bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract NTOC-091: INVOLVEMENT OF TIE–1 TYROSINE KINASE RECEPTOR IN CHEMO–RESISTANCE: POTENTIAL OF TIE1 AS A NOVEL THERAPEUTIC TARGET
Authors: Ishibashi Masumi , Toyoshima Masafumi , Egiz Mahy , Zhang Xuewei , Minato Junko , Shigeta Shogo , Kitatani Kazuyuki , Yaegashi Nobuo 
Published: June 2017

Abstract
OBJECTIVES: Platinum-resistance is one of the most challenging difficulties in the treatment of ovarian cancer patients. To overcome this problem, we have explored a target molecule which can conquer platinum-resistance of ovarian cancer cells utilizing a functional genomics approach.
MATERIALS AND METHODS: High-throughput functional siRNA screening was designed to target 6550 genes in cisplatin-resistant A2780 CP ovarian cancer cells. Cell viability was assessed by luminescent cell viability assay. After identifying a candidate molecule, cisplatin uptake was determined by atomic absorption spectrometry. DNA damages were determined by the western blotting and immunofluorescent staining using γH2AX antibodies.
RESULTS: Through a functional screening, receptor tyrosine kinase TIE 1 was identified as a top candidate gene, of which inhibition give rise to enhancement of cisplatin sensitivity in ovarian cancer cells. Conversely, over-expression of TIE 1 gene significantly decreased susceptibility to cisplatin-induced cell death without affecting cisplatin uptake. DNA damages induced by cisplatin was significantly suppressed in TIE 1 over-expressed cells, raising novel potential mechanisms of TIE 1 in nucleotide excision repair system that removes chemicals adduct to DNA. In addition, over-expression of TIE 1 increased the expression of XPC, which is responsible for nucleotide excision repair.
CONCLUSION: We have identified TIE 1 as a molecular target to overcome platinum-resistance in ovarian cancer cells. TIE 1 contribute platinum- resistance in ovarian cancer cells by promoting XPC-dependent DNA repairing system.
Citation Format: Masumi Ishibashi, Masafumi Toyoshima, Mahy Egiz, Xuewei Zhang, Junko Minato, Shogo Shigeta, Kazuyuki Kitatani, Nobuo Yaegashi. INVOLVEMENT OF TIE–1 TYROSINE KINASE RECEPTOR IN CHEMO–RESISTANCE: POTENTIAL OF TIE1 AS A NOVEL THERAPEUTIC TARGET [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-091.
Abstract NTOC-115: ASSOCIATION BETWEEN NUCLEAR SYK PHOSPHORYLATION AND EGFR/ERBB2 PATHWAY AND POOR SURVIVAL IN HIGH GRADE SEROUS OVARIAN CANCER
Authors: Yu Yu , Ardighieri Laura , Suryo Rahmanto Yohan , Chen Lin Y. , Tessarollo Nayara G. , Mizushima Taichi , Ayhan Ayse , Davidson Ben , Wang Tian L. , Shih Ie M 
Published: June 2017

Abstract
BACKGROUND: Spleen tyrosine kinase (SYK) has emerged as a cancer associated kinase of which aberrant activity contributes to tumor development and drug resistance in several types of human cancer including ovarian carcinoma. To better understand the mechanism how the SYK pathway participates in tumor progression, we studied the biochemistry and transcriptional regulation of SYK in high-grade ovarian serous carcinoma.
METHODS: Immunohistochemical analyses were performed for phosphorylated SYK (Y525/526) and total SYK levels in 42 primary serous ovarian carcinomas and 112 tumor ascites formalin-fixed paraffin embedded tissues. The relative expression of SYK long and short isoforms in peritoneal ascites and cell lines were examined by reverse transcriptase-PCR. Transcriptome analysis of gene regulated by SYK inhibition was carried out using Illumina Human HT-12 v4 arrays. Results from array was analyzed for upstream regulators. IHC data was correlated with pEGFR (Y1197) and pERBB2 (Y877) nuclear expression. Association with survival was determined by Kaplan-Meier analysis and the log-rank test.
RESULTS: We observed that active phosphorylated SYK (p-SYK, Y525/526) is mainly localized in the nucleus and cytoskeleton in cell lines and tissues. Investigation of SYK mRNA spliced variants in ascites tumors showed predominant SYK long isoform expression, consistent with its nuclear localization. Survival analyses revealed that intense nuclear p-SYK correlated with poor overall survival in two ovarian carcinoma cohorts. Patients with relatively high p-SYK in the nucleus had approximately half the median survival compared to those with undetectable or low nuclear p-SYK. SYK inhibition affected changes in gene expression that are downstream of ERBB2 and EGFR signaling. Correlation analyses in tissues suggested a relationship between p-SYK and pERBB2 or pEGFR signaling.
CONCLUSIONS: Our results suggest that activation of the SYK pathway leads to its phosphorylation and localization in cell nucleus. SYK activity plays a role in regulating EGFR and ERBB2 phosphorylation and activation. Thus, SYK may regulate tumor-promoting gene transcription through cross-talks with the EGFR/ERBB2 pathways.
Citation Format: Yu, Yu; Ardighieri, Laura; Suryo Rahmanto, Yohan; Chen, Lin Y.; Tessarollo, Nayara G.; Mizushima, Taichi; Ayhan, Ayse; Davidson, Ben; Wang, Tian L., and Shih Ie M. ASSOCIATION BETWEEN NUCLEAR SYK PHOSPHORYLATION AND EGFR/ERBB2 PATHWAY AND POOR SURVIVAL IN HIGH GRADE SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-115.
Paramedic Initiation of Neuroprotective Agent Infusions
Authors: Shkirkova Kristina , Starkman Sidney , Sanossian Nerses , Eckstein Marc , Stratton Samuel , Pratt Frank , Conwit Robin , Hamilton Scott , Sharma Latisha , Liebeskind David , Restrepo Lucas , Valdes-Sueiras Miguel , Saver Jeffrey L. 
Published: June 2017

Background and Purpose—
Paramedic use of fixed-size lumen, gravity-controlled tubing to initiate intravenous infusions in the field may allow rapid start of neuroprotective therapy for acute stroke. In a large, multicenter trial, we evaluated its efficacy in attaining target serum levels of candidate neuroprotective agent magnesium sulfate and the relation of achieved magnesium levels to outcome.

Methods—
The FAST-MAG phase 3 trial (Field Administration of Stroke Therapy – Magnesium) randomized 1700 patients within 2 hours of onset to paramedic-initiated, a 15-minute loading intravenous infusion of magnesium or placebo followed by a 24-hour maintenance dose. The drug delivery strategy included fixed-size lumen, gravity-controlled tubing for field drug administration, and a shrink-wrapped ambulance kit containing both the randomized field loading and hospital maintenance doses for seamless continuation.

Results—
Among patient randomized to active treatment, magnesium levels in the first 72 hours were assessed 987 times in 572 patients. Mean patient age was 70 years (SD±14 years), and 45% were women. During the 24-hour period of active infusion, mean achieved serum level was 3.91 (±0.8), consistent with trial target. Mg levels were increased by older age, female sex, lower weight, height, body mass index, and estimated glomerular filtration rate, and higher blood urea nitrogen, hemoglobin, and higher hematocrit. Adjusted odds for clinical outcomes did not differ by achieved Mg level, including disability at 90 days, symptomatic hemorrhage, or death.

Conclusions—
Paramedic infusion initiation using gravity-controlled tubing permits rapid achievement of target serum levels of potential neuroprotective agents. The absence of association of clinical outcomes with achieved magnesium levels provides further evidence that magnesium is not biologically neuroprotective in acute stroke.
Delayed and Unreported Drug-Susceptibility Testing Results in the US National Tuberculosis Surveillance System, 1993-2014
Authors: Jones Jefferson Michael , Armstrong Lori R. 
Published: June 2017

Objectives: Drug-susceptibility testing (DST) of Mycobacterium tuberculosis is necessary for identifying drug-resistant tuberculosis, administering effective treatment regimens, and preventing the spread of drug-resistant tuberculosis. DST is recommended for all culture-confirmed cases of tuberculosis. We examined trends in delayed and unreported DST results in the Centers for Disease Control and Prevention’s National Tuberculosis Surveillance System. Methods: We analyzed culture-confirmed tuberculosis cases reported to the National Tuberculosis Surveillance System during 1993-2014 for annual trends in initial DST reporting for first-line antituberculosis drugs and trends in on-time, delayed, and unreported results. We defined on-time reporting as DST results received during the same calendar year in which the patient’s case was reported or ≤4 months after the calendar year ended and delayed reporting as DST results received after the calendar year. We compared cases with on-time, delayed, and unreported DST results by patient and tuberculosis program characteristics. Results: The proportion of cases with reported results for all first-line antituberculosis drugs increased during 1993-2011. Reporting of pyrazinamide results was lower than reporting of other drugs. However, during 2000-2012, of 134 787 tuberculosis cases reported to the National Tuberculosis Surveillance System, reporting was on time for 125 855 (93.4%) cases, delayed for 5332 (4.0%) cases, and unreported for 3600 (2.7%) cases. Conclusions: Despite increases in the proportion of cases with on-time DST results, delayed and unreported results persisted. Carefully assessing causes for delayed and unreported DST results should lead to more timely reporting of drug-resistant tuberculosis.
Endoscopic Lateral Cartilage Graft Tympanoplasty
Authors: Wick Cameron C. , Arnaoutakis Demetri , Kaul Vivian F. , Isaacson Brandon 
Published: June 2017

ObjectiveTo describe a novel technique for lateral graft tympanoplasty.Study DesignCase series with chart review.SettingTertiary care university hospital.Subjects and MethodsPediatric and adult patients with tympanic membrane perforations deemed unfavorable for a medial graft technique due to the perforation characteristics or myringitis.ResultsBetween 2014 and 2016, 34 ears from 31 patients underwent a transcanal endoscopic lateral cartilage graft tympanoplasty. The mean age was 24.4 years (range, 6‐71 years), and 22 patients (65%) were younger than 18 years. All patients had tympanic membrane perforations. Eighteen patients (53%) had total or near‐total perforations, leaving a minimal anterior remnant, and 16 patients (47%) had extensive myringitis. A bisected tragal cartilage‐perichondrium shield graft was used in 33 patients (97%). The mean (SD) follow‐up length was 9.8 (5.7) months. Initial perforation closure rate was 88.2% (30/34). Three of the persistent perforations underwent a revision endoscopic medial graft tympanoplasty with successful closure, leaving a final closure rate of 97.1% (33/34). Five patients (15%) required topical therapy for postoperative myringitis. Mean (SD) pure‐tone average and air‐bone gap significantly improved by 11.5 (10.7) dB (P <. 001) and 11.4 (10.6) dB (P <. 001), respectively. Twenty‐seven patients (79%) closed their air‐bone gap within 20 dB.ConclusionTranscanal endoscopic lateral cartilage graft tympanoplasty is feasible, and initial data support favorable outcomes. Further data are necessary for evaluation of long‐term results and efficacy comparisons.
TGF-β1 Improves Biomechanical Strength by Extracellular Matrix Accumulation Without Increasing the Number of Tenogenic Lineage Cells in a Rat Rotator Cuff Repair Model
Authors: Arimura Hitoshi , Shukunami Chisa , Tokunaga Takuya , Karasugi Tatsuki , Okamoto Nobukazu , Taniwaki Takuya , Sakamoto Hidetoshi , Mizuta Hiroshi , Hiraki Yuji 
Published: June 2017

Background:Transforming growth factor β1 (TGF-β1) positively regulates the tenogenic marker genes scleraxis ( Scx) and tenomodulin ( Tnmd) in mesenchymal progenitors in vitro. However, little is known about the effect of TGF-β1 on the expression of tenogenic markers during rotator cuff (RC) healing in rats.Hypothesis:TGF-β1 improves the biomechanical properties and histological maturity of reparative tissue in a rat RC repair model by stimulating the growth of tenogenic cells.Study Design:Controlled laboratory study.Methods:Adult male Sprague-Dawley rats (N = 180) underwent unilateral supraspinatus tendon-to-bone surgical repair and were randomly treated with a gelatin hydrogel presoaked in TGF-β1 (100 ng) or phosphate-buffered saline. The effects of TGF-β1 on RC healing were investigated at 2, 4, 6, 8, and 12 weeks postoperatively by immunostaining for proliferating cell nuclear antigen, by real-time reverse transcription polymerase chain reaction and in situ hybridization or immunostaining for enthesis-related markers (SRY-box containing gene 9 [ Sox9], Scx, and Tnmd), and by real-time reverse transcription polymerase chain reaction and immunostaining for type I and III collagen. At 6 and 12 weeks postoperatively, biomechanical testing, micro–computed tomography, and biochemical analysis were also performed. At 2 and 4 weeks postoperatively, mesenchymal stem cell–related markers, phospho-Smad2, and matrix metalloproteinase 9 (MMP-9) and MMP-13 were assessed by immunostaining.Results:The TGF-β1-treated group had significantly higher ultimate load to failure and tissue volume at 6 and 12 weeks postoperatively and a higher collagen content at 12 weeks compared with the saline group. Tendon-related gene expression, histological maturity, cell proliferation, and mesenchymal stem cell–related marker immunoreactivity were not affected by exogenously administrated TGF-β1 at all time points. In the TGF-β1-treated group, the percentage of phospho-Smad2-positive cells within the healing tissue increased, whereas the expression of MMP-9 and MMP-13 significantly decreased at 2 and 4 weeks postoperatively.Conclusion:TGF-β1 enhances formation of tough fibrous tissues at the healing site by inhibiting MMP-9 and MMP-13 expression to increase collagen accumulation but without the growth of tenogenic lineage cells.Clinical Relevance:These findings suggest that TGF-β1 could be used for enhancing biomechanical strength after RC surgical repair.
Embedding exercise interventions as routine mental health care: implementation strategies in residential, inpatient and community settings
Authors: Lederman Oscar , Suetani Shuichi , Stanton Robert , Chapman Justin , Korman Nicole , Rosenbaum Simon , Ward Philip B , Siskind Dan 
Published: June 2017

Objectives: Evaluation of physical activity (PA) programs among populations with severe mental illness (SMI) has predominately focused on efficacy and therapeutic benefits. There is now strong evidence to support the benefits of PA in people with SMI. What remains is a gap in the implementation of pragmatic and sustainable PA interventions in mental-health settings. The current paper provides examples of interventions that have been successfully implemented in Australian settings, identifies key components of successful PA interventions and outlines practical strategies that can assist with widespread implementation of PA interventions in mental-health settings. Conclusions: There is an emergence of PA interventions being imbedded within a variety of mental-health settings. These interventions vary in terms of mode and intensity of service delivery. Yet, all aim to increase PA and reduce sedentary behaviour. Adopting the identified strategies may help facilitate successful implementation and increase access to PA interventions for mental-health service users.
Safety of Outpatient Total Ankle Arthroplasty vs Traditional Inpatient Admission or Overnight Observation
Authors: Mulligan Ryan P. , Parekh Selene G. 
Published: June 2017

Background: Total joint surgeons have successfully performed hip, knee, and shoulder arthroplasty procedures in the outpatient setting without compromising safety, satisfaction, or results. The purpose of this study was to evaluate outpatient total ankle arthroplasty (TAA) as compared with overnight or extended inpatient stay, with regard to 90-day medical and operative complications, reoperations, readmissions or emergency room visits, and pain control. Methods: The medical records of patients who underwent TAA with 1 fellowship-trained orthopedic foot and ankle surgeon were reviewed. Outcome measures included operative complications, adverse medical events, readmission or emergency room visit for any reason, or reoperation within 90 days following surgery; surgeon’s office contact before first postoperative visit regarding pain or other issues; visual analog scale pain score at the first postoperative visit; and need for narcotic refill. Outcomes were assessed by admission status: outpatient, overnight observation, or inpatient admission. Standard statistical analysis was used, and P < .05 was considered significant. Results: Eighty-one patients underwent TAA who met inclusion criteria, and 8 had a complication (10%). A significant difference in complication rate was seen among groups ( P = .01) but not rate of readmission or reoperation. Of 16 patients, 5 (31%) who were admitted for 2 or more nights following surgery had a complication, as opposed to 3 of 65 (5%) who were outpatient or admitted overnight ( P = .01). There were no differences in frequency of postoperative phone calls, narcotic refills, or visual analog scale pain scores at the first postoperative visit. There were no adverse medical events. Conclusion: With proper instruction, TAA was performed safely in the outpatient setting. As health care policy continues to evolve in the United States, safe and efficient practices will remain a priority. Level of Evidence: Level III, retrospective comparative study.
Legionnaires’ Disease: Clinicoradiological Comparison of Sporadic Versus Outbreak Cases
Authors: Hashmi Hafiz Rizwan Talib , Saladi Lakshmi , Petersen Frances , Khaja Misbahuddin , Diaz-Fuentes Gilda 
Published: June 2017

Background: In 2015, New York City experienced the worst outbreak of Legionnaires’ disease in the history of the city. We compare patients seen during the 2015 outbreak with sporadic cases of Legionella during the past 5 years. Methods: We conducted a retrospective chart review of 90 patients with Legionnaires’ disease, including sporadic cases of Legionella infection admitted from 2010 to 2015 (n = 55) and cases admitted during the 2015 outbreak (n = 35). Results: We saw no significant differences between the 2 groups regarding demographics, smoking habits, alcohol intake, underlying medical disease, or residence type. Univariate and multivariate analyses showed that patients with sporadic case of Legionella had a longer stay in the hospital and intensive care unit as well as an increased stay in mechanical ventilation. Short-term mortality, discharge disposition, and most clinical parameters did not differ significantly between the 2 groups. Conclusions: We found no specific clinicoradiological characteristics that could differentiate sporadic from epidemic cases of Legionella. Early recognition and high suspicion for Legionnaires’ disease are critical to provide appropriate treatment. Cluster of cases should increase suspicion for an outbreak.
Evaluation of the Radiation Dose–Volume Effects of Optic Nerves and Chiasm by Psychophysical, Electrophysiologic Tests, and Optical Coherence Tomography in Nasopharyngeal Carcinoma
Authors: Ozkaya Akagunduz Ozlem , Guven Yilmaz Suzan , Yalman Deniz , Yuce Berna , Demirkilinc Biler Elif , Afrashi Filiz , Esassolak Mustafa 
Published: June 2017

Purpose: To evaluate the radiation dose–volume effects of optic nerves and chiasm by visual psychophysical, electrophysiologic tests, and optical coherence tomography in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods: A series of visual tests including visual acuity, visual field, contrast sensitivity, visual evoked potential, and optical coherence tomography were administered to 20 patients with locally advanced (T3-T4) nasopharyngeal carcinoma who were treated with definitive chemoradiotherapy. Volume that received 55 Gy (V55), mean dose ( Dmean), highest dose to 5% of the volume (D5), and maximum dose (Dmax) for optic nerves and chiasm were evaluated for each patient. Cutoff values were identified as V55: 50%, Dmean: 50 Gy, D5: 55 Gy, and Dmax: 60 Gy. The effects of radiation dose–volume on ophthalmologic tests were evaluated. Results: Ophthalmological evaluation revealed optic neuropathy with simultaneous retinopathy in 6 eyes of 4 patients and radiation retinopathy alone in both eyes of 1 patient. Regarding radiation dose–volume effects of the optic nerve, significant detrimental effect of all parameters was observed on visual acuity. Visual field and contrast sensitivity were affected significantly with V55 ≥ 50% and Dmean ≥ 50 Gy. Visual evoked potential latency was affected significantly with Dmean ≥ 50 Gy, D5 ≥ 55 Gy, and Dmax ≥ 60 Gy. For the chiasm, significant detrimental effect of all parameters was observed on visual acuity as well. Retinal nerve fiber layer thickness and visual evoked potential amplitude were not affected by any of the dose–volume parameters neither optic nerves nor chiasm. Conclusion: The volume receiving the threshold dose, mean dose, and 5% of the volume receiving the maximum dose are important parameters besides maximum dose to optic nerves and chiasm. A comprehensive ophthalmological evaluation including visual field, contrast sensitivity, visual evoked potential latency, and amplitude should be performed for these patients. Visual evoked potential latency is an objective predictor of vision loss before the onset of clinical signs.
Pilot report: non-operative treatment of Mayo Type II olecranon fractures in any-age adult patient
Authors: Putnam Matthew D. , Christophersen Christy M. , Adams Julie E. 
Published: June 2017

Background We report on the non-operative treatment of Mayo Type II olecranon fractures. Methods Fourteen isolated Mayo Type II olecranon fractures were treated non-operatively, followed to discharge, and retrospectively reviewed. Treatment was splinting in extension followed by protected active motion beginning 3 weeks to 4 weeks post-injury. Mayo Elbow Performance Index (MEPI) and Shortened Disabilities of the Arm, Shoulder and Hand (QuickDASH) scores were available in 86% and 64% of cases, respectively. Follow-up radiographs were obtained. Results At discharge, the mean (SD) MEPI score was 95 (5). The mean (SD) elbow motion arc was 121° (21°). One patient re-fractured his elbow after discharge by falling on the ice. He recovered after open reduction and internal fixation. One patient (documented Marfan syndrome) developed an asymptomatic non-union. Excepting the patient who fell, no patient received additional care. Conclusions In this pilot report, Mayo Type II olecranon fractures were treated non-operatively to discharge. Good to excellent results were obtained in all patients according to the MEPI. Supportive care of these fractures should be comparatively studied. A downside risk to providing supportive care for these fractures was not identified.