bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrophage-Derived Granulin Drives Resistance to Immune Checkpoint Inhibition in Metastatic Pancreatic Cancer
Authors: Quaranta Valeria , Rainer Carolyn , Nielsen Sebastian R. , Raymant Meirion L. , Ahmed Muhammad S. , Engle Dannielle D. , Taylor Arthur , Murray Trish , Campbell Fiona , Palmer Daniel H. , Tuveson David A. , Mielgo Ainhoa , Schmid Michael C.
Published: May 2018

The ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumor microenvironment that suppresses and excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immunoprotective role of the metastatic tumor microenvironment in pancreatic cancer is not completely understood. In this study, we find that macrophage-derived granulin contributes to cytotoxic CD8+ T-cell exclusion in metastatic livers. Granulin expression by macrophages was induced in response to colony-stimulating factor 1. Genetic depletion of granulin reduced the formation of a fibrotic stroma, thereby allowing T-cell entry at the metastatic site. Although metastatic PDAC tumors are largely resistant to anti–PD-1 therapy, blockade of PD-1 in granulin-depleted tumors restored the antitumor immune defense and dramatically decreased metastatic tumor burden. These findings suggest that targeting granulin may serve as a potential therapeutic strategy to restore CD8+ T-cell infiltration in metastatic PDAC, thereby converting PDAC metastatic tumors, which are refractory to immune checkpoint inhibitors, into tumors that respond to immune checkpoint inhibition therapies.

Significance: These findings uncover a mechanism by which metastatic PDAC tumors evade the immune response and provide the rationale for targeting granulin in combination with immune checkpoint inhibitors for the treatment of metastatic PDAC.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4253/F1.large.jpg. Cancer Res; 78(15); 4253–69. ©2018 AACR.
Pericytes in the Premetastatic Niche
Authors: Paiva Ana E. , Lousado Luiza , Guerra Daniel A.P. , Azevedo Patrick O. , Sena Isadora F.G. , Andreotti Julia P. , Santos Gabryella S.P. , Gonçalves Ricardo , Mintz Akiva , Birbrair Alexander
Published: May 2018

The premetastatic niche formed by primary tumor–derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with pericyte-specific KLF4 deletion. Strikingly, genetic inactivation of KLF4 in pericytes inhibits pulmonary pericyte expansion and decreases metastasis in the lung. Here, we summarize and evaluate recent advances in the understanding of pericyte contribution to premetastatic niche formation. Cancer Res; 78(11); 2779–86. ©2018 AACR.
Genomic-Epidemiologic Evidence That Estrogens Promote Breast Cancer Development
Authors: Parl Fritz F. , Crooke Philip S. , Plummer W. Dale , Dupont William D.
Published: May 2018

Background: Estrogens are a prime risk factor for breast cancer, yet their causal relation to tumor formation remains uncertain. A recent study of 560 breast cancers identified 82 genes with 916 point mutations as drivers in the genesis of this malignancy. Because estrogens play a major role in breast cancer development and are also known to regulate the expression of numerous genes, we hypothesize that the 82 driver genes are likely to be influenced by estrogens, such as 17ß-estradiol (E2), and the estrogen receptor ESR1 (ERα). Because different types of tumors are characterized by unique sets of cancer driver genes, we also argue that the fraction of driver genes regulated by E2-ESR1 is lower in malignancies not associated with estrogens, e.g., acute myeloid leukemia (AML).

Methods: We performed a literature search of each driver gene to determine its E2-ESR1 regulation.

Results: Fifty-three of the 82 driver genes (64.6%) identified in breast cancers showed evidence of E2-ESR1 regulation. In contrast, only 19 of 54 mutated driver genes (35.2%) identified in AML were linked to E2-ESR1. Among the 916 driver mutations found in breast cancers, 813 (88.8%) were linked to E2-ESR1 compared with 2,046 of 3,833 in AML (53.4%).

Conclusions: Risk assessment revealed that mutations in estrogen-regulated genes are much more likely to be associated with elevated breast cancer risk, while mutations in unregulated genes are more likely to be associated with AML.

Impact: These results increase the plausibility that estrogens promote breast cancer development. Cancer Epidemiol Biomarkers Prev; 27(8); 899–907. ©2018 AACR.
PGC-1α as a Biomarker of Physical Activity-Protective Effect on Colorectal Cancer
Authors: de Souza-Teixeira Fernanda , Alonso-Molero Jéssica , Ayán Carlos , Vilorio-Marques Laura , Molina Antonio Jose , González-Donquiles Carmen , Dávila-Batista Veronica , Fernández-Villa Tania , de Paz Jose Antonio , Martín Vicente
Published: May 2018

Colorectal cancer is a significant public health concern. As a multistage and multifactorial disease, environmental and genetic factors interact at each stage of the process, and an individual's lifestyle also plays a relevant role. We set out to review the scientific evidence to study the need to investigate the role of the peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PGC-1α) gene as a biomarker of the physical activity's (PA) effect on colorectal cancer. PA is a protective factor against colorectal cancer and usually increases the expression of PGC-1α. This gene has pleiotropic roles and is the main regulator of mitochondrial functions. The development of colorectal cancer has been associated with mitochondrial dysfunction; in addition, alterations in this organelle are associated with colorectal cancer risk factors, such as obesity, decreased muscle mass, and the aging process. These are affected by PA acting, among other aspects, on insulin sensitivity and oxygen reactive species/redox balance. Therefore, this gene demands special attention in the understanding of its operation in the consensual protective effect of PA in colorectal cancer. A significant amount of indirect evidence points to PGC-1α as a potential biomarker in the PA-protective effect on colorectal cancer. The article focuses on the possible involvement of PGC-1α in the protective role that physical activity has on colorectal cancer. This is an important topic both in relation to advances in prevention of the development of this widespread disease and in its therapeutic treatment. We hope to generate an initial hypothesis for future studies associated with physical activity–related mechanisms that may be involved in the development or prevention of colorectal cancer. PGC-1α is highlighted because it is the main regulator of mitochondrial functions. This organelle, on one hand, is positively stimulated by physical activity; on the other hand, its dysfunction or reduction increases the probability of developing colorectal cancer. Therefore, we consider the compilation of existing information about the possible ways to understand the mechanisms of this gene to be highly relevant. This study is based on evidence of PGC-1α and physical activity, on PGC-1α and colorectal cancer, on colorectal cancer and physical activity/inactivity, and the absence of studies that have sought to relate all of these variables. Cancer Prev Res; 11(9); 523–34. ©2018 AACR.
Persistently Increased Resting Energy Expenditure Predicts Short-Term Mortality in Patients with Acute-on-Chronic Liver Failure
Authors: Yao Jia , Zhou Xiaoshuang , Wang Hui , Yuan Lili , Chen Yu , Duan Zhongping
Published: May 2018

Objective: Hypermetabolism based on measurements of resting energy expenditure (REE) is suggested to be a potential biomarker for predicting the clinical outcomes of some diseases. We aimed to evaluate the potential value of hypermetabolism for predicting the short-term (28-day) mortality of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: A total of 105 HBV-ACLF patients, 30 chronic hepatitis B (CHB) patients and 30 healthy controls (HCs) were included in this study. The REE was measured using indirect calorimetry in the morning after 8–10 h of fasting. The predicted REE (REEHB) was determined using Harris-Benedict equation. Persistent hypermetabolism was defined as the REE:REEHB ratio > 1.20 at day 1 and day 7 after admission. The severity of liver disease was estimated using the Model for End-Stage Liver Disease (MELD). Clinical and biochemical variables were determined using blood samples ordered upon admission. These variables were compared between nonsurviving and surviving patients who were classified according to the 28-day mortality. Results: The frequency of hypermetabolism at baseline was significantly higher in ACLF patients than that in HCs and CHB patients. Forty-six (43.8%) ACLF patients died within follow-up of 28 days. Persistent hypermetabolism (OR 2.10; 95% CI 1.15–3.69; p = 0.002) and MELD score (OR 1.93; 95% CI 1.47–3.51; p = 0.012) were independent predictive indicators of 28-day mortality. Furthermore, the performance of the 2 variables (persistent hypermetabolism and MELD) together with the area under the receiver operating curve (AUROC: 0.819) was significantly better than that of MELD alone ­(AUROC: 0.694) for prediction of short-term mortality (p = 0.014). Conclusion: These findings indicate that persistent hypermetabolism is predictive of short-term mortality in this small population.
Ragweed Pollen Allergy: Burden, Characteristics, and Management of an Imported Allergen Source in Europe
Authors: Chen Kuan-Wei , Marusciac Laura , Tamas Paul Tudor , Valenta Rudolf , Panaitescu Carmen
Published: May 2018

Ambrosia artemisiifolia, also known as common or short ragweed, is an invasive annual flowering herbaceous plant that has its origin in North America. Nowadays, ragweed can be found in many areas worldwide. Ragweed pollen is known for its high potential to cause type I allergic reactions in late summer and autumn and represents a major health problem in America and several countries in Europe. Climate change and urbanization, as well as long distance transport capacity, enhance the spread of ragweed pollen. Therefore ragweed is becoming domestic in non-invaded areas which in turn will increase the sensitization rate. So far 11 ragweed allergens have been described and, according to IgE reactivity, Amb a 1 and Amb a 11 seem to be major allergens. Sensitization rates of the other allergens vary between 10 and 50%. Most of the allergens have already been recombinantly produced, but most of them have not been characterized regarding their allergenic activity, therefore no conclusion on the clinical relevance of all the allergens can be made, which is important and necessary for an accurate diagnosis. Pharmacotherapy is the most common treatment for ragweed pollen allergy but fails to impact on the course of allergy. Allergen-specific immunotherapy (AIT) is the only causative and disease-modifying treatment of allergy with long-lasting effects, but currently it is based on the administration of ragweed pollen extract or Amb a 1 only. In order to improve ragweed pollen AIT, new strategies are required with higher efficacy and safety.
Angiotensin II Stimulates the NLRP3 Inflammasome to Induce Podocyte Injury and Mitochondrial Dysfunction
Authors: Zhao Min , Bai Mi , Ding Guixia , Zhang Yue , Huang Songming , Jia Zhanjun , Zhang Aihua
Published: May 2018

Background: We previously reported that the NLRP3 inflammasome played an important role in mediating the podocyte injury induced by aldosterone. However, more studies on the role of the NLRP3 inflammasome in the pathogenesis of podocytopathy are still required. The present study was undertaken to study the role of the NLRP3 inflammasome in angiotensin II (Ang II)-induced podocyte injury, as well as the potential mechanisms. Methods: In this study, we used an Ang II infusion model in NLRP3–/– mice. In cultured podocytes, we used siRNA to silence NLRP3; then we treated the podocytes with Ang II. Results: Following Ang II treatment, we found that the NLRP3 inflammasome was significantly activated in line with mitochondrial dysfunction in a dose- and time-dependent manner. Silencing NLRP3 by siRNA transfection ameliorated podocyte apoptosis, attenuated the loss of the podocyte proteins nephrin and podocin, and protected mitochondrial function. Ang II infusion activated the NLRP3 inflammasome, caused albuminuria, and induced podocyte damage, which was all blocked in the NLRP3–/– mice. At the same time, NLRP3 deletion also ameliorated the mitochondrial dysfunction induced by Ang II infusion. However, the deletion of NLRP3 did not affect the Ang II hypertension. Conclusion: Taken together, these results demonstrate an important role of the NLRP3 inflammasome in mediating Ang II-induced podocyte injury and mitochondrial dysfunction, suggesting that the NLRP3 inflammasome might be an effective therapeutic target against podocytopathy.
Robotic Thyroid Surgery: Current Perspectives and Future Considerations
Authors: Aidan Patrick , Arora Asit , Lorincz Balazs , Tolley Neil , Garas George
Published: May 2018

Robotic transaxillary thyroidectomy, pioneered in South Korea, is firmly established throughout the Far East but remains controversial in Western practice. This relates to important population differences (anthropometry and culture) compounded by the smaller mean size of thyroid nodules operated on in South Korea due to a national thyroid cancer screening programme. There is now level 2 evidence (including from Western World centres) to support the safety, feasibility, and equivalence of the robotic approach to its open counterpart in terms of recurrent laryngeal nerve injury, hypoparathyroidism, haemorrhage, and oncological outcomes for differentiated thyroid cancer. Moreover, robotic thyroidectomy has been shown to be superior to open surgery for certain patient-reported outcome measures, namely scar cosmesis and pain. Downsides include its high cost, longer operative time, and risk of complications not encountered in open thyroidectomy (brachial plexus neurapraxia). Careful patient selection is paramount as this procedure is not for every patient, surgeon, or hospital. It should only be undertaken by high-volume surgeons operating as part of a multidisciplinary robotic team in specialised centres. Novel robotic approaches utilising the retroauricular and transoral routes for thyroidectomy have recently been described but further studies are required to establish their respective role in modern thyroid surgery.
Metaplastic Breast Cancer Masquerading as Liposarcoma of the Breast: A Case Report following Oncoplastic Treatment
Authors: Elghobashy Maiar , Basu Naren , Warner Robert , Dickson John , Shaaban Abeer M.
Published: May 2018

Mammary liposarcoma is among the rarest of breast tumours. Here we report the presentation, macroscopic, microscopic, and immunohistochemical features of an extremely rare case of metaplastic carcinoma with extensive pleomorphic liposarcomatous differentiation. A 47-year-old woman presented with bilateral grade III breast ptosis and a 3 × 4 cm mass in the lower outer quadrant of the left breast. Mammography and ultrasound confirmed a well-defined mass. A core biopsy performed was diagnosed as pleomorphic liposarcoma. Microscopically, this was a well-defined, lobulated tumour comprising solid sheets of large pleomorphic and spindle cells with bizarre forms, vacuolated cytoplasm, and ample mitoses. Atypical lipoblasts were easily identifiable. Due to the strong, though patchy, cytokeratin expression, the diagnosis of metaplastic carcinoma with pleomorphic liposarcomatous differentiation was made. Extensive sampling, careful search for a biphasic pattern, ductal carcinoma in situ, and/or epithelial differentiation, and a panel of broad-spectrum cytokeratins are essential to establish the diagnosis.
Atypical Teratoid/Rhabdoid Tumor of the Spinal Cord in a Child: Case Report and Comprehensive Review of the Literature
Authors: Babgi Mohammed , Samkari Alaa , Al-Mehdar Abeer , Abdullah Shaker 
Published: May 2018

Introduction: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is characterized by SMARCB1/INI deletion or mutation in the long arm of chromosome 22 11(22q11.2), also resulting in loss of nuclear expression of INI1 protein immunohistochemically. AT/RT tumors usually occur in children below 3 years. The tumor is usually seen in the cerebellum or the cerebrum, with an extremely rare incidence in the spinal cord. Materials and Methods: We report a rare case of AT/RT in a 6-year-old boy who had a primary spinal cord lesion in the thoracolumbar junction. Pathology revealed loss of nuclear staining of INI1 immunohistochemically. This is the first case reported with mixed intraspinal lesion (intra- and extramedullary). The patient underwent two surgeries and received radiotherapy and chemotherapy; however, he died 16 months after the initial presentation. Results and Discussion: We reviewed the literature on all children with spinal cord AT/RT. The review showed that the cervical region is the most common location of origin, especially in younger children. Reported cases were treated with a combination of surgery, systemic and intrathecal chemotherapy, and radiation therapy, and a survival time of 18 months represented the best outcome. Overall mean survival time was 10 months.
Cerebrospinal Fluid BACE1 Activity and sAβPPβ as Biomarker Candidates of Alzheimer’s Disease
Authors: Alexopoulos Panagiotis , Thierjung Nathalie , Grimmer Timo , Ortner Marion , Economou Polychronis , Assimakopoulos Konstantinos , Gourzis Philippos , Politis Antonios , Perneczky Robert ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: May 2018

Background/Aims: The utility of β-site amyloid-β precursor protein (AβPP) cleaving enzyme 1 (BACE1) activity and soluble AβPP β (sAβPPβ) levels in cerebrospinal fluid (CSF) in detecting Alzheimer’s disease (AD) is still elusive. Methods: BACE1 activity and sAβPPβ concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48). In a subsample with available 18F-fluorodeoxyglucose positron emission tomography (FDG PET) data, ordinal regression models were employed to compare the contribution of BACE1 and sAβPPβ to correct diagnostic classification to that of FDG PET. Results: BACE1 activity was significantly higher in patients with MCI due to AD compared to both controls and patients with MCI with normal CSF markers. sAβPPβ did not differ between any of the studied groups. Interestingly, BACE1 activity was not found to be inferior to FDG PET as predictive covariate in differentiating between the diagnostic groups. Conclusions: Further studies using biomarker-underpinned diagnoses are warranted to shed more light on the potential diagnostic utility of BACE1 activity as AD biomarker candidate in MCI.
Characterization of Hepatocellular Carcinoma Patients with FGF19 Amplification Assessed by Fluorescence in situ Hybridization: A Large Cohort Study
Authors: Kang Hyo Jeong , Haq Farhan , Sung Chang Ohk , Choi Jene , Hong Seung-Mo , Eo Soo-Heang , Jeong Hui Jeong , Shin Jinho , Shim Ju Hyun , Lee Han Chu , An Jihyun , Kim Mi-Ju , Kim Kyu-pyo , Ahn Sung-Min , Yu Eunsil
Published: May 2018

Background: FGF19 amplification is a relatively novel type of genetic aberration that has been proposed to be a driver of hepatocarcinogenesis. Selective inhibitors of FGFR4, a receptor of FGF19, have been developed as targeted therapies for hepatocellular carcinoma (HCC). Despite the role of FGF19 in mediating HCC progression, the clinicopathological characterization of patients exhibiting FGF19 amplification remains unclear. Immunohistochemical staining is the simplest and most widely used method of identifying aberrations in the FGF19 gene, although its specificity is very low. Methods: This study investigated the prognostic significance of FGF19 amplification in a large cohort of 989 HCC patients using fluorescence in situ hybridization (FISH), which has a high degree of specificity. In addition, FISH data from formalin-fixed, paraffin-embedded sections were compared with copy number variation (CNV) data obtained from fresh frozen sections to validate the use of FISH as a diagnostic tool. Results: FGF19 amplifications were detected by FISH in 51 (5.15%) of the 989 patients, and were independently associated with poor survival and a higher risk of tumor recurrence, as well as with poor prognostic factors such as a high α-fetoprotein level, hepatitis B or C virus infection, a large tumor size, microvascular invasion, and necrosis. In addition, FGF19 amplification was associated with TP53 mutation, and was mutually exclusive with CTNNB1 mutation. The results of the FISH and CNV analyses exhibited a significant concordance rate of 96% (κ = 0.618, p < 0.001). Conclusions: These data indicate that FGF19 amplification represents a unique molecular subtype associated with poor prognostic characteristics, which supports the hypothesis that the FGF19-FGFR4 signaling pathway plays an important role in hepatocarcinogenesis. We have also demonstrated that FISH is a viable alternative to CNV analysis, offering a number of advantages in the clinical setting.
The Effect of Hidden Female Smoking on the Association between Smoking and Asthma
Authors: Kim Cheol Hong , Lee Ju Suk
Published: May 2018

Background: The association between smoking and asthma remains controversial. In our previous study, we were not able to show an association between asthma and smoking in Korean adults. One Korean study demonstrated underreporting of smoking history by female adults. The aim of the present study was to investigate the effects of hidden female smoking on the association between asthma and smoking in Korean adults. Methods: Data were acquired from 23,483 men and women aged ≥19 years who participated in the Korean National Health and Nutrition Examination Surveys (KNHANES). Results: The prevalence of asthma was 1.5%, the self-reported smoking prevalence was 32.4%, and the cotinine-verified smoking prevalence was 30.3%. Of the male cotinine-verified smokers, 6.4% were self-reported nonsmokers (2.7% never smokers and 3.7% ex–smokers), whereas 48.8% of the female cotinine-verified smokers were self-reported nonsmokers (43.2% never smokers and 5.6% ex–smokers). In males, the adjusted odds ratio of the association between smoking and asthma was 0.738 (confidence interval, CI: 0.393–1.173) in self-reported and 0.767 (CI: 0.515–1.143) in cotinine-verified smoking; in females, the adjusted odds ratio was 1.945 (CI: 1.348–2.805) in self-reported and 1.531 (CI: 1.076–2.179) in cotinine-verified smoking. Conclusions: Our study showed smoking was associated with asthma in females but not in males.
Aedes communis Reactivity Is Associated with Bee Venom Hypersensitivity: An in vitro and in vivo Study
Authors: Scala Enrico , Pirrotta Lia , Uasuf Carina G. , Mistrello Gianni  , Amato Stefano  , Guerra Emma Cristina , Locanto Maria , Meneguzzi Giorgia , Giani Mauro , Cecchi Lorenzo , Abeni Damiano , Asero Riccardo
Published: May 2018

Mosquito bite is usually followed by a local reaction, but severe or systemic reaction may, in rare cases, occur. Allergic reactions to Aedes communis (Ac) may be underestimated due to the lack of reliable diagnostic tools. In this multicenter study, 205 individuals reporting large local reactions to Ac were enrolled and studied for cutaneous or IgE reactivity to Ac, Blattella germanica, Penaeus monodon, and Dermatophagoides pteronyssinus. Extract and molecular IgE reactivity to bees, wasps, hornets, and yellow jacket venoms were also studied in 119 patients with a clinical history of adverse reaction to Hymenoptera. Immunoblot (IB) analysis and immunoCAP IgE inhibition experiments were carried out in selected sera. Ac sensitization was recorded in 96 (46.8%) patients on SPT. Strict relationship between Ac and D. pteronyssinus, B. germanica, P. monodon, or Apis mellifera reactivity on SPT was observed. Ac IgE recognition was seen in 60/131 (45.8%) patients, 49 (81.6%) of them SPT positive, and 5/14 IB reactors. Ac IgE sensitization was associated with Tabanus spp, A. mellifera, Vespula vulgaris, and Polistes dominula reactivity. A strict relationship between Ac IgE reactivity and Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was recorded. IgE reactivity to AC was inhibited in 9/15 cases after serum absorption with the A. mellifera extract. Both SPT and IgE Ac reactivity is observed in about half of patients with a history of large local reactions to mosquito bites. The significant relationship between Ac sensitization and either extract or single bee venom components is suggestive of a “bee-mosquito syndrome” occurrence.
Florêncio José Ferreira Coutinho: um compositor dos tempos coloniais
Authors: Camargo Fernando Emboaba de
Published: May 2018

O músico Florêncio José Ferreira Coutinho (Arraial do Inficionado, c. 1750 – Vila Rica, 1819) atuou em Vila Rica, atual Ouro Preto, durante a segunda metade do século XVIII e início do XIX. Além disso, participou das diversas instituições da cidade: nos Dragões (tropa com soldo, regimento de cavalaria), onde exerceu as funções de timbaleiro e, depois, trombeteiro-mor; em arrematações no Senado da Câmara, na Casa de Ópera e nas mais diversas irmandades da comarca; e com partido (ensemble) próprio, trabalhando como compositor, cantor (baixo) e instrumentista (trompista). A partir de recentes pesquisas sobre esse compositor mineiro (Ricciardi, Leoni, Castagna etc.) e de minha própria investigação em fontes primárias e secundárias, analisamos a situação desse homem pardo inserido na sociedade mineira.
“Ele militou no sonho de ver os músicos engajados politicamente”
Authors: Castro Marcos Câmara de , Toni Flávia Camargo
Published: May 2018

Entrevista com Flávia Toni. Eleita em 2017 para a cadeira nº 40 da Academia Brasileira de Música, cujo patrono é Mário de Andrade, antes ocupada por Renato Almeida e por Vasco Mariz, Flávia Camargo Toni é mestre e doutora em Artes, livre-docente, pesquisadora e professora titular do Instituto de Estudos Brasileiros (IEB/USP). Como musicóloga, especializou-se em questões envolvendo a literatura musical de Mário de Andrade, Modernismo e Música, e vida e obra de Camargo Guarnieri. Atuou em conjuntos musicais como instrumentista de viola da gamba e de violoncelo, e em 1973 participou da I Bienal Internacional de Música realizada em São Paulo. Fez cursos de especialização nos Estados Unidos e na França e atuou em congressos no Brasil e no exterior. É responsável pela edição crítica de obras de Mário de Andrade, bem como de sua correspondência com Luciano Gallet e com Camargo Guarnieri. Organizou o levantamento das fontes sobre as estadias de Villa-Lobos em São Paulo em estudo que trata da relação desse compositor com o autor de Macunaíma entre 1922 e 1945. Autora de vários livros e capítulos em obras coletivas sobre música, publicou dezenas de artigos em periódicos brasileiros e estrangeiros. Destaque especial merece sua atuação como orientadora e supervisora de dissertações de mestrado e teses de doutorado.
Biografia de Olivier Toni
Authors: Ricciardi Rubens Russomano
Published: May 2018

Uma biografia de Olivier Toni.
Elevated Potassium Levels in Patients With Congestive Heart Failure: Occurrence, Risk Factors, and Clinical Outcomes
Authors: Thomsen Reimar Wernich , Nicolaisen Sia Kromann , Hasvold Pål , Garcia‐Sanchez Ricardo , Pedersen Lars , Adelborg Kasper , Egfjord Martin , Egstrup Kenneth , Sørensen Henrik Toft
Published: May 2018

Background

Data on the true burden of hyperkalemia in patients with heart failure (HF) in a real‐world setting are limited.

Methods and Results

Incidence rates of hyperkalemia (first blood test with a potassium level >5.0 mmol/L) in primary or hospital care were assessed in a population‐based cohort of patients with incident HF diagnoses in northern Denmark from 2000 to 2012. Risk factors and clinical outcomes were compared in patients with HF with versus without hyperkalemia. Of 31 649 patients with HF, 39% experienced hyperkalemia (mean follow‐up, 2.2 years). Risks of experiencing a second, third, or fourth event were 43%, 54%, and 60%, respectively. Among patients with HF with stage 3A, 3B, 4, or 5 kidney dysfunction, 26%, 35%, 44%, and 48% experienced hyperkalemia within the first year. Important hyperkalemia risk factors included chronic kidney disease (prevalence ratio, 1.46; 95% confidence interval [CI], 1.43−1.49), diabetes mellitus (prevalence ratio, 1.38; 95% CI, 1.32−1.45), and spironolactone use (prevalence ratio, 1.48; 95% CI, 1.42−1.54). In patients with HF who developed hyperkalemia, 53% had any acute‐care hospitalization 6 months before the hyperkalemia event, increasing to 74% 6 months after hyperkalemia (before‐after risk ratio, 1.41; 95% CI, 1.38−1.44). Compared with matched patients with HF without hyperkalemia, adjusted 6‐month hazard ratios in patients with hyperkalemia were 2.75‐fold (95% CI, 2.65–2.85) higher for acute‐care hospitalization and 3.39‐fold (95% CI, 3.19–3.61) higher for death.

Conclusions

Almost 4 in 10 patients with HF develop hyperkalemia, and many patients have recurrent hyperkalemia episodes. Hyperkalemia risk is strongly associated with degree of reduced kidney function and use of spironolactone. Hyperkalemia is associated with severe clinical outcomes and death in HF.
Counterexample-Driven Genetic Programming: Heuristic Program Synthesis from Formal Specifications
Authors: Błądek Iwo , Krawiec Krzysztof , Swan Jerry
Published: May 2018

Conventional genetic programming (GP) can guarantee only that synthesized programs pass tests given by the provided input-output examples. The alternative to such a test-based approach is synthesizing programs by formal specification, typically realized with exact, nonheuristic algorithms. In this article, we build on our earlier study on Counterexample-Based Genetic Programming (CDGP), an evolutionary heuristic that synthesizes programs from formal specifications. The candidate programs in CDGP undergo formal verification with a Satisfiability Modulo Theory (SMT) solver, which results in counterexamples that are subsequently turned into tests and used to calculate fitness. The original CDGP is extended here with a fitness threshold parameter that decides which programs should be verified, a more rigorous mechanism for turning counterexamples into tests, and other conceptual and technical improvements. We apply it to 24 benchmarks representing two domains: the linear integer arithmetic (LIA) and the string manipulation (SLIA) problems, showing that CDGP can reliably synthesize provably correct programs in both domains. We also confront it with two state-of-the art exact program synthesis methods and demonstrate that CDGP effectively trades longer synthesis time for smaller program size.
Is Rewriting Translation?
Authors: Screnock John
Published: May 2018

This study considers the process of rewriting under a lens provided by the field of Translation Studies. One subset of translation, called “intralingual translation,” is translation within the same language. This concept provides a new paradigm in which to analyze “rewritten” texts, such as Chronicles and Jubilees. These texts contain changes that can be categorized within the paradigm of intralingual translation, showing that translation overlaps with rewriting and shedding significant light on the latter.
How to Date the Book of Jeremiah: Combining and Modifying Linguistic- and Profile-based Approaches
Authors: Schmid Konrad
Published: May 2018

It is impossible to deny the validity of a linguistic approach to dating biblical texts. But at the same time, it is necessary to caution against using a linguistic approach as a clear-cut tool. It should be employed in conjunction with other data and perspectives, such as theological profiles, intertextual links, as well as geographical and archaeological information. But what should one do if linguistic and alternative approaches to dating biblical texts yield seriously conflicting results, as is often the case? This question shall be discussed with some case studies from Jeremiah, doing so in discussion with Aaron Hornkohl’s recent work on the date of the book of Jeremiah.
Podarcis vaucheri (Sauria: Lacertidae) far away from home: a new invasive species in Greece
Authors: Spilani Loukia , Strachinis Ilias , Lampropoulos Andreas , Tsigas Pavlos , Poulakakis Nikos , Pafilis Panayiotis
Published: May 2018

In this study we aimed to clarify the identity of a wall lizard population that deviates phenotypically from the other Podarcis lizards that occur in the broader area (Athens, Greece). To this end we used molecular techniques. Most surprisingly, we identified the focal population as Podarcis vaucheri, a species far away from its natural range. Molecular results suggest an Iberian origin of this population. To the best of our knowledge, this is the first report of P. vaucheri outside its original range. The new population should be attributed to human-mediated introduction. The future interaction of this introduced species with native lizards, many of which are endemic to Greece, is of critical importance.
A survey investigating the diversity and distribution of entomopathogenic nematodes in the UK and the first confirmed UK record of Steinernema carpocapsae
Authors: Edmunds Cassandra , Post Rory J. , Wilding Craig S. , Rae Robbie
Published: May 2018

Entomopathogenic nematodes (EPN) of the families Steinernematidae and Heterorhabditidae are lethal insect parasites that have been commercialised as biological control agents. EPN have been isolated from across the world but it has been more than 20 years since the last survey of the UK, and species like Steinernema carpocapsae have never been found here and positively identified through molecular biology. We collected 518 soil samples from a diverse range of habitats across the UK and baited them with Galleria mellonella to isolate EPN. Dead G. mellonella were placed in White traps and emergent EPN underwent DNA barcoding analyses. From the 518 samples, 3.5% were positive for EPN. No Heterorhabditis species were found, but seven isolates of S. glaseri, one isolate of S. feltiae, eight isolates of S. affine and two isolates of S. carpocapsae were found. This was the first confirmed record of S. carpocapsae in the UK.
A new species of Alopoglossus lizard (Squamata, Alopoglossidae) from the Southern Guiana Shield, northeastern Amazonia, with remarks on diagnostic characters to the genus
Authors: RIBEIRO-JÚNIOR MARCO ANTÔNIO
Published: May 2018

I describe a new species of Alopoglossus from the Southern Guiana Shield in northern Brazilian Amazonia. The new species morphologically resembles A. angulatus in having scales on sides of neck similar in shape to dorsals, nongranular, keeled, and imbricate. Nonetheless, the presence of four pairs of chin shields, with the third pair heptagonal and separated from gulars by large scales, can distinguish the new species from A. angulatus. This description increases the species diversity of the genus Alopoglossus in eastern Amazonia, from where only one taxon was recognized to occur. In addition, I discuss the nomenclature of some diagnostic characters, on the chin region, to the genus, and I present an updated key to Alopoglossus.
A new species of Eigenmannia Jordan & Evermann (Teleostei: Gymnotiformes: Sternopygidae) from Río Ventuari, Venezuela
Authors: DUTRA GUILHERME MOREIRA , PEIXOTO LUIZ ANTÔNIO WANDERLEY , SANTANA CARLOS DAVID DE , WOSIACKI WOLMAR BENJAMIN
Published: May 2018

A new species of Eigenmannia is described from the Río Ventuari, Río Orinoco basin, Venezuela. It is distinguished from congeners by the presence of a bony dorsolateral flange on the dentary, the presence of teeth attached along a bony dorsolateral flange, and by the first premaxillary teeth attached to the anteroventral margin of the premaxilla. It is further distinguished from all remain congeners by a combination of characters, including a subterminal mouth, 99–107 scales along the lateral line until the end of the anal fin, and ii, 16–17 pectoral-fin rays.
Analysis of the 16 May 2015 Tipton, Oklahoma, EF-3 Tornado at High Spatiotemporal Resolution Using the Atmospheric Imaging Radar
Authors: Mahre Andrew , Kurdzo James M. , Bodine David J. , Griffin Casey B. , Palmer Robert D. , Yu Tian-You
Published: May 2018

In this study, data collected by the Atmospheric Imaging Radar (AIR) are analyzed in conjunction with WSR-88D data (KFDR) for a tornado near Tipton, Oklahoma, on 16 May 2015. The analysis presented herein utilizes PPIs from both radars, polarimetric data from KFDR, time–height plots from the AIR, and a ground-based velocity track display (GBVTD) analysis. This study is novel in that it uses high-resolution mobile radar data (update time of 6–7 s) in tandem with polarimetric data from KFDR in order to identify possible areas of debris, including a debris ring contained within the outer vortex circulation. Leveraging the high spatiotemporal resolution of the AIR with the polarimetric capability of KFDR leads to analysis of reflectivity distributions, debris lofting, kinematic changes, and oscillations in tornado intensity during a portion of the mature stage of the tornado, with a particular focus on the relationship between changes in the reflectivity field and dynamical changes around the tornado. Debris is lofted in a high-reflectivity concentric ring of increasing radius and height around the tornado over several minutes, within the outer weak-echo hole (WEH). Simultaneously, debris lofting and asymmetric reflectivity distribution around the WEH coincide with changes in vortex tilt on multiple occasions. In one instance, hydrometeor fallout appears to precede a possible descending reflectivity core. Using the GBVTD results, near-surface convergence intensifies at the same time and location as when the debris ring is lofted. Additionally, strengthening of the tornado via multiple modes of vertical evolution (i.e., bottom-up intensification over time vs simultaneous intensification throughout the lowest few hundred meters) is observed.
Trends and variation in prescribing of low-priority treatments identified by NHS England: a cross-sectional study and interactive data tool in English primary care
Authors: Walker Alex J , Curtis Helen J , Bacon Seb , Croker Richard , Goldacre Ben
Published: May 2018

Objectives

NHS England recently announced a consultation seeking to discourage the use of treatments it considers to be low-value. We set out to produce an interactive data resource to show savings in each NHS general practice and to assess the current use of these treatments, their change in use over time, and the extent and reasons for variation in such prescribing.

Design

Cross-sectional analysis.

Setting

English primary care.

Participants

English general practices.

Main outcome measures

We determined the cost per 1000 patients for prescribing of each of 18 treatments identified by NHS England for each month from July 2012 to June 2017, and also aggregated over the most recent year to assess total cost and variation among practices. We used mixed effects linear regression to determine factors associated with cost of prescribing.

Results

Spend on low-value treatments was £153.5 m in the last year, across 5.8 m prescriptions (mean, £26 per prescription). Among individual treatments, liothyronine had the highest prescribing cost at £29.6 m, followed by trimipramine (£20.2 m). Over time, the overall total number of low-value prescriptions decreased, but the cost increased, although this varied greatly between treatments. Three treatment areas increased in cost and two increased in volume, all others reduced in cost and volume. Annual practice level spending varied widely (median, £2262 per thousand patients; interquartile range £1439 to £3298). Proportion of patients over 65 was strongly associated with low-value prescribing, as was Clinical Commissioning Group. Our interactive data tool was deployed to OpenPrescribing.net where monthly updated figures and graphs can be viewed.

Conclusions

Prescribing of low-value treatments is extensive but varies widely by treatment, geographic area and individual practice. Despite a fall in prescription numbers, the overall cost of prescribing for low-value items has risen. Prescribing behaviour is clustered by Clinical Commissioning Group, which may represent variation in the optimisation efficiency of medicines, or in some cases access inequality.
The examination of authoritarian parenting styles, specific forms of peer-victimization, and reactive aggression in Hong Kong Youth
Authors: Chan Jacob Yuichung , Harlow Alicia J. , Kinsey Rebecca , Gerstein Lawrence H. , Fung Annis Lai Chu
Published: May 2018

This study utilized a hierarchical regression model to explore the relationship between reactive aggression, forms of peer victimization, and authoritarian parenting styles. Participants included 1,021 Hong Kong youth and their parents ( N = 1,021), drawn from ten primary schools throughout the municipality. Children completed the Reactive and Proactive Aggression Questionnaire and the Multidimensional Peer Victimization Scale, while parents completed the Parental Styles Dimensions Questionnaire. Results indicated that authoritarian parenting, parental use of verbal hostility, verbal victimization by peers, social manipulation, and attacks on property by peers, all significantly contributed to the variance in reactive aggression. Conversely, physical attacks by peers, physical coercion by parents, and non-reasoning parenting styles were not found to significantly contribute to the regression model. Additionally, gender was found to predict reactive aggression with boys reporting higher scores than girls. The implications of these findings for future research, as well as the limitations of this study are discussed.
You Gave Me a B- ?! Self-Efficacy, Implicit Theories, and Student Reactions to Grades
Authors: Ackerman David S. , Gross Barbara L.
Published: May 2018

Student reactions to grades can be unpredictable. Students may complain about grades, sometimes angrily, even when they receive a moderately high grade. This study looks at beliefs about the self as predictors of students’ reactions to an average grade received on a hypothetical assignment. It examines the effect of a student’s self-efficacy with regard to ability and performance on assignments, and the effect of a student’s implicit theory, whether the student holds a more fixed view or a more malleable view of academic ability and performance. Levels of self-efficacy (low to high) and implicit theories (more malleable view of abilities to more fixed views of abilities) are varied, with cumulative GPA included as well in regression analysis. Results show that a malleable view of abilities leads not only to lower levels of overall satisfaction with a grade but also less anger and likely influences students to strive to improve. Self-efficacy regarding the course has less of an impact than implicit theories about abilities, but students with higher overall GPAs liked the instructor less.
Selecting and Scheduling Link and Intersection Improvements in Urban Networks
Authors: Jovanovic Uros , Shayanfar Elham , Schonfeld Paul M.
Published: May 2018

Deciding which projects, alternatives or investments to implement is a complex and important problem not only in transportation engineering, but in management, operations research and economics. Projects are interrelated if their benefits or costs depend on which other projects are implemented. Furthermore, in the network development problem analyzed here, the timing of projects also affects the benefits and costs of other projects. This paper presents a method for optimizing the selection and scheduling of interrelated improvements in road networks that explicitly considers intersections. The Frank Wolfe algorithm, which is modified here to consider intersections, is used for evaluating network improvements as well as for traffic assignment. Intersections are modelled with pseudo-links whose delays are estimated with Akcelik’s generalized model. The objective is to minimize the present value of total costs (including user time) by determining which projects should be selected and when they should be completed. A genetic algorithm is used for optimizing the sequence and schedule of projects.
Virtual stenting of intracranial aneurysms: A pilot study for the prediction of treatment success based on hemodynamic simulations
Authors: Berg Philipp , Saalfeld Sylvia , Janiga Gábor , Brina Olivier , Cancelliere Nicole M , Machi Paolo , Pereira Vitor M
Published: May 2018

Endovascular treatment of intracranial aneurysms using flow-diverting devices has revolutionized the treatment of large and complex lesions due to its minimally invasive nature and potential clinical outcomes. However, incomplete or delayed occlusion and persistent intracranial aneurysm growth are still an issue for up to one-third of the patients. We evaluated two patients with intracranial aneurysm located at the internal carotid artery who were treated with flow-diverting devices and had opposite outcomes. Both patients presented with similar aneurysms and were treated with the same device, but after a 1-year follow-up, one case presented with complete occlusion (Case 1) and the other required further treatment (Case 2). To reproduce the interventions, virtual stents were deployed and blood flow simulations were carried out using the respective patient-specific geometries. Afterward, hemodynamic metrics such as aneurysmal inflow reduction, wall shear stresses, oscillatory shear, and inflow concentration indices were quantified. The hemodynamic simulations reveal that for both cases, the neck inflow was clearly reduced due to the therapy (Case 1: 19%, Case 2: 35%). In addition, relevant hemodynamic parameters such as time-averaged wall shear stress (Case 1: 35.6%, Case 2: 57%) and oscillatory shear (Case 1: 33.1%, Case 2: 26.7%) were decreased considerably. However, although stronger relative reductions occurred in the unsuccessful case, the absolute flow values in the successful case were approximately halved. The findings demonstrate that a high relative effect of endovascular devices is not necessarily associated with the desired treatment outcome. Instead, it appears that a successful intracranial aneurysm therapy requires a certain patient-specific inflow threshold.
Unraveling the Personality Profile of the Sexual Murderer
Authors: Beauregard Eric , DeLisi Matt
Published: May 2018

Although sexual homicide offenders (SHOs) evince personality disorders, few prior studies have examined all personality disorders or utilized control groups of offenders. Drawing on data from 616 adult male sex offenders including 85 who were SHOs, the current study examined the personality profile of the SHOs, by comparing them with a group of violent nonhomicidal sex offenders (VNHSOs) and a group of nonhomicidal sex offenders (NHSOs) on clinical diagnostics of personality disorders and various crime characteristics. The personality profile of SHOs is comprised primarily of Schizoid and Borderline Personality Disorders, and these offenders were significantly likely to select a victim, use a weapon, and use drugs and alcohol before their offenses, but less likely to force their victim to engage in sexual acts or humiliate them. The comorbidity of Schizoid, Borderline, and Antisocial Personality Disorder features presents unique personality dysfunction that facilitates the lethal sexual violence of SHOs relative to their nonhomicidal sexual offender peers.