bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antithrombotic management and thrombosis rates in children post–liver transplantation: A case series and literature review
Authors: Flynn Elise , Huang Joanna Y. , Hardikar Winita , Herd Lauren , Hodgson Alexandra , Monagle Paul 
Published: April 2019

AbstractThrombosis is a major postoperative complication in pediatric liver transplantation. There is marked heterogeneity in prophylactic antithrombotic therapies used, without established guidelines. This review summarizes current worldwide incidence of thrombotic events and compares antithrombotic therapies in children post–liver transplant, with comparison to our institution's experience. Of the twenty‐three articles with sufficient detail to compare antithrombotic regimens, the overall incidence of thrombosis ranged from 2.4% to 17.3%. Incidence of HAT ranged from 0% to 28.1%, of HVT from 0% to 4.7%, of PVT from 1.5% to 11.2%, and of IVC thrombosis from 0% to 2.8%. Re‐transplantation due to thrombosis ranged from 0% to 4.8%. Prophylactic antithrombotic therapies varied between studies, and bleeding complications were infrequently reported. Since 2010, 96 children underwent 100 liver transplants at our institution with thrombosis incidence comparable to international literature (HAT 6%, PVT 5%, IVC 1%, and HVT 0%). Re‐transplantation due to thrombosis occurred in 2% and major bleeding occurred in 10%. The prophylactic antithrombotic therapies used post–liver transplantation in children remain varied. Low rates of thrombosis have been reported with antiplatelet use both with and without anticoagulation. Standard definitions and consistent reporting of bleeding complications are required, in addition to thrombosis rates, so that true risk‐benefit assessment of reported regimes can be understood.
Conversation: Student self‐authorship and the goals of higher education
Authors: Fisher Kathleen , Newton Richard , McClymond Kathryn 
Published: April 2019

AbstractThis edited transcript of a roundtable “fishbowl” conversation at a session of the 2018 national conference of the American Academy of Religion brings three teaching scholars together around a shared reading of Jane Fried's book, Education, Fishbowls, and Rabbit Holes: Rethinking Teaching and Liberal Education for an Interconnected World (Stylus, 2016). Fried's concept of student “self‐authorship” quickly emerges as the dominant theme of the conversation, providing fresh perspectives on the purposes and goals of an academic classroom and the place of the study of religion within the liberal arts curriculum.
Forum: Quilting as metaphor for theological education
Authors: Park Sophia S. , Tran Mai‐Anh Le , Parker Angela , Ghali Adam A. , Helsel Carolyn B. , Cardoza‐Orlandi Carlos F. 
Published: April 2019

AbstractHow is quilt‐making both metaphor and pedagogy for early‐career faculty of theology and religion who seek to cultivate critical and creative imagination for teaching, and to probe the challenges and promises of complex identities and vocations within 21st‐century landscapes of theological education? This forum presents essays (with explanatory introduction) by five members of the 2016–2017 Workshop for Early Career Theological School Faculty, who were impelled to story their experience of being “handed over to themselves” by an “arts and craft” project which forced them to think with their hands, speak with found objects, and re‐present themselves in the form of 12 × 12‐inch quilt squares. In self‐reflexive prose, these scholar‐teachers offer through this medium a glimpse of their unexpected moments of revelatory learning, as each was pulled into deeper contemplation of their personhood, experience, know‐how, and practical wisdom, each uncovering valuable hidden sources for more expansive theological query, and each re‐thinking the possibilities for theological education and its pedagogies.
Economic evaluations of onchocerciasis interventions: a systematic review and research needs
Authors: Turner Hugo C. , Walker Martin , Pion Sébastien D. S. , McFarland Deborah A. , Bundy Donald A. P. , Basáñez María‐Gloria 
Published: April 2019

AbstractObjectiveTo provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps.MethodA systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) andISIWeb of Science electronic databases. No date or language stipulations were applied to the searches.ResultsWe identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost‐effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis‐associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost‐effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability‐adjusted life year (DALY) averted of annualMDAvaries betweenUS$3 andUS$30 (cost year variable).ConclusionsThe cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond.
Task Constraints and Coordination Flexibility in Young Swimmers
Authors: Silva Ana F. , Figueiredo Pedro , Morais Sara , Vilas-Boas João P. , Fernandes Ricardo J. , Seifert Ludovic 
Published: April 2019

This study aimed to examine young swimmers’ behavioral flexibility when facing different task constraints, such as swimming speed and stroke frequency. Eighteen (five boys and 13 girls) 13- to 15-year-old swimmers performed a 15 × 50-m front crawl with five trials, at 100%, 90%, and 70% each of their 50 m maximal swimming speed and randomly at 90%, 95%, 100%, 105%, and 110% of their preferred stroke frequency. Seven aerial and six underwater cameras were used to assess kinematics (one cycle), with upper-limb coordination computed through a continuous relative phase and index of coordination. A cluster analysis identified six patterns of coordination used by swimmers when facing various speed and stroke frequency constraints. The patterns’ nature and the way the swimmers shifted between them are more important than getting the highest number of patterns (range of repertoire), that is, a change in the motor pattern in order to adapt correctly is more important than being able to execute a great number of patterns.
Randomised prospective study of using intraoperative, intraincisional and intraperitoneal ropivacaine for the early discharge of post-laparoscopic cholecystectomy patients as a day case in a cost-effective way in government setup of low-income and middle-income countries: Opening new horizons
Authors: Kaushal-Deep Singh Mathuria , Lodhi Mehershree , Anees Afzal , Khan Shehtaj , Khan Mohammad Amanullah 
Published: April 2019

AbstractBackgroundPain is the main reason for staying overnight at hospital after an uncomplicated laparoscopic cholecystectomy.ObjectivesA randomised prospective study was planned to compare the efficacy of intraincisional and intraperitoneal use of 0.2% ropivacaine so that patients undergoing an uncomplicated laparoscopic cholecystectomy can be discharged as a day case in a cost-effective way.Methods191 patients were operated by elective four-port laparoscopic cholecystectomy. They were randomised into three groups after triple blinding according to location of 0.2% ropivacaine use. All patients were given ~23 mL of solution (drug or normal saline depending on the group), 20 mL of which was given at intraperitoneal location and ~1 mL/cm of incision intraincisionally. Pain scores (Visual Analogue Scale (VAS), Numeric Rating Scale (NRS) and Faces Pain Scale-Revised (FPS-R)) were evaluated at 4 and 8 hours postoperatively. Only those patients with a VAS ≤3, NRS ≤3 and FPS-R ≤2, no requirement of rescue analgesia, no shoulder pain, ambulated at least once, passed urine and taking oral sips were offered discharge as a day case.Results31% of patients in intraperitoneal group (n=62) could be discharged as a day case as compared with 48% in intraincisional group (n=68) (p&gt;0.05) and 89% in combined group (n=61) (p&lt;0.05, with respect to both other groups).ConclusionThe combined use of intraincisional and intraperitoneal ropivacaine is a cost-effective way of discharging approximately 9 in 10 patients as a day case. This study is unique as this is the first study in which only a local anaesthetic has been used to predict discharges as a day case.
The Origins of the ASEAN Community’s Humanitarian Component
Authors: Huang Kwei-Bo 
Published: April 2019

The birth of the ASEAN Community in 2007 has strengthened a long ignored part of ASEAN, i.e., humanitarian assistance and development. The three major pillars of the ASEAN Community have either direct or indirect influence on the institutional expansion and capacity building of ASEAN’s humanitarianism-related tasks. The direct influence is usually derived from the ASEAN Political and Security Community and the ASEAN Social and Cultural Community, while the indirect influence can rest on the advance of the ASEAN Economic Community. Meanwhile, leaders of ASEAN also work with extra-regional state and non-state actors to ensure the positive humanitarian development within the region of Southeast Asia. Yet, due to the principle of non-interference and the lack of resources, ASEAN’s early effort — mainly in capacity building — has apparently been less effective after the brief study of three cases.
Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study
Authors: Chen Fei , Childs Erica J. , Mocci Evelina , Bracci Paige , Gallinger Steven , Li Donghui , Neale Rachel E. , Olson Sara H. , Scelo Ghislaine , Bamlet William R. , Blackford Amanda L. , Borges Michael , Brennan Paul , Chaffee Kari G. , Duggal Priya , Hassan Manal J. , Holly Elizabeth A. , Hung Rayjean J. , Goggins Michael G. , Kurtz Robert C. , Oberg Ann L. , Orlow Irene , Yu Herbert , Petersen Gloria M. , Risch Harvey A. , Klein Alison P. 
Published: April 2019

Abstract

Background:
Pancreatic cancer is the fourth-leading cause of cancer death in both men and women in the United States. The currently identified common susceptibility loci account for a small fraction of estimated heritability. We sought to estimate overall heritability of pancreatic cancer and partition the heritability by variant frequencies and functional annotations.

Methods:
Analysis using the genome-based restricted maximum likelihood method (GREML) was conducted on Pancreatic Cancer Case-Control Consortium (PanC4) genome-wide association study (GWAS) data from 3,568 pancreatic cancer cases and 3,363 controls of European Ancestry.

Results:
Applying linkage disequilibrium- and minor allele frequency-stratified GREML (GREML-LDMS) method to imputed GWAS data, we estimated the overall heritability of pancreatic cancer to be 21.2% (SE = 4.8%). Across the functional groups (intronic, intergenic, coding, and regulatory variants), intronic variants account for most of the estimated heritability (12.4%). Previously identified GWAS loci explained 4.1% of the total phenotypic variation of pancreatic cancer. Mutations in hereditary pancreatic cancer susceptibility genes are present in 4% to 10% of patients with pancreatic cancer, yet our GREML-LDMS results suggested these regions explain only 0.4% of total phenotypic variance for pancreatic cancer.

Conclusions:
Although higher than previous studies, our estimated 21.2% overall heritability may still be downwardly biased due to the inherent limitation that the contribution of rare variants in genes with a substantive overall impact on disease are not captured when applying these commonly used methods to imputed GWAS data.

Impact:
Our work demonstrated the importance of rare and common variants in pancreatic cancer risk.
Plasma Fibrinogen and sP-Selectin are Associated with the Risk of Lung Cancer in a Prospective Study
Authors: Grafetstätter Mirja , Hüsing Anika , González Maldonado Sandra , Sookthai Disorn , Johnson Theron , Pletsch-Borba Laura , Katzke Verena A. , Hoffmeister Michael , Bugert Peter , Kaaks Rudolf , Kühn Tilman 
Published: April 2019

Abstract

Background:
While enhanced platelet activation and a procoagulant state may drive lung cancer progression and metastases, less is known about their role in earlier phases of cancer development. Thus, we evaluated whether prediagnostic biomarkers of platelet activation and coagulation are related to the risk of lung cancer in the prospective EPIC-Heidelberg Study using a case–cohort design.

Methods:
Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n = 2,480) and incident cases of lung cancer (n = 190). Multivariable-adjusted Cox proportional hazards regression analyses were used to obtain HRs of lung cancer across quartiles of biomarker levels.

Results:
Fibrinogen [HR highest vs. lowest quartile: 1.91 (95% confidence interval: 1.09–3.34)] and sP-Selectin [HR: 2.51 (1.39–4.52)] were significantly associated with lung cancer risk in multivariable adjusted Cox regression models. Adding both biomarkers to the established PLCOm2012 algorithm, which alone showed a C-statistic of 0.788, led to a slight increment in lung cancer risk prediction, with a C-statistic of 0.814.

Conclusion:
Our findings indicate that enhanced platelet activation and a procoagulative state contribute to lung carcinogenesis.

Impact:
The current prospective study supports the hypothesis of increased coagulation being a possible driver of lung carcinogenesis, as strong positive associations were found between two procoagulative markers, sP-Selectin and fibrinogen, with lung cancer risk. Both biomarkers could improve lung cancer risk prediction, but external validation of the results is needed.
Repurposing EGFR Inhibitor Utility in Colorectal Cancer in Mutant APC and TP53 Subpopulations
Authors: Yang Mingli , Schell Michael J. , Loboda Andrey , Nebozhyn Michael , Li Jiannong , Teer Jamie K. , Pledger W. Jack , Yeatman Timothy J. 
Published: April 2019

Abstract

Background:
EGFR is a major therapeutic target for colorectal cancer. Currently, extended RAS/RAF testing identifies only nonresponders to EGFR inhibitors (EGFRi). We aimed to develop a mutation signature that further refines drug-sensitive subpopulations to improve EGFRi outcomes.

Methods:
A prespecified, 203-gene expression signature score measuring cetuximab sensitivity (CTX-S) was validated with two independent clinical trial datasets of cetuximab-treated patients with colorectal cancer (n = 44 and n = 80) as well as an in vitro dataset of 147 cell lines. The CTX-S score was then used to decipher mutated genes that predict EGFRi sensitivity. The predictive value of the identified mutation signature was further validated by additional independent datasets.

Results:
Here, we report the discovery of a 2-gene (APC+TP53) mutation signature that was useful in identifying EGFRi-sensitive colorectal cancer subpopulations. Mutant APC+TP53 tumors were more predominant in left- versus right-sided colorectal cancers (52% vs. 21%, P = 0.0004), in microsatellite stable (MSS) versus microsatellite instable (MSI) cases (47% vs. 2%, P &lt; 0.0001), and in the consensus molecular subtype 2 versus others (75% vs. 37%, P &lt; 0.0001). Moreover, mutant APC+TP53 tumors had favorable outcomes in two cetuximab-treated patient-derived tumor xenograft (PDX) datasets (P = 0.0277, n = 52; P = 0.0008, n = 98).

Conclusions:
Our findings suggest that the APC and TP53 combination mutation may account for the laterality of EGFRi sensitivity and provide a rationale for refining treated populations. The results also suggest addition of APC+TP53 sequencing to extended RAS/RAF testing that may directly increase the response rates of EGFRi therapy in selected patients.

Impact:
These findings, if further validated through clinical trials, could also expand the utility of EGFRi therapies that are currently underutilized.
High-throughput Screening of Human Tumor Antigen–specific CD4 T Cells, Including Neoantigen-reactive T Cells
Authors: Costa-Nunes Carla , Cachot Amélie , Bobisse Sara , Arnaud Marion , Genolet Raphael , Baumgaertner Petra , Speiser Daniel E. , Sousa Alves Pedro M. , Sandoval Federico , Adotévi Olivier , Reith Walter , Protti Maria Pia , Coukos George , Harari Alexandre , Romero Pedro , Jandus Camilla 
Published: April 2019

Abstract

Purpose:
Characterization of tumor antigen–specific CD4 T-cell responses in healthy donors and malignant melanoma patients using an in vitro amplified T-cell library screening procedure.

Patients and Methods:
A high-throughput, human leukocyte antigen (HLA)-independent approach was used to estimate at unprecedented high sensitivity level precursor frequencies of tumor antigen- and neoantigen-specific CD4 T cells in healthy donors and patients with cancer. Frequency estimation was combined with isolation and functional characterization of identified tumor-reactive CD4 T-cell clones.

Results:
In healthy donors, we report frequencies of naïve tumor-associated antigen (TAA)-specific CD4 T cells comparable with those of CD4 T cells specific for infectious agents (Tetanus toxoid). Interestingly, we also identified low, but consistent numbers of memory CD4 T cells specific for several TAAs. In patients with melanoma, low frequencies of circulating TAA-specific CD4 T cells were detected that increased after peptide-based immunotherapy. Such antitumor TAA-specific CD4 T-cell responses were also detectable within the tumor-infiltrated tissues. TAA-specific CD4 T cells in patients displayed a highly polyfunctional state, with partial skewing to Type-2 polarization. Finally, we report the applicability of this approach to the detection and amplification of neoantigen-specific CD4 T cells.

Conclusions:
This simple, noninvasive, high-throughput screening of tumor- and neoantigen-specific CD4 T cells requires little biologic material, is HLA class II independent and allows the concomitant screening for a large number of tumor antigens of interest, including neoantigens. This approach will facilitate the immunomonitoring of preexisting and therapy-induced CD4 T-cell responses, and accelerate the development of CD4 T-cell–based therapies.
Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery
Authors: Hernandez Vargas Servando , Kossatz Susanne , Voss Julie , Ghosh Sukhen C. , Tran Cao Hop S. , Simien Jo , Reiner Thomas , Dhingra Sadhna , Fisher William E. , Azhdarinia Ali 
Published: April 2019

Abstract

Purpose:
Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS).

Experimental Design:
A multimodality chelator (MMC) was used as a “radioactive linker” to synthesize the fluorescently labeled somatostatin analog, 67/68Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso- and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs.

Results:
Direct labeling with 67Ga/68Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings.

Conclusions:
The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.
Phase II Trial of Chemopreventive Effects of Levonorgestrel on Ovarian and Fallopian Tube Epithelium in Women at High Risk for Ovarian Cancer: An NRG Oncology Group/GOG Study
Authors: Rodriguez Gustavo C. , Kauderer James , Hunn Jessica , Thaete Larry G. , Watkin William G , Russell Samantha , Yozwiak Michael , Basil Jack , Hurteau Jean , Lele Shashikant , Modesitt Susan C. , Zivanovic Oliver , Zhang Hao Helen , Bartels Peter H. , Alberts David S 
Published: April 2019

AbstractA large body of epidemiologic evidence has shown that use of progestin-containing preparations lowers ovarian cancer risk. The purpose of the current study was to gather further preclinical evidence supporting progestins as cancer chemopreventives by demonstrating progestin-activation of surrogate endpoint biomarkers pertinent to cancer prevention in the genital tract of women at increased risk of ovarian cancer. There were 64 women enrolled in a multi-institutional randomized trial who chose to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) and to receive the progestin levonorgestrel or placebo for 4 to 6 weeks prior to undergoing BSO. The ovarian and fallopian tube epithelia (FTE) were compared immunohistochemically for effects of levonorgestrel on apoptosis (primary endpoint). Secondary endpoints included TGFβ isoform expression, proliferation, and karyometric features of nuclear abnormality. In both the ovary and fallopian tube, levonorgestrel did not confer significant changes in apoptosis or expression of the TGFβ1, 2, or 3 isoforms. In the ovarian epithelium, treatment with levonorgestrel significantly decreased the proliferation index. The mean ovarian Ki-67 value in the placebo arm was 2.027 per 100 cells versus 0.775 per 100 cells in the levonorgestrel arm (two-sided P value via Mann–Whitney U test = 0.0114). The karyometric signature of nuclei in both the ovarian and FTE deviated significantly from normal controls (women at average risk of ovarian cancer), but was significantly less abnormal in women treated with levonorgestrel. These karyometric data further support the idea that progestins may clear genetically abnormal cells and act as chemopreventive agents against ovarian and fallopian tube cancer.