Medical Specialties Commons^™

Safety Of Nivolumab Added To Chemoradiation Therapy Platforms For Intermediate And High-Risk Locoregionally Advanced Head And Neck Squamous Cell Carcinoma: Rtog Foundation 3504, Maura L Gillison, Robert L Ferris, Jonathan Harris, A Dimitrios Colevas, Loren K Mell, Christina Kong, Richard C Jordan, Kevin L Moore, Minh-Tam Truong, Claudia Kirsch, Arnab Chakravarti, Dukagjin M Blakaj, David A Clump, James P Ohr, John F Deeken, Michael F Gensheimer, Nabil F Saba, Jennifer A Dorth, David I Rosenthal, Rom S Leidner, Randall J Kimple, Mitchell Machtay, Walter J Curran, Pedro Torres-Saavedra, Quynh Thu Le

Faculty, Staff and Student Publications

PURPOSE: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown.

METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting …

The Alpha7 Integrin Subunit In Astrocytes Promotes Endothelial Blood-Brain Barrier Integrity, Zhihua Chen, Jack R Kelly, John E Morales, Raymond C Sun, Arpan De, Dean J Burkin, Joseph H Mccarty

Faculty, Staff and Student Publications

The blood-brain barrier (BBB) is a vascular endothelial cell boundary that partitions the circulation from the central nervous system to promote normal brain health. We have a limited understanding of how the BBB is formed during development and maintained in adulthood. We used quantitative transcriptional profiling to investigate whether specific adhesion molecules are involved in BBB functions, with an emphasis on understanding how astrocytes interact with endothelial cells. Our results reveal a striking enrichment of multiple genes encoding laminin subunits as well as the laminin receptor gene Itga7, which encodes the alpha7 integrin subunit, in astrocytes. Genetic ablation of Itga7 …

Sequential Targeting Of Retinoblastoma And Dna Synthesis Pathways Is A Therapeutic Strategy For Sarcomas That Can Be Monitored In Real Time, Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N Bui, Rossana Lazcano, Davis R Ingram, Min Yi, Varshini Vakulabharanam, Linjie Luo, Marc A Pina, Cansu Karakas, Mi Li, Nicole M Kettner, Neeta Somaiah, Peter J Hougton, Osama Mawlawi, Alexander J Lazar, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective 2-step sequential combination …

Etnk1 Mutation Occurs In A Wide Spectrum Of Myeloid Neoplasms And Is Not Specific For Atypical Chronic Myeloid Leukemia, Wen Shuai, Zhuang Zuo, Nianyi Li, Sofia Garces, Fatima Zahra Jelloul, Chi Young Ok, Shaoying Li, Jie Xu, M James You, Wei Wang, Catherine Rehder, Elias J Jabbour, Keyur P Patel, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

Background: ETNK1 mutation has been suggested as a useful tool to support the diagnosis of atypical chronic myeloid leukemia. ETNK1 mutations, however, occur in other myeloid neoplasms.

Methods: The authors assessed the clinicopathologic and molecular genetic features of 80 ETNK1-mutated myeloid neoplasms.

Results: Thirty-seven neoplasms (46%) were classified as myelodysplastic syndrome, 17 (21%) were classified as myelodysplastic/myeloproliferative neoplasm, 14 (18%) were classified as acute myeloid leukemia, and 12 (15%) were classified as myeloproliferative neoplasm. ETNK1 mutations were detected at the first test in 96% of patients, suggesting that ETNK1 mutation is an early event in pathogenesis. ETNK1 mutations represented the …

Kdm6a Loss Triggers An Epigenetic Switch That Disrupts Urothelial Differentiation And Drives Cell Proliferation In Bladder Cancer, Hong Qiu, Vladimir Makarov, Jennifer K Bolzenius, Angela Halstead, Yvonne Parker, Allen Wang, Gopakumar V Iyer, Hannah Wise, Daniel Kim, Varna Thayaparan, Daniel J Lindner, Georges-Pascal Haber, Angela H Ting, Bing Ren, Timothy A Chan, Vivek Arora, David B Solit, Byron H Lee

Faculty, Staff and Student Publications

Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect the epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that KDM6A loss triggers an epigenetic switch that disrupts urothelial differentiation and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 interacted with KDM6A to activate genes instructing urothelial differentiation. KDM6A-deficient cells displayed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn repressed …

Sequential Targeting Of Retinoblastoma And Dna Synthesis Pathways Is A Therapeutic Strategy For Sarcomas That Can Be Monitored In Real Time, Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N Bui, Rossana Lazcano, Davis R Ingram, Min Yi, Varshini Vakulabharanam, Linjie Luo, Marc A Pina, Cansu Karakas, Mi Li, Nicole M Kettner, Neeta Somaiah, Peter J Hougton, Osama Mawlawi, Alexander J Lazar, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell-cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1,043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective two-step sequential combination strategy …

Delayed Thoracodorsal Artery Perforator Free Flap For Calcaneal Degloving Injury Reconstruction, Mallorie L. Huff, Ahmed M. Mansour, Mamtha S. Raj, Robert J. Allen, Sean J. Wallace

School of Medicine Faculty Publications

The thoracodorsal artery perforator (TDAP) flap has a long vascular pedicle that is ideal for lower extremity reconstruction, but it generally relies on the presence of a dominant septocutaneous perforator vessel. Surgical delay optimizes flap survival by creating relative ischemia to augment perforator vessels. In this report, we describe the use of a delayed free TDAP flap in the setting of an absent dominant perforator vessel for the reconstruction of a calcaneal degloving injury. A 22-year-old actively smoking patient with a body mass index of 33.5 presented with a nonhealing left heel wound with overlying necrotic changes after traumatic degloving …

Evolutionarily Conserved Regulators Of Tau Identify Targets For New Therapies, Jiyoen Kim, Maria De Haro, Ismael Al-Ramahi, Lorena Laura Garaicoechea, Hyun-Hwan Jeong, Jun Young Sonn, Bakhos Tadros, Zhandong Liu, Juan Botas, Huda Yahya Zoghbi

Duncan NRI Faculty and Staff Publications

Tauopathies are neurodegenerative diseases that involve the pathological accumulation of tau proteins; in this family are Alzheimer disease, corticobasal degeneration, and chronic traumatic encephalopathy, among others. Hypothesizing that reducing this accumulation could mitigate pathogenesis, we performed a cross-species genetic screen targeting 6,600 potentially druggable genes in human cells and Drosophila. We found and validated 83 hits in cells and further validated 11 hits in the mouse brain. Three of these hits (USP7, RNF130, and RNF149) converge on the C terminus of Hsc70-interacting protein (CHIP) to regulate tau levels, highlighting the role of CHIP in maintaining tau proteostasis in the brain. …

Daily Posture Behavior Patterns Derived From Multitime-Scale Topic Models Using Wearable Triaxial Acceleration For Assessment Of Concern About Falling, Changhong Wang, Yu Wang, Haitao Zhao, Guanzheng Liu, Bijan Najafi

Center on Aging Staff Publications

Concern about falling is prevalent in older population. This condition would cause a series of adverse physical and psychological consequences for older adults' health. Traditional assessment of concern about falling is relied on self-reported questionnaires and thus is too subjective. Therefore, we proposed a novel multi-time-scale topic modelling approach to quantitatively evaluate concern about falling by analyzing triaxial acceleration signals collected from a wearable pendent sensor. Different posture segments were firstly recognized to extract their corresponding feature subsets. Then, each selected feature related to concern about falling was clustered into discrete levels as feature letters of artificial words in different …

National Heart Center/Saudi Heart Association 2023 Guidelines On The Management Of Hypertension, Waleed Alhabeeb, Adel Abdulkader Tash, Mostafa Alshamiri, Mohamed Arafat, Mohammed Ali Balghith, Ali Almasood, Abdulla Eltayeb, Hossam Elghetany, Taher Hassan, Owayed Alshemmari

Journal of the Saudi Heart Association

Background: Hypertension is a highly prevalent disease in Saudi Arabia with poor control rates. Updated guidelines are needed to guide the management of hypertension and improve treatment outcomes. Methodology: A panel of experts representing the National Heart Center (NHC) and the Saudi Heart Association (SHA) reviewed existing evidence and formulated guidance relevant to the local population, clinical practice and the healthcare system. The recommendations were reviewed to ensure scientific and medical accuracy. Recommendations: Hypertension was defined and a new classification was proposed as relevant to the Saudi population. Recommendations on diagnosis, clinical evaluation, cardiovascular assessment were detailed, along with guidance …

March 2023: Region 10 Emerging Special Pathogen Treatment Center (Resptc) At Providence Sacred Heart Medical Center & Children’S Hospital, Providence - Special Pathogens Program

Special Pathogens Newsletters

REGION 10 SPECIAL PATHOGENS NEWSLETTER

Adverse Outcomes Of Atrial Fibrillation Ablation In Heart Failure Patients With And Without Cardiac Amyloidosis: A Nationwide Readmissions Database Analysis (2015-2019), Waqas Ullah, Max Ruge, Md, Alexander G. Hajduczok, Kirpal Kochar, Daniel R. Frisch, Behzad B. Pavri, René J Alvarez, Indranee N. Rajapreyar, Yevgeniy Brailovsky

Jefferson Hospital Staff Papers and Presentations

AIMS: Atrial fibrillation (AF) in patients with cardiac amyloidosis (CA) has been linked with a worse prognosis. The current study aimed to determine the outcomes of AF catheter ablation in patients with CA.

METHODS AND RESULTS: The Nationwide Readmissions Database (2015-2019) was used to identify patients with AF and concomitant heart failure. Among these, patients who underwent catheter ablation were classified into two groups, patients with and without CA. The adjusted odds ratio (aOR) of index admission and 30-day readmission outcomes was calculated using a propensity score matching (PSM) analysis. A total of 148 134 patients with AF undergoing catheter …

Magnetized Chitosan Hydrogel And Silk Fibroin, Reinforced With Pva: A Novel Nanobiocomposite For Biomedical And Hyperthermia Applications, Reza Eivazzadeh-Keihan, Zeinab Pajoum, Hooman Aghamirza Moghim Aliabadi, Adibeh Mohammadi, Amir Kashtiaray, Milad Salimi Bani, Banafshe Pishva, Ali Maleki, Majid M Heravi, Mohammad Mahdavi, Elaheh Ziaei Ziabari

Department of Orthopaedic Surgery Faculty Papers

Herein, a multifunctional nanobiocomposite was designed for biological application, amongst which hyperthermia cancer therapy application was specifically investigated. This nanobiocomposite was fabricated based on chitosan hydrogel (CS), silk fibroin (SF), water-soluble polymer polyvinyl alcohol (PVA) and iron oxide magnetic nanoparticles (Fe₃O₄ MNPs). CS and SF as natural compounds were used to improve the biocompatibility, biodegradability, adhesion and cell growth properties of the nanobiocomposite that can prepare this nanocomposite for the other biological applications such as wound healing and tissue engineering. Since the mechanical properties are very important in biological applications, PVA polymer was used to increase the …

Glut1 Is Redundant In Hypoxic And Glycolytic Nucleus Pulposus Cells Of The Intervertebral Disc, Shira N. Johnston, Elizabeth S. Silagi, Vedavathi Madhu, Duc H. Nguyen, Irving M. Shapiro, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Glycolysis is central to homeostasis of nucleus pulposus (NP) cells in the avascular intervertebral disc. Since the glucose transporter, GLUT1, is a highly enriched phenotypic marker of NP cells, we hypothesized that it is vital for the development and postnatal maintenance of the disc. Surprisingly, primary NP cells treated with 2 well-characterized GLUT1 inhibitors maintained normal rates of glycolysis and ATP production, indicating intrinsic compensatory mechanisms. We showed in vitro that NP cells mitigated GLUT1 loss by rewiring glucose import through GLUT3. Of note, we demonstrated that substrates, such as glutamine and palmitate, did not compensate for glucose restriction resulting …

T-Cell Receptor Repertoire Sequencing In The Era Of Cancer Immunotherapy, Meredith L Frank, Kaylene Lu, Can Erdogan, Yi Han, Jian Hu, Tao Wang, John V Heymach, Jianjun Zhang, Alexandre Reuben

Faculty, Staff and Student Publications

T cells are integral components of the adaptive immune system, and their responses are mediated by unique T-cell receptors (TCR) that recognize specific antigens from a variety of biological contexts. As a result, analyzing the T-cell repertoire offers a better understanding of immune responses and of diseases like cancer. Next-generation sequencing technologies have greatly enabled the high-throughput analysis of the TCR repertoire. On the basis of our extensive experience in the field from the past decade, we provide an overview of TCR sequencing, from the initial library preparation steps to sequencing and analysis methods and finally to functional validation techniques. …

Genetic Architecture Of Spatial Electrical Biomarkers For Cardiac Arrhythmia And Relationship With Cardiovascular Disease, William J Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, Aaron Isaacs, Andrew R Harper, Julia Ramirez, Sophie Garnier, Stefan Van Duijvenboden, Antoine R Baldassari, Maria Pina Concas, Thuyvy Duong, Luisa Foco, Jonas L Isaksen, Hao Mei, Raymond Noordam, Casia Nursyifa, Anne Richmond, Meddly L Santolalla, Colleen M Sitlani, Negin Soroush, Sébastien Thériault, Stella Trompet, Stefanie Aeschbacher, Fariba Ahmadizar, Alvaro Alonso, Jennifer A Brody, Archie Campbell, Adolfo Correa, Dawood Darbar, Antonio De Luca, Jean-François Deleuze, Christina Ellervik, Christian Fuchsberger, Anuj Goel, Christopher Grace, Xiuqing Guo, Torben Hansen, Susan R Heckbert, Rebecca D Jackson, Jan A Kors, Maria Fernanda Lima-Costa, Allan Linneberg, Peter W Macfarlane, Alanna C Morrison, Pau Navarro, David J Porteous, Peter P Pramstaller, Alexander P Reiner, Lorenz Risch, Ulrich Schotten, Xia Shen, Gianfranco Sinagra, Elsayed Z Soliman, Monika Stoll, Eduardo Tarazona-Santos, Andrew Tinker, Katerina Trajanoska, Eric Villard, Helen R Warren, Eric A Whitsel, Kerri L Wiggins, Dan E Arking, Christy L Avery, David Conen, Giorgia Girotto, Niels Grarup, Caroline Hayward, J Wouter Jukema, Dennis O Mook-Kanamori, Morten Salling Olesen, Sandosh Padmanabhan, Bruce M Psaty, Cristian Pattaro, Antonio Luiz P Ribeiro, Jerome I Rotter, Bruno H Stricker, Pim Van Der Harst, Cornelia M Van Duijn, Niek Verweij, James G Wilson, Michele Orini, Philippe Charron, Hugh Watkins, Charles Kooperberg, Henry J Lin, James F Wilson, Jørgen K Kanters, Nona Sotoodehnia, Borbala Mifsud, Pier D Lambiase, Larisa G Tereshchenko, Patricia B Munroe

Faculty, Staff and Student Publications

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic …

Use Of Dual Genomic Sequencing To Screen Mitochondrial Diseases In Pediatrics: A Retrospective Analysis, Teng-Hui Wu, Jing Peng, Li Yang, Yan-Hui Chen, Xiu-Lan Lu, Jiao-Tian Huang, Jie-Yu You, Wen-Xian Ou-Yang, Yue-Yu Sun, Yi-Nan Xue, Xiao Mao, Hui-Ming Yan, Rong-Na Ren, Jing Xie, Zhi-Heng Chen, Victor-Wei Zhang, Gui-Zhen Lyu, Fang He

Children’s Nutrition Research Center Staff Publications

Mitochondrial diseases (MDs) were a large group multisystem disorders, attributable in part to the dual genomic control. The advent of massively sequencing has improved diagnostic rates and speed, and was increasingly being used as a first-line diagnostic test. Paediatric patients (aged <  18 years) who underwent dual genomic sequencing were enrolled in this retrospective multicentre study. We evaluated the mitochondrial disease criteria (MDC) and molecular diagnostic yield of dual genomic sequencing. Causative variants were identified in 177 out of 503 (35.2%) patients using dual genomic sequencing. Forty-six patients (9.1%) had mitochondria-related variants, including 25 patients with nuclear DNA (nDNA) variants, 15 with mitochondrial DNA (mtDNA) variants, and six with dual genomic variants (MT-ND6 and POLG; MT-ND5 and RARS2; MT-TL1 and NARS2; MT-CO2 and NDUFS1; MT-CYB and SMARCA2; and CHRNA4 and MT-CO3). Based on the MDC, 15.2% of the patients with mitochondria-related variants were classified as "unlikely to have mitochondrial disorder". Moreover, 4.5% of the patients with non-mitochondria-related variants and 1.43% with negative genetic tests, were classified as "probably having mitochondrial disorder". Dual genomic sequencing in suspected MDs provided a more comprehensive and accurate diagnosis for pediatric patients, especially for patients with dual genomic variants.

Renal Cell Carcinoma Unclassified With Medullary Phenotype In A Patient With Neurofibromatosis Type 2, Sanila Sarkar, Whitney Throckmorton, Racheal Bingham, Pavlos Msaouel, Giannicola Genovese, John Slopis, Priya Rao, Zsila Sadighi, Cynthia E Herzog

Faculty, Staff and Student Publications

We present, to our knowledge, the first reported case of germline neurofibromatosis Type 2 (NF2) associated with renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) with somatic loss by immunohistochemistry of the SMARCB1 tumor suppressor gene located centromeric to NF2 on chromosome 22q. Our patient is a 15-year-old with germline neurofibromatosis Type 2 (NF2) confirmed by pathogenic mutation of c.-854-??46+??deletion. Her NF2 history is positive for a right optic nerve sheath meningioma, CNIII schwannoma requiring radiation therapy and post gross total resection of right frontotemporal anaplastic meningioma followed by radiation. At age 15 she developed new onset weight loss and …

Enzalutamide-Induced Signatures Revealed By Epigenetic Plasticity Using Single-Cell Multi-Omics Sequencing In Prostate Cancer, Huihui Fan, Jinze Li, Astrid M Manuel, Zhongming Zhao

Faculty, Staff and Student Publications

Prostate cancer is morphologically and molecularly heterogeneous, which poses obstacles for early diagnosis and treatment. Advancements in understanding the heterogeneity of prostate cancer will help navigate through these challenges and ultimately benefit patients. In this study, we integrated single-cell sequencing for transposase-accessible chromatin and whole transcriptome in prostate cancer cell lines, aiming to decode the epigenetic plasticity upon enzalutamide (ENZ) treatment. By comparing the cell populations representing early-treatment response or resistance to the initial tumor cells, we identified seven signature gene sets; they present consistent trends of chromatin closing co-occurred with down-regulated genes during early response and chromatin opening with …

Validation Of The Alfa-1200 Model In Older Patients With Aml Treated With Intensive Chemotherapy, Hussein A Abbas, Hanxiao Sun, Sherry Pierce, Rashmi Kanagal-Shamanna, Ziyi Li, Musa Yilmaz, Gautam Borthakur, Adam J Dipippo, Elias Jabbour, Marina Konopleva, Nicholas J Short, Courtney Dinardo, Naval Daver, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

No abstract provided.

Hypermitotic Meningiomas Harbor Dna Methylation Subgroups With Distinct Biological And Clinical Features, Abrar Choudhury, William C Chen, Calixto-Hope G Lucas, James C Bayley, Akdes S Harmanci, Sybren L N Maas, Sandro Santagata, Tiemo Klisch, Arie Perry, Wenya Linda Bi, Felix Sahm, Akash J Patel, Stephen T Magill, David R Raleigh

Faculty, Staff and Students Publications

BACKGROUND: Meningiomas, the most common primary intracranial tumors, can be separated into 3 DNA methylation groups with distinct biological drivers, clinical outcomes, and therapeutic vulnerabilities. Alternative meningioma grouping schemes using copy number variants, gene expression profiles, somatic short variants, or integrated molecular models have been proposed. These data suggest meningioma DNA methylation groups may harbor subgroups unifying contrasting theories of meningioma biology.

METHODS: A total of 565 meningioma DNA methylation profiles from patients with comprehensive clinical follow-up at independent discovery (n = 200) or validation (n = 365) institutions were reanalyzed and classified into Merlin-intact, Immune-enriched, or Hypermitotic DNA methylation …

Shedding Light On Mechanisms Of Myocarditis With Covid-19 Mrna Vaccines, Biykem Bozkurt

Faculty, Staff and Students Publications

No abstract provided.

Human Schistosomiasis Vaccines As Next Generation Control Tools, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Students Publications

No abstract provided.

Downregulated Klf2 In Polycythemia Vera And Essential Thrombocythemia Induces Prothrombotic Gene Expression, Jihyun Song, Soo Jin Kim, Jahnavi Gollamudi, Perumal Thiagarajan, Josef T Prchal

Faculty, Staff and Students Publications

Thromboses are major causes of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET) diseases associated with JAK2V617F mutation. However, the molecular mechanism(s) of increased thrombosis in PV and ET remain unknown. Kruppel-like factor 2 (KLF2) is a transcription factor that regulates expression of genes associated with inflammation and thrombosis; the absence of KLF2 in neutrophils causes thrombosis by inducing tissue factor. We studied the role of KLF2 in regulating prothrombotic gene expression in PV and ET. Neutrophils and platelets KLF2 expression in PV and ET was lower than the controls. Furthermore, in patients with thromboses, KLF2 transcripts …

Tsks Localizes To Nuage In Spermatids And Regulates Cytoplasmic Elimination During Spermiation, Keisuke Shimada, Soojin Park, Seiya Oura, Taichi Noda, Akane Morohoshi, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Spermatozoa have a streamlined shape to swim through the oviduct to fertilize oocytes. To become svelte spermatozoa, spermatid cytoplasm must be eliminated in several steps including sperm release, which is part of spermiation. Although this process has been well observed, the molecular mechanisms that underlie it remain unclear. In male germ cells, there are membraneless organelles called nuage, which are observed by electron microscopy in various forms of dense material. Reticulated body (RB) and chromatoid body remnant (CR) are two types of nuage in spermatids, but the functions of both are unknown. Using CRISPR/Cas9 technology, we deleted the entire coding …

In Vivo Functional Characterization Of Egfr Variants Identifies Novel Drivers Of Glioblastoma, Kwanha Yu, Kathleen Kong, Brittney Lozzi, Estefania Luna-Figueroa, Alexis Cervantes, Rachel Curry, Carrie A Mohila, Ganesh Rao, Ali Jalali, Gordon B Mills, Kenneth L Scott, Benjamin Deneen

Faculty, Staff and Students Publications

BACKGROUND: Glioblastoma is the most common and aggressive primary brain tumor. Large-scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering "driver" and "passenger" events amongst the vast volume of information.

METHODS: We utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased …

Review Of Orthoplastic Techniques For Lower Extremity Reconstruction: Part One, Benjamin Heddy, Brady Webb

Advances in Clinical Medical Research and Healthcare Delivery

Orthoplastic techniques are effective tools for limb salvage in the lower extremity. In order to apply proper techniques successfully, a surgeon must be aware of all the different types of flaps available. Proper pre-operative evaluation and patient selection are also important factors. The following review covers six papers that give surgeons a strong foundation in the anatomical basis and surgical technique of intrinsic muscle flaps and other fasciocutaneous or adipofascial flaps of the foot. These flaps, along with split thickness skin grafts, external fixation, and dermal regenerative templates, quickly close soft tissue deficits in the foot and ankle that often …

A New Wave Of The Overdose Epidemic Arises During The Covid-19 Pandemic, Tolga Suvar Md, Asokumar Buvanendran Md, Stephen Music Do, Wilson M. Compton Md, Mpe

Advances in Clinical Medical Research and Healthcare Delivery

Abstract

Objective:

The goal of this manuscript is to highlight the notoriety of the overdose epidemic which has been masked by the Coronavirus pandemic.

Methods:

A thorough literature review of PubMed and the latest statistics from the Centers for Disease Control and Prevention (CDC) was performed for the most relevant and updated data regarding overdose deaths.

Conclusion:

The global health crisis known as the Coronavirus Disease 2019 (COVID-19) pandemic collided with the opioid epidemic in March of 2020, with devastating consequences for the United States. By overwhelming the healthcare system, the pandemic impacted patients who require continued mental health services, …

A Case Of Maintenance Prednisone In Anca Glomerulonephritis, Arjun Sekar, Pulkit Gandhi, Vijay Sheldon, Aswanth Reddy, Ruth Campbell

Advances in Clinical Medical Research and Healthcare Delivery

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare condition that can cause rapid renal failure. Treatment involves steroids and other immunosuppressive agents. Agents for induction include rituximab, cyclophosphamide, pulse dose steroids and avacopan.

Maintenance regimens include tapered doses of steroids, azathioprine and rituximab

We present a case of severe AAV that maintained remission with a protracted course of low dose prednisone without maintenance rituximab or azathioprine.

A 70-year-old woman was admitted for acute kidney injury (AKI), with a serum creatinine (sCr) of 6.93 mg/dL (baseline sCr of 0.9 mg/dL, nil proteinuria.) Serologic work-up was positive for P-ANCA. She …

Graves' Disease And Major Histocompatibility Complex Class Ii: A Meta-Analysis Of Hla-Dq And Hla-Drb1, Dylan Thibaut, Connor Sweeney, Shannon South, Mohamed Hussein

Advances in Clinical Medical Research and Healthcare Delivery

Background: Human leukocyte antigen (HLA) class II has shown potential in determining prognosis, understanding medication reactions, and predicting onset of Graves’ disease. The aim of this study is to further investigate the association between Graves’ disease and HLA class II, specifically HLA-DQ and HLA-DR, via meta-analysis to find HLAs that can be further examined for prognostic reasons.

Methods: Statistical analysis was performed to determine if variants of HLA-DQA1, HLA-DQB1, or HLA-DRB1 were associated with significantly altered odds of Graves’ disease. A minimum of three studies pertaining to a particular HLA was required for inclusion. Studies were excluded if …