bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed spontaneous hepatitis C virus elimination in a renal transplant patient following graft rejection
Authors: Mori Ubaldini Francesca , Stratta Robert J. , Nunez Marina 
Published: March 2019

AbstractWhile elimination of the hepatitis C virus (HCV) following acute infection is not uncommon, spontaneous clearance once the infection becomes chronic is extremely rare. The mechanisms involved in the clearance of chronic HCV infection without intervening antiviral therapy are not well known. Herein we describe a case of a renal transplant recipient who acquired HCV infection while immunosuppressed, experienced a rapid histological progression, and thereafter cleared the virus spontaneously long after withdrawal of immunosuppression following kidney graft rejection and failure. We review the literature and summarize the reports of spontaneous clearance of chronic HCV infection in various settings.
Clotting factor activity in fresh frozen plasma after thawing with a new radio wave thawing device
Authors: Kuta Piotr , Melling Nathaniel , Zimmermann Robert , Achenbach Susanne , Eckstein Reinhold , Strobel Julian 
Published: March 2019

BACKGROUNDMassive hemorrhage usually results in rapid need of blood products. Patients in need of fresh frozen plasma (FFP) might benefit from shorter thawing times using a novel radio wave device. So far, only one study on the prototype has been published. Activities of clotting factors after thawing FFP with the radio wave device and with a system using water cushions were compared. This is the first study analyzing the quality of FFP using the fully developed radio wave thawing device UFT100.STUDY DESIGN AND METHODSThirty FFP units were thawed with the UFT100 and the Plasmatherm machine. Various clotting factors and inhibitors were analyzed before freezing, immediately after thawing, and after a 48‐hour storage period at +4°C.RESULTSAfter thawing, all factor activities were within normal ranges regardless of the thawing procedure. We observed significant differences in nearly all clotting factor activities regarding time as effector, whereas thawing with the Plasmatherm machine led to a significant decrease (>10%) only in factor V activity compared to the UFT100.CONCLUSIONSImmediately after rapid thawing with the UFT100, all FFP units contained adequate coagulation factor activities to maintain hemostatic activity. The UFT100 does not deteriorate FFP quality compared to a conventional system. Regardless of the thawing system, the postthaw refrigerated storage caused a decrease in several clotting factors and inhibitors (factors V, VIII, and IX; von Willebrand factor activity; protein S and C activity) and a significant increase of factor XI.
Cost–utility analysis comparing hospital‐based intravenous immunoglobulin with home‐based subcutaneous immunoglobulin in patients with secondary immunodeficiency
Authors: Windegger Tanja M. , Nghiem Son , Nguyen Kim‐Huong , Fung Yoke‐Lin , Scuffham Paul A. 
Published: March 2019

Background and ObjectiveImmunoglobulin replacement therapy (IRT) is often used to support patients with primary immunodeficiency disease (PID) and secondary immunodeficiency disease (SID). Home‐based subcutaneous immunoglobulin (SCIg) is reported to be a cheaper and more efficient option compared to hospital‐based intravenous immunoglobulin (IVIg) for PID. In contrast, there is little information on the cost‐effectiveness of IRT in SID. However, patients who develop hypogammaglobulinaemia secondary to other conditions (SID) have different clinical aetiology compared to PID. This study assesses whether SCIg provides a good value‐for‐money treatment option in patients with secondary immunodeficiency disease (SID).MethodsA Markov cohort simulation model with six health states was used to compare cost‐effectiveness of IVIg with SCIg from a healthcare system perspective. The costs of treatment, infection and quality‐adjusted life years (QALYs) for IVIg and SCIg treatment options were modelled with a time horizon of 10 years and weekly cycles. Deterministic and probabilistic sensitivity analyses were performed around key parameters.ResultsThe cumulative cost for IVIg was A$151 511 and for SCIg A$144 296. The QALYs with IVIg were 3·07 and with SCIg 3·51. Based on the means, SCIg is the dominant strategy with better outcomes and at lower cost. The probabilistic sensitivity analysis shows that 88·3% of the 50 000 iterations fall below the nominated willingness to pay threshold of A$50 000 per QALY. Therefore, SCIg is a cost‐effective treatment option.ConclusionFor SID patients in Queensland (Australia), the home‐based SCIg treatment option provides better health outcomes and cost savings.
Accountability for funds for Nurturing Care: what can we measure?
Authors: Arregoces Leonardo , Hughes Rob , Milner Kate M , Ponce Hardy Victoria , Tann Cally , Upadhyay Arjun , Lawn Joy E 
Published: March 2019

BackgroundUnderstanding donor, government and out-of-pocket funding for early child development (ECD) is important for tracking progress. We aimed to estimate a baseline for the WHO, UNICEF and World Bank Nurturing Care Framework (NCF) with a special focus on childhood disability.MethodsTo estimate development assistance spending, the Organisation for Economic Cooperation and Development’s Creditor Reporting System (OECD-CRS) database was searched for 2007–2016, using key words derived from domains of the NCF (good health, nutrition and growth, responsive caregiving, security and safety, and early learning), plus disability. Associated funds were analysed by domain, donor, recipient and region. Trends of ECD/NCF were compared with reproductive, maternal, newborn and child health (RMNCH) disbursements. To assess domestic or out-of-pocket expenditure for ECD, we searched electronic databases of indexed and grey literature.ResultsUS$79.1 billion of development assistance were disbursed, mostly for health and nutrition (US$61.9 billion, 78% of total) and least for disability (US$0.7 billion, 2% of total). US$2.3 per child per year were disbursed for non-health ECD activities. Total development assistance for ECD increased by 121% between 2007 and 2016, an average increase of 8.3% annually. Per child disbursements increased more in Africa and Asia, while minimally in Latin America and the Caribbean and Oceania. We could not find comparable sources for domestic funding and out-of-pocket expenditure.ConclusionsEstimated international donor disbursements for ECD remain small compared with RMNCH. Limitations include inconsistent donor terminology in OECD data. Increased investment will be required in the poorest countries and for childhood disability to ensure that progress is equitable.
Variation in use and outcomes related to midline catheters: results from a multicentre pilot study
Authors: Chopra Vineet , Kaatz Scott , Swaminathan Lakshmi , Boldenow Tanya , Snyder Ashley , Burris Rachel , Bernstein Steve J , Flanders Scott 
Published: March 2019

BackgroundWhile midline vascular catheters are gaining popularity in clinical practice, patterns of use and outcomes related to these devices are not well known.MethodsTrained abstractors collected data from medical records of hospitalised patients who received midline catheters in 12 hospitals. Device characteristics, patterns of use and outcomes were assessed at device removal or at 30 days. Rates of major (upper-extremity deep vein thrombosis [DVT], bloodstream infection [BSI] and catheter occlusion) and minor complications were assessed. χ2tests were used to examine differences in rates of complication by number of lumens, reasons for catheter removal l, and hospital-level differences in rates of midline use.ResultsComplete data on 1161 midlines representing 5%–72% of all midlines placed in participating hospitals between 1 January 2017 and 1 March 2018 were available. Most (70.8%) midlines were placed in general ward settings for difficult intravenous access (61.4%). The median dwell time of midlines across hospitals was 6 days; almost half (49%) were removed within 5 days of insertion. A major or minor complication occurred in 10.3% of midlines, with minor complications such as dislodgement, leaking and infiltration accounting for 71% of all adverse events. While rates of major complications including occlusion, upper-extremity DVT and BSI were low (2.2%, 1.4% and 0.3%, respectively), they were just as likely to lead to midline removal as minor complications (53.8% vs 52.5%, p=0.90). Across hospitals, absolute volume of midlines placed varied from 100 to 1837 devices, with corresponding utilisation rates of 0.97%–12.92% (p<0.001).ConclusionMidline use and outcomes vary widely across hospitals. Although rates of major complications are low, device removal as a result of adverse events is common.
Factors across life associated with remaining free from functional limitations despite lifelong exposure to socioeconomic adversity
Authors: Kok Almar A L , Stafford Mai , Cosco Theodore D , Huisman Martijn , Deeg Dorly , Kuh Diana , Cooper Rachel 
Published: March 2019

BackgroundThere are substantial socioeconomic inequalities in functional limitations in old age. Resilience may offer new insights into these inequalities by identifying constellations of factors that protect some individuals from developing functional limitations despite socioeconomic adversity.MethodsData from 1973 participants in the Medical Research Council National Survey of Health and Development (Great Britain), followed from birth until age 60–64, were used. Functional limitations were defined as reporting difficulty with at least 1 of 16 activities at age 60–64. Lifetime socioeconomic adversity was based on socioeconomic trajectories, categorised into three adversity levels. Analysis of covariance and regression models were used to compare psychosocial factors and health-related behaviours between a ‘Resilient’ group (high adversity but no functional limitations) and five groups with other combinations of adversity and limitations.ResultsPrevalence of functional limitations in high, intermediate and low adversity groups was 44%, 30% and 23% in men, and 61%, 55% and 49% in women, respectively. Compared with the other high adversity group, the resilient group had a lower prevalence of childhood illness (12% vs 19%) and obesity throughout ages 43–64 (70% vs 55%). Partially adjusted models also showed higher adolescent self-management, lower neuroticism, higher prevalence of volunteer work and physical activity (age 60–64) and lower prevalence of smoking (age 43) in the resilient. Marital status and contact frequency were not associated with resilience.ConclusionResults suggest protection against childhood illness, health-behavioural factors and self-regulation as targets for interventions across life that may particularly benefit those with long-term exposure to socioeconomic adversity.
Cataract risk in US radiologic technologists assisting with fluoroscopically guided interventional procedures: a retrospective cohort study
Authors: Velazquez-Kronen Raquel , Borrego David , Gilbert Ethel S , Miller Donald L , Moysich Kirsten B , Freudenheim Jo L , Wactawski-Wende Jean , Cahoon Elizabeth K , Little Mark P , Millen Amy E , Balter Stephen , Alexander Bruce H , Simon Steven L , Linet Martha S , Kitahara Cari M 
Published: March 2019

ObjectivesTo assess radiation exposure-related work history and risk of cataract and cataract surgery among radiologic technologists assisting with fluoroscopically guided interventional procedures (FGIP).MethodsThis retrospective study included 35 751 radiologic technologists who reported being cataract-free at baseline (1994–1998) and completed a follow-up questionnaire (2013–2014). Frequencies of assisting with 21 types of FGIP and use of radiation protection equipment during five time periods (before 1970, 1970–1979, 1980–1989, 1990–1999, 2000–2009) were derived from an additional self-administered questionnaire in 2013–2014. Multivariable-adjusted relative risks (RRs) for self-reported cataract diagnosis and cataract surgery were estimated according to FGIP work history.ResultsDuring follow-up, 9372 technologists reported incident physician-diagnosed cataract; 4278 of incident cases reported undergoing cataract surgery. Technologists who ever assisted with FGIP had increased risk for cataract compared with those who never assisted with FGIP (RR: 1.18, 95% CI 1.11 to 1.25). Risk increased with increasing cumulative number of FGIP; the RR for technologists who assisted with >5000 FGIP compared with those who never assisted was 1.38 (95% CI 1.24 to 1.53; p trend <0.001). These associations were more pronounced for FGIP when technologists were located ≤3 feet (≤0.9 m) from the patient compared with >3 feet (>0.9 m) (RRs for >5000 at ≤3 feet vs never FGIP were 1.48, 95% CI 1.27 to 1.74 and 1.15, 95% CI 0.98 to 1.35, respectively; pdifference=0.04). Similar risks, although not statistically significant, were observed for cataract surgery.ConclusionTechnologists who reported assisting with FGIP, particularly high-volume FGIP within 3 feet of the patient, had increased risk of incident cataract. Additional investigation should evaluate estimated dose response and medically validated cataract type.
HILC
Authors: Intharah Thanapong , Turmukhambetov Daniyar , Brostow Gabriel J. 
Published: March 2019

Creating automation scripts for tasks involving Graphical User Interface (GUI) interactions is hard. It is challenging because not all software applications allow access to a program’s internal state, nor do they all have accessibility APIs. Although much of the internal state is exposed to the user through the GUI, it is hard to programmatically operate the GUI’s widgets.

To that end, we developed a system prototype that learns by demonstration, called
HILC
(Help, It Looks Confusing). Users, both programmers and non-programmers, train HILC to synthesize a task script by demonstrating the task. A demonstration produces the needed screenshots and their corresponding mouse-keyboard signals. After the demonstration, the user answers follow-up questions.

We propose a user-in-the-loop framework that learns to generate scripts of actions performed on visible elements of graphical applications. Although pure programming by demonstration is still unrealistic due to a computer’s limited understanding of user intentions, we use quantitative and qualitative experiments to show that non-programming users are willing and effective at answering follow-up queries posed by our system, to help with confusing parts of the demonstrations. Our models of events and appearances are surprisingly simple but are combined effectively to cope with varying amounts of supervision.
The best available baseline, Sikuli Slides, struggled to assist users in the majority of the tests in our user study experiments. The prototype with our proposed approach successfully helped users accomplish simple linear tasks, complicated tasks (monitoring, looping, and mixed), and tasks that span across multiple applications. Even when both systems could ultimately perform a task, ours was trained and refined by the user in less time.
Personalised Reranking of Paper Recommendations Using Paper Content and User Behavior
Authors: Li Xinyi , Chen Yifan , Pettit Benjamin , Rijke Maarten De 
Published: March 2019

Academic search engines have been widely used to access academic papers, where users’ information needs are explicitly represented as search queries. Some modern recommender systems have taken one step further by predicting users’ information needs without the presence of an explicit query. In this article, we examine an academic paper recommender that sends out paper recommendations in email newsletters, based on the users’ browsing history on the academic search engine. Specifically, we look at users who regularly browse papers on the search engine, and we sign up for the recommendation newsletters for the first time. We address the task of reranking the recommendation candidates that are generated by a production system for such users.
We face the challenge that the users on whom we focus have not interacted with the recommender system before, which is a common scenario that every recommender system encounters when new users sign up. We propose an approach to reranking candidate recommendations that utilizes both paper content and user behavior. The approach is designed to suit the characteristics unique to our academic recommendation setting. For instance, content similarity measures can be used to find the closest match between candidate recommendations and the papers previously browsed by the user. To this end, we use a knowledge graph derived from paper metadata to compare entity similarities (papers, authors, and journals) in the embedding space. Since the users on whom we focus have no prior interactions with the recommender system, we propose a model to learn a mapping from users’ browsed articles to user clicks on the recommendations. We combine both content and behavior into a hybrid reranking model that outperforms the production baseline significantly, providing a relative 13% increase in Mean Average Precision and 28% in Precision@1.
Moreover, we provide a detailed analysis of the model components, highlighting where the performance boost comes from. The obtained insights reveal useful components for the reranking process and can be generalized to other academic recommendation settings as well, such as the utility of graph embedding similarity. Also, recent papers browsed by users provide stronger evidence for recommendation than historical ones.
Myc and Loss of p53 Cooperate to Drive Formation of Choroid Plexus Carcinoma
Authors: Wang Jun , Merino Diana M. , Light Nicholas , Murphy Brian L. , Wang Yong-Dong , Guo Xiaohui , Hodges Andrew P. , Chau Lianne Q. , Liu Kun-Wei , Dhall Girish , Asgharzadeh Shahab , Kiehna Erin N. , Shirey Ryan J. , Janda Kim D. , Taylor Michael D. , Malkin David , Ellison David W. , VandenBerg Scott R. , Eberhart Charles G. , Sears Rosalie C. , Roussel Martine F. , Gilbertson Richard J. , Wechsler-Reya Robert J. 
Published: March 2019

Abstract

Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the Myc oncogene and deleting the Trp53 tumor suppressor gene in murine neural stem cells or progenitors. Murine CPC resembled their human counterparts at a histologic level, and like the hypodiploid subset of human CPC, exhibited multiple whole-chromosome losses, particularly of chromosomes 8, 12, and 19. Analysis of murine and human CPC gene expression profiles and copy number changes revealed altered expression of genes involved in cell cycle, DNA damage response, and cilium function. High-throughput drug screening identified small molecule inhibitors that decreased the viability of CPC. These models will be valuable tools for understanding the biology of choroid plexus tumors and for testing novel approaches to therapy.

Significance:
This study describes new mouse models of choroid plexus carcinoma and uses them to investigate the biology and therapeutic responsiveness of this highly malignant pediatric brain tumor.
CD317 Activates EGFR by Regulating Its Association with Lipid Rafts
Authors: Zhang Guizhong , Li Xin , Chen Qian , Li Junxin , Ruan Qingguo , Chen Youhai H. , Yang Xiaolu , Wan Xiaochun 
Published: March 2019

Abstract

EGFR regulates various fundamental cellular processes, and its constitutive activation is a common driver for cancer. Anti-EGFR therapies have shown benefit in cancer patients, yet drug resistance almost inevitably develops, emphasizing the need for a better understanding of the mechanisms that govern EGFR activation. Here we report that CD317, a surface molecule with a unique topology, activated EGFR in hepatocellular carcinoma (HCC) cells by regulating its localization on the plasma membrane. CD317 was upregulated in HCC cells, promoting cell-cycle progression and enhancing tumorigenic potential in a manner dependent on EGFR. Mechanistically, CD317 associated with lipid rafts and released EGFR from these ordered membrane domains, facilitating the activation of EGFR and the initiation of downstream signaling pathways, including the Ras–Raf–MEK–ERK and JAK–STAT pathways. Moreover, in HCC mouse models and patient samples, upregulation of CD317 correlated with EGFR activation. These results reveal a previously unrecognized mode of regulation for EGFR and suggest CD317 as an alternative target for treating EGFR-driven malignancies.

Significance:
Activation of EGFR by CD317 in hepatocellular carcinoma cells suggests CD317 as an alternative target for treating EGFR-dependent tumors.
PDLIM2 Is a Marker of Adhesion and β-Catenin Activity in Triple-Negative Breast Cancer
Authors: Cox Orla T. , Edmunds Shelley J. , Simon-Keller Katja , Li Bo , Moran Bruce , Buckley Niamh E. , Bustamante-Garrido Milan , Healy Nollaig , O'Flanagan Ciara H. , Gallagher William M. , Kennedy Richard D. , Bernards René , Caldas Carlos , Chin Suet-Feung , Marx Alexander , O'Connor Rosemary 
Published: March 2019

Abstract

The PDLIM2 protein regulates stability of transcription factors including NF-κB and STATs in epithelial and hemopoietic cells. PDLIM2 is strongly expressed in certain cancer cell lines that exhibit an epithelial-to-mesenchymal phenotype, and its suppression is sufficient to reverse this phenotype. PDLIM2 supports the epithelial polarity of nontransformed breast cells, suggesting distinct roles in tumor suppression and oncogenesis. To better understand its overall function, we investigated PDLIM2 expression and activity in breast cancer. PDLIM2 protein was present in 60% of tumors diagnosed as triple-negative breast cancer (TNBC), and only 20% of other breast cancer subtypes. High PDLIM2 expression in TNBC was positively correlated with adhesion signaling and β-catenin activity. Interestingly, PDLIM2 was restricted to the cytoplasm/membrane of TNBC cells and excluded from the nucleus. In breast cell lines, PDLIM2 retention in the cytoplasm was controlled by cell adhesion, and translocation to the nucleus was stimulated by insulin-like growth factor-1 or TGFβ. Cytoplasmic PDLIM2 was associated with active β-catenin and ectopic expression of PDLIM2 was sufficient to increase β-catenin levels and its transcriptional activity in reporter assays. Suppression of PDLIM2 inhibited tumor growth in vivo, whereas overexpression of PDLIM2 disrupted growth in 3D cultures. These results suggest that PDLIM2 may serve as a predictive biomarker for a large subset of TNBC whose phenotype depends on adhesion-regulated β-catenin activity and which may be amenable to therapies that target these pathways.

Significance:
This study shows that PDLIM2 expression defines a subset of triple-negative breast cancer that may benefit from targeting the β-catenin and adhesion signaling pathways.