bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Implications of Serum Hypoxia Inducible Factor-1α and Vascular Endothelial Growth Factor in Lung Cancer
Authors: Shen Hong , Feng Ganzhu , Cui Jin , Du Qiang , Qin Yong , Cai Jiankang , Shen Li , Zhu Yina 
Published: May 2015

Aims and background Hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) have been deemed as key in angiogenesis of lung cancer. The aim of this study was to investigate diagnostic and prognostic values of HIF-1α and VEGF in patients with lung cancer. Methods From May 1, 2011, to April 20, 2014, blood samples and/or pleural effusions were collected from 100 patients with lung cancer, 18 patients with tuberculosis, 47 patients with community-acquired pneumonia, and 29 healthy controls. The pretreatment levels of HIF-1α and VEGF were measured by enzyme-linked immunoassays. Patients with lung cancer were followed up during the period of this study and survival times were recorded for analysis. Results We detected that the levels of serum and pleural HIF-1α in lung cancer were significantly higher than those in the tuberculosis population, and that the VEGF expressions were not significantly different between malignancy and benign diseases. An area under the curve of pleural HIF-1α (0.877 ± 0.053) showed a high ability to differentiate lung cancer from benign diseases. The significant negative predictors of survival in the univariate analysis were performance status (>1), no anticancer therapy, low serum albumin, advanced stage, and serum high level of VEGF (>324.17 pg/mL), while in the multivariate Cox regression analysis, only the pretreatment serum level of VEGF, stage, and anticancer therapy were identified as independent prognostic factors. Conclusions The overexpression of HIF-1α especially in pleural effusion may be an angiogenic factor for distinguishing malignancy from tuberculosis, and the pretreatment level of serum VEGF may be an independent predictor of survival.
Inflammatory Pseudotumor (IPT) and Inflammatory Myofibroblastic Tumor (IMT): A Representative Literature Review Occasioned by a Rare IMT of the Transverse Colon in a 9-year-old Child
Authors: Höhne Sven , Milzsch Monika , Adams Johannes , Kunze Christian , Finke Rainer 
Published: May 2015

Aims and Background Inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) represent different entities. However, it is only in recent years that this has been taken into increasing consideration. Some authors still use both terms synonymously or interchangeably. Inflammatory myofibroblastic tumor is a real neoplasm because of the proliferation of myofibroblastic cells. Inflammatory pseudotumor is a more inflammatory reactive or regenerative entity and shows an overlapping with immunoglobulin G4-related disease. Methods and Study Design To analyze the current situation, 443 publications from the last 5 years (2009 to February 2014) were included. Reports involved 938 patients and 956 organ sites. The age distribution is twin peaked with one maximum in childhood and the other between 50 and 60 years of age. This distribution is questionable due to the more frequent occurrence of IPT in the liver and of IMT in the lung. Inflammatory pseudotumors mainly occur in older patients; IMTs in children and young adults. Results and Conclusions The liver and biliary tract were the most commonly affected of all body regions, at 32%. This was followed by the lung, including the respiratory tract, at 27%, and by the gastrointestinal tract, at 10%. Lesions of the large bowel, as in the present case of a 9-year-old boy, are very rare. There were organ-related as well as nonspecific clinical symptoms, such as fever, weight loss, and fatigue. Laboratory test results revealed anemia and elevated inflammation-dependent parameters. The patterns in medical imaging are variable and nonspecific. Morphology often suggests a malignant process. For this reason, therapy in most cases is surgical, but this is required more often in IMTs. Many IPTs could be treated conservatively.
Thrombozytenzerstörung bei ITP
Authors: Sachs Ulrich , Bakchoul Tamam 
Published: May 2015

ZusammenfassungDie Immunthrombozytopenie (ITP) ist eine autoimmun bedingte Blutungsstörung, die durch isolierte Thrombozytopenie charakterisierte ist. Vermutlich ist die gestörte Bildung von autoreaktiven T-Zellen bei ITP Patienten für den Verlust der Selbsttoleranz gegenüber Plättchenantigenen verantwortlich. Bei ITPPatienten rufen autoreaktive T-Zellen eine unkontrollierte Proliferation von Autoantikörper bildenden B-Zellen hervor, die zu anhal-tender Autoimmunität gegen Plättchen führen. Die Autoimmunantwort bei ITP führt zu einer gesteigerten Plättchenzerstörung durch Antikörper vermittelte Phagozytose, Komplementaktivierung sowie durch T-Zell vermittelte Zytotoxizität. Zur Pathophysiologie der ITP tragen auch Anomalien in der Thrombopoese und eine durch Antikörper oder T-Zellen vermittelte Hemmung oder Zerstörung der Megakaryozyten bei. Diese Variabilität der Dysfunktionen der Effektorzellen könnte zur Heterogenität der klinischen Manifestation beitragen, aber auch zum Erfolg oder Versagen der Therapieverfahren. Das Verständnis der ITP-Pathomechanismen hilft, diagnostische und therapeutische Strategien zu optimieren.
Pursuing the Best Interest of Children in Non-Traditional Families
Authors: Amram Denise 
Published: May 2015

Pursuing the Best Interest of Children in Non-Traditional Families: A Comparative Overview
The need to build a legal paradigm corresponding to the current evolution of society is one of the most important challenges that family lawyers are facing in the last years. In this regard, this paper illustrates the new Italian, French, and Irish reforms aimed at pursuing the best interest of the child within non-traditional families.
Out of the Box? Domestic and Private International Law Aspects of Gender Registration
Authors: van den Brink Marjolein , Reuß Philipp , Tigchelaar Jet 
Published: May 2015

Out of the Box? Domestic and Private International Law Aspects of Gender Registration: A Comparative Analysis of Germany and the Netherlands
The legal regulation of gender identity seems to be in a state of flux. This paper compares the German and Dutch legal systems with regard to the registration of a person’s sex, focusing on the possibility in both countries not to register a baby’s sex until it can be clearly determined. In both systems, it has thus become possible that a person has no specified gender for a considerable period of time. These persons may encounter various kinds of legal problems, since the two jurisdictions have not been adapted to accommodate them. In addition, two potential problems regarding private international law issues are discussed.
Child Participation in Family Law Matters Affecting Children in South Africa
Authors: Cleophas Kelly-Anne , Assim Usang Maria 
Published: May 2015

Child Participation in Family Law Matters Affecting Children in South Africa
The right of children to participate in all matters affecting them is considered to be one of the fundamental principles guiding the understanding, interpretation, and application of all children’s rights. In terms of international law, this right is contained in Article 12 of the United Nations Convention on the Rights of the Child. Similar provisions are contained in the African Charter on the Rights and Welfare of the Child. Child participation establishes the right of every child to freely express his or her views, in all matters affecting him or her, as well as the ‘subsequent right’ for those views to be given due weight, in line with the age and maturity of the child involved. The right of the child to be heard, as expressed in the Convention on the Rights of the Child represents a shift in perspectives from children as ‘incomplete human beings’ to children as subjects of rights and not merely objects of legal protection. This article provides an overview of the manner in which the principle of child participation is incorporated in some family law matters affecting children in South Africa.
Article 15 Brussels II-bis
Authors: Curry-Sumner Ian , Wright Maria 
Published: May 2015

Article 15 Brussels II-bis: Two Views from Different Sides of the Channel
Article 15 Brussels II-bis provides for the transfer of jurisdiction from one Member State to another. This contribution examines the conditions and practice surrounding the application of Article 15 Brussels II-bis from two jurisdictions, namely the Netherlands, and England and Wales. From this comparison it is clear that there are evident divergent viewpoints as to the approach to be taken with Article 15 Brussels II-bis. This article is, therefore, aimed at bringing those differences in approach to the forefront so as to assist the European legislature in the ongoing evaluation of the Brussels II-bis Regulation.
Rush to judgment: the STI‐treatment trials and HIV in sub‐Saharan Africa
Authors: Stillwaggon Eileen , Sawers Larry 
Published: May 2015

IntroductionThe extraordinarily high incidence of HIV in sub‐Saharan Africa led to the search for cofactor infections that could explain the high rates of transmission in the region. Genital inflammation and lesions caused by sexually transmitted infections (STIs) were a probable mechanism, and numerous observational studies indicated several STI cofactors. Nine out of the ten randomized controlled trials (RCTs), however, failed to demonstrate that treating STIs could lower HIV incidence. We evaluate all 10 trials to determine if their design permits the conclusion, widely believed, that STI treatment is ineffective in reducing HIV incidence.DiscussionExamination of the trials reveals critical methodological problems sufficient to account for statistically insignificant outcomes in nine of the ten trials. Shortcomings of the trials include weak exposure contrast, confounding, non‐differential misclassification, contamination and effect modification, all of which consistently bias the results toward the null. In any future STI‐HIV trial, ethical considerations will again require weak exposure contrast. The complexity posed by HIV transmission in the genital microbial environment means that any future STI‐HIV trial will face confounding, non‐differential misclassification and effect modification. As a result, it is unlikely that additional trials would be able to answer the question of whether STI control reduces HIV incidence.ConclusionsShortcomings in published RCTs render invalid the conclusion that treating STIs and other cofactor infections is ineffective in HIV prevention. Meta‐analyses of observational studies conclude that STIs can raise HIV transmission efficiency two‐ to fourfold. Health policy is always implemented under uncertainty. Given the known benefits of STI control, the irreparable harm from not treating STIs and the likely decline in HIV incidence resulting from STI control, it is appropriate to expand STI control programmes and to use funds earmarked for HIV prevention to finance those programmes.
Ibn Mattawayh, al-Tadhkira fī aḥkām al-jawāhir wa-l-aʿrāḍ. Edited by Daniel Gimaret; and Kausalität in der muʿtazilitischen Kosmologie: Das Kitāb al-Muʾaṯṯirāt wa-miftāḥ al-muškilāt des Zayditen al-Ḥasan ar-Raṣṣāṣ (st. 584/1188)
Authors: Zysow Aaron 
Published: May 2015

Ibn Mattawayh, al-Tadhkira fī aḥkām al-jawāhir wa-l-aʿrāḍ. Edited by Daniel Gimaret. 2 vols. Cairo: IFAO, 2009. Pp. 818. €89 (paper).
Kausalität in der muʿtazilitischen Kosmologie: Das Kitāb al-Muʾaṯṯirāt wa-miftāḥ al-muškilāt des Zayditen al-Ḥasan ar-Raṣṣāṣ (st. 584/1188). By Jan Thiele. Islamic Philosophy, Theology, and Science, vol. 84. Leiden: Brill, 2011. Pp. x + 155 + 57 (Arabic). $136.
POES MEPED differential flux retrievals and electron channel contamination correction
Authors: Peck E. D. , Randall C. E. , Green J. C. , Rodriguez J. V. , Rodger C. J. 
Published: May 2015

AbstractA correction method to remove proton contamination from the electron channels of the Polar‐orbiting Operational Environmental Satellites Medium Energy Proton/Electron Detector (MEPED) is described. Proton contamination estimates are based on measurements in five of the MEPED proton spectral channels. A constrained inversion of the MEPED proton channel response function matrix is used to calculate proton differential flux spectra. In this inversion, the proton energy distribution is described by a weighted combination of exponential, power law, and Maxwellian distributions. Proton contamination in the MEPED electron spectral channels is derived by applying the electron channel proton sensitivities to the proton fluxes from the best fit proton spectra. Once the electron channel measurements are corrected for proton contamination, an inversion of the electron channel response function matrix is used to calculate electron differential flux spectra. A side benefit of the method is that it yields an estimate for the integrated electron flux in the energy range from 300 keV to 2.5 MeV with a center energy at ~800 keV. The final product is a differential spectrum of electron flux covering the energy range from about 10 keV to 2.5 MeV that is devoid of proton contamination except during large solar proton events. Comparisons of corrected MEPED differential fluxes to the Detection of Electromagnetic Emissions Transmitted from Earthquake Regions Instrument for Detecting Particles show that MEPED fluxes are greater than what is expected from altitude‐induced particle population changes; this is attributed at least partially to measurement differences in pitch angle range.
Measurement of the physical properties of the snowpack
Authors: Kinar N. J. , Pomeroy J. W. 
Published: May 2015

AbstractThis paper reviews measurement techniques and corresponding devices used to determine the physical properties of the seasonal snowpack from distances close to the ground surface. The review is placed in the context of the need for scientific observations of snowpack variables that provide inputs for predictive hydrological models that help to advance scientific understanding of geophysical processes related to snow in the near‐surface cryosphere. Many of these devices used to measure snow are invasive and require the snowpack to be disrupted, thereby precluding the possibility for multiple measurements to be made at the same sampling location. Moreover, many devices rely on the use of empirical calibration equations that may not be valid at all geographic locations. The spatial density of observations with most snow measurement devices is often inadequate. There is a need for improved automation of snowpack measurement instrumentation with an emphasis on field‐based feedback of measurement validity in lieu of postprocessing of samples or data at a lab or office location. The scientific future of snow measurement instrumentation thereby requires a synthesis between science and engineering principles that takes into consideration geophysics and the physics of device operation.
N,N′‐Dioxide/Zinc Bis(trifluoromethylsulfonyl)imide Complex Catalyzed Enantioselective Diels–Alder Reaction of Cyclopentadiene with Alkynones
Authors: Kang Tengfei , Wang Zhen , Lin Lili , Liao Yuting , Zhou Yuhang , Liu Xiaohua , Feng Xiaoming 
Published: May 2015

AbstractAn N,N′‐dioxide/zinc bis(trifluoromethylsulfonyl)imide complex has been developed as an efficient catalyst for the highly enantioselective Diels–Alder reaction of cyclopentadiene with alkynones. Various 2‐acyl substituted norbornadiene derivatives were obtained in moderate to high yields (up to 99 %) with good enantiomeric excesses (up to 95 %).magnified image
Selective Access to All Four Diastereomers of a 1,3‐Amino Alcohol by Combination of a Keto Reductase‐ and an Amine Transaminase‐Catalysed Reaction
Authors: Kohls Hannes , Anderson Mattias , Dickerhoff Jonathan , Weisz Klaus , Córdova Armando , Berglund Per , Brundiek Henrike , Bornscheuer Uwe T. , Höhne Matthias 
Published: May 2015

AbstractThe biocatalytic synthesis of chiral amines has become a valuable addition to the chemists’ toolbox. However, the efficient asymmetric synthesis of functionalised amines bearing more than one stereocentre, such as 1,3‐amino alcohols, remains challenging. By employing a keto reductase (KRED) and two enantiocomplementary amine transaminases (ATA), we developed a biocatalytic route towards all four diastereomers of 4‐amino‐1‐phenylpentane‐2‐ol as a representative molecule bearing the 1,3‐amino alcohol functionality. Starting from a racemic hydroxy ketone, a kinetic resolution using an (S)‐selective KRED provided optically active hydroxy ketone (86% ee) and the corresponding diketone. Further transamination of the hydroxy ketone was performed by either an (R)‐ or an (S)‐selective ATA, yielding the (2R,4R)‐ and (2R,4S)‐1,3‐amino alcohol diastereomers. The remaining two diastereomers were accessible in two subsequent asymmetric steps: the diketone was reduced regio‐ and enantioselectively by the same KRED, which yielded the (S)‐configured hydroxy ketone. Eventually, the subsequent transamination of the crude product with (R)‐ and (S)‐selective ATAs yielded the remaining (2S,4R)‐ and (2S,4S)‐diastereomers, respectively.magnified image
Continuous‐Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients
Authors: Gutmann Bernhard , Cantillo David , Kappe C. Oliver 
Published: May 2015

AbstractIn the past few years, continuous‐flow reactors with channel dimensions in the micro‐ or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of this type, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, microreactor technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. This Review discusses recent literature examples of continuous‐flow organic synthesis where hazardous reactions or extreme process windows have been employed, with a focus on applications of relevance to the preparation of pharmaceuticals.
Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation
Authors: Endo Tsutomu , Ito Koyu , Morimoto Junko , Kanayama Masashi , Ota Daichi , Ikesue Masahiro , Kon Shigeyuki , Takahashi Daisuke , Onodera Tomohiro , Iwasaki Norimasa , Uede Toshimitsu 
Published: May 2015

ObjectiveSyndecan 4 has been implicated as a critical mediator of inflammatory responses because of its functions as a coreceptor and reservoir for growth factors and chemokines. Although syndecan 4 is known to be expressed on B cells, its role in immune responses remains unclear. The purpose of this study was to investigate the contribution of syndecan 4 to the development of immune arthritis in murine models.MethodsThe clinical severity of 3 immunopathologically distinct models, collagen‐induced arthritis (CIA), antigen‐induced arthritis (AIA), and collagen antibody–induced arthritis (CAIA), was evaluated in wild‐type (WT) mice and in syndecan 4–deficient (Sdc4–/–) mice. Germinal center (GC) formation, B cell profiles, humoral immune responses, and B cell migration were analyzed during the course of CIA.ResultsSdc4–/– mice were resistant to the induction of CIA, which is T cell and B cell dependent, but AIA and CAIA, which are T cell dependent and T cell independent, respectively, occurred with equal frequency in WT mice and Sdc4–/– mice. Furthermore, Sdc4–/– mice had reduced numbers of B cells and deficient GC formation in draining lymph nodes (DLNs) during the course of CIA, resulting in reduced production of collagen‐specific autoantibodies. Compared with B cells from WT mice, B cells from Sdc4–/– mice showed reduced chemotactic migration toward stromal cell–derived factor 1 (SDF‐1) and reduced SDF‐1–mediated Akt phosphorylation. Consistent with these findings, in vivo transfer experiments showed that fewer Sdc4–/– B cells than WT B cells were found in and around the follicles in the DLNs.ConclusionOur findings suggest that syndecan 4 contributes to the development of CIA by promoting GC formation and autoantibody production through its regulation of SDF‐1–mediated B cell migration.
Medically Significant Infections Are Increased in Patients With Juvenile Idiopathic Arthritis Treated With Etanercept: Results From the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study
Authors: Davies Rebecca , Southwood Taunton R. , Kearsley‐Fleet Lianne , Lunt Mark , Hyrich Kimme L. ,   on behalf of the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study
Published: May 2015

ObjectiveThe association between anti–tumor necrosis factor therapy and increased rates of infection is widely documented in adults with rheumatoid arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have been less well documented. The aims of this analysis were to compare the rates of medically significant infections (MSIs) in children with JIA treated with etanercept (ETN) versus methotrexate (MTX) and to compare the rates between combination therapy with ETN plus MTX and monotherapy with ETN.MethodsA total of 852 ETN‐treated children and 260 MTX‐treated children had been recruited to the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR‐ETN). MSIs included infections that resulted in death or hospitalization or were deemed medically significant by the clinician. This on‐drug analysis followed the patients until the first MSI, treatment discontinuation, the last followup, or death. Cox proportional hazards models, which were adjusted using propensity deciles, were used to compare rates of MSI between cohorts. Sensitivity analyses were conducted specifically with regard to serious infections (SIs), which were defined as those requiring hospitalization or treatment with intravenous antibiotics/antivirals.ResultsThe ETN‐treated cohort was older and had a longer disease duration, but the disease activity was similar between the cohorts. A total of 133 first MSIs were reported (109 with ETN and 24 with MTX). Patients receiving ETN had higher rates of MSI than did the controls (propensity decile adjusted hazard ratio 2.13 [95% confidence interval 1.22–3.74]). The risk of MSI was higher whether patients were receiving combination or monotherapy. Sensitivity analysis showed no between‐group difference in the rate of SIs, which were much less common.ConclusionETN therapy is associated with an increased risk of MSI; however, this increased risk disappears when considering only SIs, which suggests that either there were differences in the severity of infections and/or there was a possible reporting bias.