bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving theatre efficiency and utilisation through early identification of trauma patients and enhanced communication between teams
Authors: Roberts Simon , Saithna Adnan , Bethune Rob 
Published: February 2015

AbstractSurgical departments are increasingly put under pressure to improve services, cut waiting lists, increase efficiency and save money. At a district general hospital in the west-midlands we approached the challenge of improving efficiency and optimising the services available in our orthopaedic theatres.Data was collected on: anaesthetic start times, operation start and finish times, and reasons for delay in our trauma theatre over a period from October 2014 to January 2015. During this period a change was implemented to improve the start time of the first operation of each day in the trauma theatre. Through adaptation of a method developed by Javed S et al, a patient was pre-selected by the on-call team and given the name the "golden patient" the day before they were due to be operated upon. This nominated patient would then be fixed at the start of the trauma theatre list the following day. The list would only then change if a "life or limb threatening" case was admitted overnight. The on-call team would prioritise that this patient was optimised for theatre and the theatre staff would ensure the surgical instruments were prepared.A PDSA cycle method was used, collecting data on 80 orthopaedic trauma cases during the period, and demonstrated a 59 minute (95% CI 45-72) improvement in start times from 10:49 AM to 9:50 AM with a p-value of 0.00024 with the intervention of early allocation of the first patient on the trauma list.A relatively simple intervention tool designed to improve communication within and between health-care teams can have a significant impact on the efficiency of a complex environment such as a trauma theatre.
Field study of pneumonia in vaccinated cattle associated with incorrect vaccination and Pasteurella multocida infection
Authors: Crawshaw W. M. , Caldow G. L. 
Published: February 2015

This field study used data on the vaccine courses against bovine respiratory disease sold by one pharmaceutical company in conjunction with pharmacovigilance data to explore reported suspected lack of expected efficacy and the reasons for this. The study ran from May 1, 2007, to April 30, 2010, and covered vaccines sold in Scotland and part of Northumberland. In total, 83 groups of cattle reported suspected lack of expected efficacy, representing 1.6 per cent of the 804,618 vaccine courses sold. It was possible to investigate 45 of these outbreaks in depth using a standard questionnaire and diagnostic protocol. Vaccine usage outwith the specific product characteristics (SPC) occurred in 47 per cent of cases (21/45). The proportion of vaccination courses used where a pathogen contained in the vaccine was detected in the diseased cattle and vaccine use was consistent with the SPC was estimated at 0.12 per cent of the courses sold. Pasteurella multocida was the most common pathogen detected and was found in 21 of the outbreaks. For outbreaks where a pathogen contained in the vaccine was detected, P. multocida was found at a significantly greater frequency (P=0.03) where vaccine use was compliant with the SPC (five of six outbreaks) compared with outbreaks where vaccine use had not been compliant with the SPC (one of seven outbreaks). The limitations of the study, including the diagnostic tests employed and definition of vaccination outwith the SPC, are discussed.
Going Local or Global: The Case of Online Daily Deal Company TicketMonster
Authors: Jeon Seongmin , Yoo Byungjoon 
Published: March 2015

TicketMonster is a deal-of-the-day coupon site which utilizes the Internet and mobile infrastructure to offer deals in Seoul and other cities around Korea on services at restaurants, cafes, spas, and so forth. Following the company's rapid expansion, management made the decision to expand the scope of TicketMonster beyond Korea's borders with the aim of taking on other Asian markets. To this end, TicketMonster acquired Everyday.com.my, the biggest social shopping site in Malaysia. However, it was believed that simply competing in markets across Asia would not enable TicketMonster to claim sufficient market share in light of the international expansion of Groupon and LivingSocial, two online daily deal global giants. Furthermore, competition in the online daily deal sector in Korea had escalated as local, regional and international players vied for consumer awareness and loyalty. On top of an advertising war, competition grew to the point where several sites began selling coupons while knowingly taking a loss by lowering commissions in order to attract competitive products or services for their respective deals and at times paying for the services themselves. In mid-2011, U.S.-based LivingSocial made an offer to buy TicketMonster in order to strengthen its presence in Asia. Considering these changes and challenges, what are the strategic issues regarding TicketMonster and how should the company deal with the offer to deploy its transfer of ownership to LivingSocial? This case will help readers form an opinion on the related management issues and analyses.
Search Rate and Functional Response of a Eusocial Insect (Oecophylla longinoda) in a Tanzanian Mango Orchard
Authors: Fast Thora Samsø , Axelsen Jørgen Aagaard , Lynegaard Gina Kier , Mwatawala Maulid , Offenberg Joachim 
Published: February 2015

Weaver ants,Oecophyllaspp., are famous for being efficient biological control agents as they prey on a variety of insects, and they are capable of suppressing a large number of pest species. Here, the search rate and functional response ofOecophylla longinodawere investigated in a Tanzanian mango orchard using feeding experiments. This was done by following the removal of prey, which constituted the foundation for estimating the search rate by aid of the Nicholson-Bailey and Lotka-Volterra models. The overall mean search rate was3.2 ×10-4and1.7 ×10-4over 30 minutes, when calculating the search rate using the Nicholson-Bailey equation and the Lotka-Volterra equation (modified Holling equation), respectively. The functional response investigations showed a linear relationship between removed prey and available prey, suggesting type I functional response or, alternatively, the initial phase of type II functional response. The results presented here are probably the first attempt to identify the functional response type of a colony of living predatory eusocial insects.
Heat Shock Factor 1 in Protein Homeostasis and Oncogenic Signal Integration
Authors: Home Trisha , Jensen Roy A. , Rao Rekha 
Published: February 2015

Abstract
Heat shock factor 1 (HSF1) is a stress-inducible transcription factor and has been described as a multi-faceted modulator of tumorigenesis. Heat shock, accumulation of misfolded proteins, or malignant transformation promotes the activation and nuclear translocation of HSF1, where it binds to the promoters of heat shock proteins and an array of nonheat shock–regulated proteins to upregulate their transcription. These stress-responsive and tumor-promoting genes in turn alter the ability of tumor cells to respond to a variety of stresses and enable them to thrive in less than favorable growth conditions. Although a direct role for HSF1 in promoting mRNA transcription of tumor-promoting genes has been suggested, it appears that this property is context- and cell-type dependent. Furthermore, recent studies have demonstrated a direct involvement of mTOR signaling in regulating HSF1-mediated transcription, thus establishing a direct link between protein translation and HSF1 activity. Interestingly, there is a growing understanding of the signaling pathways that are modulated by HSF1 in a variety of tumor types and the co-option of these survival pathways by HSF1 to promote tumorigenesis. This review will focus on the role of HSF1 in protein homeostasis and HSF1-mediated oncogenic signaling pathways that together promote tumorigenesis. Cancer Res; 75(6); 907–12. ©2015 AACR.
miR-137 and miR-197 Induce Apoptosis and Suppress Tumorigenicity by Targeting MCL-1 in Multiple Myeloma
Authors: Yang Yijun , Li Fei , Saha Manujendra N. , Abdi Jahangir , Qiu Lugui , Chang Hong 
Published: February 2015

Abstract
Purpose: Deregulation of miRNA has been implicated in the pathogenesis of multiple myeloma. We identified miR-137 and miR-197, mapped to the chromosome 1p (12)–(21) deletion region, and examined their antimyeloma activity as tumor suppressors.
Experimental Design: The expression of miR-137/197 was examined in multiple myeloma and normal plasma cells by qRT-PCR. Functional effect of miR-137/197 was analyzed by cell viability, apoptosis, clonogenic, and migration assays. Antimyeloma activity of miR-137/197 was further evaluated in vivo by lentiviral-based or lipid-based delivery in a mouse xenograft model of multiple myeloma.
Results: miR-137/197 expression was significantly lower in multiple myeloma cell lines and multiple myeloma patient samples compared with normal plasma cells. Transfection of miR-137/197 resulted in reduction of MCL-1 protein expression, as well as alteration of apoptosis-related genes, and induction of apoptosis, inhibition of viability, colony formation, and migration in multiple myeloma cells. MCL-1 was further validated as a direct target of miR-137/197. Conversely, overexpression of MCL-1 partially reverted the effect of miR-137/197. Importantly, in vivo lentiviral-mediated or intratumor delivery of miR-137/197 induced regression of tumors in murine xenograft models of multiple myeloma.
Conclusions: Our study reveals a novel role of miR-137/197 as tumor suppressors in mediating apoptosis in multiple myeloma cells by targeting MCL-1. Our findings provide a proof-of-principle that lentivirus-based or formulated synthetic miR-137/197 exerts therapeutic activity in preclinical models, and support a framework for development of miR-137/197-based treatment strategies in patients with multiple myeloma. Clin Cancer Res; 21(10); 2399–411. ©2015 AACR.
Angiotensin System Inhibitors and Survival Outcomes in Patients with Metastatic Renal Cell Carcinoma
Authors: McKay Rana R. , Rodriguez Gustavo E. , Lin Xun , Kaymakcalan Marina D. , Hamnvik Ole-Petter R. , Sabbisetti Venkata S. , Bhatt Rupal S. , Simantov Ronit , Choueiri Toni K. 
Published: February 2015

AbstractPurpose: The renin-angiotensin system may play a role in carcinogenesis. The purpose of this study was to evaluate the impact of angiotensin system inhibitors (ASI) on outcomes in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era.Experimental Design: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan–Meier method.Results: A total of 4,736 patients were included, of whom 1,487 received ASIs and 783 received other antihypertensive agents. Overall, ASI users demonstrated improved overall survival (OS) compared with users of other antihypertensive agents (adjusted HR, 0.838, P = 0.0105, 26.68 vs. 18.07 months) and individuals receiving no antihypertensive therapy (adjusted HR, 0.810, P = 0.0026, 26.68 vs. 16.72 months). When stratified by therapy type, a benefit in OS was demonstrated in ASI users compared with nonusers in individuals receiving VEGF therapy (adjusted HR, 0.737, P &lt; 0.0001, 31.12 vs. 21.94 months) but not temsirolimus or IFNα. An in vitro cell viability assay demonstrated that sunitinib in combination with an ASI significantly decreased RCC cell viability compared with control at physiologically relevant doses. This effect was not observed with either agent alone or with other non-ASI antihypertensives or temsirolimus.Conclusions: In the largest analysis to date, we demonstrate that ASI use improved survival in mRCC patients treated in the targeted therapy era. Further studies are warranted to investigate the mechanism underlying this interaction and verify our observations to inform clinical practice. Clin Cancer Res; 21(11); 2471–9. ©2015 AACR.
Contribution of Beta-HPV Infection and UV Damage to Rapid-Onset Cutaneous Squamous Cell Carcinoma during BRAF-Inhibition Therapy
Authors: Cohen Daniel N. , Lawson Steven K. , Shaver Aaron C. , Du Liping , Nguyen Harrison P. , He Qin , Johnson Douglas B. , Lumbang Wilfred A. , Moody Brent R. , Prescott James L. , Chandra Pranil K. , Boyd Alan S. , Zwerner Jeffrey P. , Robbins Jason B. , Tyring Stephen K. , Rady Peter L. , Chappell James D. , Shyr Yu , Infante Jeffrey R. , Sosman Jeffrey A. 
Published: February 2015

AbstractPurpose: BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. UV radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC.Experimental Design: Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology.Results: Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During vemurafenib therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional cSCC when controlled for gender and UV exposure (P value = 0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated, and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK, and EGFR mutations also detected.Conclusions: We examined clinical, histopathologic, viral, and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general. Clin Cancer Res; 21(11); 2624–34. ©2015 AACR.
Treatment Planning and Fracture Prediction in Patients with Skeletal Metastasis with CT-Based Rigidity Analysis
Authors: Nazarian Ara , Entezari Vahid , Zurakowski David , Calderon Nathan , Hipp John A. , Villa-Camacho Juan C. , Lin Patrick P. , Cheung Felix H. , Aboulafia Albert J. , Turcotte Robert , Anderson Megan E. , Gebhardt Mark C. , Cheng Edward Y. , Terek Richard M. , Yaszemski Michael , Damron Timothy A. , Snyder Brian D. 
Published: February 2015

AbstractPurpose: Pathologic fractures could be prevented if reliable methods of fracture risk assessment were available. A multicenter prospective study was conducted to identify significant predictors of physicians' treatment plan for skeletal metastasis based on clinical fracture risk assessments and the proposed CT-based Rigidity Analysis (CTRA).Experimental Design: Orthopedic oncologists selected a treatment plan for 124 patients with 149 metastatic lesions based on the Mirels method. Then, CTRA was performed, and the results were provided to the physicians, who were asked to reassess their treatment plan. The pre- and post-CTRA treatment plans were compared to identify cases in which the treatment plan was changed based on the CTRA report. Patients were followed for a 4-month period to establish the incidence of pathologic fractures.Results: Pain, lesion type, and lesion size were significant predictors of the pre-CTRA plan. After providing the CTRA results, physicians changed their plan for 36 patients. CTRA results, pain, and primary source of metastasis were significant predictors of the post-CTRA plan. Follow-up of patients who did not undergo fixation resulted in 7 fractures; CTRA predicted these fractures with 100% sensitivity and 90% specificity, whereas the Mirels method was 71% sensitive and 50% specific.Conclusions: Lesion type and size and pain level influenced the physicians' plans for the management of metastatic lesions. Physicians' treatment plans and fracture risk predictions were significantly influenced by the availability of CTRA results. Due to its high sensitivity and specificity, CTRA could potentially be used as a screening method for pathologic fractures. Clin Cancer Res; 21(11); 2514–9. ©2015 AACR.
Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression
Authors: Strekalova Elena , Malin Dmitry , Good David M. , Cryns Vincent L. 
Published: February 2015

Abstract
Purpose: Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists.
Experimental Design: Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab, or the combination.
Results: Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model.
Conclusions: Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. Clin Cancer Res; 21(12); 2780–91. ©2015 AACR.
A Phase I First-in-Human Study of Enoticumab (REGN421), a Fully Human Delta-like Ligand 4 (Dll4) Monoclonal Antibody in Patients with Advanced Solid Tumors
Authors: Chiorean Elena Gabriela , LoRusso Patricia , Strother Robert Matthew , Diamond Jennifer R. , Younger Anne , Messersmith Wells A. , Adriaens Lieve , Liu Liming , Kao Richard J. , DiCioccio Albert Thomas , Kostic Ana , Leek Russell , Harris Adrian , Jimeno Antonio 
Published: February 2015

Abstract
Purpose: Enoticumab (REGN421) is a fully human IgG1 monoclonal antibody that binds human Dll4 and disrupts Notch-mediated signaling. The main objectives of this trial were to determine the safety, dose-limiting toxicities (DLT), pharmacokinetics (PK), and recommended phase II dose (RP2D) of enoticumab.
Experimental Design: Enoticumab was administered intravenously, with dose escalations from 0.25 to 4 mg/kg every 3 weeks (Q3W) and 0.75 to 3 mg/kg every 2 weeks (Q2W).
Results: Of 53 enrolled patients, 31 patients were treated Q3W and 22 patients were treated Q2W. Two DLTs occurred: grade 3 nausea (0.5 mg/kg Q3W) and grade 3 abdominal pain (1 mg/kg Q2W). An MTD was not reached on either schedule. The most frequent adverse events (AE) were fatigue, nausea, vomiting, hypertension, headache, and anorexia. Six treatment-related serious AEs were reported in 4 patients: brain natriuretic peptide (BNP) increase (0.25 mg/kg Q3W, Gr1), troponin I increase (4 mg/kg Q3W, Gr3), right ventricular dysfunction and pulmonary hypertension (1.5 mg/kg Q2W, both Gr3), and left ventricular dysfunction and pulmonary hypertension (3 mg/kg Q2W, both Gr3). Enoticumab was characterized by nonlinear, target-mediated PK, and had a terminal half-life of 8 to 9 days. With multiple Q2W or Q3W dosing, accumulation was not observed. Antitumor activity included two partial responses (non–small cell lung cancer bronchoalveolar-type with a β-catenin mutation, and ovarian cancer) and 16 patients with stable disease (3&gt; 6 months).
Conclusions: Enoticumab was tolerated, with RP2D of 4 mg/kg Q3W and 3 mg/kg Q2W based on PK profile and clinical activity. Responses and SD were noted in ovarian cancer and other solid tumors. Clin Cancer Res; 21(12); 2695–703. ©2015 AACR.
A Phase I/II Study of the mTOR Inhibitor Everolimus in Combination with HyperCVAD Chemotherapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia
Authors: Daver Naval , Boumber Yanis , Kantarjian Hagop , Ravandi Farhad , Cortes Jorge , Rytting Michael E. , Kawedia Jitesh D. , Basnett Jordan , Culotta Kirk S. , Zeng Zhihong , Lu Hongbo , Richie Mary Ann , Garris Rebecca , Xiao Lianchun , Liu Wenbin , Baggerly Keith A. , Jabbour Elias , O'Brien Susan , Burger Jan , Bendall Linda J. , Thomas Deborah , Konopleva Marina 
Published: February 2015

Abstract
Purpose: Previous studies suggest a potential therapeutic role for mTOR inhibition in lymphoid malignancies. This single-center phase I/II study was designed to test the safety and efficacy of the mTOR inhibitor everolimus in combination with HyperCVAD chemotherapy in relapsed/refractory acute lymphoblastic leukemia (ALL).
Experimental Design: Twenty-four patients were treated; 15 received everolimus 5 mg/day and 9 received 10 mg/day with HyperCVAD.
Results: The median age of patients was 25 years (range, 11–64) and median number of prior treatments was 2 (range, 1–7). Grade 3 mucositis was the dose-limiting toxicity and the maximum tolerated everolimus dose was 5 mg/day. Responses included complete remission (CR) in 6 patients (25%), CR without platelet recovery (CRp) in 1 (4%), and CR without recovery of counts (CRi) in 1 (4%), for an overall response rate of 33%. In addition, partial response (PR) was noted in 2 patients (8%). Seven of 11 patients treated in first salvage achieved CR/CRp (64%). The median OS was 29 weeks for patients in first salvage versus 15 weeks for patients in second salvage and beyond (P ≤ 0.001). A response was noted in 5 of 10 (50%) heavily pretreated T-ALL patients (median of 4 prior salvage regimens). Everolimus significantly inhibited phosphorylation of S6RP, but this did not correlate with response. No significant decreases in p4EBP1 and pAkt levels were noted. Responders had higher everolimus dose-adjusted area under the curve (P = 0.025) and lower clearance (P = 0.025) than nonresponders.
Conclusions: The combination of HyperCVAD and everolimus is well tolerated and moderately effective in relapsed ALL, specifically T-ALL. Clin Cancer Res; 21(12); 2704–14. ©2015 AACR.