bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing the RISE second victim support programme at the Johns Hopkins Hospital: a case study
Authors: Edrees Hanan , Connors Cheryl , Paine Lori , Norvell Matt , Taylor Henry , Wu Albert W 
Published: October 2016

BackgroundSecond victims are healthcare workers who experience emotional distress following patient adverse events. Studies indicate the need to develop organisational support programmes for these workers. The RISE (Resilience In Stressful Events) programme was developed at the Johns Hopkins Hospital to provide this support.ObjectiveTo describe the development of RISE and evaluate its initial feasibility and subsequent implementation. Programme phases included (1) developing the RISE programme, (2) recruiting and training peer responders, (3) pilot launch in the Department of Paediatrics and (4) hospital-wide implementation.MethodsMixed-methods study, including frequency counts of encounters, staff surveys and evaluations by RISE peer responders. Descriptive statistics were used to summarise demographic characteristics and proportions of responses to categorical, Likert and ordinal scales. Qualitative analysis and coding were used to analyse open-ended responses from questionnaires and focus groups.ResultsA baseline staff survey found that most staff had experienced an unanticipated adverse event, and most would prefer peer support. A total of 119 calls, involving ∼500 individuals, were received in the first 52 months. The majority of calls were from nurses, and very few were related to medical errors (4%). Peer responders reported that the encounters were successful in 88% of cases and 83.3% reported meeting the caller's needs. Low awareness of the programme was a barrier to hospital-wide expansion. However, over the 4 years, the rate of calls increased from ∼1–4 calls per month. The programme evolved to accommodate requests for group support.ConclusionsHospital staff identified the need for a multidisciplinary peer support programme for second victims. Peer responders reported success in responding to calls, the majority of which were for adverse events rather than for medical errors. The low initial volume of calls emphasises the importance of promoting awareness of the value of emotional support and the availability of the programme.
Effect of vitreomacular adhesion and vitreous gel on age-related reduction of macular thickness: a retrospective observational study
Authors: Kumagai Kazuyuki , Hangai Masanori , Furukawa Mariko , Suetsugu Tetsuyuki , Ogino Nobuchika 
Published: October 2016

ObjectiveTo investigate the effects of vitreomacular adhesion (VMA), vitreomacular separation (VMS) and absence of vitreous gel due to vitrectomy on macular thickness measured in the spectral domain optical coherence tomographic (SD-OCT) images.DesignA longitudinal, retrospective, observational study.SettingSecondary multicentre study.Participants218 eyes of 218 healthy patients and 119 vitrectomised eyes of 119 patients were studied. The healthy individuals were classified into a VMA group (54 eyes) and a VMS group (164 eyes), while the vitrectomised patients were classified into an internal limiting membrane (ILM)-on group (26 eyes) and an ILM-off group (93 eyes). In all participants, 2 Cirrus HD-OCT recordings were made with an average interval of 36 months (range 24–60 months).Primary and secondary outcome measuresThe primary outcome measure was the rate of change in macular thickness in the central sector. The secondary outcomes were the rates of change in macular thickness in the inner 4 sectors.ResultsThe annual rate of change in the macular thickness of the central sector was 0.76±1.8 µm/year in the VMA group, −0.58±2.3 µm/year in the VMS group, −1.57±1.9 µm/year in the ILM-on group and −0.86±3.1 µm/year in the ILM-off group. There was a significant difference between the rate of the central sector thickness change in the VMA and VMS groups (p=0.0001). The presence of VMA was a significant factor associated with an increase in the central sector thickness (p=0.0055). When the healthy and ILM-on groups were compared, the rate of decrease in the central sector thickness was faster in the ILM-on group (p=0.0043). Multiple regression analyses showed that not peeling the ILM during the vitrectomy was a significant factor associated with a decrease in the central sector thickness (p=0.044).ConclusionsThe presence of a VMA and a vitreous gel may help restrain the macular thickness reduction.
Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in inflammatory bowel disease
Authors: Häsler Robert , Sheibani-Tezerji Raheleh , Sinha Anupam , Barann Matthias , Rehman Ateequr , Esser Daniela , Aden Konrad , Knecht Carolin , Brandt Berenice , Nikolaus Susanna , Schäuble Sascha , Kaleta Christoph , Franke Andre , Fretter Christoph , Müller Werner , Hütt Marc-Thorsten , Krawczak Michael , Schreiber Stefan , Rosenstiel Philip 
Published: October 2016

ObjectiveAn inadequate host response to the intestinal microbiota likely contributes to the manifestation and progression of human inflammatory bowel disease (IBD). However, molecular approaches to unravelling the nature of the defective crosstalk and its consequences for intestinal metabolic and immunological networks are lacking. We assessed the mucosal transcript levels, splicing architecture and mucosa-attached microbial communities of patients with IBD to obtain a comprehensive view of the underlying, hitherto poorly characterised interactions, and how these are altered in IBD.DesignMucosal biopsies from Crohn's disease and patients with UC, disease controls and healthy individuals (n=63) were subjected to microbiome, transcriptome and splicing analysis, employing next-generation sequencing. The three data levels were integrated by different bioinformatic approaches, including systems biology-inspired network and pathway analysis.ResultsMicrobiota, host transcript levels and host splicing patterns were influenced most strongly by tissue differences, followed by the effect of inflammation. Both factors point towards a substantial disease-related alteration of metabolic processes. We also observed a strong enrichment of splicing events in inflamed tissues, accompanied by an alteration of the mucosa-attached bacterial taxa. Finally, we noted a striking uncoupling of the three molecular entities when moving from healthy individuals via disease controls to patients with IBD.ConclusionsOur results provide strong evidence that the interplay between microbiome and host transcriptome, which normally characterises a state of intestinal homeostasis, is drastically perturbed in Crohn's disease and UC. Consequently, integrating multiple OMICs levels appears to be a promising approach to further disentangle the complexity of IBD.
Potential vectors of equine arboviruses in the UK
Authors: Chapman G. E. , Archer D. , Torr S. , Solomon T. , Baylis M. 
Published: October 2016

There is growing concern about the increasing risk of disease outbreaks caused by arthropod‐borne viruses (arboviruses) in both human beings and animals. There are several mosquito‐borne viral diseases that cause varying levels of morbidity and mortality in horses and that can have substantial welfare and economic ramifications. While none has been recorded in the UK, vector species for some of these viruses are present, suggesting that UK equines may be at risk. The authors undertook, therefore, the first study of mosquito species on equine premises in the UK. Mosquito magnet traps and red‐box traps were used to sample adults, and larvae were collected from water sources such as tyres, buckets, ditches and pools. Several species that are known to be capable of transmitting important equine infectious arboviruses were trapped. The most abundant, with a maximum catch of 173 in 72 hours, was Ochlerotatus detritus, a competent vector of some flaviviruses; the highest densities were found near saltmarsh habitats. The most widespread species, recorded at >75 per cent of sites, was Culiseta annulata. This study demonstrates that potential mosquito vectors of arboviruses, including those known to be capable of infecting horses, are present and may be abundant on equine premises in the UK.
Splicing recharge and groundwater flow models in the Environment Agency National Groundwater Modelling System
Authors: Farrell Rolf , Ververs Marcel , Davison Paul , Howlett Paul , Whiteman Mark 
Published: October 2016

Abstract
This paper explains the background and development of the Environment Agency National Groundwater Modelling System (NGMS) to integrate recharge functionality with the existing groundwater modelling (Modflow functionality).
The Environment Agency groundwater models were originally developed primarily as a tool for making high-level strategic decisions but their use for short-term extreme event scenarios, such as drought or flood, has been relatively limited. This functionality has been constrained by the format of the rainfall/recharge input datasets. Undertaking scenario runs based on change in climate and weather has only been possible by direct manual alteration of those input datasets, which is not always practical on a day-to-day basis.
Full implementation of recharge models into NGMS changes this, allowing the recharge models to be run in the NGMS environment and output to be generated. The fusion aspect of the process involves that output being processed in such a way that it can be used by NGMS as input into a Modflow scenario run. This process is explained using the example of a recent drought scenario in the Wessex Basin groundwater model.
The tectonomagmatic significance of Neoarchaean variably alkali-enriched gabbro and diorite intrusions of the western Karelia Province
Authors: Mikkola Perttu , Heilimo Esa , Halkoaho Tapio , Käpyaho Asko 
Published: October 2016

Abstract

This study describes a group of Neoarchaean alkali enriched gabbros and diorites from the western Karelia Province of the Fennoscandian Shield. We provide new field observations, petrography, whole-rock chemical data and additional whole-rock Sm–Nd and O-isotope data from these Neoarchean rocks. Compositionally, the rocks can be classified as shoshonitic with elevated rare earth element, K
2
O, Ba and Sr contents together with variable MgO, Ni and Cr contents. The MgO, Ni and Cr depletion observed especially in one of the intrusions could have been caused by fractionation of olivine and clinopyroxene from the system. Zircon O-isotope values from one of the intrusions (δ
18
O=7.34±0.10‰) indicate the involvement of material that had undergone low-temperature fractionation of oxygen in the genesis. Samarium–Nd data imply contribution from older material in the petrogenesis of these rocks. The above-mentioned characteristics can be explained with a magma source in the mantle that was heterogeneous owing to the variable degrees of metasomatism. The alkali-enriched gabbros and diorites provide additional evidence for magmatism derived from heterogeneously enriched mantle during the Neoarchaean in the Karelia Province and associated with the cratonization of the area.

Supplementary material:
Table detailing oxygen-isotope analyses from this study is available at
https://doi.org/10.6084/m9.figshare.c.3466575
Geochronology of Neoarchaean granitoids of the NW eastern Dharwar craton: implications for crust formation
Authors: Dey Sukanta , Halla Jaana , Kurhila Matti , Nandy Jinia , Heilimo Esa , Pal Sayantan 
Published: October 2016

Abstract

The Neoarchaean Era is characterized by large preserved record of continental crust formation. Yet the actual mechanism(s) of Neoarchaean crustal growth remains controversial. In the northwestern part of the eastern Dharwar craton (EDC) granitoid magmatism started at 2.68 Ga with gneissic granodiorites showing intermediate character between sanukitoid and tonalite–trondhjemite–granodiorite (TTG). This was followed by intrusion of transitional (large-ion lithophile element-enriched) TTGs at 2.58 Ga. Finally 2.53–2.52 Ga sanukitoid and Closepet-type magmatism and intrusion of K-rich leucogranites mark the cratonization in the area. These granitoids mostly display initial negative εNd and Mesoarchaean depleted mantle model ages, suggesting presence of older crust in the area. Available data show that most of the Neoarchaean sodic granitoids in the EDC are transitional TTGs demonstrating the importance of reworking of older crust. It is suggested that the various
c.
2.7 Ga greenstone mafic–ultramafic volcanic rocks of EDC formed in oceanic arcs and plateaus which accreted to form continental margin environment. Subsequent 2.7–2.51 Ga granitoid magmatism involved juvenile addition of crust as well as reworking of felsic crust forming transitional TTGs, sanukitoids and K-rich leucogranites. Microcratons were possibly the source of older crustal signatures and their accretion appears to be one of the important processes of Neoarchaean crustal growth globally.

Supplementary material:
Analytical techniques are available at
https://doi.org/10.6084/m9.figshare.c.3470724
Finally, An Apoptosis-Targeting Therapeutic for Cancer
Authors: Croce Carlo M. , Reed John C. 
Published: October 2016

Abstract
Resistance to cell death represents one of the hallmarks of cancer. Various genetic and epigenetic changes in malignant cells afford cytoprotection in the face of genomic instability, oncogene activation, microenvironment stress, chemotherapy, targeted anticancer drugs, and even immunotherapy. Central among the regulators of cell life and death are Bcl-2 family proteins, with the founding member of the family (B-cell lymphoma/leukemia-2) discovered via its involvement in chromosomal translocations in lymphomas. The quest for therapeutics that target cell survival protein Bcl-2 represents a long road traveled, with many dead-ends, disappointments, and delays. Finally, a Bcl-2–targeting medicine has gained approval as a new class of anticancer agent. Cancer Res; 76(20); 5914–20. ©2016 AACR.
Concepts in Cancer Modeling: A Brief History
Authors: Thomas Renee M. , Van Dyke Terry , Merlino Glenn , Day Chi-Ping 
Published: October 2016

Abstract
Modeling, an experimental approach to investigate complex biological systems, has significantly contributed to our understanding of cancer. Although extensive cancer research has been conducted utilizing animal models for elucidating mechanisms and developing therapeutics, the concepts in a good model design and its application have not been well elaborated. In this review, we discuss the theory underlying biological modeling and the process of producing a valuable and relevant animal model. Several renowned examples in the history of cancer research will be used to illustrate how modeling can be translatable to clinical applications. Finally, we will also discuss how the advances in cancer genomics and cancer modeling will influence each other going forward. Cancer Res; 76(20); 5921–5. ©2016 AACR.
The Burden of Cancer in Asian Americans: A Report of National Mortality Trends by Asian Ethnicity
Authors: Thompson Caroline A. , Gomez Scarlett Lin , Hastings Katherine G. , Kapphahn Kristopher , Yu Peter , Shariff-Marco Salma , Bhatt Ami S. , Wakelee Heather A. , Patel Manali I. , Cullen Mark R. , Palaniappan Latha P. 
Published: October 2016

Abstract
Background: Asian Americans (AA) are the fastest growing U.S. population, and when properly distinguished by their ethnic origins, exhibit substantial heterogeneity in socioeconomic status, health behaviors, and health outcomes. Cancer is the second leading cause of death in the United States, yet trends and current patterns in the mortality burden of cancer among AA ethnic groups have not been documented.
Methods: We report age-adjusted rates, standardized mortality ratios, and modeled trends in cancer-related mortality in the following AA ethnicities: Asian Indians, Chinese, Filipinos, Japanese, Koreans, and Vietnamese, from 2003 to 2011, with non-Hispanic whites (NHW) as the reference population.
Results: For most cancer sites, AAs had lower cancer mortality than NHWs; however, mortality patterns were heterogeneous across AA ethnicities. Stomach and liver cancer mortality was very high, particularly among Chinese, Koreans, and Vietnamese, for whom these two cancer types combined accounted for 15% to 25% of cancer deaths, but less than 5% of cancer deaths in NHWs. In AA women, lung cancer was a leading cause of death, but (unlike males and NHW females) rates did not decline over the study period.
Conclusions: Ethnicity-specific analyses are critical to understanding the national burden of cancer among the heterogeneous AA population.
Impact: Our findings highlight the need for disaggregated reporting of cancer statistics in AAs and warrant consideration of tailored screening programs for liver and gastric cancers. Cancer Epidemiol Biomarkers Prev; 25(10); 1371–82. ©2016 AACR.
Messages to Motivate Human Papillomavirus Vaccination: National Studies of Parents and Physicians
Authors: Malo Teri L. , Gilkey Melissa B. , Hall Megan E. , Shah Parth D. , Brewer Noel T. 
Published: October 2016

Abstract
Background: Physician communication about human papillomavirus (HPV) vaccine is a key determinant of uptake. To support physician communication, we sought to identify messages that would motivate HPV vaccination.
Methods: From 2014 to 2015, we surveyed national samples of parents of adolescents ages 11 to 17 (n = 1,504) and primary care physicians (n = 776). Parents read motivational messages, selected from nine longer messages developed by the Centers for Disease Control and Prevention and six brief messages developed by the study team. Parents indicated whether each message would persuade them to get HPV vaccine for their adolescents. Physicians read the brief messages and indicated whether they would use them to persuade parents to get HPV vaccine for 11- to 12-year-old children.
Results: The highest proportion of parents (65%) and physicians (69%) found this brief message to be persuasive: “I strongly believe in the importance of this cancer-preventing vaccine for [child's name].” Parents disinclined to vaccinate were most receptive to messages with information about HPV infection being common, cancers caused by HPV, and HPV vaccine effectiveness. Parents' endorsement did not vary by race/ethnicity, education, child age, or child sex (all P &gt; 0.05).
Conclusions: Our national surveys of parents and physicians identified messages that could motivate HPV vaccination, even among parents disinclined to vaccinate their children. The lack of difference across demographic subgroups in parental endorsement may suggest that these messages can be used across these subgroups.
Impact: Our findings support physicians' use of these messages with parents to help motivate uptake of this important cancer-preventing vaccine. Cancer Epidemiol Biomarkers Prev; 25(10); 1383–91. ©2016 AACR.
Tumor Cell–Independent Estrogen Signaling Drives Disease Progression through Mobilization of Myeloid-Derived Suppressor Cells
Authors: Svoronos Nikolaos , Perales-Puchalt Alfredo , Allegrezza Michael J. , Rutkowski Melanie R. , Payne Kyle K. , Tesone Amelia J. , Nguyen Jenny M. , Curiel Tyler J. , Cadungog Mark G. , Singhal Sunil , Eruslanov Evgeniy B. , Zhang Paul , Tchou Julia , Zhang Rugang , Conejo-Garcia Jose R. 
Published: October 2016

Abstract
The role of estrogens in antitumor immunity remains poorly understood. Here, we show that estrogen signaling accelerates the progression of different estrogen-insensitive tumor models by contributing to deregulated myelopoiesis by both driving the mobilization of myeloid-derived suppressor cells (MDSC) and enhancing their intrinsic immunosuppressive activity in vivo. Differences in tumor growth are dependent on blunted antitumor immunity and, correspondingly, disappear in immunodeficient hosts and upon MDSC depletion. Mechanistically, estrogen receptor alpha activates the STAT3 pathway in human and mouse bone marrow myeloid precursors by enhancing JAK2 and SRC activity. Therefore, estrogen signaling is a crucial mechanism underlying pathologic myelopoiesis in cancer. Our work suggests that new antiestrogen drugs that have no agonistic effects may have benefits in a wide range of cancers, independently of the expression of estrogen receptors in tumor cells, and may synergize with immunotherapies to significantly extend survival.
Significance: Ablating estrogenic activity delays malignant progression independently of the tumor cell responsiveness, owing to a decrease in the mobilization and immunosuppressive activity of MDSCs, which boosts T-cell–dependent antitumor immunity. Our results provide a mechanistic rationale to block estrogen signaling with newer antagonists to boost the effectiveness of anticancer immunotherapies. Cancer Discov; 7(1); 72–85. ©2016 AACR.
See related commentary by Welte et al., p. 17.
This article is highlighted in the In This Issue feature, p. 1
Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer
Authors: Bahcall Magda , Sim Taebo , Paweletz Cloud P. , Patel Jyoti D. , Alden Ryan S. , Kuang Yanan , Sacher Adrian G. , Kim Nam Doo , Lydon Christine A. , Awad Mark M. , Jaklitsch Michael T. , Sholl Lynette M. , Jänne Pasi A. , Oxnard Geoffrey R. 
Published: October 2016

Abstract
Amplified and/or mutated MET can act as both a primary oncogenic driver and as a promoter of tyrosine kinase inhibitor (TKI) resistance in non–small cell lung cancer (NSCLC). However, the landscape of MET-specific targeting agents remains underdeveloped, and understanding of mechanisms of resistance to MET TKIs is limited. Here, we present a case of a patient with lung adenocarcinoma harboring both a mutation in EGFR and an amplification of MET, who after progression on erlotinib responded dramatically to combined MET and EGFR inhibition with savolitinib and osimertinib. When resistance developed to this combination, a new MET kinase domain mutation, D1228V, was detected. Our in vitro findings demonstrate that METD1228V induces resistance to type I MET TKIs through impaired drug binding, while sensitivity to type II MET TKIs is maintained. Based on these findings, the patient was treated with erlotinib combined with cabozantinib, a type II MET inhibitor, and exhibited a response.
Significance: With several structurally distinct MET inhibitors undergoing development for treatment of NSCLC, it is critical to identify mechanism-based therapies for drug resistance. We demonstrate that an acquired METD1228V mutation mediates resistance to type I, but not type II, MET inhibitors, having therapeutic implications for the clinical use of sequential MET inhibitors. Cancer Discov; 6(12); 1334–41. ©2016 AACR.
See related commentary by Trusolino, p. 1306.
This article is highlighted in the In This Issue feature, p. 1293