Medical Specialties Commons^™

Architecture Of Androgen Receptor Pathways Amplifying Glucagon-Like Peptide-1 Insulinotropic Action In Male Pancreatic Β Cells, Weiwei Xu, M M Fahd Qadir, Daniela Nasteska, Paula Mota De Sa, Caroline M Gorvin, Manuel Blandino-Rosano, Charles R Evans, Thuong Ho, Evgeniy Potapenko, Rajakrishnan Veluthakal, Fiona B Ashford, Stavroula Bitsi, Jia Fan, Manika Bhondeley, Kejing Song, Venkata N Sure, Siva S V P Sakamuri, Lina Schiffer, Wandy Beatty, Rachael Wyatt, Daniel E Frigo, Xiaowen Liu, Prasad V Katakam, Wiebke Arlt, Jochen Buck, Lonny R Levin, Tony Hu, Jay Kolls, Charles F Burant, Alejandra Tomas, Matthew J Merrins, Debbie C Thurmond, Ernesto Bernal-Mizrachi, David J Hodson, Franck Mauvais-Jarvis

Faculty, Staff and Student Publications

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO

Circadian Features Of Cluster Headache And Migraine: A Systematic Review, Meta-Analysis, And Genetic Analysis, Barlas Benkli, Sun Young Kim, Nobuya Koike, Chorong Han, Celia K Tran, Emma Silva, Yuanqing Yan, Kazuhiro Yagita, Zheng Chen, Seung-Hee Yoo, Mark J Burish

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features informs their pathophysiologies.

METHODS: A librarian created search criteria in MEDLINE Ovid, Embase, PsycINFO, Web of Science, and Cochrane Library. Two physicians independently performed the remainder of the systematic review/meta-analysis using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Separate from the systematic review/meta-analysis, we performed a genetic analysis for genes with a circadian pattern of expression (clock-controlled genes or CCGs) by cross-referencing genome-wide association studies (GWASs) of headache, a nonhuman primate study of CCGs …

Glial Progenitor Heterogeneity And Key Regulators Revealed By Single-Cell Rna Sequencing Provide Insight To Regeneration In Spinal Cord Injury, Haichao Wei, Xizi Wu, Joseph Withrow, Raquel Cuevas-Diaz Duran, Simranjit Singh, Lesley S Chaboub, Jyotirmoy Rakshit, Julio Mejia, Andrew Rolfe, Juan J Herrera, Philip J Horner, Jia Qian Wu

Faculty, Staff and Student Publications

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before …

Progesterone From Ovulatory Menstrual Cycles Is An Important Cause Of Breast Cancer, Herjan J T Coelingh Bennink, Iman J Schultz, Marcus Schmidt, V Craig Jordan, Paula Briggs, Jan F M Egberts, Kristina Gemzell-Danielsson, Ludwig Kiesel, Kirsten Kluivers, Jan Krijgh, Tommaso Simoncini, Frank Z Stanczyk, Robert D Langer

Faculty, Staff and Student Publications

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting …

The Metabolic Profile Of Young, Watered Chickpea Plants Can Be Used As A Biomarker To Predict Seed Number Under Terminal Drought, Sarah J Purdy, David Fuentes, Purushothaman Ramamoorthy, Christopher Nunn, Brent N Kaiser, Andrew Merchant

Faculty, Staff and Student Publications

Chickpea is the second-most-cultivated legume globally, with India and Australia being the two largest producers. In both of these locations, the crop is sown on residual summer soil moisture and left to grow on progressively depleting water content, finally maturing under terminal drought conditions. The metabolic profile of plants is commonly, correlatively associated with performance or stress responses, e.g., the accumulation of osmoprotective metabolites during cold stress. In animals and humans, metabolites are also prognostically used to predict the likelihood of an event (usually a disease) before it occurs, e.g., blood cholesterol and heart disease. We sought to discover metabolic …

Challenges In The Clinical Understanding Of Genetic Testing In Birth Defects And Pediatric Diseases, Tina O Findley, Jacqueline G Parchem, Aarti Ramdaney, Sarah U Morton

Faculty, Staff and Student Publications

Advances in prenatal/neonatal genetic screening practices and next generation sequencing (NGS) technologies have made the detection of molecular causes of pediatric diseases increasingly more affordable, accessible, and rapid in return of results. In the past, families searching for answers often required diagnostic journeys leading to delays in targeted care and missed diagnoses. Non-invasive prenatal NGS is now used routinely in pregnancy, significantly altering the obstetric approach to early screening and evaluation of fetal anomalies. Similarly, exome sequencing (ES) and genome sequencing (GS) were once only available for research but are now used in patient care, impacting neonatal care and the …

Ca2+ Efflux Facilitated By Co-Transport Of Inorganic Phosphate Anion In The H+/Ca2+ Antiporter Yfke, Wei Niu, Wenchang Zhou, Shuo Lu, Trung Vu, Vasanthi Jayaraman, José D Faraldo-Gómez, Lei Zheng

Faculty, Staff and Student Publications

Ca2+ is an important signaling messenger. In microorganisms, fungi, and plants, H+/Ca2+ antiporters (CAX) are known to play key roles in the homeostasis of intracellular Ca2+ by catalyzing its efflux across the cell membrane. Here, we reveal that the bacterial CAX homolog YfkE transports Ca2+ in two distinct modes: a low-flux H+/Ca2+ exchange mode and a high-flux mode in which Ca2+ and phosphate ions are co-transported (1:1) in exchange for H+. Coupling with phosphate greatly accelerates the Ca2+ efflux activity of YfkE. Our studies reveal that Ca2+ and phosphate bind to adjacent sites in a central translocation pathway and lead …

Rapid Assessment Of Fish Freshness For Multiple Supply-Chain Nodes Using Multi-Mode Spectroscopy And Fusion-Based Artificial Intelligence, Hossein Kashani Zadeh, Mike Hardy, Mitchell Sueker, Yicong Li, Angelis Tzouchas, Nicholas Mackinnon, Gregory Bearman, Simon A Haughey, Alireza Akhbardeh, Insuck Baek, Chansong Hwang, Jianwei Qin, Amanda M Tabb, Rosalee S Hellberg, Shereen Ismail, Hassan Reza, Fartash Vasefi, Moon Kim, Kouhyar Tavakolian, Christopher T Elliott

Faculty, Staff and Student Publications

This study is directed towards developing a fast, non-destructive, and easy-to-use handheld multimode spectroscopic system for fish quality assessment. We apply data fusion of visible near infra-red (VIS-NIR) and short wave infra-red (SWIR) reflectance and fluorescence (FL) spectroscopy data features to classify fish from fresh to spoiled condition. Farmed Atlantic and wild coho and chinook salmon and sablefish fillets were measured. Three hundred measurement points on each of four fillets were taken every two days over 14 days for a total of 8400 measurements for each spectral mode. Multiple machine learning techniques including principal component analysis, self-organized maps, linear and …

Differential Gene Expression Of Fresh Tissue And Patient-Derived Explants’ Matricellular Proteins Augment Inflammatory Breast Cancer Metastasis: The Possible Role Of Il-6 And Mcp-1, Alshaimaa Tarek, Hossam Taha Mohamed, Aya Ali El-Sharkawy, Shrouk Khalaf El-Sayed, Jon Mark Hirshon, Wendy A Woodward, Mohamed El-Shinawi, Mona Mostafa Mohamed

Faculty, Staff and Student Publications

BACKGROUND: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behaviour. Herein, we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex vivo patient-derived explants (PDEs) and we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome.

METHODS: Fifty …

The Role Of Extracellular Heat Shock Proteins In Cardiovascular Diseases, Soumya Patnaik, Sriram Nathan, Biswajit Kar, Igor D Gregoric, Yi-Ping Li

Faculty, Staff and Student Publications

In the early 1960s, heat shock proteins (HSPs) were first identified as vital intracellular proteinaceous components that help in stress physiology and reprogram the cellular responses to enable the organism's survival. By the early 1990s, HSPs were detected in extracellular spaces and found to activate gamma-delta T-lymphocytes. Subsequent investigations identified their association with varied disease conditions, including autoimmune disorders, diabetes, cancer, hepatic, pancreatic, and renal disorders, and cachexia. In cardiology, extracellular HSPs play a definite, but still unclear, role in atherosclerosis, acute coronary syndromes, and heart failure. The possibility of HSP-targeted novel molecular therapeutics has generated much interest and hope …

Adherence To Opioid Patient Prescriber Agreements At A Safety Net Hospital, Soraira Pacheco, Linh M T Nguyen, John M Halphen, Nikitha N Samy, Nathaniel R Wilson, Gregory Sattler, Shane E Wing, Christine Feng, Rex A D Paulino, Pulin Shah, Supriyanka Addimulam, Riddhi Patel, Curtis J Wray, Joseph A Arthur, David Hui

Faculty, Staff and Student Publications

Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019. We included patients 18 years or older with cancer diagnoses who received opioids. We collected patient characteristics at consultation and information regarding PPA. The …

Measuring Symptom Burden In Patients With Cancer During A Pandemic: The Md Anderson Symptom Inventory For Covid-19 Mdasi-Covid, Loretta A Williams, Meagan S Whisenant, Tito R Mendoza, Angela E Peek, Donna Malveaux, Donna K Griffin, Darcy A Ponce, Bruno Palma Granwehr, Ajay Sheshadri, Katherine A Hutcheson, Sara M Ali, Susan K Peterson, John V Heymach, Charles S Cleeland, Ishwaria M Subbiah

Faculty, Staff and Student Publications

BACKGROUND: Symptom expression in SARS-CoV-2 infection (COVID-19) may affect patients already symptomatic with cancer. Patient-reported outcomes (PROs) can describe symptom burden during the acute and postacute stages of COVID-19 and support risk stratification for levels of care. At the start of the COVID-19 pandemic, our purpose was to rapidly develop, launch through an electronic patient portal, and provide initial validation for a PRO measure of COVID-19 symptom burden in patients with cancer.

METHODS: We conducted a CDC/WHO web-based scan for COVID-19 symptoms and a relevance review of symptoms by an expert panel of clinicians treating cancer patients with COVID-19 to …

Smarcb1 Regulates A Tfcp2l1-Myc Transcriptional Switch Promoting Renal Medullary Carcinoma Transformation And Ferroptosis Resistance, Bujamin H Vokshi, Guillaume Davidson, Nassim Tawanaie Pour Sedehi, Alexandra Helleux, Marc Rippinger, Alexandre R Haller, Justine Gantzer, Jonathan Thouvenin, Philippe Baltzinger, Rachida Bouarich, Valeria Manriquez, Sakina Zaidi, Priya Rao, Pavlos Msaouel, Xiaoping Su, Hervé Lang, Thibault Tricard, Véronique Lindner, Didier Surdez, Jean-Emmanuel Kurtz, Franck Bourdeaut, Nizar M Tannir, Irwin Davidson, Gabriel G Malouf

Faculty, Staff and Student Publications

Renal medullary carcinoma (RMC) is an aggressive tumour driven by bi-allelic loss of SMARCB1 and tightly associated with sickle cell trait. However, the cell-of-origin and oncogenic mechanism remain poorly understood. Using single-cell sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into an epithelial-mesenchymal gradient of RMC cells associated with loss of renal epithelial transcription factors TFCP2L1, HOXB9 and MITF and gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs. We describe the molecular basis for this transcriptional switch that is reversed by SMARCB1 re-expression repressing the oncogenic and ferroptosis resistance programs leading to ferroptotic …

Kras-Dependency In Pancreatic Ductal Adenocarcinoma: Mechanisms Of Escaping In Resistance To Kras Inhibitors And Perspectives Of Therapy, Enrico Gurreri, Giannicola Genovese, Luigi Perelli, Antonio Agostini, Geny Piro, Carmine Carbone, Giampaolo Tortora

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest cancers in oncology because of its increasing incidence and poor survival rate. More than 90% of PDAC patients are KRAS mutated (KRASmu), with KRASG12D and KRASG12V being the most common mutations. Despite this critical role, its characteristics have made direct targeting of the RAS protein extremely difficult. KRAS regulates development, cell growth, epigenetically dysregulated differentiation, and survival in PDAC through activation of key downstream pathways, such as MAPK-ERK and PI3K-AKT-mammalian target of rapamycin (mTOR) signaling, in a KRAS-dependent manner. KRASmu induces the occurrence of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial …

The Longitudinal Analysis Of Convergent Antibody Vdj Regions In Sars-Cov-2-Positive Patients Using Rna-Seq, Kate J Liu, Monika A Zelazowska, Kevin M Mcbride

Faculty, Staff and Student Publications

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an ongoing pandemic that continues to evolve and reinfect individuals. To understand the convergent antibody responses that evolved over the course of the pandemic, we evaluated the immunoglobulin repertoire of individuals infected by different SARS-CoV-2 variants for similarity between patients. We utilized four public RNA-seq data sets collected between March 2020 and March 2022 from the Gene Expression Omnibus (GEO) in our longitudinal analysis. This covered individuals infected with Alpha and Omicron variants. In total, from 269 SARS-CoV-2-positive patients and 26 negative patients, 629,133 immunoglobulin heavy-chain variable region V(D)J sequences were reconstructed from …

New Actions On Actionable Mutations In Lung Cancers, Xiuning Le, Yasir Y Elamin, Jianjun Zhang

Faculty, Staff and Student Publications

Actionable mutations refer to DNA alterations that, if detected, would be expected to affect patients' response to treatments [...].

Genome-Wide Association Study Of Lung Adenocarcinoma In East Asia And Comparison With A European Population, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M Funderburk, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Batel Blechter, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y Y Wong, Min-Ho Shin, Lap Ping Chung, Yang Yang, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H Hosgood, Hideo Kunitoh, Harsh Patel, Shun-Ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hongji Dai, Mitchell J Machiela, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Kun-Chieh Chen, Yu-Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G Schwartz, Richard Houlston, Margaret R Spitz, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung-Hsing Chen, Chin-Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih-Liang Wang, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Wei-Yen Lim, Fang-Yu Tsai, John K C Chan, Jihua Li, Hongyan Chen, Hsien-Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen, Pan-Chyr Yang, Jinming Yu, Victoria L Stevens, Joseph F Fraumeni, Nilanjan Chatterjee, Olga Y Gorlova, Chao Agnes Hsiung, Christopher I Amos, Hongbing Shen, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan

Faculty, Staff and Student Publications

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European …

Histological Transformation To Gliosarcoma With Combined Braf/Mek Inhibition In Braf V600e Mutated Glioblastoma, Blessie Elizabeth Nelson, Neha K Reddy, Jason T Huse, Behrang Amini, Mirella Nardo, Mohamed Gouda, Shiao-Pei Weathers, Vivek Subbiah

Faculty, Staff and Student Publications

The identification of BRAF V600 mutation in multiple cancers beyond melanoma and the development of combined BRAF and MEK targeting agents have altered the landscape of tissue-agnostic precision oncology therapies with an impact on survival outcomes. Despite initial efficacy, resistance emerges, and it is pertinent to identify putative resistance mechanisms. We report a case of recurrent glioblastoma (GBM) harboring BRAF V600E alteration who initially responded to combined BRAF + MEK inhibition and subsequently developed treatment resistance by histological transformation to gliosarcoma and acquisition of oncogenic KRAS G12D and an NF1 L1083R mutation. This documented case represents an initial evidence of …

Simple Combination Of Multiple Somatic Variant Callers To Increase Accuracy, Alexander J Trevarton, Jeffrey T Chang, W Fraser Symmans

Faculty, Staff and Student Publications

Publications comparing variant caller algorithms present discordant results with contradictory rankings. Caller performances are inconsistent and wide ranging, and dependent upon input data, application, parameter settings, and evaluation metric. With no single variant caller emerging as a superior standard, combinations or ensembles of variant callers have appeared in the literature. In this study, a whole genome somatic reference standard was used to derive principles to guide strategies for combining variant calls. Then, manually annotated variants called from the whole exome sequencing of a tumor were used to corroborate these general principles. Finally, we examined the ability of these principles to …

Transmission Of Mycobacterium Tuberculosis To Healthcare Personnel Resulting From Contaminated Bone Graft Material, United States, June 2021–August 2022, Ruoran Li, Molly Deutsch-Feldman, Tamasin Adams, Michelle Law, Chinpar Biak, Erika Pitcher, Marci Drees, Alfonso C Hernandez-Romieu, Thomas D Filardo, Tracina Cropper, Angelica Martinez, W Wyatt Wilson, Sandy P Althomsons, Sapna Bamrah Morris, Jonathan M Wortham, Isaac Benowitz, Noah G Schwartz, Kelly White, Maryam B Haddad, Janet B Glowicz, Bone Allograft Tuberculosis Investigators

Faculty, Staff and Student Publications

A nationwide tuberculosis outbreak linked to a viable bone allograft product contaminated with Mycobacterium tuberculosis was identified in June 2021. Our subsequent investigation identified 73 healthcare personnel with new latent tuberculosis infection following exposure to the contaminated product, product recipients, surgical instruments, or medical waste.

Single-Compartment Dose Prescriptions For Ablative 90y-Radioembolization Segmentectomy, Srinivas Cheenu Kappadath, Benjamin P Lopez

Faculty, Staff and Student Publications

BACKGROUND: Yttrium-90 (90Y) radioembolization is increasingly being utilized with curative intent. While single-compartment doses with respect to the perfused volume for the complete pathologic necrosis (CPN) of tumors have been reported, the actual doses delivered to the tumor and at-risk margins that leads to CPN have hitherto not been estimated. We present an ablative dosimetry model that calculates the dose distribution for tumors and at-risk margins based on numerical mm-scale dose modeling and the available clinical CPN evidence and report on the necessary dose metrics needed to achieve CPN following 90Y-radioembolization.

METHODS: Three-dimensional (3D) activity distributions (MBq/voxel) simulating spherical tumors …

Cellular And Molecular Mechanisms Of Liver Fibrosis In Patients With Nafld, Jessica I Sanchez, Edwin R Parra, Jingjing Jiao, Luisa M Solis Soto, Debora A Ledesma, Omar A Saldarriaga, Heather L Stevenson, Laura Beretta

Faculty, Staff and Student Publications

The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance …

Tet2 Truncating Mutations Predict A Worse Outcome In Blastic Plasmacytoid Dendritic Cell Neoplasm, Hannah Beird, C Cameron Yin, Joseph D Khoury, Sherry Pierce, Hussein A Abbas, Li Zhao, Anna Skwarska, Muzaffar Qazilbash, Marina Konopleva, P Andrew Futreal, Naveen Pemmaraju

Faculty, Staff and Student Publications

No abstract provided.

Publisher Correction: A Randomized Pilot Study Of Oncology Massage To Treat Chemotherapy-Induced Peripheral Neuropathy, Gabriel Lopez, Cathy Eng, Michael Overman, David Ramirez, Wenli Liu, Curtiss Beinhorn, Pamela Sumler, Sarah Prinsloo, Yisheng Li, Minxing Chen, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

No abstract provided.

Balloon Dilatation In The Management Of Congenital Obstructive Lesions Of The Heart: Review Of Author's Experiences And Observations-Part I, P Syamasundar Rao

Faculty, Staff and Student Publications

Balloon dilatation techniques became available to treat congenital obstructive lesions of the heart in the early/mid-1980s. The purpose of this review is to present the author's experiences and observations on the techniques and outcomes of balloon dilatation of pulmonary stenosis (PS), aortic stenosis (AS) and aortic coarctation (AC), both native and postsurgical re-coarctations. Balloon dilatation resulted in a reduction of peak pressure gradient across the obstructive lesion at the time of the procedure as well as at short-term and long-term follow-ups. Complications such as recurrence of stenosis, valvar insufficiency (for PS and AS cases) and aneurysm formation (for AC cases) …

Sequential Absorption Of Two Photons Creates A Bistable Form Of Rubyacr Responsible For Its Strong Desensitization, Oleg A Sineshchekov, Elena G Govorunova, Hai Li, Yumei Wang, John L Spudich

Faculty, Staff and Student Publications

Channelrhodopsins with red-shifted absorption, rare in nature, are highly desired for optogenetics because light of longer wavelengths more deeply penetrates biological tissue. RubyACRs (Anion ChannelRhodopsins), a group of four closely related anion-conducting channelrhodopsins from thraustochytrid protists, are the most red-shifted channelrhodopsins known with absorption maxima up to 610 nm. Their photocurrents are large, as is typical of blue- and green-absorbing ACRs, but they rapidly decrease during continuous illumination (desensitization) and extremely slowly recover in the dark. Here, we show that long-lasting desensitization of RubyACRs results from photochemistry not observed in any previously studied channelrhodopsins. Absorption of a second photon by …

A Phase 2 Study Of Nivolumab Combined With Ibrutinib In Patients With Diffuse Large B-Cell Richter Transformation Of Cll, Nitin Jain, Jayastu Senapati, Beenu Thakral, Alessandra Ferrajoli, Philip Thompson, Jan Burger, Sreyashi Basu, Tapan Kadia, Naval Daver, Gautam Borthakur, Marina Konopleva, Naveen Pemmaraju, Erin Parry, Catherine J Wu, Joseph Khoury, Carlos Bueso-Ramos, Naveen Garg, Xuemei Wang, Wanda Lopez, Ana Ayala, Susan O'Brien, Hagop Kantarjian, Michael Keating, James Allison, Padmanee Sharma, William Wierda

Faculty, Staff and Student Publications

Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of …

Smarcb1 Regulates The Hypoxic Stress Response In Sickle Cell Trait, Melinda Soeung, Luigi Perelli, Ziheng Chen, Eleonora Dondossola, I-Lin Ho, Federica Carbone, Li Zhang, Hania Khan, Courtney N Le, Cihui Zhu, Michael D Peoples, Ningping Feng, Shan Jiang, Niki Millward Zacharias, Rosalba Minelli, Daniel D Shapiro, Angela K Deem, Sisi Gao, Emily H Cheng, Donatella Lucchetti, Cheryl L Walker, Alessandro Carugo, Virginia Giuliani, Timothy P Heffernan, Andrea Viale, Nizar M Tannir, Giulio F Draetta, Pavlos Msaouel, Giannicola Genovese

Faculty, Staff and Student Publications

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor SMARCB1. Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels …

Stat5 Confers Lactogenic Properties In Breast Tumorigenesis And Restricts Metastatic Potential, Richard S Lampitt, Stephen Fletcher, Matthew Cole, Alice Kloker, Stefan Krause, Fran O'Hara, Peter Ryde, Mahua Saha, Anastasia Voronkova, Adrian Whyle

Faculty, Staff and Student Publications

Progress to reduce plastic pollution has been painfully slow and the consequent damage to the natural environment and to human health is likely to increase further. This has been because the views and ways of working of four distinct stakeholder communities are not sufficiently well integrated. (1) Scientists, (2) industry, (3) society at large and (4) those making policy and legislation must in future find ways to work together.

The Deleted In Oral Cancer (Doc1 Aka Cdk2ap1) Tumor Suppressor Gene Is Downregulated In Oral Squamous Cell Carcinoma By Multiple Micrornas, Roberto Stabile, Mario Román Cabezas, Mathijs P Verhagen, Francesco A Tucci, Thierry P P Van Den Bosch, Maria J De Herdt, Berdine Van Der Steen, Alex L Nigg, Meng Chen, Cristina Ivan, Masayoshi Shimizu, Senada Koljenović, Jose A Hardillo, C Peter Verrijzer, Robert J Baatenburg De Jong, George A Calin, Riccardo Fodde

Faculty, Staff and Student Publications

Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1; also known as deleted in oral cancer or DOC1) is a tumor suppressor gene known to play functional roles in both cell cycle regulation and in the epigenetic control of embryonic stem cell differentiation, the latter as a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex. In the vast majority of oral squamous cell carcinomas (OSCC), expression of the CDK2AP1 protein is reduced or lost. Notwithstanding the latter (and the DOC1 acronym), mutations or deletions in its coding sequence are extremely rare. Accordingly, CDK2AP1 protein-deficient oral cancer cell lines express as …