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David Raleigh

Jason R Pitarresi, Xin Liu, Alex Avendano, Katie A Thies, Gina M Sizemore, Anisha M Hammer, Blake E Hildreth, David J Wang, Sarah A Steck, Sydney Donohue, Maria C Cuitiño, Raleigh D Kladney, Thomas A Mace, Jonathan J Chang, Christina S Ennis, Huiqing Li, Roger H Reeves, Seth Blackshaw, Jianying Zhang, Lianbo Yu, Soledad A Fernandez, Wendy L Frankel, Mark Bloomston, Thomas J Rosol, Gregory B Lesinski, Stephen F Konieczny, Denis C Guttridge, Anil K Rustgi, Gustavo Leone, Jonathan W Song, Jinghai Wu, Michael C Ostrowski
The contribution of the tumor microenvironment to pancreatic ductal adenocarcinoma (PDAC) development is currently unclear. We therefore examined the consequences of disrupting paracrine Hedgehog (HH) signaling in PDAC stroma. Herein, we show that ablation of the key HH signaling gene Smoothened ( Smo ) in stromal fibroblasts led to increased proliferation of pancreatic tumor cells. Furthermore, Smo deletion resulted in proteasomal degradation of the tumor suppressor PTEN and activation of oncogenic protein kinase B (AKT) in fibroblasts...
October 2018: Life science alliance
David R Raleigh, Navdar Sever, Pervinder K Choksi, Monika Abedin Sigg, Kelly M Hines, Bonne M Thompson, Daniel Elnatan, Priyadarshini Jaishankar, Paola Bisignano, Francesc R Garcia-Gonzalo, Alexis Leigh Krup, Markus Eberl, Eamon F X Byrne, Christian Siebold, Sunny Y Wong, Adam R Renslo, Michael Grabe, Jeffrey G McDonald, Libin Xu, Philip A Beachy, Jeremy F Reiter
Primary cilia are required for Smoothened to transduce vertebrate Hedgehog signals, but how Smoothened accumulates in cilia and is activated is incompletely understood. Here, we identify cilia-associated oxysterols that promote Smoothened accumulation in cilia and activate the Hedgehog pathway. Our data reveal that cilia-associated oxysterols bind to two distinct Smoothened domains to modulate Smoothened accumulation in cilia and tune the intensity of Hedgehog pathway activation. We find that the oxysterol synthase HSD11β2 participates in the production of Smoothened-activating oxysterols and promotes Hedgehog pathway activity...
October 18, 2018: Molecular Cell
Efstathios D Gennatas, Ashley Wu, Steve E Braunstein, Olivier Morin, William C Chen, Stephen T Magill, Chetna Gopinath, Javier E Villaneueva-Meyer, Arie Perry, Michael W McDermott, Timothy D Solberg, Gilmer Valdes, David R Raleigh
BACKGROUND: Meningiomas are stratified according to tumor grade and extent of resection, often in isolation of other clinical variables. Here, we use machine learning (ML) to integrate demographic, clinical, radiographic and pathologic data to develop predictive models for meningioma outcomes. METHODS AND FINDINGS: We developed a comprehensive database containing information from 235 patients who underwent surgery for 257 meningiomas at a single institution from 1990 to 2015...
2018: PloS One
Jared H Hara, Ashley Wu, Javier E Villanueva-Meyer, Gilmer Valdes, Vikas Daggubati, Sabine Mueller, Timothy D Solberg, Steve E Braunstein, Olivier Morin, David R Raleigh
PURPOSE: To investigate the prognostic utility of quantitative 3-dimensional magnetic resonance imaging radiomic analysis for primary pediatric embryonal brain tumors. METHODS AND MATERIALS: Thirty-four pediatric patients with embryonal brain tumor with concurrent preoperative T1-weighted postcontrast (T1PG) and T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance images were identified from an institutional database. The median follow-up period was 5...
November 15, 2018: International Journal of Radiation Oncology, Biology, Physics
Yan Zhou, Huaping Sun, Alex Macario, Mark T Keegan, Andrew J Patterson, Mohammed M Minhaj, Ting Wang, Ann E Harman, David O Warner
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: In 2000, the American Board of Anesthesiology (Raleigh, North Carolina) began issuing time-limited certificates requiring renewal every 10 yr through a maintenance of certification program. This study investigated the association between performance in this program and disciplinary actions against medical licenses. METHODS: The incidence of postcertification prejudicial license actions was compared (1) between anesthesiologists certified between 1994 and 1999 (non-time-limited certificates not requiring maintenance of certification) and those certified between 2000 and 2005 (time-limited certificates requiring maintenance of certification); (2) within the non-time-limited cohort, between those who did and did not voluntarily participate in maintenance of certification; and (3) within the time-limited cohort, between those who did and did not complete maintenance of certification requirements within 10 yr...
July 2, 2018: Anesthesiology
Z Paul Lorenc, Lawrence M Bass, Rebecca Fitzgerald, David J Goldberg, Miles H Graivier
Paradigms in the treatment of aging have evolved to address volume loss as a central and primary hallmark of the aging face. The concept of "composite volumization" was recently proposed by Dr. Z. Paul Lorenc to describe the effect of Radiesse (Merz Aesthetics, Inc., Raleigh, NC), when placed on bone in the supraperiosteal plane, on all overlying tissues (skin, superficial and deep fat compartments, and muscle). The physiochemical properties of Radiesse make it especially well suited for efficient and effective volumization of areas especially prone to volume loss; the temple, zygomatic arch, anterior cheek, pyriform aperture, and prejowl sulcus...
April 6, 2018: Aesthetic Surgery Journal
Timo M Deist, Frank J W M Dankers, Gilmer Valdes, Robin Wijsman, I-Chow Hsu, Cary Oberije, Tim Lustberg, Johan van Soest, Frank Hoebers, Arthur Jochems, Issam El Naqa, Leonard Wee, Olivier Morin, David R Raleigh, Wouter Bots, Johannes H Kaanders, José Belderbos, Margriet Kwint, Timothy Solberg, René Monshouwer, Johan Bussink, Andre Dekker, Philippe Lambin
PURPOSE: Machine learning classification algorithms (classifiers) for prediction of treatment response are becoming more popular in radiotherapy literature. General Machine learning literature provides evidence in favor of some classifier families (random forest, support vector machine, gradient boosting) in terms of classification performance. The purpose of this study is to compare such classifiers specifically for (chemo)radiotherapy datasets and to estimate their average discriminative performance for radiation treatment outcome prediction...
July 2018: Medical Physics
Stephen T Magill, David S Lee, Adam J Yen, Calixto-Hope G Lucas, David R Raleigh, Manish K Aghi, Philip V Theodosopoulos, Michael W McDermott
OBJECTIVE Skull base meningiomas are surgically challenging tumors due to the intricate skull base anatomy and the proximity of cranial nerves and critical cerebral vasculature. Many studies have reported outcomes after primary resection of skull base meningiomas; however, little is known about outcomes after reoperation for recurrent skull base meningiomas. Since reoperation is one treatment option for patients with recurrent meningioma, the authors sought to define the risk profile for reoperation of skull base meningiomas...
May 4, 2018: Journal of Neurosurgery
Cassie N Kline, Roger J Packer, Eugene I Hwang, David R Raleigh, Steve Braunstein, Corey Raffel, Pratiti Bandopadhayay, David A Solomon, Mariam Aboian, Soonmee Cha, Sabine Mueller
Medulloblastoma is the most common malignant brain tumor affecting children. These tumors are high grade with propensity to metastasize within the central nervous system and, less frequently, outside the neuraxis. Recent advancements in molecular subgrouping of medulloblastoma refine diagnosis and improve counseling in regards to overall prognosis. Both are predicated on the molecular drivers of each subgroup-WNT-activated, SHH-activated, group 3, and group 4. The traditional therapeutic mainstay for medulloblastoma includes a multimodal approach with surgery, radiation, and multiagent chemotherapy...
September 2017: Neuro-oncology Practice
Galo Garcia, David R Raleigh, Jeremy F Reiter
Cilia, organelles that move to execute functions like fertilization and signal to execute functions like photoreception and embryonic patterning, are composed of a core of nine-fold doublet microtubules overlain by a membrane. Distinct types of cilia display distinct membrane morphologies, ranging from simple domed cylinders to the highly ornate invaginations and membrane disks of photoreceptor outer segments. Critical for the ability of cilia to signal, both the protein and the lipid compositions of ciliary membranes are different from those of other cellular membranes...
April 23, 2018: Current Biology: CB
Stephen T Magill, Jonathan W Rick, William C Chen, David A Haase, David R Raleigh, Manish K Aghi, Philip V Theodosopoulos, Michael W McDermott
BACKGROUND: Petrous face meningiomas (PFMs) are challenging tumors because of their proximity to the cranial nerves, brainstem, and critical vasculature. The objective of this study is to present surgical outcomes and support an anatomic classification for PFM based on clinical presentation. METHODS: A retrospective chart review was performed, and 51 PFMs were identified. Tumors were classified by location along the petrous face into anterior, middle, and posterior...
June 2018: World Neurosurgery
William C Chen, Stephen T Magill, Ashley Wu, Harish N Vasudevan, Olivier Morin, Manish K Aghi, Philip V Theodosopoulos, Arie Perry, Michael W McDermott, Penny K Sneed, Steve E Braunstein, David R Raleigh
OBJECTIVE The goal of this study was to investigate the impact of adjuvant radiotherapy (RT) on local recurrence and overall survival in patients undergoing primary resection of atypical meningioma, and to identify predictive factors to inform patient selection for adjuvant RT. METHODS One hundred eighty-two patients who underwent primary resection of atypical meningioma at a single institution between 1993 and 2014 were retrospectively identified. Patient, meningioma, and treatment data were extracted from the medical record and compared using the Kaplan-Meier method, log-rank tests, multivariate analysis (MVA) Cox proportional hazards models with relative risk (RR), and recursive partitioning analysis...
April 6, 2018: Journal of Neurosurgery
Mollie Rose Canzona, Christy J W Ledford, Carla L Fisher, David Garcia, Meghan Raleigh, Virginia B Kalish
INTRODUCTION: Sexual health (SH) is an important dimension of physical, emotional, and social functioning after breast cancer (BC). Research suggests that survivors' SH concerns are not being adequately addressed in oncology or primary care settings. It is important to understand why these conversations are not taking place and what can be done to enhance care for women in this context. This research aims to identify when clinicians initiate SH conversations with survivors and to uncover factors that influence these decisions...
March 2018: Families, Systems & Health: the Journal of Collaborative Family Healthcare
Harish N Vasudevan, Steve E Braunstein, Joanna J Phillips, Melike Pekmezci, Bryan A Tomlin, Ashley Wu, Gerald F Reis, Stephen T Magill, Jie Zhang, Felix Y Feng, Theodore Nicholaides, Susan M Chang, Penny K Sneed, Michael W McDermott, Mitchel S Berger, Arie Perry, David R Raleigh
Meningioma is the most common primary intracranial tumor, but the molecular drivers of aggressive meningioma are incompletely understood. Using 280 human meningioma samples and RNA sequencing, immunohistochemistry, whole-exome sequencing, DNA methylation arrays, and targeted gene expression profiling, we comprehensively define the molecular profile of aggressive meningioma. Transcriptomic analyses identify FOXM1 as a key transcription factor for meningioma proliferation and a marker of poor clinical outcomes...
March 27, 2018: Cell Reports
Dae Y Han, Lijun Ma, Steve Braunstein, David Raleigh, Patricia K Sneed, Michael McDermott
Background and Objectives Intra-parenchymal brain surgical resection cavities usually contract in volume following low dose rate (LDR) brachytherapy implants. In this study, we systematically modeled and assessed dose variability resulting from such changes for I-125 versus Cs-131 radioactive sources. Methods Resection cavity contraction was modeled based on 95 consecutive patient cases, using surveillance magnetic resonance (MR) images. The model was derived for single point source geometry and then fully simulated in 3D where I-125 or Cs-131 seeds were placed on the surface of an ellipsoidal resection cavity...
January 16, 2018: Curēus
William C Chen, Jared Hara, Stephen T Magill, Ashley Wu, Manish K Aghi, Philip V Theodosopoulos, Arie Perry, Michael W McDermott, Penny K Sneed, David R Raleigh, Steve E Braunstein
Atypical menginomas demonstrate increased clinical aggressiveness characterized by recurrence and diminished survival. The optimal management of atypical meningioma in the recurrent setting is especially not well defined. To characterize outcomes following salvage treatment of recurrent atypical meningioma and to identify risk factors for further recurrence. Retrospective chart review was performed on 65 patients who underwent salvage treatment of atypical meningioma at a single institution. Data were analyzed using the Kaplan-Meier method and Cox proportional hazards modeling...
June 2018: Journal of Neuro-oncology
Joshua Beri, Kaylie I Kirkwood, David C Muddiman, Michael S Bereman
We describe a set of new tools for the detection and quantification of β-N-methylamino-L-alanine (BMAA) which includes a novel stable isotope-labeled BMAA standard (13 C3 ,15 N2 ) and a chip-based capillary electrophoresis mass spectrometry platform for separation and detection. Baseline resolution of BMAA from its potentially confounding structural isomers N-2-aminoethylglycine (AEG) and 2,4-diaminobutyric acid (2,4-DAB) is achieved using the chip-based CE-MS system in less than 1 min. Detection and linearity of response are demonstrated across > 3...
April 2018: Analytical and Bioanalytical Chemistry
Meghan F Raleigh, Garland Anthony Wilson, David Alan Moss, Kristen A Reineke-Piper, Jeffrey Walden, Daniel J Fisher, Tracy Williams, Christienne Alexander, Brock Niceler, Anthony J Viera, Todd Zakrajsek
BACKGROUND AND OBJECTIVES: There is a push to use classroom technology and active teaching methods to replace didactic lectures as the most prevalent format for resident education. This multisite collaborative cohort study involving nine residency programs across the United States compared a standard slide-based didactic lecture, a facilitated group discussion via an engaged classroom, and a high-fidelity, hands-on simulation scenario for teaching the topic of acute dyspnea. The primary outcome was knowledge retention at 2 to 4 weeks...
February 2018: Family Medicine
Uksha Saini, Adrian A Suarez, Shan Naidu, John J Wallbillich, Kristin Bixel, Ross A Wanner, Jason Bice, Raleigh D Kladney, Jenny Lester, Beth Y Karlan, Paul J Goodfellow, David E Cohn, Karuppaiyah Selvendiran
The initial molecular events that lead to malignant transformation of the fimbria of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC) remain poorly understood. In this study, we report that increased expression of signal transducer and activator of transcription 3 ( pSTAT3 Tyr705 ) and suppression or loss of protein inhibitor of activated STAT3 ( PIAS3 ) in FT likely drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53 signature) and their target proliferation genes...
April 1, 2018: Cancer Research
Shane Lloyd, Olivier Morin, Isaac Whitman, David Raleigh, Shannon Fogh, Paul Menzel
No abstract text is available yet for this article.
March 2018: Practical Radiation Oncology
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