Genetic Phenomena Commons^™

Polatuzumab Vedotin, Venetoclax, And An Anti-Cd20 Monoclonal Antibody In Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, Sam Yuen, Tycel J Phillips, Rajat Bannerji, Paula Marlton, Giuseppe Gritti, John F Seymour, Anna Johnston, Christopher Arthur, Anna Dodero, Sunil Sharma, Jamie Hirata, Lisa Musick, Christopher R Flowers

Faculty, Staff and Student Publications

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed-dose obinutuzumab 1000 mg or rituximab 375 mg/m2 in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), respectively. Patients with complete response (CR) or partial response (PR)/stable disease (FL) or CR/PR (DLBCL) at end of induction (EOI; six 21-day cycles) received post-induction therapy with venetoclax and obinutuzumab or rituximab, respectively. Primary endpoint was CR rate at EOI. Safety-evaluable populations included 74 patients (FL cohort; median age 64 years; progression of disease within 24 months …

Cone-Beam Ct With A Noncircular (Sine-On-Sphere) Orbit: Imaging Performance Of A Clinical System For Image-Guided Interventions, A Kyle Jones, Moiz Ahmad, Shaan M Raza, Stephen R Chen, Jeffrey H Siewerdsen

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Purpose: We aim to compare the imaging performance of a cone-beam CT (CBCT) imaging system with noncircular scan protocols (sine-on-sphere) to a conventional circular orbit.

Approach: A biplane C-arm system (ARTIS Icono; Siemens Healthineers) capable of circular and noncircular CBCT acquisition was used, with the latter orbit (sine-on-sphere, "Sine Spin") executing a sinusoidal motion with ±10deg tilt amplitude over the half-scan orbit. A test phantom was used for the characterization of image uniformity, noise, noise-power spectrum (NPS), spatial resolution [modulation transfer function (MTF) in axial and oblique directions], and cone-beam artifacts. Findings were interpreted using an anthropomorphic head phantom with …

Α-Synuclein Seed Amplification Technology For Parkinson's Disease And Related Synucleinopathies, Claudio Soto

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Synucleinopathies are a group of neurodegenerative diseases (NDs) associated with cerebral accumulation of α-synuclein (αSyn) misfolded aggregates. At this time, there is no effective treatment to stop or slow down disease progression, which in part is due to the lack of an early and objective biochemical diagnosis. In the past 5 years, the seed amplification technology has emerged for highly sensitive identification of these diseases, even at the preclinical stage of the illness. Much research has been done in multiple laboratories to validate the efficacy and reproducibility of this assay. This article provides a comprehensive review of this technology, including …

Oar-Weighted Dice Score: A Spatially Aware, Radiosensitivity Aware Metric For Target Structure Contour Quality Assessment, Lucas Mccullum, Kareem A Wahid, Barbara Marquez, Clifton D Fuller

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The Dice Similarity Coefficient (DSC) is the current de facto standard to determine agreement between a reference segmentation and one generated by manual / auto-contouring approaches. This metric is useful for non-spatially important images; however, radiation therapy requires consideration of nearby Organs-at-Risk (OARs) and their radiosensitivity which are currently unaccounted for with the traditional DSC. In this work, we introduce the OAR-DSC which accounts for nearby OARs and their radiosensitivity when computing the DSC. We illustrate the importance of this through cases where two proposed contours have similar DSC, but lower OAR-DSC when one contour expands closer to the surrounding …

Apoptosis Pathway-Associated Proteins Are Frequently Expressed In Melanoma: A Study Of 32 Cases With Focus On Acral Lentiginous Melanoma, Debora A Ledesma, Mario L Marques-Piubelli, Elsa Li-Ning-Tapia, Courtney Hudgens, Jun Gu, Rossana Lazcano, Sandro Casavilca-Zambrano, Miluska Castillo, Michael A Davies, Wen-Jen Hwu, Phyu P Aung, Alessio Giubellino, Jonathan L Curry, Carlos Torres-Cabala

Faculty, Staff and Student Publications

Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and …

Clinical Exome Sequencing Uncovers Genetic Disorders In Neonates With Suspected Hypoxic-Ischemic Encephalopathy: A Retrospective Analysis, Christian M Parobek, Roni Zemet, Matthew A Shanahan, Brian A Burnett, Elizabeth Mizerik, Jill A Rosenfeld, Liesbeth Vossaert, Steven L Clark, Jill V Hunter, Seema R Lalani

Faculty, Staff and Students Publications

Hypoxic-ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal hypoxia. We hypothesized that some infants with HIE have genetic disorders that resemble encephalopathy. We reviewed genetic results for newborns with HIE undergoing exome or genome sequencing at a clinical laboratory (2014-2022). Neonates were included if they had a diagnosis of HIE and were delivered ≥35 weeks. Neonates were excluded for cardiopulmonary pathology resulting in hypoxemia or if neuroimaging suggested postnatal hypoxic-ischemic injury. Of 24 patients …

Whole-Transcriptome Sequencing-Based Profiling Of The Cutaneous Virome In Patients With Secondary Immunodeficiency, Leila Youssefian, Amir Hossein Saeidian, Zahra Saffarian, Mona Ariamanesh, Fahimeh Abdollahimajd, Sara Molkara, Mohammad Shahidi-Dadras, Reem Diab, Fatemeh Vahidnezhad, Sirous Zeinali, Vivien Béziat, Emmanuelle Jouanguy, Jean-Laurent Casanova, Jouni Uitto, Hassan Vahidnezhad

Faculty, Staff and Students Publications

Most viral infections can be self-limited, with no requirement for medical intervention. However, the same viruses can cause severe diseases in patients with compromised immunity due to single-gene diseases, acquired immune deficiency syndrome, or hematologic malignancies or those receiving immunosuppressive drugs. Occasionally, these immunocompromised patients harbor >1 infectious agent, requiring several concomitant diagnostic tests. We have developed, to our knowledge, a previously unreported whole-transcriptome sequencing-based pipeline that allows virome profiling, quantitation, and expression pattern analysis of 926 distinct viruses by sequencing of RNA isolated from a single lesional skin biopsy. This pipeline can also explore host genetics if there is …

Genetic Deletion Of Galectin-3 Inhibits Pancreatic Cancer Progression And Enhances The Efficacy Of Immunotherapy, Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

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Background & aims: Pancreatic ductal adenocarcinoma (PDAC) has a desmoplastic tumor stroma and immunosuppressive microenvironment. Galectin-3 (GAL3) is enriched in PDAC, highly expressed by cancer cells and myeloid cells. However, the functional roles of GAL3 in the PDAC microenvironment remain elusive.

Methods: We generated a novel transgenic mouse model (LSL-KrasG12D/+;Trp53loxP/loxP;Pdx1-Cre;Lgals3-/- [KPPC;Lgals3-/-]) that allows the genetic depletion of GAL3 from both cancer cells and myeloid cells in spontaneous PDAC formation. Single-cell RNA-sequencing analysis was used to identify the alterations in the tumor microenvironment upon GAL3 depletion. We investigated both the cancer cell-intrinsic function and immunosuppressive function of GAL3. We also evaluated …

Author Correction: Plasmonic Nano-Aperture Label-Free Imaging Of Single Small Extracellular Vesicles For Cancer Detection, Nareg Ohannesian, Mohammad Sadman Mallick, Jianzhong He, Yawei Qiao, Nan Li, Simona F Shaitelman, Chad Tang, Eileen H Shinn, Wayne L Hofstetter, Alexei Goltsov, Manal M Hassan, Kelly K Hunt, Steven H Lin, Wei-Chuan Shih

Faculty, Staff and Student Publications

No abstract provided.

Type I Conventional Dendritic Cells Facilitate Immunotherapy In Pancreatic Cancer, Krishnan K Mahadevan, Allison M Dyevoich, Yang Chen, Bingrui Li, Hikaru Sugimoto, Amari M Sockwell, Kathleen M Mcandrews, Lakshmi Kavitha Sthanam, Huamin Wang, Shabnam Shalapour, Stephanie S Watowich, Raghu Kalluri

Faculty, Staff and Student Publications

Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8+ T cell activation and elimination of ptPDAC with restoration of life span even upon PDAC rechallenge. Using PDAC antigen-loaded cDC1s as a vaccine, immunotherapy-resistant PDAC was rendered sensitive to iCBT with elimination of tumors. cDC1 vaccination coupled with iCBT identified specific CDR3 sequences in the tumor-infiltrating CD8+ T cells with potential therapeutic importance. This study …

The Significant Associations Between Epigenetic Clocks And Bladder Cancer Risks, Yang Deng, Chia-Wen Tsai, Wen-Shin Chang, Yifan Xu, Maosheng Huang, Da-Tian Bau, Jian Gu

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Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case-control study, we assessed the associations between four well-established epigenetic clocks-HannumAge, HorvathAge, GrimAge, and PhenoAge-and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for …

Developing A Fit-For-Purpose Composite Symptom Score As A Symptom Burden Endpoint For Clinical Trials In Patients With Malignant Pleural Mesothelioma, Charles S Cleeland, Karen N Keating, Brian Cuffel, Cem Elbi, Jonathan M Siegel, Christoph Gerlinger, Tara Symonds, Jeff A Sloan, Amylou C Dueck, Andrew Bottomley, Xin Shelley Wang, Loretta A Williams, Tito R Mendoza

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We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92-0.94) and the Lung Cancer Symptom Scale-Mesothelioma …

Mettl3-Mediated Chromatin Contacts Promote Stress Granule Phase Separation Through Metabolic Reprogramming During Senescence, Chen Wang, Hideki Tanizawa, Connor Hill, Aaron Havas, Qiang Zhang, Liping Liao, Xue Hao, Xue Lei, Lu Wang, Hao Nie, Yuan Qi, Bin Tian, Alessandro Gardini, Andrew V Kossenkov, Aaron Goldman, Shelley L Berger, Ken-Ichi Noma, Peter D Adams, Rugang Zhang

Faculty, Staff and Student Publications

METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase …

Contribution Of Matrix Metalloproteinase-2 And Matrix Metalloproteinase-9 To Upper Tract Urothelial Cancer Risk In Taiwan, Bo-Ren Wang, Hung-Huan Ma, Chao-Hsiang Chang, Cheng-Hsi Liao, Wen-Shin Chang, Mei-Chin Mong, Ya-Chen Yang, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were …

Car T-Cell Expansion: Harmful Or Helpful?, Anath C Lionel, Sattva S Neelapu

Faculty, Staff and Student Publications

No abstract provided.

Hypoxia Inducible Factor 2Α Promotes Tolerogenic Macrophage Development During Cardiac Transplantation Through Transcriptional Regulation Of Colony Stimulating Factor 1 Receptor, Matthew Deberge, Samantha Schroth, Fanfan Du, Xin Yi Yeap, Jiao-Jing Wang, Zheng Jenny Zhang, Mohammed Javeed Ansari, Evan A Scott, Edward B Thorp

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Solid organ transplantation mobilizes myeloid cells, including monocytes and macrophages, which are central protagonists of allograft rejection. However, myeloid cells can also be functionally reprogrammed by perioperative costimulatory blockade to promote a state of transplantation tolerance. Transplantation tolerance holds promise to reduce complications from chronic immunosuppression and promote long-term survival in transplant recipients. We sought to identify different mediators of transplantation tolerance by performing single-cell RNA sequencing of acute rejecting or tolerized cardiac allografts. This led to the unbiased identification of the transcription factor, hypoxia inducible factor (HIF)-2α, in a subset of tolerogenic monocytes. Using flow cytometric analyses and mice …

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results Of A Multicenter, Randomized, Controlled Trial, Wei Dai, Yaqin Wang, Jia Liao, Xing Wei, Zhen Dai, Wei Xu, Yangjun Liu, Xin Shelley Wang, Cecilia Pompili, Hongfan Yu, Yang Pu, Yuqian Zhao, Bangrong Cao, Qifeng Wang, Wenhong Feng, Yuanqiang Zhang, Fang Liu, Yuanle Deng, Jin Zhou, Juan Li, Shaohua Xie, Run Xiang, Xiang Wang, Bo Tian, Xiaozun Yang, Bin Hu, Xiaoqin Liu, Tianpeng Xie, Xiaojun Yang, Xiang Zhuang, Guibin Qiao, Qiang Li, Qiuling Shi

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where …

Keep Fingers On The Cpg Islands, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng

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The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The ideal scenario involves precise targeting of a specific genomic location by a DNA-binding domain, ensuring there are no off-target effects and that the process yields no genetic remnants aside from specific epigenetic modifications (i.e., DNA methylation). A notable example is a recent study on the mouse

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

Faculty, Staff and Student Publications

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium …

The Cdk9 Inhibitor Enitociclib Overcomes Resistance To Btk Inhibition And Car-T Therapy In Mantle Cell Lymphoma, Vivian Jiang, William Lee, Tianci Zhang, Alexa Jordan, Fangfang Yan, Qingsong Cai, Joseph Mcintosh, Jovanny Vargas, Yang Liu, Michael Wang

Faculty, Staff and Student Publications

Inhibitors of Bruton's tyrosine kinase (BTKi) and chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 are paradigm-shifting advances in treating patients with aggressive mantle cell lymphoma (MCL). However, clinical relapses following BTKi and CD19-directed CAR-T treatments are a fast-growing medical challenge. Development of novel therapies to overcome BTKi resistance (BTKi-R) and BTKi-CAR-T dual resistance (Dual-R) are urgently needed. Our single-cell RNA sequencing data revealed major transcriptomic reprogramming, with great enrichment of MYC-targets evolving as resistance to these therapies developed. Interestingly, cyclin-dependent kinase 9 (CDK9), a critical component of the positive transcription elongation factor-b complex, was among the top upregulated genes …

Neurogranin Modulates The Rate Of Association Between Calmodulin And Target Peptides, John A Putkey, Laurel Hoffman, Vladimir Berka, Xu Wang

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The best-known mode of action of calmodulin (CaM) is binding of Ca2+ to its N- and C-domains, followed by binding to target proteins. An underappreciated facet of this process is that CaM is typically bound to proteins at basal levels of free Ca2+, including the small, intrinsically disordered, neuronal IQ-motif proteins called PEP-19 and neurogranin (Ng). PEP-19 and Ng would not be effective competitive inhibitors of high-affinity Ca2+-dependent CaM targets at equilibrium because they bind to CaM with relatively low affinity, but they could influence the time course of CaM signaling by affecting the rate of association of CaM with …

Variance-Components Tests For Genetic Association With Multiple Interval-Censored Outcomes, Jaihee Choi, Zhichao Xu, Ryan Sun

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Massive genetic compendiums such as the UK Biobank have become an invaluable resource for identifying genetic variants that are associated with complex diseases. Due to the difficulties of massive data collection, a common practice of these compendiums is to collect interval-censored data. One challenge in analyzing such data is the lack of methodology available for genetic association studies with interval-censored data. Genetic effects are difficult to detect because of their rare and weak nature, and often the time-to-event outcomes are transformed to binary phenotypes for access to more powerful signal detection approaches. However transforming the data to binary outcomes can …

Deepcg: A Cell Graph Model For Predicting Prognosis In Lung Adenocarcinoma, Baoyi Zhang, Chenyang Li, Jia Wu, Jianjun Zhang, Chao Cheng

Faculty, Staff and Student Publications

Lung cancer is the first leading cause of cancer-related death in the United States, with lung adenocarcinoma as the major subtype accounting for 40% of all cases. To improve patient survival, image-based prognostic models were developed due to the ready availability of pathological images at diagnosis. However, the application of these models is hampered by two main challenges: the lack of publicly available image datasets with high-quality survival information and the poor interpretability of conventional convolutional neural network models. Here, we integrated matched transcriptomic and H&E staining data from TCGA (The Cancer Genome Atlas) to develop an image-based prognostic model, …

Persistent Gram-Negative Bloodstream Infection Increases The Risk Of Recurrent Bloodstream Infection With The Same Species, Paa Kwesi Ankrah, Andrew Bock, Felicia Ruffin, Blake M Hanson, Cesar A Arias, Stacey A Maskarinec, Joshua Parsons, Vance G Fowler, Joshua T Thaden

Faculty, Staff and Student Publications

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection.

Immunotherapy In Locally Advanced Cervical Cancer: Integrating Keynote-A18 Into Management Strategies, Jeffrey A How, Amir A Jazaeri

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In locally advanced cervical cancer (LACC), the benefit of PD-1 blockade was unknown. In KEYNOTE-A18, Lorusso et al.1 compared the efficacy and safety of adding pembrolizumab to chemoradiation in LACC and demonstrated favorable outcomes. Given multiple approved indications of pembrolizumab in cervical cancer, strategies for optimal integration into management will be needed to maximize overall survival.

Germ Cell Tumor Of The Testis: Lethal Subtypes Of A Curable Cancer, Jamaal C Jackson, Darren Sanchez, Andrew C Johns, Matthew T Campbell, Ahmet M Aydin, Neriman Gokden, Sanjay Maraboyina, Jason L Muesse, John F Ward, Louis L Pisters, Niki M Zacharias, Charles C Guo, Shi-Ming Tu

Faculty, Staff and Student Publications

Germ cell tumor of the testis (GCT) is a curable cancer even when it is widely metastatic; however, outcomes can differ based on tumor histology. Chemo-resistance in certain phenotypes, such as teratoma and yolk sac tumor, contributes to poor clinical outcomes in some patients with GCT. Despite this resistance to S-YSTemic therapy, many of these tumor subtypes remain amenable to surgical resection and possible cure. In this study, we report on a series of seven patients highlighting two chemo-resistant subtypes of nonseminomatous germ cell tumor (NSGCT), sarcomatoid yolk sac tumor (S-YST), and epithelioid trophoblastic tumor (ETT) for which early resection …

Slow Proliferation Of Bap1-Deficient Uveal Melanoma Cells Is Associated With Reduced S6 Signaling And Resistance To Nutrient Stress, Vivian Chua, Melisa Lopez-Anton, Mizue Terai, Ryota Tanaka, Usman Baqai, Timothy J Purwin, Jelan I Haj, Francis J Waltrich, Isabella Trachtenberg, Kristine Luo, Rohith Tudi, Angela Jeon, Anna Han, Inna Chervoneva, Michael A Davies, Julio A Aguirre-Ghiso, Takami Sato, Andrew E Aplin

Faculty, Staff and Student Publications

Uveal melanoma (UM) is the deadliest form of eye cancer in adults. Inactivating mutations and/or loss of expression of the gene encoding BRCA1-associated protein 1 (BAP1) in UM tumors are associated with an increased risk of metastasis. To investigate the mechanisms underlying this risk, we explored the functional consequences of BAP1 deficiency. UM cell lines expressing mutant BAP1 grew more slowly than those expressing wild-type BAP1 in culture and in vivo. The ability of BAP1 reconstitution to restore cell proliferation in BAP1-deficient cells required its deubiquitylase activity. Proteomic analysis showed that BAP1-deficient cells had decreased phosphorylation of ribosomal S6 and …

Role Of Ethanolamine Utilization And Bacterial Microcompartment Formation In Listeria Monocytogenes Intracellular Infection, Ayan Chatterjee, Karan Gautam Kaval, Danielle A Garsin

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Ethanolamine (EA) affects the colonization and pathogenicity of certain human bacterial pathogens in the gastrointestinal tract. However, EA can also affect the intracellular survival and replication of host cell invasive bacteria such as Listeria monocytogenes (LMO) and Salmonella enterica serovar Typhimurium (S. Typhimurium). The EA utilization (eut) genes can be categorized as regulatory, enzymatic, or structural, and previous work in LMO showed that loss of genes encoding functions for the enzymatic breakdown of EA inhibited LMO intracellular replication. In this work, we sought to further characterize the role of EA utilization during LMO infection of host …

Collaborative Modeling To Compare Different Breast Cancer Screening Strategies: A Decision Analysis For The Us Preventive Services Task Force, Amy Trentham-Dietz, Christina Hunter Chapman, Jinani Jayasekera, Kathryn P Lowry, Brandy M Heckman-Stoddard, John M Hampton, Jennifer L Caswell-Jin, Ronald E Gangnon, Ying Lu, Hui Huang, Sarah Stein, Liyang Sun, Eugenio J Gil Quessep, Yuanliang Yang, Yifan Lu, Juhee Song, Diego F Muñoz, Yisheng Li, Allison W Kurian, Karla Kerlikowske, Ellen S O'Meara, Brian L Sprague, Anna N A Tosteson, Eric J Feuer, Donald Berry, Sylvia K Plevritis, Xuelin Huang, Harry J De Koning, Nicolien T Van Ravesteyn, Sandra J Lee, Oguzhan Alagoz, Clyde B Schechter, Natasha K Stout, Diana L Miglioretti, Jeanne S Mandelblatt

Faculty, Staff and Student Publications

IMPORTANCE: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known.

OBJECTIVE: To estimate outcomes of various mammography screening strategies.

DESIGN, SETTING, AND POPULATION: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses.

EXPOSURES: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or …

Author Correction: Long Noncoding Rna Malat1 Protects Against Osteoporosis And Bone Metastasis, Yang Zhao, Jingyuan Ning, Hongqi Teng, Yalan Deng, Marisela Sheldon, Lei Shi, Consuelo Martinez, Jie Zhang, Annie Tian, Yutong Sun, Shinichi Nakagawa, Fan Yao, Hai Wang, Li Ma

Faculty, Staff and Student Publications

This corrects the article "Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis", 2384.