bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyaluronic Acid Induces Osteopontin via the Phosphatidylinositol 3-Kinase/Akt Pathway to Enhance the Motility of Human Glioma Cells
Authors: Kim Mi-Suk , Park Myung-Jin , Moon Eui-Jung , Kim So-Jeong , Lee Chang-Hun , Yoo Heon , Shin Sang-Hoon , Song Eun-Sook , Lee Seung-Hoon 
Published: June 2022

Abstract
Hyaluronic acid (HA) binds to cell-surface receptors such as CD44, and seems to be involved in cell adhesion, motility, and tumor progression in brain. To identify gene expression changes that are initiated by HA, we explored human cytokine arrays in U87MG glioma cells and identified osteopontin, a secreted matrix protein, as a transcriptional target of HA. Interestingly, expression of osteopontin was induced by HA in glioma cells lacking functional PTEN, a tumor suppressor gene (U87MG, U251MG, and U373MG), but not in wild-type (wt)-PTEN-harboring cells (LN18 and LN428). To confirm the role of PTEN, adenoviral (Ad)-wt-PTEN was used to induce ectopic expression of wt-PTEN in U87MG cells, leading to reduced HA-mediated osteopontin induction. Reciprocally, transfection with dominant-negative Akt repressed HA-induced osteopontin expression. Furthermore, HA promoted the motility of glioma cells, and down-regulation of induced osteopontin activity via a neutralizing anti-osteopontin antibody repressed HA-induced motility in vitro. Together, these results strongly suggest that induction of osteopontin expression by HA is dependent on activation of the phosphatidylinositol 3-kinase/Akt pathway. Furthermore, our data indicate that PTEN can effectively modulate the expression of osteopontin, and HA-induced osteopontin plays an important role in the motility response induced by HA in human glioma cells.
Low-Dose Dietary Phytoestrogen Abrogates Tamoxifen-Associated Mammary Tumor Prevention
Authors: Liu Bolin , Edgerton Susan , Yang Xiaohe , Kim Aeree , Ordonez-Ercan Dalia , Mason Terza , Alvarez Kathy , McKimmey Christine , Liu Naxin , Thor Ann 
Published: June 2022

Abstract
Wild-type erbB-2/neu transgenic mice were used to study the interactions between tamoxifen and dietary phytoestrogens (or isoflavones) by dose and form in vivo. Mice were randomized to one of four dietary formulas and implanted with an 8-week continuous-release tamoxifen or placebo pellet at 8 weeks of age. In placebo-treated mice, soy meal diet (but not diets supplemented with low-dose or high-dose isoflavones or a casein diet) resulted in prolongation of tumor latency. In tamoxifen-treated mice fed the soy meal, casein, or high-dose isoflavone enriched diets, the majority (&gt;80%) showed no tumor formation by 60 weeks of age. Of the mice that developed tumors, latency was significantly prolonged. In tamoxifen-treated mice fed the low-dose isoflavone enriched diet, a much higher rate of mammary tumor development (&gt;50%; P &lt; 0.002) and a shorter tumor latency were observed. In vitro studies of human and mouse mammary tumor cell lines confirm that low doses of genistein, co-administered with tamoxifen, promote cell proliferation. This is in contrast to tamoxifen alone or tamoxifen with higher doses of genistein that are growth inhibitory. In summary, low-dose dietary isoflavones abrogated tamoxifen-associated mammary tumor prevention in vivo. These interactions are supported by in vitro data from human and mouse mammary tumor cell lines. These dose-associated interactions likely have relevance to the human use of tamoxifen for prevention or treatment of breast cancer.
Tumor Susceptibility of Rassf1a Knockout Mice
Authors: Tommasi Stella , Dammann Reinhard , Zhang Zhongqiu , Wang Yian , Liu Limin , Tsark Walter M. , Wilczynski Sharon P. , Li Jie , You Ming , Pfeifer Gerd P. 
Published: June 2022

Abstract
The human Ras association domain family 1 (RASSF1) gene is located at 3p21.3 in an area that is believed to harbor at least one important tumor suppressor gene. The two major isoforms of RASSF1, RASSF1A and RASSF1C, are distinguished by alternative NH2-terminal exons and the two transcripts initiate in two separate CpG islands. RASSF1A is one of the most frequently inactivated genes described thus far in human solid tumors. Inactivation of RASSF1A most commonly involves methylation of the promoter and CpG island associated with the RASSF1A isoform. In contrast, RASSF1C is almost never inactivated in tumors. Here, we have derived Rassf1a knockout mice in which exon 1-α of the Rassf1 gene was deleted, leading to specific loss of Rassf1a but not Rassf1c transcripts. Rassf1a-targeted mice were viable and fertile. Rassf1a−/− mice were prone to spontaneous tumorigenesis in advanced age (18–20 months). Whereas only two tumors developed in 48 wild-type mice, six tumors were found in 35 Rassf1a+/− mice (P &lt; 0.05) and thirteen tumors were found in 41 Rassf1a−/− mice (P &lt; 0.001). The tumors in Rassf1a-targeted mice included lung adenomas, lymphomas, and one breast adenocarcinoma. Rassf1a−/− and wild-type mice were treated with two chemical carcinogens, benzo(a)pyrene and urethane, to induce skin tumors and lung tumors, respectively. Rassf1a−/− and Rassf1a+/− mice showed increased tumor multiplicity and tumor size relative to control animals. The data are consistent with the tumor-suppressive role of Rassf1a, which may explain its frequent epigenetic inactivation in human tumors.
Abstract 6296: Preclinical evaluation of a panel of FGFR inhibitors for their normal brain and brain tumor distribution
Authors: Knight William , Shaik Kamal , Margaryan Tigran , Mehta Shwetal , Sanai Nader , Tovmasyan Artak 
Published: June 2022

Abstract
Glioblastoma (GBM) is the most prevalent and lethal primary intrinsic brain tumor in adults with approximately 5-8% of GBM patients displaying fibroblast growth factor receptor (FGFR) gene mutations. This subset of GBM patients could potentially benefit from targeted FGFR inhibitor treatment, thus making it imperative to explore FGFR inhibitors as a therapeutic option. In this study, seven pan-FGFR inhibitors (infigratinib, AZD4547, debio1347, erdafitinib, LY2874455, pemigatinib, and TAS-120) were evaluated for their brain penetration ability employing cassette dosing strategy with an aim to identify the optimal candidates for brain tumor targeting. Cassette-dosing strategy was confirmed to be an acceptable approach for screening the panel of FGFR inhibitors by comparing pharmacokinetic parameters obtained from discrete- vs cassette-dosing studies. Subsequently, cassette-dosing strategy was utilized to investigate distributional kinetics of FGFR inhibitors in normal brain and brain tumor in wild-type and triple-knockout (Mdr1a/b-/-Bcrp1-/-) mice. The comparison of brain-to-plasma partition coefficients for total (Kp,brain) and unbound (Kp,brain) drug levels in wild-type and triple-knockout mice revealed the importance of major blood-brain barrier (BBB) efflux transporters in four out of seven FGFR inhibitors. The impact of BBB and efflux transporters were further evaluated in flank and orthotopic patient-derived xenograft mouse models of brain tumors. All FGFR inhibitors were shown to accumulate significantly in both flank and orthotopic brain tumors relative to normal brain. Furthermore, the levels in flank brain tumors were at least 10-fold higher as compared to the levels in orthotopic brain tumors with five FGFR inhibitors, indicating the critical role of efflux transporters and the impact of BBB disruption in the brain and brain tumor distribution. The predictive parameters of brain penetration calculated based on physico-chemical properties have been estimated and shown not to correlate with the experimentally obtained neuro-pharmacokinetic values. In summary, our study provides comprehensive evaluation of neuro-pharmacokinetic behavior of seven FGFR inhibitors and delivers rationale for selection of most optimal candidates for future investigation in brain tumor clinical trials.
Citation Format: William Knight, Kamal Shaik, Tigran Margaryan, Shwetal Mehta, Nader Sanai, Artak Tovmasyan. Preclinical evaluation of a panel of FGFR inhibitors for their normal brain and brain tumor distribution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6296.
Abstract SY23-01: Targeting the reciprocal interplay between inflammation, fibrosis, and pro-tumor immunity
Authors: Weaver Valerie M. 
Published: June 2022

Abstract
Tumors are characterized by increased levels of remodeled and crosslinked extracellular matrix (ECM) proteins that progressively stiffen the tissue stroma. Transformed cells exhibit a perturbed oncogene-stimulated and ECM-tuned mechanophenotype that further stimulates ECM remodeling and stiffening. We have been exploring how these aberrant cell and tissue level forces arise and by what means these forces contribute to malignancy and metastasis, and how they promote tumor recurrence and treatment resistance. We use two and three dimensional culture models with tuned ECM stiffness, as well as transgenic and syngeneic mouse models, human PDX models and human biospecimens, in which ECM crosslinking and stiffness and integrin mechanosignaling are manipulated and quantified. Our work has thus far revealed that the tumor ECM is progressively remodeled, and stiffened, primarily by stromal fibroblasts. We determined that infiltrating pro-tumorigenic myeloid cells secrete factors that stimulate stromal fibroblasts to remodel and crosslink the ECM and that this occurs quite early during tumor evolution. The stromal-fibroblast stiffened ECM thereafter disrupts tissue organization, promotes cell growth and survival and drives cell invasion. The stiffened tumor stroma additionally drives angiogenesis, and activates STAT3 to increase expression of cytokines and chemokines that further stimulate immune cell infiltration. The stiffened ECM thereafter reprograms the infiltrating myeloid cells by altering integrin adhesions and TGFβ SMAD signaling to induce an ECM synthetic metabolic phenotype in the myeloid cells. The metabolically reprogrammed myeloid cells ultimately compromise arginine tissue availability and increase tissue levels of ornithine that severely disrupt CD8 T cell tissue infiltration and perturb their anti-tumor function to accelerate tumor aggression and metastatic dissemination. I will discuss the dynamic and reciprocal interplay between tissue tension and innate and acquired immunity. I will then present data to show how ECM stiffness is able to promote tumor aggression and metastasis by dysregulating anti-tumor immunity. I will end with a short discussion regarding approaches to design therapies informed by these results to improve cancer treatment.
Citation Format: Valerie M. Weaver. Targeting the reciprocal interplay between inflammation, fibrosis, and pro-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY23-01.
Homofobia: um empreendimento político
Authors: Nunes Lauro Victor 
Published: June 2022

De acordo com o portal web da Autêntica Editora2, Daniel Borrillo é um ítalo-argentino radicado na França. Diplomado em Jurisprudência pela Universidade de Buenos Aires e professor de Direito na Universidade de Paris X – Nanterre, é pesquisador associado do Centre National de la Recherche Scientifique (CNRS). Borrillo é especialista nas questões jurídicas internacionais referente às minorias étnicas e sociais. Foi responsável pelo “Manifesto pela igualdade de direitos”, documento responsável pela publicização da celebração do primeiro casamento gay da França, em 2004. Em “Homofobia: história e crítica de um preconceito”, o autor traça uma periodização da história da homossexualidade, da Grécia Antiga à atualidade. Considerando a pluralidade dos contextos históricos e sociais em que esteve emergida a questão da orientação sexual de indivíduos que se relacionam com pessoas do mesmo sexo, o autor enfatiza o papel da cultura na produção de um estigma secular de marginalização, “pecado” e “doença” associado aos homossexuais e, posteriormente, à população LGBT como um todo. Neste sentido, define a homofobia como um conceito fluído e polissêmico, que descreve estratégias políticas diferenciadas de produção e reprodução da exclusão social deste coletivo tido como minoritário.
A educação vocal do ator - Terezinha Nackéd Zaratin
Authors: Cerasoli Jr Umberto 
Published: June 2022

Entrevista concedida à revista PesquisAtor pela profa. dra. Terezinha Nackéd Zaratin. Nesta entrevista a professora trata da importância do desenvolvimento da voz para o ator e defende que o ensino da técnica vocal se dê “em separado” da expressão corporal e dramática, por meio de exercícios específicos realizados na disciplina poéticas da voz.
1-year outcomes of patients admitted to critical care with treatment limitations: A dual-centre observational study
Authors: Yakubi Masseh , Devlin Annie , Venn Richard , Hodgson Luke 
Published: June 2022

Intensivists are increasingly involved in the care of frail patients as our population ages. Careful person-orientated, individualised decision-making, weighing benefits and harms of critical care are required in such situations. Few studies have reported outcomes of patients with treatment limitations. This dual-centre observational study reports outcomes of 3781 patients (2018-20). At least one treatment limitation was set at admission in 13% ( n = 486). Of this group 55% survived to hospital discharge, of whom 69% were discharged home; 39% remained alive at 1 year. These findings provide objective data to support clinicians, patients and relatives in shared decision-making. Future multi-centre work could explore how best to identify those most likely to benefit from critical care
Outcomes and molecular profile of oligomonocytic CMML support its consideration as the first stage in the CMML continuum
Authors: Calvo Xavier , Roman-Bravo David , Garcia-Gisbert Nieves , Rodriguez-Sevilla Juan Jose , Garcia-Avila Sara , Florensa Lourdes , Gibert Joan , Fernández-Rodríguez Concepción , Salido Marta , Puiggros Anna , Espinet Blanca , Colomo Luis , Bellosillo Beatriz , Ferrer Ana , Arenillas Leonor 
Published: June 2022

Abstract
Patients with oligomonocytic chronic myelomonocytic leukemia (OM-CMML) are currently classified according to the 2017 World Health Organization myelodysplastic syndromes classification. However, recent data support considering OM-CMML as a specific subtype of chronic myelomonocytic leukemia (CMML), given their similar clinical, genomic, and immunophenotypic profiles. The main purpose of our study was to provide survival outcome data of a well-annotated series of 42 patients with OM-CMML and to compare them to 162 patients with CMML, 120 with dysplastic type (D-CMML), and 42 with proliferative type (P-CMML). OM-CMML had significantly longer overall survival (OS) and acute myeloid leukemia–free survival than did patients with CMML, considered as a whole group, and when compared with D-CMML and P-CMML. Moreover, gene mutations associated with increased proliferation (ie, ASXL1 and RAS-pathway mutations) were identified as independent adverse prognostic factors for OS in our series. We found that at a median follow-up of 53.47 months, 29.3% of our patients with OM-CMML progressed to D-CMML, and at a median follow-up of 46.03 months, 28.6% of our D-CMML group progressed to P-CMML. These data support the existence of an evolutionary continuum of OM-CMML, D-CMML, and P-CMML. In this context, we observed that harboring more than 3 mutated genes, carrying ASXL1 mutations, and a peripheral blood monocyte percentage &gt;20% significantly predicted a shorter time of progression of OM-CMML into overt CMML. These variables were also detected as independent adverse prognostic factors for OS in OM-CMML. These data support the consideration of OM-CMML as the first evolutionary stage within the proliferative continuum of CMML.
Multi-view heterogeneous molecular network representation learning for protein–protein interaction prediction
Authors: Su Xiao-Rui , Hu Lun , You Zhu-Hong , Hu Peng-Wei , Zhao Bo-Wei 
Published: June 2022

Abstract
Background
Protein–protein interaction (PPI) plays an important role in regulating cells and signals. Despite the ongoing efforts of the bioassay group, continued incomplete data limits our ability to understand the molecular roots of human disease. Therefore, it is urgent to develop a computational method to predict PPIs from the perspective of molecular system.

Methods
In this paper, a highly efficient computational model, MTV-PPI, is proposed for PPI prediction based on a heterogeneous molecular network by learning inter-view protein sequences and intra-view interactions between molecules simultaneously. On the one hand, the inter-view feature is extracted from the protein sequence by k-mer method. On the other hand, we use a popular embedding method LINE to encode the heterogeneous molecular network to obtain the intra-view feature. Thus, the protein representation used in MTV-PPI is constructed by the aggregation of its inter-view feature and intra-view feature. Finally, random forest is integrated to predict potential PPIs.

Results
To prove the effectiveness of MTV-PPI, we conduct extensive experiments on a collected heterogeneous molecular network with the accuracy of 86.55%, sensitivity of 82.49%, precision of 89.79%, AUC of 0.9301 and AUPR of 0.9308. Further comparison experiments are performed with various protein representations and classifiers to indicate the effectiveness of MTV-PPI in predicting PPIs based on a complex network.

Conclusion
The achieved experimental results illustrate that MTV-PPI is a promising tool for PPI prediction, which may provide a new perspective for the future interactions prediction researches based on heterogeneous molecular network.
Euclidean distance-optimized data transformation for cluster analysis in biomedical data (EDOtrans)
Authors: Ultsch Alfred , Lötsch Jörn 
Published: June 2022

AbstractBackgroundData transformations are commonly used in bioinformatics data processing in the context of data projection and clustering. The most used Euclidean metric is not scale invariant and therefore occasionally inappropriate for complex, e.g., multimodal distributed variables and may negatively affect the results of cluster analysis. Specifically, the squaring function in the definition of the Euclidean distance as the square root of the sum of squared differences between data points has the consequence that the value 1 implicitly defines a limit for distances within clusters versus distances between (inter-) clusters.MethodsThe Euclidean distances within a standard normal distribution (N(0,1)) follow a N(0,$$\sqrt{2}$$2) distribution. The EDO-transformation of a variable X is proposed as$$EDO= X/(\sqrt{2}\cdot s)$$EDO=X/(2·s)following modeling of the standard deviationsby a mixture of Gaussians and selecting the dominant modes via item categorization. The method was compared in artificial and biomedical datasets with clustering of untransformed data, z-transformed data, and the recently proposed pooled variable scaling.ResultsA simulation study and applications to known real data examples showed that the proposed EDO scaling method is generally useful. The clustering results in terms of cluster accuracy, adjusted Rand index and Dunn’s index outperformed the classical alternatives. Finally, the EDO transformation was applied to cluster a high-dimensional genomic dataset consisting of gene expression data for multiple samples of breast cancer tissues, and the proposed approach gave better results than classical methods and was compared with pooled variable scaling.ConclusionsFor multivariate procedures of data analysis, it is proposed to use the EDO transformation as a better alternative to the established z-standardization, especially for nontrivially distributed data. The “EDOtrans” R package is available athttps://cran.r-project.org/package=EDOtrans.
Automated versus conventional perioperative glycemic control in adult diabetic patients undergoing open heart surgery
Authors: Kaddoum Roland , Khalili Amro , Shebbo Fadia M. , Ghanem Nathalie , Daher Layal Abou , Ali Arwa Bou , Chehade Nour El Hage , Maroun Patrick , Aouad Marie T. 
Published: June 2022

Abstract
Background
Intraoperative glycemic variability is associated with increased risks of mortality and morbidity and an increased incidence of hyperglycemia after cardiac surgery. Accordingly, clinicians tend to use a tight glucose control to maintain perioperative blood glucose levels and therefore the need to develop a less laborious automated glucose control system is important especially in diabetic patients at a higher risk of developing complications.

Methods
Patients, aged between 40 and 75 years old, undergoing open heart surgery were randomized to either an automated protocol (experimental) or to the conventional technique at our institution (control).

Results
We showed that the percentage of patients maintained between 7.8–10 mmol.l−1 was not statistically different between the two groups, however, through an additional analysis, we showed that the proportion of patients whose glucose levels maintained between a safety level of 6.7–10 mmol.l−1 was significantly higher in the experimental group compared to control group, 14 (26.7%) vs 5 (17.2%) P = 0.025. In addition, the percentage of patients who had at least one intraoperative hyperglycemic event was significantly higher in the control group compared to the experimental group, 17 (58.6%) vs 5 (16.7%), P < 0.001 with no hypoglycemic events in the experimental group compared to two events in the control group. We also showed that longer surgeries can benefit more from using the automated glucose control system, particularly surgeries lasting more than 210 min.

Conclusion
We concluded that the automated glucose control pump in diabetic patients undergoing open heart surgeries maintained most of the patients within a predefined glucose range with a very low incidence of hyperglycemic events and no incidence of hypoglycemic events.

Trial registration
Registered with clinicaltrials.gov (NCT #NCT03314272, Principal investigator Roland Kaddoum, date of registration: 19/10/2017).
Breastfeeding and overweight/obesity among children and adolescents: a cross-sectional study
Authors: Liu Fange , Lv Di , Wang Lumin , Feng Xiaoyu , Zhang Rongjun , Liu Wendong , Han Wenchao 
Published: June 2022

Abstract
Background
Overweight and obesity are major public health crises among children and adolescents and contribute to a significant economic burden. We aimed to investigate the relationship between breastfeeding duration and overweight and obesity in children and adolescents in Qingdao, China in 2017.

Methods
This study conducted a survey with 10,753 students (5370 boys and 5383 girls) aged 6 to 16 years from the Shibei District of Qingdao, China in 2017. Anthropometric measurements were taken by well-trained personnel and self-completed questionnaires were used to collect data from students. A variety of statistical methods were used in this study, including univariate and multivariate analyses, as well as linear and nonlinear regression models.

Results
The prevalence of overweight and obesity was 15.45% and 19.76%, respectively. There was a significant negative correlation between breastfeeding duration and BMI in children and adolescents (β = -0.025, 95% CI: -0.033, -0.005, P < 0.01). Among boys, the BMI in children and adolescences of those who have been breastfed for more than 12 months was significantly lower than that of others whose breastfeeding duration was less than 12 months (β = -0.440, 95%CI -0.655, -0.224, P < 0.01). Breastfeeding has a particularly positive effect on the prevalence of obesity in boys aged 9 to 11 years (OR = 0.978, 95% CI: 0.958,0.999, P < 0.05).

Conclusion
Breastfeeding can significantly reduce the prevalence of overweight and obesity among children and adolescents aged 6 to 16 years. Those who were breastfed for more than 12 months had a lower risk of developing overweight and obesity, especially boys between the ages of 9 and 11.