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JOURNAL ARTICLE
Zhining Wang, Tanja M Davidsen, Gina R Kuffel, KanakaDurga Addepalli, Amanda Bell, Esmeralda Casas-Silva, Hayley Dingerdissen, Keyvan Farahani, Andrey Fedorov, Sharon Gaheen, Robert L Grossman, Ron Kikinis, Erika Kim, John Otridge, Todd Pihl, Melissa Porter, Henry Rodriguez, Louis M Staudt, Ratna R Thangudu, Sudha Venkatachari, Jean Claude Zenklusen, Xu Zhang, Jill S Barnholtz-Sloan, The Crdc Program, Anthony R Kerlavage
Since 2014, the National Cancer Institute (NCI) has launched a series of data commons as part of the Cancer Research Data Commons (CRDC) ecosystem housing genomic, proteomic, imaging, and clinical data to support cancer research and promote data sharing of NCI-funded studies. This review describes each data commons (Genomic Data Commons, Proteomic Data Commons, Integrated Canine Data Commons, Cancer Data Service, Imaging Data Commons, and Clinical and Translational Data Commons), including their unique and shared features, accomplishments, and challenges...
March 15, 2024: Cancer Research
#2
JOURNAL ARTICLE
Andrea J Radtke, Ekaterina Postovalova, Arina Varlamova, Alexander Bagaev, Maria Sorokina, Olga Kudryashova, Mark Meerson, Margarita Polyakova, Ilia Galkin, Viktor Svekolkin, Sergey Isaev, Daniil Wiebe, Anna Sharun, Alexander Sarachakov, Grigory Perelman, Yaroslav Lozinsky, Ziv Yaniv, Bradley C Lowekamp, Emily Speranza, Li Yao, Stefania Pittaluga, Arthur L Shaffer, Danny Jonigk, James D Phelan, Theresa Davies-Hill, Da Wei Huang, Pavel Ovcharov, Krystle Nomie, Ekaterina Nuzhdina, Nikita Kotlov, Ravshan Ataullakhanov, Nathan Fowler, Michael Kelly, Jagan Muppidi, Jeremy L Davis, Jonathan M Hernandez, Wyndham H Wilson, Elaine S Jaffe, Louis M Staudt, Mark Roschewski, Ronald N Germain
Follicular lymphoma (FL) is a generally incurable malignancy that evolves from developmentally blocked germinal center (GC) B cells. To promote survival and immune escape, tumor B cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment. Dynamic interactions between tumor B cells and the tumor microenvironment (TME) are hypothesized to contribute to the broad spectrum of clinical behaviors observed among FL patients. Despite the urgent need, existing clinical tools do not reliably predict disease behavior...
March 11, 2024: Cancer Cell
#3
JOURNAL ARTICLE
Ryan J Duchatel, Evangeline R Jackson, Sarah G Parackal, Dylan Kiltschewskij, Izac J Findlay, Abdul Mannan, Dilana E Staudt, Bryce C Thomas, Zacary P Germon, Sandra Laternser, Padraic S Kearney, M Fairuz B Jamaluddin, Alicia M Douglas, Tyrone S Beitaki, Holly P McEwen, Mika L Persson, Emily A Hocke, Vaibhav Jain, Michael Aksu, Elizabeth E Manning, Heather C Murray, Nicole M Verrills, Claire Xin Sun, Paul Daniel, Ricardo E Vilain, David A Skerrett-Byrne, Brett Nixon, Susan Hua, Charles E de Bock, Yolanda Colino-Sanguino, Fatima Valdes-Mora, Maria Tsoli, David S Ziegler, Murray J Cairns, Eric H Raabe, Nicholas A Vitanza, Esther Hulleman, Timothy N Phoenix, Carl Koschmann, Frank Alvaro, Christopher V Dayas, Christopher L Tinkle, Helen Wheeler, James R Whittle, David D Eisenstat, Ron Firestein, Sabine Mueller, Santosh Valvi, Jordan R Hansford, David M Ashley, Simon G Gregory, Lindsay B Kilburn, Javad Nazarian, Jason E Cain, Matthew D Dun
Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma - DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR-Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across DIPG patient models, highlighting the therapeutic potential of the blood-brain barrier penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors...
February 6, 2024: Journal of Clinical Investigation
#4
JOURNAL ARTICLE
Markus Staudt, Na Liu, Fanny Malhaire, Yasaman Doroudian, Laurent Prézeau, Emma Renard, Zahra Hasanpour, Jean-Philippe Pin, Lennart Bunch
The metabotropic glutamate (Glu) receptors (mGluRs) are G-protein coupled receptors, which play a central role in modulating excitatory neurotransmission in the central nervous system (CNS). Thus, the development of tool compounds thereto, continues to interest the scientific community. In this study, we report the design and synthesis of new conformationally restricted 2-aminoadipic acid (2AA) 2-4, and glutamic acid 5, 6 analogs, which share the cyclopropane ring as the restrictor. The analogs were characterized at rat mGlu1-8 in an IP-One functional assay...
February 15, 2024: European Journal of Medicinal Chemistry
#5
JOURNAL ARTICLE
James D Phelan, Sebastian Scheich, Jaewoo Choi, George W Wright, Björn Häupl, Ryan M Young, Sara A Rieke, Martine Pape, Yanlong Ji, Henning Urlaub, Arnold Bolomsky, Carmen Doebele, Alena Zindel, Tanja Wotapek, Monica Kasbekar, Brett Collinge, Da Wei Huang, Zana A Coulibaly, Vivian M Morris, Xiaoxuan Zhuang, Julius C Enssle, Xin Yu, Weihong Xu, Yandan Yang, Hong Zhao, Zhuo Wang, Andy D Tran, Christopher J Shoemaker, Galina Shevchenko, Daniel J Hodson, Arthur L Shaffer, Louis M Staudt, Thomas Oellerich
Diffuse large B cell lymphoma (DLBCL) is an aggressive, profoundly heterogeneous cancer, presenting a challenge for precision medicine. Bruton's tyrosine kinase (BTK) inhibitors block B cell receptor (BCR) signaling and are particularly effective in certain molecular subtypes of DLBCL that rely on chronic active BCR signaling to promote oncogenic NF-κB. The MCD genetic subtype, which often acquires mutations in the BCR subunit, CD79B, and in the innate immune adapter, MYD88L265P , typically resists chemotherapy but responds exceptionally to BTK inhibitors...
February 12, 2024: Cancer Cell
#6
JOURNAL ARTICLE
Sandy Hwang Fang, Mihaela Plesa, Evie H Carchman, Nicole A Cowell, Emily Staudt, Kyleigh Ann Twaroski, Ulrike K Buchwald, Cornelia L Trimble
BACKGROUND: Ablation or surgical excision is the typical treatment of anal high-grade squamous intraepithelial lesions (HSIL). Recurrences are common due to the persistence of underlying human papillomavirus (HPV) infection. Additional well-tolerated and effective non-surgical options for HPV-associated anal disease are needed. METHODS: This 3+3 dose escalation Phase I clinical trial evaluated the safety and tolerability of artesunate suppositories in the treatment of patients with biopsy-proven HSIL...
2023: PloS One
#7
JOURNAL ARTICLE
Elif Çakan, Marie Dominique Ah Kioon, Yolanda Garcia-Carmona, Salomé Glauzy, David Oliver, Natsuko Yamakawa, Andrea Vega Loza, Yong Du, Jean-Nicolas Schickel, Joshua M Boeckers, Chao Yang, Alessia Baldo, Lionel B Ivashkiv, Ryan M Young, Louis M Staudt, Krishna L Moody, Kerstin Nündel, Ann Marshak-Rothstein, Caspar I van der Made, Alexander Hoischen, Anthony Hayward, Marzia Rossato, Timothy R D J Radstake, Charlotte Cunningham-Rundles, Changwan Ryu, Erica L Herzog, Franck J Barrat, Eric Meffre
Central B cell tolerance is believed to be regulated by B cell receptor signaling induced by the recognition of self-antigens in immature B cells. Using humanized mice with defective MyD88, TLR7, or TLR9 expression, we demonstrate that TLR9/MYD88 are required for central B cell tolerance and the removal of developing autoreactive clones. We also show that CXCL4, a chemokine involved in systemic sclerosis (SSc), abrogates TLR9 function in B cells by sequestering TLR9 ligands away from the endosomal compartments where this receptor resides...
December 4, 2023: Journal of Experimental Medicine
#8
JOURNAL ARTICLE
Keli Jaqueline Staudt, Bruna Bernar Dias, Izabel Almeida Alves, Bénédicte Lelièvre, Jean-Philippe Bouchara, Bibiana Verlindo de Araújo
Voriconazole is a triazole antifungal used empirically for the treatment of complicated meningitis associated with Cryptococcus neoformans . Biopsy studies show that the drug exhibits adequate brain penetration although levels of cerebral spinal fluid (CSF) are highly variable. Considering that CSF is one of the main surrogates for CNS exposure, the present work proposed the building of a population pharmacokinetic modeling (popPK) model able to describing the exposure achieved by voriconazole in the plasma, interstitial cerebral fluid and CSF of healthy and infected rats...
June 21, 2023: Pharmaceutics
#9
JOURNAL ARTICLE
Jerry R Mendell, Perry B Shieh, Craig M McDonald, Zarife Sahenk, Kelly J Lehman, Linda P Lowes, Natalie F Reash, Megan A Iammarino, Lindsay N Alfano, Brenna Sabo, Jeremy D Woods, Christy L Skura, Howard C Mao, Loretta A Staudt, Danielle A Griffin, Sarah Lewis, Shufang Wang, Rachael A Potter, Teji Singh, Louise R Rodino-Klapac
Introduction: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy designed for targeted expression of SRP-9001 dystrophin protein, a shortened dystrophin retaining key functional domains of the wild-type protein. Methods: This Phase 2, double-blind, two-part (48 weeks per part) crossover study (SRP-9001-102 [Study 102]; NCT03769116) evaluated delandistrogene moxeparvovec in patients, aged ≥4 to <8 years with Duchenne muscular dystrophy. Primary endpoints (Part 1) were change from baseline (CFBL) in SRP-9001 dystrophin expression (Week 12), by Western blot, and in North Star Ambulatory Assessment (NSAA) score (Week 48)...
2023: Frontiers in Cell and Developmental Biology
#10
Andrew Waack, Maximilian Fliegner, Daniel L Menkes, Michael D Staudt
Anterior cord syndrome (ACS) occurs as a result of ischemia in the territory of the anterior spinal artery (ASA). Although spinal cord strokes are rare, the ASA is the most commonly affected vessel in the spinal cord. The typical presentation of an ASA stroke is paraparesis or paraplegia, bilateral loss of pain and temperature sensation, and fecal or urinary incontinence; the underlying neural structures responsible for these symptoms include the corticospinal tracts and anterior horns, anterolateral spinothalamic tracts, and lateral horns, respectively...
June 2023: Curēus
#11
JOURNAL ARTICLE
Nina Gande, Christoph Hochmayr, Anna Staudt, Benoît Bernar, Katharina Stock, Sophia J Kiechl, Ralf Geiger, Andrea Griesmacher, Sabine Scholl-Bürgi, Michael Knoflach, Raimund Pechlaner, Ursula Kiechl-Kohlendorfer
BACKGROUND: Homocysteine (Hcy) has been associated with an adverse cardiovascular risk profile in adolescents. Assessment of the association between plasma Hcy levels and clinical/laboratory factors might improve our understanding of the pathogenesis of cardiovascular disease. METHODS: Hcy was measured in 1,900 14- to 19-year-old participants of prospective population-based EVA-TYROL Study (44.3% males, mean age 16.4 years) between 2015 and 2018. Factors associated with Hcy were assessed by physical examination, standardized interviews, and fasting blood analysis...
2023: Frontiers in Cardiovascular Medicine
#12
JOURNAL ARTICLE
Joseph A Flores-Toro, Subhashini Jagu, Gregory T Armstrong, David F Arons, Gregory J Aune, Stephen J Chanock, Douglas S Hawkins, Allison Heath, Lee J Helman, Katherine A Janeway, Jason E Levine, Ellyn Miller, Lynne Penberthy, Charles W M Roberts, Eve R Shalley, Jack F Shern, Malcolm A Smith, Louis M Staudt, Samuel L Volchenboum, Jinghui Zhang, Jean Claude Zenklusen, Douglas R Lowy, Norman E Sharpless, Jaime M Guidry Auvil, Anthony R Kerlavage, Brigitte C Widemann, Gregory H Reaman, Warren A Kibbe, James H Doroshow
Data-driven basic, translational, and clinical research has resulted in improved outcomes for children, adolescents, and young adults (AYAs) with pediatric cancers. However, challenges in sharing data between institutions, particularly in research, prevent addressing substantial unmet needs in children and AYA patients diagnosed with certain pediatric cancers. Systematically collecting and sharing data from every child and AYA can enable greater understanding of pediatric cancers, improve survivorship, and accelerate development of new and more effective therapies...
August 20, 2023: Journal of Clinical Oncology
#13
Pallavi S Utukuri, Robert Y Shih, Amna A Ajam, Kathryn E Callahan, Doris Chen, Jeffrey W Dunkle, Christopher H Hunt, Jana Ivanidze, Luke N Ledbetter, Ryan K Lee, Omojo Malu, Jeffrey S Pannell, Jeffrey M Pollock, Sonja X Potrebic, Michael Setzen, Richard D Shih, Bruno P Soares, Michael D Staudt, Lily L Wang, Judah Burns
Headache is an ancient problem plaguing a large proportion of the population. At present, headache disorders rank third among the global causes of disability, accounting for over $78 billion per year in direct and indirect costs in the United States. Given the prevalence of headache and the wide range of possible etiologies, the goal of this document is to help clarify the most appropriate initial imaging guidelines for headache for eight clinical scenarios/variants, which range from acute onset, life-threatening etiologies to chronic benign scenarios...
May 2023: Journal of the American College of Radiology: JACR
#14
JOURNAL ARTICLE
Evangeline R Jackson, Ryan J Duchatel, Dilana E Staudt, Mika L Persson, Abdul Mannan, Sridevi Yadavilli, Sarah Parackal, Shaye Game, Wai Chin Chong, W Samantha N Jayasekara, Marion Le Grand, Padraic S Kearney, Alicia M Douglas, Izac J Findlay, Zacary P Germon, Holly P McEwen, Tyrone S Beitaki, Adjanie Patabendige, David A Skerrett-Byrne, Brett Nixon, Nathan D Smith, Bryan Day, Neevika Manoharan, Sumanth Nagabushan, Jordan R Hansford, Dinisha Govender, Geoff B McCowage, Ron Firestein, Meegan Howlett, Raelene Endersby, Nicholas G Gottardo, Frank Alvaro, Sebastian M Waszak, Martin R Larsen, Yolanda Colino-Sanguino, Fatima Valdes-Mora, Andria Rakotomalala, Samuel Meignan, Eddy Pasquier, Nicolas André, Esther Hulleman, David D Eisenstat, Nicholas A Vitanza, Javad Nazarian, Carl Koschmann, Sabine Mueller, Jason E Cain, Matthew D Dun
UNLABELLED: Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9 to 11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response...
May 17, 2023: Cancer Research
#15
JOURNAL ARTICLE
Evangeline R Jackson, Ryan J Duchatel, Dilana E Staudt, Mika L Persson, Abdul Mannan, Sridevi Yadavilli, Sarah Parackal, Shaye Game, Wai Chin Chong, W Samantha Nilanthi Jayasekara, Marion Le Grand, Padraic S Kearney, Alicia M Douglas, Izac J Findlay, Zacary P Germon, Holly P McEwen, Tyrone S Beitaki, Adjanie Patabendige, David A Skerrett-Byrne, Brett Nixon, Nathan D Smith, Bryan Day, Neevika Manoharan, Sumanth Nagabushan, Jordan R Hansford, Dinisha Govender, Geoffrey B McCowage, Ron Firestein, Meegan Howlett, Raelene Endersby, Nicholas G Gottardo, Frank Alvaro, Sebastian M Waszak, Martin R Larsen, Yolanda Colino-Sanguino, Fatima Valdés-Mora, Andria Rakotomalala, Samuel Meignan, Eddy Pasquier, Nicolas Andre, Esther Hulleman, David D Eisenstat, Nicholas A Vitanza, Javad Nazarian, Carl Koschmann, Sabine Mueller, Jason E Cain, Matthew D Dun
Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response...
May 5, 2023: Cancer Research
#16
JOURNAL ARTICLE
A Vuong, S H Joshi, L A Staudt, J H Matsumoto, E G Fowler
BACKGROUND AND PURPOSE: Children with spastic cerebral palsy have motor deficits associated with periventricular leukomalacia indicating WM damage to the corticospinal tracts. We investigated whether practice of skilled lower extremity selective motor control movements would elicit neuroplasticity. MATERIALS AND METHODS: Twelve children with spastic bilateral cerebral palsy and periventricular leukomalacia born preterm (mean age, 11.5 years; age range, 7...
May 4, 2023: AJNR. American Journal of Neuroradiology
#17
JOURNAL ARTICLE
Matthew B Barajas, Matthias L Riess, Matthew J W Hampton, Zhu Li, Yaping Shi, Matthew S Shotwell, Genevieve Staudt, Franz J Baudenbacher, Ryan J Lefevre, Susan S Eagle
BACKGROUND: Early detection and quantification of perioperative hemorrhage remains challenging. Peripheral intravenous waveform analysis (PIVA) is a novel method that uses a standard intravenous catheter to detect interval hemorrhage. We hypothesize that subclinical blood loss of 2% of the estimated blood volume (EBV) in a rat model of hemorrhage is associated with significant changes in PIVA. Secondarily, we will compare PIVA association with volume loss to other static, invasive, and dynamic markers...
May 1, 2023: Anesthesia and Analgesia
#18
JOURNAL ARTICLE
Nicole Thomas, Kostiantyn Dreval, Daniela S Gerhard, Laura K Hilton, Jeremy S Abramson, Richard F Ambinder, Stefan Barta, Nancy L Bartlett, Jeffrey Bethony, Kishor Bhatia, Jay Bowen, Anthony C Bryan, Ethel Cesarman, Corey Casper, Amy Chadburn, Manuela Cruz, Dirk P Dittmer, Maureen A Dyer, Pedro Farinha, Julie M Gastier-Foster, Alina S Gerrie, Bruno M Grande, Timothy Greiner, Nicholas B Griner, Thomas G Gross, Nancy L Harris, John D Irvin, Elaine S Jaffe, David Henry, Rebecca Huppi, Fabio E Leal, Michael S Lee, Jean Paul Martin, Marie-Reine Martin, Sam M Mbulaiteye, Ronald Mitsuyasu, Vivian Morris, Charles G Mullighan, Andrew J Mungall, Karen Mungall, Innocent Mutyaba, Mostafa Nokta, Constance Namirembe, Ariela Noy, Martin D Ogwang, Abraham Omoding, Jackson Orem, German Ott, Hilary Petrello, Stefania Pittaluga, James D Phelan, Juan Carlos Ramos, Lee Ratner, Steven J Reynolds, Paul G Rubinstein, Gerhard Sissolak, Graham Slack, Shaghayegh Soudi, Steven H Swerdlow, Alexandra Traverse-Glehen, Wyndham H Wilson, Jasper Wong, Robert Yarchoan, Jean C ZenKlusen, Marco A Marra, Louis M Staudt, David W Scott, Ryan D Morin
Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL...
February 23, 2023: Blood
#19
JOURNAL ARTICLE
Tabitha Mclachlan, William C Matthews, Evangeline R Jackson, Dilana Staudt, Alicia M Douglas, Izac J Findlay, Mika L Persson, Ryan J Duchatel, Abdul Mannan, Zacary P Germon, Matthew D Dun
B-cell lymphoma 6 (BCL6) is a protooncogene in adult and pediatric cancers; first identified in diffuse large B-cell lymphoma (DLBCL) where it acts as a repressor of the tumor suppressor TP53, conferring survival, protection, and maintenance of lymphoma cells. BCL6 expression in normal B cells is fundamental in the regulation of humoral immunity, via initiation and maintenance of the germinal centers (GCs). Its role in B cells during the production of high affinity immunoglobins (that recognize and bind specific antigens) is believed to underpin its function as an oncogene...
September 27, 2022: Molecular Cancer Research: MCR
#20
JOURNAL ARTICLE
Shelia C Savell, Jeff T Howard, Christopher A VanFosson, Kimberly L Medellín, Amanda M Staudt, Julie A Rizzo, Joseph K Maddry, Leopoldo C Cancio
INTRODUCTION: The US Army Burn Center, the only burn center in the Department of Defense provides comprehensive burn care. The Burn Flight Team (BFT) provides specialized burn care during transcontinental evacuation. During Operations Iraqi and Enduring Freedom, burn injuries accounted for approximately 5% of all injuries in military personnel. To augment BFT capacity, US Air Force Critical Care Air Transport Teams (CCATTs) mobilized to transport burn patients. The purpose of this study was to describe critically ill, burn injured patients transported to the US Army Burn Center by BFT or CCATT, to compare and contrast characteristics, evacuation procedures, in-flight treatments, patient injuries/illnesses, and outcomes between the two groups...
September 27, 2022: Military Medicine
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