bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Therapy–based Combination Treatment in Rhabdomyosarcoma
Authors: van Erp Anke E.M. , Versleijen-Jonkers Yvonne M.H. , van der Graaf Winette T.A. , Fleuren Emmy D.G. 
Published: July 2018

AbstractTargeted therapies have revolutionized cancer treatment; however, progress lags behind in alveolar (ARMS) and embryonal rhabdomyosarcoma (ERMS), a soft-tissue sarcoma mainly occurring at pediatric and young adult age. Insulin-like growth factor 1 receptor (IGF1R)-directed targeted therapy is one of the few single-agent treatments with clinical activity in these diseases. However, clinical effects only occur in a small subset of patients and are often of short duration due to treatment resistance. Rational selection of combination treatments of either multiple targeted therapies or targeted therapies with chemotherapy could hypothetically circumvent treatment resistance mechanisms and enhance clinical efficacy. Simultaneous targeting of distinct mechanisms might be of particular interest in this regard, as this affects multiple hallmarks of cancer at once. To determine the most promising and clinically relevant targeted therapy–based combination treatments for ARMS and ERMS, we provide an extensive overview of preclinical and (early) clinical data concerning a variety of targeted therapy–based combination treatments. We concentrated on the most common classes of targeted therapies investigated in rhabdomyosarcoma to date, including those directed against receptor tyrosine kinases and associated downstream signaling pathways, the Hedgehog signaling pathway, apoptosis pathway, DNA damage response, cell-cycle regulators, oncogenic fusion proteins, and epigenetic modifiers. Mol Cancer Ther; 17(7); 1365–80. ©2018 AACR.
CHP2 Promotes Cell Proliferation in Breast Cancer via Suppression of FOXO3a
Authors: Zhao Xiaohui , Xie Tian , Dai Ting , Zhao Wenhui , Li Jing , Xu Rui , Jiang Chao , Li Peiqiong , Deng Junyao , Su Xiaobo , Ma Ningfang 
Published: July 2018

Abstract
Calcineurin B homologous protein isoform 2 (CHP2), an essential cofactor for Na+/H+ exchanger isoform 1 (NHE1), is identified to be expressed in various malignant cell lines. However, the clinical significance and biological role of CHP2 in breast cancer remain to be established. Here, CHP2 was markedly overexpressed in breast cancer cells and clinical tumor specimens. Immunohistochemical analysis revealed that the expression of CHP2 was significantly correlated with patients' clinicopathologic characteristics like clinical stage, and breast cancer patients with high CHP2 expression had shorter overall survival compared with patients with low CHP2 expression. Moreover, it was demonstrated that overexpressing CHP2 significantly enhanced, whereas silencing endogenous CHP2 inhibited, the proliferation and tumorigenicity of breast cancer cells in vitro and in vivo. In addition, overexpression of CHP2 accelerated, whereas inhibition of CHP2 retarded, G1–S phase cell-cycle transition in breast cancer cells. Mechanistically, overexpression of CHP2 activated AKT signaling and suppressed the transactivation of the forkhead box O3 (FOXO3/FOXO3a) transcription factor.
Implications: This study discovers a previously unrecognized role of CHP2 in the progression of breast cancer and supports the significance of this gene as a novel prognostic biomarker and a potential therapeutic target for breast cancer. Mol Cancer Res; 16(10); 1512–22. ©2018 AACR.
Macropinocytosis Fuels Prostate Cancer
Authors: Commisso Cosimo , Debnath Jayanta 
Published: July 2018

Abstract
Summary: Kim and colleagues identify necrotic debris as a macropinocytic cargo in PTEN-deficient prostate cancer cells, which is catabolized to generate the nutrients and biomass necessary to support tumor cell growth and metabolism in nutrient-limiting conditions. Cancer Discov; 8(7); 800–2. ©2018 AACR.
See related article by Kim et al., p. 866.
High Neutrophil-to-Lymphocyte Ratio Predicts Stroke-Associated Pneumonia
Authors: Nam Ki-Woong , Kim Tae Jung , Lee Ji Sung , Kwon Hyung-Min , Lee Yong-Seok , Ko Sang-Bae , Yoon Byung-Woo 
Published: July 2018

Background and Purpose—
Although there are a variety of risk factors and predictive models for stroke-associated pneumonia (SAP), more objective and easily accessible markers are still needed. In this study, we evaluated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and SAP in patients with acute ischemic stroke.

Methods—
We assessed 1317 consecutive patients with acute ischemic stroke. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. The severity of pneumonia was rated using scores from the Pneumonia Severity Index, the quick Sequential Organ Failure Assessment, and the Acute Physiology and Chronic Health Evaluation II. The NLR was calculated after dividing absolute neutrophil counts by absolute lymphocyte counts.

Results—

Among the total patients, SAP occurred in 112 (9.0%) patients. Using a multivariable analysis, the NLR (adjusted odds ratio=1.55; 95% confidence interval, 1.15–2.11;
P
=0.005) remained significant after adjusting for confounders. In addition, age, atrial fibrillation, previous stroke history, initial National Institutes of Health Stroke Scale score, and high-sensitivity C-reactive protein were also significant, independent of NLR. The NLR was higher in the severe pneumonia group when it was assessed by Pneumonia Severity Index (
P
<0.001), quick Sequential Organ Failure Assessment (
P
<0.001), and Acute Physiology and Chronic Health Evaluation II scores (
P
=0.004). Furthermore, patients who had SAP had worse clinical outcomes both during hospitalization and after discharge.

Conclusions—
We demonstrated that a higher NLR predicted SAP in patients with acute ischemic stroke. The NLR may help to identify high-risk patients in time and provide clues for further studies about preventive antibiotic therapy.
„Zabić Indianina w dziecku”. O kulturowym ludobójstwie w Kanadzie i sprawiedliwości tranzycyjnej z Kate Korycki rozmawia Anna Zawadzka [“Kill the Indian in the Child.” On cultural genocide and transitional justice in Canada. Kate Korycki in an interview by Anna Zawadzka]
Authors: Zawadzka Anna 
Published: July 2018

“Kill the Indian in the Child.” On cultural genocide and transitional justice in Canada. Kate Korycki in an interview by Anna ZawadzkaThis is an interview with Kate Korycki on the reparations for the native population in Canada for what the Canadian government defined as “cultural genocide.” Kate Korycki was born in Warsaw and has lived in Toronto for 25 years. Until 2006 she worked for the Canadian Government in a ministry delivering federal social programs, like unemployment insurance and pensions. Her last job involved the implementation of the Common Experience Payment. This was the largest government program to offer reparations for the wrongs suffered by the indigenous population in Canada in residential schools, which were run for 150 years by the Catholic and Unitarian Churches. The schools have recently been characterized as sites of cultural genocide.Kate Korycki is completing her doctorate in political science at the University of Toronto. She holds an MA in Political Science from McGill University. Her broad research agenda concerns the politics of identity, belonging, and conflict. In her doctoral work she is concentrating on the politics of identity in time of transition. „Zabić Indianina w dziecku”. O kulturowym ludobójstwie w Kanadzie i sprawiedliwości tranzycyjnej z Kate Korycki rozmawia Anna ZawadzkaAnna Zawadzka przeprowadza wywiad z Kate Korycki na temat odszkodowań przyznanychrdzennym mieszkańcom w Kanadzie za to, co rząd kanadyjski określił mianem „kulturowego ludobójstwa”. Kate Korycki urodziła się w Warszawie i mieszka w Toronto od 25 lat. Do 2006 roku pracowała dla rządu kanadyjskiego, w ministerstwie spraw społecznych, takich jak bezrobocie czy emerytury. Jej ostatnia funkcja polegała na wdrożeniu „Zadośćuczynienia Wspólnego Doświadczania” (Common Experience Payment). Ten program był najszerszym gestem władz federalnych w postaci rządowych reparacji za krzywdy wyrządzone w szkołach rezydencyjnych wobec rdzennych mieszkańców w Kanadzie. Szkoły te były prowadzone przez 150 lat przez Kościół katolicki i unitariański. To właśnie działalność tych szkół została określona mianem kulturowego ludobójstwa.Kate Korycki pisze doktorat z nauk politycznych na Uniwersytecie w Toronto, po magisterium na Uniwersytecie Mcgill. Jej zainteresowania skupiają się na polityce tożsamości, przynależności i konflikcie.
Voice Abnormalities and Laryngeal Pathology in Preterm Children
Authors: Hseu Anne , Ayele Nohamin , Kawai Kosuke , Woodnorth Geralyn , Nuss Roger 
Published: July 2018

Introduction: The prevalence of voice abnormalities in children born prematurely has been reported to be as high as 58%. Few studies have examined these abnormalities with laryngoscopic or videostroboscopic findings and characterized their laryngeal pathologies. Objective: To review voice abnormalities in patients with a history of prematurity and characterize the etiology of their voice problems. A secondary objective is to see if there is a correlation between the findings and the patient’s intubation and surgical history. Methods: A retrospective chart review was conducted of all preterm patients seen in voice clinic at a tertiary pediatric hospital. Demographic data, diagnoses, and office laryngoscopies were reviewed as well as any speech therapy evaluations and/or medical and surgical treatments. Results: Fifty-seven patients were included. Mean age at presentation was 5.1 (±4.3) years. Mean gestational age was 27.8 (±3.7) weeks. Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) perceptual evaluations included a mean overall dysphonia severity of 46.6 (±24.2). Patients who had undergone prolonged intubation (⩾28 days) in the NICU or had prolonged NICU stays (>12 weeks) had significantly higher overall dysphonia severity scores. Thirty-three patients with vocal fold hypo- or immobility had significantly greater voice deviance in breathiness, loudness, and overall severity compared to those without vocal fold immobility. Of all patients, 35% were recommended surgical intervention and 49% voice therapy. Conclusion: Intubation greater than 28 days and prolonged NICU stays are associated with more severe dysphonia in premature patients. There should be a low threshold for clinical evaluation of dysphonia in this unique patient population.
Malignant Otitis Externa Outcomes: A Study of the University HealthSystem Consortium Database
Authors: Hatch Jonathan L. , Bauschard Michael J. , Nguyen Shaun A. , Lambert Paul R. , Meyer Ted A. , McRackan Theodore R. 
Published: July 2018

Objective: To characterize factors that affect outcomes for patients with malignant otitis externa (MOE). Methods: Retrospective review of inpatients with MOE was performed. Patient demographics, comorbid conditions, complications, procedures, and mortalities were analyzed. Results: A total of 786 patients with MOE were identified. The mean hospitalization length of stay (LOS) was 18.6 days (SD = 19.7). The overall mortality rate was 2.5% (n = 20), and complication rate was 4.3% (n = 34). Increasing age significantly and positively correlated with the incidence of MOE (r = 0.979, P < .0001). Factors that were associated with an increased rate of mortality were sepsis (odds ratio [OR] = 18.5; ES = 0.94; 95% CI, 0.47-1.42), congestive heart failure (OR = 3.1; ES = 0.42; 95% CI, 0.02-0.82), weight loss (OR = 10.2; ES = 1.23; 95% CI, 0.61-1.85), and coagulopathy (OR = 8.8; ES = 1.84; 95% CI, 0.91-2.77). Surgical intervention was performed in 19.2% (n = 151) of patients. Facial nerve involvement was present in 15.5% (n = 122) of patients and was associated with a significantly longer LOS of 12.9 days (SD = 19.6; ES = 0.21; 95% CI, 0.03-0.41). Conclusions: This large multi-institutional database study of MOE demonstrates that several patient factors impact the LOS and mortality. Patients at risk for unfavorable outcomes include the elderly, male gender, comorbidities, or cranial nerve involvement.
The Administrative Regime Governing the French Regulations on Foreign Trade
Authors: Chapel Yves 
Published: July 2018

by Yves Chapel This is both a detailed account and a brief comment on the rules governing foreign trade in France. The author first comments on the three guiding principles of the relevant French legislation: 1) the individual has a right to import goods, within known procedures, 2) in the procedure of examination of applications, use is made of the services of organs which do not belong to the State as such, 3) there is a strong link with the control of currencies, and the administrative execution is markedly centralised. Monsieur CHAPEL goes on to study the two fundamental legal provisions, and the agencies entrusted with their practical enforcement: Technical Directorates in the Ministries and « Technical Committees », the Office of Currency Control (« Office des Changes »), and finally delineates the actual working of this administrative machinery. His conclusion is that the « Office des Changes » possibly enjoys excessive powers, even though they are indirect, and that this may point to a regrettable tendency towards « dirigism », but he adds that the French legislation is imbued with the principle that such concentration of powers in the hands of the State must be balanced by provisions enabling the individual to defend his interests. This hopeful attitude was justified by a recent liberation of some specified imports, a provision which is commented on in an additional note.
The Effect of Lesion Characteristic on Remineralization and Model Sensitivity
Authors: Schäfer F. , Raven S.J. , Parr T.A. 
Published: July 2018

A major criterion for assessing the value of any experimental model in scientific research is the degree of correspondence between its results and data from the real-life process it is designed to model. Intra-oral models aimed at predicting the anti-caries efficacy of toothpastes or other topical treatments should therefore be calibrated against treatments proven to be effective in a caries clinical trial. For this to be achieved, it is necessary that a model with high sensitivity be designed, while at the same time retaining relevance to the process to be modeled. This means that the effects of the various experimental conditions and parameters of the model on its performance must be understood. The purpose of this paper was to assess the influence of two specific factors on the performance of an in situ enamel remineralization model, which is based on human enamel slabs attached to partial dentures. The two factors are initial lesion severity and origin of enamel sample. The results indicated that initial lesion size affected whether net remineralization or net demineralization occurred during in situ treatment. Samples with an initial range of from 1500 to 2500 (ΔZ) tended more toward demineralization than did samples with ΔZ > 3500. This means that treatment groups must be well-balanced with respect to initial lesion size. Differences in initial demineralization severity between different tooth locations must also be considered so that systematic treatment bias can be avoided. The solution used in the model discussed here is based on a balanced experimental design, which allows this effect to be taken into account in the data analysis.
The Effect of Study Design on in situ Treatment of Carious Enamel Lesions
Authors: Vernon P.G. , Raven S.J. , Gilbert R.J. , Parr T.A. , Dundon K.A. 
Published: July 2018

The aim of this exploratory study was to investigate the influence of several factors on changes in the mineral content of carious enamel lesions treated in situ. The study involved 36 adult volunteers who used either a non-fluoride toothpaste or one of two fluoride toothpastes (1000 or 1500 ppm F). Human enamel specimens were prepared and attached to partial dentures as described previously (Schäfer, 1989) and treated in situ for between three and six weeks. The mineral content of lesions was determined by microradiography and computerized densitometry. The factors investigated in this study included study length, frequency of treatment, trial design, patient compliance, patient diet, and previous caries experience of the patient. The effects observed were small, relative to that of the treatment, and not statistically significant (p > 0.05). However, the trends in the data were all as would be intuitively predicted. Study duration correlated positively with observed lesion mineral content. Lesions worn by panelists using a fluoride toothpaste for six weeks contained greater levels of mineral with respect to placebo than did those in panelists on a three-week study. The residual variations in the three phases of the study were found to be similar, suggesting that there is no advantage in these studies having a cross-over design. Brushing frequency also correlated positively with observed lesion mineral content, with panelists brushing three times per day with a fluoridated dentifrice having lesions with greater levels of mineral, with respect to placebo, than those brushing twice per day. Overall, no clear relationship between reported diet and changes in lesion mineral levels was apparent. However, increased frequency of sugar intake was associated with lower levels of mineral in lesions. No correlation was seen in this study between lifelong caries experience of panelists (DMFT) and observed mineral changes during the test period.
Sample Size Considerations in Designing Studies with Intra-oral Models
Authors: Stookey G.K. , Katz B.P. , Beiswanger B.B. , Dunipace A.J. 
Published: July 2018

Especially during recent years, the use of pre-clinical models for predicting the efficacy of fluoride systems has assumed greater importance within the scientific community. Originally utilized primarily to screen experimental fluoride delivery systems, preclinical models are now being considered as predictors of clinical efficacy in lieu of controlled clinical caries trials. Of the various preclinical models presently available, human intra-oral models have the greatest potential for reflecting intended usage conditions and therefore may be the most meaningful models for predicting clinical efficacy. However, only with the proper consideration of numerous critical variables can studies using intra-oral models be appropriately designed to achieve the desired objectives. Clearly, these models must provide relevant information in a manner which reflects clinically established cariostatic activity and be capable of detecting established differences in the amount of cariostatic activity, i.e., dose-response effects. Three sources of variation must be considered before an appropriate study design and sample size can be chosen. Based on fluoride uptake data from an intra-oral model with proximally-located enamel specimens, estimates of variation among subjects, within subjects, and among specimens within subjects were obtained. Multiple specimens per panelist do not affect the first two sources of variation. Thus, the number of panelists, and not the number of specimens, is of primary importance when pre-test data are used to choose the appropriate study design and calculate the required sample size.
The ICT in situ Experimental Model in Dental Research
Authors: Koulourides T. , Chien M.C. 
Published: July 2018

The intra-oral cariogenicity test (ICT) in situ experimental model was introduced in 1964 for the study of caries on sample enamel in the human mouth. Slabs of human or bovine enamel are mounted with a Dacron gauze cover in the acrylic flanges of prosthetic appliances. The extent of enamel demineralization or remineralization of lesions is assessed from surface microhardness measurements and microradiography of the enamel sections. The ICT model offers the potential of studying various parameters related to caries. This publication presents a typical ICT study comparing the cariogenicity of 10% sucrose solutions containing 1, 3, 10, and 30 ppm F with that of the control solution, 10% sucrose (without fluoride). The treatments were applied to the ICT as 10-minute extra-oral immersions. The results indicate: (1) a strong effect of F in decreasing demineralization of sound enamel and increasing remineralization of pre-softened enamel in the ICT; (2) pronounced resistance to a subsequent in vitro acid test; (3) pronounced F incorporation into pre-softened enamel; and (4) a characteristic acid-resistant zone, as seen in microradiographs, associated with exposure to F. This in situ model enables one to study experimental caries with repeated testing of enamel that follows the development and/or the regression of subsurface enamel lesions, F incorporation, increased acid resistance, cariogenicity of substrates, and other parameters of caries that can be assessed under standard conditions of tooth substrate and microbial sheltering.
An Improved Intra-oral Enamel Demineralization Test Model for the Study of Dental Caries
Authors: Zero D.T. , Fu J. , Anne K.M. , Cassata S. , McCormack S.M. , Gwinner L.M. 
Published: July 2018

The intra-oral enamel demineralization test (IEDT) was introduced by Brudevold et al. (1984). This caries model involves human subjects wearing palatal appliances each holding eight bovine enamel blocks covered by a bacterial cell layer prepared by the harvesting of cultures of Streptococcus mutans (test plaque). The original model used the iodide permeability test for assessment of the extent of demineralization of bovine enamel blocks resulting from acid production by the test plaque after dietary substrate challenge. The IEDT model has been expanded and improved by us in the following ways: (1) Based on encouraging findings from an in vitro study (Zero et al., 1990), the surface microhardness test has been adopted to measure the extent of demineralization occurring at three sites on the enamel blocks corresponding to an area over which the effective plaque thickness is 0.5, 1.5, and 2.5 mm; (2) intra-oral pH of the test plaque is measured by means of a Beetrode miniature pH electrode at baseline, then at five, 10, 15, 30, and 45 min after the start of a test; (3) plaque samples are collected at the end of a test and analyzed for organic acid content by means of HPLC; (4) the bacterial test challenge has been expanded to include different cariogenic bacteria which are grown under various growth conditions. The improved model has the capability of studying fundamental aspects of the caries process, namely, the relationships among dietary substrate challenge, plaque pH change, plaque organic acid profiles, microbial virulence properties, and enamel demineralization. Furthermore, the model has the potential for use in more applied research on caries-preventive agents such as fluoride.
Ranking of Apparent Area for Different Shapes of Equal Area
Authors: Martinez Nahum , Dawson William E. 
Published: July 2018

36 figures of equal area but different form made up six form classes: triangles, quadrilaterals, polygons, ellipses, stars and irregular figures. 24 students presented with each set one at a time were asked to rank the figures from largest to smallest in perceived area. Next these Ss ranked sets including figures from the different shape classes, the sets being formed on the basis of ranks in the first task. Kendall's W and Friedman's χr2 were significant for rankings within all sets suggesting consistent and differentiated influences of form on apparent area. Significant negative correlations between figure perimeter and ranks of estimated area in Exp. 1 and their absence in Exp. 2 suggested perimeter is related to apparent area with only certain sets of figures.