bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer
Authors: Della Corte Carminia Maria , Bellevicine Claudio , Vicidomini Giovanni , Vitagliano Donata , Malapelle Umberto , Accardo Marina , Fabozzi Alessio , Fiorelli Alfonso , Fasano Morena , Papaccio Federica , Martinelli Erika , Troiani Teresa , Troncone Giancarlo , Santini Mario , Bianco Roberto , Ciardiello Fortunato , Morgillo Floriana 
Published: June 2015

Abstract
Purpose: Resistance to tyrosine kinase inhibitors (TKI) of EGF receptor (EGFR) is often related to activation of other signaling pathways and evolution through a mesenchymal phenotype.
Experimental Design: Because the Hedgehog (Hh) pathway has emerged as an important mediator of epithelial-to-mesenchymal transition (EMT), we studied the activation of Hh signaling in models of EGFR-TKIs intrinsic or acquired resistance from both EGFR-mutated and wild-type (WT) non–small cell lung cancer (NSCLC) cell lines.
Results: Activation of the Hh pathway was found in both models of EGFR-mutated and EGFR-WT NSCLC cell line resistant to EGFR-TKIs. In EGFR-mutated HCC827-GR cells, we found SMO (the Hh receptor) gene amplification, MET activation, and the functional interaction of these two signaling pathways. In HCC827-GR cells, inhibition of SMO or downregulation of GLI1 (the most important Hh-induced transcription factor) expression in combination with MET inhibition exerted significant antitumor activity.
In EGFR-WT NSCLC cell lines resistant to EGFR inhibitors, the combined inhibition of SMO and EGFR exerted a strong antiproliferative activity with a complete inhibition of PI3K/Akt and MAPK phosphorylation. In addition, the inhibition of SMO by the use of LDE225 sensitizes EGFR-WT NSCLC cells to standard chemotherapy.
Conclusions:This result supports the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. Clin Cancer Res; 21(20); 4686–97. ©2015 AACR.
Wee-1 Kinase Inhibition Sensitizes High-Risk HPV+ HNSCC to Apoptosis Accompanied by Downregulation of MCl-1 and XIAP Antiapoptotic Proteins
Authors: Tanaka Noriaki , Patel Ameeta A. , Wang Jiping , Frederick Mitchell J. , Kalu Nene N. , Zhao Mei , Fitzgerald Alison L. , Xie Tong-xin , Silver Natalie L. , Caulin Carlos , Zhou Ge , Skinner Heath D. , Johnson Faye M. , Myers Jeffrey N. , Osman Abdullah A. 
Published: June 2015

Abstract
Purpose: Although the majority of patients with HPV+ oropharyngeal cancers have a favorable prognosis, there are some patients with tumors that are resistant to aggressive chemoradiotherapy with unusual patterns of locoregional and systemic recurrences. Therefore, more effective therapies are needed. In this study, we investigated the chemosensitizing efficacy of the selective Wee-1 kinase inhibitor, AZD-1775, in HPV+ head and neck squamous cell carcinoma (HNSCC).
Experimental Design: Clonogenic survival assays and an orthotopic mouse model of HPV+ oral cancer were used to examine the in vitro and in vivo sensitivity of HPV+ HNSCC cell lines to AZD-1775 in combination with cisplatin, respectively. Cell-cycle analysis, DNA damage (γH2AX), homologous recombination (HR), and apoptosis were examined to dissect molecular mechanisms.
Results: We found that AZD-1775 displays single-agent activity and enhances the response of HPV+ HNSCC cells to cisplatin both in vitro and in vivo. The sensitivity of the HPV+ HNSCC cells to AZD-1775 alone or in combination with cisplatin was associated with G2 checkpoint abrogation, persistent DNA damage, and apoptosis induction. This finding of AZD-1775 increasing the sensitivity of HPV+ HNSCC cells to cisplatin through apoptosis was not seen previously in the HPV− HNSCC cancer cells and is accompanied by a decreased expression of the antiapoptotic proteins, MCl-1and XIAP, which appear to be cleaved following AZD-1775 treatment.
Conclusions: AZD-1775 selectively sensitizes HPV+ HNSCC cells and orthotopic oral xenografts to cisplatin through apoptosis and support the clinical investigation of AZD-1775 in combination with cisplatin particularly in patients with advanced and recurrent metastatic HPV+ HNSCC tumors. Clin Cancer Res; 21(21); 4831–44. ©2015 AACR.
A Critical Examination of the “Bad Luck” Explanation of Cancer Risk
Authors: Rozhok Andrii I. , Wahl Geoffrey M. , DeGregori James 
Published: June 2015

Abstract
Tomasetti and Vogelstein (1) argue that lifetime cancer risk for particular tissues is mostly determined by the total number of stem cell (SC) divisions within the tissue, whereby most cancers arise due to “bad luck”—mutations occurring during DNA replication. We argue that the poorly substantiated estimations of SC division parameters and assumptions that oversimplify somatic evolution prevent such a conclusion from being drawn. Cancer Prev Res; 8(9); 762–4. ©2015 AACR.
See related article by Wang et al., p. 761
O punctum no processo de escrita de W ou a memória da infância, de Georges Perec
Authors: Cavalari Tatiana Barbosa 
Published: June 2015

O texto tem como objetivo realizar uma leitura da obra W ou a memória da infância, a partir da perspectiva d’A câmara clara. Segundo Barthes, a foto não rememora o passado. Perec, por sua vez, afirma ter escrito um dos seus principais textos autobiográficos a partir da descrição de algumas fotos antigas. Como podemos pensar nesse trabalho de escrita a partir da observação e descrição detalhada das fotografias? Os conceitos de studium e punctum podem estar presentes na leitura de Perec? A relação entre a memória e a observação de fotos, tão presente em A câmara clara, será discutida aqui a partir desse texto autobiográfico, permeado por vazios, esquecimentos e imagens ausentes.
Cartógrafos e inventariantes: listas como pesquisa em artes cênicas
Authors: Terra Vinícius Demarchi Silva , Guzzo Marina Souza Lobo 
Published: June 2015

<p>Chama atenção o número de trabalhos recentes na cena contemporânea que apresentam em seu processo de criação o uso de listas, inventários e mapeamentos limitados por números, aqui compreendidos como listas cartográficas. Provocados pela radicalidade e qualidade dessas obras, partimos deles para ensaiar sobre a necessidade dessas cartografias listadas na cultura contemporânea. </p>
Characteristics of Thunderstorms That Produce Terrestrial Gamma Ray Flashes
Authors: Chronis Themistoklis , Briggs Michael S. , Priftis George , Connaughton Valerie , Brundell James , Holzworth Robert , Heckman Stan , McBreen Shelia , Fitzpatrick Gerard , Stanbro Matthew 
Published: June 2015

AbstractGround-based lightning detection systems geolocated 877 terrestrial gamma ray flashes (TGFs) from a sample of 2,279 TGFs detected with the Fermi Gamma Ray Burst Monitor (GBM). From these accurate geolocations, 24 TGFs are found within the Next Generation Weather Radar (NEXRAD) operational range in the Gulf of Mexico, the Caribbean, and the Pacific near Guam. NEXRAD-enhanced echo-top (EET) data show that these 24 TGFs are consistently adjacent to high-altitude regions of the storms. The high EET values suggest that there is likely a detection–selection effect, in which the gamma rays from lower-altitude TGFs are attenuated by the atmosphere so that such TGFs fall below the detection threshold of current space-based detectors. The vertical integrated liquid density (VILD) values and the volume scan reflectivities Z show that these 24 TGFs originate from storms of a wide range of convective strengths. Convective available potential energy (CAPE) values from reanalysis also vary widely, providing additional evidence of the range of convection in these TGF-producing storms.
Medical Advice from Lawyers
Authors: Tippett Elizabeth 
Published: June 2015

This study examined the medical information contained in a sample of television ads soliciting consumers for lawsuits against drug and medical device manufactures. Almost all such ads involved drugs or devices that have not been recalled and remain on the market. These ads raise important public health questions because they may influence the prospective medical decisions of viewers.The ads contained extensive descriptions of serious adverse events associated with the drugs or devices but almost uniformly failed to disclose information relating to the likelihood of such events. They also failed to effectively advise viewers to consult a doctor.Results also identified a subset of ads that mimicked public service announcements, claiming to be a “medical alert” “consumer alert” or “FDA warning” at the start of the ad. Most such ads did not disclose the attorney source of the advertising until the final few seconds.
HPV‐Positive Oropharyngeal Carcinoma
Authors: Wang Marilene B. , Liu Isabelle Y. , Gornbein Jeffrey A. , Nguyen Chau T. 
Published: June 2015

ObjectiveHuman papillomavirus‐positive (HPV+) head and neck squamous cell carcinoma is increasing in incidence and appears to exhibit improved response to treatment and better survival than that of HPV– head and neck squamous cell carcinoma. The purpose of this systematic review was to examine the current literature regarding treatment and prognosis of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) and identify whether type of treatment (primarily surgery vs primarily radiation) significantly affects survival rates.Data SourcesPubMed and Cochrane Library databases.Review MethodsA computerized search of the PubMed and Cochrane Library databases was performed to identify English‐language articles published between January 1, 2000, and October 21, 2014. Studies were included only if they were prospective or retrospective observational series of OPSCC patients that reported HPV status, treatment regimen, and survival outcomes. Outcomes were determined for HPV+ and HPV– OPSCC patients, with subanalyses according to the type of treatment received.ResultsFifty‐six articles were eligible for this review. In the HPV+ analysis, the unadjusted hazard rate ratio (HR) for surgery vs radiation treatment was 1.33 (P =. 114). Nine confounders were considered, and HRs were adjusted for each covariate. While HRs were almost all >1 for all covariates, none of the HRs was statistically significant at P <. 05. The HR for HPV– OPSCC was higher for radiation than surgery.ConclusionsHPV+ OPSCC has an improved prognosis and lower rates of adverse events when compared with HPV– OPSCC. HPV– OPSCC had significantly worse outcomes when treated with primary radiation as compared with primary surgery. There was no statistically significant difference in HRs for HPV+ OPSCC with primary radiation vs primary surgery treatment.
Development and Verification of a Protocol to Quantify Hip Joint Kinematics
Authors: Frayne Ryan J. , Kelleher Leila K. , Wegscheider Peter K. , Dickey James P. 
Published: June 2015

Background: The butterfly save technique is commonly used by ice hockey goaltenders and has recently been identified as a potential mechanism for hip joint injuries due to the extreme body positions involved. Unfortunately, commonly used kinematic marker sets that determine these body positions are heavily influenced by skin motion artifact and are obscured by protective equipment, making it difficult to obtain reliable measures of hip motion. Purpose: To create a new kinematic protocol that could be used when protective equipment prevents typical marker placements and to use this protocol to quantify hip kinematics and butterfly performance in 4 different goalie pad conditions. Study Design: Controlled laboratory study. Methods: A new marker set consisting of marker clusters attached to the lateral thigh and posterior leg was developed. This marker set was verified by evaluating the root mean square (RMS) difference between the developed testing marker set and the calibrated anatomic systems technique marker set during passive range of motion (ROM) tests. The testing marker set was then used in a repeated-measures study in which 12 junior goaltenders performed 5 butterfly movements on synthetic ice, in 4 different goalie pad conditions (control, flexible-wide leg channel, flexible-tight leg channel, and stiff-wide leg channel). Results: The grouped RMS differences and SDs calculated during verification were 1.43° ± 0.41°, 1.0° ± 0.39°, and 3.32° ± 1.32° for hip flexion-extension, abduction-adduction, and internal-external rotation, respectively. There was no significant main effect of goal pad condition on the peak amount of hip internal rotation; however, there was a significant main effect of goal pad condition on the butterfly width ( P = .022). Post hoc comparisons revealed that the butterfly width was significantly smaller in the control pad condition compared with the flexible-tight pad condition ( P = .03). Conclusion: The new marker set enabled measurements of hip joint kinematics while subjects are wearing protective equipment that are not possible with other marker sets. Interindividual variations in performance of the butterfly technique influenced the amount of hip internal rotation achieved; however, on average, goaltenders exceeded their active internal ROM during butterfly movements. Clinical Relevance: Exceeding internal rotation range of hip motion may make goaltenders susceptible to hip injuries such as femoral acetabular impingement.
Midtarsal Reconstructive Arthrodesis Using a Multi-Axial Correction Fixator in Charcot Midfoot Arthropathy
Authors: Matsumoto Takumi , Parekh Selene G. 
Published: June 2015

Reconstructive surgeries for Charcot foot are challenging due to complicated conditions and comorbidities including poor bone quality, sensory abnormalities, poor vascularity, and immunity impairment. Although various ﬁxation devices, including screws, plates, and external ﬁxators, have been used in the surgical reconstruction of the Charcot midfoot, all of these devices are associated with some disadvantages. This study aims to evaluate the outcome of the Multi-Axial Correction (MAC) monolateral external ﬁxation system for the reconstructive surgery of midfoot Charcot neuroarthropathy. A total of 11 feet with midfoot Charcot arthropathy were treated surgically using the MAC fixation system solely or accompanied with minimal internal fixation. The mean postoperative follow-up was 29 (range = 12-44) months. The mean postoperative timing of the MAC system removal was 8.7 (range = 5-14) weeks. No pin tract infections were observed. All patients went on to successful union and correction of a rocker bottom deformity. No cases resulted in limb amputation. All patients were able to ambulate with custom diabetic shoes and insoles in 9 patients (10 feet) and commercially available shoes in 1 patient (1 foot). This study suggests that the MAC system can be an acceptable, easy option for the surgical treatment of midfoot Charcot arthropathy. Level of Evidence: Therapeutic, Level IV: Case series
Steenbeek Brace
Authors: Agarwal Anil , Shaharyar Abbas , Kumar Anubrat , Bhat Mohd Shafi , Mishra Madhusudan 
Published: June 2015

Steenbeek foot abduction brace (SFAB) is an essential orthotic for maintaining correction in congenital talipes equinovarus treated with Ponseti method. As the brace is used up to 3 to 4 years of age, we examined the brace wear pattern according to a child’s development and age. We studied 100 SFABs that were rendered unusable or returned by parents due to advanced brace wear. SFABs returned due to other reasons such as foot outgrowing shoe size were excluded. Each part of the brace (outer sole, insole, upper leather, abduction bar, shoe laces) was carefully inspected to observe any pattern of damage. We grouped the pattern of brace wear as per the probable causative factors into 3 broad categories: due to general use in all age groups, sitters and crawlers, and walking children. Shredded tongue, elongated/torn shoelace hole, peeled paint of metal abduction bar, shredded outer sole, and frayed shoelace were due to general use. Due to sitting and crawling with the brace on, shoe wore on its anteromedial, anterolateral, and posterolateral parts at the junction of the upper leather and outer sole. The commonest area of shoe wear in walkers was the abduction bar, which either broke from the welded junction between bar and metal or was bent at midpoint. The SFAB wear pattern was related to the age of the child and his/her activities. The reusability of the brace can probably be extended with simple improvisations and instructing parents about the correct use of the brace. Levels of Evidence: Prognostic, Level IV: Case series
Evaluating the Quality, Accuracy, and Readability of Online Resources Pertaining to Hallux Valgus
Authors: Tartaglione Jason P. , Rosenbaum Andrew J. , Abousayed Mostafa , Hushmendy Shazaan F. , DiPreta John A. 
Published: June 2015

Background. The Internet is one of the most widely utilized resources for health-related information. Evaluation of the medical literature suggests that the quality and accuracy of these resources are poor and written at inappropriately high reading levels. The purpose of our study was to evaluate the quality, accuracy, and readability of online resources pertaining to hallux valgus. Methods. Two search terms (“hallux valgus” and “bunion”) were entered into Google, Yahoo, and Bing. With the use of scoring criteria specific to hallux valgus, the quality and accuracy of online information related to hallux valgus was evaluated by 3 reviewers. The Flesch–Kincaid score was used to determine readability. Statistical analysis was performed with t tests and significance was determined by P values <.05. Results. Sixty-two unique websites were evaluated. Quality was significantly higher with use of the search term “bunion” as compared to “hallux valgus” ( P = .045). Quality and accuracy were significantly higher in resources authored by physicians as compared to nonphysicians (quality, P = .04; accuracy, P < .001) and websites without commercial bias (quality, P = .038; accuracy, P = .011). However, the reading level was significantly more advanced for websites authored by physicians ( P = .035). Websites written above an eighth-grade reading level were significantly more accurate than those written at or below an eighth-grade reading level ( P = .032). Conclusion. The overall quality of online information related to hallux valgus is poor and written at inappropriate reading levels. Furthermore, the search term used, authorship, and presence of commercial bias influence the value of these materials. It is important for orthopaedic surgeons to become familiar with patient education materials, so that appropriate recommendations can be made regarding valuable resources. Levels of Evidence: Level IV
Role of Anoctamin-1 and Bestrophin-1 in Spinal Nerve Ligation-Induced Neuropathic Pain in Rats
Authors: Pineda-Farias Jorge Baruch , Barragan-Iglesias Paulino , Loeza-Alcocer Emanuel , Torres-Lopez Jorge E , Rocha-Gonzalez Héctor Isaac , Perez-Severiano Francisca , Delgado-Lezama Rodolfo , Granados-Soto Vinicio 
Published: June 2015

Background Calcium-activated chloride channels (CaCCs) activation induces membrane depolarization by increasing chloride efflux in primary sensory neurons that can facilitate action potential generation. Previous studies suggest that CaCCs family members bestrophin-1 and anoctamin-1 are involved in inflammatory pain. However, their role in neuropathic pain is unclear. In this investigation we assessed the involvement of these CaCCs family members in rats subjected to the L5/L6 spinal nerve ligation. In addition, anoctamin-1 and bestrophin-1 mRNA and protein expression in dorsal root ganglion (DRG) and spinal cord was also determined in the presence and absence of selective inhibitors. Results L5/L6 spinal nerve ligation induced mechanical tactile allodynia. Intrathecal administration of non-selective CaCCs inhibitors (NPPB, 9-AC and NFA) dose-dependently reduced tactile allodynia. Intrathecal administration of selective CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) also dose-dependently diminished tactile allodynia and thermal hyperalgesia. Anoctamin-1 and bestrophin-1 mRNA and protein were expressed in the dorsal spinal cord and DRG of naïve, sham and neuropathic rats. L5/L6 spinal nerve ligation rose mRNA and protein expression of anoctamin-1, but not bestrophin-1, in the dorsal spinal cord and DRG from day 1 to day 14 after nerve ligation. In addition, repeated administration of CaCCs inhibitors (T16Ainh-A01, CaCCinh-A01 or NFA) or anti-anoctamin-1 antibody prevented spinal nerve ligation-induced rises in anoctamin-1 mRNA and protein expression. Following spinal nerve ligation, the compound action potential generation of putative C fibers increased while selective CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) attenuated such increase. Conclusions There is functional anoctamin-1 and bestrophin-1 expression in rats at sites related to nociceptive processing. Blockade of these CaCCs suppresses compound action potential generation in putative C fibers and lessens established tactile allodynia. As CaCCs activity contributes to neuropathic pain maintenance, selective inhibition of their activity may function as a tool to generate analgesia in nerve injury pain states.
Analysis of the talocrural and subtalar joint motions in patients with medial tibial stress syndrome
Authors: Akiyama Kei , Noh Byungjoo , Fukano Mako , Miyakawa Shumpei , Hirose Norikazu , Fukubayashi Toru 
Published: June 2015

AbstractBackgroundThe rearfoot motion during sports activities in patients with the medial tibial stress syndrome (MTSS) is unknown. This study aimed to investigate the difference in kinematics of the rearfoot in MTSS patients (eight male soccer players) and control participants (eight male soccer players) during a forward step.MethodsSixteen male soccer players, including eight players with MTSS, participated. Forward step trials were recorded with cineradiographic images obtained at a sampling rate of 60 Hz. Geometric bone models of the tibia and talus/calcaneus were created from computed tomography scans of the distal part of one lower limb. Following a combination of approaches, anatomical coordinate systems were embedded in each bone model. The talocrural joint motion (relative motion of the talus with respect to the tibia) and subtalar joint motion (relative motion of the calcaneus with respect to the talus) were examined.ResultsA significantly larger range of internal/external rotation and inversion/eversion motion was observed in the subtalar joint of MTSS patients compared to healthy controls (P < 0.05) from heel contact to heel off. There were no significant differences between the MTSS patients and healthy participants in the ranges of all talocrural joint angles during the forward step.ConclusionOur results indicate that the range of subtalar joint motion is greater in patients with MTSS during the stance phase of the forward step. The kinematic results obtained of this study may have important clinical implications and add quantitative data to an in vivo database of MTSS patients.