bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of bed height and time on the quality of chest compressions delivered during cardiopulmonary resuscitation: a randomised crossover simulation study
Authors: Lewinsohn A , Sherren P B , Wijayatilake D S 
Published: September 2011

IntroductionThe 2010 International Liaison Committee on Resuscitation gave a detailed update on best practice for cardiopulmonary resuscitation (CPR) with a discussion on appropriate patient and CPR provider position, based largely on expert opinion. The objective of this study was to ascertain robust evidence on the effect of bed height and fatigue on chest compression effectiveness.MethodsA modified Laerdal manikin was connected to a Dragor ventilator (to measure intrathoracic pressures generated). The manikin was placed on a hospital trolley and CPR was performed by candidates at three different bed heights in a randomised order: (1) mid-thigh, (2) anterior superior iliac spine and (3) xiphisternum. Chest compressions were continuous and asynchronous with ventilation, and were allowed to continue for 30 s before recordings were taken. At the anterior superior iliac spine level, chest compressions were continued for 2 min, when further measurements were taken.Results101 subjects took part. The differences in intrathoracic pressures generated at different bed heights were compared using analysis of variance testing for multiple groups and were statistically significant for p<0.05. The authors also found that the effectiveness of CPR decreased 17% over a 2-minute period (p<0.05).ConclusionsThe most effective bed height position, allowing CPR providers to achieve the highest intrathoracic pressures during CPR, was one where the patient's chest was in line with the CPR provider's mid-thigh. The provider performing CPR should change every 2 min.
Solid-state nuclear magnetic resonance (NMR) spectroscopy reveals distinctive protein dynamics in closely related spider silks
Authors: Cloutier Isabelle , Leclerc Jérémie , Lefèvre Thierry , Auger Michèle 
Published: September 2011

Structurally closely related spider silks, namely, major ampullate silk (MaS) reeled at 0.5 and 10 cm/s, minor ampullate silk (MiS), and cocoon silk have been investigated by solid-state nuclear magnetic resonance (NMR). These silks exhibit different mechanical properties that are not well explained with current structural data. NMR spectra confirm that the secondary structures of these silks are similar, but that differing relaxation dynamics exist at the alanine, glycine, and glutamine residue level. MaS reeled rapidly is made of more mobile proteins in both the β-sheet and amorphous regions, suggesting that reeling speed alters molecular rearrangement during spinning, with the chain packing being less organized in the fastpull fiber. Alanine and glycine relaxation dynamics increases as MaS < MiS < cocoon silk, showing that the whole fiber displays distinctive protein dynamics, chain packing, and intermolecular interactions. Besides molecular orientation, silk extensibility is related to a more mobile structural organization.
Stable isotopes reveal strategic allocation of resources during juvenile development in a cryptic and threatened seabird, the Marbled Murrelet (Brachyramphus marmoratus)
Authors: Janssen Michael H. , Arcese Peter , Kyser T. Kurt , Bertram Douglas F. , Norris D. Ryan 
Published: September 2011

Identifying factors that influence growth throughout development is important for understanding the consequences of variation in resource quality on recruitment. Marbled Murrelets ( Brachyramphus marmoratus (J.F. Gmelin, 1789)) are threatened seabirds that are extremely cryptic in their nesting behaviour, which makes it challenging to understand how juveniles allocate resources during development. From a single capture at sea, we analyzed stable carbon isotopes in feathers and blood of juvenile murrelets to infer diet composition during both the pre- and the post-fledging periods. Consistent with the challenges juveniles face during their first year of life, we found that wing and bill growth were prioritized in the nest, whereas development of energy stores was delayed until after nest departure. We also found that diet quality after nest departure influenced bill size and body condition, two body components that continue to grow after independence. Our results provide evidence that murrelets strategically allocate resources according to their stage of development and that the availability of high-quality prey is likely to be important to juvenile development. These results identify a potential mechanism through which feeding conditions may influence reproduction of murrelets and demonstrate the utility of stable isotopes to examine the influence of diet quality on growth over multiple stages of development.
A NOTCH3-Mediated Squamous Cell Differentiation Program Limits Expansion of EMT-Competent Cells That Express the ZEB Transcription Factors
Authors: Ohashi Shinya , Natsuizaka Mitsuteru , Naganuma Seiji , Kagawa Shingo , Kimura Sotai , Itoh Hiroshi , Kalman Ross A. , Nakagawa Momo , Darling Douglas S. , Basu Devraj , Gimotty Phyllis A. , Klein-Szanto Andres J. , Diehl J. Alan , Herlyn Meenhard , Nakagawa Hiroshi 
Published: September 2011

Abstract
Zinc finger E-box–binding (ZEB) proteins ZEB1 and ZEB2 are transcription factors essential in TGF-β–mediated senescence, epithelial-to-mesenchymal transition (EMT), and cancer stem cell functions. ZEBs are negatively regulated by members of the miR-200 microRNA family, but precisely how tumor cells expressing ZEBs emerge during invasive growth remains unknown. Here, we report that NOTCH3-mediated signaling prevents expansion of a unique subset of ZEB-expressing cells. ZEB expression was associated with the lack of cellular capability of undergoing NOTCH3-mediated squamous differentiation in human esophageal cells. Genetic inhibition of the Notch-mediated transcriptional activity by dominant-negative Mastermind-like 1 (DNMAML1) prevented squamous differentiation and induction of Notch target genes including NOTCH3. Moreover, DNMAML1-enriched EMT-competent cells exhibited robust upregulation of ZEBs, downregulation of the miR-200 family, and enhanced anchorage-independent growth and tumor formation in nude mice. RNA interference experiments suggested the involvement of ZEBs in anchorage-independent colony formation, invasion, and TGF-β–mediated EMT. Invasive growth and impaired squamous differentiation were recapitulated upon Notch inhibition by DNMAML1 in organotypic three-dimensional culture, a form of human tissue engineering. Together, our findings indicate that NOTCH3 is a key factor limiting the expansion of ZEB-expressing cells, providing novel mechanistic insights into the role of Notch signaling in the cell fate regulation and disease progression of esophageal squamous cancers. Cancer Res; 71(21); 6836–47. ©2011 AACR.
Targeting FGFR/PDGFR/VEGFR Impairs Tumor Growth, Angiogenesis, and Metastasis by Effects on Tumor Cells, Endothelial Cells, and Pericytes in Pancreatic Cancer
Authors: Taeger Johannes , Moser Christian , Hellerbrand Claus , Mycielska Maria E. , Glockzin Gabriel , Schlitt Hans J. , Geissler Edward K. , Stoeltzing Oliver , Lang Sven A. 
Published: September 2011

Abstract
Activation of receptor tyrosine kinases, such as fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and VEGF receptor (VEGFR), has been implicated in tumor progression and metastasis in human pancreatic cancer. In this study, we investigated the effects of TKI258, a tyrosine kinase inhibitor to FGFR, PDGFR, and VEGFR on pancreatic cancer cell lines (HPAF-II, BxPC-3, MiaPaCa2, and L3.6pl), endothelial cells, and vascular smooth muscle cells (VSMC). Results showed that treatment with TKI258 impaired activation of signaling intermediates in pancreatic cancer cells, endothelial cells, and VSMCs, even upon stimulation with FGF-1, FGF-2, VEGF-A, and PDGF-B. Furthermore, blockade of FGFR/PDGFR/VEGFR reduced survivin expression and improved activity of gemcitabine in MiaPaCa2 pancreatic cancer cells. In addition, motility of cancer cells, endothelial cells, and VSMCs was reduced upon treatment with TKI258. In vivo, therapy with TKI258 led to dose-dependent inhibition of subcutaneous (HPAF-II) and orthotopic (L3.6pl) tumor growth. Immunohistochemical analysis revealed effects on tumor cell proliferation [bromodeoxyuridine (BrdUrd)] and tumor vascularization (CD31). Moreover, lymph node metastases were significantly reduced in the orthotopic tumor model when treatment was initiated early with TKI258 (30 mg/kg/d). In established tumors, TKI258 (30 mg/kg/d) led to significant growth delay and improved survival in subcutaneous and orthotopic models, respectively. These data provide evidence that targeting FGFR/PDFGR/VEGFR with TKI258 may be effective in human pancreatic cancer and warrants further clinical evaluation. Mol Cancer Ther; 10(11); 2157–67. ©2011 AACR.
3,5-Bis(2,4-Difluorobenzylidene)-4-piperidone, a Novel Compound That Affects Pancreatic Cancer Growth and Angiogenesis
Authors: Subramaniam Dharmalingam , Nicholes Nathan D. , Dhar Animesh , Umar Shahid , Awasthi Vibhudutta , Welch Danny R. , Jensen Roy A. , Anant Shrikant 
Published: September 2011

Abstract
Dysregulated Notch signaling plays an important role in the progression of cancer. Notch signaling affects tumor growth and angiogenesis through the actions of its ligand Jagged-1. In this study, we developed a novel compound 3,5-bis(2,4-difluorobenzylidene)-4-piperidone (DiFiD) and determined that it inhibits cancer cell growth and its effects on Notch signaling. Intraperitoneal administration of DiFiD significantly suppressed growth of pancreatic cancer tumor xenografts. There was a reduction in CD31-positive blood vessels, suggesting that there was an effect on angiogenesis. In vitro, DiFiD inhibited the proliferation of various human and mouse pancreatic cancer cells while increasing activated caspase-3. Cell-cycle analyses showed that DiFiD induced G2–M arrest and decreased the expression of cell-cycle–related proteins cyclin A1 and D1 while upregulating cyclin-dependent kinase inhibitor p21WAF1. We next determined the mechanism of action. DiFiD reduced Notch-1 activation, resulting in reduced expression of its downstream target protein Hes-1. We further determined that the reduced Notch-1 activation was due to reduction in the ligand Jagged-1 and two critical components of the γ-secretase enzyme complex presenilin-1 and nicastrin. Ectopic expression of the Notch intracellular domain rescued the cells from DiFiD-mediated growth suppression. DiFiD-treated tumor xenografts also showed reduced levels of Jagged-1 and the γ-secretase complex proteins presenilin-1 and nicastrin. Taken together, these data suggest that DiFiD is a novel potent therapeutic agent that can target different aspects of the Notch signaling pathway to inhibit both tumor growth and angiogenesis. Mol Cancer Ther; 10(11); 2146–56. ©2011 AACR.
Identification of Small-Molecule Inhibitors of the Colorectal Cancer Oncogene Krüppel-like Factor 5 Expression by Ultrahigh-Throughput Screening
Authors: Bialkowska Agnieszka B. , Crisp Melissa , Bannister Thomas , He Yuanjun , Chowdhury Sarwat , Schürer Stephan , Chase Peter , Spicer Timothy , Madoux Franck , Tian Chenlu , Hodder Peter , Zaharevitz Daniel , Yang Vincent W. 
Published: September 2011

Abstract
The transcription factor Krüppel-like factor 5 (KLF5) is primarily expressed in the proliferative zone of the mammalian intestinal epithelium, where it regulates cell proliferation. Studies showed that inhibition of KLF5 expression reduces proliferation rates in human colorectal cancer cells and intestinal tumor formation in mice. To identify chemical probes that decrease levels of KLF5, we used cell-based ultrahigh-throughput screening (uHTS) to test compounds in the public domain of NIH, the Molecular Libraries Probe Production Centers Network library. The primary screen involved luciferase assays in the DLD-1/pGL4.18hKLF5p cell line, which stably expressed a luciferase reporter driven by the human KLF5 promoter. A cytotoxicity counterscreen was done in the rat intestinal epithelial cell line, IEC-6. We identified 97 KLF5-selective compounds with EC50 &lt; 10 μmol/L for KLF5 inhibition and EC50 &gt; 10 μmol/L for IEC-6 cytotoxicity. The two most potent compounds, CIDs (PubChem Compound IDs) 439501 and 5951923, were further characterized on the basis of computational, Western blot, and cell viability analyses. Both of these compounds, and two newly synthesized structural analogs of CID 5951923, significantly reduced endogenous KLF5 protein levels and decreased viability of several colorectal cancer cell lines without any apparent impact on IEC-6 cells. Finally, when tested in the NCI-60 panel of human cancer cell lines, compound CID 5951923 was selectively active against colon cancer cells. Our results show the feasibility of uHTS in identifying novel compounds that inhibit colorectal cancer cell proliferation by targeting KLF5. Mol Cancer Ther; 10(11); 2043–51. ©2011 AACR.
Mentor and Mentee Skills: Tools from Residency to Practice and Beyond
Authors: Abaza Mona M. , Wax Mark K. , Fried Marvin P. , Ivey Chandra M. , Kuppersmith Ronald B. , Tadros Monica 
Published: September 2011

Program DescriptionThe ability to mentor and be mentored is important to the individual and collective success of our specialty. Successful organizations have long benefited from the voluntary contributions of individuals stimulated by a mentoring relationship. On a professional level, mentoring is critical to recruit, retain, and promote a diverse and dynamic otolaryngology work force in a time of changing needs. While the apprentice model of mentoring is familiar, understanding the various options available to aid career transitions and professional development is increasingly important. The panel will explore several aspects attributable to the changing environment of the mentor relationship and provide tools for addressing these needs. Generational differences will be discussed as they relate to changing priorities of the younger mentee and transformation of the traditional mentor role. A successful residency‐mentoring program will be presented and this model adapted to various practice applications. The concept of mentorship will be explored from the perspective of the mentor and mentee and topics of physician practice, academy involvement, and work‐life balance will be covered. The panel, providing tools for those seeking mentoring, will discuss the needs, expectations, and responsibilities of the mentee. Resources available within medicine, the AAO‐HNS, and the business world will be provided for use.Educational Objectives1) Understand the changing mentor/mentee relationship and have the tools to apply to those situations. 2) Improve the mentoring process by incorporating systematic methods reviewed and learn about resources available. 3) Identify individual mentor and mentee needs by encouraging an active role.
Current Solutions in Facial Soft Tissue Reconstruction: The Expert Panel
Authors: Fedok Fred G. , Lazor John B. , Carniol Paul J. , Shockley William W. , Dolan Robert W. , Tatum Sherard A. , Weber Stephen M. , Doerr Timothy D. 
Published: September 2011

Program DescriptionThe reconstruction of facial soft tissue defects occurring after cancer surgery and trauma is a cornerstone discipline of facial plastic and reconstructive surgery. Long‐standing basic principles exist, however techniques continue to evolve and advance. In this miniseminar the panel of experts relates their experience and recommendations for the approach to and the reconstruction of key facial structures. The speakers and the topics addressed will be: Dr Carniol ‐ Logical Approach to Reconstruction of Facial Defects, Dr Lazor ‐ Reconstruction of Auricular Defects, Dr Dolan ‐ Cheek Reconstruction: Moderate and Large Defects, Dr Shockley ‐ Skin Grafts for Small to Moderate Size Nasal Defects, Dr Weber ‐ Forehead Flap Reconstruction for Nasal Defects, Dr Tatum ‐ My Approach to Lip Reconstruction, Dr Doerr ‐ Scalp Defects. Dr Fedok will serve as moderator for the panel discussions.Educational Objectives1) Evaluate patients with soft tissue defects with firm principles of facial aesthetics and wound healing. 2) Approach patients with soft tissue defects with a variety of credible surgical options. 3) Design and execute optimal facial soft tissue repairs utilizing a variety of techniques.
Ethnic Considerations in the International Rhinoplasty Patient
Authors: Cobo‐Sefair Roxana , Pham Tuan V. , Nolsttrenite Gilbert , Palma Pietro , Kim David W. , Montes Jose J. 
Published: September 2011

Program DescriptionCosmetic rhinoplasty has grown in demand over the years. Because of migration patterns around the world, specialists who perform rhinoplasties will frequently be performing surgery on patients coming from different ethnic groups. Characteristic ethnic features can be hard to define and it can be very difficult to try and “fit” a patient in a specific geographical group. Rhinoplasty in ethnic patients, no matter where they come from, will involve most of the usual techniques that are employed in rhinoplasty. However, how the patient is evaluated, what problems are encountered, and what possible solutions are offered make it a challenging operation. The goal in rhinoplasty today is to achieve a natural non‐operated looking nose that will blend in with the patient’s face preserving its main ethnic features. Radical changes in appearance have been replaced by techniques that offer refinement and will provide stable long term results. This panel of experts coming from different countries around the world will be showing the audience how they approach the different types of ethnic patients. The discussion will focus on specific problems encountered and how they are approached surgically. Demonstrative cases showing pre‐ and postsurgical results with intraoperative photographs and videos on the different surgical techniques used will be shown. At the end of each presentation panelists will be showing the attendees how they try to prevent complications on their specific patients. Some final controversies regarding patient satisfaction and revision cases will be discussed at the end of the session.Educational Objectives1) Identify the main anatomic and aesthetic differences encountered in ethnic groups around the world. 2) Be able to identify problems encountered in ethnic noses and establish possible surgical solutions. 3) Acquire a general overview on the prevention and management of possible complications.
Repairing the Externally Crooked Nose: Are There Any Straight Answers?
Authors: Chang C. W. David , Tollefson Travis T. , Marcus Benjamin C. , Wayne Ivan , Chang Edward W. 
Published: September 2011

Program DescriptionThe crooked nose—and its aesthetic and functional issues—is a challenge frequently encountered by practicing otolaryngologists. Repair is not always straightforward and residual deformities can be distressing for the patient as well as the surgeon. With the prominence of the nose as a central defining feature of the face, any deviation is easily recognized since it detracts from overall facial symmetry. The purpose of this miniseminar, created by the Facial Plastic and Reconstructive Surgery Education Committee, is to shed light on the diagnostic and technical challenges of repairing the crooked nose. Panelists will focus on careful analysis of the anatomic factors responsible and highlight a repertoire of corrective surgical techniques. Discussion of the topic will be divided into the various thirds of the nose: the bony nasal vault, the cartilaginous mid‐vault, and the nasal tip and caudal septum. Management strategies to be discussed include new osteotomy techniques, suture techniques, cartilage grafting, extracorporeal septoplasty, and tip‐plasty. In contrast to the external rhinoplasty approach, the endonasal approach provides an alternative strategy—and perhaps a different philosophy—to addressing asymmetries of the nose. The role of endonasal rhinoplasty techniques will be presented. Whenever possible, literature will be referenced to support the discussion. The crooked nose is often caused by a complex interplay between bony and cartilaginous deformities, as well as scarring forces especially in traumatic and revision cases. Surgical strategies combine anatomic restoration with camouflage. A surgical plan requires not only an understanding of operative technique but also an understanding of the surgical expectations of the patient. Therefore, cases and patient scenarios will be presented by the moderator to the panelists (and the audience) for discussion. This miniseminar hopes to provide a nuanced understanding of rhinoplasty concepts and techniques that would be appreciated by seasoned surgeons and provide insight to the novice.Educational Objectives1) Recognize the various deformities and anatomic factors responsible for the crooked nose. 2) Learn to correct the bony nasal vault, cartilaginous mid‐vault, and nasal tip and caudal septum. 3) Appreciate benefits and limitations of the external versus endonasal rhinoplasty approach to straighten the nose.
Alternative Treatments to Common Otolaryngology Problems: Help or Harm?
Authors: Pribitkin Edmund A. , Mann Eric A. , Nguyen Chau T. , Artz Gregory J. , Seidman Michael D. , Wang Marilene B. , Shah Udayan K. 
Published: September 2011

Program DescriptionEach speaker will review the evidence‐based rationale for integrative therapy of common but difficult to treat ENT ailments. Topics will include: Ear wax: Dangers of ear candling—Eric Mann, MD; Tinnitus: What’s the evidence for gingko biloba, bioflavanoid and antioxidant therapies?—Michael Seidman, MD; Meniere’s Disease & vertigo: Should the FDA approve Betahistamine for Meniere’s Disease in the United States? Can acupuncture and cervical manipulation prevent symptoms? What are the best diet‐based regimens?—Gregory Artz, MD; Allergic rhinosinusitis: Do clinical trials support the use of Quercetin, Sinupret, Butterbur, and other herbal remedies? Should patients irrigate their nasal passages and, if so, what should they use?—Marilyn B. Wang, MD; Atypical Facial Pain: Does Acupuncture provide superior analgesia?—Chao T. Nguyen, MD; Perioperative Considerations: Can arnica and bromelain really lessen bruising and speed healing? What herbals and supplements must be avoided before and after surgery?—Edmund Pribitkin, MD; Medicolegal risks and opportunities related to integrative therapies—Udayan Shah, MDEducational Objectives1) Be able to identify harmful and helpful alternative therapies and counsel patients accordingly. 2) Integrate alternative therapies into their treatment regimens for common ENT ailments. 3) Understand medicolegal ramifications of introducing alternative therapies into their practice.