bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcaval access for the emergency delivery of 5.0 liters per minute mechanical circulatory support in cardiogenic shock
Authors: Afana Majed , Altawil Mahmoud , Basir Mir , Alqarqaz Mohammad , Alaswad Khaldoon , Eng Marvin , O'Neill William W. , Lederman Robert J. , Greenbaum Adam B.
Published: September 2020

Objectives

The purpose of this study was to describe the feasibility and early outcomes of transcaval access for delivery of emergency mechanical circulatory support (MCS) in cardiogenic shock.

Background

Vascular access for implantation of MCS in patients with cardiogenic shock is often challenging due to peripheral arterial disease and vasoconstriction. Transcaval delivery of MCS may be an alternative. We describe a series of patients we implanted an Impella 5.0 device, on‐table without CT planning, through a percutaneous transcaval access route.

Methods

Ten patients with progressive or refractory cardiogenic shock underwent Impella 5.0 implantation via transcaval access. Demographic, clinical and procedural variables and in‐hospital outcomes were collected.

Results

All ten underwent emergency implantation of the 7 mm diameter Impella 5.0 device via transcaval access. Six were women, with median age of 55.5 years (range, 29–69). Cardiogenic shock was attributed to idiopathic nonischemic cardiomyopathy (n = 4), myocarditis (n = 2), ischemic cardiomyopathy (n = 2), heart transplant rejection (n = 1), and unknown etiology (n = 1). Median duration of support was 92.1 hr (range, 21.2–165.4). Seven (70%) survived to device explant, with six (60%) surviving to access port closure and discharge. Among survivors, five recovered heart function and one received destination therapy left ventricular assist device.

Conclusions

Transcaval access is feasible for emergency nonsurgical implantation of the Impella 5.0 device in cardiogenic shock with small or diseased iliofemoral arteries. This allows early institution of higher‐flow MCS than conventional femoral artery implantation of the 3.5 L Impella CP device, and enables a bridge‐to‐recovery or bridge‐to‐destination strategy.
Regioselective Isomerization of Terminal Alkenes Catalyzed by a PC(sp3)Pincer Complex with a Hemilabile Pendant Arm
Authors: De‐Botton Sophie , Filippov D.Sc. Oleg A. , Shubina Elena S. , Belkova Natalia V. , Gelman Dmitri
Published: September 2020

We describe an efficient protocol for the regioselective isomerization of terminal alkenes employing a previously described bifunctional Ir‐based PC(sp3)complex (4) possessing a hemilabile sidearm. The isomerization, catalyzed by 4, results in a one‐step shift of the double bond in good to excellent selectivity, and good yield. Our mechanistic studies revealed that the reaction is driven by the stepwise migratory insertion of Ir−H species into the terminal double bond/β‐H elimination events. However, the selectivity of the reaction is controlled by dissociation of the hemilabile sidearm, which acts as a selector, favoring less sterically hindered substrates such as terminal alkenes; importantly, it prevents recombination and further isomerization of the internal ones.
Evaluation of temperature compensation methods for a near‐infrared calibration to predict the viscosity of micellar liquids
Authors: Haroon Kiran , Arafeh Ali , Rodgers Thomas , Mendoza Ćesar , Baker Michael , Martin Philip
Published: September 2020

Near‐infrared (NIR) spectroscopy is a popular technique for the measurement of chemical and physical properties in‐line using predictive models. The success of these models in industrial settings, in terms of accuracy and precision, often relies on the removal or avoidance of non‐linear spectral changes associated with fluctuating process parameters like temperature. In this work, a NIR calibration model developed to predict the viscosity of micellar liquids in‐line is used to evaluate various methods designed to account for temperature fluctuations. The viscosity of these liquids can vary on average by ±0.5 Pa s with a 1° change in temperature. The methods trialled include global linear techniques, a multivariate filter (generalised least squares weighting [GLSW]) and direct standardisation. The performances of these techniques were compared against one another based on root mean square error of prediction (RMSEP), prediction bias and rank. The best method was found to be GLSW, which was the least complex (five latent variables) and showed the lowest RMSEP (0.429 Pa s). This study provides insight into the use of recognised methods to remove temperature‐induced spectral variation in a PLS model developed to predict viscosity, where both NIR spectra and the property of viscosity itself are sensitive to temperature.
Programmable DNA Nanoflowers for Biosensing, Bioimaging, and Therapeutics
Authors: Lv Jigang , Dong Yuhang , Gu Zi , Yang Dayong
Published: September 2020

DNA nanostructures have shown excellent prospects in biomedical applications owing to their unique sequence programmability, function designability, and biocompatibility. As a type of unique DNA–inorganic hybrid nanostructures, DNA nanoflowers (DNFs) have attracted considerable attention in the past few years. Precise design of the DNA sequence enables the functions of DNFs to be customized. Specifically, DNFs exhibit high physiological stability and more diverse properties by virtue of the incorporation of inorganic materials, which in turn have been applied in an assortment of biomedical fields. In this review, the design, synthesis, and biomedical applications of programmable DNFs are discussed. First, the background of DNA‐based materials and the fundamentals of DNFs are briefly introduced. In the second part, two synthetic methods of DNFs are categorized as the rolling circle amplification and salt aging method, focusing on the formation mechanism of DNFs and differences between the synthetic methods. In the third part, the biomedical applications of DNFs functional materials are summarized, including biosensing, bioimaging, and therapeutics. Finally, the challenges and future opportunities of DNFs are discussed toward more widespread applications.
Structure–Property Relationships in Bithiophenes with Hydrogen‐Bonded Substituents
Authors: Özen Bilal , Fadaei Tirani Farzaneh , Schenk Kurt , Lin Kun‐Han , Scopelliti Rosario , Corminboeuf Clémence , Frauenrath Holger
Published: September 2020

The use of crystal engineering to control the supramolecular arrangement of π‐conjugated molecules in the solid‐state is of considerable interest for the development of novel organic electronic materials. In this study, we investigated the effect of combining of two types of supramolecular interaction with different geometric requirements, amide hydrogen bonding and π‐interactions, on the π‐overlap between calamitic π‐conjugated cores. To this end, we prepared two series of bithiophene diesters and diamides with methylene, ethylene, or propylene spacers between the bithiophene core and the functional groups in their terminal substituents. The hydrogen‐bonded bithiophene diamides showed significantly denser packing of the bithiophene cores than the diesters and other known α,ω‐disubstituted bithiophenes. The bithiophene packing density reach a maximum in the bithiophene diamide with an ethylene spacer, which had the smallest longitudinal bithiophene displacement and infinite 1D arrays of electronically conjugated, parallel, and almost linear N−H⋅⋅⋅O=C hydrogen bonds. The synergistic hydrogen bonding and π‐interactions were attributed to the favorable conformation mechanics of the ethylene spacer and resulted in H‐type spectroscopic aggregates in solid‐state absorption spectroscopy. These results demonstrate that the optoelectronic properties of π‐conjugated materials in the solid‐state may be tailored systematically by side‐chain engineering, and hence that this approach has significant potential for the design of organic and polymer semiconductors.
Cycling between Molybdenum‐Dinitrogen and ‐Nitride Complexes to Support the Reaction Pathway for Catalytic Formation of Ammonia from Dinitrogen
Authors: Arashiba Kazuya , Tanaka Hiromasa , Yoshizawa Kazunari , Nishibayashi Yoshiaki
Published: September 2020

Invited for the featured front cover of Kazuya Arashiba, Hiromasa Tanaka, Kazunari Yoshizawa, and Yoshiaki Nishibayashi at The University of Tokyo, Daido University, and Kyushu University. The image depicts a roulette wheel to represent the cycling reaction used in this work. Read the full text of the article at 10.1002/chem.202002200.
Breslow Intermediates (Amino Enols) and Their Keto Tautomers: First Gas‐Phase Characterization by IR Ion Spectroscopy
Authors: Paul Mathias , Peckelsen Katrin , Thomulka Thomas , Martens Jonathan , Berden Giel , Oomens Jos , Neudörfl Jörg‐M. , Breugst Martin , Meijer Anthony J. H. M. , Schäfer Mathias , Berkessel Albrecht
Published: September 2020

Breslow intermediates (BIs) are the crucial nucleophilic amino enol intermediates formed from electrophilic aldehydes in the course of N‐heterocyclic carbene (NHC)‐catalyzed umpolung reactions. Both in organocatalytic and enzymatic umpolung, the question whether the Breslow intermediate exists as the nucleophilic enol or in the form of its electrophilic keto tautomer is of utmost importance for its reactivity and function. Herein, the preparation of charge‐tagged Breslow intermediates/keto tautomers derived from three different types of NHCs (imidazolidin‐2‐ylidenes, 1,2,4‐triazolin‐5‐ylidenes, thiazolin‐2‐ylidenes) and aldehydes is reported. An ammonium charge tag is introduced through the aldehyde unit or the NHC. ESI‐MS IR ion spectroscopy allowed the unambiguous conclusion that in the gas phase, the imidazolidin‐2‐ylidene‐derived BI indeed exists as a diamino enol, while both 1,2,4‐triazolin‐5‐ylidenes and thiazolin‐2‐ylidenes give the keto tautomer. This result coincides with the tautomeric states observed for the BIs in solution (NMR) and in the crystalline state (XRD), and is in line with our earlier calculations on the energetics of BI keto–enol equilibria.
Pitch‐Based Laminated Carbon Formed by Pressure Driving at Low Temperature as High‐Capacity Anodes for Lithium Energy Storage Systems
Authors: Yang Tao , Song Yan , Tian Xiaodong , Song Huaihe , Liu Zhanjun
Published: September 2020

Pitch has been used to prepare electrodes by high‐temperature heat treatments for supercapacitors, lithium‐ion batteries, on account of its rich aromatic ring structure. Here, the toluene‐soluble component of pitch is used to prepare a kind of laminated carbon. This was realized by a template‐free synthesis at low temperature with the addition of pressure. The toluene‐soluble component has a small molecular weight, which makes the thermal deformation ability stronger and then enhances the orientation of the carbon layer with the help of pressure. The prepared anode exhibits a splendid electrochemical performance compared with the traditional graphite anode. A high stable capacity of approximately 550 mAh g−1 at 50 mA g−1, which is much higher than graphite (372 mAh g−1), is obtained. Also, when the current density is up to 2 A g−1, the capacity is about 150 mAh g−1. Surprisingly, it also delivers a superior cycling performance. And when used as the anode/cathode electrode for lithium‐ion capacitors, a high energy density can be obtained. The present work offers an opportunity to utilize the pitch source in lithium energy storage with promising cycle life, high energy/power density, and low cost.
Intermolecular C−H Activation at the Allylic/Benzylic and Homoallylic/Homobenzylic Positions of Cyclic Hydrocarbons by a Stable Divalent Silicon Species
Authors: Koike Taichi , Kosai Tomoyuki , Iwamoto Takeaki
Published: September 2020

Direct activation of inert C(sp3)−H bonds by main group element species is yet a formidable challenge. Herein, the dehydrogenation of cyclohexene and 1,2,3,4‐tetrahydronaphthalene through the allylic/benzylic and homoallylic/homobenzylic C−H bond activation by cyclic (alkyl)(amino)silylene 1 in neat conditions is reported to yield the corresponding aromatic compounds. As for the reaction of cyclohexene, allylsilane 3 and 7‐silanorbornene 4 were also observed, which could be interpreted as a direct dehydrogenative silylation reaction of monoalkenes at the allylic positions. Experimental and computational studies suggest that the dehydrogenation of cyclohexene at the homoallylic position was accomplished by a combination of silylene 1 and radical intermediates such as hydrosilyl radical INT1 or cyclohexenyl radical H, which are generated in the initial step of the reaction.
Rh‐Catalyzed Decarbonylative Cross‐Coupling between o‐Carboranes and Twisted Amides: A Regioselective, Additive‐Free, and Concise Late‐Stage Carboranylation
Authors: Li Chun‐Xiao , Ning Qian , Zhao Wenxuan , Cao Hou‐Ji , Wang Yi‐Ping , Yan Hong , Lu Chang‐Sheng , Liang Yong
Published: September 2020

The convenient cross‐coupling of sp2 or sp3 carbons with a specific boron vertex on carborane cage represents significant synthetic values and insurmountable challenges. In this work, we report an Rh‐catalyzed reaction between o‐carborane and N‐acyl‐glutarimides to construct various Bcage−C bonds. Under the optimized condition, the removable imine directing group (DG) leads to B(3)− or B(3,6)−C couplings, while the pyridyl DG leads to B(3,5)−Ar coupling. In particular, an unexpected rearrangement of amide reagent is observed in pyridyl directed B(4)−C(sp3) formation. This scalable protocol has many advantages, including easy access, the use of cheap and widely available coupling agents, no requirement of an external ligand, base or oxidant, high efficiency, and a broad substrate scope. Leveraging the RhI dimer and twisted amides, this method enables straightforward access to diversely substituted and therapeutically important carborane derivatives at boron site, and provides a highly valuable vista for carborane‐based drug screening.
Molybdenum‐Catalyzed Deoxygenation Coupling of Lignin‐Derived Alcohols for Functionalized Bibenzyl Chemicals
Authors: Jiang Huifang , Lu Rui , Luo Xiaolin , Si Xiaoqin , Xu Jie , Lu Fang
Published: September 2020

With the growing demand for sustainability and reducing CO2 footprint, lignocellulosic biomass has attracted much attention as a renewable, carbon‐neutral and low‐cost feedstock for the production of chemicals and fuels. To realize efficient utilization of biomass resource, it is essential to selectively alter the high degree of oxygen functionality of biomass‐derivates. Herein, we introduced a novel procedure to transform renewable lignin‐derived alcohols to various functionalized bibenzyl chemicals. This strategy relied on a short deoxygenation coupling pathway with economical molybdenum catalyst. A well‐designed H‐donor experiment was performed to investigate the mechanism of this Mo‐catalyzed process. It was proven that benzyl carbon‐radical was the most possible intermediate to form the bibenzyl products. It was also discovered that the para methoxy and phenolic hydroxyl groups could stabilize the corresponding radical intermediates and then facilitate to selectively obtain bibenzyl products. Our research provides a promising application to produce functionalized aromatics from biomass‐derived materials.
Metal–Organic Framework (MOF)‐Derived Electron‐Transfer Enhanced Homogeneous PdO‐Rich Co3O4 as a Highly Efficient Bifunctional Catalyst for Sodium Borohydride Hydrolysis and 4‐Nitrophenol Reduction
Authors: Dou Shasha , Zhou Shuqing , Huang Hexiu , Yan Puxuan , Shoko Elvis , Isimjan Tayirjan Taylor , Yang Xiulin
Published: September 2020

Developing a bifunctional catalyst with low cost and high catalytic performance in NaBH4 hydrolysis for H2 generation and selective reduction of nitroaromatics will make a significant impact in the field of sustainable energy and water purification. Herein, a low‐loading homogeneously dispersed Pd oxide‐rich Co3O4 polyhedral catalyst (PdO‐Co3O4) with concave structure is reported by using a metal–organic framework (MOF)‐templated synthesis method. The results show that the PdO‐Co3O4 catalyst has an exceptional turnover frequency (3325.6 molH2 min−1 molPd−1), low activation energy (43.2 kJ mol−1), and reasonable reusability in catalytic H2 generation from NaBH4 hydrolysis. Moreover, the optimized catalyst also shows excellent catalytic performance in the NaBH4 selective reduction of 4‐nitrophenol to 4‐aminiphenol with a high first‐order reaction rate of approximately 1.31 min−1. These excellent catalytic properties are mainly ascribed to the porous concave structure, monodispersed Pd oxide, as well as the unique synergy between PdO and Co3O4 species, which result in a large specific surface area, high conductivity, and fast solute transport and gas emissions.
Non‐Planar Structures of Sterically Overcrowded Trialkylamines
Authors: Banert Klaus , Heck Manuel , Ihle Andreas , Shoker Tharallah , Wörle Michael , Boese A. Daniel
Published: September 2020

Several amines with three bulky alkyl groups at the nitrogen atom, which exceed the steric crowding of triisopropylamine significantly, were synthesized, mainly by treating N‐chlorodialkylamines with Grignard reagents. In six cases, namely tert‐butyldiisopropylamine, 1‐adamantyl‐tert‐butylisopropylamine, di‐1‐adamantylamines with an additional N‐cyclohexyl or N‐exo‐2‐norbonyl substituent, as well as 2,2,6,6‐tetramethylpiperidine derivatives with N‐cyclohexyl or N‐neopentyl groups, appropriate single crystals were generated that enabled X‐ray diffraction studies and analysis of the molecular structures. The four noncyclic amines adopt triskele‐like conformations, and the sum of the three C−N−C angles is always in the range of 351.1° to 352.4°. Consequently, these amines proved to be structurally significantly flatter than trialkylamines without steric congestion, which is also signalized by the smaller heights of the NC3 pyramids (0.241–0.259 Å). There is no clear correlation between the heights of these pyramids and the degree of the steric crowding in the new amines, presumably because steric repulsion is partly compensated by dispersion interaction. In the cases of the two heterocyclic amines, the steric stress is smaller, and the molecular structures include quite different conformations. Quantum chemical calculations led to precise gas‐phase structures of the sterically overcrowded trialkylamines exhibiting heights of the NC3 pyramids and preferred molecular conformers which are similar to those resulting from the X‐ray studies.
An Unprecedented Bird Nest Molybdenum(V) Cobalto‐Phosphate Nanosized Wheel Constructed from the [H55(Mo24O48)(Co4O)2Co16(PO4)42(py)6(EtOH)2(H2O)11]3− Anion
Authors: Kang Run‐Kun , Dong Ya‐Yu , Cao Jia‐Peng , Luo Xi‐Ming , Du Ze‐Yu , Zhu Dunru , Xu Yan
Published: September 2020

An unprecedented bird‐nest high‐nuclear molybdenum(V) cobalto‐phosphate nanosized wheel modified by imidazole (im) and pyridine (py), {[H55(Mo24O48)(Co4O)2Co16(PO4)42(py)6(EtOH)2(H2O)11]‐ @[(Him)2(Hpy)]}(N‐Et‐py)(H2PO4)(py)7(EtOH)⋅12 H2O (1), has been successfully synthesized by self‐assembly. The anionic huge wheel consists of two rare {Co4O} squares, four {Co4} tetramers, four {Mo4} tetramers and four {Mo2} dimers, linked by bridging oxygen atoms and [PO4] groups and encloses two imidazolium cations and a protonated pyridium for charge balance. Surprisingly, 1 represents the first twisted wheel‐shaped cluster with a record high‐nuclear molybdenum(V) cobalto‐phosphate. The delocalized electron effects of the cluster are enhanced with the help of coordinated py ligands, which endows 1 with an excellent third‐order nonlinear optical (NLO) response. Additionally, 1 also shows a better photocatalytic water oxidation activity than Co(NO3)2 with the O2 production of 205 μmol during 6 h in the absence of the [Ru(bpy)3]2+ photosensitizer.
Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike‐ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics**
Authors: Gil‐Moles Maria , Basu Uttara , Büssing Rolf , Hoffmeister Henrik , Türck Sebastian , Varchmin Agnieszka , Ott Ingo
Published: September 2020

Gold complexes have a long tradition in medicine and for many examples antirheumatic, anticancer or anti‐infective effects have been confirmed. Herein, we evaluated the lead compound Auranofin and five selected gold organometallics as inhibitors of two relevant drug targets of severe acute respiratory syndrome coronaviruses (SARS‐CoV). The gold metallodrugs were effective inhibitors of the interaction of the SARS‐CoV‐2 spike protein with the angiotensin converting enzyme 2 (ACE2) host receptor and might thus interfere with the viral entry process. The gold metallodrugs were also efficient inhibitors of the papain‐like protease (PLpro) of SARS‐CoV‐1 and SARS‐CoV‐2, which is a key enzyme in the viral replication. Regarding PLpro from SARS‐CoV‐2, the here reported inhibitors are among the very first experimentally confirmed examples with activity against this target enzyme. Importantly, the activity of the complexes against both PLpro enzymes correlated with the ability of the inhibitors to remove zinc ions from the labile zinc center of the enzyme. Taken together, the results of this pilot study suggest further evaluation of gold complexes as SARS‐CoV antiviral drugs.
Is a polar bond a prerequisite for an acid? Analysis of a widely accepted explanation
Authors: Fleischer Holger
Published: September 2020

Die Erklärung der Acidität eines Moleküls HA durch die Polarität einer Element‐Wasserstoff‐Bindung („Polaritätskonzept“) ist nicht tragfähig. Die Analyse der Protolyse verschiedener Säuren HA mit der Base H2O in einem thermodynamischen Kreisprozess zeigt drei wesentliche Beiträge, die für Aciditätsunterschiede verantwortlich sind: Die freie Standardbindungsenthalpie, ΔBG0(H−A), die freie Standardhydratationsenthalpie der korrespondierenden Base A−, ΔhydG(A−), und die Ionisierungsenergie von A−, IE(A−). In vielen Fällen steigt der Betrag von ΔBG0(H−A), d.h. die Bindungsstärke der Element‐Wasserstoff‐Bindung, mit deren Polarität. Das steht dem Polaritätskonzept entgegen. Je größer hingegen IE(A−), desto stabiler ist A− und umso acider ist HA. Es wird die Hypothese aufgestellt, dass IE(A−) mit der Möglichkeit zur Delokalisierung der negativen Ladung zunimmt. Eine Analyse der Orbitale von CH3−, NH2−, OH− und F− zeigt, dass die Delokalisierung der Valenzelektronen und damit auch der negativen Ladung in dieser Reihe zunimmt. Dieser Effekt, und nicht die Polarität der H−A‐Bindung, bedingt den Anstieg der Acidität in der Reihe CH4−NH3−H2O−HF. Die Delokalisierung der negativen Ladung lässt sich mit dem Kugelwolkenmodell im Chemieunterricht der Sekundarstufe 1 anschaulich darstellen. Daher wird ein „Delokalisierungskonzept“ statt des „Polaritätskonzepts“ zur Vorhersage und zur Erklärung unterschiedlicher Aciditäten vorgeschlagen.
Transcatheter vs surgical aortic valve replacement in low to intermediate surgical risk aortic stenosis patients: A systematic review and meta‐analysis of randomized controlled trials
Authors: Zhang Dengshen , Mao Xin , Liu Daxing , Zhang Jian , Luo Gang , Luo Liangliang
Published: September 2020

Background

Transcatheter aortic valve replacement (TAVR) is regarded as the most superior alternative treatment approach for patients with aortic stenosis (AS) who are associated with high surgical risk, whereas the effectiveness of TAVR vs surgical aortic valve replacement (SAVR) in low to intermediate surgical risk patients remained inconclusive. This study aimed to determine the best treatment strategies for AS with low to intermediate surgical risk based on published randomized controlled trials (RCTs).

Hypothesis and Methods

RCTs that compared TAVR vs SAVR in AS patients with low to intermediate surgical risk were identified by PubMed, EmBase, and the Cochrane library from inception till April 2019. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated for the data collected using random‐effects models.

Results

Seven RCTs with a total of 6929 AS patients were enrolled. We noted that TAVR significantly increased the risk of transient ischemic attack (TIA) (RR: 1.43; 95%CI: 1.04‐1.96; P = .029), and permanent pacemaker implantation (RR: 3.00; 95%CI: 1.70‐5.30; P < .001). However, TAVR was associated with lower risk of post‐procedural bleeding (RR: 0.57; 95%CI: 0.33‐0.98; P = .042), new‐onset or worsening of atrial fibrillation (RR: 0.32; 95%CI: 0.23‐0.45; P < .001), acute kidney injury (RR: 0.40; 95%CI: 0.25‐0.63; P < .001), and cardiogenic shock (RR: 0.34; 95%CI: 0.19‐0.59; P < .001). The risk of aortic‐valve reintervention at 1‐ (RR: 2.63; 95%CI: 1.34‐5.15; P = .005), and 2 years (RR: 3.19; 95%CI: 1.63‐6.24; P = .001) in low to intermediate surgical risk patients who received TAVR was significantly increased than those who received SAVR.

Conclusions

These findings indicated that low to intermediate surgical risk patients who received TAVR had low risk of complications, whereas the risk of TIA, permanent pacemaker implantation, and aortic‐valve reintervention was increased.
Development of Selective TGR5 Ligands Based on the 5,6,7,8‐Tetrahydro‐5,5,8,8‐tetramethylnaphthalene Skeleton
Authors: Terui Ryusei , Yanase Yuta , Yokoo Hidetomo , Suhara Yoshitomo , Makishima Makoto , Demizu Yosuke , Misawa Takashi
Published: September 2020

TGR5, a G‐protein‐coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8‐tetrahydro‐5,5,8,8‐tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N‐(2‐chlorophenyl)‐5,6,7,8‐tetrahydro‐5,5,8,8‐tetramethyl‐2‐naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC50 value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia.
Process mining‐constrained scheduling in the hybrid cloud
Authors: Azumah Kenneth K. , Sørensen Lene T. , Montella Raffaele , Kosta Sokol
Published: September 2020

Hybrid cloud, typically a combination of public and private cloud deployment models, is a rising paradigm due to the benefits it offers: full control of data and applications in the private cloud and elastic computing resource availability in the public cloud. This combination however brings an extra layer of complexity that can potentially erode the benefits and present serious challenges if not managed well. Among the challenges, ensuring business constraint compliance across the combination of cloud deployment models is a growing concern. Our article brings a sensitive, data‐ and process‐aware framework to bear on task scheduling in hybrid clouds with compliance to business constraints. Our proposed approach utilizes data from a real hybrid cloud‐based hospital billing system that is governed by complex and dynamic data processing rules. Our system successfully employs a process mining controlled algorithm to schedule tasks in the hybrid cloud to comply with the given set of business constraints.
Rapid‐Scan Electron Paramagnetic Resonance of Highly Resolved Hyperfine Lines in Organic Radicals.
Authors: McPeak Joseph E. , Höfer Peter , Kacprzak Sylwia , Carl Patrick , Weber Ralph , Eaton Sandra S. , Eaton Gareth R.
Published: September 2020

X‐band (ca. 9 GHz) fluid solution rapid‐scan electron paramagnetic resonance spectra are reported for radicals with multiline spectra and resolution of hyperfine lines as narrow as 30 mG. Highly‐resolved spectra of 3‐carbamoyl‐2,2,5,5‐tetramethylpyrrolidin‐1‐yloxy, diphenylnitroxide, galvinoxyl, and perylene cation radical with excellent signal‐to‐noise are shown, demonstrating the capabilities of the rapid‐scan technique to characterize very small, well‐resolved hyperfine couplings. To acquire high resolution spectra the signal bandwidth must be less than the resonator bandwidth. Signal bandwidth is inversely proportional to linewidth and proportional to scan rate. Resonator bandwidth is inversely proportional to resonator Q. Proper selection of scan rate and resonator Q is needed to achieve resolution of closely‐spaced narrow EPR lines.
The Mechanism of Flex‐Activation in Mechanophores Revealed By Quantum Chemistry
Authors: Mier Lennart J. , Adam Gheorghe , Kumar Sourabh , Stauch Tim
Published: September 2020

Flex‐activated mechanophores can be used for small‐molecule release in polymers under tension by rupture of covalent bonds that are orthogonal to the polymer main chain. Using static and dynamic quantum chemical methods, we here juxtapose three different mechanical deformation modes in flex‐activated mechanophores (end‐to‐end stretching, direct pulling of the scissile bonds, bond angle bendings) with the aim of proposing ways to optimize the efficiency of flex‐activation in experiments. It is found that end‐to‐end stretching, which is a traditional approach to activate mechanophores in polymers, does not trigger flex‐activation, whereas direct pulling of the scissile bonds or displacement of adjacent bond angles are efficient methods to achieve this goal. Based on the structural, energetic and electronic effects responsible for these observations, we propose ways of weakening the scissile bonds experimentally to increase the efficiency of flex‐activation.
Quantitative Proteomic Profiling of Murine Ocular Tissue and the Extracellular Environment
Authors: Yeung Jason , Lamb Jeffrey , Krieger Jonathan R. , Gadjeva Mihaela , Geddes‐McAlister Jennifer
Published: September 2020

Mass spectrometry‐based proteomics provides a robust and reliable method for detecting and quantifying changes in protein abundance among samples, including cells, tissues, organs, and supernatants. Physical damage or inflammation can compromise the ocular surface permitting colonization by bacterial pathogens, commonly Pseudomonas aeruginosa, and the formation of biofilms. The interplay between P. aeruginosa and the immune system at the site of infection defines the host's ability to defend against bacterial invasion and promote clearance of infection. Profiling of the ocular tissue following infection describes the nature of the host innate immune response and specifically the presence and abundance of neutrophil‐associated proteins to neutralize the bacterial biofilm. Moreover, detection of unique proteins produced by P. aeruginosa enable identification of the bacterial species and may serve as a diagnostic approach in a clinical setting. Given the emergence and prevalence of antimicrobial resistant bacterial strains, the ability to rapidly diagnose a bacterial infection promoting quick and accurate treatment will reduce selective pressure towards resistance. Furthermore, the ability to define differences in the host immune response towards bacterial invasion enhances our understanding of innate immune system regulation at the ocular surface. Here, we describe murine ocular infection and sample collection, as well as outline protocols for protein extraction and mass spectrometry profiling from corneal tissue and extracellular environment (eye wash) samples. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Murine model of ocular infection

Basic Protocol 2: Murine model sample collection

Basic Protocol 3: Protein extraction from eye wash

Basic Protocol 4: Protein extraction from corneal tissue

Basic Protocol 5: Mass spectrometry‐based proteomics and bioinformatics from eye wash and corneal tissue samples
Time trends in treatment modes of anorexia nervosa in a nationwide cohort with free and equal access to treatment
Authors: Støving René Klinkby , Larsen Pia Veldt , Winkler Laura Al‐Dakhiel , Bilenberg Niels , Røder Michael Ejnar , Steinhausen Hans‐Christoph
Published: September 2020

Background

Treating patients with anorexia nervosa (AN) remains a major challenge. The choice between an inpatient or an outpatient care setting is an essential issue for the patients and for their relatives with major health economic implications. However, health services‐related studies are lacking. The present study was a descriptive exploration of time‐trends in treatment modes of patients with free and equal access to health services.

Methods

The study was based on a nationwide cohort of patients diagnosed for the first time with AN, each followed for 5 years in the registers covering the years 1994–2018. The per patient number of hospital admissions, cumulated number of days of hospitalization and number of outpatient visits during the first 5 years after initial diagnosis were considered.

Results

The cohort of patients with AN with at least 5 years of follow‐up amounted to N = 7,505. A clear trend was observed in the per patient five‐year cumulated number of inpatient days, decreasing by 6% per year after adjustment for age at diagnosis, parental mental diagnosis, and family income. The five‐year number of hospital admissions after initial diagnosis decreased by 2% per year, while no trend was observed for outpatient visits.

Conclusions

The per patient number of hospitalizations and cumulated days of hospitalization during 5 years after diagnosis were reduced for patients initially diagnosed with AN while there was no change in the number of outpatient visits. The factors contributing to these changes of treatment modes over time are in need of further study.
Cascading implications of a single climate change event for fragile ecosystems on the Qinghai‐Tibetan Plateau
Authors: Lu Shanlong , Chen Fu , Zhou Jinfeng , Hughes Alice C. , Ma Xiaoqi , Gao Wenwen
Published: September 2020

With changing climates globally, we see changes in not just average conditions, but also in extreme events, and such events require special attention due to their unpredictable yet significant impact on native biotas. One such event is the formation of a landscape scar at Zonag Lake caused by a climate change‐induced outburst flooding event that occurred on 15 September 2011. During the winter, the scar region became a new birthplace for sandstorms, and since the flooding, remote sensing monitoring shows that between 2011 and 2020, there were 285 sandstorm days (between November and March), relative to none prior. The outburst flooding event and consequential sandstorms threaten the key lambing area of the Tibetan antelope (Chiru), affect the water balance of the Zonag Lake and downstream lakes, and may even impact on the flow in the Yangtze River. Active human intervention may be needed to repair this new desert spit and reverse the slew of consequences which may otherwise lead to significant population declines in one of the major Chiru breeding grounds due to the progressive loss of vegetation productivity across their main breeding area.
Forest conversion to oil palm compresses food chain length in tropical streams
Authors: Wilkinson Clare L. , Chua Kenny W. J. , Fiala Roswitha , Liew Jia H. , Kemp Victoria , Hadi Fikri Arman , Ewers Robert M. , Kratina Pavel , Yeo Darren C. J.
Published: September 2020

In Southeast Asia, biodiversity‐rich forests are being extensively logged and converted to oil palm monocultures. Although the impacts of these changes on biodiversity are largely well documented, we know addition to samples we collected in 201 little about how these large‐scale impacts affect freshwater trophic ecology. We used stable isotope analyses (SIA) to determine the impacts of land‐use changes on the relative contribution of allochthonous and autochthonous basal resources in 19 stream food webs. We also applied compound‐specific SIA and bulk‐SIA to determine the trophic position of fish apex predators and meso‐predators (invertivores and omnivores). There was no difference in the contribution of autochthonous resources in either consumer group (70–82%) among streams with different land‐use type. There was no change in trophic position for meso‐predators, but trophic position decreased significantly for apex predators in oil palm plantation streams compared to forest streams. This change in maximum food chain length was due to turnover in identity of the apex predator among land‐use types. Disruption of aquatic trophic ecology, through reduction in food chain length and shift in basal resources, may cause significant changes in biodiversity as well as ecosystem functions and services. Understanding this change can help develop more focused priorities for mediating the negative impacts of human activities on freshwater ecosystems.
Certain detection of uncertain taxa: eDNA detection of a cryptic mountain sucker (Pantosteus jordani) in the Upper Missouri River, USA
Authors: Mason Daniel H. , Dysthe Joseph C. , Franklin Thomas W. , Williams Chris L. , Young Michael K. , McKelvey Kevin S. , Schwartz Michael K.
Published: September 2020

A lineage of the Mountain Sucker species complex (Pantosteus jordani) exists as a genetically and morphologically distinct taxon restricted to the Missouri River basin. This species is thought to be declining throughout its range and is assumed to be extirpated from the southern portion of its distribution. We developed a quantitative PCR‐based environmental DNA assay for P. jordani to help define and monitor its current range. The assay is both specific to P. jordani and sensitive to low amounts of DNA, with a detection limit of 10 DNA copies per reaction. In vitro experiments involved testing DNA from twenty tissue samples, collected from the Missouri River basin in Montana and Wyoming. The assay efficiently detected DNA of all P. jordani samples and did not amplify DNA of any closely related nontarget species. Additionally, 29 environmental DNA samples were taken in 19 waterbodies within P. jordani range and its presence or absence was determined prior to sampling at six of 29 sites. All sites where P. jordani was known absent produced negative results, and all sites where it was known present were confirmed with environmental DNA detections. The new assay was able to detect P. jordani at ten sites which were not previously known to contain individuals, demonstrating that this tool has the potential to rapidly expand the current understanding of this taxon's distribution.
Impact of an extended audit on identifying heart failure patients in general practice: baseline results of the OSCAR‐HF pilot study
Authors: Smeets Miek , Vaes Bert , Aertgeerts Bert , Raat Willem , Penders Joris , Vercammen Jan , Droogne Walter , Mullens Wilfried , Janssens Stefan
Published: September 2020

Aims

Identifying heart failure (HF) patients in general practice is challenging, and little is known about the current quality of care. We implemented an extended audit from the electronic health records (EHRs) of general practitioners (GPs) to identify HF patients and investigate patient characteristics and quality of care.

Methods and results

This study describes the baseline results of the OSCAR‐HF pilot study in eight general practices (51 GPs) in Flanders, Belgium. This prospective trial ran for 6 months. Interventions included an extended audit, an N‐terminal pro‐B‐type natriuretic peptide point‐of‐care test, and assistance of a specialist HF nurse. The extended audit searched on risk factors for HF, HF symptoms, signs, and medication in the GPs' EHR to generate a list of possible HF patients. GPs determined which patients had HF. Those HF patients constituted the OSCAR‐HF study population. Each patient file was manually revised to extract biomarker measurements, echocardiography data, and quality indicators. An independent panel of experts assessed the validity of GPs' HF diagnoses. Feedback about the validity of the HF diagnosis was given to the GP. Out of 18 011 patients ≥ 40 years, we identified 310 patients with a registered HF diagnosis before the study start (HF prevalence: 1.7%). The extended audit led to a 74% increase in identified HF patients (n = 538, HF prevalence: 3.0%) with a mean age of 79 ± 11 years. The prevalence of HF with reduced ejection fraction (HFrEF) was 20% (n = 110). A high proportion of patients underwent echocardiography in the past 5 years (86%, n = 462). Natriuretic peptides were rarely available in patients' files (19%, n = 100). Medical specialists should improve communication about the HF diagnosis because a specialist diagnosis was present in only 225 patients (42%) while 67% (n = 359) of the HF diagnoses were judged objectified by a panel of experts. Assigning a diagnosis of HF was particularly difficult in HF patients with preserved EF (HFpEF). HFrEF treatment rates with renin–angiotensin–aldosterone system blockers (84%, n = 92) and beta‐blockers (86%, n = 94) were very good; however, target doses were hardly reached (34% and 14%, respectively).

Conclusions

This study highlighted the need to improve case finding for HF in general practice and showed that an extended audit in the GPs' EHR was a successful strategy to do so. To improve the quality of HF care in general practice, specific strategies are needed to diagnose HFpEF and to reach target doses of disease‐modifying drugs in HFrEF patients.
Partial De‐Stoning of Olive Paste to Increase Olive Oil Quality, Yield, and Sustainability of the Olive Oil Extraction Process
Authors: Tamborrino Antonia , Servili Maurizio , Leone Alessandro , Romaniello Roberto , Perone Claudio , Veneziani Gianluca
Published: September 2020

Stone recovery in the olive oil extraction process can be an opportunity to increase both incomes and environmental sustainability. To this aim a new partial de‐stoning machine (called Moliden) is installed at the first stage of an olive oil extraction plant to investigate its influence on the quality and sustainability of the extraction process. Quantitative and qualitative results are compared with those achieved using a conventional extraction process. Despite the 60% of stone recovered, no significant differences are registered for oil yield and extractability. A high‐quality biomass is recovered by the partial de‐stoner machine, belonging to A1 class quality when compared to the standard of the wood pellet, with the only exception of the moisture content. The partial de‐stoning also improves the extra virgin olive oil (EVOO) quality in terms of hydrophilic phenols resulting in an enhancement of bitter and pungent sensory notes and most of all provides a beneficial effect for human health.

Practical Applications: The new concept of partial de‐stoner machine proposed in this work allows reducing the equipment employed in the extraction process of olive oil, since it consists of two sections: crushing and de‐stoning. When compared with a standard unit, which recover pits from pomace, it provides a higher quality stone to be used as a biomass fuel. This leads to economic benefits for the millers and has a significant impact on the environmental sustainability of the process.
A detailed process design for conventional friction stir welding of aluminum alloys and an overview of related knowledge
Authors: El‐Moayed Mohamed H. , Shash Ahmed Y. , Rabou Mahmoud Abd , El‐Sherbiny Mahmoud G.
Published: September 2020

Friction stir welding (FSW) has matured considerably since its introduction in 1991. Over the last decades, it has indeed branched and been applied in different fields, such as automotive, aerospace, railway, and shipbuilding. This article aims to survey the basic knowledge related to the conventional FSW of aluminum alloys in order to provide a tool for understanding the friction stir processes. The review covers the five basic process parameters: rotational speed, welding speed, tool geometry, tilt angle, and plunge depth. Furthermore, it presents the related equations and recommended ranges of those parameters to facilitate the process design step for industrial implementation. A sample of 30 published articles was drawn for that purpose. The current article also discusses the main five properties most researchers are interested in, namely, microstructure, microhardness, tensile strength, residual stresses, and distortion.
Caregiver accommodation in adolescents with avoidant/restrictive food intake disorder and anorexia nervosa: Relationships with distress, eating disorder psychopathology, and symptom change
Authors: Wagner Allison F. , Zickgraf Hana F. , Lane‐Loney Susan
Published: September 2020

Objective

The role of family and caregiver accommodation is a well‐defined maintenance factor for anxiety disorders and OCD. Family accommodation for patients with eating disorders is beginning to be described and characterized, but gaps in the literature remain. The current project compares levels of accommodation in families of those with anorexia nervosa (AN) to those with avoidant/restrictive food intake disorder (ARFID). It additionally establishes whether accommodation changes over the course of treatment and the extent to which these changes are related to changes in eating disorder pathology.

Methods

A total of 39 adolescents with ARFID and 59 with AN presenting to a partial hospitalization program were included, with measures completed at intake and discharge.

Results

Caregivers of adolescents with AN and those with ARFID reported similar levels of accommodation, with the exception of the Reassurance Seeking subscale of the Accommodation and Enabling Scale for Eating Disorders (AESED). Additionally, accommodation decreased significantly from intake to discharge for both patient groups. Intake AESED scores were also significantly related to caregiver distress, and changes in AESED scores were related to decreases in relevant eating disorder psychopathology for both groups.

Conclusions

The results of the current study highlight the importance of considering family accommodation for ARFID patients and point to the need for future research to capture changes in accommodation over the course of treatment in relation to the delivery of evidence‐based interventions and subsequent changes in ED symptoms.
Set‐based genetic association and interaction tests for survival outcomes based on weighted V statistics
Authors: Li Chenxi , Wu Di , Lu Qing
Published: September 2020

With advancements in high‐throughout technologies, studies have been conducted to investigate the role of massive genetic variants in human diseases. While set‐based tests have been developed for binary and continuous disease outcomes, there are few computationally efficient set‐based tests available for time‐to‐event outcomes. To facilitate the genetic association and interaction analyses of time‐to‐event outcomes, We develop a suite of multivariant tests based on weighted V statistics with or without considering potential genetic heterogeneity. In addition to the computation efficiency and nice asymptotic properties, all the new tests can deal with left truncation and competing risks in the survival data, and adjust for covariates. Simulation studies show that the new tests run faster, are more accurate in small samples, and account for confounding effect better than the existing multivariant survival tests. When the genetic effect is heterogeneous across individuals/subpopulations, the association test considering genetic heterogeneity is more powerful than the existing tests that do not account for genetic heterogeneity. Using the new methods, we perform a genome‐wide association analysis of the genotype and age‐to‐Alzheimer's data from the Rush Memory and Aging Project and the Religious Orders Study. The analysis identifies two genes, APOE and APOC1, associated with age to Alzheimer's disease onset.