bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of DNMT3A by miR-708-5p Inhibits Lung Cancer Stem Cell–like Phenotypes through Repressing Wnt/β-catenin Signaling
Authors: Liu Tianchi , Wu Xiaoping , Chen Tong , Luo Zewei , Hu Xiaohua
Published: October 2017

Purpose: Lung cancer is the leading cause of cancer-related death in the world, and emerging evidences suggest that lung cancer stem cells (CSC) are associated with its poor prognosis, tumor recurrence, and therapy resistance. Here we reveal a novel role for miR-708-5p in inhibiting lung CSC–like features.

Experimental Design: Phenotypic effects of miR-708-5p on the lung CSC–like properties were examined by in vitro sphere formation assay and in xenografted animal models. Immunoblotting, dual luciferase reporter, and immunocytochemistry were performed to determine the target of miR-708-5p. DNA methylation of CDH1 promoter region was tested using bisulfate sequencing. Genome-wide miRNA sequencing data of 990 patients from The Cancer Genome Atlas (TCGA) dataset and 148 patients from China cohort were analyzed to excavate the pathogenic implications of miR-708-5p.

Results: Expression of miR-708-5p inhibits the CSC traits of NSCLC cells in vitro while antagonizing miR-708-5p promotes tumorigenesis in vivo. miR-708-5p directly suppresses the translation of DNMT3A, which results in a substantial reduction of global DNA methylation and the upregulated expression of tumor suppressor CDH1. The upregulation of CDH1 decreased the activity of Wnt/β-catenin signaling and then impaired the stemness characteristics of NSCLC cells. Clinically, patients with high miR-708-5p expression show significantly better survival and lower recurrence. Furthermore, miR-708-5p has a promising potential to apply to differentiating histologic subtypes in NSCLC.

Conclusions: Our findings support that miR-708-5p suppresses NSCLC initiation, development, and stemness through interfering DNMT3A-dependent DNA methylation. miR-708-5p may function as a novel diagnostic and prognostic biomarker in NSCLC. Clin Cancer Res; 24(7); 1748–60. ©2017 AACR.
Gene Expression Signatures and Immunohistochemical Subtypes Add Prognostic Value to Each Other in Breast Cancer Cohorts
Authors: Lundberg Arian , Lindström Linda S. , Harrell J. Chuck , Falato Claudette , Carlson Joseph W. , Wright Paul K. , Foukakis Theodoros , Perou Charles M. , Czene Kamila , Bergh Jonas , Tobin Nicholas P.
Published: October 2017

Purpose: Gene signatures and Ki67 stratify the same breast tumor into opposing good/poor prognosis groups in approximately 20% of patients. Given this discrepancy, we hypothesized that the combination of a clinically relevant signature and IHC markers may provide more prognostic information than either classifier alone.

Experimental Design: We assessed Ki67 alone or combined with ER, PR and HER2 (forming IHC subtypes), and the research versions of the Genomic Grade Index, 70-gene, cell-cycle score, recurrence score (RS), and PAM50 signatures on matching TMA/whole tumor sections and microarray data in two Swedish breast cancer cohorts of 379 and 209 patients, with median follow-up of 12.4 and 12.5 years, respectively. First, we fit Cox proportional hazards models and used the change in likelihood ratio (Δ LR) to determine the additional prognostic information provided by signatures beyond that of (i) Ki67 and (ii) IHC subtypes. Second and uniquely, we then assessed whether signatures could compete well with pathology-based IHC classifiers by calculating the additional prognostic information of Ki67/IHC subtypes beyond signatures.

Results: In cohort 1, only RS and PAM50 provided additional prognostic information beyond Ki67 and IHC subtypes (Δ LR-χ2 Ki67: RS = 12.8, PAM50 = 20.7, IHC subtypes: RS = 12.9, PAM50 = 11.7). Conversely, IHC subtypes added prognostic information beyond all signatures except PAM50. Similar results were observed in cohort 2.

Conclusions: RS and PAM50 provided more prognostic information than the IHC subtypes in all breast cancer patients; however, the IHC subtypes did not add any prognostic information to PAM50. Clin Cancer Res; 23(24); 7512–20. ©2017 AACR.
Neuroblastoma Patients' KIR and KIR-Ligand Genotypes Influence Clinical Outcome for Dinutuximab-based Immunotherapy: A Report from the Children's Oncology Group
Authors: Erbe Amy K. , Wang Wei , Carmichael Lakeesha , Kim KyungMann , Mendonça Eneida A. , Song Yiqiang , Hess Dustin , Reville Patrick K. , London Wendy B. , Naranjo Arlene , Hank Jacquelyn A. , Diccianni Mitchell B. , Reisfeld Ralph A. , Gillies Stephen D. , Matthay Katherine K. , Cohn Susan L. , Hogarty Michael D. , Maris John M. , Park Julie R. , Ozkaynak M. Fevzi , Gilman Andrew L. , Yu Alice L. , Sondel Paul M.
Published: October 2017

Purpose: In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL2, and isotretinoin compared with treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via natural killer (NK) cells. Killer immunoglobulin-like receptors (KIR) on NK cells and their interactions with KIR-ligands can influence NK cell function. We investigated whether KIR/KIR-ligand genotypes were associated with EFS or OS in this trial.

Experimental Design: We genotyped patients from COG study ANBL0032 and evaluated the effect of KIR/KIR-ligand genotypes on clinical outcomes. Cox regression models and log-rank tests were used to evaluate associations of EFS and OS with KIR/KIR-ligand genotypes.

Results: In this trial, patients with the “all KIR-ligands present” genotype as well as patients with inhibitory KIR2DL2 with its ligand (HLA-C1) together with inhibitory KIR3DL1 with its ligand (HLA-Bw4) were associated with improved outcome if they received immunotherapy. In contrast, for patients with the complementary KIR/KIR-ligand genotypes, clinical outcome was not significantly different for patients who received immunotherapy versus those receiving isotretinoin alone.

Conclusions: These data show that administration of immunotherapy is associated with improved outcome for neuroblastoma patients with certain KIR/KIR-ligand genotypes, although this was not seen for patients with other KIR/KIR-ligand genotypes. Further investigation of KIR/KIR-ligand genotypes may clarify their role in cancer immunotherapy and may enable KIR/KIR-ligand genotyping to be used prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens. Clin Cancer Res; 24(1); 189–96. ©2017 AACR.

See related commentary by Cheung and Hsu, p. 3
PAM50 Provides Prognostic Information When Applied to the Lymph Node Metastases of Advanced Breast Cancer Patients
Authors: Tobin Nicholas P. , Lundberg Arian , Lindström Linda S. , Harrell J. Chuck , Foukakis Theodoros , Carlsson Lena , Einbeigi Zakaria , Linderholm Barbro K. , Loman Niklas , Malmberg Martin , Fernö Mårten , Czene Kamila , Perou Charles M. , Bergh Jonas , Hatschek Thomas
Published: October 2017

Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting.

Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable loco-regional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, recurrence score, cell-cycle score, risk of recurrence score, and PAM50) were applied to all metastases, and their relationship to long- (5-year) and short-term (1.5-year) postrelapse survival at all and locoregional lymph nodes (n = 40) versus other metastatic sites (n = 69) combined was assessed using Kaplan–Meier and/or multivariate Cox regression analyses.

Results: The majority of metastases were classified into intermediate or high-risk groups by all signatures, and a significant association was found between metastatic signature subgroups and primary tumor estrogen receptor status and histologic grade (P < 0.05). When considering all sites of metastasis, only PAM50 was statistically significant in Kaplan–Meier analysis (Log-rank P = 0.008 and 0.008 for long- and short-term postrelapse breast cancer–specific survival, respectively). This significance remained in both uni- and multivariate models when restricting analyses to lymph node metastases only, and a similar trend was observed in other metastatic sites combined, but did not reach formal significance.

Conclusions: Our findings are the first to demonstrate that the PAM50 signature can provide prognostic information from the lymph node metastases of ABC patients. Clin Cancer Res; 23(23); 7225–31. ©2017 AACR.
NFκB-Mediated Invasiveness in CD133+ Pancreatic TICs Is Regulated by Autocrine and Paracrine Activation of IL1 Signaling
Authors: Nomura Alice , Gupta Vineet K. , Dauer Patricia , Sharma Nikita S. , Dudeja Vikas , Merchant Nipun , Saluja Ashok K. , Banerjee Sulagna
Published: October 2017

Tumor-initiating cells (TIC) have been implicated in pancreatic tumor initiation, progression, and metastasis. Among different markers that define this cell population within the tumor, the CD133+ cancer stem cell (CSC) population has reliably been described in these processes. CD133 expression has also been shown to functionally promote metastasis through NF-κB activation in this population, but the mechanism is unclear. In the current study, overexpression of CD133 increased expression and secretion of IL1β (IL1B), which activates an autocrine signaling loop that upregulates NF-κB signaling, epithelial–mesenchymal transition (EMT), and cellular invasion. This signaling pathway also induces CXCR4 expression, which in turn is instrumental in imparting an invasive phenotype to these cells. In addition to the autocrine signaling of the CD133 secreted IL1β, the tumor-associated macrophages (TAM) also produced IL1β, which further activated this pathway in TICs. The functional significance of the TIC marker CD133 has remained elusive for a very long time; the current study takes us one step closer to understanding how the downstream signaling pathways in these cells regulate the functional properties of TICs.

Implications: This study demonstrates the important role of tumor- and macrophage-derived IL1β stimulation in pancreatic cancer. IL1 signaling is increased in cells with CD133 expression, leading to increased NF-kB activity, EMT induction, and invasion. Increased invasiveness via IL1β stimulation is mediated by the upregulation of CXCR4 expression. The study highlights the importance of IL1-mediated signaling in TICs. Mol Cancer Res; 16(1); 162–72. ©2017 AACR.
Functional Impact of Chromatin Remodeling Gene Mutations and Predictive Signature for Therapeutic Response in Bladder Cancer
Authors: Duex Jason E. , Swain Kalin E. , Dancik Garrett M. , Paucek Richard D. , Owens Charles , Churchill Mair E.A. , Theodorescu Dan
Published: October 2017

Urothelial carcinoma accounts for most of the bladder cancer cases. Using next-generation sequencing (NGS) technology, we found that a significant percentage (83%) of tumors had mutations in chromatin-remodeling genes. Here, we examined the functional relevance of mutations in two chromatin-remodeling genes, EP300 and its paralog, CREBBP, which are mutated in almost one-third of patients. Interestingly, almost half of missense mutations cluster in the histone-acetyltransferase (HAT) domain of EP300/CREBBP. This domain catalyzes the transfer of an acetyl group to target molecules such as histones, thereby regulating chromatin dynamics. Thus, patients with EP300 or CREBBP mutations may have alterations in the ability of the corresponding proteins to modify histone proteins and control transcriptional profiles. In fact, it was determined that many of the missense HAT mutations in EP300 (64%) and CREBBP (78%) were HAT-inactivating. These inactivating mutations also correlated with invasive disease in patients. Strikingly, the prediction software Mutation Assessor accurately predicted the functional consequences of each HAT missense mutation. Finally, a gene expression signature was developed that associated with loss of HAT activity and that this signature was associated with more aggressive cancer in four patient datasets. Further supporting the notion that this score accurately reflects HAT activity, we found it is responsive to treatment of cancer cells to mocetinostat, a histone deacetylase (HDAC) inhibitor.

Implication: This study provides a rationale for targeted sequencing of EP300 and CREBBP and use of a gene profiling signature for predicting therapeutic response in patients. Mol Cancer Res; 16(1); 69–77. ©2017 AACR.
Duas leituras do livro Eu me chamo Antônio: análise da visualidade semiótica
Authors: Rossetti Regina , Almeida Marialda De Jesus
Published: October 2017

O objetivo deste artigo é indicar alguns aspectos comunicacionais do livro Eu me chamo Antônio, estimado como o segundo livro mais vendido de 2014. Essa obra antes de ser publicada, passou pelo crivo das redes sociais on-line de maneira fragmentada. Trata-se de estudo de caso único holístico e os procedimentos de coleta de dados abrangem revisão bibliográfica, entrevista com o autor do livro e análise documental de redes sociais na Internet (Facebook, Twitter e Instagram). A análise semiótica indicou que o leitor poderá ler a obra de duas formas, como poemas individuais ou como um romance linear.
O tempo no cinema: a influências da montagem na linguagem sincrética
Authors: Guirado Natália Cipolaro
Published: October 2017

A arte do cinema possui especificidades materiais e formais em sua construção enquanto linguagem, tendo em vista que se constitui como um sistema de significação com funcionamento específico, o que o torna diferente das linguagens verbal, sonora, visual e de outras formas de expressão. Compreendemos que a importância da técnica de montagem na organização e na concepção da narrativa fílmica era fundamental para os realizadores e os teóricos do cinema desde o início do século XX, pois os diversos efeitos conferidos à significação a partir desse artifício técnico eram investigados e experimentados. Em relação à construção temporal nas composições fílmicas lineares, geralmente a noção de anterioridade e posterioridade é construída na ordem direta do tempo cronológico que corresponde ao fluxo narrativo e move sua continuidade. A dimensão do tempo possui a peculiaridade de se desenvolver em valores formais específicos, de organizar o espaço e outros elementos diegéticos, como a música, em uma série temporal, bem como conferir a impressão de realidade ao cinema. Observaremos, portanto, algumas formas peculiares da montagem influenciar a construção temporal dos filmes. Dessa maneira, analisaremos trechos dos filmes Gata velha ainda mia (2013), de Rafael Primot; 2001, uma odisseia no espaço (1968), de Stanley Kubrick e Melancolia (2011), de Lars von Trier, para comentar especificidades da montagem na linguagem sincrética.
O tema da emancipação e a escravidão no Brasil: por um olhar semiótico
Authors: Leite Daniel
Published: October 2017

Neste artigo investigamos as formas semióticas presentes em alguns discursos que tratam da escravidão entre os séculos XVI e XIX no território do que hoje conhecemos como o Brasil. A emancipação, tomada como tema semiótico, é investigada a partir da categoria modal do poder. A oposição narrativa entre relações de transitividade (fazer-ser) e factitividade (fazer-fazer) desencadeia reflexões a respeito do status atribuído aos indivíduos escravizados naquele âmbito. O debate se dá a partir de textos jurídicos, acadêmicos e policiais produzidos em diferentes contextos geográficos e históricos.
En cas de catastrophe. Les systèmes casuels et la dynamique qualitative
Authors: Wildgen Wolfgang
Published: October 2017

Ocupando um lugar ora menos, ora mais central a depender da perspectiva adotada pelos pesquisado- res, a problemática dos casos atravessa, há séculos, os estudos da linguagem e das línguas naturais. Este artigo comenta, em primeiro lugar, os pontos de vista trazidos, desde a conhecida contribuição de Charles Fillmore, pelos autores contemporâneos. De passagem, constata-se que, entre estes, muitos conceberam tal problemática na esteira das teorias localistas e até mesmo, por vezes, em termos bastante próximos das intuições morfodinâmicas de René Thom ou Jean Petitot, embora geralmente não os citem. Sem ter a pretensão de fixar leis gerais, que a desconcertante diversidade dos casos nas línguas naturais desautoriza, resumo aqui certas tendências em direção a uma tipologia dos sistemas casuais; em especial a cisão, diacronicamente mais pronunciada ou menos, entre os sistemas de tipo ergativo / absolutivo, por um lado, e os que se baseiam na oposição nominativo / acusativo, por outro. Isso está, por sinal, em estreita dependência com a ordem sintática (SVO, SOV, etc.) das línguas em pauta. Ultrapassando a descrição dos tipos casuais nas línguas, examino a seguir as hipóteses explicativas da gênese de tais sistemas, contemplando os roteiros plausíveis de sua emergência no decorrer da hominização. Para tanto, relembro o desenvolvimento da actância (ou, como dizia Tesnière, da valência verbal) em seus principais patamares, pois ela terá desempenhado um papel primordial nesse longo processo. Depois de discutir o esquema actancial e sua análise cognitiva, assim como a morfogênese gramatical em seus múltiplos estágios, assinalo, na conclusão, algumas das vias hoje trilháveis para que o saber linguístico possa dar novos passos em direção à generalização teórica.
Gênese e Formação Socioespacial da Região do Vale do Itajaí, SC, Brasil: projeto Acolhida na Colônia
Authors: Rocha Elisângela da Silva , Flores Luiz Carlos da Silva , Pereira Raquel Maria Fontes do Amaral
Published: October 2017

O projeto Acolhida na Colônia é uma forma de turismo rural em que as famílias de agricultores imigrantes europeus recebem os turistas em suas propriedades e apresentam seu modo de viver junto à natureza. Esta pesquisa objetiva discutir a gênese e os aspectos socioespaciais do Alto Vale do Itajaí e, mais especificamente, dos municípios que compõem o projeto Acolhida na Colônia, visando a compreender os aspectos que antecederam o momento atual e contribuíram para a inserção das cidades no projeto. Para atingir o objetivo proposto, optou-se pela adoção de um estudo de caso com pesquisa descritiva e bibliográfica de caráter exploratório a fim de contextualizar a formação socioespacial do local estudado. Os resultados demonstram que o contexto socioespacial da região investigada contribui de forma significativa para a expansão e reconfiguração da atividade turística e, por consequência, contribui também para o desenvolvimento regional.
Choosing a Restaurant: important attributes and related features of a consumer’s decision making process
Authors: Azevedo Lorna das Graças Martins Rosa P. Pinheiro de , Moura Luiz Rodrigo Cunha , Souki Gustavo Quiroga
Published: October 2017

The identification of the attributes considered by consumers in their decision-making process is a competitive factor for organizations and consists of a field of research on the products and services available on the market. This study aimed at identifying which are the attributes and related features taken into account by consumers in their decision-making process for choosing a restaurant. Two studies were thus conducted, the first being a qualitative study based on interviews with 23 restaurant consumers. The research contributions were used for the development of a questionnaire for the second study carried out in the city of Belo Horizonte, Brazil, in March 2014, which consisted of a survey made up of a sample of 600 customers of fast-food restaurants, continuous service (all-you-can-eat restaurants), buffet, and a la carte, totaling 438 valid questionnaires analyzed statistically, obtaining 12 groups with 46 attributes (service, beauty, comfort, nearby location, convenient location, choices, children, convenience, offers, perceived value, entertainment, and queue). On food evaluation, two groups were identified (organoleptic and presentation), regarding beverages, a single group was formed for seven indicators. The attributes on hygiene, food quality, service, and price made up the list of the most important aspects in the consumers’ decisionmaking process for choosing a restaurant (fast-food, continuous service – “all-you-caneat restaurants” –, buffet and a la carte). The identification of these attributes showed similarities between the restaurants surveyed and allowed the comparison of results with other surveys conducted in that field.
Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell–Derived Endothelial Cells Encapsulated in a Nanomatrix Gel
Authors: Lee Shin-Jeong , Sohn Young-Doug , Andukuri Adinarayana , Kim Sangsung , Byun Jaemin , Han Ji Woong , Park In-Hyun , Jun Ho-Wook , Yoon Young-sup
Published: October 2017

Background:

Human pluripotent stem cell (hPSC)–derived endothelial cells (ECs) have limited clinical utility because of undefined components in the differentiation system and poor cell survival in vivo. Here, we aimed to develop a fully defined and clinically compatible system to differentiate hPSCs into ECs. Furthermore, we aimed to enhance cell survival, vessel formation, and therapeutic potential by encapsulating hPSC-ECs with a peptide amphiphile (PA) nanomatrix gel.

Methods:

We induced differentiation of hPSCs into the mesodermal lineage by culturing on collagen-coated plates with a glycogen synthase kinase 3β inhibitor. Next, vascular endothelial growth factor, endothelial growth factor, and basic fibroblast growth factor were added for endothelial lineage differentiation, followed by sorting for CDH5 (VE-cadherin). We constructed an extracellular matrix–mimicking PA nanomatrix gel (PA-RGDS) by incorporating the cell adhesive ligand Arg-Gly-Asp-Ser (RGDS) and a matrix metalloproteinase-2–degradable sequence. We then evaluated whether the encapsulation of hPSC-CDH5
+
cells in PA-RGDS could enhance long-term cell survival and vascular regenerative effects in a hind-limb ischemia model with laser Doppler perfusion imaging, bioluminescence imaging, real-time reverse transcription–polymerase chain reaction, and histological analysis.

Results:

The resultant hPSC-derived CDH5
+
cells (hPSC-ECs) showed highly enriched and genuine EC characteristics and proangiogenic activities. When injected into ischemic hind limbs, hPSC-ECs showed better perfusion recovery and higher vessel-forming capacity compared with media-, PA-RGDS–, or human umbilical vein EC–injected groups. However, the group receiving the PA-RGDS–encapsulated hPSC-ECs showed better perfusion recovery, more robust and longer cell survival (> 10 months), and higher and prolonged angiogenic and vascular incorporation capabilities than the bare hPSC-EC–injected group. Surprisingly, the engrafted hPSC-ECs demonstrated previously unknown sustained and dynamic vessel-forming behavior: initial perivascular concentration, a guiding role for new vessel formation, and progressive incorporation into the vessels over 10 months.

Conclusions:

We generated highly enriched hPSC-ECs via a clinically compatible system. Furthermore, this study demonstrated that a biocompatible PA-RGDS nanomatrix gel substantially improved long-term survival of hPSC-ECs in an ischemic environment and improved neovascularization effects of hPSC-ECs via prolonged and unique angiogenic and vessel-forming properties. This PA-RGDS–mediated transplantation of hPSC-ECs can serve as a novel platform for cell-based therapy and investigation of long-term behavior of hPSC-ECs.
Direct Comparison of Cardiac Myosin-Binding Protein C With Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction
Authors: Kaier Thomas E. , Twerenbold Raphael , Puelacher Christian , Marjot Jack , Imambaccus Nazia , Boeddinghaus Jasper , Nestelberger Thomas , Badertscher Patrick , Sabti Zaid , Giménez Maria Rubini , Wildi Karin , Hillinger Petra , Grimm Karin , Loeffel Sarah , Shrestha Samyut , Widmer Dayana Flores , Cupa Janosch , Kozhuharov Nikola , Miró Òscar , Martín-Sánchez F. Javier , Morawiec Beata , Rentsch Katharina , Lohrmann Jens , Kloos Wanda , Osswald Stefan , Reichlin Tobias , Weber Ekkehard , Marber Michael , Mueller Christian
Published: October 2017

Background:

Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI.

Methods:

Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality.

Results:

Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L,
P
<0.001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.924), hs-cTnT (AUC, 0.927), and hs-cTnI (AUC, 0.922) and superior to cTnI measured by a contemporary sensitivity assay (AUC, 0.909). The combination of cMyC with hs-cTnT or standard-sensitivity cTnI (but not hs-cTnI) led to an increase in AUC to 0.931 (
P
<0.0001) and 0.926 (
P
=0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categories: Net Reclassification Improvement +0.149 versus hs-cTnT, +0.235 versus hs-cTnI (
P
<0.001). In early presenters (chest pain <3 h), the improvement in rule-in/rule-out classification with cMyC was larger compared with hs-cTnT (Net Reclassification Improvement +0.256) and hs-cTnI (Net Reclassification Improvement +0.308; both
P
<0.001). Comparing the C statistics, cMyC was superior to hs-cTnI and standard sensitivity cTnI (
P
<0.05 for both) and similar to hs-cTnT at predicting death at 3 years.

Conclusions:

cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00470587.
Latent Rheumatic Heart Disease
Authors: Beaton Andrea , Aliku Twalib , Dewyer Alyssa , Jacobs Marni , Jiang Jiji , Longenecker Chris T. , Lubega Sulaiman , McCarter Robert , Mirabel Mariana , Mirembe Grace , Namuyonga Judith , Okello Emmy , Scheel Amy , Tenywa Emmanuel , Sable Craig , Lwabi Peter
Published: October 2017

Background:

Screening echocardiography has emerged as a potentially powerful tool for early diagnosis of rheumatic heart disease (RHD). The utility of screening echocardiography hinges on the rate of RHD progression and the ability of penicillin prophylaxis to improve outcome. We report the longitudinal outcomes of a cohort of children with latent RHD and identify risk factors for unfavorable outcomes.

Methods:

This was a prospective natural history study conducted under the Ugandan RHD registry. Children with latent RHD and ≥1 year of follow-up were included. All echocardiograms were re-reviewed by experts (2012 World Heart Federation criteria) for inclusion and evidence of change. Bi- and multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards models, as well, were developed to search for risk factors for unfavorable outcome and compare progression-free survival between those treated and not treated with penicillin. Propensity and other matching methods with sensitivity analysis were implemented for the evaluation of the penicillin effect.

Results:

Blinded review confirmed 227 cases of latent RHD: 164 borderline and 63 definite (42 mild, 21 moderate/severe). Median age at diagnosis was 12 years and median follow-up was 2.3 years (interquartile range, 2.0–2.9). Penicillin prophylaxis was prescribed in 49.3% with overall adherence of 84.7%. Of children with moderate-to-severe definite RHD, 47.6% had echocardiographic progression (including 2 deaths), and 9.5% had echocardiographic regression. Children with mild definite and borderline RHD showed 26% and 9.8% echocardiographic progression and 45.2% and 46.3% echocardiographic improvement, respectively. Of those with mild definite RHD or borderline RHD, more advanced disease category, younger age, and morphological mitral valve features were risk factors for an unfavorable outcome.

Conclusions:

Latent RHD is a heterogeneous diagnosis with variable disease outcomes. Children with moderate to severe latent RHD have poor outcomes. Children with both borderline and mild definite RHD are at substantial risk of progression. Although long-term outcome remains unclear, the initial change in latent RHD may be evident during the first 1 to 2 years following diagnosis. Natural history data are inherently limited, and a randomized clinical trial is needed to definitively determine the impact of penicillin prophylaxis on the trajectory of latent RHD.
Creative Media + the Internet of Things = Media Multiplicities
Authors: Bown Oliver , Ferguson Sam
Published: October 2017

This paper proposes the term “media multiplicities” to describe contemporary media artworks that create multiples of “internet of things” devices. It discusses the properties that distinguish media multiplicities from other forms of media artwork, provides parameters for categorizing media multiplicities, and discusses aesthetic and creative factors in the production of media multiplicities.
Validating the lectotypification of Myrtus silvestris Vellozo, the basionym of Plinia silvestris (Myrtaceae)
Authors: HE HAI
Published: October 2017

When publishing the combination Plinia silvestris (Vellozo) Mazine & Sobral in Sobral et al. (2017: 89), the type of the basionym Myrtus silvestris Vellozo (1829: 215) was cited as “probably lost” and hence a lectotype was proposed (Sobral et al. 2017). It was generally acknowledged that Vellozo’s material for Flora Fluminensis was not successfully traceable (Stafleu & Cowan 1986). In the protologue of Myrtus silvestris Vellozo, an illustration “Tab. 64, T. 5” was cited (Vellozo 1829). This citation corresponded to the pagination and volume of Florae Fluminensis Icones (Vellozo et al. 1831), which is considered as part of the original material though it was published two years later. It is reasonable that Sobral et al. (2017) selected that illustration as its lectotype of Myrtus silvestris. However, a lectotypification can only be achieved when the typification statement includes the phrase “designated here” or an equivalent after 1 January 2001 following Art. 7.10 of ICN (McNeil et al. 2012). For this reason the lectotypification by Sobra et al. is not valid. Here I validate it.
A clandestine in the flora of Brazil: Commelina clandestina (Commelinaceae)
Authors: HASSEMER GUSTAVO
Published: October 2017

Commelina clandestina has been for a long time a problematic citation for the flora of Brazil. Here, I clarify the original publication and authorship of C. clandestina Mart. and C. clandestina Hort.Berol. ex Kunth, designate lectotypes for these names, propose their synonymisation with C. tuberosa, and argue that the seeds from which the type specimens were grown in Munich and Berlin did not originate from Brazil. Finally, to summarise recent advances to the taxonomic knowledge of Commelina, I provide here an updated identification key for the genus in Brazil.
Validation of Impatiens trigonopteris (Balsaminaceae)
Authors: ARISDASON WILSON , GOGOI RAJIB
Published: October 2017

The nomen nudum Impatiens trigonopteris is here validated, and the species is described along with illustration and image of the type. Its affinities with other closely resembling species and a note on its geographic distribution are also provided.
A new species and a new form of leafhopper from the Great Smoky Mountains National Park (Hemiptera: Cicadellidae: Typhlocybinae)
Authors: DMITRIEV DMITRY A. , ZAHNISER JAMES N.
Published: October 2017

A new species Erasmoneura tricuspidata sp.n. and a new morphological variant of Erythridula stolata McAtee are described from the Great Smoky Mountains National Park.
A new species of the genus Neobubastes Blackburn, 1892 from Western Australia (Coleoptera: Buprestidae: Buprestinae: Pterobothrini)
Authors: BÍLÝ SVATOPLUK , POWELL MICHAEL
Published: October 2017

A description of Neobubastes obscura sp. nov. from Western Australia is provided. The new species is illustrated and compared with other species of the genus. A key to and images of all species of the genus Neobubastes Blackburn, 1892 are provided.
Pterostichus neilgaimani sp. nov., a new species of ground beetles (Coleoptera: Carabidae) from relict sacred grove in Eastern Georgia
Authors: CHALADZE GIORGI , KALATOZISHVILI LEVAN , JANIASHVILI ZURAB , BAKURADZE GIORGI
Published: October 2017

A new species of ground beetles (Coleoptea: Carabidae) belonging to the subgenus Aphaonus Reitter, 1887 (genus Pterostichus Bonelli, 1810) is described, based on two specimens collected from the sacred grove of Khevsha (Eastern Georgia).
Low-Frequency Climate Modes and Antarctic Sea Ice Variations, 1982–2013
Authors: Cerrone D. , Fusco G.
Published: October 2017

The NCEP–NCAR composite dataset (comprising sea level pressure, 500-hPa geopotential height, 500-hPa temperature, and meridional wind stress at 10 m above the surface) is used for compiling a set of climate indices describing the most important physical modes of variability in the Southern Hemisphere (SH): the southern annular mode (SAM), semiannual oscillation (SAO), Pacific–South American (PSA), and quasi-stationary zonal wavenumber 3 (ZW3) patterns. Compelling evidence indicates that the large increase in the SH sea ice, recorded over recent years, arises from the impact of climate modes and their long-term trends. The examination of variability ranging from seasonal to interdecadal scales, and of trends within the climate patterns and total Antarctic sea ice concentration (SIC) for the 32-yr period (1982–2013), is the key focus of this paper. The results herein indicate that a progressive cooling has affected the year-to-year climate of the sub-Antarctic since the 1990s. This feature is found in association with increased positive SAM and SAO phases detected in terms of upward annual and seasonal trends (in autumn and summer) and upward decadal trends. In addition, the SIC shows upward annual, spring, and summer trends, indicating the insulation of Antarctica from the warmer flows in the midlatitudes. This picture of variations is also found to be consistent with the upward trends detected for the PSA and ZW3 patterns on the annual scale and during the last two decades. Evidence of a more frequent occurrence of the PSA–ZW3 combination could explain, in part, the significant increase of the regional and total Antarctic sea ice coverages.
Testing a Novel Method for Initializing Air Parcel Back Trajectories in Precipitating Clouds Using Reanalysis Data
Authors: Putman Annie L. , Feng Xiahong , Posmentier Eric S. , Faiia Anthony M. , Sonder Leslie J.
Published: October 2017

Lagrangian air parcel tracking is a powerful tool for estimating vapor source locations, particularly for isotope hydrology applications. Identified vapor source regions may be sensitive to the distribution of altitudes at which back trajectories are initiated. Ideally, those initial altitudes should reflect the altitudes where precipitation forms. This paper introduces a novel method for estimating these heights from reanalysis data and an air parcel lofting routine, which is referred to as the “Reanalysis” method. Using Barrow, Alaska (now known as Utqiaġvik), as a test site, the study compares the distribution of air parcel initiation heights and vapor source conditions from back trajectories initiated at 1) heights determined by the Reanalysis method and 2) heights acquired from 35-GHz vertically resolved cloud radar, termed the “Cloud Radar” method. Only 2 of the 70 events failed to produce condensation at any elevation. The distribution of air parcels generated by each method was compared on the basis of the median height and the median-adjusted overlap, and yielded excellent (n = 28), good (n = 20), fair (n = 6), and poor (n = 14) matches between the two methods. The excellent and good category events tended to produce condensation profiles with lower median heights, which translated to more similar vapor source characteristics. Poorly matched events tended to result from rain events where the Reanalysis method yielded much higher median heights than the Cloud Radar method.
Feasibility of a Clinic-Community Partnership to Treat Childhood Obesity
Authors: Andrews Maria , Sawyer Carolyn , Frerichs Leah , Skinner Asheley Cockrell , Hoffman Jessica , Gaskin Kiah , Armstrong Sarah
Published: October 2017

Background. “Bull City Fit” is a childhood obesity treatment partnership between Duke Children’s pediatric weight management clinic and Durham Department of Parks and Recreation. Objectives. Report on feasibility and implementation, characteristics of participants, and predictors of attendance. Methods. Mixed methods study consisting of (1) a retrospective cohort analysis (n = 171) reporting demographic, attendance, and clinical data and (2) structured focus groups among stakeholders to identify implementation facilitators and barriers. Results. Higher attendance was associated with Spanish language ( P = .07), more clinic visits ( P = .03), shorter time to first attendance ( P = .06), lower child z–body mass index (BMI) at baseline ( P = .08), and lower parent BMI ( P = .02). Associations were mitigated after controlling for demographic characteristics. BMI z-score did not differ between low- and moderate/high attenders at 6 months. Family inclusion and community engagement emerged as positive themes during focus groups. Conclusions. Clinic-community partnerships engage diverse populations in fitness and nutrition activities, but no specific patient characteristics appear to predict greater attendance.
Jesus’ Philoi vs. Jesus’ Douloi: Conflicts over the Paraclete’s Function and Authority in the Johannine Community
Authors: Lee Sang Mok
Published: October 2017

This study discusses the Paraclete-related texts in the Fourth Gospel concerning the competition for authority between the Beloved Disciple’s written testimony and the Paraclete’s prophetic messages. The Johannine community experienced an internal conflict between the two groups, i.e., Jesus’ friends and Jesus’ slaves. Each group held its view on the function and authority of the Paraclete. The former understood the Paraclete as a reminder to the disciples of what Jesus already taught during his earthly ministry, as well as an interpreter of such teachings; it promoted the authority of the written tradition through the Beloved Disciple’s testimony. The latter, nevertheless, viewed the Paraclete as intending to reveal new teachings beyond those of the earthly Jesus; it advocated the authority of prophetic activities in the community, relying on the Paraclete. The evangelist supported the friend group, contending for the reliability and authority of Jesus’ tradition via the Beloved Disciple’s tradition preserved in the Gospel.
Blackness the Color of Red: Negotiating Race at the US Legation in Riga, Latvia, 1922–33
Authors: Matusevich Maxim
Published: October 2017

This article draws on the archival records of the United States Consulate in Riga, Latvia, during the interwar period and other primary sources to reconstruct the rites of passage by African American citizens of the USA traveling to and from the Soviet Union. In the absence of established diplomatic relations between the USA and the USSR (until 1933), the US legation in Riga served as a popular entry point for American tourists and contract workers attracted by the mystique and job opportunities of the first socialist state. The consular records of the US legation in Riga contain a wealth of materials related to some of these travels. In the course of formal interviews with consular officials, US citizens, including the minority of black visitors, revealed remarkable details of their Soviet odysseys. The archival records bring to life a unique story of ‘race tourism’ by African Americans to the first socialist state and thus provide a rare insight into the early Soviet society and its accepted attitudes toward racial difference; and such accounts are usually juxtaposed with an eviscerating critique of North American and Western racism during the interwar period.
‘A Plague of Salaried Marxists’: Sexuality and Subsistence in the Revolutionary Imaginary of Concha Michel
Authors: Olcott Jocelyn
Published: October 2017

This article examines work of Mexican singer and activist Concha Michel, particularly the pamphlet Marxistas y ‘marxistas’ that sealed her expulsion from the Mexican Communist Party (Partido Comunista de México, PCM). Michel wrote the pamphlet after her return from the Soviet Union, where her experiences only confirmed her belief that revolutionary governments in Mexico and the Soviet Union alike had failed to attend to the massive amounts of social and cultural labor performed overwhelmingly by women. In particular, Communists' emphasis on modernization and scientific theory privileged the ‘social economy’ of commodified production and devalued what she dubbed the ‘natural economy’ of subsistence, reproduction, and artistic labors. The pamphlet draws parallels with the capitalist exploitation of laborers and the sexual exploitation of women perpetrated even by Communist Party leaders. Michel’s refusal to submit to the Party line resulted in her high-profile expulsion from the party, a fate that befell much of her social circle. Over subsequent decades, however, her commitment to activism on behalf of women, celebration of Mexico’s indigenous cultures, and persistent critique of the elision of subsistence labors would earn her celebrity among Mexican maternalist feminists.
Sino-Soviet Romance: An Emotional History of Revolutionary Geopolitics
Authors: McGuire Elizabeth
Published: October 2017

This article argues that the relationship between the Russian and Chinese revolutions can be interpreted as a romance, to create an emotional history of elite revolutionary geopolitics. Tracing the stories of two prominent Sino-Soviet couples – President of Taiwan Jiang Jingguo and his wife Faina Vakhreva, and PRC Labor Minister Li Lisan and his wife Elizaveta Kishkina – against a larger backdrop of cultural exchange highlights continuities in a relationship most often described in terms of its ruptures. In the 1920s, when Jiang Jingguo first arrived in the Soviet Union, attitudes toward love and sex in both cultures were shifting, and the Chinese Revolution was celebrated in Moscow, rendering early Chinese experiences there romantic on several levels. The Liza-Li affair, begun in the difficult circumstances of the 1930s, highlights the ways in which the choices of one partner, personal or geopolitical, could come to constrain those of the other, through the 1950s and beyond. Such deeply felt and publicly prominent cross-cultural romances gave China’s relationship with Russia an emotional complexity and cultural depth that were lacking before the advent of twentieth century communism – and have survived its demise.
Varieties of civil war and mass killing
Authors: Krcmaric Daniel
Published: October 2017

Why do some civil wars feature the mass killing of civilians while others do not? Recent research answers this question by adopting a ‘varieties of civil war’ approach that distinguishes between guerrilla and conventional civil wars. One particularly influential claim is that guerrilla wars feature more civilian victimization because mass killing is an attractive strategy for states attempting to eliminate the civilian support base of an insurgency. In this article, I suggest that there are two reasons to question this ‘draining the sea’ argument. First, the logic of ‘hearts and minds’ during guerrilla wars implies that protecting civilians – not killing them – is the key to success during counterinsurgency. Second, unpacking the nature of fighting in conventional wars gives compelling reasons to think that they could be particularly deadly for civilians caught in the war’s path. After deriving competing predictions on the relationship between civil war type and mass killing, I offer an empirical test by pairing a recently released dataset on the ‘technology of rebellion’ featured in civil wars with a more nuanced dataset of mass killing than those used in several previous studies. Contrary to the conventional wisdom, I find that mass killing onset is more likely to occur during conventional wars than during guerrilla wars.
Review: Statutory regulation of invasive complementary therapies, such as hijama and acupuncture, is the only effective way of ensuring both patient safety and good practice
Authors: Mayberry John F
Published: October 2017

The development of statutory regulation of healthcare professionals first emerged in the 15th century in the UK. However, it was not until the 20th century that statutory regulation of complementary therapies emerged with the Osteopath and Chiropractors Acts. However, during that period, acupuncture failed to gain statutory regulation but was rather subject to the equivalent of trading standards. This review explores the background to this failure and the present need for statutory regulation. It draws comparisons with the need for regulation of hijama, another invasive therapy, for which there is at present no regulation. The benefits of the negative licensing model developed in Australia are considered.
The Emotional Underpinnings of Attitudes toward Transitional Justice
Authors: Barceló Joan
Published: October 2017

What explains citizens’ attitudes toward transitional justice? Studies that examined the support for transitional justice mechanisms identified three sets of factors: individual, socialization, and contextual. Building on the hot cognition theory, this article argues that the past political regime is an emotionally charged sociopolitical object encoded with its evaluative history with consequences in people’s opinion-formation process. Drawing on a specialized survey in Spain, the results first suggest that negative emotions, especially anger and fear, significantly influence the support for stronger transitional justice measures, even after adjusting for relevant confounders such as ideology, religiosity, or victimization. Second, the findings show that those who lack an emotional engagement toward the past regime, the so-called bystanders, hold attitudes toward transitional justice that are indistinguishable from those who report positive feelings (pride, patriotism, and nostalgia) toward the past regime. The effects of emotions are sizable relative to other important determinants, including ideology, religiosity, and family’s ideology.