bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of temperature‐sensitive mutations and characterization of thermolabile RNase II variants
Authors: Reis Filipa P. , Bárria Cátia , Gomez‐Puertas Paulino , Gomes Cláudio M. , Arraiano Cecília M.
Published: December 2018

The RNase II family of ribonucleases is ubiquitous and critical for RNA metabolism. The rnb500 allele has been widely used for over 30 years; however, the underlying genetic changes which result in RNase II thermolabile activity remain unknown. Here, we combine molecular and biophysical studies to carry out an in vivo and in vitro investigation of RNase II mutation(s) that confer the rnb500 phenotype. Our findings indicate that RNase II thermolability is due to the Cys284Tyr mutation within the RNB domain, which abolishes activity by increasing protein kinetic instability at the nonpermissive temperature. These findings have important implications for the design of temperature‐sensitive variants of other RNase II enzymes, namely those with yet unknown functions.
Bcl‐2 inhibitors enhance FGFR inhibitor‐induced mitochondrial‐dependent cell death in FGFR2‐mutant endometrial cancer
Authors: Packer Leisl M. , Stehbens Samantha J. , Bonazzi Vanessa F. , Gunter Jennifer H. , Ju Robert J. , Ward Micheal , Gartside Michael G. , Byron Sara A. , Pollock Pamela M.
Published: December 2018

Endometrial cancer is the most commonly diagnosed gynaecological malignancy. Unfortunately, 15–20% of women demonstrate persistent or recurrent tumours that are refractory to current chemotherapies. We previously identified activating mutations in fibroblast growth factor receptor 2 (FGFR2) in 12% (stage I/II) to 17% (stage III/IV) endometrioid ECs and found that these mutations are associated with shorter progression‐free and cancer‐specific survival. Although FGFR inhibitors are undergoing clinical trials for treatment of several cancer types, little is known about the mechanism by which they induce cell death. We show that treatment with BGJ398, AZD4547 and PD173074 causes mitochondrial depolarization, cytochrome c release and impaired mitochondrial respiration in two FGFR2‐mutant EC cell lines (AN3CA and JHUEM2). Despite this mitochondrial dysfunction, we were unable to detect caspase activation following FGFR inhibition; in addition, the pan‐caspase inhibitor Z‐VAD‐FMK was unable to prevent cell death, suggesting that the cell death is caspase‐independent. Furthermore, while FGFR inhibition led to an increase in LC3 puncta, treatment with bafilomycin did not further increase lipidated LC3, suggesting that FGFR inhibition led to a block in autophagosome degradation. We confirmed that cell death is mitochondrial‐dependent as it can be blocked by overexpression of Bcl‐2 and/or Bcl‐XL. Importantly, we show that combining FGFR inhibitors with the BH3 mimetics ABT737/ABT263 markedly increased cell death in vitro and is more effective than BGJ398 alone in vivo, where it leads to marked tumour regression. This work may have implications for the design of clinical trials to treat a wide range of patients with FGFR‐dependent malignancies.
Molecular characterization of an MLL1 fusion and its role in chromosomal instability
Authors: Parameswaran Sreejit , Vizeacoumar Frederick S. , Kalyanasundaram Bhanumathy Kalpana , Qin Fujun , Islam Md. Fahmid , Toosi Behzad M. , Cunningham Chelsea E. , Mousseau Darrell D. , Uppalapati Maruti C. , Stirling Peter C. , Wu Yuliang , Bonham Keith , Freywald Andrew , Li Hui , Vizeacoumar Franco J.
Published: December 2018

Chromosomal rearrangements involving the mixed‐lineage leukemia (MLL1) gene are common in a unique group of acute leukemias, with more than 100 fusion partners in this malignancy alone. However, do these fusions occur or have a role in solid tumors? We performed extensive network analyses of MLL1‐fusion partners in patient datasets, revealing that multiple MLL1‐fusion partners exhibited significant interactions with the androgen‐receptor signaling pathway. Further exploration of tumor sequence data from TCGA predicts the presence of MLL1 fusions with truncated SET domain in prostate tumors. To investigate the physiological relevance of MLL1 fusions in solid tumors, we engineered a truncated version of MLL1 by fusing it with one of its known fusion partners, ZC3H13, to use as a model system. Functional characterization with cell‐based assays revealed that MLL1‐ZC3H13 fusion induced chromosomal instability, affected mitotic progression, and enhanced tumorsphere formation. The MLL1‐ZC3H13 chimera consistently increased the expression of a cancer stem cell marker (CD44); in addition, we detected potential collateral lethality between DOT1L and MLL1 fusions. Our work reveals that MLL1 fusions are likely prevalent in solid tumors and exhibit a potential pro‐tumorigenic role.
EPID‐based in vivo dosimetry using Dosimetry Check™: Overview and clinical experience in a 5‐yr study including breast, lung, prostate, and head and neck cancer patients
Authors: Nailon William H. , Welsh Daniel , McDonald Kim , Burns Donna , Forsyth Julie , Cooke Gillian , Cutanda Francisco , Carruthers Linda J. , McLaren Duncan B. , Puxeu Vaqué Josep , Kehoe Terence , Andiappa Sankar
Published: December 2018

Background

Independent verification of the dose delivered by complex radiotherapy can be performed by electronic portal imaging device (EPID) dosimetry. This paper presents 5‐yr EPID in vivo dosimetry (IVD) data obtained using the Dosimetry Check (DC) software on a large cohort including breast, lung, prostate, and head and neck (H&N) cancer patients.

Material and Methods

The difference between in vivo dose measurements obtained by DC and point doses calculated by the Eclipse treatment planning system was obtained on 3795 radiotherapy patients treated with volumetric modulated arc therapy (VMAT) (n = 842) and three‐dimensional conformal radiotherapy (3DCRT) (n = 2953) at 6, 10, and 15 MV. In cases where the dose difference exceeded ±10% further inspection and additional phantom measurements were performed.

Results

The mean and standard deviation of the percentage difference in dose obtained by DC and calculated by Eclipse in VMAT was: in brain, in H&N, and in prostate cancer. In 3DCRT, this was in brain, in breast, in bladder, in H&N, 2.60 ± 5.35% in lung and in prostate cancer. A total of 153 plans exceeded the ±10% alert criteria, which included: 88 breast plans accounting for 7.9% of all breast treatments; 28 H&N plans accounting for 4.4% of all H&N treatments; and 12 prostate plans accounting for 3.5% of all prostate treatments. All deviations were found to be as a result of patient‐related anatomical deviations and not from procedural errors.

Conclusions

This preliminary data shows that EPID‐based IVD with DC may not only be useful in detecting errors but has the potential to be used to establish site‐specific dose action levels. The approach is straightforward and has been implemented as a radiographer‐led service with no disruption to the patient and no impact on treatment time.
Iatrogenic Critical Care Procedure Complication Boot Camp: A Simulation‐based Pilot Study
Authors: Riefkohl‐Ortiz Elaine , Frey Jennifer A. , Yee Jennifer , David Gothard M. , Hughes Patrick G. , Ballas Derek A. , Ahmed Rami A.
Published: December 2018

Background

Traditional medical education strategies teach learners how to correctly perform procedures while neglecting to provide formal training on iatrogenic error management. Error management training (EMT) requires active exploration as well as explicit encouragement for learners to make and learn from errors during training. Simulation provides an excellent methodology to execute a curriculum on iatrogenic procedural complication management. We hypothesize that a standardized simulation‐based EMT curriculum will improve learner's confidence, cognitive knowledge, and performance in iatrogenic injury management.

Methods

This was a pilot, prospective, observational study performed in a simulation center using a curriculum developed to educate resident physicians on iatrogenic procedural complication management. Pre‐ and postintervention assessments included confidence surveys, cognitive questionnaires, and critical action checklists for six simulated procedure complications. Assessment data were analyzed using medians and interquartile ranges (IQRs), and the paired change scores were tested for median equality to zero via Wilcoxon signed rank tests with p < 0.05 considered statistically significant.

Results

Eighteen residents participated in the study curriculum. The median (IQR) confidence increased significantly by a summed score of 12.5 (8.75–17.25; p < 0.001). Similarly, the median (IQR) knowledge significantly increased by 6 (3–8) points from the pre‐ to postintervention assessment (p < 0.001). For each of the simulation cases, the number of critical actions performed increased significantly (p < 0.001 to p = 0.002).

Conclusion

We demonstrated significant improvement in the confidence, clinical knowledge, and performance of critical actions after the completion of this curriculum. This pilot study provides evidence that a structured EMT curriculum is an effective method to teach management of iatrogenic injuries.
Neutropenia in the age of genetic testing: Advances and challenges
Authors: Furutani Elissa , Newburger Peter E. , Shimamura Akiko
Published: December 2018

Identification of genetic causes of neutropenia informs precision medicine approaches to medical management and treatment. Accurate diagnosis of genetic neutropenia disorders informs treatment options, enables risk stratification, cancer surveillance, and attention to associated medical complications. The rapidly expanding genetic testing options for the evaluation of neutropenia have led to exciting advances but also new challenges. This review provides a practical guide to germline genetic testing for neutropenia.
A new method to quantify mandibular corpus shape in extant great apes and its potential application to the hominoid fossil record
Authors: Pitirri M. Kathleen , Begun David
Published: December 2018

Objectives

Mandibular corpus robusticity (corpus breadth/corpus height) is the most commonly utilized descriptor of the mandibular corpus in the great ape and hominin fossil records. As a consequence of its contoured shape, linear metrics used to characterize mandibular robusticity are inadequate to quantify the shape of the mandibular corpus. Here, we present an alternative to the traditional assessment of mandibular shape by analyzing the outline of the mandibular corpus in cross‐section using landmarks and semilandmarks.

Materials and methods

Outlines of the mandibular corpus in cross‐section between M1and M2were quantified in a sample of hominoids and analyzed using generalized Procrustes analysis, ProcrustesANOVA, CVA, and cluster analysis. Corpus breadth and width were also collected from the same sample and analyzed using regression,ANOVA,and cluster analysis.

Results

Analysis of corpus outline shape revealed significant differences in mandibular corpus shape that are independent of size and sex at the genus level across hominoids. Cluster analysis based on the analysis of corpus outline shape results in almost all specimens grouping based on taxonomic affinity (99.28% correct classification). Comparison of these results to results using traditional measures of mandibular robusticity shows that analysis of the outline of the corpus in cross‐section discriminate extant great apes more reliably.

Conclusion

The strong taxonomic signal revealed by this analysis indicates that quantification of the outline of the mandibular corpus more fully captures mandibular corpus shape and offers the potential for greater power in discriminating among taxa in the hominoid fossil record.
Reduction of Carbon Oxides by an Acyclic Silylene: Reductive Coupling of CO
Authors: Protchenko Andrey V. , Vasko Petra , Do Dinh Cao Huan , Hicks Jamie , Fuentes M. Ángeles , Jones Cameron , Aldridge Simon
Published: December 2018

Reactions of a boryl‐substituted acyclic silylene with carbon dioxide and monoxide are reported. The former proceeds through oxygen atom abstraction, generating CO (with rearrangement of the putative silanone product through silyl‐group transfer). The latter is characterized by reductive coupling of CO to give an ethynediolate fragment, which undergoes formal insertion into the Si−B bond. The net conversion of carbon dioxide with two equivalents of silylene offers a route for the three‐electron reduction of CO2 to [C2O2]2−.
Skeletons of the Eye: An Evolutionary and Developmental Perspective
Authors: Franz‐Odendaal Tamara Anne
Published: December 2018

The ocular skeleton, composed of the scleral cartilage and scleral ossicles, is present in many vertebrates. The morphology of the scleral cartilage and ossicles varies within different extant reptiles (including birds) and also varies dramatically from the morphology in extant teleosts. This incredible range of diverse morphologies is the result of millions of years of evolution. Both the position of these elements within the eye and the timing of development vary amongst different vertebrates. While the development of both the scleral cartilage and scleral ossicles is somewhat understood in reptiles and in teleosts, the functional advantage of these elements is still debated. Most reptiles have a multi‐component scleral ossicle ring composed of a series of flat bone plates and a scleral cartilage cup lining the retina, some sharks have calcified cartilage plates, and some teleosts have two bones while most others only have a ring of scleral cartilage. The data presented shows that different vertebrates have adapted to similar selective pressures in different ways. However, the reason why sarcopterygians have a series of overlapping bones in the sclera remains unclear. A better understanding of the ocular skeletal diversity in Reptilia as well as a better understanding of the mechanisms of vision within different environments (i.e., air vs. water) and that used by secondarily aquatic organisms is needed. This review discusses the observed variation in morphology and development of the ocular skeleton in the context of evolution and highlights our knowledge gaps in these areas. Anat Rec, 2018. © 2018 American Association for Anatomy.
Saws, Scissors, and Sharks: Late Paleozoic Experimentation with Symphyseal Dentition
Authors: Tapanila Leif , Pruitt Jesse , Wilga Cheryl D. , Pradel Alan
Published: December 2018

Sharks of Late Paleozoic oceans evolved unique dentitions for catching and eating soft bodied prey. A diverse but poorly preserved clade, edestoids are noted for developing biting teeth at the midline of their jaws. Helicoprion has a continuously growing root to accommodate >100 crowns that spiraled on top of one another to form a symphyseal whorl supported and laterally braced within the lower jaw. Reconstruction of jaw mechanics shows that individual serrated crowns grasped, sliced, and pulled prey items into the esophagus. A new description and interpretation of Edestus provides insight into the anatomy and functional morphology of another specialized edestoid. Edestus has opposing curved blades of teeth that are segmented and shed with growth of the animal. Set on a long jaw the lower blade closes with a posterior motion, effectively slicing prey across multiple opposing serrated crowns. Further examples of symphyseal whorls among Edestoidae are provided from previously undescribed North American examples of Toxoprion, Campyloprion, Agassizodus, and Sinohelicoprion. The symphyseal dentition in edestoids is associated with a rigid jaw suspension and may have arisen in response to an increase in pelagic cephalopod prey during the Late Paleozoic. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 303:363–376, 2020. © 2018 American Association for Anatomy
Safe Casting and Reliable Cusp Reconstruction Assisted by Micro‐Computed Tomographic Scans of Fossil Teeth
Authors: O'Hara Mackie C. , Le Cabec Adeline , Xing Song , Skinner Mark F. , Guatelli‐Steinberg Debbie
Published: December 2018

Dental replicas are frequently utilized in paleoanthropological studies of perikymata and enamel hypoplasia. However, fossil teeth are often fragile and worn, causing two problems: (1) the risk of damage by removing enamel fragments when impression‐making material is separated from the fossil tooth surface, and (2) the need to reconstruct worn portions of the crown to assess perikymata number, distribution, and hypoplasia timing. This study presents the advantages of μCT data of canines and lateral incisors for (1) detecting cracks along the enamel‐dentine junction (EDJ) which could cause damage when casting, and (2) reliably and non‐destructively reconstructing worn or broken cusps. Fragile teeth of Homo naledi, Miocene, and Pleistocene specimens were μCT‐scanned: 2D virtual sections and 3D models allowed for inspecting crack pattern beyond the external surface and 2D virtual sections were used to digitally reconstruct cusp tips (only Homo naledi). Micro‐CT scans allowed cracks running along the EDJ and communicating with radial cracks in the enamel to be identified prior to casting. Cusp reconstructions using μCT data were conducted as precisely as when using thin‐sections or photographs, and with high intra‐ and inter‐observer agreement, while preserving the original specimen and affording numerous planes of virtual section. When available, μCT data should be inspected prior to tooth casting to exclude teeth that show a pattern of cracks that could lead to damage. Virtual sections allow for accessible, reliable, and non‐destructive cusp reconstructions that may be used for developmental (e.g., perikymata and enamel hypoplasia) or enamel thickness studies. Anat Rec, 302:1516–1535, 2019. © 2018 American Association for Anatomy
The Effects of a Functional Three‐dimensional (3D) Printed Knee Joint Simulator in Improving Anatomical Spatial Knowledge
Authors: Cai Bohong , Rajendran Kanagasuntheram , Bay Boon Huat , Lee Jieying , Yen Ching‐Chiuan
Published: December 2018

In recent decades, three‐dimensional (3D) printing as an emerging technology, has been utilized for imparting human anatomy knowledge. However, most 3D printed models are rigid anatomical replicas that are unable to represent dynamic spatial relationships between different anatomical structures. In this study, the data obtained from a computed tomography (CT) scan of a normal knee joint were used to design and fabricate a functional knee joint simulator for anatomical education. Utility of the 3D printed simulator was evaluated in comparison with traditional didactic learning in first‐year medical students (n = 35), so as to understand how the functional 3D simulator could assist in their learning of human anatomy. The outcome measure was a quiz comprising 11 multiple choice questions based on locking and unlocking of the knee joint. Students in the simulation group (mean score = 85.03%, ±SD 10.13%) performed significantly better than those in the didactic learning group, P < 0.05 (mean score = 70.71%, ±SD 15.13%), which was substantiated by large effect size, as shown by a Cohen’s d value of 1.14. In terms of learning outcome, female students who used 3D printed simulators as learning aids achieved greater improvement in their quiz scores as compared to male students in the same group. However, after correcting for the modality of instruction, the sex of the students did not have a significant influence on the learning outcome. This randomized study has demonstrated that the 3D printed simulator is beneficial for anatomical education and can help in enriching students’ learning experience.
Cyber‐human systems of thought and understanding
Authors: Fonseca Fred , Marcinkowski Michael , Davis Clodoveu
Published: December 2018

The present challenge faced by scientists working with Big Data comes in the overwhelming volume and level of detail provided by current data sets. Exceeding traditional empirical approaches, Big Data opens a new perspective on scientific work in which data comes to play a role in the development of the scientific problematic to be developed. Addressing this reconfiguration of our relationship with data through readings of Wittgenstein, Macherey, and Popper, we propose a picture of science that encourages scientists to engage with the data in a direct way, using the data itself as an instrument for scientific investigation. Using GIS as a theme, we develop the concept of cyber‐human systems of thought and understanding to bridge the divide between representative (theoretical) thinking and (non‐theoretical) data‐driven science. At the foundation of these systems, we invoke the concept of the “semantic pixel” to establish a logical and virtual space linking data and the work of scientists. It is with this discussion of the relationship between analysts in their pursuit of knowledge and the rise of Big Data that this present discussion of the philosophical foundations of Big Data addresses the central questions raised by social informatics research.
Curcumin in tissue engineering: A traditional remedy for modern medicine
Authors: Ahangari Najmeh , Kargozar Saeid , Ghayour‐Mobarhan Majid , Baino Francesco , Pasdar Alireza , Sahebkar Amirhossein , Ferns Gordon A. A. , Kim Hae‐Won , Mozafari Masoud
Published: December 2018

Curcumin is the principal polyphenolic compound present in turmeric with broad applications in tissue engineering and regenerative medicine. It has some important inherent properties with the potential to facilitate tissue healing, including anti‐inflammatory, anti‐oxidant, and antibacterial activities. Therefore, curcumin has been used for the treatment of various damaged tissues, especially wound injuries. There are different forms of curcumin, among which nano‐formulations are of a great importance in regenerative medicine. It is also important to design sophisticated delivery systems for controlled/localized delivery of curcumin to the target tissues and organs. Although there are many reports on the advantages of this compound, further research is required to fully explore its clinical usage. The review describes the physicochemical and biological properties of curcumin and the current state of the evidence on its applications in tissue engineering. © 2018 BioFactors, 45(2):135–151, 2019
Dual‐responsive pegylated polypeptoids with tunable cloud point temperatures
Authors: Fu Xiaohui , Tian Jiliang , Li Zheng , Sun Jing , Li Zhibo
Published: December 2018

A series of pegylated polypeptoids have been readily synthesized by a strategy combining ring‐opening polymerization (ROP) and thiol‐yne photoaddition. The polypeptoids simultaneously incorporated branched oligo(ethylene glycol) (OEG) units and thioether bonds in the side‐chains. All the polypeptoids are readily soluble in aqueous solution and show reversible thermo‐responsive properties. The cloud points (CPs) were demonstrated to be readily tunable in the range of ~25 °C‐60 °C by varying the chemical composition, OEG chain length and the degree of polymerization. Attractively, the chemical compositions of the side chains are readily tunable via adjusting the molar ratios of a mixture of thiol terminated OEG molecules, which avoid synthesizing new monomers or copolymerization of different monomers. Further, the oxidation/reduction of thioether groups shows significant influence on the CPs, providing a second stimulus to tune the phase transition behaviors. Considering the biocompatibility and degradability, the dual‐responsive polypeptoids are potential candidates for various biomedical or biotechnological applications.
Characterization of a novel method for the production of single‐span membrane proteins in Escherichia coli
Authors: Smith Sarah M. , Walker Kelly L. , Jones Alexander S. , Smith Corinne J. , Robinson Colin
Published: December 2018

The large‐scale production and isolation of recombinant protein is a central element of the biotechnology industry and many of the products have proved extremely beneficial for therapeutic medicine. Escherichia coli is the microorganism of choice for the expression of heterologous proteins for therapeutic application, and a range of high‐value proteins have been targeted to the periplasm using the well characterized Sec protein export pathway. More recently, the ability of the second mainstream protein export system, the twin‐arginine translocase, to transport fully‐folded proteins into the periplasm of not only E. coli, but also other Gram‐negative bacteria, has captured the interest of the biotechnology industry.

In this study, we have used a novel approach to block the export of a heterologous Tat substrate in the later stages of the export process, and thereby generate a single‐span membrane protein with the soluble domain positioned on the periplasmic side of the inner membrane. Biochemical and immuno‐electron microscopy approaches were used to investigate the export of human growth hormone by the twin‐arginine translocase, and the generation of a single‐span membrane‐embedded variant. This is the first time that a bonafide biotechnologically relevant protein has been exported by this machinery and visualized directly in this manner. The data presented here demonstrate a novel method for the production of single‐span membrane proteins in E. coli.
Population collapse and adaptive rescue during long‐term chemostat fermentation
Authors: Rai Navneet , Huynh Linh , Kim Minseung , Tagkopoulos Ilias
Published: December 2018

Microbial fermentation is an essential process for research and industrial applications, yet our understanding of cellular dynamics during long‐term fermentation is limited. Here, we report a reproducible phenomenon of abrupt population collapse followed by a rapid population rescue that was observed during long‐term chemostat cultivations, for various strains of Escherichia coli in minimal media. Through genome resequencing and whole‐genome transcriptional profiling of replicate runs over time, we identified that changes in the tRNA and carbon catabolic genes are the genetic basis of this phenomenon. Since current fermentation models are unable to capture the observed dynamics, we present an extended model that takes into account critical biological processes during fermentation, and we further validated carbon source predictions through forward experimentation. This study extends the predictability of current models for microbial fermentation and adds to our system‐level knowledge of cellular adaptation during this crucial biotechnological process.
Ready‐to‐use thermally stable mastermix pills for molecular biology applications
Authors: Leung Vincent , Brooks Meredith , Emerson Sophia , Ali Monsur , Filipe Carlos D. M.
Published: December 2018

Rolling circle amplification (RCA), polymerase chain reaction (PCR), and loop‐mediated isothermal amplification (LAMP), are powerful tools that can be used for gene manipulation, pathogen detection, and infectious disease diagnostics. However, these techniques require trained personnel, as the pipetting steps involved can lead to contamination and, consequently, erroneous results. Furthermore, many of the reagents used in molecular biology are thermally labile and must be kept within a cold‐chain. In this article, we present a simple and cost‐effective method that allows molecular biology reagents to be thermally stabilized into ready‐to‐use mastermixes via drying in pullulan and trehalose films. Our experimental results demonstrate that this method is capable of preserving the activity of RCA, PCR, LAMP, ligase, polynucleotide kinase, and Klenow fragment mastermixes for at least 3 months at ambient conditions. Thus, stabilizing reagents via drying in pullulan and trehalose film may allow for a drastic reduction in the number of pipetting steps and the elimination of the need for a cold chain. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2764, 2019.
Acetylcholine spasm provocation test by trans‐radial artery and brachial vein approach
Authors: Sueda Shozo , Fujimoto Kaori , Sasaki Yasuhiro , Sakaue Tomoki , Habara Hirokazu , Kohno Hiroaki
Published: December 2018

Background

Temporary pace maker is necessary because of transient block or bradycardia during the intracoronary acetylcholine spasm provocation tests based on the Japanese Circulation Society guidelines.

Objectives

We examined the feasibility and safety of the acetylcholine spasm provocation test via the radial artery and brachial vein approach.

Methods

We tried to perform the acetylcholine spasm provocation tests in 252 patients via the radial artery and brachial vein approach procedures during 5 years. Acetylcholine was injected in incremental doses of 20/50/80 μg into the right coronary artery (RCA) and 20/50/100/200 μg into the left coronary artery (LCA). Back‐up pacing rate was set at 40 beats/min. Positive spasm was defined as transient ≥90% luminal narrowing and ischemic electrocardiographic change or usual chest pain.

Results

The procedure success of radial artery and brachial vein access was 94.4% (238/252) and 93.3% (235/252), respectively. We performed 221 patients (87.7%) with acetylcholine tests by radial artery and brachial vein approach. We changed to the brachial approach due to the failures of radial artery access in 14 patients. We also changed to the femoral vein in 11 patients and internal jugular vein in two patients. Back‐up pace maker rhythm was observed in 92.1% (232/252) of all study patients, while it was significantly higher in the RCA testing than that in the LCA tests (84.9% (191/225) vs. 52.2% (131/251), P < 0.001). No irreversible complication was found.

Conclusions

We recommend the radial artery and brachial vein approach for safety and convenience when performing the acetylcholine spasm provocation tests.
Trans‐radial closure of coronary artery fistulae using Amplatzer vascular plug IV: A case series
Authors: Valsecchi Orazio , Vassileva Angelina , Martella Francesco , Cereda Alberto Francesco
Published: December 2018

Background

Trans‐catheter closure of coronary artery fistulae (CAF) has become a successful alternative to cardiac surgery with excellent results and acceptable low rate of complications. Different techniques and devices are available to treat the extreme anatomical variability of CAF.

Aim

We retrospectively describe our case series of five patients trans‐radially treated using an Amplatzer vascular plug IV (AVP‐IV) with telescoping catheter technique.

Results

Trans‐radial closure of CAF using the “Child in Mother” technique with dedicated catheters to deliver the vascular plugs AVP‐IV was successfully performed in all patients, in one case for a complex CAF, an hybrid step approach using coils and plugs was needed.

Conclusions

Trans‐radial closure of CAF using AVP‐IV and a telescoping catheter appeared to be safe and feasible in our case series. A persistent closure of CAF was achieved in all patients at 2 year coronary angiography follow‐up.
Electrocatalytic Study of Ethylene Glycol Oxidation on Pt3Sn Alloy Nanoparticles
Authors: Liu Yifan , Hu Pingfan , Wei Miaojin , Wang Chao
Published: December 2018

Ethylene glycol is a potential feedstock for direct alcohol fuel cells (DAFCs). The electro‐oxidation of ethylene glycol is, however, challenged by poor selectivity toward the complete‐oxidation product, CO2. Herein, we report an electrocatalytic study of ethylene glycol oxidation on monodisperse and homogeneous Pt3Sn alloy nanoparticles. The catalytic activity and selectivity toward CO2 are evaluated under potentiostatic conditions by using gas chromatography‐mass spectrometry. A comparative study is performed on the alloy catalyst with surface tin (oxide) species removed through an alkaline treatment. By comparing the electrocatalytic performances of the pristine and treated Pt3Sn catalysts, as well as commercial Pt/C, we are able to reveal the distinct roles of surface tin oxide and subsurface metallic tin species in the bimetallic electrocatalyst for complete oxidation of ethylene glycol: the former enhances the cleavage of C−C bond and the latter facilitates oxidative removal of the *CO intermediate.
Lead‐Free Semiconductors: Soft Chemistry, Dimensionality Control, and Manganese‐Doping of Germanium Halide Perovskites
Authors: Men Long , Rosales Bryan A. , Gentry Noreen E. , Cady Sarah D. , Vela Javier
Published: December 2018

Lead halide perovskites have drawn enormous interest due to their exceptional photovoltaic and optoelectronic properties. However, the heavy metal lead is harmful to humans and the environment resulting in a need for strategies to replace this toxic element. Herein, we report a facile aqueous synthesis of CsGeX3 (X=I, Br) perovskite nanocrystals with size control achieved by varying the concentration of a cysteammonium halide ligand. We observe a variety of morphologies including pyramidal, hexagonal, and spheroidal. CsGeX3 nanocrystals undergo a lattice expansion due to partial replacement of Cs+ with larger cysteNH3+ cations into their lattice. We successfully dope Mn2+ into the CsGeX3 lattice for the first time with incorporation of up to 29% in bulk and 16% in nano samples. XRD peak shifts and EPR hyperfine splitting strongly indicate that Mn2+ is doped into the lattice. Our results introduce a new member to the lead‐free halide perovskite family and set the fundamental stage for their use in optoelectronic devices.
Characterization of Brain Metabolism by Nuclear Magnetic Resonance
Authors: Downes Daniel P. , Collins James H. P. , Lama Bimala , Zeng Huadong , Nguyen Tan , Keller Gabrielle , Febo Marcelo , Long Joanna R.
Published: December 2018

The noninvasive, quantitative ability of nuclear magnetic resonance (NMR) spectroscopy to characterize small molecule metabolites has long been recognized as a major strength of its application in biology. Numerous techniques exist for characterizing metabolism in living, excised, or extracted tissue, with a particular focus on 1H‐based methods due to the high sensitivity and natural abundance of protons. With the increasing use of high magnetic fields, the utility of in vivo 1H magnetic resonance spectroscopy (MRS) has markedly improved for measuring specific metabolite concentrations in biological tissues. Higher fields, coupled with recent developments in hyperpolarization, also enable techniques for complimenting 1H measurements with spectroscopy of other nuclei, such as 31P and 13C, and for combining measurements of metabolite pools with metabolic flux measurements. We compare ex vivo and in vivo methods for studying metabolism in the brain using NMR and highlight insights gained through using higher magnetic fields, the advent of dissolution dynamic nuclear polarization, and combining in vivo MRS and ex vivo NMR approaches.
Utility of microdissected cytology smears for molecular analysis of thyroid malignancy
Authors: Kumar Gyanendra , Timmaraju Venkata Arun , Song‐Yang Joanna Wanmin , Repko Brittany , Narick Christina , Mireskandari Alidad , Finkelstein Sydney
Published: December 2018

Background

Molecular testing of thyroid fine‐needle aspirates has demonstrated value in cases of indeterminate cytology (Bethesda categories III, IV, and V) enabling optimized individual patient management leading to better outcomes with health economic benefits. For most molecular testing modalities, including mutational panels and classifier analyses, part or all of a dedicated needle aspiration pass is required to obtain an adequate sample for testing. Our analysis, which is based on a combination approach (mutation detection and microRNA classifier status), has documented clinical validity and utility when performed on thyroid fine‐needle aspirates placed directly into RNA preservative fluid. Here we show that the combination approach can be extended to microdissected stained cytology slides provides the physician greater opportunity to resolve cytological indeterminacy.

Methods

Extracted nucleic acid from needle aspirate and corresponding cytology preparations of 47 thyroid nodules were analyzed using identical methodology and results were compared.

Results

Of 94 molecular analyses (47 mutational analyses, 47 microRNA classifier assessments based on a validated 10 marker panel) only 5 samples showed discordant results.

Conclusion

These findings, together with supplementary work using archival specimens shows that the combination approach can be effectively applied to both direct aspirated thyroid nodule aspirates or to nucleic acid extracted from macrodissected and microdissected cytology slide smears, with the expectation of equivalent results. The advantages of both specimen sources, direct aspirate, and cytology slide smears are discussed.
Primary pulmonary meningioma: A rare case report of aspiration cytological features and immunohistochemical assessment
Authors: Ohashi‐Nakatani Kumi , Shibuki Yasuo , Fujima Mizuho , Watanabe Reiko , Yoshida Akihiko , Yoshida Hiroshi , Matsumoto Yuji , Tsuchida Takaaki , Watanabe Shun‐ichi , Motoi Noriko
Published: December 2018

Ectopic meningioma is a generally rare type of benign tumor that very rarely occurs in the lung. Here, we report the cytological findings of a primary pulmonary meningioma with a particular focus on immunohistochemical (IHC) assessment. A healthy 60‐year‐old woman visited our hospital with an asymptomatic nodule in the right lower lung lobe. She had no particular past‐history and no other tumors in the central nervous system or elsewhere according to an imaging examination. Transbronchial fine‐needle aspiration cytology revealed clusters of spindle cells in a whorled formation and psammoma bodies. The tumor cells exhibited spindle‐shaped cytoplasm, small fusiform or round nuclei and numerous intranuclear cytoplasmic inclusions. IHC staining of the cytological specimen revealed that the tumor cells were positive for epithelial membrane antigen, negative for thyroid transcription factor‐1 and p40, and equivocal for claudin‐1. Progesterone receptor immunoreactivity of cytology specimen resulted negative at first by manual method but retrieved positive by an autostainer. Following segmentectomy, the pathological diagnosis was a meningothelial meningioma. The patient has remained well without recurrence for 36 months postoperatively. Because the cytological preparation exhibited characteristic findings of meningioma, a correct diagnosis based on pre‐operative cytological findings with appropriate IHC would be possible. Here, we report the cytological and IHC features of this case and highlight the importance of IHC‐quality assurance.
Banded Iron Travertines at the Ilia Hot Spring (Greece): An interplay of biotic and abiotic factors leading to a modern Banded Iron Formation analogue?
Authors: Kanellopoulos Christos , Thomas Camille , Xirokostas Nikolaos , Ariztegui Daniel
Published: December 2018

A hot spring at Ilia in the Greek Island of Euboea precipitates iron‐rich travertine at an ore‐grade concentration (up to 35.3 wt% Fe). This hydrothermal chemical sediment system deposits bands of iron oxyhydroxides (ferrihydrite), millimetres to centimetres thick, alternating with calcium carbonate‐dominated layers, creating “Banded Iron Travertine” (BIT). The ferrihydrite laminae display a dendritic texture formed of spherical nodules often covering filaments identified as bacterial stalks of Zetaproteobacteria. These microaerophilic iron‐oxidizing bacteria were identified by their 16S rRNA gene sequences in ferrihydrite‐enriched samples from areas under high water flow. They were missing in the aragonite/calcite‐dominated samples exhibiting features of aerial exposure and cyanobacteria instead. These characteristics, and the relative depletion in Fe‐rich layers of redox‐sensitive elements like Mn and Ce, as well as the presence of halite in Ca‐rich layers, suggest that the bands form by successive changes in hydrothermal flow. This allowed microaerophilic iron oxidation to form Fe‐rich layers, while Ca‐rich bands precipitated when the hydrothermal water had time to equilibrate with the atmosphere. This sea water‐dominated hydrothermal system is enriched in reduced iron and rapidly precipitating carbonates and ferrihydrite in the form of bands, having similarities to “Banded Iron Formation” (BIF). BIF represents archives of Earth's primitive biogeochemistry although the combined abiotic and biotic processes that have likely led to their formation are not fully resolved. Diagenesis and metamorphism have a strong imprint on BIF. Thus, continuous efforts are pursued to identify modern analogues that could help unravel their formation. Although carbonate is not a common feature of BIFs, Ilia system provides an interesting analogue for their depositional processes and potential microbial–mineral associations they may have hosted. It also presents pre‐diagenesis facies association and mineralogy that could bring new clues for unravelling BIF modes of formation and the salient biogeochemical conditions characteristic of their original depositional environment.
Tau PET Imaging for Staging of Alzheimer's Disease in Down Syndrome
Authors: Rafii Michael S.
Published: December 2018

Alzheimer's disease (AD) pathology and early‐onset dementia develop almost universally in Down syndrome (DS). AD is defined neuropathologically by the presence of extracellular plaques of aggregated amyloid β protein and intracellular neurofibrillary tangles (NFTs) of aggregated hyperphosphorylated tau protein. The development of radiolabeled positron emission tomography (PET) ligands for amyloid plaques and tau tangles enables the longitudinal assessment of the spatial pattern of their accumulation in relation to symptomatology. Recent work indicates that amyloid pathology develops 15–20 years before neurodegeneration and symptom onset in the sporadic and autosomal dominant forms of AD, while tau pathology correlates more closely with symptomatic stages evidenced by cognitive decline and dementia. Recent work on AD biomarkers in DS illustrates similarities between DS and sporadic AD. It may soon be possible to apply recently developed staging classifications to DS to obtain a more nuanced understanding of the development AD in DS and to provide more accurate diagnosis and prognosis in the clinic.
Ontogenetic trajectories of body coloration reveal its function as a multicomponent nonsenescent signal
Authors: Bonnaffé Willem , Martin Mélissa , Mugabo Marianne , Meylan Sandrine , Le Galliard Jean‐François
Published: December 2018

The understanding of developmental patterns of body coloration is challenging because of the multicomponent nature of color signals and the multiple selective pressures acting upon them, which further depend on the sex of the bearer and area of display. Pigmentary colors are thought to be strongly involved in sexual selection, while structural colors are thought to generally associate with conspecifics interactions and improve the discrimination of pigmentary colors. Yet, it remains unclear whether age dependency in each color component is consistent with their potential function. Here, we address lifelong ontogenetic variation in three color components (i.e. UV, pigmentary, and skin background colors) in a birth cohort of common lizards Zootoca vivipara across three ventral body regions (i.e. throat, chest, and belly). All three color components developed sexual dichromatism, with males displaying stronger pigmentary and UV colors but weaker skin background coloration than females. The development of color components led to a stronger sexual dichromatism on the concealed ventral region than on the throat. No consistent signs of late‐life decay in color components were found except for a deceleration of UV reflectance increase with age on the throat of males. These results suggest that body color components in common lizards are primarily nonsenescent sexual signals, but that the balance between natural and sexual selection may be altered by the conspicuousness of the area of display. These results further support the view that skin coloration is a composite trait constituted of multiple color components conveying multiple signals depending on age, sex, and body location.
The role of Eomes in human CD4 T cell differentiation: A question of context
Authors: Dejean Anne S. , Joulia Emeline , Walzer Thierry
Published: December 2018

Eomesodermin (Eomes) is a transcription factor (TF) of the T‐box family closely related to T‐bet known for its role in CD8 T cell and natural killer cell differentiation. However, the role of Eomes in CD4 T‐cell differentiation is less well appreciated. In this issue of the European Journal of Immunology [Eur. J. Immunol. 2019. 49: 79–95] Mazzoni et al. and [Eur. J. Immunol. 2019. 49: 96–111] Gruarin et al. studied the role of Eomes in human CD4 T‐cell differentiation. Mazzoni et al. showed that Eomes plays a key role in helper T cell (Th) plasticity by favoring the phenotype shift of Th17 cells toward non‐classic Th1 cells; while Gruarin et al. proposed Eomes as a lineage‐defining TF for human IL‐10 and IFN‐γ co‐producing regulatory T‐cells (Tr1 cells). Both studies show that Eomes drives IFN‐γ secretion and stamps a “cytotoxic” signature, while it also represses Th17 features. However, additional signals including the cytokine milieu may further influence the fate of Eomes+ CD4 T cells. A common feature of Eomes+ CD4 T cells appears to be their accumulation in inflamed tissues in patients with chronic inflammatory disorders. Whether Eomes favors expression of the proinflammatory cytokines or on the contrary, promotes the anti‐inflammatory cytokines, remains a matter of debate.
Dual‐Mode Calixarene‐Based Chemosensor: Highly Selective Fluorogenic Detection of Hg2+ and Chromogenic Detection of Cu2+ with a Single Ionophore
Authors: Patra Subrata , Boricha Vinod P. , Paul Parimal
Published: December 2018

A fluorescent molecular sensor has been synthesized incorporating a ReI‐bipyridine moiety as a fluorogenic unit and amide‐incorporated modified calix[4]arene as recognition moiety. This molecule behaves as a dual sensor, it exhibited highly selective turn‐on fluorescent sensing for Hg2+ and naked eye colourimetric detection of Cu2+ over a wide range of metal ions. The ion‐competition study revealed no significant interference from any other metal ion used in this study. Mechanistic studies revealed that the combination of soft (nitrogen) and hard (oxygen) donors in the large and flexible macrocyclic coordination site promoted interaction of Hg2+ with nitrogen atoms, which perturbed the fluorescence properties of the molecule restricting the PeT process, and the coordination of Cu2+ with oxygen atoms resulted in new ICT absorption band in the visible region triggering color change. This is a rare example, particularly with calixarene, where a single receptor exhibited dual‐mode selectivity in different sensing channels.
Isoprene Polymerization with Pyrazolylimine Cobalt(II) Complexes: Manipulation of 3,4‐Selectivities by Ligand Design and Use of Triphenylphosphine
Authors: Fang Liang , Zhao Wenpeng , Han Chao , Liu Heng , Hu Yanming , Zhang Xuequan
Published: December 2018

A series of pyrazolylimine CoCl2 complexes were synthesized and well characterized. The single crystal structures and coordination geometries of these complexes were confirmed by X‐ray diffraction, which revealed dimeric and monomeric structures, and thereby distorted trigonal bipyramidal and distorted tetrahedral geometries, respectively. In combination with diethylaluminum chloride (DEAC) and methylaluminoxane (MAO) as cocatalysts, the present cobalt complexes displayed high activity toward isoprene polymerization, affording cis‐1,4/3,4‐polyisoprenes. Polymerization parameters have significant influence on the polymerization behavior. Additionally, incorporation of the external donor triphenylphosphine led to a switch in selectivity of the system from cis‐1,4 to 3,4, providing an effective method to adjust the 3,4‐moieties on a large scale.