bluuebunny/crossref_metadata_2025 huggingface dataset:
Type of education and civic and political attitudes
Authors: Witschge Jacqueline , Rözer Jesper , van de Werfhorst Herman G.
Published: January 2019

In addition to increasing cognitive skills and preparing students for the labour market, one of the core tasks of education is to prepare citizens for participation in democracy. Considering the ideal of democratic equality, it is important to know the degree to which civic outcomes of education are distributed equally. One feature of the education system that can lead to differential civic outcomes is tracking, that is, the sorting of students into different types of education. In this study, we examine the relationship between type of education (general/academic or vocational) and five attitudinal dimensions of civic and political engagement between the ages of 14 and 49 years in the Netherlands. By using panel data from the Netherlands Longitudinal Lifecourse Study (n = 5,312) and applying linear fixed effects models, we can observe the effect of a transition in the type of education on the within‐person change in our outcome variables. The findings demonstrate that transitions in the type of education have little effect on intention to vote, trust in institutions or ethnic tolerance. However, students making transitions in general/academic education develop higher levels of interest in politics and generalised trust than do students in vocational education or people outside the education system. This point suggests that general/academic education fosters civic and political participation.
Desmoplastic small round cell tumors: Multimodality treatment and new risk factors
Authors: Scheer Monika , Vokuhl Christian , Blank Bernd , Hallmen Erika , von Kalle Thekla , Münter Marc , Wessalowski Rüdiger , Hartwig Maite , Sparber‐Sauer Monika , Schlegel Paul‐Gerhardt , Kramm Christof M. , Kontny Udo , Spriewald Bernd , Kegel Thomas , Bauer Sebastian , Kazanowska Bernarda , Niggli Felix , Ladenstein Ruth , Ljungman Gustaf , Jahnukainen Kirsi , Fuchs Jörg , Bielack Stefan S. , Klingebiel Thomas , Koscielniak Ewa ,   the Cooperative Weichteilsarkom Studiengruppe [CWS]
Published: January 2019

Background

To evaluate optimal therapy and potential risk factors.

Methods

Data of DSRCT patients <40 years treated in prospective CWS trials 1997‐2015 were analyzed.

Results

Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high‐dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three‐year event‐free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra‐abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse.

Conclusion

Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.
Biomolecule‐Assisted Synthesis of Hierarchical Multilayered Boehmite and Alumina Nanosheets for Enhanced Molybdenum Adsorption
Authors: Saptiama Indra , Kaneti Yusuf Valentino , Yuliarto Brian , Kumada Hiroaki , Tsuchiya Kunihiko , Fujita Yoshitaka , Malgras Victor , Fukumitsu Nobuyoshi , Sakae Takeji , Hatano Kentaro , Ariga Katsuhiko , Sugahara Yoshiyuki , Yamauchi Yusuke
Published: January 2019

The effective utilization of various biomolecules for creating a series of mesoporous boehmite (γ‐AlOOH) and gamma‐alumina (γ‐Al2O3) nanosheets with unique hierarchical multilayered structures is demonstrated. The nature and concentration of the biomolecules strongly influence the degree of the crystallinity, the morphology, and the textural properties of the resulting γ‐AlOOH and γ‐Al2O3 nanosheets, allowing for easy tuning. The hierarchical γ‐AlOOH and γ‐Al2O3 multilayered nanosheets synthesized by using biomolecules exhibit enhanced crystallinity, improved particle separation, and well‐defined multilayered structures compared to those obtained without biomolecules. More impressively, these γ‐AlOOH and γ‐Al2O3 nanosheets possess high surface areas up to 425 and 371 m2 g−1, respectively, due to their mesoporous nature and hierarchical multilayered structure. When employed for molybdenum adsorption toward medical radioisotope production, the hierarchical γ‐Al2O3 multilayered nanosheets exhibit Mo adsorption capacities of 33.1–40.8 mg g−1. The Mo adsorption performance of these materials is influenced by the synergistic combination of the crystallinity, the surface area, and the pore volume. It is expected that the proposed biomolecule‐assisted strategy may be expanded for the creation of other 3D mesoporous oxides in the future.
Preparation of cadmium sulfide nanoparticles and their application for improving the properties of the electrochemical sensor for the determination of enrofloxacin in real samples
Authors: Yuting Liu , Jing Zhang , Donghui Li
Published: January 2019

An advanced electrochemical sensor for the detection of enrofloxacin (ENR) based on the use of a modified electrode containing cadmium sulfide (CdS) nanoparticles (NPs) is reported. The CdS NPs were synthesized and characterized and then coated onto the electrode to fabricate a modified electrode that exhibited a lower limit of detection of 9.5 × 10−8 mol·L−1. This detection limit compares with a traditional electrode that exhibited a concentration detection range of 1.0 × 10−2 to 1.0 × 10−7 mol·L−1. This modified electrode demonstrated good selectivity, reproducibility, response time (<40 s), lifetime (up to 12 wk), and pH range (3.3‐7.2) for the determination of ENR in real samples (eg, pig urine).
smartLAB – Interaktives Arbeiten in digitalisierter Laborumgebung
Authors: Porr Marc , Marquard Daniel , Stanislawski Nils , Austerjost Jonas , Russo Mario , Bungers Simon , Klimmt Christoph , Scheper Thomas , Beutel Sascha , Lindner Patrick
Published: January 2019

Das smartLAB ist ein Verbund aus akademischen und nicht‐akademischen Partnern mit dem Ziel eine realistische Vision des Labors der Zukunft zu entwickeln. Hierfür wird eine digitale und interaktive Laborumgebung geschaffen, die den Menschen im Laboralltag anleitet und unterstützt, nicht ersetzt. In diesem Artikel werden dabei die Gebiete Geräteansteuerung, Workflow‐Entwicklung, Dokumentation und Nutzerinteraktion beleuchtet sowie das Zusammenspiel dieser Bereiche. Außerdem wird die hardwareseitige Umsetzung dargestellt und wichtige Konzepte erläutert.
Rückgewinnung von CaCO3 aus dem Nephelinschlamm der Aluminiumoxidproduktion
Authors: Kononchuk Olga O. , Goncharova Maria V. , Hippmann Sebastian , Kraft Michael , Bertau Martin , Alexeev Alexey I.
Published: January 2019

Bei der Produktion von Aluminiumoxid aus dem Na‐Aluminiumsilikat Nephelin fallen trotz einer integrierten Prozessführung große Reststoffmengen an, die der Deponierung zugeführt werden müssen. Mithilfe einer Rückgewinnung von Pirssonit, ist es möglich, aus dem anfallenden Nephelinschlamm Calciumcarbonat und Kieselsäurehydrogel zu gewinnen und so das Schlammaufkommen erheblich zu reduzieren. Das zurückgewonnene Calciumcarbonat kann in den Aufbereitungsprozess zurückgeführt und das Kieselsäurehydrogel für die Herstellung von Baustoffen und Geopolymeren eingesetzt werden.
Development of novel apoferritin formulations for antitumour benzothiazoles
Authors: Breen Alastair F. , Wells Geoffrey , Turyanska Lyudmila , Bradshaw Tracey D.
Published: January 2019

Background

The benzothiazole structure is important in medicinal chemistry, and 5‐fluoro‐2‐(3,4‐dimethoxyphenyl) benzothiazole (GW 610) is of particular interest as it shows outstanding anticancer activity in sensitive breast and colorectal carcinoma cell lines via generation of lethal DNA adducts in sensitive cancer cells. Despite promising activity, poor water solubility limits its applications. The apoferritin (AFt) protein cage has been proposed as a robust and biocompatible drug delivery vehicle.

Aims

Here, we aim to enhance solubility of GW 610 by developing amino acid prodrug conjugates and utilizing the AFt capsule as drug delivery vessel.

Methods and results

The potent experimental antitumour agent, GW 610, has been successfully encapsulated within AFt with more than 190 molecules per AFt cage. The AFt‐GW 610 complex exhibits dose‐dependent growth inhibition and is more potent than GW 610 alone in 5/7 cancer cell lines. To enhance both aqueous solubility and encapsulation efficiency, a series of amino acid esters of GW 608 prodrug were synthesized via N,N′‐dicyclohexylcarbodiimide ester coupling to produce molecules with different polarity. A dramatic increase in encapsulation efficiency was achieved, with more than 380 molecules of GW 608‐Lys molecules per AFt cage. Release studies show sustained release of the cargo over 12 hours at physiologically relevant pH. The AFt‐encapsulated amino acid modified GW 608 complexes are sequestered more rapidly and exhibit more potent anticancer activity than unencapsulated agent.

Conclusion

These results indicate that AFt‐encapsulation of GW 610 prodrug provides a biocompatible delivery option for this potent, selective experimental antitumour agent and for amino acid‐modified GW 608. Of particular interest is the encapsulation efficiency and in vitro antitumour activity of AFt‐GW 608‐Lys, which warrants further preclinical evaluation.
Helicenes as Chiroptical Photoswitches
Authors: Ravat Prince , Šolomek Tomáš , Juríček Michal
Published: January 2019

In this Concept Article, we analyze known helicene systems that function as chiroptical photoswitches from a stereochemical perspective and classify them based on the type of transformation of the helicene core that takes place during the switching process. In every case, we inspect the stereodynamics of each of the two forms of the switch and the stereospecificity of their interconversion, and we discuss the chemical working principles and chiroptical responses of the switches. We hope that our analysis will motivate the design of new types of helicene photoswitches to expand the structural diversity of this, at present rare but beautiful, class of compounds.
MicroRNAs control eyelid development through regulating Wnt signaling
Authors: Nagai Takahiro , Trakanant Supaluk , Kawasaki Maiko , Kawasaki Katsushige , Yamada Yurie , Watanabe Momoko , Blackburn James , Otsuka‐Tanaka Yoko , Hishinuma Mitsue , Kitatmura Atsushi , Meguro Fumiya , Yamada Akane , Kodama Yasumitsu , Maeda Takeyasu , Zhou Qiliang , Saijo Yasuo , Yasue Akihiro , Sharpe Paul T. , Hindges Robert , Takagi Ritsuo , Ohazama Atsushi
Published: January 2019

Background: The timing, location, and level of gene expression are crucial for normal organ development, because morphogenesis requires strict genetic control. MicroRNAs (miRNAs) are noncoding small single‐stranded RNAs that play a critical role in regulating gene expression level. Although miRNAs are known to be involved in many biological events, the role of miRNAs in organogenesis is not fully understood. Mammalian eyelids fuse and separate during development and growth. In mice, failure of this process results in the eye‐open at birth (EOB) phenotype. Results: It has been shown that conditional deletion of mesenchymal Dicer (an essential protein for miRNA processing; Dicer
fl/fl;Wnt1Cre) leads to the EOB phenotype with full penetrance. Here, we identified that the up‐regulation of Wnt signaling resulted in the EOB phenotype in Dicer mutants. Down‐regulation of Fgf signaling observed in Dicer mutants was caused by an inverse relationship between Fgf and Wnt signaling. Shh and Bmp signaling were down‐regulated as the secondary effects in Dicer
fl/fl;Wnt1Cre mice. Wnt, Shh, and Fgf signaling were also found to mediate the epithelial–mesenchymal interactions in eyelid development.Conclusions: miRNAs control eyelid development through Wnt. Developmental Dynamics 248:201‐210, 2019. © 2019 Wiley Periodicals, Inc.
Incremental Introduction of Organocatalytic Activity into Conformationally Engineered Porphyrins
Authors: Kielmann Marc , Grover Nitika , Kalisch Werner W. , Senge Mathias O.
Published: January 2019

To study the correlation of macrocycle nonplanarity and catalytic activity of free base porphyrins in detail, a series of six tetraphenylporphyrins with graded degree of β‐ethyl substitution (“H2EtxTPPs” 1–6; x = 0, 2, 4, 6, 8) was applied in organocatalyzed reactions. The macrocycles display incrementally increasing nonplanarity due to repulsive peri‐interactions. This creates an out‐of‐plane vector and better accessibility of the core amine and imine groups as the number of alkyl substituents increases. Following such a molecular engineering approach, the inner core system could be used to activate small molecules as a result of significant saddle distortion. The potential organocatalyst “H2EtxTPPs” were used in benchmark sulfa‐Michael reactions and we found a distinct relationship between nonplanarity and conversion. These observations were attributed to the combined effect of enhanced basicity and increased H‐bonding potential that could facilitate bifunctional organocatalysis. Ultimately, density functional theory (DFT) calculations were performed on 1–6 to monitor some electronic properties of the title compounds.
A HELIXOL‐Derived Bisphosphinite Ligand: Synthesis and Application in Gold‐Catalyzed Enynes Cycloisomerization
Authors: Medena Caleb , Calogero Francesco , Lemoine Quentin , Aubert Corinne , Derat Etienne , Fensterbank Louis , Gontard Geoffrey , Khaled Omar , Vanthuyne Nicolas , Moussa Jamal , Ollivier Cyril , Petit Marc , Barbazanges Marion
Published: January 2019

The synthesis, optical resolution through derivatization, characterization, and utilization of a new helical bis(phosphinite gold) complex derived from HELIXOL are described. By using an efficient cobalt catalyst, neither irradiation nor high catalytic loading was required to access the helicene of interest. The latter was phosphorylated to afford a new chiral ligand that was studied. Especially, treatment with AuCl(SMe2) gives a dinuclear gold complex that was used in cycloisomerization reactions.
Detection and Determination of Released Ions in the Presence of Nanoparticles: Selectivity or Strategy?
Authors: Hernández Deamelys , Cepriá Gemma , Laborda Francisco , Castillo Juan R.
Published: January 2019

Metallic nanoparticles can release ionic species, but also both species can occur in the same samples. Therefore, there is a need of efficient and cost‐effective methods to determine these ionic species in the presence of the corresponding nanoparticles. Electroanalytical techniques open the door to this selective detection of NPs and their ions. In this work, a methodology that allows the direct determination of ionic silver (Ag+) in the presence of silver nanoparticles based on anodic stripping voltammetry was implemented. Silver nanoparticles were determined, after acidic digestion of the sample, by difference with respect to the total content of silver. The method was validated in terms of specific identification of silver ions, linearity, working range, limit of detection, limit of quantification, recovery, repeatability and ruggedness. All parameters are adequate for an analytical method following Eurachem recommendations. The validated method was used to determine the concentration of Ag+ and total silver in two commercial products of colloidal silver. The results were compared with those obtained by atomic absorption spectrometry in combination with an ultrafiltration step for isolation of ionic silver. There were no significant differences in the results. The proposed methodology benefits from the intrinsic selectivity of the electroanalysis methods, allowing to eliminate the steps of pretreatments of the samples, which are necessary in other techniques. The novelty of the article lies in the direct determination of Ag (I) ions in the presence of AgNPs, without the use of previous separation steps.
Determination of formaldehyde in single cell by capillary electrophoresis with LIF detection
Authors: Fu Yu‐Jia , Chen Liu , Guo Xiao‐Feng , Wang Hong
Published: January 2019

As a small molecule gas, formaldehyde (FA) is the simplest carbonyl active material and plays an important role in the carbon cycle of metabolism. However, due to the volatile nature of the gas, it is difficult to accurately quantify its content, which limits the study of the mechanism of action in life activities. Thus, an efficient approach to quantitative detection of FA in cells especially in single cell is urgent needed. Nevertheless, no method for quantifying FA in single cell has been reported to date. In this work, a fluorescent probe N‐propyl‐4‐hydrazino‐naphthalimide (NPHNA), which has highly desirable attributes and has been applied to living biological samples, was chosen as labeling reagent to detect endogenous FA at single cell level. After optimization of separation conditions, fast baseline separation of the FA derivative N‐propyl‐4‐hydrazone‐naphthalimide product (NPHNA‐FA) and NPHNA was achieved in about 5 min by CE with LIF detection. The detection limit for FA was 5 amol (S/N ratio of 3). The developed method was validated by the measurements of intracellular levels of FA in single cell.
Experimental and numerical analysis of fire scenarios involving two mechanically ventilated compartments connected together with a horizontal vent
Authors: Pretrel Hugues , Vaux Samuel
Published: January 2019

This work deals with an experimental and numerical investigation of a fire scenario involving two rooms mechanically ventilated and connected together with a horizontal vent. The objective is to improve the understanding of the physical phenomena and to assess the capability of computational fluid dynamics (CFD) numerical simulations to predict flow field for such a fire scenario. The study is based on a set of large‐scale fire experiments performed in the framework of the OECD PRISME‐2 project in the DIVA multi‐room facility of the Institut de Radioprotection et de Sûreté Nucléaire (IRSN) and of numerical simulations performed with the ISIS CFD code. The fire scenario consists of two rooms, one above the other, mechanically ventilated and connected to each other with a horizontal vent of 1 m2. The fire is a heptane pool fire located in the lower room. The analysis focuses on the coupling between the burning rate, the flow at the vent, and the configuration of the mechanical ventilation. Several regimes of combustion are encountered from well‐ventilated steady fire to under‐ventilated unsteady and oscillatory fire. The results show that the burning rate is controlled by both the mechanical ventilation and the downward flow from the vent. The numerical simulations highlight the specific pattern of the oxygen concentration field induced by the downward flow at the vent.
Impedance Study on Estimating Electrochemical Mechanisms in a Polymer Electrolyte Fuel Cell During Gradual Water Accumulation
Authors: Cruz‐Manzo S. , Cano‐Castillo U. , Greenwood P.
Published: January 2019

In this study, the change of electrochemical parameters during the gradual water accumulation of a polymer electrolyte fuel cell (PEFC) are estimated using electrochemical impedance spectroscopy (EIS) measurements and an impedance model based on electrode theory during a two‐step oxygen reduction reaction (ORR). EIS measurements were carried out in a 5 cm2 H2/O2 PEFC operated under a dead‐ended configuration of the gas reactants and during gradual accumulation of water. Kramers‐Kronig evaluation demonstrated that the EIS measurements comply with stability and linearity properties and the inductive loops featured at low frequencies are attributed to electrochemical mechanisms within the PEFC and not to instability during gradual water accumulation. The impedance model has been reported in a previous study and simulates inductive loops at low frequencies which are attributed to platinum oxide formation during the ORR. The estimated parameters obtained from this EIS‐modeling analysis can provide an insight into the decrease in PEFC performance during flooding conditions. A further qualitative analysis considering the effect of long‐term water accumulation on the oxygen‐reduction charge transfer resistance is discussed. It is possible to have an insight into the physical mechanisms of the PEFC, by combining different experimental techniques and fundamental theory in a complimentary manner.
Properties and the predictive power of implied volatility in the New Zealand dairy market
Authors: Fernandez‐Perez Adrian , Frijns Bart , Gafiatullina Ilnara , Tourani‐Rad Alireza
Published: January 2019

This study develops a dairy implied volatility index (DVIX), derived from New Zealand Exchange traded options on whole milk powder (WMP) futures. We document an inverse return–volatility relation which is asymmetric, where increases in WMP futures prices are associated with larger absolute changes in the DVIX than decreases. In sample, the results strongly suggest that the DVIX has a high information content regarding conditional variance and that the inclusion of historical information further improves the predictive power. Out of sample, we find that the DVIX provides substantial information about future realized volatility. We also document that a combination of historical volatility and the DVIX provides the best out‐of‐sample forecasts.
Impact of varying anatomic sites on advanced stage and survival of oral cancer: 9‐year prospective cohort of 27 717 cases
Authors: Su William Wang‐Yu , Su Chiu‐Wen , Chang Dun‐Cheng , Chuang Shu‐Lin , Chen Sam Li‐Sheng , Hsu Chen‐Yang , Yen Amy Ming‐Fang , Chiu Sherry Yueh‐Hsia , Fann Jean Ching‐Yuan , Lee Yi‐Huah , Jeng Ya‐Chung , Lee Yi‐Chia , Chiu Han‐Mo , Chen Tony Hsiu‐Hsi , Wang Cheng‐Ping , Chen Mu‐Kuan
Published: January 2019

Background

To elucidate the impact of varying anatomic sites on advanced stage of and death from oral cancer.

Methods

A total of 27 717 oral cancers mainly from a population‐based visual inspection program in Taiwan from 2004 to 2009 was followed until the end of 2012.

Results

Using lip cancer as reference, the odds ratios (95% confidence interval [CI]) of advanced stage of cancer were 2.20 (1.92‐2.51) for tongue, 2.60 (2.28‐2.97) for buccal, 2.68 (2.20‐3.28) for floor of mouth, 2.96 (2.52‐3.47) for hard palate, 6.04 (5.17‐7.05) for gingiva, and 10.83 (9.20‐12.74) for oropharynx. The estimated hazard ratios (95% CI) for oral cancer death increased from 1.48 (1.31‐1.67) in buccal, 1.61 (1.43‐1.82) in tongue, 1.68 (1.41‐1.99) in floor of mouth, 1.79 (1.57‐2.05) in gingiva, 1.97 (1.71‐2.26) in hard palate, and 2.15 (1.89‐2.45) in oropharynx.

Conclusion

Different anatomic sites had variations in advanced stage of and death from oral cancer and need vigilant surveillance.
African head and neck fellowships: A model for a sustainable impact on head and neck cancer care in developing countries
Authors: Fagan Johannes J. , Otiti Jeffrey , Aswani Joyce , Konney Anna , Diom Evelyne S. , Baidoo Kenneth , Onakoya Paul A. , Mugabo Rajab M. , Noah Patrick , Mashamba Victor , Kundiona Innocent , Garba Mainasara , Biadgelign Melesse G. , Macharia Chege , Bogale Mesele , Koch Wayne M.
Published: January 2019

Background

There is an extreme shortage of head and neck surgeons in Africa. Fourteen head and neck surgeons have completed fellowships in Cape Town and Cameroon. This study determines whether such Africa‐based fellowships are a good model for developing countries by making a sustainable impact on head and neck cancer care.

Methods

An observational study was conducted by emailing questionnaires to past fellows.

Results

All fellows had returned to teaching hospitals in their counties. Seven established new multidisciplinary cancer teams. Head and neck operations had increased by >335%, as had complexity of the surgery. There was effective transfer of surgical skills to trainees. All considered head and neck fellowships to be the best model to grow head and neck care.

Conclusion

Head and neck fellowships in developing countries are effective models for establishing training programs and for increasing provision of specialized surgical services in a sustainable fashion.
The Role of Complement in Liver Injury, Regeneration, and Transplantation
Authors: Thorgersen Ebbe Billmann , Barratt‐Due Andreas , Haugaa Håkon , Harboe Morten , Pischke Søren Erik , Nilsson Per H. , Mollnes Tom Eirik
Published: January 2019

The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells such as Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that likely makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation, and regeneration. Notably, complement is a double‐edged sword as activation is detrimental by inducing inflammatory tissue damage in, for example, ischemia–reperfusion injury and transplant rejection yet is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings, including liver injury and regeneration after major surgery and preservation of the organ during transplantation.
IL‐22 and IL‐22‐Binding Protein Are Associated With Development of and Mortality From Acute‐on‐Chronic Liver Failure
Authors: Schwarzkopf Katharina , Rüschenbaum Sabrina , Barat Samarpita , Cai Chengcong , Mücke Marcus M. , Fitting Daniel , Weigert Andreas , Brüne Bernhard , Zeuzem Stefan , Welsch Christoph , Lange Christian M.
Published: January 2019

Interleukin‐22 (IL‐22) has context‐dependent hepatoprotective or adverse properties in vitro and in animal models. IL‐22 binding protein (IL‐22BP) is a soluble inhibitor of IL‐22 signaling. The role of IL‐22 and IL‐22BP in patients with acute‐on‐chronic liver failure (ACLF) is unclear. Beginning in August 2013, patients with liver cirrhosis with and without ACLF were prospectively enrolled and followed at predefined time points. IL‐22 and IL‐22BP concentrations were quantified and associated with clinical endpoints. The impact of IL‐22BP on hepatocellular IL‐22 signaling was assessed by functional experiments. A total of 139 patients were analyzed, including 45 (32%), 52 (37%), and 42 (30%) patients with compensated/stable decompensated liver cirrhosis, acute decompensation of liver cirrhosis, and ACLF at baseline, respectively. Serum levels of IL‐22 and IL‐22BP were strongly associated with the presence of, or progression to, ACLF (P < 0.001), and with mortality (P < 0.01). Importantly, the mean IL‐22BP levels exceeded IL‐22 levels more than 300‐fold. Furthermore, IL‐22BP/IL‐22 ratios were lowest in patients with adverse outcomes (i.e., ACLF and death). In vitro experiments showed that IL‐22BP at these concentrations inhibits hepatocellular IL‐22 signaling, including the induction of acute‐phase proteins. The capacity of patient serum to induce signal transducer and activator of transcription 3 phosphorylation was substantially higher in the presence of low versus high IL‐22BP/IL‐22 ratios. Conclusion: Our study reveals that high IL‐22 levels and low ratios of IL‐22BP/IL‐22 are associated with ACLF and mortality of patients with cirrhosis. Excessive secretion of IL‐22BP can neutralize IL‐22 in vitro and may prevent—likely in a context‐specific manner—hepatoprotective, but also adverse effects, of IL‐22 in patients with cirrhosis.
A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors
Authors: Arnaud‐Coffin Patrick , Maillet Denis , Gan Hui K. , Stelmes Jean‐Jacques , You Benoit , Dalle Stephane , Péron Julien
Published: January 2019

The advent of immune checkpoint‐inhibitors (CPI) has transformed treatment for several cancer types. This review was performed to assess the rate of adverse events (AEs) associated with the use of CPI, alone or in combinations. A review of AEs reporting quality was also performed. All publications of Randomized Clinical Trials (RCTs) assessing CPI published before December 2017 were included. To investigate the quality of AEs reporting, a set of items was defined based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, and study‐withdrawal related AEs were collected in each treatment category. Specific immune related AEs (irAEs) were also collected when available. Pooled estimates of adverse event rates were calculated by using generalized linear mixed model. A total of 35 RCTs including 16,485 patients were included. The overall quality of AEs reporting was satisfactory, but items pertaining to methods of data collection and analysis were infrequently reported. Grade ≥ 3 AEs were reported for 14% (95% CI 12–16) of patients treated with PD(L)‐1 inhibitors, 34% (95% CI 27–42) of patients treated with CTLA‐4 inhibitors, 55% (95% CI 51–59) of patients on CPI combinations and 46% (95% CI 40–53) of patients on immunotherapy‐chemotherapy combination. The profile of irAEs was different among the treatment categories. The use of CPI, especially in combination, is associated with significant rates of Grade ≥ 3 AEs. Healthcare planning should anticipate the expected high number of patients presenting with irAEs in the future.
Recurrence of endometrial carcinoma presenting as vulvar lesions
Authors: Rottenstreich Misgav , Armon Shunit , Beller Uzi , Rosengarten Ora , Vernea Fiona , Reichman Orna
Published: January 2019

Vulvar metastasis is an unusual presentation of recurrent endometrial cancer and should be part of the differential diagnosis of vulvar lesion.
Case of caval lobular capillary hemangioma mimicking tumor thrombus
Authors: Hashimoto Sho , Obinata Daisuke , Yamaguchi Kenya , Sakurai Fuminori , Yoshida Toshiyuki , Yoshizawa Tsuyoshi , Matsui Tsuyoshi , Mochida Junichi , Masuda Shinobu , Takahashi Satoru
Published: January 2019

Introduction

We presented a rare case of caval lobular capillary hemangioma.

Case presentation

A 66‐year‐old female visited our department complaint with shadow defect in vena cava of right renal hilum appeared on computed tomography for periodically checking 3 years after radical hysterectomy with bilateral ovariectomy. Abdominal computed tomography identified a shadow defect of 35 mm in diameter in the inferior vena cava continuing posteriorly to a 35 mm mass of retroperitoneum. During the total removal of this lesion, we identified the lesion was connected to right ovarian vein. The specimen consisted of microcapillaries which formed reticular structure. Immunostaining of specimens identified positive CD31, CD34, and Factor 8 in all cells. Ki67 antibody was positive at 2–3% of all cells. These findings suggested the tumor was intravenous lobular papillary hemangioma.

Conclusion

This is the first report of intravenous lobular papillary hemangioma originated from right ovarian vein and extended to inferior vena cava.
Tests of asset pricing with time‐varying factor loads
Authors: Galvao Antonio F. , Montes‐Rojas Gabriel , Olmo Jose
Published: January 2019

This paper proposes an empirical asset pricing test based on the homogeneity of the factor risk premia across risky assets. Factor loadings are considered to be dynamic and estimated from data at higher frequencies. The factor risk premia are obtained as estimates from time series regressions applied to each risky asset. We propose Swamy‐type tests robust to the presence of generated regressors and dependence between the pricing errors to assess the homogeneity of the factor risk premia and the zero intercept hypothesis. An application to US industry portfolios shows overwhelming evidence rejecting the capital asset pricing model, and the three and five factor models developed by Fama and French (Journal of Financial Economics, 1993, 33, 3–56; Journal of Financial Economics, 2015, 116, 1–22). In particular, we reject the null hypotheses of a zero intercept, homogeneous factor risk premia across risky assets, and the joint test involving both hypotheses.
The potential of biobanked liquid based cytology samples for cervical cancer screening using Raman spectroscopy
Authors: Traynor Damien , Duraipandian Shiyamala , Bhatia Ramya , Cuschieri Kate , Martin Cara M. , O'Leary John J. , Lyng Fiona M.
Published: January 2019

Patient samples are unique and often irreplaceable. This allows biobanks to be a valuable source of material. The aim of this study was to assess the ability of Raman spectroscopy to screen for histologically confirmed cases of Cervical Intraepithelial neoplasia (CIN) using biobanked liquid based cytology (LBC) samples. Two temperatures for long term storage were assessed; 80°C and −25°C. The utility of Raman spectroscopy for the detection of CIN was compared for fresh LBC samples and biobanked LBC samples. Two groups of samples were used for the study with one group associated with disease (CIN 3) and the other associated with no disease (cytology negative). The data indicates that samples stored at −80°C are not suitable for assessment by Raman spectroscopy due to a lack of cellular material and the presence of cellular debris. However, the technology can be applied to fresh LBC samples and those stored at −25°C and is, moreover, effective in the discrimination of negative samples from those where CIN 3 has been confirmed. Pooled fresh and biobanked samples are also amenable to the technology and achieve a similar sensitivity and specificity for CIN 3. This study demonstrates that cervical cytology samples stored within biobanks at temperatures that preclude cell lysis can act as a useful resource for Raman spectroscopy and will facilitate research and translational studies in this area.
Release of simvastatin from scaffolds of poly(lactic‐co‐glycolic) acid and biphasic ceramic designed for bone tissue regeneration
Authors: Encarnação Isis C. , Sordi Mariane B. , Aragones Águedo , Müller Carmen Maria Olivera , Moreira Anderson C. , Fernandes Celso P. , Ramos Jeferson V. , Cordeiro Mabel M. R. , Fredel Márcio C. , Magini Ricardo S.
Published: January 2019

The aim of this study was to evaluate the release of simvastatin from scaffolds composed of poly(lactic‐co‐glycolic) acid (PLGA) and biphasic ceramic designed for bone engineering and to assess the physico‐chemical and mechanical properties of the scaffolds. Samples with 30% and 70% porosity were obtained with 0, 2, 5, and 8 wt %. of simvastatin through the solvent evaporation technique and leaching of sucrose particles. Scaffold degradation and simvastatin release were evaluated in phosphate‐buffered saline. Scaffolds were analyzed by scanning electron microscopy and microtomography for two‐dimensional and three‐dimensional morphological characterization of the porosity, connectivity, and intrinsic permeability. The mechanical characterization was conducted based on the compressive strength and the chemical characterization by differential scanning calorimetry and energy dispersive X‐ray spectroscopy. Gradual and prolonged simvastatin release from the scaffolds was observed. The release followed the Korsmeyer kinetics model with the predominance of case II transport for 30% porosity scaffolds, and anomalous behavior for the 70% porosity samples. Simvastatin release was also influenced by the slow scaffold degradation due to the strong chemical interaction between simvastatin and PLGA, as observed by differential scanning calorimetry. The scaffolds presented spherical and sucrose crystal‐shaped pores that resulted in a homogenous porosity, with a predominance of open pores, ensuring interconnectivity. Simvastatin incorporation into the scaffolds and increased porosity did not influence the mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico‐chemical and mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico‐chemical and mechanical properties, a promise for applications in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2152–2164, 2019.
LncRNA‐UCA1 modulates progression of colon cancer through regulating the miR‐28‐5p/HOXB3 axis
Authors: Cui Mingfu , Chen Mingyan , Shen Zhaoming , Wang Ruijie , Fang Xuedong , Song Bin
Published: January 2019

Emerging evidence has shown that the long noncoding RNA urothelial carcinoma–associated 1 (UCA1) plays a tumor‐promoting role in colorectal cancer, while miR‐28‐5p shows tumor‐inhibitory activity in several tumor types. However, the mechanisms both of these in colon cancer progression are still unknown. In this work, the detailed roles and mechanisms of UCA1 and its target genes in colon cancer were studied. The results showed that UCA1 was upregulated in colon cancer tissues when compared with the adjacent nonhumorous tissues, as well as in the various colon cancer cell lines, but the expression of miR‐28‐5p showed an opposite trend. Furthermore, a high UCA1 level in colon cancer tissues is positively associated with the tumor size and advanced tumor stages. Functional assays revealed that both UCA1 knockdown and miR‐28‐5p overexpression could inhibit colon cancer cell growth and migration. Further mechanistic studies indicated that UCA1 knockdown played tumor suppressive roles in SW480 and HT116 cells through binding with miR‐28‐5p. We also, for the first time, identified HOXB3 as the target gene of miR‐28‐5p and that HOXB3 overexpression could mediate the functions of UCA1 in cell proliferation and migration of colon cancer cells. In conclusion, our data provided evidence for the regulatory network of UCA1/miR‐28‐5p/HOXB3 in colon cancer, suggesting that UCA1, miR‐28‐5p, and HOXB3 are the potential targets for colon cancer therapy.
RhoGDIβ affects HeLa cell spindle orientation following UVC irradiation
Authors: Doi Natsumi , Kunimatsu Yuuki , Fujiura Kouhei , Togari Hiro , Minagi Kenji , Nakaoji Koichi , Hamada Kazuhiko , Temme Achim , Tatsuka Masaaki
Published: January 2019

The molecular signals that regulate mitotic spindle orientation to determine the proper division axis play a critical role in the development and maintenance of tissue homeostasis. However, deregulation of signaling events can result in spindle misorientation, which in turn can trigger developmental defects and cancer progression. Little is known about the cellular signaling pathway involved in the misorientation of proliferating cells that evade apoptosis after DNA damage. In this study, we found that perturbations to spindle orientation were induced in ultraviolet C (UVC)‐irradiated surviving cells. N‐terminal truncated Rho GDP‐dissociation inhibitor β (RhoGDIβ), which is produced by UVC irradiation, distorted the spindle orientation of HeLa cells cultured on Matrigel. The short hairpin RNA‐mediated knockdown of RhoGDIβ significantly attenuated UVC‐induced misorientation. Subsequent expression of wild‐type RhoGDIβ, but not a noncleavable mutant, RhoGDIβ (D19A), again led to a relative increase in spindle misorientation in response to UVC. Our findings revealed that RhoGDIβ impacts spindle orientation in response to DNA damage.
Ring Opening and Recyclization Reactions with Chromone‐3‐carbonitrile
Authors: Ibrahim Magdy A. , El‐Kazak Azza M.
Published: January 2019

Chemical transformations of chromone‐3‐carbonitrile (1) with some substituted hydrazines, namely, thiosemicarbazide, S‐methyl/benzyldithiocarbazate, 7‐chloro‐4‐hydrazinoquinoline, and 3‐hydrazino‐5,6‐diphenyl‐1,2,4‐triazine, led to substituted pyrazoles 2, 5–8. Ring opening of carbonitrile 1 followed by recyclization with 3‐amino‐1,2,4‐triazole and 2‐aminobenzimidazole gave triazolo[1,5‐a]pyrimidine 9 and pyrimido[1,2‐a]benzimidazole 10, respectively. Treatment of carbonitrile 1 with some heterocyclic amines produced 2‐amino‐3‐substituted‐chromones 11 and 12. The novel 3‐hydroxychromeno[4,3‐b]pyrazolo[4,3‐e]pyridin‐5(1H)‐one (13) was efficiently synthesized from the ring conversion of carbonitrile 1 with cyanoacetohydrazide. A mixture of chromeno[2,3‐b]naphthyridine 14 and chromeno[4,3‐b]pyridine 15 was obtained from base catalyzed transformation of carbonitrile 1 with malononitrile dimer. A diversity of novel annulated chromeno[2,3‐b]pyridines 16–22 was also synthesized. Chromeno[2,3‐b]pyrrole‐2‐carboxylate 23 was obtained from the reaction of carbonitrile 1 with ethyl chloroacetate. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.
Assessments of downscaled climate data with a high‐resolution weather station network reveal consistent but predictable bias
Authors: Roberts David R. , Wood Wendy H. , Marshall Shawn J.
Published: January 2019

Ecological analyses often incorporate high‐resolution environmental data to capture species‐environment relationships in modelling applications, and downscaled climate data are increasingly being used for such analyses. While such data products provide high precision, the accuracy of these data is seldom directly tested. Consequently, introduced bias from downscaling algorithms may propagate through analyses that incorporate these data products. Here, we utilize data from the Foothills Climate Array (FCA), a mesoscale grid of 232 weather stations in the prairies and eastern slopes of the Rocky Mountains in southern Alberta, Canada, to evaluate several publicly available downscaled climate products. We consider daily, monthly, and annual records for a suite of temperature and humidity variables. The FCA data are ideal to evaluate climate downscaling because they contain multi‐year observations and cover a range of topographic conditions, from flat prairie grass‐ and croplands to mountainous terrain. We find that the downscaling algorithms improve the accuracy of climate variables over simple interpolations of low‐resolution data, but errors are often large at validation locations (e.g., several °C for temperature variables), and downscaled datasets show notable elevational and seasonal bias for all variables. A bias adjustment analysis demonstrates that such bias can be greatly reduced with relatively simple regression‐based models, even when only a small subset of observational data are used, provided they cover a relatively large spread of elevations. We discuss our findings in the context of climate change and ecological modelling and make general recommendations for consumers of downscaled climate data products.
Evaluation of synoptic‐scale patterns during extreme temperature and precipitation events in Alaska
Authors: DeLaFrance Andrew , McAfee Stephanie A.
Published: January 2019

Synoptic‐scale patterns associated with daily temperature and precipitation extremes in Alaska are identified and evaluated for daily variability in order to understand consistency in forcing mechanisms associated with extreme events as well as the tendency for each pattern to produce an extreme event. Daily station data at five locations for the 29‐year period from 1982 to 2010 are used. The widely recognized ClimDex indices are used to identify extreme high temperature, low temperature, and single‐day precipitation events. Pressure patterns during extreme events are evaluated seasonally for summer (JJA) and winter (DJF) at mean sea level pressure, 700 and 500‐hPa geopotential heights. Temperature extremes are largely characterized by synoptic‐scale patterns associated with substantial warm and cold air advection, and precipitation extremes are associated with moisture advection from the North Pacific. Extreme warm and cold temperature events are generally associated with more consistent daily synoptic‐scale patterns than precipitation. Considerable dissimilarities among daily synoptic‐scale patterns associated with extreme events based on location, type of extreme event and season highlight the need for careful consideration in the practice of applying synoptic‐scale forcing patterns to forecast or downscale extreme weather events in Alaska.
Motives for Creativity: Exploring the What and Why of Everyday Creativity
Authors: Benedek Mathias , Bruckdorfer Raphaela , Jauk Emanuel
Published: January 2019

People spend a lot of time on creative activities in their leisure time, but we still know little about what these activities are and what drives them. The literature suggests that several specific motives may be relevant for everyday creative behavior, including enjoyment, expression, challenge, coping, prosocial, social, material, recognition, and duty motives. Across two online studies totaling 750 participants, enjoyment was the strongest motive for everyday creativity, consistent with previous research linking creativity to intrinsic motivation and positive affect. Importantly, however, the relevance of motives differed across creative domains: visual arts, literature, and music were more strongly motivated by expression and coping motives, whereas handicrafts and creative cooking were more strongly motivated by prosocial and recognition motives. Intrinsic motives for creative activities were substantially related to high openness to experience, but explained incremental variance in the prediction of self‐reported creativity as well as rated creative achievements. Together, these findings provide new insights into the motivational basis and function of everyday creativity.