Medical Specialties Commons^™

Defective Rab31-Mediated Megakaryocytic Early Endosomal Trafficking Of Vwf, Egfr, And M6pr In Runx1 Deficiency, Gauthami Jalagadugula, Guangfen Mao, Lawrence E Goldfinger, Jeremy Wurtzel, Fabiola Del Carpio-Cano, Michele P Lambert, Brian Estevez, Deborah L French, Mortimer Poncz, A Koneti Rao

Cardeza Foundation for Hematologic Research

Transcription factor RUNX1 is a master regulator of hematopoiesis and megakaryopoiesis. RUNX1 haplodeficiency (RHD) is associated with thrombocytopenia and platelet granule deficiencies and dysfunction. Platelet profiling of our study patient with RHD showed decreased expression of RAB31, a small GTPase whose cell biology in megakaryocytes (MKs)/platelets is unknown. Platelet RAB31 messenger RNA was decreased in the index patient and in 2 additional patients with RHD. Promoter-reporter studies using phorbol 12-myristate 13-acetate-treated megakaryocytic human erythroleukemia cells revealed that RUNX1 regulates RAB31 via binding to its promoter. We investigated RUNX1 and RAB31 roles in endosomal dynamics using immunofluorescence staining for markers of …

Delineating Covid-19 Immunological Features Using Single-Cell Rna Sequencing, Wendao Liu, Johnathan Jia, Yulin Dai, Wenhao Chen, Guangsheng Pei, Qiheng Yan, Zhongming Zhao

Faculty, Staff and Student Publications

Understanding the molecular mechanisms of coronavirus disease 2019 (COVID-19) pathogenesis and immune response is vital for developing therapies. Single-cell RNA sequencing has been applied to delineate the cellular heterogeneity of the host response toward COVID-19 in multiple tissues and organs. Here, we review the applications and findings from over 80 original COVID-19 single-cell RNA sequencing studies as well as many secondary analysis studies. We describe that single-cell RNA sequencing reveals multiple features of COVID-19 patients with different severity, including cell populations with proportional alteration, COVID-19-induced genes and pathways, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in single cells, and adaptation …

Serpinb3 Drives Cancer Stem Cell Survival In Glioblastoma, Adam Lauko, Josephine Volovetz, Soumya M Turaga, Defne Bayik, Daniel J Silver, Kelly Mitchell, Erin E Mulkearns-Hubert, Dionysios C Watson, Kiran Desai, Manav Midha, Jing Hao, Kathleen Mccortney, Alicia Steffens, Ulhas Naik, Manmeet S Ahluwalia, Shideng Bao, Craig Horbinski, Jennifer S Yu, Justin D Lathia

Department of Medicine Faculty Papers

Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. Knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced …

A Response To: Letter To The Editor Regarding "Importance Of Early Screening And Diagnosis Of Chronic Kidney Disease In Patients With Type 2 Diabetes"., Neil Skolnik, Alyssa Style

Department of Family & Community Medicine Faculty Papers

No abstract provided.

Pleomorphic Dermal Sarcoma Of The Scalp: Review Of Management And Distinguishing Features From Atypical Fibroxanthoma, Alexa J Cohen, Sahithi Talasila, Bojan Lazarevic, Laura Gleason, Viral Patel, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Bet Inhibition Induces Vulnerability To Mcl1 Targeting Through Upregulation Of Fatty Acid Synthesis Pathway In Breast Cancer, Gonghong Yan, Augustin Luna, Heping Wang, Behnaz Bozorgui, Xubin Li, Maga Sanchez, Zeynep Dereli, Nermin Kahraman, Goknur Kara, Xiaohua Chen, Caishang Zheng, Daniel Mcgrail, Nidhi Sahni, Yiling Lu, Ozgun Babur, Murat Cokol, Bora Lim, Bulent Ozpolat, Chris Sander, Gordon B Mills, Anil Korkut

Faculty, Staff and Student Publications

Therapeutic options for treatment of basal-like breast cancers remain limited. Here, we demonstrate that bromodomain and extra-terminal (BET) inhibition induces an adaptive response leading to MCL1 protein-driven evasion of apoptosis in breast cancer cells. Consequently, co-targeting MCL1 and BET is highly synergistic in breast cancer models. The mechanism of adaptive response to BET inhibition involves the upregulation of lipid synthesis enzymes including the rate-limiting stearoyl-coenzyme A (CoA) desaturase. Changes in lipid synthesis pathway are associated with increases in cell motility and membrane fluidity as well as re-localization and activation of HER2/EGFR. In turn, the HER2/EGFR signaling results in the accumulation …

Transcatheter Atrial Septal Defect Closure Before Versus After Adulthood, Mohamed Saber Hafez, Mohamed Ibrahim Abdelrahman El-Sayed, Maiy Hamdy El Sayed

Journal of the Saudi Heart Association

Objectives: To evaluate the long term outcome of patients who underwent percutaneous transcatheter closure of secundum atrial septal defects during teenage life versus adulthood. Methods: The study included 100 patients with secundum type ASD who were treated by transcatheter closure of their defects 2-5 years before enrollment. The study population was subdivided into 2 equal groups: group 1 who underwent transcatheter closure during teenage life (13-19 years) and group 2 who underwent transcatheter closure after the age of 30 years. The two groups were compared according to resting 12 lead ECG, 24 hour Holter ECG and transthoracic echocardiographic findings (Right …

Openkbp-Opt: An International And Reproducible Evaluation Of 76 Knowledge-Based Planning Pipelines, Aaron Babier, Rafid Mahmood, Binghao Zhang, Victor G L Alves, Ana Maria Barragán-Montero, Joel Beaudry, Carlos E Cardenas, Yankui Chang, Zijie Chen, Jaehee Chun, Kelly Diaz, Harold David Eraso, Erik Faustmann, Sibaji Gaj, Skylar Gay, Mary Gronberg, Bingqi Guo, Junjun He, Gerd Heilemann, Sanchit Hira, Yuliang Huang, Fuxin Ji, Dashan Jiang, Jean Carlo Jimenez Giraldo, Hoyeon Lee, Jun Lian, Shuolin Liu, Keng-Chi Liu, José Marrugo, Kentaro Miki, Kunio Nakamura, Tucker Netherton, Dan Nguyen, Hamidreza Nourzadeh, Alexander F I Osman, Zhao Peng, José Darío Quinto Muñoz, Christian Ramsl, Dong Joo Rhee, Juan David Rodriguez, Hongming Shan, Jeffrey V Siebers, Mumtaz H Soomro, Kay Sun, Andrés Usuga Hoyos, Carlos Valderrama, Rob Verbeek, Enpei Wang, Siri Willems, Qi Wu, Xuanang Xu, Sen Yang, Lulin Yuan, Simeng Zhu, Lukas Zimmermann, Kevin L Moore, Thomas G Purdie, Andrea L Mcniven, Timothy C Y Chan

Faculty, Staff and Student Publications

Objective.To establish an open framework for developing plan optimization models for knowledge-based planning (KBP).

Approach.Our framework includes radiotherapy treatment data (i.e. reference plans) for 100 patients with head-and-neck cancer who were treated with intensity-modulated radiotherapy. That data also includes high-quality dose predictions from 19 KBP models that were developed by different research groups using out-of-sample data during the OpenKBP Grand Challenge. The dose predictions were input to four fluence-based dose mimicking models to form 76 unique KBP pipelines that generated 7600 plans (76 pipelines × 100 patients). The predictions and KBP-generated plans were compared to the reference …

Social Media Impact Of Articles Published By Dermatology Residents During Medical School: Cross-Sectional Study, Austin Huang, Harrison Zhu, Kelvin Zhou, R Parker Kirby, Nina Dasari, Gianmarco A Calderara, Kathryn Cordova, Ryan Sorensen, Anshul Bhatnagar, Soo Jung Kim

Faculty, Staff and Students Publications

BACKGROUND: The Altmetric score (AS) is a novel measure of publication impact that is calculated by the number of mentions across various social media websites. This method may have advantages over traditional bibliometrics in the context of research by medical students.

OBJECTIVE: This study aimed to determine whether dermatology matriculants who graduated from higher-ranked medical schools published more articles with greater impact (ie, a higher AS) than those from lower-ranked institutions.

METHODS: A PubMed search for articles published by dermatology residents who started medical school in 2020 was conducted. Demographic information and Altmetric data were collected, and medical schools were …

Transmembrane Helices Mediate The Formation Of A Stable Ternary Complex Of B5r, Cyt B5, And Scd1, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Students Publications

Mammalian cytochrome b5 (cyt b5) and cytochrome b5 reductase (b5R) are electron carrier proteins for membrane-embedded oxidoreductases. Both b5R and cyt b5 have a cytosolic domain and a single transmembrane (TM) helix. The cytosolic domains of b5R and cyt b5 contain cofactors required for electron transfer, but it is not clear if the TM helix has function beyond being an anchor to the membrane. Here we show that b5R and cyt b5 form a stable binary complex, and so do cyt b5 and stearoyl-CoA desaturase-1 (SCD1). We also show that b5R, cyt b5 and SCD1 form a stable ternary complex. …

Computer-Vision-Based Vibration Tracking Using A Digital Camera: A Sparse-Optical-Flow-Based Target Tracking Method, Guang-Yu Nie, Saran Srikanth Bodda, Harleen Kaur Sandhu, Kevin Han, Abhinav Gupta

Faculty, Staff and Student Publications

Computer-vision-based target tracking is a technology applied to a wide range of research areas, including structural vibration monitoring. However, current target tracking methods suffer from noise in digital image processing. In this paper, a new target tracking method based on the sparse optical flow technique is introduced for improving the accuracy in tracking the target, especially when the target has a large displacement. The proposed method utilizes the Oriented FAST and Rotated BRIEF (ORB) technique which is based on FAST (Features from Accelerated Segment Test), a feature detector, and BRIEF (Binary Robust Independent Elementary Features), a binary descriptor. ORB maintains …

Measure Dx: Implementing Pathways To Discover And Learn From Diagnostic Errors, Andrea Bradford, Marjorie Shofer, Hardeep Singh

Faculty, Staff and Students Publications

Despite the high frequency of diagnostic errors, multiple barriers, including measurement, make it difficult learn from these events. This article discusses Measure Dx, a new resource from the Agency for Healthcare Research and Quality that translates knowledge from diagnostic safety measurement research into actionable recommendations. Measure Dx guides healthcare organizations to detect, analyze, and learn from diagnostic safety events as part of a continuous learning and feedback cycle. Wider adoption of Measure Dx, along with the implementation of solutions that result, can advance new frontiers in reducing preventable diagnostic harm to patients.

A Case Report And Literature Review On Argatroban Refractory Heparin-Induced Thrombocytopenia, Imad Ud Deen, Swati Ajay Jha, Sadaf Mustafa

Journal of Community Hospital Internal Medicine Perspectives

Heparin-induced thrombocytopenia (HIT) is characterized by low platelets and thrombosis after exposure to Heparin products. It is classically characterized by a rapid and significant drop in platelets and life-threatening thrombosis. Thrombosis can occur up to 50% of the cases if left untreated. It requires immediate discontinuation of all heparin products and switching to a non-heparin anticoagulant to prevent further thrombosis. Here we present a case of a 56-year-old male who presented to the Emergency Department with sudden onset of severe left leg pain. Duplex study showed arterial thrombosis in the common iliac and distal iliac arteries. He received TPA at …

A Rare Case Of Pembrolizumab Associated Encephalopathy, Sijan Basnet, Rajanbir Singh, Biswaraj Tharu, Tushar Pawar, Garima Basnet

Journal of Community Hospital Internal Medicine Perspectives

We present a unique case of a 55-year-old man with confusion thought to be due to pembrolizumab which he was receiving for renal cell carcinoma. His workup for other possible etiologies for encephalopathy was negative. He was treated with high dose intravenous methylprednisolone followed by prednisone taper and intravenous immunoglobulin with gradual improvement in his mentation.

Evidence-Based Role Of Aspirin In Giant Cell Arteritis: A Literature Review, Anum Qureshi, Fatima Halilu, Sam W. Serafi, Howard Hauptman, Tristan Flack

Journal of Community Hospital Internal Medicine Perspectives

Giant cell arteritis (GCA), or temporal arteritis, is a medium to large vessel vasculitis seen in the elderly. Its presentation varies from fever of unknown origin to cranial ischemic complications including complete vision loss. The early initiation of steroids is key to preventing complications of GCA. Here we discuss the role of aspirin in the treatment of GCA, both as an antithrombotic agent and its increasingly utilized antiinflammatory properties. The aim of this review article is to examine the evidence behind the rationale of aspirin use as an adjunct to steroids for the prevention of cranial ischemic complications.

Covid-19 Newsletter (Vol. 135), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

Mutations In Bcor, A Co-Repressor Of Crx/Otx2, Are Associated With Early-Onset Retinal Degeneration, Maéva Langouët, Christine Jolicoeur, Awais Javed, Pierre Mattar, Micah D Gearhart, Stephen P Daiger, Mette Bertelsen, Lisbeth Tranebjærg, Nanna D Rendtorff, Karen Grønskov, Catherine Jespersgaard, Rui Chen, Zixi Sun, Hui Li, Najmeh Alirezaie, Jacek Majewski, Vivian J Bardwell, Ruifang Sui, Robert K Koenekoop, Michel Cayouette

Faculty, Staff and Student Publications

Many transcription factors regulating the production, survival, and function of photoreceptor cells have been identified, but little is known about transcriptional co-regulators in retinal health and disease. Here, we show that BCL6 co-repressor (BCOR), a Polycomb repressive complex 1 factor mutated in various cancers, is involved in photoreceptor degenerative diseases. Using proteomics and transcription assays, we report that BCOR interacts with the transcription factors CRX and OTX2 and reduces their ability to activate the promoters of photoreceptor-specific genes. CUT&RUN sequencing further shows that BCOR shares genome-wide binding profiles with CRX/OTX2, consistent with a general co-repression activity. We also identify missense …

Covid-19 And Children, Carl A Pierce, Kevan C Herold, Betsy C Herold, Janet Chou, Adrienne Randolph, Binita Kane, Sammie Mcfarland, Deepti Gurdasani, Christina Pagel, Peter Hotez, Sarah Cobey, Scott E Hensley

Center for Medical Ethics and Health Policy Staff Publications

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in …

Coexistence Of Cutaneous Squamous Cell Carcinoma And Basal Cell Carcinoma In A Renal Transplant Recipient: A Case Report., Diana Voloshyna, Tanveer Ahamad Shaik, Sunita Shrestha, Ajmat Ansari, Faraz Saleem, Muhammad Abu Zar Ghaffari

Faculty and Staff Scholarship

In solid organ transplant patients, non-melanoma skin cancer remains a leading cause of mortality. The most common skin malignancies in solid organ transplant patients are squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In organ transplant patients, SCC is 100 times more prevalent, and BCC is 10 times more prevalent than in the general population. Many risk factors for developing such malignancies are equivalent to those in the general population. However, in the transplant population, such cancers occur at an earlier age, act more aggressively, and often appear at multiple locations. Thus, assiduousness on the patient's part and healthcare …

A Case Of Malpositioned Endotracheal Tube With Resultant Left Lung Collapse., Anushri Naga, Anushri Naga

Digital Journal of Clinical Medicine

BACKGROUND

ENDOTRACHEAL INTUBATION IS USUALLY DONE AS A PART OF EMERGENCY MANAGEMENT OF PATIENTS WITH A THREATENED AIRWAY AND GENERAL ANAESTHSIA, IN ORDER TO ENSURE PATENCY OF THE AIRWAY AS WELL AS PROPER VENTILATION. POSITIONING AN ET TUBE CORRECTLY IS OF PARAMOUNT IMPORTANCE IN ORDER TO PREVENT HYPOVENTILATION, INAPPROPRIATE VENTILATION AND ALSO COLLAPSE OF LUNG DUE TO MALPOSITIONING OF ET TUBE.

ETT POSITION IS USUALLY ASSESSED USING FRONTAL CHEST RADIOGRAPH. THE POSITION OF THE ETT IS DEPENDENT ON THE POSITION OF THE HEAD & NECK. THE MANDIBLE CAN BE USED FOR ASSESSMENT OF WHETHER THE NECK IS IN A NEUTRAL …

Post Covid-19 Cognitive Impairment In A Patient With Bipolar Disorder, Nilanjana Dutta, Raghav Gupta, Dr. M Kishor Mbbs, Md

Digital Journal of Clinical Medicine

COVID-19 has caused widespread health conditions, psychological and social distress among people and there is evidence that shows profound neuropsychiatric complications during acute and post-recovery phases of the infection. Cognitive impairment occurring after COVID-19 infection can be explained by various mechanisms, including persistent systemic inflammation, direct viral invasion, alteration in the blood-brain barrier, and cerebrovascular endothelial injury.There are few studies that have explored the impact of COVID-19 on pre-existing psychiatric conditions. This case report highlights the temporal association of cognitive impairment with COVID-19 and the need for cognitive assessment and management in post-COVID-19 patients with pre-existing psychiatric conditions.

Obsessive Compulsive Disorder With Porn Addiction During The Covid-19 Pandemic, Varuni Pragya, M Kishor Dr.

Digital Journal of Clinical Medicine

BACKGROUND:

COVID-19 Pandemic is an unprecedented humanitarian crisis that has affected the mental health of individuals immensely. OCD was among the mental health conditions that emerged with the new norm that is associated with repeated hand wash, social distancing and testing to confirm COVID-19. Nissen et al. (2020) found that there was a significant positive correlation between total OCD severity scores and the occurrence of OCD aggressive and sexual symptoms. [6] The COVID-19 lockdown translated into physical isolation, driving individuals to waste time online with no definite purpose, spending longer, abnormal durations of time online when bored, leading to increased …

Methodological Characteristics, Physiological And Physical Effects, And Future Directions For Velocity-Based Training In Soccer: A Systematic Review, Jorge Ribeiro, José Afonso, Miguel Camões, Hugo Sarmento, Mário Sá, Ricardo Lima, Filipe Manuel Clemente

Baltic Journal of Health and Physical Activity

Introduction. This systematic review was conducted to (1) characterize the main elements of studies of velocity-based training (VBT) (e.g., training protocols) conducted in soccer, (2) summarize the main physiological and physical effects of VBT on soccer players, and (3) provide future directions for research. Methods: A systematic review of Cochrane Library, EBSCO, PubMed, Scielo, Scopus, SPORTDiscus, and Web of Science databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: The database search initially identified 127 titles. Of those, five articles were deemed eligible for the systematic review, two studies used a traditional …

Persistent Left Superior Vena Cava, Connected To The Left Atrium Via The Left Superior Pulmonary Vein. An Unusual Cause Of Air Lock, Abdelkader Boukhmis, Mohamed El Amin Nouar

Journal of the Saudi Heart Association

The intraoperative diagnosis of a persistent left superior vena cava (LSVC) that drains into the left atrium (LA) via the left superior pulmonary vein may be difficult because of its extrapericardial pathway. We report here the case of a 48-year-old man, operated for a mitro-aortic endocarditis complicating a Laubry-Pezzi syndrome. The opening of the LA was followed immediately by a sudden air lock. It was only after opening of the left pleura that we were able to find and then ligate the LSVC. The patient underwent mitral valve repair, closure of the infundibular septal defect and aortic valve replacement.

Oncocytic Papillary Cystadenoma Of The Larynx: A Rare And Masquerading Entity., Samuel Bosco, James Ding, Christopher Fundakowski

Otolaryngology (ENT) Resident Research

We cared for a 59-year-old female smoker who presented with a supraglottic lesion mimicking a laryngeal saccular cyst. The lesion was found to be a oncocytic papillary cystadenoma. This is a rare, benign neoplasm that accounts for 2–4.7% of minor salivary gland neoplasms. Oncocytic papillary cystadenoma of the larynx is even more rare, compromising less than 1% of all benign laryngeal neoplasms. This case highlights the importance of comprehensive differential diagnosis for cystic laryngeal lesions.

Characterizing Metastatic Uveal Melanoma Patients Who Develop Symptomatic Brain Metastases., Alexander Z Wei, Matan Uriel, Agata Porcu, Michael P Manos, Ann C Mercurio, Michael M Caplan, Liam Hulse, Rino S Seedor, Marta Holovatska, Jasmine Francis, Shaheer A Khan, Diana E Mcdonnell, Dmitry Bogomolny, Takami Sato, Brian P Marr, Rizwan Haq, Marlana Orloff, Alexander Shoushtari, Richard D Carvajal

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma (mUM) is an advanced ocular malignancy characterized by a hepatotropic pattern of spread. As the incidence of brain metastases (BM) in mUM patients has been thought to be low, routine CNS surveillance has not been recommended. Notably, no formal assessment of BM incidence in mUM has to date been published to support this clinical practice. We aimed to determine the true rate of BM in mUM and to clarify the clinical and genomic risk factors associated with BM patients through a collaborative multicenter, retrospective research effort. Data collected from 1,845 mUM patients in databases across four NCI-designated …

Next-Generation Sequencing Supports Targeted Antibiotic Treatment For Culture Negative Orthopedic Infections, Ravina Kullar, Emanuele Chisari, James Snyder, Christopher Cooper, Javad Parvizi, Jason Sniffen

Rothman Institute Papers

The isolation of an infective pathogen can be challenging in some patients with active, clinically apparent infectious diseases. Despite efforts in the microbiology lab to improve the sensitivity of culture in orthopedic implant-associated infections, the clinically relevant information often falls short of expectations. The management of peri-prosthetic joint infections (PJI) provides an excellent example of the use and benefits of newer diagnostic technologies to supplement the often-inadequate yield of traditional culture methods as a substantial percentage of orthopedic infections are culture-negative. Next-generation sequencing (NGS) has the potential to improve upon this yield. Bringing molecular diagnostics into practice can provide critical …

Role Of Sympathetic Pathway In Light-Phase Time-Restricted Feeding-Induced Blood Pressure Circadian Rhythm Alteration, Tianfei Hou, Aaron Chacon, Wen Su, Yuriko Katsumata, Zhenheng Guo, Ming Gong

Sanders-Brown Center on Aging Faculty Publications

Disruption of blood pressure (BP) circadian rhythm, independent of hypertension, is emerging as an index for future target organ damage and is associated with a higher risk of cardiovascular events. Previous studies showed that changing food availability time alters BP rhythm in several mammalian species. However, the underlying mechanisms remain largely unknown. To address this, the current study specifically investigates (1) the relationship between rhythms of food intake and BP in wild-type mice; (2) effects of light-phase time-restricted feeding (TRF, food only available during light-phase) on BP circadian rhythm in wild-type and diabetic db/db mice; (3) the roles of the …

Characterization Of The Plastic Scintillator Detector System Exradin W2 In A High Dose Rate Flattening-Filter-Free Photon Beam, Sara Thrower, Surendra Prajapati, Shannon Holmes, Emil Schüler, Sam Beddar

Faculty, Staff and Student Publications

(1) Background: The Exradin W2 is a commercially available scintillator detector designed for reference and relative dosimetry in small fields. In this work, we investigated the performance of the W2 scintillator in a 10 MV flattening-filter-free photon beam and compared it to the performance of ion chambers designed for small field measurements. (2) Methods: We measured beam profiles and percent depth dose curves with each detector and investigated the linearity of each system based on dose per pulse (DPP) and pulse repetition frequency. (3) Results: We found excellent agreement between the W2 scintillator and the ion chambers for beam profiles …

Turning Nonselective Inhibitors Of Type I Protein Arginine Methyltransferases Into Potent And Selective Inhibitors Of Protein Arginine Methyltransferase 4 Through A Deconstruction-Reconstruction And Fragment-Growing Approach, Giulia Iannelli, Ciro Milite, Nils Marechal, Vincent Cura, Luc Bonnefond, Nathalie Troffer-Charlier, Alessandra Feoli, Donatella Rescigno, Yalong Wang, Alessandra Cipriano, Monica Viviano, Mark T Bedford, Jean Cavarelli, Sabrina Castellano, Gianluca Sbardella

Faculty, Staff and Student Publications

Protein arginine methyltransferases (PRMTs) are important therapeutic targets, playing a crucial role in the regulation of many cellular processes and being linked to many diseases. Yet, there is still much to be understood regarding their functions and the biological pathways in which they are involved, as well as on the structural requirements that could drive the development of selective modulators of PRMT activity. Here we report a deconstruction-reconstruction approach that, starting from a series of type I PRMT inhibitors previously identified by us, allowed for the identification of potent and selective inhibitors of PRMT4, which regardless of the low cell …