bluuebunny/crossref_metadata_2025_split huggingface dataset:
Communication training for inter‐specialty clinicians
Authors: October Tessie W , Dizon Zoelle B , Hamilton Melinda F , Madrigal Vanessa N , Arnold Robert M 
Published: August 2018

SummaryBackgroundInter‐specialty clinicians often co‐lead family conferences for hospitalised patients. Families frequently report receiving different messages from different clinicians. We developed a communication training workshop that crosses disciplines and co‐trains clinicians in one setting to create a culture of delivering a unified message.MethodsWe developed a 2‐day paediatric communication skills workshop to teach the skills necessary to conduct a family conference. The workshop was targeted at nurse‐practitioners and faculty clinicians representing the different specialties that co‐manage children in an intensive care unit. Our primary outcomes were learner self‐assessment of skills attainment and workshop satisfaction. We also evaluated the feasibility of recruiting busy clinicians.ResultsFifteen clinicians, including eight critical care faculty members (80% of eligible participants), three subspecialty faculty members (100% of eligible participants) and four nurse‐practitioners (100% of eligible participants), participated. Learners' self‐reported confidence improved in all communication metrics assessed. From pre‐ to post‐workshop, confidence increased from 39% to 94% for ‘giving bad news’ (p < 0.05), from 50% to 83% for ‘conducting a family conference’ (p < 0.05), and from 39% to 100% for ‘eliciting a family’s values/preferences (p < 0.05). Every learner rated the workshop as important to their clinical practice and 100% would strongly recommend it to others. All reported the time commitment was not burdensome and 74% would choose this 2‐day format over shorter formats.When clinicians learn together, they are more likely to speak the same language when communicating with each other, and ultimately to deliver the same message to familiesConclusionsAn inter‐specialty communication training workshop for different types of clinician was well received. It is feasible to co‐train different types of clinician in a joint session. When clinicians learn together, they are more likely to speak the same language when communicating with each other, and ultimately to deliver the same message to families.
Validation of three‐dimensional wound measurements using a novel 3D‐WAM camera
Authors: Jørgensen Line Bisgaard , Skov‐Jeppesen Sune Møller , Halekoh Ulrich , Rasmussen Benjamin Schnack , Sørensen Jens Ahm , Jemec Gregor B.E. , Yderstræde Knud Bonnet 
Published: August 2018

ABSTRACTTo monitor wound healing, it is essential to obtain accurate and reliable wound measurements. Various methods have been used to measure wound size including three‐dimensional (3D) measurement devices enabling wound assessment from a volume perspective. However, the currently available methods are inaccurate, costly, or complicated to use. As a consequence, we have developed a 3D‐wound assessment monitor (WAM) camera, which is able to measure wound size in three‐dimension and to assess wound characteristics. The aim of the study was to assess the intrarater and interrater reliability of the 3D wound measurements using the 3D camera and to compare these with traditional measurement methods. Four raters measured 48 wounds using the 3D camera, digital imaging method (2D area), and gel injection into the wound cavity (volume). The data were analyzed using linear mixed effect model. Intraclass and interclass correlation coefficient (ICC) and Bland–Altman plots were used to assess intrarater and interrater reliability for the 3D camera and agreement between the methods. The Bland–Altman plots for intrarater reliability showed minor differences between the measurements, especially the 3D area and perimeter measurements. Moreover, ICCs were very high for both the intrarater and interrater reliability for the 2D area, 3D area, and perimeter measurements (ICCs > 0.99), although slightly lower for the volume measurements (ICC = 0.946–0.950). Finally, a high agreement was found between the 3D camera and the traditional methods (2D area and volume) assessed by narrow 95% prediction intervals and high ICCs above 0.97. In conclusion, the 3D‐WAM camera is an accurate and reliable method, which is useful for several types of wounds. However, the volume measurements were primarily useful in large, deep wounds. Moreover, the 3D images are based on digital technology and therefore carry the possibility for use in remote settings.
Race and Exercise Engagement: Investigating the High-Calorie-Burning Activities of White and Black Collegiate Women
Authors: Longmire-Avital Buffie , Madzima Takudzwa , Bierut Elyse 
Published: August 2018

Previous research has documented the comprehensive health benefits of regular physical activity. However, just over a third of Black women report meeting the suggested amount of physical activity per week. Research also indicates that collegiate emerging adults often reduce their physical activity as well. Given that Black collegiate women represent the intersection of two groups that report a reduction in physical activity, the primary purpose of this descriptive study was to examine whether or not the rate of engagement in high-calorie-burning (HCB) activity by collegiate females differed by race. A secondary purpose was to explore how the chronic stress of racism for Black women was related to their HCB activity. Three hundred and eighty-three collegiate females between the ages of 18 and 25 (M = 19.67, SD = 1.45) participated; (61.1% [n = 234] self-identified as White, while the remaining 38.9% [n = 149] self-identified as Black). All eligible participants took a 10–15 min anonymous online survey. Results from a chi-squared analysis (χ2 [1] = 8.40, p = .004) revealed that White collegiate women (70.3%) were more likely to report participation in weekly HCB activity than Black collegiate women (55.7%). Additional analyses also suggested that chronic experience with racism (F [1, 147] = 5.13, p = .03) was associated with more frequent HCB activity for the Black women sampled. Campus health promotion campaigns should not overlook how the experience of race may shape health behaviors for their racial minority students and sustain emerging health disparities.
Poststroke cognitive impairment and hippocampal neurovascular remodeling: the impact of diabetes and sex
Authors: Ward Rebecca , Valenzuela John Paul , Li Weiguo , Dong Guangkuo , Fagan Susan C. , Ergul Adviye 
Published: August 2018

Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. Pathological remodeling of the cerebrovasculature has been postulated to contribute to poor neuronal repair and worsened cognitive deficits in diabetes. However, little is known about the effect of diabetes on the vascularization of hippocampus, a domain critical to memory and learning. Therefore, we had two aims for this study: 1) to determine the impact of diabetes on hippocampal neurovascular remodeling and the resulting cognitive impairment after stroke using two models with varying disease severity, and 2) to compare the effects of ischemia on hippocampal neurovascular injury in diabetic male and female animals. Stroke was induced by middle cerebral artery occlusion (MCAO) by either the suture or embolic method in control and diabetic age-matched male and female Wistar rats. Hippocampal neuronal density, vascular architecture, and microglial activation as well as cognitive outcomes were measured. Embolic MCAO induced greater neuronal degeneration, pathological vascularization, microglial activation, and cognitive impairment in diabetes as compared with control animals or 60-min MCAO. Although diabetic males had lower neuronal density at baseline, diabetic females had more neurodegeneration after stroke. Control animals recovered cognitive function by day 14 after stroke; diabetic animals showed deficits regardless of sex. These results suggest that mechanisms underlying cognitive decline in diabetes may differ in males and females and provide further insight to the impact of diabetes on stroke severity and poststroke cognitive impairment. NEW & NOTEWORTHY The present study is the first to provide comparative information on the effects of diabetes and ischemia on cognitive outcomes in both sexes while also evaluating the neurovascular structure in the hippocampus, a critical region for cognitive and memory-related tasks.
Mutant voltage-gated Na+ channels can exert a dominant negative effect through coupled gating
Authors: Clatot Jérôme , Zheng Yang , Girardeau Aurore , Liu Haiyan , Laurita Kenneth R. , Marionneau Céline , Deschênes Isabelle 
Published: August 2018

Mutations in voltage-gated Na+ channels have been linked to several channelopathies leading to a wide variety of diseases including cardiac arrhythmias, epilepsy, and myotonia. We have previously demonstrated that voltage-gated Na+ channel (Nav)1.5 trafficking-deficient mutant channels could lead to a dominant negative effect by impairing trafficking of the wild-type (WT) channel. We also reported that voltage-gated Na+ channels associate as dimers with coupled gating properties. Here, we hypothesized that the dominant negative effect of mutant Na+ channels could also occur through coupled gating. This was tested using cell surface biotinylation and single channel recordings to measure the gating probability and coupled gating of the dimers. As previously reported, coexpression of Nav1.5-L325R with WT channels led to a dominant negative effect, as reflected by a 75% reduction in current density. Surprisingly, cell surface biotinylation showed that Nav1.5-L325R mutant is capable of trafficking, with 40% of Nav1.5-L325R reaching the cell surface when expressed alone. Importantly, even though a dominant negative effect on the Na+ current is observed when WT and Nav1.5-L325R are expressed together, the total Nav channel cell surface expression was not significantly altered compared with WT channels alone. Thus, the trafficking deficiency could not explain the 75% decrease in inward Na+ current. Interestingly, single channel recordings showed that Nav1.5-L325R exerted a dominant negative effect on the WT channel at the gating level. Both coupled gating and gating probability of WT:L325R dimers were drastically impaired. We conclude that dominant negative suppression exerted by Nav1.5 mutants can also be caused by impairing the WT gating probability, a mechanism resulting from the dimerization and coupled gating of voltage-gated Na+ channel α-subunits. NEW & NOTEWORTHY The presence of dominant negative mutations in the Na+ channel gene leading to Brugada syndrome was supported by our recent findings that Na+ channel α-subunits form dimers. Up until now, the dominant negative effect was thought to be caused by the interaction of the wild-type Na+ channel with trafficking-deficient mutant channels. However, the present study demonstrates that coupled gating of voltage-gated Na+ channels can also be responsible for the dominant negative effect leading to arrhythmias.
Abstract A002: Evidence of pazopanib-induced epithelial-mesenchymal transition (EMT) in human tumors
Authors: Navas Tony , Srivastava Apurva K. , Ferry-Galow Katherine , Makhlouf Hala , Chuaqui Rodrigo , Kinders Robert J. , Bottaro Donald P. , Chen Alice P. , Parchment Ralph E. , Kummar Shivaani , Doroshow James H. 
Published: August 2018

Abstract
Background: VEGFR inhibition by pazopanib slows tumor growth through vascular pruning, although compensatory factors associated with angiogenic inhibitors (e.g., induced HIF1-α from increased hypoxia) can lead to enhanced tumor invasion and metastasis by triggering EMT in some preclinical models (Sennino et al., 2012, Cancer Discovery 2(3);270-87). The development of a clinically suitable, validated assay for EMT has made possible the analysis of EMT in a clinical trial of the VEGFR inhibitor pazopanib. Methods: Paired tumor biopsies were obtained at baseline and on cycle 1, day 7 during a phase I trial (NCT01468922) of single-agent pazopanib (800 mg/day, PO). Biopsies were formalin fixed and paraffin embedded, and tissue sections were evaluated for EMT using a multiplex immunofluorescence assay (EMT-IFA) to quantify E-cadherin (E) and vimentin (V) expression and co-localization in tumor-segmented β-catenin+ regions of interests (ROIs) using Definiens software (Navas et al., NCI-EORTC 2015). EMT-IFA quantitative data were calculated from a minimum of 8 ROIs and 2 tissue sections per biopsy. Results: Paired biopsies from 7 patients (pts) with advanced cancer were evaluable for EMT based on H&E pathologist evaluation. As expected, the mesenchymal phenotype of a patient with chondrosarcoma was stable during treatment, but 4 of 6 carcinomas exhibited significant levels of drug-associated EMT towards more transitional (E+V+) or mesenchymal (V+) phenotypes (increased ratio of V+ to E+ area, log10 V:E; P = 0.0030 to &lt; 0.0001). Two of 4 pts with drug-induced EMT additionally displayed significant increases in the area of V+E+ co-localization (um2/cell) in individual tumor cells (P &lt;0.0001), while the other 2 pts did not show evidence of active transitional cells, but only showed increased E+ or decreased V+ tissue areas (um2/cell) within tumor regions. These results indicate that EMT occurs in some carcinoma of pts treated with pazopanib, consistent with results from preclinical models (Navas et al., 2017, AACR). Conclusions: We report for the first time pazopanib-induced EMT and direct evidence of tumor adaptation to anti-angiogenic therapy in clinical samples. Funded by NCI Contract No. HHSN261200800001E.
Citation Format: Tony Navas, Apurva K. Srivastava, Katherine Ferry-Galow, Hala Makhlouf, Rodrigo Chuaqui, Robert J. Kinders, Donald P. Bottaro, Alice P. Chen, Ralph E. Parchment, Shivaani Kummar, James H. Doroshow. Evidence of pazopanib-induced epithelial-mesenchymal transition (EMT) in human tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A002.
Abstract A006: Preclinical tumor models in humanized mice for translational immuno-oncology research
Authors: Stecklum Maria , Wulf-Goldenberg Annika , Paterka Magdalena , Brzezicha Bernadette , Fichtner Iduna , Hoffmann Jens 
Published: August 2018

Abstract
The recent clinical success of immune checkpoint modulators has stimulated immune-oncology research leading to the identification of new tumor immunology targets. However, both target validation and drug development require appropriate humanized preclinical models. Translational research further urgently needs such models for identification of clinically relevant biomarkers and defining rational combination strategies. In previous studies, we have demonstrated that hematopoietic stem cells (HSC) can proliferate and differentiate in immunodeficient mice and establish a functional human immune system with T cells, B cells, NK cells, monocytes, and dendritic cells. Further, we have shown engraftment of patient- (PDX) and cellline-derived xenografts (CDX) on these humanized mice. All CDX and most of the PDX showed no difference in tumor growth compared to non-humanized mice (fully immune resistant). However, some PDX showed a delayed tumor growth on the humanized mice (partly immune resistant), whereas only one model did not grow at all (immune sensitive). This model is demonstrating the functionality of the established human immune system against a PDX. In the next step, we determined PD-L1 expression on different CDX and PDX on RNA and on protein level. Engraftment seems to be dependent on PD-L1 expression on the PDX, with a higher PD-L1 expression correlating with a stronger tumor growth delay. In the last step the PDX/humanized mice system was evaluated for response to the treatment with checkpoint inhibitors alone and in combination therapy with radiation. So far we treated over 20 PDX and CDX models (lung, colon, melanoma, mammary, ovarian, lymphoma) with ipilimumab, nivolumab, and radiation. In most cases we observed a slight tumor growth delay and increased numbers of T cells in the blood and in the tumor. In our fully humanized model system we identified a correlation between response to checkpoint inhibitor treatment and PD-L1 expression on the PDX or CDX. These results demonstrate that fully humanized PDX models enable appropriate preclinical studies on tumor immune biology, evaluation of new immune therapies and combinations, as well as the identification and validation of biomarkers for immune therapy.
Citation Format: Maria Stecklum, Annika Wulf-Goldenberg, Magdalena Paterka, Bernadette Brzezicha, Iduna Fichtner, Jens Hoffmann. Preclinical tumor models in humanized mice for translational immuno-oncology research [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A006.
Abstract A027: Analytic validation of a pan-cancer tumor mutational burden assay
Authors: Nesselbush Monica , Jones Sian , Keefer Laurel , Sengamalay Naomi , Velculescu Victor , Diaz Luis , Sausen Mark , Angiuoli Samuel 
Published: August 2018

Abstract
Checkpoint inhibitors (CPIs) have been approved for front-line or subsequent therapies in several indications over the last few years. While patient response can be remarkably durable, many patients do not benefit. Current clinical biomarkers of response to CPIs include microsatellite instability (MSI) and PD-L1 expression. While a proportion of many solid tumor display microsatellite instability, the prevalence is often very low. Similarly, while clinically informative, PD-L1 expression alone is not sufficient to predict therapeutic outcomes. The lack of predictive biomarkers for response highlights the need for improved biomarkers with greater prevalence across tumor types to predict response to CPIs. Multiple clinical studies have revealed that high tumor mutational burden (TMB) is associated with better clinical response. Here, we describe the development of an assay and system that can be used to infer mutational burden from a discrete targeted region of interest in the exome. The assay has been analytically validated across several different solid tumor types, and provides proof-of-concept for the pan-cancer approach. Determining mutational burden on this fit-for-purpose assay was compared to whole exome sequencing, and high concordance was observed across a large dynamic range of mutations per megabase of coding sequence. Our data indicate that the assay can be used to accurately determine mutational burden in a range of tumor types, across a spectrum of potential mutational burden cut-offs using automated, complex mutation-identification algorithms.
Citation Format: Monica Nesselbush, Sian Jones, Laurel Keefer, Naomi Sengamalay, Victor Velculescu, Luis Diaz, Mark Sausen, Samuel Angiuoli. Analytic validation of a pan-cancer tumor mutational burden assay [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A027.
Abstract A035: CRC MRD detection using Accu-ActTM NGS technology
Authors: Li Xinxing , Zhao Grace , Zhang Xianwen , Sun Yanping , Wang Yi , Ruan Canping , Tang Paul , Faham Malek , Lin Shengrong , Ying Kang , Hu Zhiqian 
Published: August 2018

Abstract
Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and for monitoring treatment of patients with colorectal cancers (CRC). Any technology used for this purpose, however, will face extreme performance demands. In order to build a high-performance multiplex next-generation sequencing (NGS) platform suitable for cancer MRD using ctDNA, we developed Accu-ActTM, an NGS-based assay capable of detecting low-frequency variants in plasma ctDNA with high precision. In our protocol, rolling-circle amplification is used to circularize denatured double-stranded cell-free DNA (cfDNA) and convert it into long tandem repeats, thus enabling consensus-based concatemer error correction. We demonstrated Accu-ActTM’s sensitivity and specificity by testing it on cfDNA samples with known variant frequencies and cfDNA collected from healthy individuals (n = 100). Our results showed that the sensitivity of Accu-Act was 0.1% with an error rate of 1 in 1 million for 20ng of input cfDNA. Concordance analysis was performed using Accu-Act, a 61-gene assay, on 152 tumor/plasma pairings of preoperative samples derived from patients with CRC (stage I-IV). Depending on stage, we report 66-92% patient detection rate. Post-surgery ctDNA profiling was performed on 52 patients (stage I-IV) enrolled in our prospective MRD study. The results showed that 26% of patients had detectable postoperative ctDNA, among whom 72% had disease progression within two years. Only one out of the 41 patients without detectable postoperative ctDNA went on to relapse, and one patient died of a lung infection. Our study showed that ctDNA is a promising prognostic biomarker for CRC relapse after R0 resection (HR (95%CI) 33.00 (4.05 - 270), P&lt;0.001). The Accu-ActTM NGS-based ctDNA assay has high accuracy and is suitable for MRD in CRC patients. Accu-ActTM should make a significant contribution in the development of personalized cancer treatment.
Citation Format: Xinxing Li, Grace Zhao, Xianwen Zhang, Yanping Sun, Yi Wang, Canping Ruan, Paul Tang, Malek Faham, Shengrong Lin, Kang Ying, Zhiqian Hu. CRC MRD detection using Accu-ActTM NGS technology [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A035.