Medical Specialties Commons^™

Does Receiving A Sars-Cov-2 Antibody Test Result Change Covid-19 Protective Behaviors? Testing Risk Compensation In Undergraduate Students With A Randomized Controlled Trial, Christina Ludema, Molly S Rosenberg, Jonathan T Macy, Sina Kianersi, Maya Luetke, Chen Chen, Lilian Golzarri-Arroyo, Erin Ables, Kevin Maki, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Risk compensation, or matching behavior to a perceived level of acceptable risk, can blunt the effectiveness of public health interventions. One area of possible risk compensation during the SARS-CoV-2 pandemic is antibody testing. While antibody tests are imperfect measures of immunity, results may influence risk perception and individual preventive actions. We conducted a randomized control trial to assess whether receiving antibody test results changed SARS-CoV-2 protective behaviors.

Purpose: Assess whether objective information about antibody status, particularly for those who are antibody negative and likely still susceptible to SARS-CoV-2 infection, increases protective behaviors. Secondarily, assess whether a positive antibody test …

Spatial Heterogeneity Of Infiltrating T Cells In High-Grade Serous Ovarian Cancer Revealed By Multi-Omics Analysis, Bin Yang, Xiong Li, Wei Zhang, Junpeng Fan, Yong Zhou, Wenting Li, Jingjing Yin, Xiaohang Yang, Ensong Guo, Xi Li, Yu Fu, Si Liu, Dianxing Hu, Xu Qin, Yingyu Dou, Rourou Xiao, Funian Lu, Zizhuo Wang, Tianyu Qin, Wei Wang, Qinghua Zhang, Shuaicheng Li, Ding Ma, Gordon B Mills, Gang Chen, Chaoyang Sun

Faculty, Staff and Student Publications

Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune "cold" patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T …

Does The Anastatica Hierochuntica Plant Shorten The Duration Of Labour? A Prospective Observational Study, Filiz Okumuş, Halime Öncü-Çelik, Nevin Şahin

Journal of Asian Midwives (JAM)

Objective: This study aims to investigate the effect of Anastatica Hierochuntica L. on the duration of labour in primiparous women.
Methods: A prospective, case-controlled study with an intervention (n=28) and control (n=29) group. Participants were not randomized; their preferences related to the use of the A. Hierochuntica L. determined the group in which they would be included. In the intervention group, Anastatica Hierochuntica L. was used by all women. Standard care continued for both the intervention and control group. The duration of the first and second stage of labour were evaluated and compared between groups.
Results: Participants’ mean of age …

The Role Of Lncrnas In The Tumor Microenvironment And Immunotherapy Of Melanoma, Wencheng Zhou, Xuewen Xu, Ying Cen, Junjie Chen

Faculty, Staff and Student Publications

Melanoma is one of the most lethal tumors with highly aggressive and metastatic properties. Although immunotherapy and targeted therapy have certain therapeutic effects in melanoma, a significant proportion of patients still have drug resistance after treatment. Recent studies have shown that long noncoding RNAs (lncRNAs) are widely recognized as regulatory factors in cancer. They can regulate numerous cellular processes, including cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) progression and the immune microenvironment. The role of lncRNAs in malignant tumors has received much attention, whereas the relationship between lncRNAs and melanoma requires further investigation. Our review summarizes tumor suppressive and oncogenic lncRNAs …

Accumulation Of Sublethal Radiation Damage And Its Effect On Cell Survival, Oleg N Vassiliev

Faculty, Staff and Student Publications

Objective. Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival. Approach. We developed a novel formalism to account for accumulation of SRD with increasing dose. It is based on a very general formula for cell survival that correctly predicts the basic properties of cell survival curves, such as the transition from the linear-quadratic to a linear dependence at high doses. Using this formalism we analyzed extensive experimental data for photons, protons and heavy ions to evaluate model parameters, quantify the extent …

Image Fusion Involving Real-Time Transabdominal Or Endoscopic Ultrasound For Gastrointestinal Malignancies: Review Of Current And Future Applications, Ben S Singh, Irina M Cazacu, Carlos A Deza, Bastien S Rigaud, Adrian Saftoiu, Gabriel Gruionu, Lucian Guionu, Kristy K Brock, Eugene J Koay, Joseph M Herman, Manoop S Bhutani

Faculty, Staff and Student Publications

Image fusion of CT, MRI, and PET with endoscopic ultrasound and transabdominal ultrasound can be promising for GI malignancies as it has the potential to allow for a more precise lesion characterization with higher accuracy in tumor detection, staging, and interventional/image guidance. We conducted a literature review to identify the current possibilities of real-time image fusion involving US with a focus on clinical applications in the management of GI malignancies. Liver applications have been the most extensively investigated, either in experimental or commercially available systems. Real-time US fusion imaging of the liver is gaining more acceptance as it enables further …

Nuclear S6k1 Enhances Oncogenic Wnt Signaling By Inducing Wnt/Β-Catenin Transcriptional Complex Formation, Min Gyu Lee, Hwamok Oh, Jong Woo Park, Jueng Soo You, Jeung-Whan Han

Faculty, Staff and Student Publications

Ribosomal protein S6 kinase 1 (S6K1), a key downstream effector of the mammalian target of rapamycin (mTOR), regulates diverse functions, such as cell proliferation, cell growth, and protein synthesis. Because S6K1 was previously known to be localized in the cytoplasm, its function has been mainly studied in the cytoplasm. However, the nuclear localization and function of S6K1 have recently been elucidated and other nuclear functions are expected to exist but remain elusive. Here, we show a novel nuclear role of S6K1 in regulating the expression of the Wnt target genes. Upon activation of the Wnt signaling, S6K1 translocated from the …

Integrated Multi-Omic Analysis Of Low-Grade Ovarian Serous Carcinoma Collected From Short And Long-Term Survivors, Kwong-Kwok Wong, Nicholas W Bateman, Chun Wai Ng, Yvonne T M Tsang, Charlotte S Sun, Joseph Celestino, Tri V Nguyen, Anais Malpica, R Tyler Hillman, Jianhua Zhang, P Andrew Futreal, Christine Rojas, Kelly A Conrads, Brian L Hood, Clifton L Dalgard, Matthew D Wilkerson, Neil T Phippen, Thomas P Conrads, George L Maxwell, Anil K Sood, David M Gershenson

Faculty, Staff and Student Publications

BACKGROUND: Low-grade serous ovarian cancer (LGSOC) is a rare disease that occurs more frequently in younger women than those with high-grade disease. The current treatment is suboptimal and a better understanding of the molecular pathogenesis of this disease is required. In this study, we compared the proteogenomic analyses of LGSOCs from short- and long-term survivors (defined as < 40 and > 60 months, respectively). Our goal was to identify novel mutations, proteins, and mRNA transcripts that are dysregulated in LGSOC, particularly in short-term survivors.

METHODS: Initially, targeted sequencing of 409 cancer-related genes was performed on 22 LGSOC and 6 serous borderline ovarian tumor samples. …

Research Infrastructure Core Facilities At Research Centers In Minority Institutions: Part I-Research Resources Management, Operation, And Best Practices, Paul B Tchounwou, Mohamad Malouhi, Elizabeth O Ofili, Emma Fernández-Repollet, Daniel F Sarpong, Richard Yanagihara, Renato J Aguilera, Cecilia Ayón, Xiaoxin Chen, Asok Dasmahapatra, Song Gao, Cimona V Hinton, Robert Holt, Vladimir Kolesnichenko, Michael D Powell, Fatima Merchant, Kinfe K Redda, Abiel Roche-Lima, Cecilia M Shikuma, Jacqueline J Stevens, Jose A Torres, Robert T Trotter, James Wachira, Paul Wang, Kristen J Wells, Jason White, Yanyuan Wu

Faculty, Staff and Student Publications

Funded by the National Institutes of Health (NIH), the Research Centers in Minority Institutions (RCMI) Program fosters the development and implementation of innovative research aimed at improving minority health and reducing or eliminating health disparities. Currently, there are 21 RCMI Specialized (U54) Centers that share the same framework, comprising four required core components, namely the Administrative, Research Infrastructure, Investigator Development, and Community Engagement Cores. The Research Infrastructure Core (RIC) is fundamentally important for biomedical and health disparities research as a critical function domain. This paper aims to assess the research resources and services provided and evaluate the best practices in …

In Vivo Characterization Of Glutamine Metabolism Identifies Therapeutic Targets In Clear Cell Renal Cell Carcinoma, Akash K Kaushik, Amy Tarangelo, Lindsey K Boroughs, Mukundan Ragavan, Yuanyuan Zhang, Cheng-Yang Wu, Xiangyi Li, Kristen Ahumada, Jui-Chung Chiang, Vanina T Tcheuyap, Faeze Saatchi, Quyen N Do, Cissy Yong, Tracy Rosales, Christina Stevens, Aparna D Rao, Brandon Faubert, Panayotis Pachnis, Lauren G Zacharias, Hieu Vu, Feng Cai, Thomas P Mathews, Giannicola Genovese, Barbara S Slusher, Payal Kapur, Xiankai Sun, Matthew Merritt, James Brugarolas, Ralph J Deberardinis

Faculty, Staff and Student Publications

Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed the metabolism of patient-derived xenografts (tumorgrafts) from diverse subtypes of RCC. Tumorgrafts from VHL-mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engaged in oxidative and reductive glutamine metabolism. Genetic silencing of isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 impaired reductive labeling of tricarboxylic acid (TCA) cycle intermediates in vivo and suppressed growth of tumors generated from tumorgraft-derived cells. Glutaminase inhibition reduced the contribution of glutamine to the TCA cycle and resulted in modest suppression of tumorgraft growth. Infusions with …

Protocol For Mathematical Prediction Of Patient Response And Survival To Immune Checkpoint Inhibitor Immunotherapy, Joseph D Butner, Maguy Farhat, Vittorio Cristini, Caroline Chung, Zhihui Wang

Faculty, Staff and Student Publications

This protocol describes the application of a mechanistic mathematical model of immune checkpoint inhibitor (ICI) immunotherapy to patient tumor imaging data for predicting solid tumor response and patient survival under ICI intervention. We describe steps for data collection and processing, data pipelines, and approaches to increase precision. The protocol is highly predictive as early as the first restaging after treatment start and can be used with standard-of-care imaging measures. For complete details on the use and execution of this protocol, please refer to Butner et al. (2020)

Processing And Cryopreservation Of Human Ureter Tissues For Single-Cell And Spatial Transcriptomics Assays, Emily E Fink, Surbhi Sona, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Characterizing the cellular heterogeneity of human ureter tissues using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics provides a detailed atlas of cell types, signaling networks, and potential cell-cell cross talk underlying developmental and regenerative pathways. We describe an optimized protocol for generating, cryopreserving, and thawing single-cell suspensions from ureter tissues isolated post-cystectomy for scRNA-seq. In addition, we describe an optimized protocol for cryopreserving human ureter tissues for 10x Genomics Visium spatial gene expression platform. For complete details on the use and execution of this protocol, please refer to Fink et al. (2022).

Isolation, Culture, And Immunophenotypic Analysis Of Bone Marrow Hspcs From Patients With Myelodysplastic Syndromes, Irene Ganan-Gomez, Karen Clise-Dwyer, Simona Colla

Faculty, Staff and Student Publications

Drug testing assays in hematopoietic stem and progenitor cells (HSPCs) are fundamental in biological studies of myelodysplastic syndromes (MDS) but have historically entailed a technical challenge. This protocol allows the efficient isolation of MDS HSPCs from bone marrow mononuclear cell fractions and their culturing with the support of stromal cells for improved maintenance during drug testing. Lastly, specific steps are given to quantify surviving cells and assess changes in the HSPC hierarchies.

For complete details on the use and execution of this protocol, please refer to Ganan-Gomez et al. (2022).

Deciphering The Mechanism And Function Of Hsp100 Unfoldases From Protein Structure, Grace Lee, Rebecca S Kim, Sang Bum Lee, Sukyeong Lee, Francis T F Tsai

Faculty, Staff and Students Publications

Hsp100 chaperones, also known as Clp proteins, constitute a family of ring-forming ATPases that differ in 3D structure and cellular function from other stress-inducible molecular chaperones. While the vast majority of ATP-dependent molecular chaperones promote the folding of either the nascent chain or a newly imported polypeptide to reach its native conformation, Hsp100 chaperones harness metabolic energy to perform the reverse and facilitate the unfolding of a misfolded polypeptide or protein aggregate. It is now known that inside cells and organelles, different Hsp100 members are involved in rescuing stress-damaged proteins from a previously aggregated state or in recycling polypeptides marked …

Egfr Is A Master Switch Between Immunosuppressive And Immunoactive Tumor Microenvironment In Inflammatory Breast Cancer, Xiaoping Wang, Takashi Semba, Ganiraju C Manyam, Jing Wang, Shan Shao, Francois Bertucci, Pascal Finetti, Savitri Krishnamurthy, Lan Thi Hanh Phi, Troy Pearson, Steven J Van Laere, Jared K Burks, Evan N Cohen, James M Reuben, Fei Yang, Hu Min, Nicholas Navin, Van Ngu Trinh, Toshiaki Iwase, Harsh Batra, Yichao Shen, Xiang Zhang, Debu Tripathy, Naoto T Ueno

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC), the most aggressive breast cancer subtype, is driven by an immunosuppressive tumor microenvironment (TME). Current treatments for IBC have limited efficacy. In a clinical trial (NCT01036087), an anti-EGFR antibody combined with neoadjuvant chemotherapy produced the highest pathological complete response rate ever reported in patients with IBC having triple-negative receptor status. We determined the molecular and immunological mechanisms behind this superior clinical outcome. Using novel humanized IBC mouse models, we discovered that EGFR-targeted therapy remodels the IBC TME by increasing cytotoxic T cells and reducing immunosuppressive regulatory T cells and M2 macrophages. These changes were due to …

Frequency And Burden Of Neurological Manifestations Upon Hospital Presentation In Covid-19 Patients: Findings From A Large Brazilian Cohort, Milena Soriano Marcolino, Fernando Anschau, Luciane Kopittke, Magda Carvalho Pires, Izabela Guimarães Barbosa, Daniella Nunes Pereira, Lucas Emanuel Ferreira Ramos, Luís Fernando Israel Assunção, André Soares De Moura Costa, Matheus Carvalho Alves Nogueira, Helena Duani, Karina Paula Medeiros Prado Martins, Leila Beltrami Moreira, Carla Thais Cândida Alves Da Silva, Neimy Ramos De Oliveira, Patricia Klarmann Ziegelmann, Milton Henriques Guimarães-Júnior, Mauro Oscar Soares De Souza Lima, Rubia Laura Oliveira Aguiar, Luanna Silva Monteiro Menezes, Talita Fischer Oliveira, Maíra Dias Souza, Bárbara Lopes Farace, Christiane Corrêa Rodrigues Cimini, Amanda De Oliveira Maurílio, Silvana Mangeon Mereilles Guimarães, Silvia Ferreira Araújo, Guilherme Fagundes Nascimento, Daniel Vitório Silveira, Karen Brasil Ruschel, Thainara Conceição De Oliveira, Alexandre Vargas Schwarzbold, Luiz Antônio Nasi, Maiara Anschau Floriani, Veridiana Baldon Dos Santos, Carolina Marques Ramos, Joice Coutinho De Alvarenga, Ana Luiza Bahia Alves Scotton, Euler Roberto Fernandes Manenti, Gabriela Petry Crestani, Joanna D'Arc Lyra Batista, Daniela Ponce, Juliana Machado-Rugolo, Adriana Falangola Benjamin Bezerra, Petrônio José De Lima Martelli, Heloisa Reniers Vianna, Luís César De Castro, Cássia Regina Gotler Medeiros, Giovanna Grunewald Vietta, Elayne Crestani Pereira, José Miguel Chatkin, Mariana Frizzo De Godoy, Polianna Delfino-Pereira, Antonio Lucio Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection and outcomes in the Brazilian population.

METHODS: This study is part of the Brazilian COVID-19 Registry, a multicentric cohort, including data from 37 hospitals. For the present analysis, patients were grouped according to the presence of reported symptoms (i.e., headache; anosmia and ageusia; syncope and dizziness) vs. clinically-diagnosed neurological manifestations (clinically-defined neurological syndrome: neurological signs or diagnoses captured by clinical evaluation) and matched with patients without neurological manifestations by …

The Challenges And Opportunities Of Scrna-Seq In Covid-19 Research And Clinical Translation, Wendao Liu, Xiaohua Ye, Zhiqiang An, Zhongming Zhao

Faculty, Staff and Student Publications

The application of single-cell RNA sequencing in COVID-19 research has greatly improved our understanding of COVID-19 pathogenesis and immunological characteristics. In this commentary, we discuss the current challenges, limitations, and perspectives in harnessing the power of single-cell RNA sequencing to accelerate both basic research and therapeutic development for COVID-19 and other emerging infectious diseases.

Outcomes In Patients With Poor-Risk Cytogenetics With Or Without Tp53 Mutations Treated With Venetoclax And Azacitidine, Daniel A Pollyea, Keith W Pratz, Andrew H Wei, Vinod Pullarkat, Brian A Jonas, Christian Recher, Sunil Babu, Andre C Schuh, Monique Dail, Yan Sun, Jalaja Potluri, Brenda Chyla, Courtney D Dinardo

Faculty, Staff and Student Publications

PURPOSE: To evaluate efficacy and safety of venetoclax + azacitidine in treatment-naïve patients with acute myeloid leukemia harboring poor-risk cytogenetics and TP53mut or TP53wt.

PATIENTS AND METHODS: We analyzed data from a phase III study (NCT02993523) comparing venetoclax (400 mg orally days 1-28) + azacitidine (75 mg/m2 days 1-7) or placebo + azacitidine, and from a phase Ib study (NCT02203773) of venetoclax + azacitidine. Patients were ineligible for intensive therapy. TP53 status was analyzed centrally; cytogenetic studies were performed locally.

RESULTS: Patients (n = 127) with poor-risk cytogenetics receiving venetoclax + azacitidine (TP53wt = 50; TP53mut = 54) were compared …

3d Imaging Analysis On An Organoid-Based Platform Guides Personalized Treatment In Pancreatic Ductal Adenocarcinoma, Ya'an Kang, Jenying Deng, Jianhua Ling, Xinqun Li, Yi-Ju Chiang, Eugene J Koay, Huamin Wang, Jared K Burks, Paul J Chiao, Mark W Hurd, Manoop S Bhutani, Jeffrey H Lee, Brian R Weston, Anirban Maitra, Naruhiko Ikoma, Ching-Wei D Tzeng, Jeffrey E Lee, Ronald A Depinho, Robert A Wolff, Shubham Pant, Florencia Mcallister, Matthew Hg Katz, Jason B Fleming, Michael P Kim

Faculty, Staff and Student Publications

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care …

Tiam1-Mediated Synaptic Plasticity Underlies Comorbid Depression-Like And Ketamine Antidepressant-Like Actions In Chronic Pain, Qin Ru, Yungang Lu, Ali Bin Saifullah, Francisco A Blanco, Changqun Yao, Juan P Cata, De-Pei Li, Kimberley F Tolias, Lingyong Li

Faculty, Staff and Students Publications

Chronic pain often leads to depression, increasing patient suffering and worsening prognosis. While hyperactivity of the anterior cingulate cortex (ACC) appears to be critically involved, the molecular mechanisms underlying comorbid depressive symptoms in chronic pain remain elusive. T cell lymphoma invasion and metastasis 1 (Tiam1) is a Rac1 guanine nucleotide exchange factor (GEF) that promotes dendrite, spine, and synapse development during brain development. Here, we show that Tiam1 orchestrates synaptic structural and functional plasticity in ACC neurons via actin cytoskeleton reorganization and synaptic N-methyl-d-aspartate receptor (NMDAR) stabilization. This Tiam1-coordinated synaptic plasticity underpins ACC hyperactivity and drives chronic pain-induced depressive-like behaviors. …

Detection Of Stroke With Retinal Microvascular Density And Self-Supervised Learning Using Oct-A And Fundus Imaging, Samiksha Pachade, Ivan Coronado, Rania Abdelkhaleq, Juntao Yan, Sergio Salazar-Marioni, Amanda Jagolino, Charles Green, Mozhdeh Bahrainian, Roomasa Channa, Sunil A Sheth, Luca Giancardo

Faculty, Staff and Student Publications

Acute cerebral stroke is a leading cause of disability and death, which could be reduced with a prompt diagnosis during patient transportation to the hospital. A portable retina imaging system could enable this by measuring vascular information and blood perfusion in the retina and, due to the homology between retinal and cerebral vessels, infer if a cerebral stroke is underway. However, the feasibility of this strategy, the imaging features, and retina imaging modalities to do this are not clear. In this work, we show initial evidence of the feasibility of this approach by training machine learning models using feature engineering …

A Gating Lever And Molecular Logic Gate That Couple Voltage And Calcium Sensor Activation To Opening In Bk Potassium Channels, Liang Sun, Frank T Horrigan

Faculty, Staff and Students Publications

BK channels uniquely integrate voltage and calcium signaling in diverse cell types through allosteric activation of their K+-conducting pore by structurally distinct V and Ca2+ sensor domains. Here, we define mechanisms and interaction pathways that link V sensors to the pore by analyzing effects on allosteric coupling of point mutations in the context of Slo1 BK channel structure. A gating lever, mediated by S4/S5 segment interaction within the transmembrane domain, rotates to engage and stabilize the open conformation of the S6 inner pore helix upon V sensor activation. In addition, an indirect pathway, mediated by the carboxyl-terminal cytosolic domain (CTD) …

Single Cell Rna Sequencing Of The Adult Drosophila Eye Reveals Distinct Clusters And Novel Marker Genes For All Major Cell Types, Kelvin Yeung, Komal Kumar Bollepogu Raja, Yoon-Kyung Shim, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The adult Drosophila eye is a powerful model system for phototransduction and neurodegeneration research. However, single cell resolution transcriptomic data are lacking for this tissue. We present single cell RNA-seq data on 1-day male and female, 3-day and 7-day old male adult eyes, covering early to mature adult eyes. All major cell types, including photoreceptors, cone and pigment cells in the adult eye were captured and identified. Our data sets identified novel cell type specific marker genes, some of which were validated in vivo. R7 and R8 photoreceptors form clusters that reflect their specific Rhodopsin expression and the specific Rhodopsin …

Hypermethylation Of Nc886 In Hpv-Positive Oropharyngeal Cancer And Its Clinical Implications: An Epigenome-Wide Association Study, Yifan Xu, Ziqiao Wang, Peng Wei, Richa Gairola, Karl T Kelsey, Andrew G Sikora, Guojun Li, Jian Gu

Faculty, Staff and Student Publications

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased rapidly in the United States, driven by rising human papillomavirus (HPV) infections in the U.S. population. HPV-positive OPSCC patients have a better prognosis than HPV-negative patients. To gain insights into the unique biology of HPV(+) OPSCC that may contribute to its clinical behaviors, we performed a multi-stage epigenome-wide methylation profiling of leukocyte and tumor DNA in OPSCC patients and compared the methylation levels of CpG sites between HPV(+) and HPV(-) OPSCC patients. We identified and validated a significantly differentially methylated region (DMR) of 1,355 bp encompassing non-coding RNA 886 ( …

Evaluation Of Recombinant Live-Attenuated Respiratory Syncytial Virus (Rsv) Vaccines Rsv/Δns2/Δ1313/I1314l And Rsv/276 In Rsv-Seronegative Children, Coleen K Cunningham, Ruth A Karron, Petronella Muresan, Matthew S Kelly, Elizabeth J Mcfarland, Charlotte Perlowski, Jennifer Libous, Jennifer Oliva, Patrick Jean-Philippe, Jack Moye, Elizabeth Schappell, Emily Barr, Vivian Rexroad, Benjamin Johnston, Ellen G Chadwick, Mikhaela Cielo, Mary Paul, Jaime G Deville, Mariam Aziz, Lijuan Yang, Cindy Luongo, Peter L Collins, Ursula J Buchholz, International Maternal Pediatric Adolescent Aids Clinical Trials (Impaact) 2018 Study Team

Children’s Nutrition Research Center Staff Publications

Background: This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion.

Methods: RSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season.

Results: Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more …

Histopathological Tumour Response Scoring In Resected Pancreatic Cancer Following Neoadjuvant Therapy: International Interobserver Study (Isgpp-1), Boris V Janssen, Stijn Van Roessel, Susan Van Dieren, Onno De Boer, Volkan Adsay, Olca Basturk, Lodewijk Brosens, Fiona Campbell, Deyali Chatterjee, Angela Chou, Claudio Doglioni, Irene Esposito, Roger Feakins, Talia L Fuchs, Noriyoshi Fukushima, Anthony J Gill, Seung-Mo Hong, Ralph H Hruban, Jeffrey Kaplan, Alyssa Krasinkas, Claudio Luchini, Chanjuan Shi, Aatur Singhi, Elizabeth Thompson, Marie-Louise F Velthuysen, Marc G Besselink, Joanne Verheij, Huamin Wang, Caroline Verbeke, Arantza Fariña

Faculty, Staff and Student Publications

Background: Most tumour response scoring systems for resected pancreatic cancer after neoadjuvant therapy score tumour regression. However, whether treatment-induced changes, including tumour regression, can be identified reliably on haematoxylin and eosin-stained slides remains unclear. Moreover, no large study of the interobserver agreement of current tumour response scoring systems for pancreatic cancer exists. This study aimed to investigate whether gastrointestinal/pancreatic pathologists can reliably identify treatment effect on tumour by histology, and to determine the interobserver agreement for current tumour response scoring systems.

Methods: Overall, 23 gastrointestinal/pancreatic pathologists reviewed digital haematoxylin and eosin-stained slides of pancreatic cancer or treated tumour bed. The …

Consensus Opinion From An International Group Of Experts On Measurable Residual Disease In Hairy Cell Leukemia, Farhad Ravandi, Robert J Kreitman, Enrico Tiacci, Leslie Andritsos, Versha Banerji, Jacqueline C Barrientos, Seema A Bhat, James S Blachly, Alessandro Broccoli, Timothy Call, Dai Chihara, Claire Dearden, Judit Demeter, Sasha Dietrich, Monica Else, Narendranath Epperla, Brunangelo Falini, Francesco Forconi, Douglas E Gladstone, Alessandro Gozzetti, Sunil Iyengar, James B Johnston, Jeffrey Jorgensen, Gunnar Juliusson, Francesco Lauria, Gerard Lozanski, Sameer A Parikh, Jae H Park, Aaron Polliack, Graeme Quest, Tadeusz Robak, Kerry A Rogers, Alan Saven, John F Seymour, Tamar Tadmor, Martin S Tallman, Constantine S Tam, Philip A Thompson, Xavier Troussard, Clive S Zent, Thorsten Zenz, Pier Luigi Zinzani, Bernhard Wörmann, Kanti Rai, Michael Grever

Faculty, Staff and Student Publications

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the …

Using Patient Flow Analysis With Real-Time Patient Tracking To Optimize Radiation Oncology Consultation Visits, Shane Mesko, Julius Weng, Prajnan Das, Albert C Koong, Joseph M Herman, Dorothy Elrod-Joplin, Ashley Kerr, Thomas Aloia, John Frenzel, Katy E French, Wendi Martinez, Iris Recinos, Abdulaziz Alshaikh, Utpala Daftary, Amy C Moreno, Quynh-Nhu Nguyen

Faculty, Staff and Student Publications

PURPOSE: Clinical efficiency is a key component of the value-based care model and a driver of patient satisfaction. The purpose of this study was to identify and address inefficiencies at a high-volume radiation oncology clinic.

METHODS AND MATERIALS: Patient flow analysis (PFA) was used to create process maps and optimize the workflow of consultation visits in a gastrointestinal radiation oncology clinic at a large academic cancer center. Metrics such as cycle times, waiting times, and rooming times were assessed by using a real-time patient status function in the electronic medical record for 556 consults and compared between before vs after …

Defining Cellular Population Dynamics At Single-Cell Resolution During Prostate Cancer Progression, Alexandre A Germanos, Sonali Arora, Ye Zheng, Erica T Goddard, Ilsa M Coleman, Anson T Ku, Scott Wilkinson, Hanbing Song, Nicholas J Brady, Robert A Amezquita, Michael Zager, Annalysa Long, Yu Chi Yang, Jason H Bielas, Raphael Gottardo, David S Rickman, Franklin W Huang, Cyrus M Ghajar, Peter S Nelson, Adam G Sowalsky, Manu Setty, Andrew C Hsieh

Faculty, Staff and Student Publications

Advanced prostate malignancies are a leading cause of cancer-related deaths in men, in large part due to our incomplete understanding of cellular drivers of disease progression. We investigate prostate cancer cell dynamics at single-cell resolution from disease onset to the development of androgen independence in an in vivo murine model. We observe an expansion of a castration-resistant intermediate luminal cell type that correlates with treatment resistance and poor prognosis in human patients. Moreover, transformed epithelial cells and associated fibroblasts create a microenvironment conducive to pro-tumorigenic immune infiltration, which is partially androgen responsive. Androgen-independent prostate cancer leads to significant diversification of …

Mir21 Modulates The Hippo Signaling Pathway Via Interference With Pp2a Bβ To Inhibit Trophoblast Invasion And Cause Preeclampsia, Mingyu Hu, Yangxi Zheng, Jiujiang Liao, Li Wen, Juan Cheng, Jiayu Huang, Biao Huang, Li Lin, Yao Long, Yue Wu, Xuan Ye, Yong Fu, Hongbo Qi, Philip N Baker, Chao Tong

Faculty, Staff and Student Publications

Preeclampsia (PE) is a pregnancy-specific disorder attributed to deficient extravillous trophoblast (EVT) invasion into the uterus, but the mechanism of EVT invasion remains unclear. In this study, we found significantly elevated expression of microRNA 21 (miR21), which negatively regulates trophoblast invasion and migration, in preeclamptic placentae. Whole-genome RNA sequencing revealed that PPP2R2B, which encodes PP2A Bβ, and the Hippo pathway are downstream targets of miR21. The effects of miR21 on trophoblast mobility were abolished in LATS1T1079A/S909A and YAP-5SA mutants. Moreover, we found that PP2A Bβ dephosphorylates LATS1 via direct protein-protein interactions and thus modulates the phosphorylation and subcellular distribution …