophage Migration Inhibitory Factor (Mif) Makes Complex Contributions To Pain-Related Hyperactivity Of Nociceptors After Spinal Cord Injury, Alexis Bavencoffe, Emily A Spence, Michael Y Zhu, Anibal Garza-Carbajal, Kerry E Chu, Ona E Bloom, Carmen W Dessauer, Edgar T Walters

Faculty, Staff and Student Publications

Neuropathic pain is a major, inadequately treated challenge for people with spinal cord injury (SCI). While SCI pain mechanisms are often assumed to be in the CNS, rodent studies have revealed mechanistic contributions from primary nociceptors. These neurons become chronically hyperexcitable after SCI, generating ongoing electrical activity that promotes ongoing pain. A major question is whether extrinsic chemical signals help to drive ongoing electrical activity after SCI. People living with SCI exhibit acute and chronic elevation of circulating levels of macrophage migration inhibitory factor (MIF), a cytokine implicated in preclinical pain models. Probable nociceptors isolated from male rats and exposed …

Vitamin E Enhances Cancer Immunotherapy By Reinvigorating Dendritic Cells Via Targeting Checkpoint Shp1, Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Yuan Zhang, Zamal Ahmed, Davide Moiani, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C Chang, John A Tainer, Dihua Yu

Faculty, Staff and Student Publications

Despite the popular use of dietary supplements during conventional cancer treatments, their impacts on the efficacies of prevalent immunotherapies, including immune-checkpoint therapy (ICT), are unknown. Surprisingly, our analyses of electronic health records revealed that ICT-treated patients with cancer who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DC). VitE entered DCs via the SCARB1 receptor and restored tumor-associated DC functionality by directly binding to and inhibiting protein tyrosine phosphatase SHP1, a DC-intrinsic checkpoint. SHP1 inhibition, genetically or by VitE treatment, enhanced tumor antigen cross-presentation by DCs and …

Drug-Target Network Study Reveals The Core Target-Protein Interactions Of Various Covid-19 Treatments, Yulin Dai, Hui Yu, Qiheng Yan, Bingrui Li, Andi Liu, Wendao Liu, Xiaoqian Jiang, Yejin Kim, Yan Guo, Zhongming Zhao

Faculty, Staff and Student Publications

The coronavirus disease 2019 (COVID-19) pandemic has caused a dramatic loss of human life and devastated the worldwide economy. Numerous efforts have been made to mitigate COVID-19 symptoms and reduce the death rate. We conducted literature mining of more than 250 thousand published works and curated the 174 most widely used COVID-19 medications. Overlaid with the human protein-protein interaction (PPI) network, we used Steiner tree analysis to extract a core subnetwork that grew from the pharmacological targets of ten credible drugs ascertained by the CTD database. The resultant core subnetwork consisted of 34 interconnected genes, which were associated with 36 …

Synthetic Essentiality Of Tryptophan 2,3-Dioxygenase 2 In Apc-Mutated Colorectal Cancer, Rumi Lee, Jiexi Li, Jun Li, Chang-Jiun Wu, Shan Jiang, Wen-Hao Hsu, Deepavali Chakravarti, Peiwen Chen, Kyle A Labella, Jing Li, Denise J Spring, Di Zhao, Y Alan Wang, Ronald A Depinho

Faculty, Staff and Student Publications

Inactivation of adenomatous polyposis coli (APC) is common across many cancer types and serves as a critical initiating event in most sporadic colorectal cancers. APC deficiency activates WNT signaling, which remains an elusive target for cancer therapy, prompting us to apply the synthetic essentiality framework to identify druggable vulnerabilities for APC-deficient cancers. Tryptophan 2,3-dioxygenase 2 (TDO2) was identified as a synthetic essential effector of APC-deficient colorectal cancer. Mechanistically, APC deficiency results in the TCF4/β-catenin-mediated upregulation of TDO2 gene transcription. TDO2 in turn activates the Kyn-AhR pathway, which increases glycolysis to drive anabolic cancer cell growth and CXCL5 secretion to recruit …

A Spatiotemporal Map Of Reading Aloud, Oscar Woolnough, Cristian Donos, Aidan Curtis, Patrick S Rollo, Zachary J Roccaforte, Stanislas Dehaene, Simon Fischer-Baum, Nitin Tandon

Faculty, Staff and Student Publications

Reading words aloud is a fundamental aspect of literacy. The rapid rate at which multiple distributed neural substrates are engaged in this process can only be probed via techniques with high spatiotemporal resolution. We probed this with direct intracranial recordings covering most of the left hemisphere in 46 humans (26 male, 20 female) as they read aloud regular, exception and pseudo-words. We used this to create a spatiotemporal map of word processing and to derive how broadband γ activity varies with multiple word attributes critical to reading speed: lexicality, word frequency, and orthographic neighborhood. We found that lexicality is encoded …

Novel Markers For Liquid Biopsies In Cancer Management: Circulating Platelets And Extracellular Vesicles, Sara Corvigno, Anna Maria Johnson, Kwong-Kwok Wong, Min Soon Cho, Vahid Afshar-Kharghan, David G Menter, Anil K Sood

Faculty, Staff and Student Publications

Although radiologic imaging and histologic assessment of tumor tissues are classic approaches for diagnosis and monitoring of treatment response, they have many limitations. These include challenges in distinguishing benign from malignant masses, difficult access to the tumor, high cost of the procedures, and tumor heterogeneity. In this setting, liquid biopsy has emerged as a potential alternative for both diagnostic and monitoring purposes. The approaches to liquid biopsy include cell-free DNA/circulating tumor DNA, long and micro noncoding RNAs, proteins/peptides, carbohydrates/lectins, lipids, and metabolites. Other approaches include detection and analysis of circulating tumor cells, extracellular vesicles, and tumor-activated platelets. Ultimately, reliable use …

Arrhythmia Monitoring And Outcomes In Patients With Cardiac Sarcoidosis: Insights From The Cardiac Sarcoidosis Consortium, Edoardo Bressi, Thomas C Crawford, Frank M Bogun, Xiaokui Gu, Kenneth A Ellenbogen, Alexandra B Chicos, Henri Roukoz, Peter J Zimetbaum, Steven J Kalbfleisch, Francis D Murgatroyd, David A Steckman, Lynda E Rosenfeld, Ann C Garlitski, Kyoko Soejima, Adarsh K Bhan, Vasanth Vedantham, Timm M Dickfeld, David B De Lurgio, Pyotr G Platonov, Matthew M Zipse, Suguru Nishiuchi, Matthew L Ortman, Calambur Narasimhan, Kris K Patton, David G Rosenthal, Siddharth S Mukerji, Jarieke C Hoogendoorn, Katja Zeppenfeld, William H Sauer, Jordana Kron

Faculty, Staff and Student Publications

No abstract provided.

Webcsea: Web-Based Cell-Type-Specific Enrichment Analysis Of Genes, Yulin Dai, Ruifeng Hu, Andi Liu, Kyung Serk Cho, Astrid Marilyn Manuel, Xiaoyang Li, Xianjun Dong, Peilin Jia, Zhongming Zhao

Faculty, Staff and Student Publications

Human complex traits and common diseases show tissue- and cell-type- specificity. Recently, single-cell RNA sequencing (scRNA-seq) technology has successfully depicted cellular heterogeneity in human tissue, providing an unprecedented opportunity to understand the context-specific expression of complex trait-associated genes in human tissue-cell types (TCs). Here, we present the first web-based application to quickly assess the cell-type-specificity of genes, named Web-based Cell-type Specific Enrichment Analysis of Genes (WebCSEA, available at https://bioinfo.uth.edu/webcsea/). Specifically, we curated a total of 111 scRNA-seq panels of human tissues and 1,355 TCs from 61 different general tissues across 11 human organ systems. We adapted our previous decoding tissue-specificity …

Modeling The Prognostic Impact Of Circulating Tumor Cells Enumeration In Metastatic Breast Cancer For Clinical Trial Design Simulation, Lorenzo Gerratana, Jean-Yves Pierga, James M Reuben, Andrew A Davis, Firas H Wehbe, Luc Dirix, Tanja Fehm, Franco Nolé, Rafael Gisbert-Criado, Dimitrios Mavroudis, Salvatore Grisanti, Jose A Garcia-Saenz, Justin Stebbing, Carlos Caldas, Paola Gazzaniga, Luis Manso, Rita Zamarchi, Marta Bonotto, Angela Fernandez De Lascoiti, Leticia De Mattos-Arruda, Michail Ignatiadis, Maria-Teresa Sandri, Daniele Generali, Carmine De Angelis, Sarah-Jane Dawson, Wolfgang Janni, Vicente Carañana, Sabine Riethdorf, Erich-Franz Solomayer, Fabio Puglisi, Mario Giuliano, Klaus Pantel, François-Clément Bidard, Massimo Cristofanilli

Faculty, Staff and Student Publications

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent). The model had a 65.1% accuracy and …

The Use Of Second-Generation Antipsychotics And The Changes In Physical Growth In Children And Adolescents With Perinatally Acquired Hiv, Nan Xin, Jenni Durieux, Chunxia Yang, Suzanne Wolff, Hyun-Eui Kim, Andrew Dillin

Faculty, Staff and Student Publications

The mitochondrial unfolded protein response (UPRmt) is dedicated to promoting mitochondrial proteostasis and is linked to extreme longevity. The key regulator of this process is the transcription factor ATFS-1, which, upon UPRmt activation, is excluded from the mitochondria and enters the nucleus to regulate UPRmt genes. However, the repair proteins synthesized as a direct result of UPRmt activation must be transported into damaged mitochondria that had previously excluded ATFS-1 owing to reduced import efficiency. To address this conundrum, we analyzed the role of the import machinery when the UPRmt was induced. Using in vitro and in vivo analysis of mitochondrial …

Pd-1/Pd-L1 Pathway: A Therapeutic Target In Cd30+ Large Cell Lymphomas, Wei Xie, L Jeffrey Medeiros, Shaoying Li, Guilin Tang, Guang Fan, Jie Xu

Faculty, Staff and Student Publications

The programmed death-ligands, PD-L1 and PD-L2, reside on tumor cells and can bind with programmed death-1 protein (PD-1) on T-cells, resulting in tumor immune escape. PD-1 ligands are highly expressed in some CD30+ large cell lymphomas, including classic Hodgkin lymphoma (CHL), primary mediastinal large B-cell lymphoma (PMBL), Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL), and anaplastic large cell lymphoma (ALCL). The genetic alteration of the chromosome 9p24.1 locus, the location of

Heart Transplant Recipient 1-Year Outcomes During The Covid-19 Pandemic, Gabriel Esmailian, Nikhil Patel, Jignesh K Patel, Lawrence Czer, Matthew Rafiei, Dominick Megna, Dominic Emerson, Danny Ramzy, Alfredo Trento, Joanna Chikwe, Fardad Esmailian, Jon A Kobashigawa

Faculty, Staff and Student Publications

The COVID-19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post-transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1-year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted …

Effects Of Combined Gentamicin And Furosemide Treatment On Cochlear Macrophages, Liana Sargsyan, Austin R Swisher, Alisa P Hetrick, Hongzhe Li

Faculty, Staff and Student Publications

Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in

Assessment Of Electronic Health Record For Cancer Research And Patient Care Through A Scoping Review Of Cancer Natural Language Processing, Liwei Wang, Sunyang Fu, Andrew Wen, Xiaoyang Ruan, Huan He, Sijia Liu, Sungrim Moon, Michelle Mai, Irbaz B Riaz, Nan Wang, Ping Yang, Hua Xu, Jeremy L Warner, Hongfang Liu

Faculty, Staff and Student Publications

Purpose: The advancement of natural language processing (NLP) has promoted the use of detailed textual data in electronic health records (EHRs) to support cancer research and to facilitate patient care. In this review, we aim to assess EHR for cancer research and patient care by using the Minimal Common Oncology Data Elements (mCODE), which is a community-driven effort to define a minimal set of data elements for cancer research and practice. Specifically, we aim to assess the alignment of NLP-extracted data elements with mCODE and review existing NLP methodologies for extracting said data elements.

Methods: Published literature studies were searched …

Deep Learning-Based Nlp Data Pipeline For Ehr-Scanned Document Information Extraction, Enshuo Hsu, Ioannis Malagaris, Yong-Fang Kuo, Rizwana Sultana, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: Scanned documents in electronic health records (EHR) have been a challenge for decades, and are expected to stay in the foreseeable future. Current approaches for processing include image preprocessing, optical character recognition (OCR), and natural language processing (NLP). However, there is limited work evaluating the interaction of image preprocessing methods, NLP models, and document layout.

MATERIALS AND METHODS: We evaluated 2 key indicators for sleep apnea, Apnea hypopnea index (AHI) and oxygen saturation (SaO

RESULTS: Our proposed method using ClinicalBERT reached an AUROC of 0.9743 and document accuracy of 94.76% for AHI, and an AUROC of 0.9523 and document …

Muc1 And Polarity Markers Inadl And Scrib Identify Salivary Ductal Cells, D Wu, P J Chapela, C M L Barrows, D A Harrington, D D Carson, R L Witt, N G Mohyuddin, S Pradhan-Bhatt, M C Farach-Carson

Faculty, Staff and Student Publications

Current treatments for xerostomia/dry mouth are palliative and largely ineffective. A permanent clinical resolution is being developed to correct hyposalivation using implanted hydrogel-encapsulated salivary human stem/progenitor cells (hS/PCs) to restore functional salivary components and increase salivary flow. Pluripotent epithelial cell populations derived from hS/PCs, representing a basal stem cell population in tissue, can differentiate along either secretory acinar or fluid-transporting ductal lineages. To develop tissue-engineered salivary gland replacement tissues, it is critical to reliably identify cells in tissue and as they enter these alternative lineages. The secreted protein α-amylase, the transcription factor MIST1, and aquaporin-5 are typical markers for acinar …

Prevalence And Clustering Of Congenital Heart Defects Among Boys With Hypospadias, Melissa A Richard, Jenil Patel, Renata H Benjamin, Emine Bircan, Stephen J Canon, Lisa K Marengo, Mark A Canfield, A J Agopian, Philip J Lupo, Wendy N Nembhard

Faculty, Staff and Student Publications

IMPORTANCE: Hypospadias is a common birth defect of the male urinary tract that may be isolated or may co-occur with other structural malformations, including congenital heart defects (CHDs). The risk for co-occurring CHDs among boys with hypospadias remains unknown, which limits screening and genetic testing strategies.

OBJECTIVE: to characterize the risk of major CHDs among boys born with hypospadias.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from population-based birth defect surveillance programs on all male infants born in 11 US states from January 1, 1995, to December 31, 2014. Statistical analysis was performed from September 2, 2020, …

Potential Impact Of Revised Nci Eligibility Criteria Guidance: Prior Malignancy Exclusion In Breast Cancer Clinical Trials, Matthew Perez, Caitlin C Murphy, Sandi L Pruitt, Sawsan Rashdan, Asal Rahimi, David E Gerber

Faculty, Staff and Student Publications

BACKGROUND: Many individuals with cancer have survived a prior cancer and for this reason may have been excluded from clinical trials. Recent NCI guidance recommends including these individuals, especially when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. Using breast cancer as an example, we determined the potential effect this policy change may have on clinical trial accrual.

PATIENTS AND METHODS: We reviewed protocols of NCI-sponsored breast cancer clinical trials activated in 1991 through 2016. We quantified prevalence of prior cancer-related exclusion criteria and assessed the association with trial characteristics using Fisher's …

Cas9/Nickase-Induced Allelic Conversion By Homologous Chromosome-Templated Repair In Drosophila Somatic Cells, Sitara Roy, Sara Sanz Juste, Marketta Sneider, Ankush Auradkar, Carissa Klanseck, Zhiqian Li, Alison Henrique Ferreira Julio, Victor Lopez Del Amo, Ethan Bier, Annabel Guichard

Faculty, Staff and Student Publications

Repair of double-strand breaks (DSBs) in somatic cells is primarily accomplished by error-prone nonhomologous end joining and less frequently by precise homology-directed repair preferentially using the sister chromatid as a template. Here, a

Vaccine Hesitancy And Betrayal Aversion, Abdelaziz Alsharawy, Esha Dwibedi, Jason Aimone, Sheryl Ball

Faculty, Staff and Student Publications

The determinants of vaccine hesitancy remain complex and context specific. Betrayal aversion occurs when an individual is hesitant to risk being betrayed in an environment involving trust. In this pre-registered vignette experiment, we show that betrayal aversion is not captured by current vaccine hesitancy measures despite representing a significant source of unwillingness to be vaccinated. Our survey instrument was administered to 888 United States residents via Amazon Mechanical Turk in March 2021. We find that over a third of participants have betrayal averse preferences, resulting in an 8-26% decline in vaccine acceptance, depending on the betrayal source. Interestingly, attributing betrayal …

Pirtobrutinib Inhibits Wild-Type And Mutant Bruton’S Tyrosine Kinase-Mediated Signaling In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells.

We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide preserves CD23.CAR T cells in vitro effector functions in terms of antigen-specific cytotoxicity, cytokine release and proliferation. Overall, lenalidomide …

Covid-Associated Avascular Necrosis Of The Maxilla-A Rare, New Side Effect Of Covid-19, Victoria A Mañón, Steven Balandran, Simon Young, Mark Wong, James C Melville

Faculty, Staff and Student Publications

Purpose: The purpose of this article is to present an interesting, rare case of a patient who experienced avascular necrosis of the maxilla associated with COVID-19 infection.

Methods and results: Our team retrospectively evaluated this patient's chart after completion of surgical management. The patient is a 72-year-old male who presented to the University of Texas Health Science Center at Houston for surgical management of his infarcted maxilla, which developed as a sequela of infection with COVID-19. A literature review was completed using PubMed. Twenty-five articles are reviewed and discussed.

Conclusions: Infection with COVID-19 confers a hypercoagulable state in patients, leading …

Impact Of Explainable Artificial Intelligence Assistance On Clinical Decision-Making Of Novice Dental Clinicians, Aaron Glick, Mackenzie Clayton, Nikola Angelov, Jennifer Chang

Faculty, Staff and Student Publications

OBJECTIVE: Despite artificial intelligence (AI) being used increasingly in healthcare, implementation challenges exist leading to potential biases during the clinical decision process of the practitioner. The interaction of AI with novice clinicians was investigated through an identification task, an important component of diagnosis, in dental radiography. The study evaluated the performance, efficiency, and confidence level of dental students on radiographic identification of furcation involvement (FI), with and without AI assistance.

MATERIALS AND METHODS: Twenty-two third- and 19 fourth-year dental students (DS3 and DS4, respectively) completed remotely administered surveys to identify FI lesions on a series of dental radiographs. The control …

Vaccine Hesitancy And Betrayal Aversion, Abdelaziz Alsharawy, Esha Dwibedi, Jason Aimone, Sheryl Ball

Faculty, Staff and Student Publications

The determinants of vaccine hesitancy remain complex and context specific. Betrayal aversion occurs when an individual is hesitant to risk being betrayed in an environment involving trust. In this pre-registered vignette experiment, we show that betrayal aversion is not captured by current vaccine hesitancy measures despite representing a significant source of unwillingness to be vaccinated. Our survey instrument was administered to 888 United States residents via Amazon Mechanical Turk in March 2021. We find that over a third of participants have betrayal averse preferences, resulting in an 8-26% decline in vaccine acceptance, depending on the betrayal source. Interestingly, attributing betrayal …

Maternal Obesity, Pregnancy Weight Gain, And Birth Weight And Risk Of Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Minjae Lee, Timothy Zaki, Ezra Burstein, Barbara A Cohn

Faculty, Staff and Student Publications

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect on cancer in adulthood. We examined associations of maternal obesity, pregnancy weight gain, and birth weight and CRC in adult offspring.

Design: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California (N=18 751 live births among 14 507 mothers). Clinical information was abstracted from mothers' medical records 6 months prior to pregnancy through delivery. Diagnoses of …

The 5th Edition Of The World Health Organization Classification Of Haematolymphoid Tumours: Lymphoid Neoplasms, Rita Alaggio, Catalina Amador, Ioannis Anagnostopoulos, Ayoma D Attygalle, Iguaracyra Barreto De Oliveira Araujo, Emilio Berti, Govind Bhagat, Anita Maria Borges, Daniel Boyer, Mariarita Calaminici, Amy Chadburn, John K C Chan, Wah Cheuk, Wee-Joo Chng, John K Choi, Shih-Sung Chuang, Sarah E Coupland, Magdalena Czader, Sandeep S Dave, Daphne De Jong, Ming-Qing Du, Kojo S Elenitoba-Johnson, Judith Ferry, Julia Geyer, Dita Gratzinger, Joan Guitart, Sumeet Gujral, Marian Harris, Christine J Harrison, Sylvia Hartmann, Andreas Hochhaus, Patty M Jansen, Kennosuke Karube, Werner Kempf, Joseph Khoury, Hiroshi Kimura, Wolfram Klapper, Alexandra E Kovach, Shaji Kumar, Alexander J Lazar, Stefano Lazzi, Lorenzo Leoncini, Nelson Leung, Vasiliki Leventaki, Xiao-Qiu Li, Megan S Lim, Wei-Ping Liu, Abner Louissaint, Andrea Marcogliese, L Jeffrey Medeiros, Michael Michal, Roberto N Miranda, Christina Mitteldorf, Santiago Montes-Moreno, William Morice, Valentina Nardi, Kikkeri N Naresh, Yasodha Natkunam, Siok-Bian Ng, Ilske Oschlies, German Ott, Marie Parrens, Melissa Pulitzer, S Vincent Rajkumar, Andrew C Rawstron, Karen Rech, Andreas Rosenwald, Jonathan Said, Clémentine Sarkozy, Shahin Sayed, Caner Saygin, Anna Schuh, William Sewell, Reiner Siebert, Aliyah R Sohani, Reuben Tooze, Alexandra Traverse-Glehen, Francisco Vega, Beatrice Vergier, Ashutosh D Wechalekar, Brent Wood, Luc Xerri, Wenbin Xiao

Faculty, Staff and Student Publications

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as …

Functional Genomic Analysis Of Epithelioid Sarcoma Reveals Distinct Proximal And Distal Subtype Biology, Samuel V Rasmussen, Jia Xiang Jin, Lissett R Bickford, Andrew D Woods, Felix Sahm, Kenneth A Crawford, Kiyo Nagamori, Hiroaki Goto, Keila E Torres, Angelo Sidoni, Erin R Rudzinski, Khin Thway, Robin L Jones, Alessio Ciulli, Hollis Wright, Melvin Lathara, Ganapati Srinivasa, Kavya Kannan, Paul H Huang, Thomas G P Grünewald, Noah E Berlow, Charles Keller

Faculty, Staff and Student Publications

Background: Metastatic epithelioid sarcoma (EPS) remains a largely unmet clinical need in children, adolescents and young adults despite the advent of EZH2 inhibitor tazemetostat.

Methods: In order to realise consistently effective drug therapies, a functional genomics approach was used to identify key signalling pathway vulnerabilities in a spectrum of EPS patient samples. EPS biopsies/surgical resections and cell lines were studied by next-generation DNA exome and RNA deep sequencing, then EPS cell cultures were tested against a panel of chemical probes to discover signalling pathway targets with the most significant contributions to EPS tumour cell maintenance.

Results: Other biologically inspired functional …

Leveraging Single-Cell Sequencing To Unravel Intratumour Heterogeneity And Tumour Evolution In Human Cancers, Amy L Bowes, Maxime Tarabichi, Nischalan Pillay, Peter Van Loo

Faculty, Staff and Student Publications

Intratumour heterogeneity (ITH) and tumour evolution are well-documented phenomena in human cancers. While the advent of next-generation sequencing technologies has facilitated the large-scale capture of genomic data, the field of single-cell genomics is nascent but rapidly advancing and generating many new insights into the complex molecular mechanisms of tumour biology. In this review, we provide an overview of current single-cell DNA sequencing technologies, exploring how recent methodological advancements have enumerated new insights into ITH and tumour evolution. Areas highlighted include the potential power of single-cell genome sequencing studies to explore evolutionary dynamics contributing to tumourigenesis through to progression, metastasis, and …

Hypertension In Pregnancy And Adverse Outcomes Among Low-Risk Nulliparous People Expectantly Managed At Or After 39 Weeks: A Secondary Analysis Of A Randomized Controlled Trial, Michal Fishel Bartal, Ashish Premkumar, Madeline Murguia Rice, Uma M Reddy, Alan T N Tita, Robert M Silver, Yasser Y El-Sayed, Ronald J Wapner, Dwight J Rouse, George R Saade, John M Thorp, Maged M Costantine, Edward K Chien, Brian M Casey, Sindhu K Srinivas, Geeta K Swamy, Hyagriv N Simhan, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy (HDP) among low-risk nulliparous women expectantly managed at or after 39 weeks of gestation are associated with adverse outcomes.

DESIGN: Secondary analysis of a randomised trial.

SETTING: Multicentre, USA.

POPULATION: Individuals in the expectantly managed group who delivered on or after 39 weeks.

METHODS: Multivariable analysis to estimate adjusted relative risks (aRR) for binomial outcomes, adjusted odds ratios (aOR) for multinomial outcomes and 95% CI.

MAIN OUTCOME MEASURES: Composite adverse maternal outcome including placental abruption, pulmonary oedema, postpartum haemorrhage, postpartum infection, venous thromboembolism or intensive care unit admission. Secondary outcomes included a …