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A Survey Of Feature Extraction And Fusion Of Deep Learning For Detection Of Abnormalities In Video Endoscopy Of Gastrointestinal-Tract, Hussam Ali, Muhammad Sharif, Mussarat Yasmin, Mubashir Husain Rehmani, Farhan Riaz Apr 2020

A Survey Of Feature Extraction And Fusion Of Deep Learning For Detection Of Abnormalities In Video Endoscopy Of Gastrointestinal-Tract, Hussam Ali, Muhammad Sharif, Mussarat Yasmin, Mubashir Husain Rehmani, Farhan Riaz

Publications

A standard screening procedure involves video endoscopy of the Gastrointestinal tract. It is a less invasive method which is practiced for early diagnosis of gastric diseases. Manual inspection of a large number of gastric frames is an exhaustive, time-consuming task, and requires expertise. Conversely, several computer-aided diagnosis systems have been proposed by researchers to cope with the dilemma of manual inspection of the massive volume of frames. This article gives an overview of different available alternatives for automated inspection, detection, and classification of various GI abnormalities. Also, this work elaborates techniques associated with content-based image retrieval and automated systems for …


Analysis Of Ptv Margins For Vmat Treatment Of Rectal Cancers Utilizing Prone Bellyboard Device., Ben Armbuster Apr 2020

Analysis Of Ptv Margins For Vmat Treatment Of Rectal Cancers Utilizing Prone Bellyboard Device., Ben Armbuster

Masters Projects

Utilization of a bellyboard device reduces small bowel dose for patients receiving radiation therapy for rectal cancer. The reduction of small bowel dose with the bellyboard is even more significant in intensity modulated radiation therapy rectal treatments, as opposed to conventional 3D treatments. However, there is evidence of increased setup variation with prone bellyboard positioning, especially in pitch and roll. The purpose of this study is to determine the margin needed between the clinical target volume and the planning target volume to adequately account for these setup variations when planning volumetric modulated arc therapy rectal cases utilizing the bellyboard device. …


Neurochemical Characterization Of Brainstem Pro-Opiomelanocortin Cells, Teodora Georgescu, David Lyons, Barbora Doslikova, Ana Paula Garcia, Oliver Marston, Luke K Burke, Raffaella Chianese, Brian Y H Lam, Giles S H Yeo, Justin J Rochford, Alastair S Garfield, Lora K Heisler Apr 2020

Neurochemical Characterization Of Brainstem Pro-Opiomelanocortin Cells, Teodora Georgescu, David Lyons, Barbora Doslikova, Ana Paula Garcia, Oliver Marston, Luke K Burke, Raffaella Chianese, Brian Y H Lam, Giles S H Yeo, Justin J Rochford, Alastair S Garfield, Lora K Heisler

Faculty, Staff and Student Publications

Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by …


Vital Signs, Spring 2020, Boonshoft School Of Medicine Apr 2020

Vital Signs, Spring 2020, Boonshoft School Of Medicine

Vital Signs

A thirty-one page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, alumni profiles, class notes, and more.


Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan Apr 2020

Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan

Nebraska Center for Virology: Faculty Publications

Intracellular iron concentration is tightly regulated to maintain cell viability. Iron plays important roles in electron transport, nucleic acid synthesis, and oxidative stress. A Mycobacterium avium subsp. paratuberculosis (MAP)-specific genomic island carries a putative metal transport operon that includes MAP3773c, which encodes a Fur-like protein. Although well characterized as a global regulator of iron homeostasis in multiple bacteria, the function of Fur (ferric uptake regulator) in MAP is unknown as this organism also carries IdeR (iron dependent regulator), a native iron regulatory protein specific to mycobacteria. Computational analysis using PRODORIC identified 23 different pathways involved in respiration, metabolism, and virulence …


27 Å Cryo-Em Structure Of Rotavirus Core Protein Vp3, A Unique Capping Machine With A Helicase Activity, Dilip Kumar, Xinzhe Yu, Sue E Crawford, Rodolfo Moreno, Joanita Jakana, Banumathi Sankaran, Ramakrishnan Anish, Soni Kaundal, Liya Hu, Mary K Estes, Zhao Wang, B V Venkataram Prasad Apr 2020

27 Å Cryo-Em Structure Of Rotavirus Core Protein Vp3, A Unique Capping Machine With A Helicase Activity, Dilip Kumar, Xinzhe Yu, Sue E Crawford, Rodolfo Moreno, Joanita Jakana, Banumathi Sankaran, Ramakrishnan Anish, Soni Kaundal, Liya Hu, Mary K Estes, Zhao Wang, B V Venkataram Prasad

Faculty, Staff and Students Publications

In many viruses, including rotavirus (RV), the major pathogen of infantile gastroenteritis, capping of viral messenger RNAs is a pivotal step for efficient translation of the viral genome. In RV, VP3 caps the nascent transcripts synthesized from the genomic dsRNA segments by the RV polymerase VP1 within the particle core. Here, from cryo-electron microscopy, x-ray crystallography, and biochemical analyses, we show that VP3 forms a stable tetrameric assembly with each subunit having a modular domain organization, which uniquely integrates five distinct enzymatic steps required for capping the transcripts. In addition to the previously known guanylyl- and methyltransferase activities, we show …


Impedance Analysis Of Tissues In Nspef Treatment For Cancer Therapy, Edwin Ayobami Oshin Apr 2020

Impedance Analysis Of Tissues In Nspef Treatment For Cancer Therapy, Edwin Ayobami Oshin

Biomedical Engineering Theses & Dissertations

Nanosecond pulsed electric field (nsPEF) for cancer therapy is characterized by applications of high voltage pulses with low pulsed energy to induce non-thermal effects on tissues such as tumor ablation. It nonthermally treats tissues via electroporation. Electroporation is the increase in permeabilization of a cell membrane due to the application of high pulsed electric field. The objective of this study was to investigate the effect of nsPEF on tissue by monitoring the tissue’s impedance in real-time. Potato slices (both untreated and electroporated), and tumors extracted from female BALBc mice were studied. 100ns, 1-10kV pulses were applied to the tissues using …


Protection Against Ionizing Radiation And Chemotherapy Toxicity Via Latexin Regulation, Gary Van Zant, Ying Liang, Yi Liu Mar 2020

Protection Against Ionizing Radiation And Chemotherapy Toxicity Via Latexin Regulation, Gary Van Zant, Ying Liang, Yi Liu

Internal Medicine Faculty Patents

The present invention relates to methods for protecting against damage caused by radiation and/or chemotherapy, and methods for treating bone marrow damage by reducing/ inhibiting Latexin expression and/or Latexin activity. The methods comprise administering to a subject in need thereof a pharmaceutical composition comprising an antagonist that reduces expression and/or activity of latexin, wherein latexin is a latexin polynucleotide variant and/or a latexin polypeptide variant that binds to the antagonist.


Hepatitis B Virus Hbx Protein Mediates The Degradation Of Host Restriction Factors Through The Cullin 4 Ddb1 E3 Ubiquitin Ligase Complex, Marissa M Minor, F Blaine Hollinger, Adrienne L Mcnees, Sung Yun Jung, Antrix Jain, Joseph M Hyser, Karl-Dimiter Bissig, Betty L Slagle Mar 2020

Hepatitis B Virus Hbx Protein Mediates The Degradation Of Host Restriction Factors Through The Cullin 4 Ddb1 E3 Ubiquitin Ligase Complex, Marissa M Minor, F Blaine Hollinger, Adrienne L Mcnees, Sung Yun Jung, Antrix Jain, Joseph M Hyser, Karl-Dimiter Bissig, Betty L Slagle

Faculty, Staff and Students Publications

The hepatitis B virus (HBV) regulatory HBx protein is required for infection, and its binding to cellular damaged DNA binding protein 1 (DDB1) is critical for this function. DDB1 is an adaptor protein for the cullin 4A Really Interesting New Gene (RING) E3 ubiquitin ligase (CRL4) complex and functions by binding cellular DDB1 cullin associated factor (DCAF) receptor proteins that recruit substrates for ubiquitination and degradation. We compared the proteins found in the CRL4 complex immunoprecipitated from uninfected versus HBV-infected hepatocytes from human liver chimeric mice for insight into mechanisms by which HBV and the cell interact within the CRL4 …


Covid-19 Newsletter (Vol. 2), Center For Disaster Medicine, New York Medical College Mar 2020

Covid-19 Newsletter (Vol. 2), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.


Nr2f1 Heterozygous Knockout Mice Recapitulate Neurological Phenotypes Of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome And Show Impaired Hippocampal Synaptic Plasticity, Chun-An Chen, Wei Wang, Steen E Pedersen, Ayush Raman, Michelle L Seymour, Fernanda R Ruiz, Anping Xia, Meike E Van Der Heijden, Li Wang, Jiani Yin, Joanna Lopez, Megan E Rech, Richard A Lewis, Samuel M Wu, Zhandong Liu, Fred A Pereira, Robia G Pautler, Huda Y Zoghbi, Christian P Schaaf Mar 2020

Nr2f1 Heterozygous Knockout Mice Recapitulate Neurological Phenotypes Of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome And Show Impaired Hippocampal Synaptic Plasticity, Chun-An Chen, Wei Wang, Steen E Pedersen, Ayush Raman, Michelle L Seymour, Fernanda R Ruiz, Anping Xia, Meike E Van Der Heijden, Li Wang, Jiani Yin, Joanna Lopez, Megan E Rech, Richard A Lewis, Samuel M Wu, Zhandong Liu, Fred A Pereira, Robia G Pautler, Huda Y Zoghbi, Christian P Schaaf

Faculty, Staff and Students Publications

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) has been identified as an autosomal-dominant disorder characterized by a complex neurological phenotype, with high prevalence of intellectual disability and optic nerve atrophy/hypoplasia. The syndrome is caused by loss-of-function mutations in NR2F1, which encodes a highly conserved nuclear receptor that serves as a transcriptional regulator. Previous investigations to understand the protein's role in neurodevelopment have mostly used mouse models with constitutive and tissue-specific homozygous knockout of Nr2f1. In order to represent the human disease more accurately, which is caused by heterozygous NR2F1 mutations, we investigated a heterozygous knockout mouse model and found that this model …


Association Of Immunophenotype With Expression Of Topoisomerase Ii Α And Β In Adult Acute Myeloid Leukemia., Andrew P Michelson, Shannon Mcdonough, Cheryl L Willman, Eric R Koegle, John E Godwin, Stephen H Petersdorf, Alan F List, Megan Othus, Frederick R Appelbaum, Jerald P Radich, Mahrukh K Ganapathi, Anjali S Advani, Ram N Ganapathi Mar 2020

Association Of Immunophenotype With Expression Of Topoisomerase Ii Α And Β In Adult Acute Myeloid Leukemia., Andrew P Michelson, Shannon Mcdonough, Cheryl L Willman, Eric R Koegle, John E Godwin, Stephen H Petersdorf, Alan F List, Megan Othus, Frederick R Appelbaum, Jerald P Radich, Mahrukh K Ganapathi, Anjali S Advani, Ram N Ganapathi

Articles, Abstracts, and Reports

Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase II (topo II) isoforms, topo II α and topo IIβ. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo IIα and topo IIβ by RT-PCR and its relationship to immunophenotype (IP) and outcomes. Treatment outcomes were analyzed by logistic or Cox regression. In 211 patients, available for analysis, topo IIα expression was significantly lower than topo IIβ (P < 0.0001). In contrast to topo IIα, topo IIβ was significantly associated with blast percentage in marrow or blood (P = 0.0001), CD7 (P = 0.01), CD14 (P < 0.0001) and CD54 (P < 0.0001). Event free survival was worse for CD56-negative compared to CD56-high (HR = 1.9, 95% CI [1.0-3.5], p = 0.04), and overall survival was worse for CD-15 low as compared to CD15-high (HR = 2.2, 95% CI [1.1-4.2], p = 0.02). Ingenuity pathway analysis indicated topo IIβ and immunophenotype markers in a network associated with cell-to-cell signaling, hematological system development/function and inflammatory response. Topo IIβ expression reflects disease biology of highly proliferative disease and distinct IP but does not appear to be an independent variable influencing outcome in adult AML patients treated with anthracycline-based therapy.


Primary & Secondary Prevention Of Cardiovascular Disease In Primary Care, Marshall Miller, Md Mar 2020

Primary & Secondary Prevention Of Cardiovascular Disease In Primary Care, Marshall Miller, Md

Department of Family & Community Medicine Presentations and Grand Rounds

Overview

Review historical perspective and complexity of primary CVD prevention

Discuss primary & secondary prevention of CAD and the 2019 ACC/AHA guidelines

-- Review of the evidence & primary literature

  • Focus on CV risk assessment, DM, ASA/DAPT
  • Practical guidance and management considerations

-- CASES- let’s practice and discuss


Artificial Intelligence And Digital Microscopy Applications In Diagnostic Hematopathology, Hanadi El Achi, Joseph D Khoury Mar 2020

Artificial Intelligence And Digital Microscopy Applications In Diagnostic Hematopathology, Hanadi El Achi, Joseph D Khoury

Faculty, Staff and Student Publications

Digital Pathology is the process of converting histology glass slides to digital images using sophisticated computerized technology to facilitate acquisition, evaluation, storage, and portability of histologic information. By its nature, digitization of analog histology data renders it amenable to analysis using deep learning/artificial intelligence (DL/AI) techniques. The application of DL/AI to digital pathology data holds promise, even if the scope of use cases and regulatory framework for deploying such applications in the clinical environment remains in the early stages. Recent studies using whole-slide images and DL/AI to detect histologic abnormalities in general and cancer in particular have shown encouraging results. …


Molecular Genetics Of Keratinization Disorders - What's New About Ichthyosis, Jouni Uitto, Leila Youssefian, Amir Hossein Saeidian, Hassan Vahidnezhad Mar 2020

Molecular Genetics Of Keratinization Disorders - What's New About Ichthyosis, Jouni Uitto, Leila Youssefian, Amir Hossein Saeidian, Hassan Vahidnezhad

Department of Dermatology and Cutaneous Biology Faculty Papers

The heritable forms of keratinization disorders, including various forms of ichthyosis and keratodermas, comprise a phenotypically heterogeneous group of diseases which can be divided into syndromic and non-syndromic forms. In the non-syndromic forms, the clinical manifestations are limited to the cutaneous structures while the syndromic ones are associated with a spectrum of extracutaneous manifestations. The inheritance in different families can be autosomal dominant, autosomal recessive or either X-linked dominant or recessive. Currently at least 67 distinct genes have been associated with different forms of ichthyosis. These genes can be grouped on the basis of their physiological involvement, including genes encoding …


Arthritis In Chronic Hepatitis C Infection: Is It Rheumatoid Like Arthritis Or True Rheumatoid Arthritis?, Jefri P. Susanto, Syifa Mustika, Bogi Pratomo Mar 2020

Arthritis In Chronic Hepatitis C Infection: Is It Rheumatoid Like Arthritis Or True Rheumatoid Arthritis?, Jefri P. Susanto, Syifa Mustika, Bogi Pratomo

Jurnal Penyakit Dalam Indonesia

No abstract provided.


Associations Between Aquaglyceroporin Gene Polymorphisms And Risk Of Stroke Among Patients With Hypertension, Qingyun Tu, Li Yan, Chun Wang, Aohan Han, Yu Qin, Lan Cui, Quanyong Xiang Mar 2020

Associations Between Aquaglyceroporin Gene Polymorphisms And Risk Of Stroke Among Patients With Hypertension, Qingyun Tu, Li Yan, Chun Wang, Aohan Han, Yu Qin, Lan Cui, Quanyong Xiang

Department of Medical Oncology Faculty Papers

Background: Dysregulations ofAQP7andAQP9were found to be related to lipid metabolism abnormality, which had been provento be one of the mechanisms of stroke. However, limited epidemiological studies explore the associations betweenAQP7andAQP9and the risk of stroke among patients with hypertension in China.

Aims: We aimed to investigate the associations between genetic variants in AQP7andAQP9and the risk of stroke among patients with hypertension, as well as to explore gene-gene andgene-environment interactions.

Methods: Baseline blood samples were drawn from 211 cases with stroke and 633 matched controls. Genomic DNA was extracted by a commercially available kit. Genotyping of 5 single nucleotide polymorphisms (SNPs) in …


The Relationship Between Serum Calcidiol Deficiency And The Degree Of Sarcopenia In Elderly Communities In Surabaya, Hemma Wahyuda Indirayani, Novira Widajanti, Hadiq Firdausi Mar 2020

The Relationship Between Serum Calcidiol Deficiency And The Degree Of Sarcopenia In Elderly Communities In Surabaya, Hemma Wahyuda Indirayani, Novira Widajanti, Hadiq Firdausi

Jurnal Penyakit Dalam Indonesia

No abstract provided.


Dietary Alterations Modulate The Microrna 29/30 And Igf-1/Akt Signaling Axis In Breast Cancer Liver Metastasis., Anuradha A. Shastri, Anthony Saleh, Jason E. Savage, Tiziana Deangelis, Kevin Camphausen, Nicole L. Simone Mar 2020

Dietary Alterations Modulate The Microrna 29/30 And Igf-1/Akt Signaling Axis In Breast Cancer Liver Metastasis., Anuradha A. Shastri, Anthony Saleh, Jason E. Savage, Tiziana Deangelis, Kevin Camphausen, Nicole L. Simone

Department of Radiation Oncology Faculty Papers

Background: Metastatic cancer is incurable and understanding the molecular underpinnings is crucial to improving survival for our patients. The IGF-1/Akt signaling pathway is often impaired in cancer leading to its progression and metastases. Diet modification is known to alter the IGF-1/Akt pathway and affect the expression of microRNA involved in tumor initiation, growth and metastases. Liver metastases are one of the most common type of metastases in breast and colon cancer. In the present study, we looked at the effect of diet modification on the expression of microRNA in normal liver and liver with breast cancer metastases using in vivo …


Late Weaning And Maternal Closeness, Associated With Advanced Motor And Visual Maturation, Reinforce Autonomy In Healthy, 2-Year-Old Children, José Villar, Roseline Ochieng, Eleonora Staines-Urias, Michelle Fernandes, Marc Ratcliff, Manorama Purwar, Fernando Barros, Bernardo Horta, Maria Carvalho, Zulfiqar Ahmed Bhutta Mar 2020

Late Weaning And Maternal Closeness, Associated With Advanced Motor And Visual Maturation, Reinforce Autonomy In Healthy, 2-Year-Old Children, José Villar, Roseline Ochieng, Eleonora Staines-Urias, Michelle Fernandes, Marc Ratcliff, Manorama Purwar, Fernando Barros, Bernardo Horta, Maria Carvalho, Zulfiqar Ahmed Bhutta

Woman and Child Health

We studied neurodevelopmental outcomes and behaviours in healthy 2-year old children (N = 1306) from Brazil, India, Italy, Kenya and the UK participating in the INTERGROWTH-21st Project. There was a positive independent relationship of duration of exclusive breastfeeding (EBF) and age at weaning with gross motor development, vision and autonomic physical activities, most evident if children were exclusively breastfed for ≥7 months or weaned at ≥7 months. There was no association with cognition, language or behaviour. Children exclusively breastfed from birth to6 months had, in a dose-effect pattern, adjusting for confounding factors, higher scores for "emotional reactivity". The positive …


Comparison Of Clinical Presentation And Out-Comes Of Chikungunya And Dengue Virus Infections In Patients With Acute Undifferentiated Febrile Illness From The Sindh Region Of Pakistan, Uzma Shahid, Joveria Farooqi, Kelli L. Barr, Syed Faisal Mahmood, Bushra Jamil, Kehkashan Imtiaz, Zahida Azizullah, Faisal Malik, Dhani Prakoso, Maureen T. Long, E. Khan Mar 2020

Comparison Of Clinical Presentation And Out-Comes Of Chikungunya And Dengue Virus Infections In Patients With Acute Undifferentiated Febrile Illness From The Sindh Region Of Pakistan, Uzma Shahid, Joveria Farooqi, Kelli L. Barr, Syed Faisal Mahmood, Bushra Jamil, Kehkashan Imtiaz, Zahida Azizullah, Faisal Malik, Dhani Prakoso, Maureen T. Long, E. Khan

Department of Pathology and Laboratory Medicine

Background: Arboviruses are a cause of acute febrile illness and outbreaks worldwide. Recent outbreaks of Chikungunya virus (CHIKV) in dengue endemic areas have alarmed clinicians as unique clinical features differentiating CHIKV from Dengue virus (DENV) are limited. This has complicated diagnostic efforts especially in resource limited countries where lab testing is not easily available. Therefore, it is essential to analyse and compare clinical features of laboratory confirmed cases to assist clinicians in suspecting possible CHIKV infection at time of clinical presentation.
Methodology: A prospective point prevalence study was conducted, with the hypothesis that not all patients presenting with clinical suspicion …


Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin Mar 2020

Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

The elucidation of better treatments for solid tumors and especially malignant glial tumors is a priority. Better understanding of the molecular underpinnings of treatment response and resistance are critical determinants in the success for this endeavor. Recently, a battery of novel tools have surfaced that allow to interrogate tumor cell metabolism to more precise extent than this was possible in the earlier days. At the forefront of these developments are the extracellular flux and carbon tracing analyses. Through utilization of these techniques our group made the recent observation that acute and chronic c-MET inhibition drives fatty acid oxidation that in …


The Sineb1 Element In The Long Non-Coding Rna Malat1 Is Necessary For Tdp-43 Proteostasis, Tuan M Nguyen, Elena B Kabotyanski, Lucas C Reineke, Jiaofang Shao, Feng Xiong, Joo-Hyung Lee, Julien Dubrulle, Hannah Johnson, Fabio Stossi, Phoebe S Tsoi, Kyoung-Jae Choi, Alexander G Ellis, Na Zhao, Jin Cao, Oluwatoyosi Adewunmi, Josephine C Ferreon, Allan Chris M Ferreon, Joel R Neilson, Michael A Mancini, Xi Chen, Jongchan Kim, Li Ma, Wenbo Li, Jeffrey M Rosen Mar 2020

The Sineb1 Element In The Long Non-Coding Rna Malat1 Is Necessary For Tdp-43 Proteostasis, Tuan M Nguyen, Elena B Kabotyanski, Lucas C Reineke, Jiaofang Shao, Feng Xiong, Joo-Hyung Lee, Julien Dubrulle, Hannah Johnson, Fabio Stossi, Phoebe S Tsoi, Kyoung-Jae Choi, Alexander G Ellis, Na Zhao, Jin Cao, Oluwatoyosi Adewunmi, Josephine C Ferreon, Allan Chris M Ferreon, Joel R Neilson, Michael A Mancini, Xi Chen, Jongchan Kim, Li Ma, Wenbo Li, Jeffrey M Rosen

Faculty, Staff and Students Publications

Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the …


Proteins Inform Survival-Based Differences In Patients With Glioblastoma, L. C. Stetson, Daniela M. Schlatzer, Peter Liao, Karen Devine, Kristin Waite, Marta E. Couce, Andrew E. Sloan, Mark R. Chance, Jill S. Barnholtz-Sloan Mar 2020

Proteins Inform Survival-Based Differences In Patients With Glioblastoma, L. C. Stetson, Daniela M. Schlatzer, Peter Liao, Karen Devine, Kristin Waite, Marta E. Couce, Andrew E. Sloan, Mark R. Chance, Jill S. Barnholtz-Sloan

Faculty Scholarship

Background: Improving the care of patients with glioblastoma (GB) requires accurate and reliable predictors of patient prognosis. Unfortunately, while protein markers are an effective readout of cellular function, proteomics has been underutilized in GB prognostic marker discovery. Methods: For this study, GB patients were prospectively recruited and proteomics discovery using liquid chromatography-mass spectrometry analysis (LC-MS/MS) was performed for 27 patients including 13 short-term survivors (STS) (≤10 months) and 14 long-term survivors (LTS) (≥18 months). Results: Proteomics discovery identified 11 941 peptides in 2495 unique proteins, with 469 proteins exhibiting significant dysregulation when comparing STS to LTS. We verified the differential …


Students As Investigators: Utilizing Active Learning To Engage Genetic Counseling Students, Stacey E. Wahl Ph.D., Dana L. Ladd Ph.D. Mar 2020

Students As Investigators: Utilizing Active Learning To Engage Genetic Counseling Students, Stacey E. Wahl Ph.D., Dana L. Ladd Ph.D.

Transforming Libraries for Graduate Students

Providing one-shot instruction sessions can be difficult, particularly in the graduate learning environment. As librarians, we want to provide students with the skills to search effectively for health information without overwhelming or confusing them. In health science graduate programs, we are expected to connect literature searching skills with the content of the courses in a manner that is engaging to students. This challenge can be exacerbated when students are new to graduate school and have not yet become familiar with scientific literature searching or the research process. Two medical librarians sought to overcome these challenges by empowering genetic counseling students …


Atrx Loss In Pediatric Glioma Results In Epigenetic Dysregulation Of G2/M Checkpoint Maintenance And Sensitivity To Atm Inhibition, Brendan Mullan, Tingting Qin, Ruby Siada, Carla Danussi, Jacqueline Brosnan-Cashman, Drew Pratt, Taylor Garcia, Viveka Nand Yadav, Xinyi Zhao, Meredith Morgan, Sriram Venneti, Alan Meeker, Alnawaz Rehemtulla, Pedro Lowenstein, Maria Castro, Carl Koschmann Mar 2020

Atrx Loss In Pediatric Glioma Results In Epigenetic Dysregulation Of G2/M Checkpoint Maintenance And Sensitivity To Atm Inhibition, Brendan Mullan, Tingting Qin, Ruby Siada, Carla Danussi, Jacqueline Brosnan-Cashman, Drew Pratt, Taylor Garcia, Viveka Nand Yadav, Xinyi Zhao, Meredith Morgan, Sriram Venneti, Alan Meeker, Alnawaz Rehemtulla, Pedro Lowenstein, Maria Castro, Carl Koschmann

Medical Student Research Symposium

ATRX is a histone chaperone protein recurrently mutated in pediatric glioma. The mechanism which mediates the proliferative advantage of ATRX loss in pediatric glioma remains unexplained. Recent data revealed a distinct pattern of DNA binding sites of the ATRX protein using ChIP-seq in mouse neuronal precursor cells (mNPCs). Using the ATRX peaks identified in p53-/- mNPCs, we confirmed that ATRX binding sites were significantly enriched in gene promoters (p < 0.0001) and CpG islands (p < 0.0001) compared with random regions. Gene set enrichment (GSE) analysis identified that cell cycle and regulation of cell cycle were among the most significantly enriched gene sets (p=2.52e-16 and 1.61e-9, respectively). We found that ATRX loss resulted in dysfunction of G2/M checkpoint maintenance: (1) ATRX-deficient pediatric glioblastoma (GBM) cells exhibited a seven-fold increase in mitotic index at 16 hours after sub-lethal radiation, and (2) murine GBM cells with ATRX knockdown demonstrated impaired pChk1 signaling on western blot at multiple time points after radiation compared to controls (p=0.0187). Notably, the ATM signaling (pChk2) remained intact in those cells, suggesting a potential therapeutic target. ATRX-deficient mouse cells were uniquely sensitive to ATM inhibitors at 1 uM alongside 8 Gy radiation compared to controls with intact ATRX (AZD0156: p=0.0027 and AZD01390: p=0.0436). Mice intra-cranially implanted with ATRX-deficient GBM cells showed improved survival (n=10, p=0.0018) when treated with AZD0156 combined with radiation. Our findings suggest that ATRX loss in glioma results in unique sensitivity to ATM inhibition via epigenetic dysregulation of G2/M checkpoint maintenance.


Quality Improvement In Ibd Care: The Influence Of A Qi Specific Conference For Fellows, Olayinka Afolabi, Alexis Faber, Raya Kutaimy, Paul Naylor, Murray Ehrinpreis Mar 2020

Quality Improvement In Ibd Care: The Influence Of A Qi Specific Conference For Fellows, Olayinka Afolabi, Alexis Faber, Raya Kutaimy, Paul Naylor, Murray Ehrinpreis

Medical Student Research Symposium

Given the complexity of management of inflammatory bowel disease (IBD), medical societies such as the American Gastroenterological Association (AGA) and Crohn’s and Colitis Foundation of America (CCFA) have established measures aimed at defining quality of care. In 2011, the AGA proposed 10 quality metrics for IBD, eight of these measures relate to outpatient management and two focus on inpatient management. Our objective was to evaluate compliance with these measures in our own general GI practice and determine whether a GI conference discussing quality improvement (QI) in 2017 was effective.


Public Social Media Consultations For Dermatologic Conditions: An Online Survey, Elizabeth Schoenberg, Doaa Shalabi, Jordan Wang, Nazanin Saedi, Matthew Keller Mar 2020

Public Social Media Consultations For Dermatologic Conditions: An Online Survey, Elizabeth Schoenberg, Doaa Shalabi, Jordan Wang, Nazanin Saedi, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

The use of social media in medicine has been increasingly studied in recent years, especially concerning its role in patient outreach, education, diagnosis, and management. Dermatology is a unique field in that patients can post photographs of their skin ailments when seeking online medical advice and information. This study examines the role of public social media consultations for dermatologic conditions. A large portion of patients utilize social media for dermatologic consultations and many do not seek care from a dermatologist afterward. Future studies should trend this phenomenon, especially as the use of social media continues to expand.


Flavonoids And Other Polyphenols Act As Epigenetic Modifiers In Breast Cancer., Priyanga Selvakumar, Aja Badgeley, Paige Murphy, Hina Anwar, Urvashi Sharma, Katharine Lawrence, Ashakumary Lakshmikuttyamma Mar 2020

Flavonoids And Other Polyphenols Act As Epigenetic Modifiers In Breast Cancer., Priyanga Selvakumar, Aja Badgeley, Paige Murphy, Hina Anwar, Urvashi Sharma, Katharine Lawrence, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Breast cancer is a common cancer that occurs due to different epigenetic alterations and genetic mutations. Various epidemiological studies have demonstrated an inverse correlation between breast cancer incidence and flavonoid intake. The anti-cancer action of flavonoids, a class of polyphenolic compounds that are present in plants, as secondary metabolites has been a major topic of research for many years. Our review analysis demonstrates that flavonoids exhibit anti-cancer activity against breast cancer occurring in different ethnic populations. Breast cancer subtype and menopausal status are the key factors in inducing the flavonoid's anti-cancer action in breast cancer. The dose is another key …


Emerging Therapeutic Strategies For Covid-19 Patients, Shudong Zhu, Xialing Guo, Kyla Geary, Dianzheng Zhang Mar 2020

Emerging Therapeutic Strategies For Covid-19 Patients, Shudong Zhu, Xialing Guo, Kyla Geary, Dianzheng Zhang

PCOM Scholarly Works

Over 100,000 cases of COVID-19 patients infected with the novel coronavirus SARS-COV-2 have been reported worldwide in approximately 2 months, resulting in over 3000 deaths. Potential therapeutic strategies, including remdesivir, chloroquine phosphate, abidol, lopinavir/ritonavir, plasma, antibody, vaccine and stem cells are discussed in this review. With the number of patients increasing daily, there is an urgent need for effective therapeutic intervention.