bluuebunny/crossref_metadata_2025_split huggingface dataset:
OLFM4, LY6D and S100A7 as potent markers for distant metastasis in estrogen receptor‐positive breast carcinoma
Authors: Mayama Akifumi , Takagi Kiyoshi , Suzuki Hiroyoshi , Sato Ai , Onodera Yoshiaki , Miki Yasuhiro , Sakurai Minako , Watanabe Takanori , Sakamoto Kazuhiro , Yoshida Ryuichi , Ishida Takanori , Sasano Hironobu , Suzuki Takashi 
Published: August 2018

Metastatic breast cancer is a highly lethal disease, and it is very important to evaluate the biomarkers associated with distant metastasis. However, molecular features of distant metastasis remain largely unknown in breast cancer. Estrogens play an important role in the progression of breast cancer and the majority of stage IV breast carcinomas express estrogen receptor (ER). Therefore, in this study, we examined molecular markers associated with distant metastasis in ER‐positive breast carcinoma by microarray and immunohistochemistry. When we examined the gene expression profile of ER‐positive stage IV breast carcinoma tissues (n = 7) comparing ER‐positive stage I‐III cases (n = 11) by microarray analysis, we newly identified OLFM4, LY6D and S100A7, which were closely associated with the distant metastasis. Subsequently, we performed immunohistochemistry for OLFM4, LY6D and S100A7 in 168 ER‐positive breast carcinomas. OLFM4, LY6D and S100A7 immunoreactivities were significantly associated with stage, pathological T factor, distant metastasis and Ki67 status in the ER‐positive breast carcinomas. Moreover, these immunoreactivities were significantly associated with a worse prognostic factor for distant metastasis‐free and breast cancer‐specific survival in ER‐positive stage I‐III breast cancer patients. However, when we performed immunohistochemistry for OLFM4, LY6D and S100A7 in 40 ER‐negative breast carcinomas, these immunoreactivities were not generally associated with the clinicopathological factors examined, including distant metastasis and prognosis of patients, in this study. These results suggest that OLFM4, LY6D and S100A7 immunoreactivity are associated with an aggressive phenotype of ER‐positive breast carcinoma, and these are potent markers for distant metastasis of ER‐positive breast cancer patients.
Neoadjuvant chemotherapy with docetaxel, nedaplatin, and fluorouracil for resectable esophageal cancer: A phase II study
Authors: Ohnuma Hiroyuki , Sato Yasushi , Hayasaka Naotaka , Matsuno Teppei , Fujita Chisa , Sato Masanori , Osuga Takahiro , Hirakawa Masahiro , Miyanishi Koji , Sagawa Tamotsu , Fujikawa Koshi , Ohi Motoh , Okagawa Yutaka , Tsuji Yasushi , Hirayama Michiaki , Ito Tatsuya , Nobuoka Takayuki , Takemasa Ichiro , Kobune Masayoshi , Kato Junji 
Published: August 2018

Cisplatin plus 5‐fluorouracil is regarded as standard neoadjuvant chemotherapy for esophageal squamous cell carcinoma (ESCC) in Japan, but the prognosis remains poor. We have previously described how definitive chemoradiotherapy with docetaxel, nedaplatin, and 5‐fluorouracil (DNF) led to a very high response rate and promising survival times. We therefore undertook a phase II trial to evaluate the feasibility and efficacy of neoadjuvant DNF. The study included patients with clinical stage Ib‐III ESCC. Chemotherapy consisted of i.v. docetaxel (30 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 8, and a continuous infusion of 5‐fluorouracil (400 mg/m2/day) on days 1‐5 and 8‐12, every 3 weeks. After three courses of chemotherapy, esophagectomy was carried out. The primary end‐point was the completion rate of the protocol treatment. Twenty‐eight patients were enrolled (cStage Ib/II/III, 2/3/23) and all received at least two cycles of chemotherapy. Twenty‐five patients underwent surgery, all of whom achieved an R0 resection, leading to a completion rate of 89.3%. The overall response rate was 87.0%. A pathological complete response was confirmed in eight (32.0%) cases. Grade 3/4 adverse events included leukopenia (32.1%), neutropenia (39.3%), febrile neutropenia (10.7%), thrombocytopenia (10.7%), and diarrhea (14.3%), but were manageable. Treatment‐related deaths and major surgical complications did not occur. Estimated 2‐year progression‐free and overall survival rates were 70.4% and 77.2%, respectively. Thus, DNF therapy was well tolerated and deemed feasible, with a strong tumor response in a neoadjuvant setting for ESCC. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014305).
Machine learning in major depression: From classification to treatment outcome prediction
Authors: Gao Shuang , Calhoun Vince D. , Sui Jing 
Published: August 2018

AbstractAimsMajor depression disorder (MDD) is the single greatest cause of disability and morbidity, and affects about 10% of the population worldwide. Currently, there are no clinically useful diagnostic biomarkers that are able to confirm a diagnosis of MDD from bipolar disorder (BD) in the early depressive episode. Therefore, exploring translational biomarkers of mood disorders based on machine learning is in pressing need, though it is challenging, but with great potential to improve our understanding of these disorders.DiscussionsIn this study, we review popular machine‐learning methods used for brain imaging classification and predictions, and provide an overview of studies, specifically for MDD, that have used magnetic resonance imaging data to either (a) classify MDDs from controls or other mood disorders or (b) investigate treatment outcome predictors for individual patients. Finally, challenges, future directions, and potential limitations related to MDD biomarker identification are also discussed, with a goal of offering a comprehensive overview that may help readers to better understand the applications of neuroimaging data mining in depression.ConclusionsWe hope such efforts may highlight the need for an urgently needed paradigm shift in treatment, to guide personalized optimal clinical care.
Development and the effects of extended parenting in the cold‐breeding burying beetle Nicrophorus sayi
Authors: Benowitz Kyle M. , Amukamara Ashley U. , Mckinney Elizabeth C. , Moore Allen J. 
Published: August 2018

1. Burying beetles (Nicrophorus spp.) provide an excellent model system to test predictions about the relationships between environment, life‐history and behaviour. All species in the genus display similar natural histories, breeding on vertebrate carcasses and providing parental care to developing offspring. However, variations in other aspects of species' ecologies provide a rich framework to examine the evolution of parental behaviours and other traits.2. One little‐studied species, N. sayi, breeds in substantially colder temperatures than its congeners, creating a potentially harsh environment for offspring. Here, we examined the timing of reproductive and developmental events in this species, and also investigated the effects of removing parents on offspring performance.3. We find that development is not only extremely slow in this species, but it is also delayed even in comparison to other burying beetles reared at similar temperatures. However, the presence of parents reduces the time that offspring take to leave the carcass. This decrease in development time does not appear to result in a trade‐off with mortality or body size.4. From these results, we suggest that very slow development may be advantageous when living in a particularly cold environment. Additionally, one role of extended parental care may be to assist offspring in dealing with these harsh conditions, and to mitigate the potentially negative consequences of adopting such a slow life‐history strategy.
Elites and the expansion of education in nineteenth‐century Sweden
Authors: Andersson Jens , Berger Thor 
Published: August 2018

AbstractA large literature emphasizes that elite capture of political institutions hampered the spread of mass schooling in the nineteenth and twentieth century. We collect new data on investments in elementary education and the distribution of voting rights for more than 2,000 local governments in nineteenth‐century Sweden and document that educational expenditure was higher where the distribution of political power was more unequal. In particular, areas governed by local landed elites—even those where a single landowner had de jure dictatorial powers—invested substantially more in mass schooling relative to areas where political power was more widely shared, or where it lay in the hands of capitalist elites. Our findings lend quantitative support to an earlier literature produced by economic and social historians which argues that landed elites advanced mass schooling as part of their historical role as patrons of the local community and as a response to the increasing proletarianization of the rural population, while also furthering our understanding of how Sweden maintained a high level of human capital despite its low level of economic development and restricted franchise in the nineteenth century.
How friends with money affect corporate cash policies? The international evidence
Authors: Javakhadze David , Rajkovic Tijana 
Published: August 2018

AbstractWe examine the association between managerial social capital and the cash flow sensitivity of cash in an international setting. We find that social capital reduces the marginal propensity to save cash out of cash flows. This association is stronger for more financially constrained firms, firms with high hedging needs, and firms with more uncertain cash flows. The effect of social capital is partially moderated by the extent of legal protection standards and financial development. We also show that social capital matters for valuation. These findings are robust to alternative model specifications, alternative variable measurement, and tests for endogeneity.
Knowledge discovery using maximization of the spread of influence in an expert system
Authors: Tselykh Alexander , Tselykh Larisa , Vasilev Vladislav , Barkovskii Simon 
Published: August 2018

AbstractThe problem of knowledge acquisition (KA) and the automation of this process is a bottleneck of expert systems (ESs) and remains a topical issue. The present study is an attempt to develop an ES in which inference attributes are formed on the basis of automated discovery of tacit knowledge. The structure of the KA module provides an opportunity to discover new knowledge from the cognitive representations of domain models. The algorithmic processing mechanism consists of three blocks: cluster analysis, influence analysis, and modelling of the equivalent graph. In the proposed expert system based on effective controls, a method of finding influences that highlights the main characteristics of the system is presented. These parameters are used as attributes for the further development of the rule base, expertise, or independent use in decision‐making. A qualitative decrease in user subjectivity is achieved using this algorithm and through elimination of the knowledge engineer from the cycle of KA, which transforms it into a discovery knowledge cycle. Quality assurance of the knowledge base is achieved using three approaches: system presentation, mathematical support, and automation.
Intonation Plays a Role in Language Discrimination by Infants
Authors: Chong Adam J. , Vicenik Chad , Sundara Megha 
Published: August 2018

Previous research on infant language discrimination has focused primarily on the role of prosody, specifically rhythmic timing cues. This, however, ignores the potentially useful role that intonation, another aspect of prosody, might play in aiding discrimination. In this article, we investigated how and when American English‐learning infants discriminate between prosodically similar languages, specifically American English and German, focusing on the role of intonation in infant language discrimination. We found that the ability to distinguish American English and German develops between 5 and 7 months. However, 7‐month‐olds failed to discriminate the two languages when the natural pitch variation was replaced by a monotone. Thus, intonation is necessary for infants’ discrimination of American English and German. Based on these results, we argue for a greater role of intonation in supporting language discrimination by infants.
“Differential risk of hospitalization among single virus infections causing influenza‐like illnesses”
Authors: Ortiz‐Hernández Ana A. , Nishimura Katherine K. , Noyola Daniel E. , Moreno‐Espinosa Sarbelio , Gamiño Ana , Galindo‐Fraga Arturo , Valdéz Vázquez Rafael , Magaña Aquino Martín , Ramirez‐Venegas Alejandra , Valdés Salgado Raydel , Andrade‐Platas Diana , Estevez‐Jimenéz Juliana , Ruiz‐Palacios Guillermo M. , Guerrero Maria Lourdes , Beigel John , Smolskis Mary C. , Hunsberger Sally , Freimanis‐Hence Laura , Llamosas‐Gallardo Beatriz ,   the Mexico Emerging Infectious Diseases Clinical Research Network (La Red)
Published: August 2018

BackgroundAcute respiratory infections are a major cause of morbidity in children and are often caused by viruses. However, the relative severity of illness associated with different viruses is unclear. The objective of this study was to evaluate the risk of hospitalization from different viruses in children presenting with an influenza‐like illness (ILI).MethodsData from children 5 years old or younger participating in an ILI natural history study from April 2010 to March 2014 was analyzed. The adjusted odds ratio for hospitalization was estimated in children with infections caused by respiratory syncytial virus (RSV), metapneumovirus, bocavirus, parainfluenza viruses, rhinovirus/enterovirus, coronavirus, adenovirus, and influenza.ResultsA total of 1486 children (408 outpatients and 1078 inpatients) were included in this analysis. At least one virus was detected in 1227 (82.6%) patients. The most frequent viruses detected as single pathogens were RSV (n = 286), rhinovirus/enterovirus (n = 251), parainfluenza viruses (n = 104), and influenza A or B (n = 99). After controlling for potential confounders (age, sex, recruitment site, days from symptom onset to enrollment, and underlying illnesses), children with RSV and metapneumovirus infections showed a greater likelihood of hospitalization than those infected by parainfluenza viruses (OR 2.7 and 1.9, respectively), rhinovirus/enterovirus (OR 3.1 and 2.1, respectively), coronaviruses (OR 4.9 and 3.4, respectively), adenovirus (OR 4.6 and 3.2, respectively), and influenza (OR 6.3 and 4.4, respectively).ConclusionsChildren presenting with ILI caused by RSV and metapneumovirus were at greatest risk for hospitalization, while children with rhinovirus/enterovirus, parainfluenza, coronavirus, adenovirus, and influenza were at lower risk of hospitalization.
Effects of surface initial condition on aqueous corrosion of glass—A study with a model nuclear waste glass
Authors: Liu Hongshen , Ngo Dien , Ren Mengguo , Du Jincheng , Kim Seong H. 
Published: August 2018

AbstractBeing a nonequilibrium material, the structure of glass varies with the sample history. Thus, the initial surface condition of a glass can vary with the preparation condition and have a large impact on its reactivity. This paper shows that the aqueous corrosion behavior of international simple glass (ISG) varies depending on the initial surface state. The ISG glass samples were prepared as‐polished‐only and polished‐then‐annealed and they were immersed in aqueous solution saturated with soluble SiO2 at 30°C (modeling a mild condition) and at 90°C (modeling a severe condition). Molecular dynamics simulations were performed to obtain coordination numbers of network formers of ISG to assist oxygen speciation calculations. The surface structures of as‐prepared and corroded ISG samples were analyzed using various imaging and spectroscopic techniques. Among these analyses, only the oxygen speciation with x‐ray photoelectron spectroscopy showed discernable differences between two uncorroded surfaces with different preparation histories; all other methods could not differentiate the surface preparation history before aqueous corrosion. Such minor difference in chemical structures was found to have a profound impact on corrosion behaviors in the mild condition. In the harsh condition, the surface history dependence was not as drastic as the corrosion in the mild condition. The analysis results of the corroded surfaces suggested that the thickness and structure of the alteration layer formed on ISG in aqueous corrosion can vary with the initial surface state.
Learning performance and cognitive load in mobile learning: Impact of interaction complexity
Authors: Wang Cixiao , Fang Ting , Miao Rong 
Published: August 2018

AbstractIn the increasing pervasiveness of today's digital society, mobile devices are changing the face of education. Students can interact with mobile devices in context‐aware environment. This paper presents a mobile application based on expert system (Plant‐E) for students to acquire knowledge about plant classification by answering decision‐making questions. In order to study effectiveness of Plant‐E and cognitive load of students who experience different kinds of interaction in learning process, another mobile application (Plant‐G) only providing information pages of plants was developed. A quasi‐experiment was conducted with three classes of 137 seventh graders. The three classes, Class A with 46 students using Plant‐E in campus, Class B with 44 students using Plant‐G in campus, and Class C with 47 students using Plant‐G in a traditional classroom, constitute three groups with different interaction complexity. The research conducted pretest, posttest, and delayed test to evaluate learning performance of students in three classes and used a questionnaire to investigate their perceptions and attitudes towards proposed system. Results show that interaction complexity has an impact on students' learning performance and mental effort in mobile learning; the higher the interaction complexity is, the higher mental effort and the better learning performance in mobile learning will be.
Notch pathway activation enhances cardiosphere in vitro expansion
Authors: Secco Ilaria , Barile Lucio , Torrini Consuelo , Zentilin Lorena , Vassalli Giuseppe , Giacca Mauro , Collesi Chiara 
Published: August 2018

AbstractCardiospheres (CSps) are self‐assembling clusters of a heterogeneous population of poorly differentiated cells outgrowing from in vitro cultured cardiac explants. Scanty information is available on the molecular pathways regulating CSp growth and their differentiation potential towards cardiac and vascular lineages. Here we report that Notch1 stimulates a massive increase in both CSp number and size, inducing a peculiar gene expression programme leading to a cardiovascular molecular signature. These effects were further enhanced using Adeno‐Associated Virus (AAV)‐based gene transfer of activated Notch1‐intracellular domain (N1‐ICD) or soluble‐Jagged1 (sJ1) ligand to CSp‐forming cells. A peculiar effect was exploited by selected pro‐proliferating miRNAs: hsa‐miR‐590‐3p induced a cardiovascular gene expression programme, while hsa‐miR‐199a‐3p acted as the most potent stimulus for the activation of the Notch pathway, thus showing that, unlike in adult cardiomyocytes, these miRNAs involve Notch signalling activation in CSps. Our results identify Notch1 as a crucial regulator of CSp growth and differentiation along the vascular lineage, raising the attracting possibility that forced activation of this pathway might be exploited to promote in vitro CSp expansion as a tool for toxicology screening and cell‐free therapeutic strategies.
Should sulfonylurea be discontinued or maintained at the lowest dose when starting ipragliflozin? A multicenter observational study in Japanese patients with type 2 diabetes
Authors: Takahashi Kiyohiko , Cho Kyu Yong , Nakamura Akinobu , Miya Aika , Miyoshi Arina , Yamamoto Chiho , Nomoto Hiroshi , Niwa Hirokatsu , Takahashi Kiyohito , Manda Naoki , Kurihara Yoshio , Aoki Shin , Ito Yoichi M , Atsumi Tatsuya , Miyoshi Hideaki 
Published: August 2018

AbstractAims/IntroductionWe investigated the difference in efficacy and safety between discontinuation and maintaining of sulfonylurea when adding a sodium–glucose cotransporter 2 inhibitor.Materials and MethodsIn the present multicenter, prospective observational study, 200 patients with type 2 diabetes treated with sulfonylurea and with a need to add ipragliflozin were enrolled and divided into two groups: discontinued sulfonylurea (Discontinuation group) or maintained sulfonylurea, but at the lowest dose (Low‐dose group) when adding ipragliflozin. We compared the two groups after 24 weeks using propensity score matching to adjust for differences between the groups.ResultsIn the matched cohort (58 patients in each group), baseline characteristics of both groups were balanced. The primary outcome of the proportion of patients with non‐exacerbation in glycated hemoglobin after 24 weeks was 91.4% in the Low‐dose group and 75.9% in the Discontinuation group, a significant difference (P = 0.024). However, bodyweight was significantly decreased in the Discontinuation group compared with the Low‐dose group (−4.4 ± 2.1 kg vs −2.9 ± 1.9 kg, P < 0.01). Similarly, liver enzyme improvement was more predominant in the Discontinuation group. A logistic regression analysis showed that high‐density lipoprotein cholesterol, age and sulfonylurea dose were independent factors associated with non‐exacerbation of glycated hemoglobin in the Discontinuation group.ConclusionsThe purpose of using ipragliflozin should be considered when making the decision to discontinue or maintain sulfonylurea at the lowest dose. Furthermore, low high‐density lipoprotein cholesterol level, low dose of sulfonylurea and younger age were possible markers to not show worsening of glycemic control by discontinuing sulfonylurea.
Efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus: A focus on hypoglycemia
Authors: Fukuda Masahiro , Doi Kunihiro , Sugawara Masahiro , Mochizuki Koichi 
Published: August 2018

AbstractAims/IntroductionTo investigate the efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus, with a focus on hypoglycemia.Materials and MethodsType 2 diabetes mellitus patients who started sitagliptin therapy and were followed for 52 weeks were enrolled in the Impact of Sitagliptin on Diabetes Mellitus in Japanese Elderly Patients study. The frequency of hypoglycemia and knowledge of hypoglycemia were analyzed using a questionnaire.ResultsIn total, 5,130 patients (aged 73.8 ± 6.1 years) were analyzed. A significant reduction in glycated hemoglobin (−0.7 ± 1.1%, P < 0.001) and glycoalbumin levels (−2.2 ± 3.8%, P < 0.001) was observed at week 52. The percentage of patients with hypoglycemia did not increase from the baseline (3.3%) to week 52 (2.8%) of sitagliptin administration. Hypoglycemia incidence was significantly higher for combination therapy with insulin (odds ratio 17.75, P < 0.001) or sulfonylurea (odds ratio 2.22, P < 0.001). The increase in sitagliptin dose for combination therapy with antidiabetic drug(s) increased the percentage of patients with hypoglycemia (5.6% in sitagliptin increased subgroup, 2.4% in sitagliptin maintained subgroup, P < 0.01). The awareness of hypoglycemia symptoms and attitude to carry glucose as a countermeasure to prevent hypoglycemia increased during the study.ConclusionsSitagliptin did not increase the percentage of patients with hypoglycemia among elderly patients with type 2 diabetes mellitus. However, hypoglycemia occurred more frequently in add‐on therapy to sulfonylurea or when the sitagliptin dose was increased in combination therapy, showing that sitagliptin should be used with caution.