bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Polyphenol Conjugate Sensitizes Cisplatin-Resistant Head and Neck Cancer Cells to Cisplatin via Nrf2 Inhibition
Authors: Kim Eun Hye , Jang Hyejin , Roh Jong-Lyel 
Published: August 2016

Abstract
Many cancer cells show acquired resistance to chemotherapeutic agents, such as cisplatin. This is a major cause of cancer treatment failure, and novel agents to overcome resistance are thus urgently required. A novel synthetic polyphenol conjugate, (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP-23), selectively kills tumor cells via the reactive oxygen species (ROS)–mediated unfolded protein response. We investigated the ability of DPP-23 to overcome cisplatin resistance in head and neck cancer (HNC) cells and further clarified its molecular mechanisms of action. Cisplatin-resistant HNC cell lines and their parental and other HNC cell lines were used. The effects of cisplatin and DPP-23 were assessed alone and in combination in HNC and normal cells using cell viability, cell cycle, and cell death assays, by measuring glutathione (GSH), ROS, and protein levels, and via preclinical mouse studies. DPP-23 induced selective cell death in HNC cells, including cisplatin-resistant HNC cells, but spared normal cells, via cellular GSH depletion and ROS accumulation. The effect was blocked by the antioxidant N-acetyl-L-cysteine. DPP-23 activated p53 and its related cell death pathways via a robust accumulation of cellular ROS that involved inhibition of nuclear factor erythroid 2–related factor 2 antioxidant defense mechanisms. Thus, DPP-23 significantly overcame cisplatin resistance in HNC cells in vitro and in vivo. As a promising anticancer strategy, ROS generation and subsequent selective cancer cell killing by DPP-23 might help to overcome cisplatin resistance in HNC. Mol Cancer Ther; 15(11); 2620–9. ©2016 AACR.
A Multiregion Model Evaluation and Attribution Study of Historical Changes in the Area Affected by Temperature and Precipitation Extremes
Authors: Dittus Andrea J. , Karoly David J. , Lewis Sophie C. , Alexander Lisa V. , Donat Markus G. 
Published: August 2016

AbstractThe skill of eight climate models in simulating the variability and trends in the observed areal extent of daily temperature and precipitation extremes is evaluated across five large-scale regions, using the climate extremes index (CEI) framework. Focusing on Europe, North America, Asia, Australia, and the Northern Hemisphere, results show that overall the models are generally able to simulate the decadal variability and trends of the observed temperature and precipitation components over the period 1951–2005. Climate models are able to reproduce observed increasing trends in the area experiencing warm maximum and minimum temperature extremes, as well as, to a lesser extent, increasing trends in the areas experiencing an extreme contribution of heavy precipitation to total annual precipitation for the Northern Hemisphere regions. Using simulations performed under different radiative forcing scenarios, the causes of simulated and observed trends are investigated. A clear anthropogenic signal is found in the trends in the maximum and minimum temperature components for all regions. In North America, a strong anthropogenically forced trend in the maximum temperature component is simulated despite no significant trend in the gridded observations, although a trend is detected in a reanalysis product. A distinct anthropogenic influence is also found for trends in the area affected by a much-above-average contribution of heavy precipitation to annual precipitation totals for Europe in a majority of models and to varying degrees in other Northern Hemisphere regions. However, observed trends in the area experiencing extreme total annual precipitation and extreme number of wet and dry days are not reproduced by climate models under any forcing scenario.
A Theory of the Wind-Driven Beaufort Gyre Variability
Authors: Manucharyan Georgy E. , Spall Michael A. , Thompson Andrew F. 
Published: August 2016

AbstractThe halocline of the Beaufort Gyre varies significantly on interannual to decadal time scales, affecting the freshwater content (FWC) of the Arctic Ocean. This study explores the role of eddies in the Ekman-driven gyre variability. Following the transformed Eulerian-mean paradigm, the authors develop a theory that links the FWC variability to the stability of the large-scale gyre, defined as the inverse of its equilibration time. The theory, verified with eddy-resolving numerical simulations, demonstrates that the gyre stability is explicitly controlled by the mesoscale eddy diffusivity. An accurate representation of the halocline dynamics requires the eddy diffusivity of 300 ± 200 m2 s−1, which is lower than what is used in most low-resolution climate models. In particular, on interannual and longer time scales the eddy fluxes and the Ekman pumping provide equally important contributions to the FWC variability. However, only large-scale Ekman pumping patterns can significantly alter the FWC, with spatially localized perturbations being an order of magnitude less efficient. Lastly, the authors introduce a novel FWC tendency diagnostic—the Gyre Index—that can be conveniently calculated using observations located only along the gyre boundaries. Its strong predictive capabilities, assessed in the eddy-resolving model forced by stochastic winds, suggest that the Gyre Index would be of use in interpreting FWC evolution in observations as well as in numerical models.
Team Training for Dynamic Cross-Functional Teams in Aviation
Authors: Littlepage Glenn E. , Hein Michael B. , Moffett Richard G. , Craig Paul A. , Georgiou Andrea M. 
Published: August 2016

Objective: This study evaluates the effectiveness of a training program designed to improve cross-functional coordination in airline operations. Background: Teamwork across professional specializations is essential for safe and efficient airline operations, but aviation education primarily emphasizes positional knowledge and skill. Although crew resource management training is commonly used to provide some degree of teamwork training, it is generally focused on specific specializations, and little training is provided in coordination across specializations. Method: The current study describes and evaluates a multifaceted training program designed to enhance teamwork and team performance of cross-functional teams within a simulated airline flight operations center. The training included a variety of components: orientation training, position-specific declarative knowledge training, position-specific procedural knowledge training, a series of high-fidelity team simulations, and a series of after-action reviews. Results: Following training, participants demonstrated more effective teamwork, development of transactive memory, and more effective team performance. Conclusion: Multifaceted team training that incorporates positional training and team interaction in complex realistic situations and followed by after-action reviews can facilitate teamwork and team performance. Application: Team training programs, such as the one described here, have potential to improve the training of aviation professionals. These techniques can be applied to other contexts where multidisciplinary teams and multiteam systems work to perform highly interdependent activities.
Racial/Ethnic Disparities in Rates of Traumatic Injury in Arizona, 2011-2012
Authors: Chikani Vatsal , Brophy Maureen , Vossbrink Anne , Blust Robyn N. , Benkert Mary , Salvino Chris , Diven Conrad , Martinez Rogelio 
Published: August 2016

Objective: The purpose of this study was to compare the rates of traumatic injury among five racial/ethnic groups in Arizona and to identify which mechanisms and intents of traumatic injury were predominant in each group. Methods: We obtained 2011 and 2012 data on traumatic injury from Arizona’s trauma registry and data on mortality from Arizona's death registry. We calculated location- and age-adjusted rates (aRs) of traumatic injury and rates of mortality per 100,000 Arizona residents and rate ratios (RRs) for each racial/ethnic group. We also calculated race/ethnicity specific aRs and RRs by mechanism of injury, intent of injury, and alcohol use. Results: We analyzed data on 58,034 cases of traumatic injury. After adjusting for age and location, American Indians/Alaska Natives (AI/ANs) had the highest overall rate of traumatic injury ( n = 6,287; aR = 729) and Asian Americans/Pacific Islanders had the lowest overall rate of traumatic injury ( n = 553; aR = 141). By intent, AI/ANs had the highest rate of homicide/assault-related traumatic injury ( n = 2,170; aR = 221) and by mechanism, non-Hispanic black/African American people had the highest rate of firearm-related traumatic injury ( n = 265; aR = 40). In 2011-2012, 8,868 deaths in Arizona were related to traumatic injury. AI/ANs had the highest adjusted mortality rate ( n = 716; aR = 95). Conclusion: Racial/ethnic disparities in traumatic injuries persisted after adjusting for age and injury location. Understanding how these disparities differ by mechanism, intent, and alcohol use may lead to the development of more effective initiatives to prevent traumatic injury.
Early Lactation and Infant Feeding Practices Differ by Maternal Gestational Diabetes History
Authors: Oza-Frank Reena , Moreland Jennifer J. , McNamara Kelly , Geraghty Sheela R. , Keim Sarah A. 
Published: August 2016

Background: Detailed data on lactation practices by gestational diabetes mellitus (GDM) history are lacking, precluding potential explanations and targets for interventions to improve lactation intensity and duration and, ultimately, long-term maternal and child health. Objective: This study aimed to examine breastfeeding practices through 12 months postpartum by GDM history. Methods: Women who delivered a singleton, liveborn infant at The Ohio State University Wexner Medical Center (Columbus, OH), in 2011 completed a postal questionnaire to assess lactation and infant feeding practices and difficulties. Bivariate and multivariate associations between GDM history and lactation and infant feeding practices were examined. Results: The sample included 432 women (62% response rate), including 7.9% who had GDM during the index pregnancy. Women with GDM initiated breastfeeding (at-the-breast or pumping) as often as women without any diabetes but were more likely to report introduction of formula within the first 2 days of life (79.4% vs 53.8%, P < .01; adjusted odds ratio: 3.48; 95% confidence interval, 1.47-8.26). Women with GDM initiated pumping 4 days earlier than women without diabetes ( P < .05), which was confirmed in adjusted analyses. There was no difference in the proportion of women reporting breastfeeding difficulty (odds ratio: 2.08; 95% confidence interval, 0.78-5.52). However, there was a trend toward women with GDM reporting more formula feeding and less at-the-breast feeding as strategies to address difficulty compared with women without diabetes. Conclusion: Additional research is needed to understand why women with GDM engage in different early lactation and infant feeding practices, and how best to promote and sustain breastfeeding among these women.
Os Trigonum Excision in Dancers via an Open Posteromedial Approach
Authors: Heyer Jessica H. , Rose Donald J. 
Published: August 2016

Background: An os trigonum is a potential source of posterior ankle pain in dancers, often associated with flexor hallucis longus (FHL) pathology. Options for operative excision include open excision, subtalar arthroscopy, and posterior endoscopy. The purpose of this paper was to present a series of dancers who underwent excision of a symptomatic os trigonum via an open posteromedial approach. Methods: This study is a retrospective case series of 40 ankles in 38 dancers who underwent os trigonum excision via an open posteromedial approach with FHL tenolysis between 2000 and 2013. All patients were interviewed and charts retrospectively analyzed. Collected variables included pre- and postoperative pain level, time to return to dance, and subjective satisfaction. The average age was 19.2 years; ballet was the primary dance form in 36 (95%) of patient-cases. Eight (20%) of the patient-cases were professional dancers, and 30 (75%) were students or preprofessional dancers. Results: Average preoperative pain level was 7.7/10, which decreased to 0.6/10 postoperatively. Seventeen (42.5%) experienced concurrent preoperation-associated FHL symptomatology, all of whom experienced relief postoperatively. The average time to return to dance was 7.9 weeks, and time to pain-free dance was 17.7 weeks. Of the 37 patient-cases desiring to return to dance, 35 (94.6%) returned to their preoperative level of dance. There were no neurovascular or other major complications. Four (10%) had minor wound complications that resolved, and 38 cases (95%) considered the procedure a success. Conclusion: Open posteromedial excision of an os trigonum in dancers provided satisfactory pain relief, return to dance, and complication rates compared to other approaches, and allowed for identifying and treating any associated FHL pathology. Level of Evidence: Level IV, retrospective case series.
Epidemiology of Flexor Tendon Injuries of the Hand in a Northern Finnish Population
Authors: Manninen M. , Karjalainen T. , Määttä J. , Flinkkilä T. 
Published: August 2016

Background: Flexor tendon injuries cause significant morbidity in working-age population. The epidemiology of these injuries in adult population is not well known. The aim of this study was to describe the epidemiology of flexor tendon injuries in a Northern Finnish population. Material and Methods: Data on flexor tendon injuries, from 2004 to 2010, were retrieved from patient records from four hospitals, which offer surgical repair of the flexor tendon injuries in a well-defined area in Northern Finland. The incidence of flexor tendon injury as well as the gender-specific incidence rates was calculated. Mechanism of injury, concomitant nerve injuries, and re-operations were also recorded. Results: The incidence rate of flexor tendon injury was 7.0/100,000 person-years. The incidence was higher in men and inversely related to age. The most common finger to be affected was the fifth digit. In 37% of injuries also digital nerve was affected. The most common finger to have simultaneous digital nerve injury was the thumb. Conclusion: Flexor tendon laceration is a relatively rare injury. It predominantly affects working-aged young males and frequently includes a nerve injury, which requires microsurgical skills from the surgeon performing the repair. This study describes epidemiology of flexor tendon injuries and therefore helps planning the surgical and rehabilitation services needed to address this entity.
Exploring obstacles to critical care trials in the UK: A qualitative investigation
Authors: Pattison Natalie , Arulkumaran Nishkantha , Humphreys Sally , Walsh Tim 
Published: August 2016

Background Clinical trials in critical care are often resource-intense, with many unique challenges. Barriers to effective recruitment and implementation of study intervention have not been explored in a UK context. Aim To identify facilitating factors and barriers to enrolling patients into critical care clinical trials within the UK from clinician’s perspectives. Methods A qualitative interview study was undertaken on behalf of the National Institute of Health Research critical care specialty group, in which research active clinicians across different Clinical Research Networks were interviewed. A loosely structured interview schedule was used, based on themes generated from the literature associated with accessing critical care trials. Research teams (critical care doctors, research nurses, and trial coordinators) from hospitals from each Clinical Research Network were contacted to try to achieve representation across the UK. Results Interviews were carried out across nine UK Clinical Research Networks with a range of doctors and research nurses. All hospitals were teaching hospitals with varying research nurse numbers and allocated consultant research sessions. There were a range of six to nine ongoing clinical trials in critical care for each centre representative interviewed. Data were analysed using framework analysis, and six final themes were identified related to factors associated with: centre, unit, resources, study, clinician, and patient/family. The most commonly cited barrier to conducting clinical trials was related to resources, namely insufficient human and financial resources, leading to staff and study recruitment difficulties. Clinical uncertainty and equipoise regarding comparative merits of trials were challenging in terms of engaging critical care teams. A number of patient and family factors added complexities in terms of recruitment; however, refusal rates were generally reported as low. Conclusion Flexibility in funding and employment by research teams enables continuity of studies and staff. Innovative measures to incentivise research nurses and clinical teams can help recruit more patients into trials. Research teams are highly committed to providing cover to recruit critical care trials, and a significant effort to anticipate barriers is undertaken; these endeavours are summarised to provide guidance for other teams wishing to address any potential difficulties.
Fetal development of the corpus callosum: Insights from a 3T DTI and tractography study in a patient with segmental callosal agenesis
Authors: Scola Elisa , Sirgiovanni Ida , Avignone Sabrina , Cinnante Claudia Maria , Biffi Riccardo , Fumagalli Monica , Triulzi Fabio 
Published: August 2016

Commissural embryology mechanisms are not yet completely understood. The study and comprehension of callosal dysgenesis can provide remarkable insights into embryonic or fetal commissural development. The diffusion tensor imaging (DTI) technique allows the in vivo analyses of the white-matter microstructure and is a valid tool to clarify the disturbances of brain connections in patients with dysgenesis of the corpus callosum (CC). The segmental callosal agenesis (SCAG) is a rare partial agenesis of the corpus callosum (ACC). In a newborn with SCAG the DTI and tractography analyses proved that the CC was made of two separate segments consisting respectively of the ventral part in the genu and body of the CC, connecting the frontal lobes, and the dorsal part in the CC splenium and the attached hippocampal commissure (HC), connecting the parietal lobes and the fornix. These findings support the embryological thesis of a separated origin of the ventral and the dorsal parts of the CC.
Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes
Authors: Nasrallah Rabab , Fast Eva M. , Solaimani Parham , Knezevic Kathy , Eliades Alexia , Patel Rahima , Thambyrajah Roshana , Unnikrishnan Ashwin , Thoms Julie , Beck Dominik , Vink Chris S. , Smith Aileen , Wong Jason , Shepherd Mairi , Kent David , Roychoudhuri Rahul , Paul Fabian , Klippert Julia , Hammes Annette , Willnow Thomas , Göttgens Bertie , Dzierzak Elaine , Zon Leonard I. , Lacaud George , Kouskoff Valerie , Pimanda John E. 
Published: August 2016

Key PointsENG regulatory elements target hemogenic mesoderm and hemogenic endothelium. Hemogenic progenitors can be enriched using these elements as molecular probes to discover novel regulators of hematopoiesis.
FastProject: a tool for low-dimensional analysis of single-cell RNA-Seq data
Authors: DeTomaso David , Yosef Nir 
Published: August 2016

Abstract
Background
A key challenge in the emerging field of single-cell RNA-Seq is to characterize phenotypic diversity between cells and visualize this information in an informative manner. A common technique when dealing with high-dimensional data is to project the data to 2 or 3 dimensions for visualization. However, there are a variety of methods to achieve this result and once projected, it can be difficult to ascribe biological significance to the observed features. Additionally, when analyzing single-cell data, the relationship between cells can be obscured by technical confounders such as variable gene capture rates.

Results
To aid in the analysis and interpretation of single-cell RNA-Seq data, we have developed FastProject, a software tool which analyzes a gene expression matrix and produces a dynamic output report in which two-dimensional projections of the data can be explored. Annotated gene sets (referred to as gene ‘signatures’) are incorporated so that features in the projections can be understood in relation to the biological processes they might represent. FastProject provides a novel method of scoring each cell against a gene signature so as to minimize the effect of missed transcripts as well as a method to rank signature-projection pairings so that meaningful associations can be quickly identified. Additionally, FastProject is written with a modular architecture and designed to serve as a platform for incorporating and comparing new projection methods and gene selection algorithms.

Conclusions
Here we present FastProject, a software package for two-dimensional visualization of single cell data, which utilizes a plethora of projection methods and provides a way to systematically investigate the biological relevance of these low dimensional representations by incorporating domain knowledge.