bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organisational perspectives on addressing differential attainment in postgraduate medical education: a qualitative study in the UK
Authors: Woolf Katherine , Viney Rowena , Rich Antonia , Jayaweera Hirosha , Griffin Ann 
Published: March 2018

ObjectivesTo explore how representatives from organisations with responsibility for doctors in training perceive risks to the educational progression of UK medical graduates from black and minority ethnic groups (BME UKGs), and graduates of non-UK medical schools (international medical graduates (IMGs)). To identify the barriers to and facilitators of change.DesignQualitative semistructured individual and group interview study.SettingPostgraduate medical education in the UK.ParticipantsIndividuals with roles in examinations and/or curriculum design from UK medical Royal Colleges. Employees of NHS Employers.ResultsRepresentatives from 11 medical Royal Colleges (n=29) and NHS Employers (n=2) took part (55% medically qualified, 61% male, 71% white British/Irish, 23% Asian/Asian British, 6% missing ethnicity). Risks were perceived as significant, although more so for IMGs than for BME UKGs. Participants based significance ratings on evidence obtained largely through personal experience. A lack of evidence led to downgrading of significance. Participants were pessimistic about effecting change, two main barriers being sensitivities around race and the isolation of interventions. Participants felt that organisations should acknowledge problems, but felt concerned about being transparent without a solution; and talking about race with trainees was felt to be difficult. Participants mentioned 63 schemes aiming to address differential attainment, but these were typically local or specialty-specific, were not aimed at BME UKGs and were largely unevaluated. Participants felt that national change was needed, but only felt empowered to effect change locally or within their specialty.ConclusionsRepresentatives from organisations responsible for training doctors perceived the risks faced by BME UKGs and IMGs as significant but difficult to change. Strategies to help organisations address these risks include: increased openness to discussing race (including ethnic differences in attainment among UKGs); better sharing of information and resources nationally to empower organisations to effect change locally and within specialties; and evaluation of evidence-based interventions.
Is it feasible to conduct a randomised controlled trial of pretransplant exercise (prehabilitation) for patients with multiple myeloma awaiting autologous haematopoietic stem cell transplantation? Protocol for the PREeMPT study
Authors: Keen Carol , Skilbeck Julie , Ross Helen , Smith Lauren , Collins Karen , Dixey Joanne , Walters Stephen , Greenfield Diana M , Snowden John A , Mawson Susan 
Published: March 2018

IntroductionWhile myeloma is an incurable malignancy, developments in disease management have led to increased life expectancy in recent years. Treatment typically involves stem-cell transplantation. Increased survival rates equate to more patients living with the burden of both the disease and its treatment for increasing number of years, rendering myeloma a long-term condition.Evidence exists to demonstrate the benefits of exercise for patients recovering from stem-cell transplantation, and prehabilitation—exercise before treatment—has been shown to be effective in other disease areas. To date there has been no research into prehabilitation in patients with myeloma awaiting transplantation treatment.Our objective is to determine whether it is feasible to conduct a randomised controlled trial into pretransplant exercise for patients with multiple myeloma who are awaiting autologous stem-cell transplantation.Methods and analysisThis mixed methods study identifies patients with diagnosis of multiple myeloma who have been assigned to the autologous transplantation list and invites them to participate in six weekly sessions of individualised, supervised exercise while awaiting transplantation.Quantitative data to determine feasibility targets include rates of recruitment, adherence and adverse events, and outcome measures including 6 min walking distance test and quality of life.Qualitative interviews are undertaken with a purposive sample of patients to capture their experiences of the study and the intervention.Ethics and disseminationEthics committee approval has been obtained. Dissemination will be through open-access publications and presentations and will seek to reach multiprofessional bases as well as patients and carer groups, addressing the widespread interest in this area of research.Trial registration numberNCT03135925; Pre-results.
Making medical decisions for an incompetent older adult when both a proxy and an advance directive are available: which is more likely to reflect the older adult’s preferences?
Authors: Bravo Gina , Sene Modou , Arcand Marcel 
Published: March 2018

ObjectivesTo investigate which of two sources of information about an older adult’s wishes—choices made in an advance directive or proxy’s opinion—provides better insight into the older adult’s preferences measured in hypothetical clinical situations involving decisional incapacity.MethodsSecondary analyses of data collected from 157 community-dwelling, decisionally competent adults aged 70 years and over who attended a group information session on advance directives with their proxy. Older adults were invited to complete a directive introduced during the session, designed to express healthcare preferences. An average of 3 months later, older adults were asked during an interview whether they would want to receive each of four medical interventions and what their goals of care would be should they develop one of three sudden health events, assuming that they had severe dementia. Proxies were asked to guess the older adult’s answers in each of the seven scenarios.ResultsEighty per cent of the older adults completed the directive. Choices they made in the directive were more in line with the preferences they stated during the interview than were their proxies’ guesses at their answers. However, concordance was relatively low, with percentages of agreement ranging from 43% to 83% across scenarios.ConclusionsFindings suggest that a directive might provide better insight into a person’s wishes than the person’s proxy, although neither source is perfect. A multifaceted decision-making model that includes both sources of information might better serve the interests of older adults who have lost the capacity to make decisions on their own.Trial registration numberISRCTN89993391; Post-results.
Resuscitation decisions at the end of life: medical views and the juridification of practice
Authors: MacCormick Fiona MA , Emmett Charlotte , Paes Paul , Hughes Julian C 
Published: March 2018

BackgroundConcerns about decision making related to resuscitation have led to two important challenges in the courts resulting in new legal precedents for decision-making practice. Systematic research investigating the experiences of doctors involved in decisions about resuscitation in light of the recent changes in law remains lacking.AimTo analyse the practice of resuscitation decision making on hospital wards from the perspectives of doctors.DesignThe data presented in this paper were collected as part of a wider research study of end-of-life care in an acute hospital setting. Data collection comprised ethnographic non-participant observation on two acute hospital wards and individual interviews with patients, relatives and healthcare professionals caring for patients thought to be approaching the end of life. Data were analysed using a constructivist grounded theory approach.ResultsDiscussions and decision making about resuscitation present many challenges for those involved on acute medical wards. The data highlight the potential for multiple interpretations of legal precedents, creating misunderstandings that may impact patient care in less positive ways.ConclusionsThis paper provides unique insights into how doctors respond to the changing medico-legal culture and the subsequent effects on patient care. It demonstrates how the juridification of medical practice can occur. It highlights the potential benefit of a structure to support clinicians, patients and relatives in discussing and navigating decisions around care at the end of life in line with the patient’s wishes and preferences. Recommendations for future research are made and legal ramifications are discussed.
Management of tandem occlusions in acute ischemic stroke – intracranial versus extracranial first and extracranial stenting versus angioplasty alone: a systematic review and meta-analysis
Authors: Wilson Mitchell P , Murad Mohammad H , Krings Timo , Pereira Vitor M , O’Kelly Cian , Rempel Jeremy , Hilditch Christopher A , Brinjikji Waleed 
Published: March 2018

BackgroundOptimal technical approaches of large-vessel anterior circulation acute ischemic strokes with concomitant extracranial internal carotid artery tandem occlusions is controversial.PurposeThis systematic review and meta-analysis evaluates: the overall outcomes of patients with tandem occlusions treated with second-generation mechanical thrombectomy devices; differences in outcomes of extracranial versus intracranial first approaches; and differences in outcomes of extracranial stenting at time of procedure versus angioplasty alone.MethodsMEDLINE, EMBASE, and the Web of Science was searched through September 2017 for studies evaluating patients presenting with acute tandem occlusions of the extracranial ICA and intracranial ICA, and/or proximal MCA treated with second-generation mechanical thrombectomy devices. Outcomes were pooled across studies using the random-effects model and expressed as cumulative incidence (event rate) and 95% CI.ResultsThirty-three studies were included in analysis. Overall mRS≤0–2 at 90 days was 47% (95% CI 42% to 51%). No statistical difference was seen in 90-day mRS≤0–2 for patients treated with extracranial versus intracranial first approaches, 53% (95% CI 44% to 61%) vs 49% (95% CI 44% to 57%) (P=0.58). No statistical difference was seen in 90-day mRS≤0–2 for patients treated with extracranial stenting versus angioplasty alone, 49% (95% CI 42% to 56%) vs 49% (95% CI 33% to 65%) (P=0.39). No other statistical differences in outcome or safety were identified.ConclusionsNearly half of all tandem occlusion patients treated with mechanical thrombectomy have good neurological outcomes. No statistical differences in outcome are identified between extracranial first versus intracranial first approaches, nor extracranial stenting versus angioplasty alone.
Identification of monosodium urate crystal deposits in patients with asymptomatic hyperuricemia using dual-energy CT
Authors: Wang Penny , Smith Stacy E , Garg Rajesh , Lu Fengxin , Wohlfahrt Alyssa , Campos Anarosa , Vanni Kathleen , Yu Zhi , Solomon Daniel H , Kim Seoyoung C 
Published: March 2018

ObjectivesDual-energy CT (DECT) scan is a sensitive and specific tool used to visualise and quantify monosodium urate (MSU) crystal deposits in the joints. Few studies have examined MSU crystal deposits in patients with asymptomatic hyperuricemia (ie, hyperuricemia in the absence of gout) using DECT.MethodsWe conducted a prospective, non-interventional cross-sectional study to detect MSU crystal deposits on DECT scans among patients with asymptomatic hyperuricemia. We also examined patient factors associated with subclinical MSU crystal deposits. Out of 130 subjects aged ≥40 years with metabolic syndrome screened for serum uric acid (sUA) levels ≥6.5 mg/dL, 46 underwent a foot/ankle DECT scan.ResultsThe mean age of the study participants was 62 (±8) years, 41% were men and the mean sUA level was 7.8 (±1.0) mg/dL. Seven (15%) of 46 patients had MSU crystal deposits on DECT with a mean total volume of 0.13 (±0.14) cm3. In the univariable logistic regression analysis, older age had a significant association with presence of MSU crystal deposits (OR 1.20, 95% CI 1.03 to 1.39), but sUA did not (OR 1.36, 95% CI 0.63 to 2.95). In the univariable analysis, sUA levels showed a trend towards a modest linear association (β=0.11, P=0.09) with total volume of MSU crystal deposits.ConclusionsFifteen per cent of patients with asymptomatic hyperuricemia had subclinical MSU crystal deposits on foot/ankle DECT scans. Older age, but not sUA, was significantly associated with presence of subclinical MSU crystal deposits among patients with asymptomatic hyperuricemia. Clinical significance of these subclinical MSU crystal deposits needs to be determined.
Registry report on prediction by Pocock cardiovascular score of cerebral microemboli acutely following carotid endarterectomy
Authors: Saedon Mahmud , Saratzis Athanasios , Lee Rachel W S , Hutchinson Charles E , Imray Christopher H E , Singer Donald R J 
Published: March 2018

BackgroundCerebral microemboli may lead to ischaemic neurological complications after carotid endarterectomy (CEA). The association between classical cardiovascular risk factors and acute cerebral microemboli following carotid surgery has not been studied. The aim of this study was to explore whether an established cardiovascular risk score (Pocock score) predicts the presence of cerebral microemboli acutely after CEA.Subjects and methodsPocock scores were assessed for the 670 patients from the Carotid Surgery Registry (age 71±1 (SEM) years, 474 (71%) male, 652 (97%) Caucasian) managed from January 2002 to December 2012 in the Regional Vascular Centre at University Hospitals Coventry and Warwickshire NHS Trust, which serves a population of 950 000. CEA was undertaken in 474 (71%) patients for symptomatic carotid stenosis and in 196 (25%) asymptomatic patients during the same period. 74% of patients were hypertensive, 71% were smokers and 49% had hypercholesterolaemia.ResultsA high Pocock score (≥2.3%) was significantly associated with evidence of cerebral microemboli acutely following CEA (P=0.039, Mann-Whitney (MW) test). A Pocock score (≥2.3%) did not predict patients who required additional antiplatelet therapy (microemboli signal (MES) rate >50 hour-1: P=0.164, MW test). Receiver operating characteristic analysis also showed that the Pocock score predicts acute postoperative microemboli (area under the curve (AUC) 0.546, 95% CI 0.502 to 0.590, P=0.039) but not a high rate of postoperative microemboli (MES >50 hour−1: AUC 0.546, 95% CI 0.482 to 0.610, P=0.164). A Pocock score ≥2.3% showed a sensitivity of 74% for the presence of acute postoperative cerebral microemboli. A Pocock score ≥2.3% also showed a sensitivity of 77% and a negative predictive value of 90% for patients who developed a high microembolic rate >50 hour−1after carotid surgery.ConclusionThese findings demonstrate that the Pocock score could be used as a clinical tool to identify patients at high risk of developing acute postoperative microemboli.
The waning of the WIMP? A review of models, searches, and constraints
Authors: Arcadi Giorgio , Dutra Maíra , Ghosh Pradipta , Lindner Manfred , Mambrini Yann , Pierre Mathias , Profumo Stefano , Queiroz Farinaldo S. 
Published: March 2018

Abstract
Weakly Interacting Massive Particles (WIMPs) are among the best-motivated dark matter candidates. No conclusive signal, despite an extensive search program that combines, often in a complementary way, direct, indirect, and collider probes, has been detected so far. This situation might change in near future due to the advent of one/multi-TON Direct Detection experiments. We thus, find it timely to provide a review of the WIMP paradigm with focus on a few models which can be probed at best by these facilities. Collider and Indirect Detection, nevertheless, will not be neglected when they represent a complementary probe.
Fault system evolution in the Baltic Sea area west of Rügen, NE Germany
Authors: Deutschmann André , Meschede Martin , Obst Karsten 
Published: March 2018

Abstract
Based on reprocessed offshore seismic lines acquired during oil and gas exploration in the 1980s, we reconstruct the formation and reactivation of major fault systems in the southern Baltic Sea area since the late Paleozoic. The geological evolution of different crustal blocks from the Caledonian Avalonia–Baltica collision until the Late Cretaceous–Paleogene inversion tectonics is also examined. The detected fault systems occur in the northern part of the Trans-European Suture Zone (TESZ) and belong either to the late Paleozoic Tornquist Fan or to the complex Western Pomeranian Fault System (WPFS) generated during Mesozoic extensional movements. While the NW–SE-trending deep Wiek Fault separates the Arkona High from the Middle Rügen Block, the NNW–SSE-trending Agricola Fault demarcates the Middle Rügen Block to the Falster Block in the west. Together with the Plantagenet Fault and numerous younger faults in the Mesozoic cover, it forms the Agricola Fault System. Furthermore, structural analyses of the Prerow Fault Zone above the Prerow salt pillow and the Werre Fault Zone crossing the Grimmen High indicate a complex fault history.
Functional Toll-like Receptor 4 Overexpression in Papillary Thyroid Cancer by MAPK/ERK–Induced ETS1 Transcriptional Activity
Authors: Peyret Victoria , Nazar Magalí , Martín Mariano , Quintar Amado A. , Fernandez Elmer A. , Geysels Romina C. , Fuziwara Cesar S. , Montesinos María M. , Maldonado Cristina A. , Santisteban Pilar , Kimura Edna T. , Pellizas Claudia G. , Nicola Juan P. , Masini-Repiso Ana M. 
Published: March 2018

Abstract
Emerging evidence suggests that unregulated Toll-like receptor (TLR) signaling promotes tumor survival signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillary thyroid carcinomas (PTC) mainly harboring the BRAFV600E mutation was studied. TLR4 was overexpressed in PTC compared with nonneoplastic thyroid tissue. Moreover, paired clinical specimens of primary PTC and its lymph node metastasis showed a significant upregulation of TLR4 levels in the metastatic tissues. In agreement, conditional BRAFV600E expression in normal rat thyroid cells and mouse thyroid tissue upregulated TLR4 expression levels. Furthermore, functional TLR4 expression was demonstrated in PTC cells by increased NF-κB transcriptional activity in response to the exogenous TLR4-agonist lipopolysaccharide. Of note, The Cancer Genome Atlas data analysis revealed that BRAFV600E-positive tumors with high TLR4 expression were associated with shorter disease-free survival. Transcriptomic data analysis indicated a positive correlation between TLR4 expression levels and MAPK/ERK signaling activation. Consistently, chemical blockade of MAPK/ERK signaling abrogated BRAFV600E-induced TLR4 expression. A detailed study of the TLR4 promoter revealed a critical MAPK/ERK–sensitive Ets-binding site involved in BRAFV600E responsiveness. Subsequent investigation revealed that the Ets-binding factor ETS1 is critical for BRAFV600E-induced MAPK/ERK signaling-dependent TLR4 gene expression. Together, these data indicate that functional TLR4 overexpression in PTCs is a consequence of thyroid tumor-oncogenic driver dysregulation of MAPK/ERK/ETS1 signaling.
Implications: Considering the participation of aberrant NF-κB signaling activation in the promotion of thyroid tumor growth and the association of high TLR4 expression with more aggressive tumors, this study suggests a prooncogenic potential of TLR4 downstream signaling in thyroid tumorigenesis. Mol Cancer Res; 16(5); 833–45. ©2018 AACR.
Targeting CREB Pathway Suppresses Small Cell Lung Cancer
Authors: Xia Yifeng , Zhan Cheng , Feng Mingxiang , Leblanc Mathias , Ke Eugene , Yeddula Narayana , Verma Inder M. 
Published: March 2018

Abstract
Small cell lung cancer (SCLC) is the most deadly subtype of lung cancer due to its dismal prognosis. We have developed a lentiviral vector-mediated SCLC mouse model and have explored the role of both the NF-κB and CREB families of transcription factors in this model. Surprisingly, induction of NF-κB activity, which promotes tumor progression in many cancer types including non–small cell lung carcinoma (NSCLC), is dispensable in SCLC. Instead, suppression of NF-κB activity in SCLC tumors moderately accelerated tumor development. Examination of gene expression signatures of both mouse and human SCLC tumors revealed overall low NF-κB but high CREB activity. Blocking CREB activation by a dominant-negative form of PKA (dnPKA) completely abolished the development of SCLC. Similarly, expression of dnPKA or treatment with PKA inhibitor H89 greatly reduced the growth of SCLC tumors in syngeneic transplantation models. Altogether, our results strongly suggest that targeting CREB is a promising therapeutic strategy against SCLC.
Implications: Activity of the transcription factor CREB is elevated in SCLC tumors, which helps to maintain its neuroendocrine signature and cell proliferation. Our results highlight the importance of targeting the CREB pathway to develop new therapeutics to combat SCLC. Mol Cancer Res; 16(5); 825–32. ©2018 AACR.
Molecular Response to Neoadjuvant Chemotherapy in High-Grade Serous Ovarian Carcinoma
Authors: Arend Rebecca C. , Londoño Angelina I. , Montgomery Allison M. , Smith Haller J. , Dobbin Zachary C. , Katre Ashwini A. , Martinez Alba , Yang Eddy S. , Alvarez Ronald D. , Huh Warner K. , Bevis Kerri S. , Straughn J. Michael , Estes Jacob M. , Novak Lea , Crossman David K. , Cooper Sara J. , Landen Charles N. , Leath Charles A. 
Published: March 2018

Abstract
While high-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants [by DNA next-generation sequencing (NGS) using a 50 gene Ion Torrent panel] and gene expression (using the NanoString PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n = 14) to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted, whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways.
Implications: Gene expression profiles at the time of interval debulking provide additional genetic information that could help impact treatment decisions after NACT; although, continued collection and analysis of matched tumor and cfDNA from multiple time points are needed to determine the role of cfDNA in the management of HGSOC. Mol Cancer Res; 16(5); 813–24. ©2018 AACR.