bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600–Mutant Colorectal Cancer
Authors: Corcoran Ryan B. , Atreya Chloe E. , Falchook Gerald S. , Kwak Eunice L. , Ryan David P. , Bendell Johanna C. , Hamid Omid , Messersmith Wells A. , Daud Adil , Kurzrock Razelle , Pierobon Mariaelena , Sun Peng , Cunningham Elizabeth , Little Shonda , Orford Keith , Motwani Monica , Bai Yuchen , Patel Kiran , Venook Alan P. , Kopetz Scott 
Published: September 2015

Purpose To evaluate dabrafenib, a selective BRAF inhibitor, combined with trametinib, a selective MEK inhibitor, in patients with BRAF V600–mutant metastatic colorectal cancer (mCRC). Patients and Methods A total of 43 patients with BRAF V600–mutant mCRC were treated with dabrafenib (150 mg twice daily) plus trametinib (2 mg daily), 17 of whom were enrolled onto a pharmacodynamic cohort undergoing mandatory biopsies before and during treatment. Archival tissues were analyzed for microsatellite instability, PTEN status, and 487-gene sequencing. Patient-derived xenografts were established from core biopsy samples. Results Of 43 patients, five (12%) achieved a partial response or better, including one (2%) complete response, with duration of response > 36 months; 24 patients (56%) achieved stable disease as best confirmed response. Ten patients (23%) remained in the study > 6 months. All nine evaluable during-treatment biopsies had reduced levels of phosphorylated ERK relative to pretreatment biopsies (average decrease ± standard deviation, 47% ± 24%). Mutational analysis revealed that the patient achieving a complete response and two of three evaluable patients achieving a partial response had PIK3CA mutations. Neither PTEN loss nor microsatellite instability correlated with efficacy. Responses to dabrafenib plus trametinib were comparable in patient-derived xenograft–bearing mice and the biopsied lesions from each corresponding patient. Conclusion The combination of dabrafenib plus trametinib has activity in a subset of patients with BRAF V600–mutant mCRC. Mitogen-activated protein kinase signaling was inhibited in all patients evaluated, but to a lesser degree than observed in BRAF-mutant melanoma with dabrafenib alone. PIK3CA mutations were identified in responding patients and thus do not preclude response to this regimen. Additional studies targeting the mitogen-activated protein kinase pathway in this disease are warranted.
C-Jun NH2-Terminal Kinase and p38 Inhibition Suppresses Prostaglandin E2-Stimulated Aromatase and Estrogen Receptor Levels in Human Endometriosis
Authors: Zeng Cheng , Xu Jia-ning , Zhou Yan , Yang Hui-xia , Zhou Ying-fang , Xue Qing 
Published: September 2015

Context:
Endometriosis is an estrogen-dependent disease. P38 and C-jun NH2-terminal kinase (JNK) inhibitors may have a therapeutic effect on endometriosis through regulation of prostaglandin E2 (PGE2)-induced estrogen metabolism.

Objective:
The objective of this study was to determine whether the activated MAPKs signaling pathway observed in human ectopic endometrial stromal cells (ESCs) from ovarian endometriomas influences levels of aromatase and estrogen receptor β (ERβ) protein regulated by PGE2. In turn, the effects of inhibiting MAPKs in the presence of PGE2 on estrogen production were investigated in vitro and in vivo.

Results:
Expression of aromatase and ERβ regulated by PGE2 were much higher in ESCs than eutopic ESCs from the same person. Activation of p38, JNK, ERK 1/2 and ERK 5 MAPKs by PGE2 were observed in ESCs, where PGE2-stimulated aromatase and ERβ expression mainly through p38 and JNK pathway. P38 and JNK inhibition or small interfering RNA knockdown blocked PGE2-induced aromatase and ERβ expression. PGE2 enhanced binding of downstream p38 and JNK transcription factors activating transcription factor-2 and c-Jun to aromatase and ERB promoter regions in ESCs. Moreover, treatment of endometriosis xenografts with inhibitors of p38 and JNK abrogated PGE2-amplified estradiol synthesis and xenograft growth.

Conclusions:
PGE2 activates p38 and JNK signaling pathways, further stimulating c-Jun and activating transcription factor-2 binding to aromatase and ERB promoter regions with elevated estradiol production. Inhibition of JNK and P38 may be a potential method of treating human endometriosis.
Heavy skies and a cold Soviet feel: Helsinki as a Cold War cinematic body double
Authors: Paasonen Susanna 
Published: September 2015

Abstract
During the 1970s and 1980s, American and British films, and spy films in particular, situated in Moscow and Leningrad were regularly shot in the Finnish capital of Helsinki, since the film crews could not work inside the Soviet Union. This article addresses the creation of a ‘Soviet feel’ through the use of Helsinki locations in films such as Gorky Park (Apted, 1983) and Telefon (Siegel, 1977) in the geopolitical context of the Cold War and Finland’s location as both a hub for international espionage and something of a border zone between the eastern and western power blocs. This analysis is connected to a broader consideration of Cold War geography, cinematic cities as body doubles and the ‘agentiality’ of urban spaces in film.
Remarks on a failed film archival project
Authors: Snickars Pelle 
Published: September 2015

Abstract
This brief article assesses an ongoing infrastructural research project focusing on filmarkivet.se, a website devoted to historical Swedish non-fiction film. As a collaboration between film researchers and film heritage institutions, the project has to date failed to overcome conflicting archival interests. Film scholars in general need open online archives and contextual resources, while some heritage institutions seek to give access solely to a curated filmic past. While cooperation between the heritage sector and scholars is regularly envisioned as being mutually beneficial, it also faces difficulties that need to be addressed and overcome.
National innovation systems in developing countries: Barriers to university–industry collaboration in Egypt
Authors: Attia Ahmed M. 
Published: September 2015

Abstract
The purpose of this article is to investigate the Egyptian national innovation system and its main components. It aims to identify the barriers and the drivers to university–industry collaboration. Four hypotheses are proposed to measure the barriers and drivers to university–industry collaboration. These hypotheses are tested using correlation analysis and Z test based on data collected from 162 companies from industrial areas and free zones around Cairo and Alexandria. The results of the study support the proposed four hypotheses.
Power Analysis of Soliton Pulse for ROF-OFDM System
Authors: Singh Kulwinder , Bhatia Kamaljit Singh , Ryait Hardeep Singh , Kaur Amandeep 
Published: September 2015

AbstractIn this paper, propagation behavior of Soliton pulse in optical fiber communication is analyzed. Ultra high speed transmission of data over optical fiber is possible by choosing appropriate pulse shape. Soliton pulse transmission using different modulation formats is performed to minimize jitter. Also analysis is done to calculate optical power, electrical power and average peak electrical power at different frequencies.
Kidney injury molecule-1 and neutrophil gelatinase associated lipocalin in normoalbuminuric diabetic children
Authors: Ucakturk Ahmet , Avci Bahattin , Genc Gurkan , Ozkaya Ozan , Aydin Murat 
Published: September 2015

AbstractWe aimed at evaluating the urinary levels of kidney injury molecule-1 ( KIM-1) and neutrophil gelatinase associated lipocalin (NGAL), and the relationship between these markers and clinical and laboratory variables in normoalbuminuric children with type 1 diabetes (T1D).The study group consisted of 60 (F/M: 28/32) children with T1D with a median age of 13 (min: 7.1–max: 17.9) years and a mean HbAUrinary KIM-1 and NGAL levels were significantly elevated in the diabetic group (KIM-1: 0.50±0.34 ng/mg-cr; NGAL: 33±31 ng/mg-cr) compared with the nondiabetic control subjects (KIM-1: 0.26±0.25 ng/mg-cr, NGAL 13.3±14.5 ng/mg-cr) (p<0.001). No significant associations were observed between NGAL or KIM-1 and the duration of diabetes and HbANGAL and KIM are high in normoalbuminuric diabetic children before reduction in glomerular filtration rate. High NGAL and KIM-1 levels may indicate early diabetic kidney injury; however, we did not observe any relationship between these markers and diabetic indices. For clinical usefulness of these markers, long-term studies are required.
Rational laboratory diagnostics of primary immunodeficiency disorders
Authors: Hauck Fabian , Bangol Barbara , Rakhmanov Mirzokhid , Klein Hanns-Georg , Klein Christoph 
Published: September 2015

Abstract:
Primary immunodeficiency disorders (PIDs) are a group of more than 300 conditions associated with inborn defects of different elements of the immune system. First symptoms usually occur during early infancy, but some PIDs may present at first in adolescence or adulthood or after infections with specific pathogens. Typically, the underlying defect results in recurrent and persistent infections that are difficult to treat. However, patients may have a variable and wide set of symptoms ranging from mild to severe and some requiring immediate lifesaving intervention. As PIDs are relatively rare and fundamental immunological knowledge is required to understand them, an accurate diagnosis is often made too late and many patients probably may remain undiagnosed. In this article, we first give an overview on the human immune system and how PIDs are classified according to clinical features and immunological defects. Next, we focus on the possibilities of immunological and molecular genetic diagnostics of PIDs. Benefits and challenges of current diagnostic methods, especially with regard to next-generation sequencing techniques, are discussed.
Formation of homogenous copper film on MWCNTs by an efficient electroless deposition process
Authors: Sahraei Abolfazl Alizadeh , Saeed Hamidreza Naser , Fathi Alireza , Baniassadi Majid , Afrookhteh Sepehr Sima , Besharati Givi Mohammad Kazem 
Published: September 2015

Abstract
In this study, copper-coated multi-walled carbon nanotubes (MWCNTs) were prepared using electroless deposition process with an efficient bath composition. As-received MWCNTs underwent acid treatment and subsequent sensitization with tin and activation with palladium before the copper coating process. The electroless deposition process was performed in a bath, which contained copper sulphate pentahydrate as a copper precursor, potassium sodium tartrate as a complexing agent, and formaldehyde as a reducing agent. Surface modifications of MWCNTs were studied by Fourier transform infrared spectroscopy, imaging techniques (scanning electron microscopy, transmission electron microscopy), and X-ray diffraction. On the basis of the results, it was observed that the coating layer covers most surfaces of the nanotubes. Furthermore, copper oxide is also deposited on the surfaces of MWCNTs. The total amount of metals after each sensitization, activation, and metallization step was determined by thermo gravimetric method and induced coupled plasma atomic emission spectroscopy. Coating of MWCNTs was accomplished successfully through adjusting proper chemical ratios and concentrations. The calculated bath efficiency was about 99%.
A novel biaxial double-negative metamaterial for electromagnetic rectangular cloaking operation
Authors: Islam Sikder Sunbeam , Iqbal Faruque Mohammd Rashed , Islam Mohammad Tariqul 
Published: September 2015

Abstract
This paper presents the design and analysis of a novel biaxial double-negative (DNG) metamaterial for electromagnetic cloaking operation in the microwave range. The proposed metamaterial exhibits DNG characteristics for the three axes (x, y, and z axes) wave propagation through the material. For the z-axis wave propagation, it shows resonance in the X-band and shows DNG characteristics there. Similarly, for the x-axis wave propagation, the material displays resonances in the multi-band (S-, C-, and X-bands) microwave frequency ranges with DNG characteristics at the S-, C-, and X-bands. The material exhibits DNG properties at the S- and C-bands for y-axis wave propagation as well. In the basic design, a new metamaterial structure was developed that was split into two arms. The commercially available finite-difference time-domain (FDTD)-based computer simulation technology (CST) Microwave Studio software was adopted to obtain the reflection and transmission parameters of the unit cell. The metamaterial was then used in designing a rectangular electromagnetic cloaking device where a metal cylinder was perfectly cloaked in the C-band region of the microwave spectra. The metamaterial shows near-zero refractive-index property as well in the cloaked zone. This is a novel and promising design in the electromagnetic paradigm for its biaxial DNG characteristics and rectangular cloaking operation.
Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study
Authors: Thevenon J , Bourredjem A , Faivre L , Cardot-Bauters C , Calender A , Le Bras M , Giraud S , Niccoli P , Odou M F , Borson-Chazot F , Barlier A , Lombard-Bohas C , Clauser E , Tabarin A , Pasmant E , Chabre O , Castermans E , Ruszniewski P , Bertherat J , Delemer B , Christin-Maitre S , Beckers A , Guilhem I , Rohmer V , Goichot B , Caron P , Baudin E , Chanson P , Groussin L , Du Boullay H , Weryha G , Lecomte P , Schillo F , Bihan H , Archambeaud F , Kerlan V , Bourcigaux N , Kuhn J M , Vergès B , Rodier M , Renard M , Sadoul J L , Binquet C , Goudet P 
Published: September 2015

BackgroundMEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1.MethodsThe study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software.ResultsIntrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs.ConclusionThe present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.
History before diagnosis in childhood craniopharyngioma: associations with initial presentation and long-term prognosis
Authors: Hoffmann Anika , Boekhoff Svenja , Gebhardt Ursel , Sterkenburg Anthe S , Daubenbüchel Anna M M , Eveslage Maria , Müller Hermann L 
Published: September 2015

ObjectiveChildhood craniopharyngiomas (CP) are often diagnosed after a long duration of history (DOH). Tumor size, hypothalamic involvement (HI), and obesity are associated with reduced overall survival (OS) and functional capacity (FC). The effect of DOH and specific symptoms in history on presentation at initial diagnosis and long-term prognosis are unknown.DesignRetrospective analysis of patients' records and prospective longitudinal follow-up.MethodsHistories of 411 CP patients recruited in HIT Endo, KRANIOPHARYNGEOM 2000 were retrospectively evaluated for DOH, symptoms, and characteristics. The effect of specific manifestations and DOH on clinical presentation and tumor characteristics at time of initial CP diagnosis and long-term outcome were analyzed. Main outcome measures were 10-year OS and progression-free survival (PFS), FC, and BMI during longitudinal follow-up.ResultsMedian DOH was 6 months (range: 0.1–108 months) and correlated with age at diagnosis. Tumor size, HI, degree of resection, and BMI at diagnosis were not related to DOH. In multivariate analysis adjusted for age at diagnosis, only hydrocephalus was found to have a relevant influence on DOH. Visual and neurological deficits were associated with larger initial tumor size and impaired 10-year OS. Weight gain and growth failure were observed with longest DOH. PFS and FC were not related to any specific symptom. Endocrine deficits at diagnosis were associated with long DOH.ConclusionsCP is frequently diagnosed after long DOH, especially in older children. However, DOH was not associated with tumor size, HI, survival, or FC. Visual and neurological deficits necessitate rapid diagnostic workup.
Survival of Children With Hypoplastic Left Heart Syndrome
Authors: Siffel Csaba , Riehle-Colarusso Tiffany , Oster Matthew E. , Correa Adolfo 
Published: September 2015

OBJECTIVE:
To examine the survival of infants with hypoplastic left heart syndrome (HLHS) and potential influence of demographic and clinical characteristics on survival using population-based data.

METHODS:
Infants with nonsyndromic HLHS (n = 212) born between 1979 and 2005 were identified through the Metropolitan Atlanta Congenital Defects Program. Vital status was ascertained through 2009 based on linkage with vital records. We estimated Kaplan-Meier survival probabilities stratified by select demographic and clinical characteristics.

RESULTS:
The overall survival probability to 2009 was 24% and significantly improved over time: from 0% in 1979–1984 to 42% in 1999–2005. Survival probability was 66% during the first week, 27% during the first year of life, and 24% during the first 10 years. Survival of very low and low birth weight or preterm infants and those born in high-poverty neighborhoods was significantly poorer. For children with information on surgical intervention (n = 88), the overall survival was 52%, and preterm infants had significantly poorer survival (31%) compared with term infants (56%). For children who survived to 1 year of age, long-term survival was ∼90%.

CONCLUSIONS:
Survival to adolescence of children with nonsyndromic HLHS born in metropolitan Atlanta has significantly improved in recent years, with those born full term, with normal birth weight, or in a low-poverty neighborhood having a higher survival probability. Survival beyond infancy to adolescence is high. A better understanding of the growing population of survivors with HLHS is needed to inform resource planning.
Improving the Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department
Authors: Kavanagh Patricia L. , Sprinz Philippa G. , Wolfgang Tahlia L. , Killius Kelly , Champigny Maria , Sobota Amy , Dorfman David , Barry Karan , Miner Renee , Moses James M. 
Published: September 2015

OBJECTIVES:Vaso-occlusive episodes (VOEs) account for the majority of emergency department (ED) visits for children with sickle cell disease (SCD). We hypothesized that addressing key barriers to VOE care would improve receipt of analgesics and outcomes.METHODS:A quality improvement (QI) initiative was conducted from September 2010 to April 2014 to streamline VOE care in an urban pediatric ED. Four interventions were used: a standardized time-specific VOE protocol; intranasal fentanyl as the first parenteral pain medication; an SCD pain medication calculator; and provider and patient/family education. Data were collected for 3 outcome measures (mean time from triage to first parenteral opioid and admission/discharge decision, and proportion discharged from the ED); 1 process measure (mean time from triage to initiation of patient-controlled analgesia); and 4 balancing measures (mean time from triage to second intravenous opioid dose, 24-hour ED readmission, respiratory depression, and length of stay).RESULTS:There were 289 ED visits in the study period. Improvements were seen in mean time to: first dose of parenteral opioid (56 to 23 minutes); second opiate intravenous dose (106 to 83 minutes); admission and discharge decisions (163 to 109 minutes and 271 to 178 minutes, respectively); and initiation of patient-controlled analgesia (216 to 141 minutes). The proportion discharged from the ED increased from 32% to 48% (χ2 = 6.5402, P = .01). No increase in 24-hour readmission, respiratory depression, or inpatient length of stay was observed.CONCLUSIONS:Using VOE-specific interventions, we significantly improved VOE care for children. Studies are needed to determine if these results can be replicated.
Parental Supervision and Alcohol Abuse Among Adolescent Girls
Authors: Dickson Daniel J. , Laursen Brett , Stattin Håkan , Kerr Margaret 
Published: September 2015

OBJECTIVE:Inadequate parent supervision during the early adolescent years forecasts a host of conduct problems, including illicit alcohol consumption. Early pubertal maturation may exacerbate problems, because girls alienated from same-age peers seek the company of older, more mature youth. The current study examines overtime associations between parent autonomy granting and adolescent alcohol abuse during a developmental period when alcohol consumption becomes increasingly normative, to determine if early maturing girls are at special risk for problems arising from a lack of parent supervision.METHODS:At annual intervals for 4 consecutive years, a community sample of 957 Swedish girls completed surveys beginning in the first year of secondary school (approximate age: 13 years) describing rates of alcohol intoxication and perceptions of parent autonomy granting. Participants also reported age at menarche.RESULTS:Multiple-group parallel process growth curve models revealed that early pubertal maturation exacerbated the risk associated with premature autonomy granting: Alcohol intoxication rates increased 3 times faster for early maturing girls with the greatest autonomy than they did for early maturing girls with the least autonomy. Child-driven effects were also found such that higher initial levels of alcohol abuse predicted greater increases in autonomy granting as parent supervision over children engaged in illicit drinking waned.CONCLUSIONS:Early maturing girls are at elevated risk for physical and psychological adjustment difficulties. The etiology of escalating problems with alcohol can be traced, in part, to a relative absence of parent supervision during a time when peer interactions assume special significance.