bluuebunny/crossref_metadata_2025_split huggingface dataset:
56 Rapid review of dissemination strategies and activities as listed in published protocol papers
Authors: Palmieri Maria Giovanna , Morgan Fiona , Longo Mirella , Gregory Clive , Nelson Annmarie , Hepburn Julie 
Published: August 2018

BackgroundDissemination of research results is now recognised as an important part of the research process. UK funding agencies and the Health Research Authority require that researchers have a clear plan about how findings should be reported back to patients and members of the public. Wider dissemination using a range of mechanisms specifically targeting the lay community enables the work to have impact outside its academic base and accelerate implementation. The study evolves over three stages: a review of the literature surveys of key stakeholders (research partners study participants members of the public and researchers) and a consensus meeting.AimTo present a literature review of dissemination activities planned by researchers as reported in published protocol papers.MethodologyThe MEDLINE electronic database was searched to identify study protocols published in 2017 and covering a range of study designs.Results138 papers published in 2017 were reviewed. Most papers lacked a clear and detailed dissemination plan. In general descriptions of dissemination plans were short and listed a very limited number of stakeholder groups targeted for dissemination and few dissemination channels. A few papers contained additional information on dissemination strategies and activities. Four papers mentioned specific feedback to participants by newsletter or other methods. A full and detailed dissemination plan was present in three protocol papers.ConclusionMost of the previous research has focused on the researchers’ perspective. The guidelines will embed the views of other stakeholders including the general public patient participants in research trials funding bodies and policy makers.
58 Support needs of informal carers of patients with copd and implications for improving carer support
Authors: Micklewright Kerry , Farquhar Morag 
Published: August 2018

IntroductionInformal carers play a key supportive role for patients with chronic obstructive pulmonary disease (COPD) but with considerable impact on their health and wellbeing.1 2The literature on support needs of these carers has not been fully synthesised and our knowledge of the comprehensiveness of the Carer Support Needs Assessment Tool3(CSNAT) for carers of patients with COPD is limited.AimTo identify relevant carer support needs from the published literature in order to explore the comprehensiveness of the CSNAT for carers of patients with COPD.MethodsEnglish language studies published between 1997–2017 were identified against predetermined inclusion/exclusion criteria through searches of MEDLINE, CINAHL, EMBASE, CDSR, ASSIA, PsycINFO and Scopus. Further studies were identified through searching reference lists and citations of included papers. Papers were critically appraised and data extracted and synthesised by two reviewers. Identified needs were mapped to CSNAT items.Results24 studies were included in the review. Preliminary results (synthesis ongoing: completes September 2018) indicate that carers have support needs in a range of domains that include physical psychological spiritual and social needs. Early findings suggest additional CSNAT items may be required in order to encompass the full range of needs of this group particularly relating to difficulties within the patient-carer relationship and accessing services.ConclusionBased on preliminary results there is evidence to suggest the need for additional CSNAT items for COPD carers and that these carers would benefit from identification and response to their support needs by healthcare professionals to improve carer support.References. Cruz J, Marques A, Figueiredo D. Impacts of COPD on family carers and supportive interventions: A narrative review.Health and Social Care in the Community2017;25(1):11–25.. Grant M, Cavanagh A, Yorke J. The impact of caring for those with chronic obstructive pulmonary disease (COPD) on carers’ psychological well-being: A narrative review. International Journal of Nursing Studies2012;49:1459–1471.. Ewing G, Grande G.The CSNAT2018. Available at: http://csnat.org/ (Accessed: 29/05/18)
6 Compassionate neighbours – an innovative model building caring communities
Authors: Attridge Carly , Richardson Heather 
Published: August 2018

IntroductionIn 2014 St Joseph’s Hospice set up compassionate neighbours (CN) to address social isolation for those experiencing a chronic or terminal illness. Built on foundations of community development principles the neighbours provide emotional and social support to community members. With significant funding from Nesta we are upscaling the project with seven other hospices.AimOur aim is to build a wider network of CN who are supporting people in their local communities; we will test and learn how the project can be replicated in other areas. Our ultimate aim is to create a social movement establishing a network of CNs across the country.MethodWe are training and mentoring other hospice adopters to replicate the project in their own areas whilst testing which ingredients are key to the success of the project. Our review of the programme including formal evaluation will form the basis for a potential national roll out across the country.ResultsReview of our progress including a recent conference for CN feedback from hospice CEOs and project leads describes ongoing interest in the CN programme. There is additional interest from other hospices and other organisations outside of the Nesta programme. That said challenges exist around local implementation of a model shaped elsewhere translation of particular principles underpinning the CN programme and concerns around long-term sustainability and ownership of the network.ConclusionFurther thought is required about how to build the social movement and whether this effort should sit within the hospice sector or within a community development context in the future.
9 Using what people value to develop new interventions in palliative care: a multilevel level review approach
Authors: Candy B , Armstrong M , Amey R , Booth J , Flemming K , Kupeli N , Maclean V , Preston J , Stone P , Wilkinson S 
Published: August 2018

IntroductionComplex interventions are common in palliative care (PC) but are difficult to evaluate. Complementary therapies (CT) are one type of widely-used complex intervention for which there is inconclusive evidence. No systematic review has been conducted in PC of trials or of qualitative studies of patients’ views of CTs. There are novel approaches with established exemplars of using both types of reviews to help develop more clinically appropriate interventions. These approaches are in their infancy in PC research and have much to offer the specialism.AimsUsing our on-going review on CT we present as an exemplar in PC an approach to draw together the findings of trials and qualitative studies in a data table (matrix) to contrast what patients value and want with how the intervention is tested.MethodsWe sought trials on the effectiveness of CT and qualitative studies on patients’ perspectives about these therapies. Our primary outcomes for trials included anxiety. Eight databases were searched in 2017. Citations and full-text papers were reviewed to identify relevant studies. Meta-analyses pooled trial data where appropriate and a thematic synthesis is being undertaken to understand patient experience. These findings will be combined in a matrix to explore similarities and differences.Results19 trials and five qualitative studies were included. Data analysis and development of the matrix which includes intervention content and patients’ needs is currently underway. We will present the final matrix framework.ConclusionsOur approach demonstrates a potential way in PC to enhance development of practice appropriate complex interventions.
Eighty-nine-year-old woman with abdominal pain and vomiting
Authors: Schramm Joerg , Rickenbacher Andreas , Keller Dagmar Iris 
Published: August 2018

Clinical introductionAn 89-year-old female patient presented to the ED with mild abdominal pain and a history of vomiting for 3 days. Because of dementia, further history was unclear. Vital signs were normal. Clinical examination revealed mild abdominal pain without defence or signs of peritonism. Bowel sounds were normal. Lab results showed a white cell count of 16x109/L, otherwise normal. There was no episode of vomiting during the ED consultation. A supine AXR was performed (figure 1).Figure 1Supine AXR.What is the diagnosis?Foreign bodyGallstone ileusColon obstructionIntestinal volvulus
Man with severe abdominal pain
Authors: Chen Chia-Wei , Lee Wei-Jing 
Published: August 2018

Clinical introductionA 59-year-old man with no medical history presented to the ED with abdominal distension, vomiting and diffuse abdominal pain after drinking seven cups of white gourd drink (an authentic Asian drink composed mainly of white gourd). A chest radiograph was performed (figure 1).Figure 1Chest radiograph. AP, anteroposterior.QuestionWhat is the most likely diagnosis?Crescent in doughnut sign, intussusceptionFalciform ligament sign, pneumoperitoneumStepladder sign, small bowel obstructionCoffee-bean sign, sigmoid colon volvulus
BET 1: Prehospital cardiac troponin testing to ‘rule out’ acute coronary syndromes using point of care assays
Authors: Alghamdi Abdulrhman , Body Richard 
Published: August 2018

A shortcut review of the literature was carried out to establish whether prehospital point of care (POC) troponin tests are reliable and accurate enough to detect acute coronary syndrome (ACS) in adult patients.Nine papers were found to be relevant to the clinical question following the below-described search strategies. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of those best papers are tabulated. It is concluded that based on the currently available evidence, POC troponin assays are insufficiently sensitive to ‘rule out’ ACS in the prehospital environment.
BET 2: Twist score in cases of suspected paediatric testicular torsion
Authors: Ridgway Alex , Hulme Peter 
Published: August 2018

A shortcut review of the literature was carried out to establish whether the Testicular Workup for Ischemia and Suspected Torsion (TWIST) score was reliable and accurate enough to rule out testicular torsion in the paediatric population.Four papers were found to be relevant to the clinical question following the below-described search strategies. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of those best papers are tabulated. It is concluded that based on the currently available evidence, a low-risk TWIST score has a high sensitivity and can be used in line with clinical judgement to rule out testicular torsion.
Kernza intermediate wheatgrass (Thinopyrum intermedium) grain production as influenced by legume intercropping and residue management
Authors: Dick C. , Cattani D. , Entz M.H. 
Published: August 2018

Intermediate wheatgrass yielded 519 and 446 kg seed ha−1in years one and two after establishment. Autumn grazing increased seed yield compared with post-harvest residue removal or chopping. Inter-seeding legumes (alfalfa (Medicago sativa), sweet clover (Melilotus officinalis), and white clover (Trifolium repens) did not affect intermediate wheatgrass seed production.
Provocative decompression causes diffuse vascular injury in mice mediated by microparticles containing interleukin-1β
Authors: Thom Stephen R. , Bhopale Veena M. , Yu Kevin , Yang Ming 
Published: August 2018

Inflammatory mediators are known to be elevated in association with decompression from elevated ambient pressure, but their role in tissue damage or overt decompression sickness is unclear. Circulating microparticles (MPs) are also known to increase, and because interleukin (IL)-1β is packaged within these particles, we hypothesized that IL-1β was responsible for tissue injuries. Here, we demonstrate that elevations of circulating MPs containing up to ninefold higher concentrations of IL-1β occur while mice are exposed to high air pressure (790 kPa), whereas smaller particles carrying proteins specific to exosomes are not elevated. MPs number and intra-particle IL-1β concentration increase further over 13 h post decompression. MPs also exhibit intra-particle elevations of tumor necrosis factor-α, caspase-1, inhibitor of κB kinase-β, and inhibitor of κB kinase-γ, and elevated IL-6 is adsorbed to the surface of MPs. Contrary to lymphocytes, neutrophil nucleotide-binding oligomerization domain-like receptor, pyrin domain containing 3 (NLRP3) inflammasome oligomerization and cell activation parameters occur during high pressure exposure, and additional evidence for activation is manifested post decompression. Diffuse vascular damage, although not apparent immediately post decompression, was present 2 h later and remained elevated for at least 13 h. Prophylactic administration of an IL-1β receptor inhibitor or neutralizing antibody to IL-1β inhibited MPs elevations, increases of all MPs-associated pro-inflammatory agents, and vascular damage. We conclude that an auto-activation process triggered by high pressure stimulates MPs production and concurrent inflammasome activation, and IL-1β is a proximal factor responsible for further cytokine production and decompression-associated vascular injuries. NEW & NOTEWORTHY Elevations in circulating microparticles due to decompression have been documented in humans and animals. This report shows that intra-particle interleukin-1β causes vascular damage that can be abrogated by interventions directed against this cytokine.
CD44-Targeting PLGA Nanoparticles Incorporating Paclitaxel and FAK siRNA Overcome Chemoresistance in Epithelial Ovarian Cancer
Authors: Byeon Yeongseon , Lee Jeong-Won , Choi Whan Soo , Won Ji Eun , Kim Ga Hee , Kim Min Gi , Wi Tae In , Lee Jae Myeong , Kang Tae Heung , Jung In Duk , Cho Young-Jae , Ahn Hyung Jun , Shin Byung Cheol , Lee Young Joo , Sood Anil K. , Han Hee Dong , Park Yeong-Min 
Published: August 2018

Abstract
Chemotherapy is commonly used in the treatment of ovarian cancer, yet most ovarian cancers harbor inherent resistance or develop acquired resistance. Therefore, novel therapeutic approaches to overcome chemoresistance are required. In this study, we developed a hyaluronic acid-labeled poly(d,l-lactide-co-glycolide) nanoparticle (HA-PLGA-NP) encapsulating both paclitaxel (PTX) and focal adhesion kinase (FAK) siRNA as a selective delivery system against chemoresistant ovarian cancer. The mean size and zeta potential of the HA-PLGA-NP were 220 nm and -7.3 mV, respectively. Incorporation efficiencies for PTX and FAK siRNA in the HA-PLGA-NPs were 77% and 85%, respectively. HA-PLGA-NP showed higher binding efficiency for CD44-positive tumor cells as compared with CD44-negative cells. HA-PLGA (PTX+FAK siRNA)-NP caused increased cytotoxicity and apoptosis in drug-resistant tumor cells. Treatment of human epithelial ovarian cancer tumor models HeyA8-MDR (P &lt; 0.001) and SKOV3-TR (P &lt; 0.001) with HA-PLGA (PTX+FAK siRNA)-NP resulted in significant inhibition of tumor growth. Moreover, in a drug-resistant, patient-derived xenograft (PDX) model, HA-PLGA (PTX+FAK siRNA)-NP significantly inhibited tumor growth compared with PTX alone (P &lt; 0.002). Taken together, HA-PLGA-NP acts as an effective and selective delivery system for both the chemotherapeutic and the siRNA in order to overcome chemoresistance in ovarian carcinoma.
Significance: These findings demonstrate the efficacy of a novel, selective, two-in-one delivery system to overcome chemoresistance in epithelial ovarian cancer. Cancer Res; 78(21); 6247–56. ©2018 AACR.
In Vivo Estimation of Oncolytic Virus Populations within Tumors
Authors: Jung Mi-Yeon , Offord Chetan P. , Ennis Matthew K. , Kemler Iris , Neuhauser Claudia , Dingli David 
Published: August 2018

Abstract
The use of replication-competent viruses as oncolytic agents is rapidly expanding, with several oncolytic viruses approved for cancer therapy. As responses to therapy are highly variable, understanding the dynamics of therapy is critical for optimal application of virotherapy in practice. Although mathematical models have been developed to understand the dynamics of tumor virotherapy, a scarcity of in vivo data has made difficult parametrization of these models. To tackle this problem, we studied the in vitro and in vivo spread of two oncolytic measles viruses that induce expression of the sodium iodide symporter (NIS) in cells. NIS expression enabled infected cells to concentrate radioactive isotopes that could be reproducibly and quantitatively imaged using SPECT/CT. We observed a strong linear relationship in vitro between infectious virus particles, viral N and NIS gene expression, and radioactive isotope uptake. In vivo radioisotope uptake was highly correlated with viral N and NIS gene expression. Similar expression patterns between viral N and NIS gene expression in vitro and in vivo implied that the oncolytic virus behaved similarly in both scenarios. Significant titers of viable virus were consistently isolated from tumors explanted from mice that had been injected with oncolytic measle viruses. We observed a weaker but positive in vivo relationship between radioisotope uptake and the viable virus titer recovered from tumors; this was likely due to anisotropies in the viral distribution in vivo. These data suggest that methods that enable quantitation of in vivo anisotropies are required for continuing development of oncolytic virotherapy.
Significance: These findings address a fundamental gap in our knowledge of oncolytic virotherapy by presenting technology that gives insight into the behavior of oncolytic viruses in vivo. Cancer Res; 78(20); 5992–6000. ©2018 AACR.
ErbB3 Targeting Enhances the Effects of MEK Inhibitor in Wild-Type BRAF/NRAS Melanoma
Authors: Capparelli Claudia , Purwin Timothy J. , Heilman Shea A. , Chervoneva Inna , McCue Peter A. , Berger Adam C. , Davies Michael A. , Gershenwald Jeffrey E. , Krepler Clemens , Aplin Andrew E. 
Published: August 2018

Abstract
MEK–ERK1/2 signaling is elevated in melanomas that are wild-type for both BRAF and NRAS (WT/WT), but patients are insensitive to MEK inhibitors. Stromal-derived growth factors may mediate resistance to targeted inhibitors, and optimizing the use of targeted inhibitors for patients with WT/WT melanoma is a clinical unmet need. Here, we studied adaptive responses to MEK inhibition in WT/WT cutaneous melanoma. The Cancer Genome Atlas data set and tumor microarray studies of WT/WT melanomas showed that high levels of neuregulin-1 (NRG1) were associated with stromal content and ErbB3 signaling. Of growth factors implicated in resistance to targeted inhibitors, NRG1 was effective at mediating resistance to MEK inhibitors in patient-derived WT/WT melanoma cells. Furthermore, ErbB3/ErbB2 signaling was adaptively upregulated following MEK inhibition. Patient-derived cancer-associated fibroblast studies demonstrated that stromal-derived NRG1 activated ErbB3/ErbB2 signaling and enhanced resistance to a MEK inhibitor. ErbB3- and ErbB2-neutralizing antibodies blocked the protective effects of NRG1 in vitro and cooperated with the MEK inhibitor to delay tumor growth in both cell line and patient-derived xenograft models. These results highlight tumor microenvironment regulation of targeted inhibitor resistance in WT/WT melanoma and provide a rationale for combining MEK inhibitors with anti-ErbB3/ErbB2 antibodies in patients with WT/WT cutaneous melanoma, for whom there are no effective targeted therapy options.
Significance: This work suggests a mechanism by which NRG1 regulates the sensitivity of WT NRAS/BRAF melanomas to MEK inhibitors and provides a rationale for combining MEK inhibitors with anti-ErbB2/ErbB3 antibodies in these tumors. Cancer Res; 78(19); 5680–93. ©2018 AACR.
Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis
Authors: Tomaszewski Michal R. , Gehrung Marcel , Joseph James , Quiros-Gonzalez Isabel , Disselhorst Jonathan A. , Bohndiek Sarah E. 
Published: August 2018

Abstract
Measuring the functional status of tumor vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatiotemporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that may overcome these challenges. By acquiring data at multiple wavelengths, OT can interrogate hemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found that vascular maturity led to changes in vascular function that affected tumor perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumor and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumor hypoxia quantified ex vivo. Our findings indicate that OT may offer a significant advantage for localized imaging of tumor response to vascular-targeted therapies when compared with existing clinical DCE methods.
Significance: Imaging biomarkers derived from optoacoustic tomography can be used as surrogate measures of tumor perfusion and hypoxia, potentially yielding rapid, multiparametric, and noninvasive cancer staging and therapeutic response monitoring in the clinic.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5980/F1.large.jpg. Cancer Res; 78(20); 5980–91. ©2018 AACR.
CDK4/6 Inhibitors: What Is the Best Cocktail?
Authors: Malumbres Marcos 
Published: August 2018

Abstract
CDK4/6 inhibitors have shown great potential in the new armamentarium against cancer. However, their effect as single agents is limited, and the hopes are on new combinatory strategies. Recent data suggest that inhibiting mTOR may significantly cooperate with cell-cycle arrest in a variety of cancers.
See related article by Song et al., p. 403
Impeding Circulating Tumor Cell Reseeding Decelerates Metastatic Progression and Potentiates Chemotherapy
Authors: Qian Chen , Worrede-Mahdi Asurayya , Shen Fei , DiNatale Anthony , Kaur Ramanpreet , Zhang Qiang , Cristofanilli Massimo , Meucci Olimpia , Fatatis Alessandro 
Published: August 2018

AbstractCirculating tumor cells (CTCs) are commonly detected in the systemic blood of patients with cancer with metastatic tumors. However, the mechanisms controlling the viability of cancer cells in blood and length of time spent in circulation, as well as their potential for generating additional tumors are still undefined. Here, it is demonstrated that CX3CR1, a chemokine receptor, drives reseeding of breast CTCs to multiple organs. Antagonizing this receptor dramatically impairs the progression of breast cancer cells in a relevant model of human metastatic disease, by affecting both tumor growth and numerical expansion. Notably, therapeutic targeting of CX3CR1 prolongs CTC permanence in the blood, both promoting their spontaneous demise by apoptosis and counteracting metastatic reseeding. These effects lead to containment of metastatic progression and extended survival. Finally, targeting CX3CR1 improves blood exposure of CTCs to doxorubicin and in combination with docetaxel shows synergistic effects in containing overall tumor burden.Implications:The current findings shed light on CTCs reseeding dynamics and support the development of CX3CR1 antagonism as a viable strategy to counteract metastatic progression.