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JOURNAL ARTICLE
Yong Yean Kim, Berkley E Gryder, Ranuka Sinniah, Megan L Peach, Jack F Shern, Abdalla Abdelmaksoud, Silvia Pomella, Girma M Woldemichael, Benjamin Z Stanton, David Milewski, Joseph J Barchi, John S Schneekloth, Raj Chari, Joshua T Kowalczyk, Shilpa R Shenoy, Jason R Evans, Young K Song, Chaoyu Wang, Xinyu Wen, Hsien-Chao Chou, Vineela Gangalapudi, Dominic Esposito, Jane Jones, Lauren Procter, Maura O'Neill, Lisa M Jenkins, Nadya I Tarasova, Jun S Wei, James B McMahon, Barry R O'Keefe, Robert G Hawley, Javed Khan
Fusion-positive rhabdomyosarcoma (FP-RMS) is an aggressive pediatric sarcoma driven primarily by the PAX3-FOXO1 fusion oncogene, for which therapies targeting PAX3-FOXO1 are lacking. Here, we screen 62,643 compounds using an engineered cell line that monitors PAX3-FOXO1 transcriptional activity identifying a hitherto uncharacterized compound, P3FI-63. RNA-seq, ATAC-seq, and docking analyses implicate histone lysine demethylases (KDMs) as its targets. Enzymatic assays confirm the inhibition of multiple KDMs with the highest selectivity for KDM3B...
February 24, 2024: Nature Communications
#2
JOURNAL ARTICLE
Silvia Pomella, Matteo Cassandri, Lucrezia D'Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R Vakoc, Enrico Velardi, Beat W Schafer, Ernesto Guccione, Susanne A Gatz, Ajla Wasti, Marielle Yohe, Myron Ignatius, Concetta Quintarelli, Janet Shipley, Lucio Miele, Javed Khan, Peter J Houghton, Francesco Marampon, Berkley E Gryder, Biagio De Angelis, Franco Locatelli, Rossella Rota
Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer...
December 15, 2023: Nature Communications
#3
JOURNAL ARTICLE
Michał Tomczyk
No abstract text is available yet for this article.
December 2023: Journal of Enzyme Inhibition and Medicinal Chemistry
#4
JOURNAL ARTICLE
Hubert Wojtasek
No abstract text is available yet for this article.
December 2023: Journal of Enzyme Inhibition and Medicinal Chemistry
#5
JOURNAL ARTICLE
Crystal A Perkins, Ryan P Coene, Patricia E Miller, Chris N Anderson, Kianna D Nunally, Shital N Parikh, Michael T Busch, Henry G Chambers, Melissa A Christino, Frank A Cordasco, Eric W Edmonds, Peter D Fabricant, Theodore J Ganley, Daniel W Green, Benton E Heyworth, John Todd R Lawrence, Matthew J Matava, Lyle J Micheli, Matthew D Milewski, Jeffrey Nepple, Andrew T Pennock, Paul M Saluan, Kevin G Shea, Eric J Wall, Samuel C Willimon, Mininder S Kocher
BACKGROUND: Radiographic measurements of limb alignment in skeletally immature patients with anterior cruciate ligament (ACL) tears are frequently used for surgical decision-making, preoperative planning, and postoperative monitoring of skeletal growth. However, the interrater and intrarater reliability of these radiographic characteristics in this patient population is not well documented. HYPOTHESIS: Excellent reliability across 4 raters will be demonstrated for all digital measures of length, coronal plane joint orientation angles, mechanical axis, and tibial slope in skeletally immature patients with ACL tears...
October 1, 2023: Journal of Pediatric Orthopedics
#6
JOURNAL ARTICLE
Matthew D Milewski, Jessica L Traver, Ryan P Coene, Kathryn Williams, Dai Sugimoto, Dennis E Kramer, Mininder S Kocher, Lyle J Micheli, Yi-Meng Yen, Melissa A Christino
BACKGROUND: Successful return to sport after anterior cruciate ligament (ACL) reconstruction (ACLR) can be affected by a patient's physical and psychological state throughout the rehabilitation process. PURPOSE: To prospectively compare differences in patients at 6 months after primary ACLR with the ACL-Return to Sport after Injury (ACL-RSI), International Knee Documentation Committee (IKDC) or pediatric (Pedi)-IKDC, Hospital for Special Surgery Pediatric Functional Activity Brief Scale (Pedi-FABS), and Patient-Reported Outcomes Measurement Information System-Psychological Stress Experiences (PROMIS-PSE) scores...
June 2023: Orthopaedic Journal of Sports Medicine
#7
JOURNAL ARTICLE
Fenghua Bian, Ying-Wei Lan, Shuyang Zhao, Zicheng Deng, Samriddhi Shukla, Anusha Acharya, Johnny Donovan, Tien Le, David Milewski, Matthew Bacchetta, Ahmed Emad Hozain, Yuliya Tipograf, Ya-Wen Chen, Yan Xu, Donglu Shi, Vladimir V Kalinichenko, Tanya V Kalin
Pulmonary fibrosis results from dysregulated lung repair and involves multiple cell types. The role of endothelial cells (EC) in lung fibrosis is poorly understood. Using single cell RNA-sequencing we identified endothelial transcription factors involved in lung fibrogenesis, including FOXF1, SMAD6, ETV6 and LEF1. Focusing on FOXF1, we found that FOXF1 is decreased in EC within human idiopathic pulmonary fibrosis (IPF) and mouse bleomycin-injured lungs. Endothelial-specific Foxf1 inhibition in mice increased collagen depositions, promoted lung inflammation, and impaired R-Ras signaling...
May 4, 2023: Nature Communications
#8
MULTICENTER STUDY
Ankeet S Bhatt, Anubodh S Varshney, Alea Moscone, Brian L Claggett, Zi Michael Miao, Safia Chatur, Mathew S Lopes, John W Ostrominski, Maria A Pabon, Ozan Unlu, Xiaowen Wang, Thomas D Bernier, Leo F Buckley, Bryan Cook, Rachael Eaton, Jillian Fiene, Dareen Kanaan, Julie Kelly, Danielle M Knowles, Kenneth Lupi, Lina S Matta, Liriany Y Pimentel, Megan N Rhoten, Rhynn Malloy, Clara Ting, Rosette Chhor, Joshua R Guerin, Scott L Schissel, Brenda Hoa, Connie H Lio, Kristina Milewski, Michelle E Espinosa, Zhenzhen Liu, Ralph McHatton, Jonathan W Cunningham, Karola S Jering, John H Bertot, Gurleen Kaur, Adeel Ahmad, Muhammad Akash, Farideh Davoudi, Mona Z Hinrichsen, David L Rabin, Patrick L Gordan, David J Roberts, Daniela Urma, Erin E McElrath, Emily D Hinchey, Niteesh K Choudhry, Mahan Nekoui, Scott D Solomon, Dale S Adler, Muthiah Vaduganathan
BACKGROUND: Scalable and safe approaches for heart failure guideline-directed medical therapy (GDMT) optimization are needed. OBJECTIVES: The authors assessed the safety and effectiveness of a virtual care team guided strategy on GDMT optimization in hospitalized patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In a multicenter implementation trial, we allocated 252 hospital encounters in patients with left ventricular ejection fraction ≤40% to a virtual care team guided strategy (107 encounters among 83 patients) or usual care (145 encounters among 115 patients) across 3 centers in an integrated health system...
May 2, 2023: Journal of the American College of Cardiology
#9
JOURNAL ARTICLE
Harry M Williams, Sigurdur R Thorkelsson, Dominik Vogel, Morlin Milewski, Carola Busch, Stephen Cusack, Kay Grünewald, Emmanuelle R J Quemin, Maria Rosenthal
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.6 Å...
January 18, 2023: Nucleic Acids Research
#10
JOURNAL ARTICLE
David Milewski, Hyun Jung, G Thomas Brown, Yanling Liu, Ben Somerville, Curtis Lisle, Marc Ladanyi, Erin R Rudzinski, Hyoyoung Choo-Wosoba, Donald A Barkauskas, Tammy Lo, David Hall, Corinne M Linardic, Jun S Wei, Hsien-Chao Chou, Stephen X Skapek, Rajkumar Venkatramani, Peter K Bode, Seth M Steinberg, George Zaki, Igor B Kuznetsov, Douglas S Hawkins, Jack F Shern, Jack Collins, Javed Khan
PURPOSE: Rhabdomyosarcoma (RMS) is an aggressive soft-tissue sarcoma, which primarily occurs in children and young adults. We previously reported specific genomic alterations in RMS, which strongly correlated with survival; however, predicting these mutations or high-risk disease at diagnosis remains a significant challenge. In this study, we utilized convolutional neural networks (CNN) to learn histologic features associated with driver mutations and outcome using hematoxylin and eosin (H&E) images of RMS...
January 17, 2023: Clinical Cancer Research
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MULTICENTER STUDY
Rafał Wolny, Ilona Kowalik, Rafał Januszek, Jacek Bil, Tomasz Figatowski, Marek Milewski, Brunon Tomasiewicz, Tomasz Walczak, Bruno Hrymniak, Piotr Desperak, Piotr Niezgoda, Magdalena Chudzik, Łukasz Kuźma, Paweł Kralisz, Fabrizio D'Ascenzo, Damian Hudziak, Miłosz Jaguszewski, Krzysztof Reczuch, Jacek Kubica, Robert J Gil, Sławomir Dobrzycki, Stanisław Bartuś, Mariusz Gąsior, Andrzej Ochała, Adam Witkowski, Wojciech Wojakowski, Wojciech Wańha
BACKGROUND: There is limited data on the optimal revascularization strategy in patients with recurrent in-stent restenosis (R-ISR). AIMS: To compare the long-term outcomes of patients treated with either a thin-strut drug-eluting stent (thin-DES) or a drug-eluting balloon (DEB) for R-ISR in a drug-eluting stent (DES). METHODS: A multicenter DEB-DRAGON registry was used to retrospectively identify patients with R-ISR who received either a thin-DES or a DEB...
2022: Kardiologia Polska
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JOURNAL ARTICLE
Andrew R Milewski, Kevin S Ackerman, Tara C Pilato, Pooja D Shah, Thomas P Kalman
Medical school asylum clinics are complex organizations that blend medical and legal expertise with service to assist individuals seeking refuge from human rights violations. The balance of power shared by the students and faculty who lead these clinics varies widely across institutions, usually in an inverse reciprocal relationship. The Weill Cornell Center for Human Rights will observe its 10th anniversary in 2020 and is notable for espousing maximal student autonomy in the organization's governance with minimal faculty control or administration participation...
July 2021: Journal of Human Rights Practice
#13
JOURNAL ARTICLE
Tomas Kouba, Dominik Vogel, Sigurdur R Thorkelsson, Emmanuelle R J Quemin, Harry M Williams, Morlin Milewski, Carola Busch, Stephan Günther, Kay Grünewald, Maria Rosenthal, Stephen Cusack
Lassa virus is endemic in West Africa and can cause severe hemorrhagic fever. The viral L protein transcribes and replicates the RNA genome via its RNA-dependent RNA polymerase activity. Here, we present nine cryo-EM structures of the L protein in the apo-, promoter-bound pre-initiation and active RNA synthesis states. We characterize distinct binding pockets for the conserved 3' and 5' promoter RNAs and show how full-promoter binding induces a distinct pre-initiation conformation. In the apo- and early elongation states, the endonuclease is inhibited by two distinct L protein peptides, whereas in the pre-initiation state it is uninhibited...
December 2, 2021: Nature Communications
#14
JOURNAL ARTICLE
Andrew S Brohl, Sivasish Sindiri, Jun S Wei, David Milewski, Hsien-Chao Chou, Young K Song, Xinyu Wen, Jeetendra Kumar, Hue V Reardon, Uma S Mudunuri, Jack R Collins, Sushma Nagaraj, Vineela Gangalapudi, Manoj Tyagi, Yuelin J Zhu, Katherine E Masih, Marielle E Yohe, Jack F Shern, Yue Qi, Udayan Guha, Daniel Catchpoole, Rimas J Orentas, Igor B Kuznetsov, Nicolas J Llosa, John A Ligon, Brian K Turpin, Daniel G Leino, Shintaro Iwata, Irene L Andrulis, Jay S Wunder, Silvia R C Toledo, Paul S Meltzer, Ching Lau, Beverly A Teicher, Heather Magnan, Marc Ladanyi, Javed Khan
We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients...
November 23, 2021: Cell Reports
#15
JOURNAL ARTICLE
Mihir S Dekhne, Isabelle D Kocher, Zaamin B Hussain, Aliya G Feroe, Saritha Sankarankutty, Kathryn A Williams, Benton E Heyworth, Matthew D Milewski, Mininder S Kocher
BACKGROUND: Anterior cruciate ligament (ACL) injuries demand individualized treatments based on an accurate estimation of the child's skeletal age. Wrist radiographs, which have traditionally been used to determine skeletal age, have a number of limitations, including cost, radiation exposure, and inconvenience. PURPOSE: To evaluate the reliability and validity of a radiographic staging system using tibial apophyseal landmarks as hypothetical proxies for skeletal age to use in the preoperative management of pediatric ACL tears...
September 2021: Orthopaedic Journal of Sports Medicine
#16
JOURNAL ARTICLE
Barbara Jankowiak, Beata Kowalewska, Elżbieta Krajewska-Kułak, Rafał Milewski, Maria Anna Turosz
INTRODUCTION: Psoriasis is a chronic disease with intermittent flares and remissions. Each individual perceives the disease, its somatic effects, resultant dysfunction and related problems differently. This attitude is primarily determined by one's characterological traits and type of illness. A primary response to the diagnosis can be denial, underestimation, acceptance or overestimation of the disease. The aim of the study was to analyze the level of illness acceptance and its effect on the quality of life in moderate psoriasis depending on sociodemographic and clinical characteristics of the patients...
2021: Clinical, Cosmetic and Investigational Dermatology
#17
JOURNAL ARTICLE
Briana Lui, Roniel Weinberg, Andrew R Milewski, Xiaoyue Ma, Maria A Bustillo, Patricia F Mack, Robert S White
OBJECTIVES: Opioid use disorder (OUD) has previously been shown to negatively impact postoperative outcomes. As the number of spine surgeries continues to rise annually, more patients with preexisting OUD will be seen in operating rooms. Our retrospective cohort study aims to expand on the independent association between preoperative OUD and outcomes following lumbar-spine surgery. PATIENTS AND METHODS: Using 2007-2014 data from the State Inpatient Databases (SID) for the states of California (2007-2011), Florida, New York, Maryland, and Kentucky, we identified patients ≥18 years of age undergoing lumbar-spine surgery...
September 2021: Clinical Neurology and Neurosurgery
#18
JOURNAL ARTICLE
Yasmine Gomaa, Chandana Kolluru, Mikolaj Milewski, Dinah Lee, Jingtao Zhang, Robert Saklatvala, Mark R Prausnitz
Oxytocin is a nonapeptide hormone used in labor to initiate uterine contractions and to prevent and treat postpartum hemorrhage. Oxytocin is currently administered by injection and requires refrigerated transport and storage, which limits access, especially during home birth in developing countries. Here, we propose a thermostable, simple-to-administer microneedle (MN) patch for rapid delivery of oxytocin suitable for use by healthcare workers with limited training, like traditional birth attendants. Oxytocin (10 IU, 16...
September 10, 2021: Journal of Controlled Release
#19
JOURNAL ARTICLE
Matthew S Fury, Nikolaos K Paschos, Peter D Fabricant, Christian N Anderson, Michael T Busch, Henry G Chambers, Melissa A Christino, Frank A Cordasco, Eric W Edmonds, Theodore J Ganley, Daniel W Green, Benton E Heyworth, J Todd R Lawrence, Matthew J Matava, Lyle J Micheli, Matthew D Milewski, Jeffrey J Nepple, Shital N Parikh, Andrew T Pennock, Crystal A Perkins, Paul M Saluan, Kevin G Shea, Eric J Wall, Samuel C Willimon, Mininder S Kocher
BACKGROUND: Growth disturbance is an uncommon but potentially serious complication after anterior cruciate ligament (ACL) reconstruction in skeletally immature patients. PURPOSE: To describe how the pediatric ACL literature has assessed preoperative skeletal maturity and the amount of growth remaining and to comprehensively review the incidence, reporting, and monitoring of postoperative growth disturbance. STUDY DESIGN: Systematic review; Level of evidence, 4...
April 2022: American Journal of Sports Medicine
#20
JOURNAL ARTICLE
R J Keogh, M Milewski, K Browne, K Egan, M A Hennessy, Z Coyne, D Cowzer, A Linehan, B T Hennessy, L Grogan, P G Morris, O S Breathnach
PURPOSE: This study aimed to provide a better understanding of the impact of paclitaxel chemotherapy on breath alcohol in an Irish population. METHODS: Patients attending the Oncology Day Unit at Beaumont Hospital were invited to participate on the day of their treatment. The brand of paclitaxel used was Actavis Pharma Inc and contained 6 mg/mL paclitaxel in 50% Ethanol/ 50% Cremophor EL. Breath alcohol concentration was measured using the AlcoSense ™ Breathalyser on three separate visits...
August 2021: Cancer Chemotherapy and Pharmacology
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