bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of Dioxygenase‐Based Chemoenzymatic Processes to the Total Synthesis of Natural Products
Authors: Lan Ping , Ye Sebastian , Banwell Martin G.
Published: October 2019

This Minireview describes the exploitation of certain enzymatically derived, readily accessible, and enantiomerically pure cis‐1,2‐dihydrocatechols as starting materials in the chemical synthesis of a range of biologically active natural products, most notably sesquiterpenoids and alkaloids.
Does in vitro fertilization affect the expression of miRNAs and their biogenesis pathway in preimplantation mouse embryos?
Authors: Azizi Elham , Ghaffari Novin Marefat , Naji Mohammad , Amidi Fardin , Shams Mofarahe Zahra
Published: October 2019

Background

In vitro fertilization (IVF) is a well‐accepted procedure which has been utilized for the treatment of infertile patients. As embryos at early stages of development are very vulnerable, the IVF conditions may influence genetic and epigenetic regulation of preimplantation mouse embryo.

Methods

We assessed the effect of IVF on the expression of developmental and implantation related miRNAs (miR‐21, miR‐93, miR‐24, and let‐7a), their common presumptive target (Stat3), and miRNA biogenesis pathway genes (Drosha, Dgcr8, Exportin‐5, Dicer, and Ago2). in vivo 8‐cell and blastocysts were compared to IVF embryos. Expression levels of miRNAs, Stat3, and miRNA biogenesis pathway genes were evaluated by qRT‐PCR in in vivo (n = 8) and IVF (n = 4) embryos.

Results

The expression levels of let‐7a and Stat3 were significantly reduced in IVF blastocyst when compared with in vivo (p = .004 and p = .009, respectively). Nevertheless, the IVF procedure did not influence the expression levels of miRNA biogenesis pathway components in 8‐cell and blastocyst embryos.

Conclusions

Downregulation of let‐7a and developmental related transcription factor, Stat3, in IVF mouse blastocysts may affect preimplantation development and implantation of embryos. Moreover, the genes of the miRNA biogenesis pathway were not changed in preimplantation mouse embryos through the IVF procedure.
Multiorgan microfluidic platform with breathable lung chamber for inhalation or intravenous drug screening and development
Authors: Miller Paula G. , Chen Chen‐Yu , Wang Ying I. , Gao Emily , Shuler Michael L.
Published: October 2019

Efficient and economical delivery of pharmaceuticals to patients is critical for effective therapy. Here we describe a multiorgan (lung, liver, and breast cancer) microphysiological system (“Body‐on‐a‐Chip”) designed to mimic both inhalation therapy and/or intravenous therapy using curcumin as a model drug. This system is “pumpless” and self‐contained using a rocker platform for fluid (blood surrogate) bidirectional recirculation. Our lung chamber is constructed to maintain an air‐liquid interface and contained a “breathable” component that was designed to mimic breathing by simulating gas exchange, contraction and expansion of the “lung” using a reciprocating pump. Three cell lines were used: A549 for the lung, HepG2 C3A for the liver, and MDA MB231 for breast cancer. All cell lines were maintained with high viability (>85%) in the device for at least 48 hr. Curcumin is used to treat breast cancer and this allowed us to compare inhalation delivery versus intravenous delivery of the drug in terms of effectiveness and potentially toxicity. Inhalation therapy could be potentially applied at home by the patient while intravenous therapy would need to be applied in a clinical setting. Inhalation therapy would be more economical and allow more frequent dosing with a potentially lower level of drug. For 24 hr exposure to 2.5 and 25 µM curcumin in the flow device the effect on lung and liver viability was small to insignificant, while there was a significant decrease in viability of the breast cancer (to 69% at 2.5 µM and 51% at 25 µM). Intravenous delivery also selectively decreased breast cancer viability (to 88% at 2.5 µM and 79% at 25 µM) but was less effective than inhalation therapy. The response in the static device controls was significantly reduced from that with recirculation demonstrating the effect of flow. These results demonstrate for the first time the feasibility of constructing a multiorgan microphysiological system with recirculating flow that incorporates a “breathable” lung module that maintains an air‐liquid interface.
Incidence and risk factors of gastrointestinal neuroendocrine neoplasm metastasis in liver, lung, bone, and brain: A population‐based study
Authors: Zheng Zhibo , Chen Chuyan , Jiang Lingjuan , Zhou Xingtong , Dai Xiaoyan , Song Yimin , Li Yongning
Published: October 2019

Background

Neuroendocrine neoplasm is a rare solid tumor. Metastatic pattern of the gastrointestinal neuroendocrine neoplasm (GI‐NEN) has not been fully explored.

Methods

Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (SEER‐9 registry) from 1973 to 2015. Incidence was estimated by Joinpoint regression analyses. Data with additional treatment fields of GI‐NEN were extracted from the SEER‐18 registry from 1 January 2010 to 31 December 2015. A total of 14 685 GI‐NEN patients were included in this study. Statistical analyses were performed with SPSS 25.0, the Intercooled Stata SE 15.0, and GraphPad Prism 7.

Results

Incidence of GI‐NENs increased from 0.51 per 100 000 patients in 1973 to 6.20 per 100 000 patients in 2015. Of them, 2003 patients were stage IV GI‐NEN at the time of diagnosis, including 1459 (72.84%) patients with liver metastasis, 144 (7.19%) lung metastasis, 115 (5.74%) bone metastasis, and 27 (1.35%) brain metastasis. Esophageal NEN had the highest risk of metastasis (52.68%). The median survival for patients with liver, lung, bone, and brain metastasis was 38, 6, 9, and 2 months, respectively. The presence of lung or liver metastasis indicated higher risk of concurrent existence of bone and brain metastasis than those without.

Conclusion

Bone and brain metastasis should be screened in the GI‐NEN patients if they had lung or liver metastasis. Findings of the current study could help clinicians to identify distant metastasis of GI‐NENs as early as possible, and by which, to improve survival rate of GI‐NENs.
Synthesis and Evaluation of Aminothiazole Derivatives as Hedgehog Pathway Inhibitors
Authors: Sun Chiyu , Zhang Ying , Lin Lin , Liu Shuyuan , Wang Rui , Zang Wei , Meng Weijia , Chen Xiaofeng
Published: October 2019

A series of aminothiazole derivatives bearing the benzimidazole moiety were synthesized and evaluated in Gli luciferase reporter assays. Lead optimization led to the discovery of potent hedgehog pathway antagonist 18 (2‐[3‐(1H‐benzimidazol‐2‐yl)‐4‐chloroanilino]‐N‐[4‐(trifluoromethyl)phenyl]‐1,3‐thiazole‐4‐carboxamide), with IC50 values in nanomolar range. The molecular basis ascribed to hindering sonic hedgehog‐driven Smoothened (Smo) localization within the primary cilium (PC). Moreover, compound 18 inhibited Gli1 mRNA expression in mutant Smo cell line and displayed moderate cytotoxicity against DAOY cancer cell.
Anti‐Lipid Peroxidation, α‐Glucosidase and α‐Amylase Inhibitory Effects of the Extract of Capitula of Coreopsis tinctoriaNutt. and Protection Effects on High‐Fat/High‐Sugar and Streptozotocin‐Induced Type 2 Diabetes in Mice
Authors: Zhang Yushan , Luo Li , Li Zuoming , Li Huifang , Yao Xincheng , Luo Ruiling
Published: October 2019

Coreopsis tinctoria capitula (CTC) of the Compositae family has been used traditionally to treat various diseases in China, particularly type 2 diabetes mellitus (T2DM). This study evaluated the anti‐lipid peroxidation, α‐glucosidase and α‐amylase inhibitory effects of CTC extracts, and analyzed its chemical composition by HPLC. Moreover, the antioxidant activity and protection effects of CTC extracts were investigated on high‐fat/high‐sugar and streptozotocin‐induced T2DM mice. In vitro study, the ethyl acetate extract (EAE) and butanol extract (BE) of CTC exhibited anti‐lipid peroxidation (IC50: BHA>BE or EAE>ascorbic acid, p<0.05) and α‐glucosidase inhibitory activity (IC50: BE>EAE, p<0.05). In vivo, the BE at the dose of 600 mg/kg was intragastrically given to T2DM mice, which exhibited a certain extent of repair and improvement of the levels of CAT, GSH, GSH‐PX, SOD, as well as plasma biomarkers, compared with those in the model group (p<0.05). These results demonstrated that CTC extracts have a positive effect to treat T2DM and it can be used for the treatment of T2DM in the future.
Use of 3D rotational angiography to perform computational fluid dynamics and virtual interventions in aortic coarctation
Authors: Armstrong Aimee K. , Zampi Jeffrey D. , Itu Lucian M. , Benson Lee N.
Published: October 2019

Computational fluid dynamics (CFD) can be used to analyze blood flow and to predict hemodynamic outcomes after interventions for coarctation of the aorta and other cardiovascular diseases. We report the first use of cardiac 3‐dimensional rotational angiography for CFD and show not only feasibility but also validation of its hemodynamic computations with catheter‐based measurements in three patients.
Implantable pulmonary artery pressure monitoring device in patients with palliated congenital heart disease: Technical considerations and procedural outcomes
Authors: Salavitabar Arash , Bradley Elisa A. , Chisolm Joanne L. , Hickey Jenne , Boe Brian A. , Armstrong Aimee K. , Daniels Curt J. , Berman Darren P.
Published: October 2019

Objective

We describe the technical considerations of transcatheter implantation of the CardioMEMS™ HF System (Abbott, Abbott Park, IL) in adult patients with complex palliated congenital heart disease (CHD) and advanced heart failure (HF).

Background

Ambulatory pulmonary artery (PA) pressure monitoring with implantable hemodynamic monitors (IHMs) has been shown to reduce HF‐related hospital admissions in non‐CHD populations. HF is a common late cardiovascular complication in adult CHD necessitating better understanding of IHM application in this population.

Methods

We analyzed adults with complex CHD and advanced HF who were referred for CardioMEMS™ device implantation (2015–2018). Feasibility of device implantation, defined by successful device implantation and calibration, and procedural outcomes were evaluated.

Results

CardioMEMS™ was successfully implanted in all 14 adults (35.5 ± 9.2 years old, 72 ± 12 kg) with complex CHD (single ventricle/Fontan, n = 8 [57%]; d‐transposition of the great arteries/atrial switch, n = 6 [43%]). The device was delivered via femoral venous access in 13 (93%) patients and implanted in the left PA in 12 (86%). A long sheath was used in 8 (57%) patients, including 5/6 with an atrial switch operation. There was one device migration that did not require retrieval.

Conclusions

Transcatheter implantation of an IHM is feasible in select complex adult CHD patients with advanced HF. Further studies evaluating integration of ambulatory hemodynamics and the impact on clinical care are needed. This technology has the potential to improve medical management of advanced HF in patients with Fontan and atrial switch physiologies and provide new insights into their ambulatory hemodynamics.
A single center 10‐year clinical experience with superior vena cava retrievable filters
Authors: Lopera Jorge E. , Barnes Laura
Published: October 2019

Purpose

To report a 10‐year clinical experience with superior vena cava (SVC) retrievable filters.

Methods

A retrospective review of patients with SVC filters was performed between 2008 and 2018 in a single tertiary medical center. Patient demographics, indications for filter placement, type of filter placed, and clinical evolution were recorded. Complications during placement, retrieval, and follow‐up were determined.

Results

Fifty patients ages 17–89 years (average 54) underwent SVC retrievable filter placement. Main indication for filter placement was deep venous thrombosis of the major upper extremity and/or internal jugular veins with contraindications to anticoagulation. Complications during placement included inadvertent filter placement in the right brachiocephalic vein in two patients, another patient had a leg of the filter entrapped in the tip of a hemodialysis catheter that required filter reposition and line exchange. Thirteen patients had attempted retrieval with 12 filters successfully removed 7–420 days after placement (mean 170). On follow‐up images available in 24 patients, 13 filters were noted to be significantly tilted and 10 filters had evidence of leg penetration. No other serious late complications were noted.

Conclusion

The use of retrievable SVC filters in patients with upper extremity DVT is highly questionable. There is a high incidence of filter malposition, filter tilting, and leg penetration.
Kolbe Electrolysis of Biomass‐Derived Fatty Acids Over Pt Nanocrystals in an Electrochemical Cell
Authors: Yuan Gang , Wu Chan , Zeng Guorong , Niu Xiaopo , Shen Guoqiang , Wang Li , Zhang Xiangwen , Luque Rafael , Wang Qingfa
Published: October 2019

Electrochemical valorization of non‐food biomass‐derived carboxylates into fuels is promising for the conversion, storage, and distribution of renewable electricity. Herein, we demonstrate that biofuels, hydrogen, and bicarbonate can be simultaneously produced in an electrochemical cell by one‐step electrolysis of free fatty acids under ambient conditions on 3D self‐supported ultralow Pt loading (2 wt %) electrode. The three valuable products can naturally separate from each other during the electrolysis in the alkaline aqueous solution. The experimental suggests that Pt(100) and Pt(110) are favorable for the production of non‐Kolbe and Kolbe hydrocarbons, respectively. DFT calculation further clarifies the adsorption and stabilization of the reaction intermediates on Pt(100) and Pt(110).
Enhanced Light Absorption and Charge Carrier Management in Core‐Shell Fe2O3@Nickel Nanocone Photoanodes for Photoelectrochemical Water Splitting
Authors: Singh Ashutosh K. , Sarkar Debasish
Published: October 2019

Solar driven photoelectrochemical (PEC) water splitting is a clean and sustainable approach to generate green fuel, Hydrogen. Hematite (Fe2O3) is considered as potential photoanode because of its abundance, chemical stability and suitable band gap, though its short carrier diffusion length puts a limit on the film thickness and subsequent light absorption capability. In this regard, here we have designed and constructed a unique photoanode by depositing ultrathin films of Fe2O3 on purpose‐built three‐dimensional (3D) nickel nanocone arrays. In this design, 3D nanostructures not only provide ameliorated surface area for PEC reactions but also enhance light absorption capability in ultrathin Fe2O3 films, while ultrathin films promote charge carrier separation and effective transfer to the electrolyte. The 3D electrodes exhibit a substantial improvement in light absorption capability within the entire visible region of solar spectrum, as well as enhanced photocurrent density as compared to the planar Fe2O3 photoelectrode. Detailed investigation of reaction kinetics suggests an optimum Fe2O3 film thickness on 3D nanocone arrays obtained after 6 deposition cycles in achieving maximum charge carrier separation and transfer efficiencies (82 % and 88 %, respectively), mainly ascribable to the increased charge carrier lifetime overcoming recombination losses.
Functionalized Resins for the Synthesis of Peptide Alcohols
Authors: Ferrer‐Gago Fernando J. , Koh Li Quan , Lane David P.
Published: October 2019

Peptide alcohols are clinically important compounds that are underexplored in structure–activity relationship (SAR) studies in drug discovery. One reason for this underutilization is that current syntheses are laborious and time consuming. Herein, we describe the preparation and utility of Rink, Ramage, and Sieber‐chloride resins, which enables the use of a general, easy and practical method for the attachment of fluorenylmethoxycarbonyl (Fmoc)‐amino alcohols to a solid support, in the synthesis of peptide alcohols. This method is the first straightforward Fmoc/tBu synthesis of peptide alcohols starting from a pre‐loaded resin. The synthesized peptide alcohols can be detached from the linkers through conventional methods. Treatment with trifluoroacetic acid (TFA) (95 %) and scavengers such as triisopropylsilane and water for 2 h is sufficient to obtain a fully deprotected peptide alcohol, while treatment with 20 % hexafluoroisopropanol in dichloromethane renders a fully protected peptide alcohol that can be further modified at the C‐terminus. As examples, the new resins were used in straightforward, relatively rapid syntheses of the peptide alcohols octreotide, alamethicin, and a segment of trichogin GA IV, as well as the first synthesis of stapled peptide alcohols.
Spatiotemporal gene expression patterns reveal molecular relatedness between retinal laminae
Authors: Jiang Danye , Burger Courtney A. , Casasent Anna K. , Albrecht Nicholas E. , Li Fenge , Samuel Melanie A.
Published: October 2019

In several areas of the central nervous system, neurons are regionally organized into groups or layers that carry out specific activities. In this form of patterning, neurons of distinct types localize their cell bodies to just one or a few of the layers within a structure. However, little is known about whether diverse neuron types within a lamina share molecular features that coordinate their organization. To begin to identify such candidates, we used the laminated murine retina to screen 92 lacZ reporter lines available through the Knockout Mouse Project. Thirty‐two of these displayed reporter expression in restricted subsets of inner retina neurons. We then identified the spatiotemporal expression patterns of these genes at key developmental stages. This uncovered several that were heavily enriched in development but reduced in adulthood, including the transcriptional regulator Hmga1. An additional set of genes displayed maturation associated laminar enrichment. Among these, we identified Bbox1 as a novel gene that specifically labels all neurons in the ganglion cell layer but is largely excluded from otherwise molecularly similar neurons in the inner retina. Finally, we established Dbn1 as a new marker enriched in amacrines and Fmnl3 as a marker for subsets of αRGCs. Together, these data provide a spatiotemporal map for laminae‐specific molecules and suggest that diverse neuron types within a lamina share coordinating molecular features that may inform their fate or function.
Effect of ingredients of accent base on shade development in point of sale tinting
Authors: Rose Elvina , Nikam Pramod , Joshi Amit
Published: October 2019

The proper dispersion and stabilization of titanium dioxide/extender in a coating is critical for color development. Color development is much more challenging when it comes to point of sale tinting. This color needs to be reproducible and accurate after machine tinting. What decides the color development in a zero rutile base containing extenders? This article studies the raw material interactions and its effect on color development.
Reducing Properties of Superalkalis on Pyridinic Graphene Surfaces: a Computational Study
Authors: Ramondo Fabio , Leonzi Ilenia , Meloni Giovanni
Published: October 2019

The hyperlithiated species
(k=1, 2, 3, and 4) have been studied by quantum mechanical (QM) methods. Different structures have been localized for each molecule by the CBS‐QB3 composite method: all the isomers show superalkali properties and strong tendency to donate an electron to carbon dioxide forming stable
complexes. With the aim to find molecular systems able to stabilize superalkalis, geometries of complexes between superalkalis and pyridine and superalkalis and graphene surfaces doped with a pyridinic vacancy were calculated. The pyridinic graphene sheets were modeled with two finite molecular systems C69H21N3 and C117H27N3. The interaction with one pyridine molecule is quite weak and the superalkali maintains its structure and electron properties. The affinity for graphene sheets is instead stronger and the superalkalis tend to deform their geometry to better interact with the graphene surface. However, the superalkalis continue to show the tendency to transfer electrons to carbon dioxide reducing CO2, as found in graphene absence.
Evaluating the Role of Solubility in Oral Absorption of Poorly Water‐Soluble Drugs Using Physiologically‐Based Pharmacokinetic Modeling
Authors: Fink Christina , Sun Dajun , Wagner Knut , Schneider Melanie , Bauer Holger , Dolgos Hugues , Mäder Karsten , Peters Sheila‐Annie
Published: October 2019

Poor aqueous solubility and dissolution of drug candidates drive key decisions on lead series optimization during drug discovery, on formulation optimization, and clinical studies planning during drug development. The interpretation of the in vivo relevance of early pharmaceutical profiling is often confounded by the multiple factors affecting oral systemic exposure. There is growing evidence that in vitro drug solubility may underestimate the true in vivo solubility and lead to drug misclassification. Based on 10 poorly water‐soluble tyrosine kinase inhibitors, this paper demonstrates the use of physiologically‐based pharmacokinetic (PK) analysis in combination with early clinical PK data to identify drugs whose absorption is truly limited by solubility in vivo and, therefore, expected to exhibit food effect. Our study supports a totality of evidence approach using early clinical data to guide decisions on conducting drug interaction studies with food and acid‐reducing agents.
Fibrous Network of C@MoS2 Nanocapsule‐Decorated Cotton Linters Interconnected by Bacterial Cellulose for Lithium‐ and Sodium‐Ion Batteries
Authors: Zhou Huimin , Lv Pengfei , Lu Xiaomin , Hou Xuebin , Zhao Min , Huang Jieyu , Xia Xin , Wei Qufu
Published: October 2019

To protect the structure of MoS2 from collapse, a strong skeleton is expected to help maintain the integrity. In this study, cotton linters burdened with hollow C@MoS2 nanocapsules are added into nutrient medium for the growth of a bacterial cellulose membrane. Benefitting from good conductivity and structural integrity, the resultant fibrous membrane anode gives reversible capacities of 559 and 155 mAh g−1 for Li‐ion batteries and Na‐ion batteries after 100 cycles, respectively. The structural transformation and component evolution in lithiation–delithiation and sodiation–desodiation was elucidated by in situ Raman spectroscopy. After sodiation, the Na2S did not transform back into MoS2 but was more likely converted into elemental sulfur during the conversion reaction. Layered semiconducting transition metal chalcogenides, such as molybdenum disulfide (MoS2), feature open 2 D ion‐transport channels amenable to receive various guest ions with high theoretical capacities.[2] One serious challenge curtailing the applicability of such materials is their volume changes during discharge–charge processes.[3, 4] However, particular morphologies of MoS2 are proposed to improve the specific capacity.[5,6,7] Many works have focused on core–shell and hollow MoS2 micro‐ and nanostructures, and the results validate the advantages of shortening the lithium‐ion diffusion distance and enhancing specific capacity.[8,9] Unfortunately, the issue of inferior capacity stability is not resolved, because the structure is not effectively protected and is prone to collapse.
Type I interferons are important co‐stimulatory signals during T cell receptor mediated human MAIT cell activation
Authors: Lamichhane Rajesh , Galvin Henry , Hannaway Rachel F , de la Harpe Sara M , Munro Fran , Tyndall Joel DA , Vernall Andrea J , McCall John L , Husain Matloob , Ussher James E
Published: October 2019

Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells that can be stimulated either via their TCR or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also co‐stimulatory signals, such as TLR agonists, that can modulate TCR‐mediated activation. Recently, type I interferons (T1‐IFNs) have been identified as contributing to cytokine‐mediated MAIT cell activation. However, it is unknown whether T1‐IFNs also have a role during TCR‐mediated MAIT cell activation. In this study, we investigated the co‐stimulatory role of T1‐IFNs during TCR‐mediated activation of MAIT cells by the MR1 ligand 5‐amino‐6‐d‐ribitylaminouracil/methylglyoxal. We found that T1‐IFNs were able to boost interferon‐γ and granzyme B production in 5‐amino‐6‐d‐ribitylaminouracil/methylglyoxal‐stimulated MAIT cells. Similarly, influenza virus‐induced T1‐IFNs enhanced TCR‐mediated MAIT cell activation. An essential role of T1‐IFNs in regulating MAIT cell activation by riboflavin synthesising bacteria was also demonstrated. The co‐stimulatory role of T1‐IFNs was also evident in liver‐derived MAIT cells. T1‐IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1‐IFNs during TCR‐mediated MAIT cell activation.
A Facile Route toward Ceric Silylamide [Ce{N(SiHMe2)2}4]
Authors: Bayer Uwe , Bock Lorenz , Maichle‐Mössmer Cäcilia , Anwander Reiner
Published: October 2019

Treatment of the ate complex [Ce{N(SiHMe2)2}4Li(thf)] with neutral donor molecules (do) gave several solvent(do)‐separated ion‐pair complexes of the composition [Ce{N(SiHMe2)2}4][Li(do)n] (do = thf, pyridine, tmeda, dme, 12‐crown‐4). Their solid‐state structures have been analyzed by X‐ray diffraction and DRIFTS. Displacement of the [Li(do)n] entity, resulting in a solvent‐separated ion pair with a symmetric environment around the Ce(III) center, was also revealed in solution by 7Li NMR spectroscopy. The oxidation of [Ce{N(SiHMe2)2}4][Li(do)n] with 1,4‐benzoquinone to afford homoleptic ceric [Ce{N(SiHMe2)2}4] has been investigated and screened. Overall, the separated ion pairs [Ce{N(SiHMe2)2}4][Li(do)n] performed better than the intramolecular ate complex [Ce{N(SiHMe2)2}4Li(thf)], with pyridine as donor giving the best results.
Metallated Container Molecules: A Capsular Nickel Catalyst for Enhanced Butadiene Polymerisation
Authors: Elaieb Fethi , Sameni Soheila , Awada Mouhamad , Jeunesse Catherine , Matt Dominique , Toupet Loic , Harrowfield Jack , Takeuchi Daisuke , Takano Shigenaga
Published: October 2019

A unique, covalently constructed capsular catalyst obtained by reaction of [Ni(η5‐C5H5)(1,5‐cyclooctadiene)] BF4 with the double‐calixarene‐derived diphosphine 1,3‐bis(5‐diphenylphosphino‐25,26,27,28‐tetrapropoxycalix[4]aren‐17‐yl)benzene (1) has been shown to polymerise butadiene at a rate considerably superior to that of previously known catalysts. The reported results indicate that the container structure of the covalent complex is retained during catalysis.
Synthesis of a Threosyl‐C‐nucleoside Phosphonate
Authors: Nie Peng , Groaz Elisabetta , Herdewijn Piet
Published: October 2019

A general synthetic route for the preparation of the first analogue of a new series of sugar‐modified C‐nucleoside phosphonates is detailed. Such derivative contains a four‐carbon l‐threose sugar moiety substituted with a phosphonomethoxy group at the 3′‐position and pyrrolo[2,1‐f][1,2,4]triazin‐4‐amine as nucleobase. A C‐nucleoside was initially prepared by coupling a benzyl protected l‐threono‐1,4‐lactone intermediate with the corresponding aglycon moiety. The choice of a tert‐butyldiphenylsilyl group was found to be crucial to achieve the regioselective protection of the hydroxyl group at the 3′‐position. Moreover, it allowed to smoothly perform further synthetic manipulations, including the introduction of a benzyl protected phosphonate synthon under basic conditions, which eventually led to the desired compound after final deprotection.
Predicting battery life with early cyclic data by machine learning
Authors: Zhu Shan , Zhao Naiqin , Sha Junwei
Published: October 2019

This work applies machine learning tools to achieve the early prediction of commercial battery life. We compared the prediction accuracy of different machine learning algorithms to the battery database. Among various algorithms, the decision tree (DT) method exhibits the highest accuracy of 95.2% to predict whether the battery can maintain above 80% initial capacity after 550 cycles. Using the initial two cycles of data, DT proposes that the change of discharge capacity is the main feature to estimate the lifetime type of batteries. Given the first 100 cycles, the factor with the maximum weight turns to the internal resistance for estimating the battery lifetime.
Importance of Surface Coating to Accumulation Dynamics and Acute Toxicity of Copper Nanomaterials and Dissolved Copper in Daphnia magna
Authors: Gajda-Meissner Zuzanna , Matyja Konrad , Brown David M. , Hartl Mark G.J. , Fernandes Teresa F.
Published: October 2019

We evaluated the effect of copper oxide nanomaterials (CuO NMs), uncoated and with 3 different surface coatings (carboxylated, pegylated, and ammonia groups), on acute toxicity and accumulation dynamics in Daphnia magna. With the use of biodynamic modelling, biosorption and elimination rate constants were determined for D. magna following waterborne exposure to dissolved Cu and CuO NMs. The relationship between modeled parameters and acute toxicity endpoints was evaluated to investigate whether accumulation dynamics parameters could be used as a predictor of acute toxicity. The Langmuir equation was used to characterize the biosorption dynamics of Cu NMs and Cu chloride, used as dissolved Cu control. Uptake rates showed the following NM rankings: pristine-CuO > NH3-CuO > aqueous Cu > polyethylene glycol (PEG)-CuO > COOH-CuO. To determine Cu elimination by D. magna, a one-compartment model was used. Different elimination rate constants were estimated for each chemical substance tested. Those that were easily biosorbed were also easily removed from organisms. Biosorption and depuration properties of NMs were correlated with zeta potential values and diameters of NM agglomerates in the suspensions. No link was found between biosorption and toxicity. Waterborne exposures to more difficult-to-biosorb CuO NMs were more likely to induce adverse effects than those that biosorbed easily. It is proposed that some physicochemical properties of NMs in media, including zeta potential and agglomerate diameter, can lead to higher biosorption but do not necessarily affect toxicity. The mode of interaction of the NMs with the organism seems to be complex and to depend on chemical speciation and physicochemical properties of the NMs inside an organism. Moreover, our findings highlight that coating type affects the biosorption dynamics, depuration kinetics, and dissolution rate of NMs in media. Environ Toxicol Chem 2020;39:287–299. © 2019 SETAC

Abstract

We evaluated the effect of copper oxide nanomaterials (CuO NMs), uncoated and with 3 different surface coatings (carboxylated, pegylated, and ammonia groups), on acute toxicity and accumulation dynamics in Daphnia magna. Our findings highlight that coating type affects the biosorption dynamics, depuration kinetics, and dissolution rate of NMs in media No link was found between biosorption and toxicity.
Return dynamics during periods of high speculation in a thinly traded commodity market
Authors: Bohl Martin T. , Stefan Martin
Published: October 2019

This article studies the effects of speculation in a thinly traded commodity futures market, paying particular attention to periods characterized by high‐speculative activity of long–short speculators. Using the speculation ratio as a daily measure for long–short speculation, we employ generalized autoregressive conditional heteroscedasticity regressions to study its impact on return dynamics. Our results for the Chicago Mercantile Exchange feeder cattle futures market suggest that futures returns are predominantly explained by fundamentals, but their volatility is significantly driven by the speculation ratio. This relationship holds for periods of high‐ and low‐speculative activity alike.
Regional heterogeneous temporal–spatial distribution of gold deposits in theNorth China Craton: A review
Authors: Zhang Lian‐Chang , Bai Yang , Zhu Ming‐Tian , Huang Ke , Peng Zi‐dong
Published: October 2019

The gold mineralization of the North China Craton (NCC) is characterized by regional heterogeneous distribution. Such a feature is mainly reflected by the spatial dispersity and local concentration, as well as multiperiods of gold‐forming events. Gold deposits are principally converged in the Jiaodong, Xiaoqinling‐Xiong'er Mountain, Jidong, Liaodong, and Taihang Mountain regions. The northern margin of the NCC is strongly enriched in Au, Mo, and Cu elements, whereas its southern and eastern margins trend to show significant enrichment of Au–Mo and Au, respectively. Among them, the early period of Mesozoic mineralization is Au–Mo–Pb–Zn combination, the peak is Au, and the late period is Au–Ag combination. The Early Cretaceous is the main gold metallogenic epoch of the NCC followed by the Middle–Late Triassic and Jurassic. Generally, gold mineralization time of the Xiaoqinling‐Xiong'er Mountain and Taihang Mountain is a little earlier than those of Jiaodong gold deposits; some of Jidong (Jinchangyu, Yuerya, and Niuxinshan) and the Liaodong (Baiyun and Maoling) gold deposits were formed in the Triassic–Jurassic. Overall, the uneven distribution of gold deposits in the NCC is generally controlled by the tectonic evolution and interaction of the regional geological blocks, the hydrothermal alteration and gold activation in the metamorphic basement, and the Mesozoic magma activity. In the Middle Jurassic and before, the tectonic evolution of the NCC was mainly influenced by the Central Asian Orogenic Belt and the Qinling Orogenic Belt. Tectonic system transition from extrusion to extension, locally developed mantle upwelling and lithospheric thinning, as well as a series of Middle Triassic–Jurassic magmatic activities, and even the presence of alkaline rocks along the east–west direction occurred on the northern margin of the NCC, which generated a series of Au–Mo deposits. This is the first craton destruction and gold mineralization event that occurred in the northern margin of the NCC after its formation. In the Cretaceous and after, the geological evolution of the NCC was mainly controlled by the ancient Pacific Plate. The NCC was subjected to extensive lithospheric thinning, which in turn led to a more large‐scale gold mineralization. In addition, it is found that these ore‐forming materials sourced from the metamorphic rock are not entirely dependent on the gold content but also affected by one or more geological processes, which activate and extract gold from the wall rock and upgrade it in suitable tectonic environments. The influence of granitoids and intermediate–basic dikes in these gold deposits seems like a “hot machine,” which is the source of metallogenic hydrothermal fluid, and it is also a possible source of some ore‐forming minerals.
Building the bodily self‐awareness: Evidence for the convergence between interoceptive and exteroceptive information in a multilevel kernel density analysis study
Authors: Salvato Gerardo , Richter Fabian , Sedeño Lucas , Bottini Gabriella , Paulesu Eraldo
Published: October 2019

Exteroceptive and interoceptive signals shape and sustain the bodily self‐awareness. The existence of a set of brain areas, supporting the integration of information coming from the inside and the outside of the body in building the sense of bodily self‐awareness has been postulated, yet the evidence remains limited, a matter of discussion never assessed quantitatively. With the aim of unrevealing where in the brain interoceptive and exteroceptive signals may converge, we performed a meta‐analysis on imaging studies of the sense of body ownership, modulated by external visuotactile stimulation, and studies on interoception, which involves the self‐awareness for internal bodily sensations. Using a multilevel kernel density analysis, we found that processing of stimuli of the two domains converges primarily in the supramarginal gyrus bilaterally. Furthermore, we found a right‐lateralized set of areas, including the precentral and postcentral, and superior temporal gyri. We discuss these results and propose this set of areas as ideal candidates to match multiple body‐related signals contributing to the creation of a multidimensional representation of the bodily self.
Mapping language with resting‐state functional magnetic resonance imaging: A study on the functional profile of the language network
Authors: Branco Paulo , Seixas Daniela , Castro São L.
Published: October 2019

Resting‐state functional magnetic resonance imaging (rsfMRI) is a promising technique for language mapping that does not require task‐execution. This can be an advantage when language mapping is limited by poor task performance, as is common in clinical settings. Previous studies have shown that language maps extracted with rsfMRI spatially match their task‐based homologs, but no study has yet demonstrated the direct participation of the rsfMRI language network in language processes. This demonstration is critically important because spatial similarity can be influenced by the overlap of domain‐general regions that are recruited during task‐execution. Furthermore, it is unclear which processes are captured by the language network: does it map rather low‐level or high‐level (e.g., syntactic and lexico‐semantic) language processes? We first identified the rsfMRI language network and then investigated task‐based responses within its regions when processing stimuli of increasing linguistic content: symbols, pseudowords, words, pseudosentences and sentences. The language network responded only to language stimuli (not to symbols), and higher linguistic content elicited larger brain responses. The left fronto‐parietal, the default mode, and the dorsal attention networks were examined and yet none showed language involvement. These findings demonstrate for the first time that the language network extracted through rsfMRI is able to map language in the brain, including regions subtending higher‐level syntactic and semantic processes.
Does acknowledgement matter? An exploratory study of the value of a Healthy Workplace Recognition Scheme
Authors: Lewis Virginia , Marsh Geraldine , Macmillan Jenny , Mullins Robyn
Published: October 2019

Issues addressed

Strategies motivating employers and high‐level management to provide workplace‐based health and well‐being programs are needed. Recognition Schemes, acknowledging organisations for providing a healthy workplace, may help to motivate them.

Methods

Semi‐structured telephone interviews with representatives of 35 workplaces that had achieved Awards in the Recognition Scheme of a state government Healthy Workplace program.

Results

Interviewees were mainly interested in having the work they were already doing recognised by staff and management internally. For some, external recognition was also important. Many were disappointed with the form the recognition took, feeling it did not have the gravitas it needed to be useful. Despite this, most Bronze and Silver Award winners indicated they would reapply in future, though some Gold recipients were not convinced the rigorous process was worthwhile.

Conclusions

Recognition schemes may encourage organisations to offer or improve Healthy Workplace programs. This project demonstrated that the form the recognition takes and the way it is awarded is important to recipients, and that the scheme must be well promoted externally if it is to achieve its potential benefits.

So what?

Effective workplace health and well‐being programs require commitment from high‐level management including providing adequate time and resources. Recognition schemes may lead to greater effort and investment by workplaces, but the Schemes must be well promoted and highly visible for participating workplaces to feel the effort that goes into applying for recognition is worthwhile. If recognition is not valued within and outside organisations, the potential benefits will not be realised.
Mycophenolic acid is a drug with the potential to be repurposed for suppressing tumor growth and metastasis in osteosarcoma treatment
Authors: Klangjorhor Jeerawan , Chaiyawat Parunya , Teeyakasem Pimpisa , Sirikaew Nutnicha , Phanphaisarn Areerak , Settakorn Jongkolnee , Lirdprapamongkol Kriengsak , Yama Sarawoot , Svasti Jisnuson , Pruksakorn Dumnoensun
Published: October 2019

Our previous review of proteomics data showed that in osteosarcoma, some overexpressed proteins were targets of FDA‐approved immunosuppressive and anti‐arrhythmic drugs, including mycophenolate mofetil (MMF), ribavirin, leflunomide, azathioprine and digoxin. Here, these drugs were screened for growth inhibitory effects in human osteosarcoma cell lines, including MNNG/HOS, U2OS, SaOS‐2, MG‐63 and 143B cells. Only mycophenolic acid (MPA), an active metabolite of MMF, efficiently inhibited osteosarcoma cell growth with IC50 values of 0.46‐7.3 μM; these values are in the therapeutic range for organ transplant patients. At a therapeutic dose (10 μM), MPA significantly inhibited colony formation, caused cell cycle arrest in the S phase, and induced apoptosis. Moreover, the in vitro invasion of osteosarcoma cells was reduced by MPA by inhibiting cell migration capability. The in vivo antitumor effect of MMF was determined in nude mice harboring 143B cell xenografts. Daily oral administration of 200 mg/kg/day MMF for 2 weeks significantly suppressed tumor growth in treated mice, achieving 57.4 ± 11.1% tumor growth inhibition. Compared with the vehicle group, the MMF group treated with 50–200 mg/kg/day for 3 weeks had a significant reduction in the number of lung metastatic nodules in a tail vein‐lung metastasis model of 143B cells. MMF doses of 50, 100 and 200 mg/kg/day are approximately equivalent to the non‐toxic doses of 0.25, 0.5 and 1 g/day in humans, respectively. These findings indicate that MPA/MMF can effectively control osteosarcoma tumor growth and metastasis. Thus, the potential to repurpose MPA/MMF for use in osteosarcoma chemotherapy is of great interest.
Platinum‐based regimens versus cetuximab in definitive chemoradiation for human papillomavirus‐unrelated head and neck cancer
Authors: Beckham Thomas H. , Barney Christian , Healy Erin , Wolfe Adam R. , Branstetter Andrew , Yaney Alexander , Riaz Nadeem , McBride Sean M. , Tsai C. Jillian , Kang Julie , Yu Yao , Chen Linda , Sherman Eric , Dunn Lara , Pfister David G. , Tan Jeremy , Rupert Robert , Bonomi Marcelo , Zhang Zhigang , Lobaugh Stephanie M. , Grecula John C. , Mitchell Darrion L. , Wobb Jessica L. , Miller Eric D. , Blakaj Dukagjin M. , Diavolitsis Virginia M. , Lee Nancy , Bhatt Aashish D.
Published: October 2019

For patients ineligible for cisplatin with definitive radiotherapy (CP‐CRT) for locally advanced head and neck squamous cell carcinoma (LA‐HNSCC), concurrent cetuximab (C225‐RT) is a popular substitute. Carboplatin‐based chemoradiation (CB‐CRT) is another option; however, relative efficacies of CP‐CRT, CB‐CRT and C225‐RT are unclear, particularly in the human papillomavirus (HPV)‐unrelated population. We identified 316 patients with stage III‐IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225‐RT (N = 61), CB‐CRT (N = 74) or CP‐CRT (N = 181). Kaplan‐Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3‐year cumulative incidences for CP‐CRT, CB‐CRT and C225‐RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan‐Meier estimates for 3 year OS were: CP‐CRT: 71%; CB‐CRT: 59% and C225‐RT: 54%; p = 0.0094. CP‐CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203–0.557, p < 0.01) and CB‐CRT (HR 0.279; 95% CI 0.141–0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP‐CRT (HR 0.548; 95% CI 0.355–0.845, p < 0.01) and CB‐CRT (HR 0.549; 95% CI 0.334–0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB‐CRT group compared to C225‐RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB‐CRT group compared to C225‐RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB‐CRT is an effective alternative to CP‐CRT in HPV‐unrelated LA‐HNSCC with superior locoregional control and OS compared to C225‐RT.
Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma
Authors: Sjödahl Gottfrid , Eriksson Pontus , Patschan Oliver , Marzouka Nour‐Al‐Dain , Jakobsson Lovisa , Bernardo Carina , Lövgren Kristina , Chebil Gunilla , Zwarthoff Ellen , Liedberg Fredrik , Höglund Mattias
Published: October 2019

Molecular changes occurring during invasion and clinical progression of cancer are difficult to study longitudinally in patient‐derived material. A unique feature of urothelial bladder cancer (UBC) is that patients frequently develop multiple nonmuscle invasive tumors, some of which may eventually progress to invade the muscle of the bladder wall. Here, we use a cohort of 73 patients that experienced a total of 357 UBC diagnoses to study the stability or change in detected molecular alterations during cancer progression. The tumors were subtyped by gene expression profiling and analyzed for hotspot mutations in FGFR3, PIK3CA and TERT, the most frequent early driver mutations in this tumor type. TP53 alterations, frequent in advanced UBC, were inferred from p53 staining pattern, and potential genomic alterations were inferred by gene expression patterns at regions harboring frequent copy number alterations. We show that early driver mutations were largely preserved in UBC recurrences. Changes in FGFR3, PIK3CA or TERT mutation status were not linked to changes in molecular subtype and aggressive behavior. Instead, changes into a more aggressive molecular subtype seem to be associated with p53 alterations. We analyze changes in gene expression from primary tumors, to recurrences and progression tumors, and identify two modes of progression: Patients for whom progression is preceded by or coincides with a radical subtype shift, and patients who progress without any systematic molecular changes. For the latter group of patients, progression may be either stochastic or depending on factors already present at primary tumor initiation.
Use of an antiemetic to shorten the length of labor in nulliparous women, exploring a potential role of an old drug: A randomized controlled trial
Authors: Ellaithy Mohamed , Rasheed Suriaya , Shafik Adel , Abees Sara
Published: October 2019

Objective

To assess whether metoclopramide is effective in shortening the duration of the first stage of labor in primiparous women.

Methods

The present randomized, double‐blind, placebo‐controlled trial was conducted at King Faisal Hospital, Saudi Arabia (between July 30, 2013, and September 1, 2016), and sequentially recruited young nulliparous women admitted in spontaneous active labor with or without ruptured membranes. Eligible participants were randomly assigned to receive a slow intravenous injection of either metoclopramide or placebo and consistently managed according to the local institutional intrapartum protocol and received identical monitoring and supportive care. The primary outcome was the cervical dilatation rate.

Results

Fifty‐nine women were included in the metoclopramide group and 52 in the placebo group. The first stage of labor was significantly shorter in the metoclopramide group (203 minutes vs 230 minutes in the placebo group, P=0.019), with a faster cervical dilatation rate (2.4 ± 0.4 cm/h vs 1.9 ± 0.5 cm/h in the placebo group, P<0.001) and shorter interval from treatment administration until full cervical dilatation. There was a significantly higher probability of faster delivery among women who were treated with metoclopramide (log‐rank test, χ2=5.997, P=0.014).

Conclusion

Metoclopramide safely reduced the duration of the first stage of labor and was not associated with major maternal or neonatal adverse outcomes.

ClinicalTrials.gov

NCT01937234