bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors associated with Richter’s transformation in patients with chronic lymphocytic leukaemia: protocol for a retrospective population-based cohort study
Authors: Hleuhel Mariam Hussein , Ben-Dali Yasmin , Da Cunha-Bang Caspar , Brieghel Christian , Clasen-Linde Erik , Niemann Carsten Utoft , Andersen Michael Asger 
Published: March 2019

IntroductionRichter’s transformation (RT) refers to the development of an aggressive lymphoma in patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma. Studies have shown that 2–10% of patients with CLL develop RT including diffuse large B-cell lymphoma (DLBCL) and less common Hodgkin lymphoma (HL). This study aims to assess the risk factors for RT of CLL in a nationwide cohort. Additionally, we want to examine prognostic factors in patients with RT. These findings may guide management of treated as well as untreated patients with CLL in the risk of RT.MethodsClinical data for patients diagnosed with CLL between 2008 and 2016 will be retrieved from the Danish National CLL registry (DCLLR). Using the Danish unique person identification number, clinical data will be merged with histologically verified DLBCL and/or HL diagnoses retrieved from the Danish National Pathology Data Bank. This will ensure complete follow-up for all patients.The DCLLR includes data from more than 4000 patients with CLL ensuring a median follow-up of 3 years. With the reported incidences (2-10%) of RT, we expect to identify 80–200 CLL patients with RT enabling analysis of overall survival following RT. From time of CLL diagnosis, estimates of cumulative incidence of RT will be calculated using the Aalen-Johansen estimator. From time of RT diagnosis, survival analysis will be performed by Kaplan-Meier method. Cox proportional hazards models will be used for multivariable survival analysis.Ethics and disseminationApprovals for data collection and analysis was obtained from the Danish Data Protection Agency and the Danish Health Authorities. All data will be managed confidentially according to guidelines and legislation. The dissemination will include a publication of scientific papers and/or presentations of the study findings at international conferences.
Code sets for respiratory symptoms in electronic health records research: a systematic review protocol
Authors: Jayatunga Wikum , Stone Philip , Aldridge Robert W , Quint Jennifer K , George Julie 
Published: March 2019

IntroductionAsthma and chronic obstructive pulmonary disease (COPD) are common respiratory conditions, which result in significant morbidity worldwide. These conditions are associated with a range of non-specific symptoms, which in themselves are a target for health research. Such research is increasingly being conducted using electronic health records (EHRs), but computable phenotype definitions, in the form of code sets or code lists, are required to extract structured data from these large routine databases in a systematic and reproducible way. The aim of this protocol is to specify a systematic review to identify code sets for respiratory symptoms in EHRs research.Methods and analysisMEDLINE and Embase databases will be searched using terms relating to EHRs, respiratory symptoms and use of code sets. The search will cover all English-language studies in these databases between January 1990 and December 2017. Two reviewers will independently screen identified studies for inclusion, and key data will be extracted into a uniform table, facilitating cross-comparison of codes used. Disagreements between the reviewers will be adjudicated by a third reviewer. This protocol has been produced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines.Ethics and disseminationAs a review of previously published studies, no ethical approval is required. The results of this review will be submitted to a peer-reviewed journal for publication and can be used in future research into respiratory symptoms that uses electronic healthcare databases.PROSPERO registration numberCRD42018100830.
Support for, and perceived effectiveness of, the UK soft drinks industry levy among UK adults: cross-sectional analysis of the International Food Policy Study
Authors: Pell David , Penney Tarra , Hammond David , Vanderlee Lana , White Martin , Adams Jean 
Published: March 2019

ObjectivesTo answer four questions: What are attitudes, knowledge and social norms around sugar-sweetened beverages (SSBs)? What are current levels of trust in messages on SSBs? What is current support for, and perceived effectiveness of, the UK soft drinks industry levy (SDIL)? What is the association between attitudes, knowledge, social norms, trust, SSB consumption and sociodemographic factors; and support for, and perceived effectiveness of, the SDIL?DesignCross-sectional online survey.SettingUK.ParticipantsUK respondents to the 2017 International Food Policy Study aged 18–64 years who provided information on all variables of interest (n=3104).Outcome measuresSelf-reported perceived effectiveness of, and support for, the SDIL.ResultsMost participants supported the SDIL (70%), believed it would be effective (71%), had a positive attitude to SSBs (62%), had knowledge of the link between SSBs and obesity (90%), and trusted messages from health experts (61%), but not those from the food and beverage industry (73%). Nearly half (46%) had negative social norms about drinking SSBs. In adjusted models, older age, non-consumption of SSBs, social norms to not drinks SSBs, knowledge of the link between SSBs and obesity and trust in health expert messages were associated with greater support for the SDIL, whereas having dependent children and trusting messages from the food and beverage industry were associated with less support. In adjusted models, older age was associated with lower perceived effectiveness of the SDIL, whereas social norms to not drink SSBs, negative attitudes to SSBs and trusting messages from health experts and the food and beverage industry were associated with greater perceived effectiveness.ConclusionsThere was strong support for the SDIL and belief that it would be effective. Those with more ‘public health’ orientated norms and trust were generally more likely to support the SDIL or believe that it would be effective.
Sharing learning from hospital trusts on a journey of quality improvement
Authors: Thorne Iona , Cox Jeremy , Baker Edward 
Published: March 2019

BackgroundQuality improvement (QI) has been shown to deliver better patient outcomes, and improved operational, organisational and financial performance when led effectively and supported by organisational systems and training. Surveys of staff and patient satisfaction also show positive effects. In many trusts that Care Quality Commission (CQC) has rated as outstanding, a culture of QI has been embedded throughout the organisation.ObjectivesWe wanted to hear trusts’ experiences of using QI as a systematic approach to improving service quality, efficiency and morale, and share learning from these organisations to drive further improvement to quality of care.MethodsUsing CQC’s comprehensive inspection programme of all healthcare providers nationally, we identified 19 trusts for inclusion and carried out an in-depth review of their improvement journeys.ResultsWe found that commitment from the board and senior leadership is crucial to ensuring success on the QI journey, modelling effective leadership behaviours that enable all staff to deliver improvement. These organisations have a systematic approach to QI, using a consistent model, anchored in a systems perspective, and often across a health system. The model of improvement requires leaders of all backgrounds and frontline staff to work together in improvement, and can help to break down barriers between managers and clinicians, and providers and patients, so there is a shared purpose to deliver better care to patients.ConclusionsQI is not a magic bullet, but is an important factor in the evolution of an organisation from a traditional ‘command and control’ form of management towards higher performing approaches to the design and management of work.
What are the motivations and barriers to pre-exposure prophylaxis (PrEP) use among black men who have sex with men aged 18–45 in London? Results from a qualitative study
Authors: Witzel T Charles , Nutland Will , Bourne Adam 
Published: March 2019

BackgroundBlack men who have sex with men (BMSM) have higher HIV incidence and prevalence when compared with other men who have sex with men, despite similar risk profiles. New prevention technologies, including pre-exposure prophylaxis (PrEP), may be effective in responding to these inequalities, provided they are appropriately targeted and acceptable to their intended beneficiaries. This study aims to understand the motivations and barriers of BMSM aged 18–45 to PrEP uptake.MethodsTwenty-five BMSM recruited through geolocation social networking apps took part in in-depth interviews between April and August 2016. Intersectionality theory was used as an organising principle. Interviews were transcribed verbatim and analysed using a thematic framework analysis.ResultsFor BMSM with heterogeneous social groups, discussions about sexual health were challenging because of the intersection of ethnic background, family history and religion. This limited conversations about PrEP to gay male friends who often held stigmatising views of condomless anal intercourse. BMSM reported exclusion from gay male spaces (online and offline) which could serve to restrict exposure to PrEP messages. Stereotypes of BMSM intersected with negative conceptions of PrEP users, limiting acknowledgement of PrEP candidacy. For those who had attempted to or successfully accessed it, PrEP was framed as a strategy to mitigate risk and to guard against further stigma associated with HIV infection.DiscussionBMSM operate within a complex set of circumstances related to the intersection of their sexual, ethnic, cultural and religious identities, which shape PrEP acceptability. Interventions which seek to facilitate uptake in this group must be attentive to these. Health promotion and clinical services could seek to facilitate nuanced discussions about the merits of PrEP for those at frequent risk, perhaps while also providing publicly visible PrEP role models for BMSM and other marginalised groups.
Solar energy harvesting with ultra-broadband metamaterial absorber
Authors: Bagmanci Mehmet , Karaaslan Muharrem , Unal Emin , Akgol Oguzhan , Bakır Mehmet , Sabah Cumali 
Published: March 2019

In this study, a novel metamaterial absorber (MA) is designed and numerically demonstrated for solar energy harvesting. The structure is composed of three layers with different thicknesses. The interactions of three layers bring about the plasmonic resonances. Although the main operation frequency of the structure is chosen between 430 and 770 THz, which is the visible light regime, the proposed structure is also investigated in the ultra-violet (UV) region. One can see from the results that the proposed structure carries nearly perfect absorption capacity that is more than 91% at the whole visible light spectrum. The proposed structure even has the absorption capacity of 99% between 556 and 657 THz. In addition, the designed MA is also investigated in terms of its polarization and angle independency. Results show that the proposed structure is independent from the polarization and incident angles. Lastly, the designed structure can be considered to be used in solar energy applications as a harvester since it has an ultra-broadband absorption characteristic in visible light regime.
A Multiband, Spectrally-Efficient Impulse Radio Transmitter Design with Low-Complexity CMOS Pulse Generator for IEEE 802.15.4a Application
Authors: Saoudi Hanen , Ghariani Hamadi , Lahiani Mongi 
Published: March 2019

A novel multiband impulse radio ultra-wideband (MB-IR-UWB) transmitter with an energy-efficient and low-complexity pulse generator design technique compliant with the IEEE 802.15.4a standard is investigated in this paper. This transmitter is made up of a new differential narrow triangular pulse generator, a new multiband voltage-controlled oscillator (VCO), an active mixer and a variable-gain power amplifier (PA). It operates at 14 UWB bands and generates an output signal with the duration of 3[Formula: see text]ns, more than 500[Formula: see text]MHz of channel bandwidth and more than 20[Formula: see text]dB of sidelobe suppression, while achieving an average energy efficiency of 51.36 pJ/pulse from 1.4-V supply. Improving spectral flexibility and worldwide compliance is the major contribution brought by this paper to make this circuit as a multifunction wireless device well suited for low-cost, low-power multiband applications.
Epigenetic Regulation of the PTEN–AKT–RAC1 Axis by G9a Is Critical for Tumor Growth in Alveolar Rhabdomyosarcoma
Authors: Bhat Akshay V. , Palanichamy Kala Monica , Rao Vinay Kumar , Pignata Luca , Lim Huey Jin , Suriyamurthy Sudha , Chang Kenneth T. , Lee Victor K. , Guccione Ernesto , Taneja Reshma 
Published: March 2019

Abstract

Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer with poor prognosis. As transient and stable modifications to chromatin have emerged as critical mechanisms in oncogenic signaling, efforts to target epigenetic modifiers as a therapeutic strategy have accelerated in recent years. To identify chromatin modifiers that sustain tumor growth, we performed an epigenetic screen and found that inhibition of lysine methyltransferase G9a significantly affected the viability of ARMS cell lines. Targeting expression or activity of G9a reduced cellular proliferation and motility in vitro and tumor growth in vivo. Transcriptome and chromatin immunoprecipitation–sequencing analysis provided mechanistic evidence that the tumor-suppressor PTEN was a direct target gene of G9a. G9a repressed PTEN expression in a methyltransferase activity–dependent manner, resulting in increased AKT and RAC1 activity. Re-expression of constitutively active RAC1 in G9a-deficient tumor cells restored oncogenic phenotypes, demonstrating its critical functions downstream of G9a. Collectively, our study provides evidence for a G9a-dependent epigenetic program that regulates tumor growth and suggests targeting G9a as a therapeutic strategy in ARMS.

Significance:
These findings demonstrate that RAC1 is an effector of G9a oncogenic functions and highlight the potential of G9a inhibitors in the treatment of ARMS.
Recruiting for an Online Survey through Social Media: Testing Variations in Messaging, Compensation, and Platform
Authors: Selvan P , Kearney M , Massey PM , Leader AE 
Published: March 2019

Abstract
To test three recruitment strategies for parents on social media (Facebook and Twitter) to complete a brief survey about the human papillomavirus (HPV) vaccine. Methods: We created three campaigns with ads on Facebook and promoted tweets on Twitter that invited parents of children ages 9–15 to complete a brief survey about the HPV vaccine. Iterative, yet varied, campaigns were conducted to determine the ideal social media platform, compensation amount, and messaging. Ads depicted vaccine-eligible children (11–12 years of age) of various ethnicities. Ad messaging was adapted from social media toolkits at the CDC and the HPV Roundtable. Parents who clicked on our ad were first screened for eligibility. Those who were eligible then completed a 20-item survey via Qualtrics that included questions about HPV, the vaccine, and social media use. Survey compensation was either $5 or $10. At the end of the survey, we provided information about HPV and the vaccine. The campaign was available in English and Spanish. Results: The first campaign was launched on both Facebook and Twitter and offered $5 compensation. The Facebook component yielded 18,527 impressions; two adults were confirmed eligible by the screener and both completed the survey (100% screener to completion rate). Cost per survey was $349.45. The Twitter component received 143,661 impressions and yielded 18 completed surveys, with a screener to completion rate of 26% and a cost of $42.99 per survey. For the second campaign, we dropped Facebook and focused solely on Twitter, offering $10 compensation. We received 50,475 impressions that yielded 55 completed surveys (screener to completion rate = 71%) costing $4.78 each. The final campaign tested simpler messaging on Twitter with $10 compensation, and received 8,897 impressions, 38 survey completions (screener to completion rate = 88%), and cost $1.19 per survey. Conclusions: While Facebook is widely used among Americans, our findings may suggest that Twitter is more engaging and cost-effective. Recent Facebook policy changes may explain the differences seen in cost and survey completion. Understanding the reach and effectiveness of the different platforms will help ensure the success of an intervention using social media.
Are Skeletal Muscle Mass and Density Associated with Fatigue In Early-Stage Colorectal Cancer Patients?
Authors: Winkels RM , van Baar H , Beijer S , Kampman E 
Published: March 2019

Abstract
Both low skeletal muscle mass and low radiographic muscle density are associated with higher complication rates after surgery for colorectal cancer and with worse survival rates although data are not fully consistent. Whether skeletal muscle mass and density are also associated with patient-reported outcomes, such as fatigue, is less well studied. We hypothesized that low skeletal muscle mass and density may be associated with fatigue in early stage colorectal cancer (CRC) patients. Methods: Within a prospective cohort of 594 early-stage (stage I-III) CRC patients, we collected information on fatigue using the EORTC QLQ-C30 questionnaire 6 months after diagnosis; fatigue was defined as a score of &gt;39 based on literature. Skeletal muscle mass and -density were assessed using pre-operative Computed Tomography (CT) images. Low muscle mass and -density were identified using previously determined cut- off values. Cox regression models were used to calculate prevalence ratios (PRs). All PRs were adjusted for age, sex, stage of disease. Results: The average age of the study population was 65.7 ± 9.0; 37% were women and 67% of the patients had a tumor located in the colon. Low muscle mass was present in 26% of the patients and low muscle density in 25%; 26% of patients had fatigue. Low muscle mass was not associated with prevalence of fatigue (PR for low versus normal muscle mass 0.83 (95%CI 0.56–1.24). Low muscle density was associated with higher prevalence of fatigue: PR for low versus normal muscle density 1.94 (95% CI 1.34–2.81). Conclusion: Among colorectal cancer patients, low skeletal muscle density at diagnosis - indicative for fat infiltration in the muscle- was associated with a higher prevalence of fatigue six months after diagnosis. Future studies should assess how lifestyle interventions can help to prevent or decrease fatigue, and should further clarify whether there is a causal link between fat infiltration in the muscle and fatigue.
Neddylation Inactivation Facilitates FOXO3a Nuclear Export to Suppress Estrogen Receptor Transcription and Improve Fulvestrant Sensitivity
Authors: Jia Xiaoqing , Li Chunjie , Li Lihui , Liu Xiaoli , Zhou Lisha , Zhang Wenjuan , Ni Shuaishuai , Lu Yun , Chen Li , Jeong Lak Shin , Yu Jinha , Zhang Yingjian , Zhang Jianping , He Simin , Hu Xin , Sun Hefen , Yu Keda , Liu Guangyu , Zhao Hu , Zhang Yanmei , Jia Lijun , Shao Zhi-Ming 
Published: March 2019

Abstract

Purpose:
How the neddylation pathway functions in breast tumor and regulation of estrogen receptor (ER) expression is rarely reported. The purpose of this study was to identify the role of neddylation in breast cancer and ER expression, and further explore the underlying mechanisms.

Experimental Design:
Expression patterns of nedd8-activating enzyme (NAE) and nedd8, two key proteins in the neddylation pathway, were examined in human breast specimens. ER-α expression was investigated using animal 18F-FES-PET/CT and immunoblotting upon NAE inhibitor MLN4924 treatment. Chromatin immunoprecipitation assay, luciferase reporter promoter assay, and the CRISPR-Cas9 system were used to elucidate the mechanism of ER-α regulation by MLN4924. The ER-positive breast cancer mouse model was used to determine the synergetic effect of MLN4924 and fulvestrant on tumor growth. All statistical tests were two-sided.

Results:
Both NAE1 and nedd8 expressions were higher in the ER-positive subgroup. Higher expressions of NAE1 and nedd8 indicated poorer prognosis. Importantly, ER-α expression was significantly downregulated upon MLN4924 treatment in vitro and in vivo. Mechanistically, MLN4924 treatment delayed serum and glucocorticoid-induced protein kinase (SGK) degradation and induced Forkhead box O3a (FOXO3a) nuclear export as well as decreased binding to the ESR1 promoter. Importantly, MLN4924 single or synergized with fulvestrant significantly suppressed the growth of ER-positive breast cancer in vitro and in vivo.

Conclusions:
Our proof-of-principle study determines the activation of neddylation in breast tumor tissues for the first time and reveals a new ER-α regulatory mechanism, as well as further explores an effective approach to improve fulvestrant sensitivity through a neddylation inactivation combination.
The Immune Subtypes and Landscape of Squamous Cell Carcinoma
Authors: Li Bailiang , Cui Yi , Nambiar Dhanya K. , Sunwoo John B. , Li Ruijiang 
Published: March 2019

Abstract

Purpose:
To identify immune subtypes and investigate the immune landscape of squamous cell carcinomas (SCC), which share common etiology and histologic features.

Experimental Design:
Based on the immune gene expression profiles of 1,368 patients with SCC in the Cancer Genome Atlas (TCGA), we used consensus clustering to identify robust clusters of patients and assessed their reproducibility in an independent pan-SCC cohort of 938 patients. We further applied graph structure learning-based dimensionality reduction to the immune profiles to visualize the distribution of individual patients.

Results:
We identified and independently validated six reproducible immune subtypes associated with distinct molecular characteristics and clinical outcomes. An immune-cold subtype had the least amount of lymphocyte infiltration and a high level of aneuploidy, and these patients had the worst prognosis. By contrast, an immune-hot subtype demonstrated the highest infiltration of CD8+ T cells, activated NK cells, and elevated IFNγ response. Accordingly, these patients had the best prognosis. A third subtype was dominated by M2-polarized macrophages with potent immune-suppressive factors such as TGFβ signaling and reactive stroma, and these patients had relatively inferior prognosis. Other subtypes showed more diverse immunologic features with intermediate prognoses. Finally, our analysis revealed a complex immune landscape consisting of both discrete clusters and continuous spectrum.

Conclusions:
This study provides a conceptual framework to understand the tumor immune microenvironment of SCCs. Future work is needed to evaluate its relevance in the design of combination treatment strategies and guiding optimal selection of patients for immunotherapy.