bluuebunny/crossref_metadata_2025 huggingface dataset:
Using healthcare claims data to analyze the prevalence of BCR‐ABL‐positive chronic myeloid leukemia in France: A nationwide population‐based study
Authors: Foulon Stéphanie , Cony‐Makhoul Pascale , Guerci‐Bresler Agnès , Delord Marc , Solary Eric , Monnereau Alain , Bonastre Julia , Tubert‐Bitter Pascale
Published: May 2019

Background

Data on Chronic Myeloid Leukemia (CML) prevalence are scarce. Here we provide an estimation of the prevalence of CML in France for the year 2014 using French national health insurance data.

Methods

We selected patients claiming reimbursement for tyrosine kinase inhibitors (TKI) or with hospital discharge diagnoses for CML, BCR/ABL‐positive or with full reimbursement of health care expenses for myeloid leukemia. We built an algorithm which we validated on a random sample of 100 potential CML patients by comparing the results obtained using the algorithm and the opinion of two hematologists who reviewed the patient demographics and sequence of care abstracted from claims data (internal validity). For external validity, we compared the number of incident CML patients identified using the algorithm with those recorded in French population‐based cancer registries in departments covered by such a registry.

Results

We identified 10 789 prevalent CML patients in 2014, corresponding to a crude prevalence rate of 16.3 per 100 000 inhabitants [95% confidence interval (CI) 16.0‐16.6]: 18.5 in men [18.0‐19.0] and 14.2 in women [13.8‐14.6]. The crude CML prevalence was less than 1.6 per 100 000 [1.2‐2.0] under age 20, increasing to a maximum of 48.2 [45.4‐51.2) at ages 75‐79. It varied from 10.2 to 23.8 per 100 000 across French departments. The algorithm showed high internal and external validity. Concordance rate between the algorithm and the hematologists was 96%, and the numbers of incident CML patients identified using the algorithm and the registries were 162 and 150, respectively.

Conclusion

We built and validated an algorithm to identify CML patients in administrative healthcare databases. In addition to prevalence estimation, the algorithm could be used for future economic evaluations or pharmaco‐epidemiological studies in this population.
Multiple exposure to environmental factors and variations in CYP27B1 and the microRNA‐binding site of IL‐13 are associated with breast cancer risk
Authors: Zhang Nannan , Chen Yanbo , Li Shuo , Yin Huihui , Li Liangliang , Shan Ming , Long Zhiping , Tian Jingshen , Li Jing , Yu Hongyuan , Xie Kun , Wu Zhen , Daria Volontovich , Wang Fan , Zhao Yashuang
Published: May 2019

Purpose

Several molecular epidemiology studies have evidenced an association of environmental factors and genetic polymorphisms with breast cancer (BC) risk. However, most have considered the functions of a single element rather than combined effects.

Methods

This case‐control study of 693 newly‐diagnosed BC cases and 714 cancer‐free controls evaluated the effect of multiple exposures to environmental factors and polymorphisms in CYP27B1 and IL‐13 on BC risk. Genotypes were detected using TaqMan genotyping. Combinations and interactions were analyzed using cross‐over analysis and multivariate logistic regression. Combining exposure models were assessed using classification and regression tree and multivariate logistic regression analyses.

Results

No significant independent association was observed for any polymorphism in CYP27B1 or IL‐13 with the risk of BC. However, significant combined effects were noted for ≥1 time/wk physical activity with rs10877012 (adjusted odds ratio [ORadj] = 0.21, 95% confidence interval [CI] = 0.11‐0.39) and rs4646536 (ORadj = 0.21, 95% CI = 0.11‐0.39) in CYP27B1. Furthermore, taking garlic ≥4 times/wk, ≥1 time/wk physical activity, and a psychological index score ≥33 all displayed significant combined effects with three IL‐13 polymorphisms. These relationships remained significant after Bonferroni correction for multiple comparisons. Combining exposure models indicated that compared with consuming garlic ≥4 times/wk, five models (model 5, ORadj = 2.94, 95% CI = 1.07‐8.06; model 6, ORadj = 10.26, 95% CI = 5.81‐18.10; model 7, ORadj = 5.05, 95% CI = 2.78‐9.17; model 8, ORadj = 3.95, 95% CI = 2.79‐5.58; and model 9, ORadj = 7.97, 95% CI = 5.26‐12.07) showed a significant increased risk.

Conclusions

Our findings suggest that personalized adjustments to diet and behavioral patterns may aid BC prevention in variant carriers of CYP27B1 and IL‐13.
A Fusion Method to Develop an Expanded Artificial Genomic RNA Replicable by Qβ Replicase
Authors: Ueda Kensuke , Mizuuchi Ryo , Matsuda Fumio , Ichihashi Norikazu
Published: May 2019

RNA‐based genomes are used to synthesize artificial cells that harbor genome replication systems. Previously, continuous replication of an artificial genomic RNA that encoded an RNA replicase was demonstrated. The next important challenge is to expand such genomes by increasing the number of encoded genes. However, technical difficulties are encountered during such expansions because the introduction of new genes disrupts the secondary structure of RNA and makes RNA nonreplicable through replicase. Herein, a fusion method that enables the construction of a longer RNA from two replicable RNAs, while retaining replication capability, is proposed. Two replicable RNAs that encode different genes at various positions are fused, and a new parameter, the unreplicable index, which negatively correlates with the replication ability of the fused RNAs better than that of the previous parameter, is determined. The unreplicable index represents the expected value of the number of G or C nucleotides that are unpaired in both the template and complementary strands. It is also observed that some of the constructed fused RNAs replicate efficiently by using the internally translated replicase. The method proposed herein could contribute to the development of an expanded RNA genome that can be used for the purpose of artificial cell synthesis.
Nuclear delivery of plasmid DNA determines the efficiency of gene expression
Authors: Liu Hui , Yang Zhen , Xun Zhe , Gao Zihao , Sun Yanping , Yu Jiankun , Yang Tianzhi , Zhao Xiaoyun , Cai Cuifang , Ding Pingtian
Published: May 2019

As a cationic non‐viral gene delivery vector, poly(agmatine/
N,
N′‐cystamine‐bis‐acrylamide) (AGM‐CBA) showed significantly higher plasmid DNA (pDNA) transfection ability than polyethylenimine (PEI) in NIH/3T3 cells. The transfection expression of AGM‐CBA/pDNA polyplexes was found to have a non‐linear relationship with AGM‐CBA/pDNA weight ratios. To further investigate the mechanism involved in the transfection process of poly(AGM‐CBA), we used pGL3‐control luciferase reporter gene (pLUC) as a reporter pDNA in this study. The distribution of pLUC in NIH/3T3 cells and nuclei after AGM‐CBA/pLUC and PEI/pLUC transfection were determined by quantitative polymerase chain reaction (qPCR) analysis. The intracellular trafficking of the polyplexes was evaluated by cellular uptake and nuclei delivery of pLUC, and the intracellular availability was evaluated by the ratio of transfection expression to the numbers of pLUC delivered in nuclei. It was found that pLUC intracellular trafficking did not have any correlation with the transfection expression, while an excellent correlation was found between the nuclei pLUC availability and transfection expression. These results suggested that the intracellular availability of pLUC in nuclei was the rate‐limiting step for pLUC transfection expression. Further optimization of the non‐viral gene delivery system can be focused on the improvement of gene intracellular availability.
Vrl1 relies on its VPS9‐domain to play a role in autophagy in Saccharomyces cerevisiae
Authors: Li Wenjing , Wu Zulin , Liang Yongheng
Published: May 2019

Autophagy is an intracellular degradation process involving many Atg proteins, which are recruited hierarchically to regulate this process. Rab/Ypt GTPases and their activators, guanine nucleotide exchange factors (GEFs), which are critical for regulating vesicle trafficking, are also involved in autophagy. Previously, we reported that yeast Vps21 and its GEF Vps9 are required for autophagy. Later, a third yeast VPS9‐domain‐containing protein, VARP‐like 1 (Vrl1), which was identified as a mutant in major laboratory strains, had partially overlapping functions with Vps9 in trafficking. In this study, we showed that Vrl1 performed roles in autophagy, and its VPS9‐domain was crucial for its role in autophagy. We found that localization of Vrl1 differed from the other two VPS9‐domain‐containing proteins, Vps9 and Muk1, and only Vrl1 changed from multipoint to diffusion after starvation. Like Vps9, Vrl1 suppressed autophagic defects caused by the VPS9 deletion. We further showed that these VPS9‐domain‐containing proteins, Vps9, Muk1, and Vrl1, all co‐localized with Atg8 on autophagosomes in cells blocked in any late step of starvation‐induced autophagy, with Vrl1 most often co‐localizing with Atg8. A small portion (<25%) of these VPS9‐domain‐containing proteins were degraded through autophagy. However, a large portion (>60%) of Vrl1 decreased independently of autophagy. We propose that Vrl1 may regulate autophagy in a similar way as Vps9, and the level of Vrl1 partly decreases through both autophagy‐dependent and ‐independent routes.
How active management survives
Authors: Heaton J. B. , Pennington Ginger L.
Published: May 2019

There is much evidence that passive equity strategies dominate active equity management, but many investors remain committed to active investing despite its poor relative performance. We explore the behavioral‐economic hypothesis that investors fall prey to the conjunction fallacy, believing good returns are more likely if investment is accompanied by hard work. This is an especially plausible manifestation of the conjunction fallacy, because in most areas of life, hard work leads to greater success than laziness. Our internet survey results show that from 30% to over 60% of higher‐income, over‐30 individuals fall prey to the conjunction fallacy in this context, raising significant questions for law and regulatory policy, including whether actively managed equity products should carry warnings, at least for retail investors.
Highly Enantio‐ and Diastereoselective Catalytic Asymmetric Tamura Cycloaddition Reactions
Authors: Collar Aarón Gutiérrez , Trujillo Cristina , Connon Stephen J.
Published: May 2019

The first broad‐scope catalytic asymmetric Tamura cycloaddition reactions are reported. Under the influence of anion‐binding bifunctional catalysis a wide range of α,β‐unsaturated N‐trityl imines undergo reactions with enolisable anhydrides to form highly synthetically useful α‐tetralone structures with excellent enantio‐ and ‐diastereocontrol. In stark contrast to the previous literature benchmarks, doubly activated or highly electron deficient alkenes are not required. A facile two‐step, high yielding sequence can convert the cycloadducts to α‐haloketones (challenging to generate catalytically by other means) with the net formation of two new C−C bonds and three new contiguous stereocentres with exquisite stereocontrol. A DFT study has provided insight into the catalyst mode of action and the origins of the observed enantiocontrol.
A Modular Access to Divinyldiphosphenes with a Strikingly Small HOMO–LUMO Energy Gap
Authors: Rottschäfer Dennis , Sharma Mahendra K. , Neumann Beate , Stammler Hans‐Georg , Andrada Diego M. , Ghadwal Rajendra S.
Published: May 2019

The olefinic C−H bond functionalization of (NHC)CHPh (NHC=IPr=C{(NAr)CH}2 1; SIPr=C{(NAr)CH2}2 2; Ar=2,6‐iPr2C6H3), derived from classical N‐heterocyclic carbenes (NHCs), with PCl3 affords the dichlorovinylphosphanes {(NHC)C(Ph)}PCl2 (NHC=IPr 3, SIPr 4). Two‐electron reduction of 3 and 4 with magnesium leads to the formation of the divinyldiphosphenes [{(NHC)C(Ph)}P]2 (NHC=IPr 5, SIPr 6) as crystalline solids. Unlike literature‐known diphosphenes, which are mostly yellow or orange, 5 is a green whereas 6 is a purple solid. Although the P=P bond lengths of 5 (2.062(1)) and 6 (2.055(1) Å) are comparable to those of the known diphosphenes (2.02–2.08 Å), the C−P bond lengths of 5 (1.785(1)) and 6 (1.797(1) Å) are, however, considerably shorter than a C
−P single bond length (1.85 Å), indicating a considerable π‐conjugation between C=C and P=P moieties. The HOMO–LUMO energy gap for 5 (4.15) and 6 (4.52 eV) is strikingly small and thus the narrowest among the diphosphenes (>4.93 eV) reported as yet. Consequently, 5 readily undergoes P=P bond cleavage at room temperature on treatment with sulfur to form the unique dithiophosphorane {(IPr)C(Ph)}P(S)2 7. Interestingly, reaction of 5 with selenium gives the selenadiphosphirane [{(IPr)C(Ph)}P]2Se 8 with an intact P−P bond.
Brodie's or Hummers’ Method: Oxidation Conditions Determine the Structure of Graphene Oxide
Authors: Feicht Patrick , Biskupek Johannes , Gorelik Tatiana E. , Renner Julian , Halbig Christian E. , Maranska Maria , Puchtler Florian , Kaiser Ute , Eigler Siegfried
Published: May 2019

Synthesis and studies of graphite oxide started more than 150 years ago and turned into a boom by the measurements of the outstanding physical properties of graphene. A series of preparation protocols emanated trying to optimize the synthesis of graphene oxide in order to obtain a less defective material, as source for graphene. However, over‐oxidation of the carbon framework hampered establishing structure‐property relationships. Here, the fact that two different synthetic methods for graphene oxide preparation lead to very similar types of graphene oxide with a preserved graphene lattice is demonstrated. Either sodium chlorate in nitric acid (similar to Brodie's method) or potassium permanganate in sulfuric acid (similar to Hummers’ method) treatment are possible; however, reaction conditions must be controlled. With a preserved carbon lattice analytical differences between the samples relate to the altered on‐plane functionality. Consequently, terming preparation protocols “according to Brodie's/Hummers’ method” is not sufficient.
Strategien zur gezielten Verbesserung des anodenseitigen Elektronentransfers in mikrobiellen Brennstoffzellen
Authors: Heydorn Raymond Leopold , Engel Christina , Krull Rainer , Dohnt Katrin
Published: May 2019

Das Konzept der mikrobiellen Brennstoffzelle (microbial fuel cell, MFC) existiert seit über 100 Jahren, doch erst im letzten Jahrzehnt ist deren praktische Anwendung in der Abwasseraufbereitung auch in Maßstäben bis 1000 L realisiert worden. In diesem Beitrag werden verfügbare Strategien vorgestellt, um den bislang noch limitierenden extrazellulären Elektronentransfer (EET) im Anodenraum von MFCs zu erhöhen. Dafür werden Organismen‐basierte Ansätze sowie der Einfluss von (Bio‐)Polymeren und Redox‐Mediatoren auf den EET vorgestellt.
Patient‐centered engagement and symptom/toxicity monitoring in the new era of tumor next‐generation sequencing and immunotherapy: The OncoTool and OncoPRO platforms
Authors: Yanez Betina , Bouchard Laura C. , Cella David , Sosman Jeffrey A. , Kircher Sheetal M. , Mohindra Nisha A. , Cristofanilli Massimo , Penedo Frank J.
Published: May 2019

The growing use of tumor next‐generation sequencing and immunotherapy has led to an increasing need among providers and patients for educational resources and supportive resources for remote and routine symptom and toxicity monitoring. This article describes the development of the OncoTool and OncoPRO platforms, which have been designed to provide easy‐to‐comprehend patient education about advanced cancer treatment options, generate more accurate expectations about tumor next‐generation sequencing and treatment toxicities, and conduct remote and routine monitoring of patient‐reported symptoms, toxicities, and quality of life.
Does social support reduce distress and worry among Aboriginal and Torres Strait Islander people with cancer?
Authors: Bernardes Christina Maresch , Langbecker Danette , Beesley Vanessa , Garvey Gail , Valery Patricia Casarolli
Published: May 2019

Background

Connections to people and place are particularly important for Indigenous Australians. It is currently unknown what role social support plays in helping this population cope with a diagnosis of cancer.

Aims

This study describes components of social support available for Indigenous Australians with cancer and investigates its association with distress and/or worry.

Methods and results

Secondary data of a cross‐sectional study involving 248 Aboriginal and Torres Strait Islander cancer patients was used to map out social support dimensions (structural, functional, and appraisal) using Cheng et al's27 social support framework. Distress was measured by the distress thermometer and worry by the worry chart. Overall, 67% of participants reported significant distress, and 49% worry about their cancer. In the functional dimension of social support, participants who had someone caring for them during diagnosis and treatment had increased odds of reporting worry. In the appraisal dimension, participants with unmet social support needs had significantly increased odds of reporting distress and worry compared with participants who were satisfied with the support received. Components in the structural dimension were not associated with distress or worry.

Conclusion

While many aspects of social support did not appear to affect cancer distress or worry, having a carer or having unmet social support needs had a negative impact on these outcomes. Health professionals should consider the worries of the bonded relationship and monitor patients' needs and their satisfaction with the support provided as an integral part of cancer care.
Cationic Gold(I) Diarylallenylidene Complexes: Bonding Features and Ligand Effects
Authors: Sorbelli Diego , Nunes dos Santos Comprido Laura , Knizia Gerald , Hashmi A. Stephen K. , Belpassi Leonardo , Belanzoni Paola , Klein Johannes E. M. N.
Published: May 2019

Using computational approaches, we qualitatively and quantitatively assess the bonding components of a series of experimentally characterized Au(I) diarylallenylidene complexes (N.Kim, R.A.Widenhoefer, Angew. Chem. Int. Ed. 2018, 57, 4722–4726). Our results clearly demonstrate that Au(I) engages only weakly in π‐backbonding, which is, however, a tunable bonding component. Computationally identified trends in bonding are clearly correlated with the substitution patterns of the aryl substituents in the Au(I) diarylallenylidene complexes and good agreement is found with the previously reported experimental data, such as IR spectra, 13C NMR chemical shifts and rates of decomposition together with their corresponding barrier heights, further substantiating the computational findings. The description of the bonding patterns in these complexes allow predictions of their spectroscopic features, their reactivity and stability.
Fabrication and Characterization of Hollow Microcapsules from Polyelectrolytes Bearing Thymine Pendant Groups for Ultraviolet‐B (UVB)‐Induced Crosslinking
Authors: Giménez Rodrigo E. , Serrano Mariana P. , Álvarez Rosa María S. , Martino Débora M. , Borsarelli Claudio D.
Published: May 2019

DNA – bioinspired polyelectrolytes poly[vinylbenzylthymine (VBT)‐4‐vinylbenzyltriethylammonium chloride (VBA)] and poly[vinylbenzylthymine (VBT)‐4‐vinylphenylsufonate (VPS)] were used for the preparation of hollow microcapsules (HMC) using the layer‐by‐layer method and CaCO3 microspheres as removable molds. Stable aqueous suspensions of spherical‐shaped HMCs with a shell composed of six layers of VBA‐based polyelectrolytes were obtained, of approximately (7.0±1.5) μm diameter and a shell thickness of 1 μm. Ultraviolet‐B irradiation of the HMC suspensions induces an efficient crosslinking between adjacent polyelectrolyte chains through the formation of thymine photodimers, such as the cyclobutane pyrimidine dimer (CPD) and the (6–4) pyrimidine–pyrimidone photoproduct (6–4PP). This process resulted in a reduction of the average interstitial mesh size of the HMC shells, modulating their permeability properties and increasing the mechanical stability of the HMC without a noticeable modification of size and shape. Thus, the DNA‐bioinspired polyelectrolytes are promising materials for the preparation of UVB‐responsive HMCs.
Immobilization of DNA on Biosensing Devices with Nitrogen Mustard–Modified Linkers
Authors: Kurinomaru Takaaki , Kojima Naoshi , Kurita Ryoji
Published: May 2019

Immobilization of DNA is an important step in relation to DNA‐based biosensors and bioassays with multiple applications. This unit describes synthesis and applications of novel bifunctional linker molecules containing nitrogen mustard and one of two types of functional groups: cyclic disulfide or biotin. Two ways of immobilizing DNA on a surface are described. With the first method, a bifunctional alkylating linker molecule is first reacted with the target DNA to form alkylated DNA and then immobilized on a specific surface. With the second method, the bifunctional alkylating linker molecule is first attached to the surface, and then the target DNA is immobilized through an alkylating reaction with a nitrogen mustard moiety. We have also achieved immunochemical detection and quantification of 5‐methylcytosine in a target DNA immobilized by the above methods. The methods for immobilization of intact DNA using novel bifunctional linker molecules are applicable to a wide range of biological analysis techniques. © 2019 by John Wiley & Sons, Inc.
Highly Selective Single‐Component Formazanate Ferrate(II) Catalysts for the Conversion of CO2 into Cyclic Carbonates
Authors: Kamphuis Aeilke J. , Milocco Francesca , Koiter Luuk , Pescarmona Paolo P. , Otten Edwin
Published: May 2019

The development of new families of active and selective single‐component catalysts based on earth‐abundant metal is of interest from a sustainable chemistry perspective. In this context, anionic mono(formazanate) iron(II) complexes bearing labile halide ligands, which possess both Lewis acidic and nucleophilic functionalities, have been developed as novel single‐component homogeneous catalysts for the reaction of CO2 with epoxides to produce cyclic carbonates. The influence of the halide ligand and the electronic properties of the formazanate ligand backbone on the catalytic activity are investigated by employing the iron(II) complexes with and without an additional nucleophile. Very high selectivity is achieved towards the formation of the cyclic carbonate products from various terminal and internal epoxides without the need of a cocatalyst.
A charge sharing–based switching scheme for SAR ADCs
Authors: Akbari Meysam , Hashemipour Omid , Nazari Masoud , Moradi Farshad
Published: May 2019

This paper presents an energy‐efficient switching scheme for successive approximation register (SAR) analogue‐to‐digital converter (ADC). The proposed scheme employs charge recycling method to keep the capacitor arrays free of transitional energy between bit generations except reset phase. In comparison with the conventional switching scheme, the proposed one achieves 100% transitional energy saving without considering reset phase. In addition, configuration of a 10‐bit SAR ADC shows that the proposed switching scheme reduces the capacitor area by 25% compared with the conventional switching scheme.
Ultrasound‐guided fine‐needle aspiration of axillary lymph nodes in breast cancer: Diagnostic accuracy and role in surgical management
Authors: Iwamoto Naoko , Aruga Tomoyuki , Horiguchi Shinichiro , Asami Hidekazu , Saita Chiaki , Onishi Mai , Goto Risa , Ishiba Toshiyuki , Honda Yayoi , Miyamoto Hiromi , Kuroi Katsumasa
Published: May 2019

Background

The objective of this study was to evaluate the accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes (LN) in breast cancer, to compare the results of FNAC and pathological examination, and to distinguish patients with 1 to 2 metastatic LNs from those with ≥3 metastatic LNs in patients with FNAC‐positive patients.

Patients and Methods

This study included 198 breasts of 196 patients with breast cancer who underwent FNAC and surgery for the primary and axilla without neoadjuvant chemotherapy from January 2010 to August 2016. Axillary nodal status was assessed by ultrasound (US), and whether FNAC‐positive had three or more suspicious LNs on US imaging was examined.

Results

The results of FNAC were positive in 75 (38%), negative in 97 (49%), suspicious in 2 (1%), indeterminate in 5 (2.5%), and insufficient in 19 patients (9.5%). FNAC sensitivity, specificity, positive predictive value, and negative predictive value were 62.6%, 100%, 100%, and 62.0%, respectively. Whereas 53% (18/34) of patients with false‐negative FNAC had one metastatic LN on final pathology, 61% (47/77) patients who were FNAC‐positive had three or more metastatic LNs. In the FNAC‐positive patients, all patients had ≥3 metastatic LNs if they had ≥3 suspicious LNs on US imaging.

Conclusion

Patients with positive cytology were more likely to have ≥3 positive LNs compared to false‐negative cytology patients. Patients with ≥3 abnormal LNs on US and positive FNAC might require axillary dissection.
Zebrafish mab21l2 mutants possess severe defects in optic cup morphogenesis, lens and cornea development
Authors: Gath Natalie , Gross Jeffrey M.
Published: May 2019

Background

Mutations in MAB21L2 result in severe ocular defects including microphthalmia, anophthalmia, coloboma, microcornea, and cataracts. The molecular and cellular underpinnings of these defects are unknown, as is the normal cellular function of MAB21L2. Zebrafish mab21l2
au10 mutants possess ocular defects resembling those in humans with MAB21L2 mutations, providing an excellent model to characterize mab21l2 functions during eye development.

Results

mab21l2
−/− mutants possessed a host of ocular defects including microphthalmia and colobomas as well as small, disorganized lenses and cornea dysgenesis. Decreased proliferation, increased cell death, and defects in marker gene expression were detected in the lens. Cell death in the optic stalk was elevated in mab21l2
−/− mutants and the basement membrane between the edges of the choroid fissure failed to break down. Neuronal differentiation in the retina was normal, however. mab21l2
−/− mutant corneas were disorganized, possessed an increased number of cells, some of which proliferated ectopically, and failed to differentiate the corneal stroma.

Conclusions

mab21l2 function is required for morphogenesis and cell survival in the lens and optic cup, and basement membrane breakdown in the choroid fissure. mab21l2 function also regulates proliferation in the lens and cornea; in its absence, the lens is small and mispatterned, and corneal morphogenesis and patterning are also disrupted.
Convenient Assembly of Privileged (Hetero)Arene‐Fused Benzo[1.4]oxazepines by Two Tandem SNAr Events. Part 2 – The Use of o‐[N‐(Hetero)aryl]aminomethyl Phenols
Authors: Firsov Andrey , Sapegin Alexander , Krasavin Mikhail
Published: May 2019

As was anticipated based on mechanistic reasoning, bis‐nucleophilic o‐(arylamino)methyl phenols underwent a facile, base‐promoted cyclocondensation with reactivity matched bis‐electrophilic (hetero)aromatic substrates to give a rare type of substituted diarene‐fused [1.4]oxazepines. This finding further supports the idea of the importance of the Smiles rearrangement in the interim of two SNAr events ultimately leading to the formation of the central cycle in the newly formed tricylic scaffold.
Stereodivergent Diversity‐Oriented Synthesis: Exploiting the Versatility of 2‐Piperidine Ethanol
Authors: Bonandi Elisa , Marzullo Paola , Foschi Francesca , Perdicchia Dario , Presti Leonardo Lo , Sironi Maurizio , Pieraccini Stefano , Gambacorta Guido , Saupe Joern , Dalla Via Lisa , Passarella Daniele
Published: May 2019

A sequence of seven reactions (stereocontrolled allylation, Mitsunobu reaction, ring closing metathesis, and amino/amido intramolecular nucleophilic addition) efficiently convert the inexpensive starting 2‐piperidine ethanol into a small library of enatiomerically pure nitrogen containing compounds characterized by three new scaffolds that present a relevant diversity. This simple approach encroaches the further exploration of the chemical space.
Palladium‐Catalyzed meta‐Selective C‐H Alkenylation and Acetoxylation of Arylacetic Acid Using a Pyrimidine Template
Authors: Jiao Bo , Peng Zhen , Dai Zhen‐Hua , Li Lei , Wang He , Zhou Ming‐Dong
Published: May 2019

Palladium‐catalyzed remote meta‐selective C‐H functionalization of arylacetic acid has been developed using a pyrimidine template. This transformation is not only tolerated to a diverse range of arylacetic acid and alkene substrates but also applicable to the synthesis of pharmaceutically active ibuprofen derivatives. Moreover, the pyrimidine template was readily removable and recyclable under mild conditions.
Palladium‐Catalyzed Double Cyclization Processes Leading to Polycyclic Heterocycles: Recent Advances
Authors: Gabriele Bartolo , Mancuso Raffaella , Veltri Lucia , Ziccarelli Ida , Della Ca' Nicola
Published: May 2019

In this minireview, we discuss some recently reported methods for the synthesis of polycyclic heterocycles by palladium‐catalyzed double cyclization processes. Paradigmatic examples taken by the most recent literature (from 2014 to the beginning of 2019) are presented. Only transformations in which palladium is involved in at least one cyclization stage are taken into consideration. The first part deals will Pd(0)‐catalyzed processes. Double cyclizations initiated by the oxidative addition of an Ar–X bond or other functional groups are treated first, followed by processes beginning with carbopalladation by Pd(0) attack to unsaturated bonds. The second part concerns Pd(II)‐catalyzed reactions, and begins with double cyclizations initiated by intramolecular nucleophilic attack to unsaturated bonds coordinated to Pd(II), followed by processes initiated by aromatic palladation.
Synthesis of Cyclic and Acyclic Nucleoside Phosphonates and Sulfonamides Derived from 6‐(Thiophen‐2‐yl)‐7‐fluoro‐7‐deazapurine
Authors: Malnuit Vincent , Smoleń Sabina , Tichý Michal , Poštová Slavětínská Lenka , Hocek Michal
Published: May 2019

Ribonuclosides derived from 6‐hetaryl‐7‐dezapurines are potent cytostatics, but their mechanism of action is unknown. Here we designed and synthesized a series of cyclic and acyclic nucleoside phosphonates, as well as carboxy, cyano, sulfo, and sulfonamide acyclic analogues derived from 6‐thiophen‐2‐yl‐7‐deazapurine and 7‐fluoro‐6‐thiophen‐2‐yl‐7‐deazapurine as ribonucleoside monophosphate mimics. None of these analogues exerted significant cytotoxic and antiviral activity.
Conditioning pain modulation reduces pain only during the first stimulation of the temporal summation of pain paradigm in healthy participants
Authors: Holden Sinead , Petersen Kristian Kjær , Arendt‐Nielsen Lars , Graven‐Nielsen Thomas
Published: May 2019

Background

Pro‐nociceptive and anti‐nociceptive mechanisms are commonly assessed in clinical and experimental pain studies, but their potential interaction is not well understood.

Objectives

Investigate the effect of conditioning pain modulation (CPM) on temporal summation of pain (TSP).

Methods

Twenty healthy participants underwent cuff algometry assessment on the lower legs to establish the pressure pain tolerance threshold (PTT). For the TSP assessment, ten stimuli at the level of the PTT were delivered by computerised cuff inflations (1‐s stimulation, 1‐s break) while participants rated pain intensity on a 10‐cm electronic visual analogue scale (VAS). This TSP paradigm was then repeated with a simultaneous conditioning stimulus induced by a cuff on the contralateral leg, inflated to a constant pressure corresponding to 30% (mild), 70% (moderate) or 100% (severe) of the PTT. These were assessed in a randomised order, with a fifteen‐minute break between tests. A final TSP test without conditioning was reassessed at the end (post‐recording).

Results

An interaction between stimuli (1–10) and repetition (p < 0.05) was found for VAS scores. VAS scores for the first stimulus were decreased during 30%, 70%, and 100% conditioning intensities, compared to baseline and post‐recordings (p < 0.05). There was a significant increase in TSP during conditioning (p < 0.05). There were no significant differences between baseline and post‐recordings for any stimuli (p > 0.05).

Conclusions

The current study indicates that mild to severe stimuli administered by cuff algometry does not modulate summation effect of temporal summation of pain, which could indicate that pain facilitatory mechanisms are more potent compared with pain inhibitory mechanisms.

Significance

Current knowledge on the interaction effect of pro and anti‐nociceptive paradigms are the lacking. The current study indicates that conditioning pain modulation does not modulate the summation effect of temporal summation of pain, when evaluated by computerized pressure algometry. This finding was independent of the mild, moderate and severe painful conditioning intensities.
The European epidemic: Pain prevalence and socioeconomic inequalities in pain across 19 European countries
Authors: Todd Adam , McNamara Courtney L. , Balaj Mirza , Huijts Tim , Akhter Nasima , Thomson Katie , Kasim Adetayo , Eikemo Terje A. , Bambra Clare
Published: May 2019

Background

Using data from the European Social Survey (ESS) 2014, this study presents an update of pain prevalence amongst men and women across Europe and undertakes the first analysis of socioeconomic inequalities in pain.

Methods

Data from the ESS 2014 survey were analysed for three pain variables: back/neck pain (n = 11,032), hand/arm pain (n = 5,954) and foot/leg pain (n = 6,314). Education was used as the indicator of socioeconomic status (SES). Age‐adjusted risk differences and age‐adjusted risk ratios were calculated from predicted probabilities generated by means of binary logistic regression. These analyses compared the lower education group with the higher education group (the socioeconomic gap), and the medium education group with the higher education group (the gradient).

Results

High prevalence rates were reported for all three types of pain across European countries. At a pan‐European level, back/neck pain was the most prevalent with 40% of survey participants experiencing pain; then hand/arm pain at 22%, and then foot/leg pain at 21%. There was considerable cross‐national variation in pain across European counties, as well as significant socioeconomic inequalities in the prevalence of pain—with social gradients or socioeconomic gaps evident for both men and women; socioeconomic inequalities were most pronounced for hand/arm pain, and least pronounced for back/neck pain. The magnitudes of the socioeconomic pain inequalities differed between countries, but were generally higher for women.

Conclusions

Future strategies to reduce the burden of pain should acknowledge and consider the associated socioeconomic inequalities of pain to ensure the “pain gap” does not widen.

Significance

This is a pan European study that has explored socioeconomic inequalities in pain. Across Europe, pain is more prevalent in people of lower socioeconomic position; these pain inequalities were most significant for hand/arm pain, and least significant for back/neck pain.
A realistic expectation of electricity production from current design concentrated solar power solar tower with thermal energy storage
Authors: Boretti Alberto
Published: May 2019

The costs and electricity production of concentrated solar power (CSP) solar tower (ST) with molten salt (MS) thermal energy storage (TES) technology are here analyzed for the latest, recently dismissed, Aurora project. For a 135 MW net nominal capacity, the likely electricity production is less than the planned 495 GWh/year, corresponding to a capacity factor (CF) of 42%. The dispatchability of this electricity production is also less than the expected. The costs of the electricity produced by this technology are larger than the AU$ 78/MWh of the power purchase agreement (PPA). The larger costs are due to the large‐scale generation certificates (LGCs), valued at around AU$80/MWh, the low‐interest loan of 110 m$AU, and the indirect costs of the larger share of intermittent and unreliable electricity. In a state with peak power prices already up to AU$14000/MWh, the peak power costs are indeed expected to rise further, if the PPA does not specify any minimum amount of electricity to be produced. Given the electricity production of the similar plant of Crescent Dunes, one‐third of the planned, despite more than double the cost, it has been impossible to secure the investments needed even at a cost of AU$ 158/MWh.
The involvement of astrocytes in early‐life adversity induced programming of the brain
Authors: Abbink Maralinde R. , van Deijk Anne‐Lieke F. , Heine Vivi M. , Verheijen Mark H. , Korosi Aniko
Published: May 2019

Early‐life adversity (ELA) in the form of stress, inflammation, or malnutrition, can increase the risk of developing psychopathology or cognitive problems in adulthood. The neurobiological substrates underlying this process remain unclear. While neuronal dysfunction and microglial contribution have been studied in this context, only recently the role of astrocytes in early‐life programming of the brain has been appreciated. Astrocytes serve many basic roles for brain functioning (e.g., synaptogenesis, glutamate recycling), and are unique in their capacity of sensing and integrating environmental signals, as they are the first cells to encounter signals from the blood, including hormonal changes (e.g., glucocorticoids), immune signals, and nutritional information. Integration of these signals is especially important during early development, and therefore we propose that astrocytes contribute to ELA induced changes in the brain by sensing and integrating environmental signals and by modulating neuronal development and function. Studies in rodents have already shown that ELA can impact astrocytes on the short and long term, however, a critical review of these results is currently lacking. Here, we will discuss the developmental trajectory of astrocytes, their ability to integrate stress, immune, and nutritional signals from the early environment, and we will review how different types of early adversity impact astrocytes.
Axoglial interactions in myelin plasticity: Evaluating the relationship between neuronal activity and oligodendrocyte dynamics
Authors: Foster Antoinette Y. , Bujalka Helena , Emery Ben
Published: May 2019

Myelin is a critical component of the vertebrate nervous system, both increasing the conduction velocity of myelinated axons and allowing for metabolic coupling between the myelinating cells and axons. An increasing number of studies demonstrate that myelination is not simply a developmentally hardwired program, but rather that new myelinating oligodendrocytes can be generated throughout life. The generation of these oligodendrocytes and the formation of myelin are influenced both during development and adulthood by experience and levels of neuronal activity. This led to the concept of adaptive myelination, where ongoing activity‐dependent changes to myelin represent a form of neural plasticity, refining neuronal functioning, and circuitry. Although human neuroimaging experiments support the concept of dynamic changes within specific white matter tracts relevant to individual tasks, animal studies have only just begun to probe the extent to which neuronal activity may alter myelination at the level of individual circuits and axons. Uncovering the role of adaptive myelination requires a detailed understanding of the localized interactions that occur between active axons and myelinating cells. In this review, we focus on recent animal studies that have begun to investigate the interactions between active axons and myelinating cells and review the evidence for—and against—the ability of neuronal activity to alter myelination at an axon‐specific level.
Comparative transcriptome analysis of sinonasal inverted papilloma and associated squamous cell carcinoma: Out‐HOXing developmental genes
Authors: Bell Diana , Bell Achim H. , Kupferman Michael E. , Prieto Victor G. , Weber Randal S. , Hanna Ehab Y.
Published: May 2019

Background

Sinonasal papilloma has a tendency toward local destruction, recurrence, and malignant transformation. This study aimed to unravel mechanisms in the malignant transformation of sinonasal papillomas using RNA‐seq.

Methods

The cohort consisted of 37 consecutive patients; tumor histology included a continuum spectrum (sinonasal papillomas/dysplastic/carcinomas‐in‐situ/invasive squamous cell carcinomas). These were microdissected and RNA was subjected to whole‐transcriptome shotgun sequencing.

Results

RNA‐seq and pathway analysis showed that the highest expressed genes/potential drivers were development‐ and differentiation‐related genes. The protein expression of six highly upregulated genes (HOXA9, EN1, DUX4, CA9, CD1a, and CK5/6) validated the RNA‐seq results. HOXA9 and CA9 were found to be expressed in most of the carcinoma samples but were largely negative in papillomas; all of the CA9‐negative carcinomas were recurrent.

Conclusions

We conclude that sinonasal carcinomas arising from papillomas are mainly defined by overexpressed developmental/homeobox genes, which provide the potential for transformation/plasticity, along with differentiation and proliferation behavior of neoplastic cells. Our results support HOXA9 and CA9 as biomarkers for carcinomas, with CA9 emerging as a predictive marker of recurrence.
Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
Authors: Sanikini Harinakshi , Muller David C. , Sophiea Marisa , Rinaldi Sabina , Agudo Antonio , Duell Eric J. , Weiderpass Elisabete , Overvad Kim , Tjønneland Anne , Halkjær Jytte , Boutron‐Ruault Marie‐Christine , Carbonnel Franck , Cervenka Iris , Boeing Heiner , Kaaks Rudolf , Kühn Tilman , Trichopoulou Antonia , Martimianaki Georgia , Karakatsani Anna , Pala Valeria , Palli Domenico , Mattiello Amalia , Tumino Rosario , Sacerdote Carlotta , Skeie Guri , Rylander Charlotta , Chirlaque López María‐Dolores , Sánchez Maria‐Jose , Ardanaz Eva , Regnér Sara , Stocks Tanja , Bueno‐de‐Mesquita Bas , Vermeulen Roel C.H. , Aune Dagfinn , Tong Tammy Y.N. , Kliemann Nathalie , Murphy Neil , Chadeau‐Hyam Marc , Gunter Marc J. , Cross Amanda J.
Published: May 2019

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow‐up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist‐to‐hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.
Synergetic effect of chemical and topological signals of gingival regeneration scaffold on the behavior of human gingival fibroblasts
Authors: Yang Moyang , Guo Zhenzhao , Li Tong , Li Jing , Chen Liyu , Wang Junmei , Wu Jincheng , Wu Zhe
Published: May 2019

Achievement of gingiva regeneration poses a substantial challenge for dental aesthetics and periodontal disease repair, but reports of a bioactive and easily available gingival regeneration scaffold are rare. Cell behaviors can be affected by multiple kinds of bioactive signals; thus, it is important to explore the effects of the chemical and topological signals of the scaffold on the behavior of human gingival fibroblasts (HGFs). We hypothesized that the synergetic effect of the chemical and topological scaffold signals were beneficial to gingival regeneration. In this study, HGF behavior on random/aligned poly (e‐caprolactone) (PCL) and polydopamine (PDA)‐coated PCL electrospun scaffolds was investigated in a common medium and in basic fibroblast growth factor (bFGF) medium. The results showed that the synergistic effect of three signals was better than that of one or two signals. The cell proliferation of the aligned scaffold group was higher than that of the random scaffold, and the PCL/PDA‐Aligned+bFGF group showed the highest cell proliferation. Even if two chemical signals were present, the HGFs still maintained an ordered distribution on the aligned scaffold. Cell differentiation and protein secretion analysis indicated that gene and protein expression of focal adhesion kinase and fibronectin were the highest in the PCL/PDA‐Aligned+bFGF group. Taken together, the chemical and topographic signals within the electrospun scaffold were considered to display a synergistic effect on HGF behaviors, suggesting the potential usefulness of the PCL/PDA‐Aligned+bFGF scaffold for gingiva tissue engineering.
Composition control in biphasic silicate microspheres on stimulating new bone regeneration and repair of osteoporotic femoral bone defect
Authors: Ghamor‐Amegavi Edem P. , Yang Xianyan , Qiu Jiandi , Xie Lijun , Pan Zhijun , Wang Juncheng , Zhang Xiangfeng , Ke Xiurong , Zhao Tengfei , Zhang Lei , Gou Zhongru
Published: May 2019

Application of bioactive materials as synthetic bone graft substitutes in regenerative medicine has seen great evolution over the past decades in treating challengeable bone defects. However, balancing the preparation conditions and biological performances of inorganic biomaterials remain a great challenge, especially when there is lack of biomaterial design on how to control component distribution and how pathological bone responds to the biomaterial stimulations and osteogenesis. Here, our objective is to develop yolk‐shell Ca‐silicate microspheres and to investigate the potential biological performances to overcome the limitations in repair of osteoporotic bone defects. The introduction of β‐calcium silicate (CaSiO3) or mesoporous bioactive glass (MBG) into self‐curing β‐dicalcium silicate (Ca2SiO4) cement shell to form spherical granules (CaSiO3@Ca2SiO4, MBG@Ca2SiO4) was to retain the physicochemical property and/or microstructure of each component for optimizing bioactive ion release that could maximize osteostimulation in osteoporosis. We report a scalable shape‐controlled mild fabrication protocol to yield the yolk‐shell granules, endowing to different phases in yolk layer and interconnected macropore networks in the closely packed granule scaffolds. This unique heterostructure preparation is governed by coaxially aligned bilayer nozzle, inorganic powders and biocompatible binders. Extensive in vitro and in vivo evaluation showed that the CaSiO3@Ca2SiO4 and MBG@Ca2SiO4 granules exhibited many superior properties such as controllable ion release, improved biodegradation and enhanced osteogenic capability in comparison with the pure Ca2SiO4@Ca2SiO4, thereby opening new mild‐condition approach in fabricating osteogenesis‐tailored silicate biomaterials for bone regenerative medicine, especially for efficient reconstruction of challenging pathological bone defects.