bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalytic Aerobic Dehydrogenatin of N‐Heterocycles by N‐Hydoxyphthalimide
Authors: Chen Weidong , Tang Hao , Wang Weilin , Fu Qiang , Luo Junfei
Published: July 2020

Catalytic methods for the aerobic dehydrogenation of N‐heterocycles are reported. In most cases, indoles are accessed efficiently from indolines using catalytic N‐hydroxyphthalimide (NHPI) as the sole additive under air. Further studies revealed an improved catalytic system of NHPI and copper for the preparation of other heteroaromatics, for example quinolines.

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Coupling NiCo Alloy and CeO2 to Enhance Electrocatalytic Hydrogen Evolution in Alkaline Solution
Authors: Sun Hongming , Tian Caiying , Li Yilin , Wu Jing , Wang Quanle , Yan Zhenhua , Li Cheng‐Peng , Cheng Fangyi , Du Miao
Published: July 2020

Robust and durable non‐precious metal electrocatalysts for the hydrogen evolution reaction (HER) are crucial to realize sustainable hydrogen production by electrocatalytic water splitting. In this work, a superhydrophilic NiCo nanoparticle array coupled with CeO2 is integrated on graphite plate (NiCo–CeO2/GP) by electrodeposition and subsequent high‐temperature selective reduction. The coupled CeO2 can accelerate dissociation of H2O and favor adsorption of hydrogen, prominently boosting the electrocatalytic HER activity of NiCo alloy. Also, the superhydrophilic self‐supported electrode can promote electron conduction, facilitate bubble release, and prevent catalyst shedding, ensuring an efficient and stable working condition. As a result, NiCo–CeO2/GP exhibits an outstanding HER catalytic activity with low overpotentials of 34 mV at 10 mA cm−2 and 140 mV at 500 mA cm−2, as well as remarkable durability in alkaline media. Notably, this catalyst activation strategy by CeO2 is also applicable to other Ni‐based alloys such as NiFe and NiCu, demonstrating its versatility. An alkaline electrolyzer with NiCo–CeO2/GP as cathode and the NiCo(OH)x–CeO2/GP precursor electrode as anode delivers a current density of 10 mA cm−2 at an ultralow potential (1.45 V@10 mA cm−2), surpassing that of the traditional Pt/C||RuO2 electrolyzer (1.54 V@10 mA cm−2).
Experiences of Participants During In Situ Simulation With a Learner Present
Authors: Balakumaran Janatani , Forestell Benjamin , Dowhos Krista , Nagji Alim
Published: July 2020

Background

While in situ simulation (ISS) provides robust value for health care teams, it is less clear how medical learners affect the experiences of other participants.

Methods

This was a single‐center qualitative analysis of a community hospital’s emergency department ISS program that included medical learners (medical students, family and emergency medicine residents). Focus groups were conducted before and after with nurses, staff physicians, and resident physicians. Phenomenologic analysis using a constructivist framework was used to examine themes.

Results

Fifty‐two ISSs were held from February 2019 to March 2020. Of those simulations, 36 had learners present. Positive effects included creating an open learning environment and offering staff physicians a safe teaching space. Negative effects arose when objectives of ISS were highly team based or latent safety threat (LST) focused. All groups thought learners added value to ISS.

Conclusion

Thought should be given to ISS objectives when considering how learners affect other participants. When including learners, review objectives, clarify expectations in prebriefing, and ensure that debriefing begins with LSTs and process objectives before diving into medical objectives. This study provides insight into the effect of medical learners on ISS.
Introduction to Health Systems Science: Experiential Learning Through Patient Interviews in the Emergency Department
Authors: Sawyer Nicolas T. , Danielson Aaron , Johl Karnjit , Williams Donna M.
Published: July 2020

Increased complexity in health care delivery is now a problem of national proportions. Traditional medical education fails to sufficiently prepare students for the realities of practicing medicine in the 21st century. To address this critical problem, health systems science (HSS), which focuses on the broader system of care, has emerged as the “third pillar” of undergraduate medical education complementing the basic and clinical sciences. The authors identified a need to increase the amount and quality of HSS education in a way that would engage students and provide a platform to learn how patients interact with the health care system. UNITED (Understanding Needs in the Emergency Department) was thus designed and implemented to introduce preclinical medical students to HSS through patient interactions in the emergency department (ED). EDs serve as America's health care “safety net” and there is no lack of opportunity to learn how the current system of care does and does not work for patients. Qualitative analysis of students’ written reflections revealed the following themes of the UNITED experience: 1) medical students question their understanding of the health care system after listening to patients' stories, 2) focused patient interviews about the health care system provides a unique perspective of the patient experience not found elsewhere in the preclinical curriculum, and 3) discussing the realities of being a patient in the U.S. health care system is an emotional experience for students. Based on these data, the authors concluded that asking preclinical students to interview patients about their experience in the health care system leads to emotional activation and a subsequent stated desire to improve care delivery.
Soft rock increases the colloid content and crop yield in sandy soil
Authors: Guo Zhen , Zhang Haiou , Wang Huanyuan
Published: July 2020

Desertification is reducing the amount of land available to produce food in semi arid and arid regions worldwide. Management techniques to reduce this problem are needed. This paper investigated if the addition of soft rocks to sandy soils would improve soil resilience and productivity. The model system selected for this study was located in Mu Us, China. Soft rocks are defined as a loose rock layer. Collected soft rock and sand from the same study area were compounded in the volume ratios of 0:1 (CK), 1:5 (C1), 1:2 (C2), and 1:1 (C3). The results revealed that the average content of soil organic carbon (SOC) with increasing soil depth and was 3.11 g kg−1 in the 20 to 30 cm soil depth. The highest average content of particulate organic carbon (POC) was observed in the 10‐20 cm soil layer (2.72 g kg−1). In the 10 to 20 cm soil depth, the polysaccharide content was the highest (125.3 and 119.08 μg g−1) in the C1 and C2 treatments. However, in all soil layers the C2 treatment had the highest (0.11 g kg−1) content of calcium carbonate. Compared with the CK treatment, the addition of soft rock increased of corn yield, the C2 treatment had the largest increase (65.46%). The corn yield showed a significantly positive correlation with polysaccharides at 10–20 cm. The overall results showed that soft rock o sand ratio of 1:2 could increase the crops yield, which was of great significance to the sustainable development of agriculture in the sand area.
Habitat determinants of golden‐headed lion tamarin (Leontopithecus chrysomelas) occupancy of cacao agroforests: Gloomy conservation prospects for management intensification
Authors: de Almeida‐Rocha Juliana M. , Peres Carlos A. , Monsalvo Julio A. B. , Oliveira Leonardo De C.
Published: July 2020

Organismal distributions in human‐modified landscapes largely depend on the capacity of any given species to adapt to changes in habitat structure and quality. The golden‐headed lion tamarin (GHLT; Leontopithecus chrysomelas) is an Endangered primate from the Brazilian Atlantic Forest whose remaining populations occupy heterogeneous landscapes consisting primarily of shade cacao (Theobroma cacao) agroforestry, locally known as cabrucas. This cash crop can coexist with high densities of native tree species and holds a significant proportion of the native fauna, but its widely extolled wildlife‐friendly status is increasingly threatened by management intensification. Although this potentially threatens to reduce the distribution of GHLTs, the main determinants of tamarin's occupancy of cabrucas remain unknown, thereby limiting our ability to design and implement appropriate conservation practices. We surveyed 16 cabruca patches in southern Bahia, Brazil, and used occupancy modeling to identify the best predictors of GHLT patch occupancy. Key explanatory variables included vegetation structure, critical resources, landscape context, human disturbance, and predation pressure. We found a negative relationship between GHLT occupancy and the prevalence of jackfruit trees (Artocarpus heterophylus), which is likely associated with the low representation of other key food species for GHLTs. Conversely, cabrucas retaining large‐diameter canopy trees have a higher probability of GHLT occupancy, likely because these trees provide preferred sleeping sites. Thus, key large tree resources (food and shelter) are currently the main drivers of GHLT occupancy within cabruca agroecosystems. Since both factors can be directly affected by crop management practices, intensification of cabrucas may induce significant habitat impacts on GHLT populations over much of their remaining range‐wide distribution.
A new phenothiazine‐based fluorescence sensor for imaging Hg2+ in living cells
Authors: Sun Yucheng , Wang Lizhen , Zhou Jianhua , Qin Dawei , Duan Hongdong
Published: July 2020

A new phenothiazine‐based sensor PHE‐Ad for monitoring Hg2+ has been designed and synthesized based on the intramolecular charge transfer (ICT) mechanism. The probes were characterized by FTIR, 1H NMR, and HRMS, and their optical properties were detected by UV and FL. It's showed the probes detection of Hg2+ compared to other metal ions (Mg2+, Cu2+, Hg2+, Ag+, Co2+, Cr3+, Al3+, Ni2+, Zn2+, Ca2+, Fe3+, Fe2+, K+, Na+, and Cd2+) based on the test results. Besides, the detection limits were determined to be 2.12 × 10−8 M through the standard curve plot. In addition, sensor PHE‐Ad shows high selectivity and sensitivity for Hg2+ with a fast response in a suitable pH range. Furthermore, taking into account its good “turn‐on” fluorescent sensing behavior and low cell cytotoxicity, PHE‐Ad was successfully applied to detect and image Hg2+ in real water samples and living cells, which shows great potentials for application in environmental and biological systems.
Design and green synthesis of 1‐(4‐ferrocenylbutyl)piperazine chemically grafted reduced graphene oxide for supercapacitor application
Authors: Hadi Raha , Rahimpour Keshvar , Payami Elmira , Teimuri‐Mofrad Reza
Published: July 2020

In this paper, we report the green synthesis of 1‐(4‐ferrocenylbutyl)piperazine chemically grafted rGO (P.Fc/rGO) as a battery‐type supercapacitor electrode material. For this purpose, initially, the ability of the aqueousDamsonfruit extract is investigated in the reduction reaction of graphene oxide (GO). 1‐(4‐ferrocenylbutyl)piperazine (P.Fc) is synthesizedvianucleophilic substitution reaction of piperazine with as‐synthesized 4‐chlorobutylferrocene. In continue, P. Fc is incorporated to GO by ring‐opening reaction of epoxide groups on the GO surface. In the next step, the modified reduction method by aqueousDamsonfruit extract was used to prepare the P.Fc/rGO from P.Fc/GO. The prepared materials were characterized by various techniques including FT‐IR, Uv–vis, XRD, SEM, EDX, and BET. N2adsorption–desorption data of P.Fc/rGO nanocomposite shows that the surface area is 37.746 m2g−1. The capability of P.Fc/rGO nanocomposite for using as an energy storage electrode material in battery‐type supercapacitor was examined by investigation of its electrochemical behavior by CV, EIS, and GCD measurements. The charge storage capacity of 1,102 mAh g−1is achieved at 2.5 A g−1. This nanocomposite shows 89% retention of charge storage capacity after 2000 CV cycles.
A synthesized semi‐aromatic copolyamaide through synergy of three different kinds of monomers: Toward high transparency, excellent heat resistance and melt flowing property
Authors: Guo Jiabao , Li Haijie , Xue Bingfeng , Zhu Donghui , Zhang Xiaomeng , Zhao Haitao , Qiao Xiaoguang , Cui Zhe , Fu Peng , Zhao Qingxiang , Pang Xinchang , Liu Minying
Published: July 2020

To fabricate the low‐cost transparent polyamide with high heat resistance and good melt flowing property simultaneously is a huge challenge in many high‐end fields due to the contradiction between these two properties. In order to balance this contradiction, in this paper, by using isophthalic acid (IPA, aromatic monomer), 4,4′‐methylenebis(cyclohexylamine) (PACM, alicyclic monomer) as rigid stereoscopic monomers, 1,6‐hexanediamine (HMD, aliphatic monomer) as the flexible monomer, a series of transparent poly(hexamethylene isophthalamide/poly(m‐benzoyl4,4′‐methylenebis(cyclohexylamine)) (PA6I/PACMI) with rigid and stereoscopic structure (corresponding to the large distance between adjacent molecular chains) were successfully synthesized. The results indicated that the newly synthesized PA6I/PACMI copolymer has an intrinsically amorphous structure and high optical transparency, which could reach as high as 90%. Furthermore, the highest glass transition temperature (Tg) of the copolymer is over 153.9°C, at the same time, the copolymer also possesses excellent melt flowing property, which can be melt processed easily. Therefore, the newly synthesized copolymer has great advantages in many fields, and it can also shed light on the design and fabrication of high‐performance materials.
American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 1
Authors: Henderson Lauren A. , Canna Scott W. , Friedman Kevin G. , Gorelik Mark , Lapidus Sivia K. , Bassiri Hamid , Behrens Edward M. , Ferris Anne , Kernan Kate F. , Schulert Grant S. , Seo Philip , F. Son Mary Beth , Tremoulet Adriana H. , Yeung Rae S. M. , Mudano Amy S. , Turner Amy S. , Karp David R. , Mehta Jay J.
Published: July 2020

Objective

To provide guidance on the management of multisystem inflammatory syndrome in children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) infection, and to provide recommendations for children with hyperinflammation during coronavirus disease 2019 (COVID‐19), the acute, infectious phase of SARS–CoV‐2 infection.

Methods

A multidisciplinary task force was convened by the American College of Rheumatology (ACR) to provide guidance on the management of MIS‐C associated with SARS–CoV‐2 and hyperinflammation in COVID‐19. The task force was composed of 9 pediatric rheumatologists, 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS‐C and hyperinflammation in COVID‐19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved 2 rounds of anonymous voting and 2 webinars. A 9‐point scale was used to determine the appropriateness of each statement (median scores of 1–3 for inappropriate, 4–6 for uncertain, and 7–9 for appropriate), and consensus was rated as low, moderate, or high based on dispersion of the votes along the numeric scale. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, as prespecified prior to voting.

Results

The ACR task force approved a total of 128 guidance statements addressing the management of MIS‐C and hyperinflammation in pediatric COVID‐19. These statements were refined into 40 final clinical guidance statements, accompanied by a flow diagram depicting the diagnostic pathway for MIS‐C.

Conclusion

Our understanding of SARS–CoV‐2–related syndromes in the pediatric population continues to evolve. The guidance provided in this “living document” reflects currently available evidence, coupled with expert opinion, and will be revised as further evidence becomes available.
Nonlinear disturbance observer based adaptive super twisting sliding mode load frequency control for nonlinear interconnected power network
Authors: Dev Ark , Anand Sumant , Sarkar Mrinal Kanti
Published: July 2020

This article revisits the study of load frequency control (LFC) problem in an interconnected nonlinear power network under mismatched disturbance. Unlike previous works, a more realistic interconnected power network with nonlinear coupling between control areas and also including nonlinearities like generation rate constraint (GRC) and governor dead band (GDB) is under study. An adaptive super twisting sliding mode controller (ST‐SMC) is designed based on system states and estimated disturbance. The nonlinear disturbance observer (NDO) estimates the mismatch between the electrical and mechanical power and then the estimated value is employed in the controller design to compensate the disturbance. The proposed control scheme ensures faster frequency and tie‐line power stabilization compared with techniques existing in the literature. The robustness of the proposed design is validated under random varying step load disturbance and with two area four machine Kundur's test system. The closed loop system stability is theoretically proved using the Lyapunov function. Simulation results confirm the effectiveness of the proposed design in a two‐area interconnected power network.
Design and in vitro antibiofilm activity of propolis diffusion‐controlled biopolymers
Authors: Ceylan Ozgur , Karakus Hatice , Cicek Huseyin
Published: July 2020

In this study, a novel pH‐sensitive hydrogel beads that is based on gelatin/sodium alginate/chitosan (GEL/SA/CS) loaded with propolis ethanolic extracts (PE) were synthesized. The swelling behavior of GEL/SA/CS hydrogel beads was studied in different pH solutions and compared with unloaded CS (GEL/SA) hydrogel beads. The in vitro release studies have been revealed using four different pH (1.3, 5.0, 6.0, and 6.8), a saliva environment (pH 6.8), a simulated gastric fluid (SGF) (pH 1.3), and a simulated intestinal fluid (SIF) (pH 6.8) to simulate the physiological conditions in gastrointestinal (GI) tract. Propolis‐loaded hydrogel beads were found to be stable at pH 1.3, 5.0, 6.0, simulated saliva, SGF, and SIF mediums, whereas the beads lose their stability at pH 6.8 buffer solution. Tested microorganisms displayed greater sensitivity to PE‐loaded hydrogel beads compared with pure propolis. Contrary to antimicrobial activity results, antibiofilm activity results of PE‐loaded GEL/SA and GEL/SA/CS hydrogel beads were found at low levels. According to the obtained results, the propolis‐loaded GEL/SA/CS hydrogel beads synthesized within this study can be used in the treatment of GI tract diseases such as oral mucositis, gastric ulcer, ulcerative colitis, and GI cancer, as controlled releasing carriers of propolis.
Surgical training rotation design: effects of hospital type, rotation theme and duration
Authors: Robinson D B T , Hopkins L , James O P , Brown C , Powell A G M T , Hemington-Gorse S , Abdelrahman T , Lewis W G , Egan R J
Published: July 2020

Background

Entrants into UK surgical specialty training undertake a 2-year programme of core surgical training, rotating through specialties for varying lengths of time, at different hospitals, to gain breadth of experience. This study aimed to assess whether these variables influenced core surgical trainee (CST) work productivity.

Methods

Intercollegiate Surgical Curriculum Programme portfolios of consecutive CSTs between 2016 and 2019 were examined. Primary outcome measures were workplace-based assessment (WBA) completion, operative experience and academic outputs (presentations to learned societies, publications and audits).

Results

A total of 344 rotations by 111 CSTs were included. Incremental increases in attainment were observed related to the duration of core surgical training rotation. The median number of consultant-validated WBAs completed during core surgical training were 48 (range 0–189), 54 (10–120) and 75 (6–94) during rotations consisting of 4-, 6- and 12-month posts respectively (P < 0·001). Corresponding median operative caseloads (as primary surgeon) were 84 (range 3–357), 110 (44–394) and 134 (56–366) (P < 0·001) and presentations to learned societies 0 (0–12), 0 (0–14) and 1 (0–5) (P = 0·012) respectively. Hospital type and specialty training theme were unrelated to workplace productivity. Multivariable analysis identified length of hospital rotation as the only factor independently associated with total WBA count (P = 0·001), completion of audit (P = 0·015) and delivery of presentation (P = 0·001) targets.

Conclusion

Longer rotations with a single educational supervisor, in one training centre, are associated with better workplace productivity. Consideration should be given to this when reconfiguring training programmes within the arena of workforce planning.
Determination of cannabinoids in plasma using salting‐out‐assisted liquid–liquid extraction followed by LC–MS/MS analysis
Authors: da Silva Cristiane Pires , Dalpiaz Luiz Paulo Pugen , Gerbase Fernando Engel , Muller Victoria Vendramini , Cezimbra da Silva Anne , Lizot Lilian Feltraco , Hahn Roberta Zilles , da Costa José Luiz , Antunes Marina Venzon , Linden Rafael
Published: July 2020

The detection of the markers of Cannabis consumption in biological specimens is an important task for drug testing laboratories in varous contexts. A simple assay combining salting‐out assisted liquid–liquid extraction sample preparation and LC–MS/MS analysis was applied to the measurement of Δ9‐tetrahydrocannabinol, 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THC‐COOH), 11‐hydroxy‐Δ9‐tetrahydrocannabinol, cannabinol and cannabidiol concentrations in 100 μl plasma specimens. The assay had linearity of 1–100 ng ml−1 for THC‐COOH and 0.5–50 ng ml−1 for the other tested cannabinoids. Assay validation criteria were fulfilled. Extraction yields (88.7–97.3%) and internal‐standard correct matrix effects (−9.6 to +5.4%) were acceptable. The assay was applied to 238 clinical specimens from trauma patients, with 19 samples presenting quantifiable concentrations of at least one of the target compounds. The developed assay is a simple and efficient strategy for simultaneous measurement of Δ9‐tetrahydrocannabinol, THC‐COOH, 11‐hydroxy‐Δ9‐tetrahydrocannabinol, cannabinol and cannabidiol concentrations in plasma specimens.
Micellar liquid chromatographic green enantioseparation of racemic amino alcohols and determination of elution order
Authors: Alwera Vijay , Sehlangia Suman , Alwera Shiv
Published: July 2020

A micellar liquid chromatographic method was developed for the green enantioseparation of racemic amino alcohols using an aqueous solution of the mixed surfactants as an alternative for organic solvents. In this study, the derivatives of the amino alcohols were synthesized using highly reactive chiral esters of (S)‐levofloxacin (Lfx) under microwave conditions, and an aqueous solution of the surfactants (Brij‐35 and SDS) was used for the enantioseparation of the synthesized diastereomeric derivatives (DDs) of amino alcohols using reversed‐phase HPLC. The activated ester of Lfx was synthesized by reacting with N‐hydroxybenzotriazole and characterized using UV, IR, 1H NMR, high‐resolution mass spectrometry, and elemental analysis. The DDs of racemic amino alcohols were separated on a C18 column using micellar LC. Chromatographic conditions were optimized by varying the concentration of the surfactants in aqueous solution and by varying the concentration and pH of the buffer. The green assessment score was calculated for the developed method (score: 82, an excellent green method). In addition, the density functional theory calculations were performed to develop the lowest energy‐optimized structures of DDs. The method was validated according to the International Conference of Harmonization guidelines, and the retention factor (k), selectivity factor (α), resolution factor (RS), limit of detection (0.198 ng mL−1 or 0.291 pM mL−1), and limit of quantification (0.594 ng mL−1 or 0.873 pM mL−1) were calculated.
Extracellular matrix proteins are time‐dependent and regional‐specific markers in experimental diffuse brain injury
Authors: Griffiths Daniel R. , Jenkins Taylor M. , Addington Caroline P. , Stabenfeldt Sarah E. , Lifshitz Jonathan
Published: July 2020

Introduction

The extracellular matrix (ECM) provides structural support for neuronal, glial, and vascular components of the brain, and regulates intercellular signaling required for cellular morphogenesis, differentiation and homeostasis. We hypothesize that the pathophysiology of diffuse brain injury impacts the ECM in a multi‐dimensional way across brain regions and over time, which could facilitate damage and repair processes.

Methods

Experimental diffuse TBI was induced in male Sprague‐Dawley rats (325–375 g) by midline fluid percussion injury (FPI); uninjured sham rats serve as controls. Tissue from the cortex, thalamus, and hippocampus was collected at 15 min, 1, 2, 6, and 18 hr postinjury as well as 1, 3, 7, and 14 days postinjury. All samples were quantified by Western blot for glycoproteins: fibronectin, laminin, reelin, and tenascin‐C. Band intensities were normalized to sham and relative to β‐actin.

Results

In the cortex, fibronectin decreased significantly at 15 min, 1 hr, and 2 hr postinjury, while tenascin‐C decreased significantly at 7 and 14 days postinjury. In the thalamus, reelin decreased significantly at 2 hr, 3 and 14 days postinjury. In the hippocampus, tenascin‐C increased significantly at 15 min and 7 days postinjury.

Conclusion

Acute changes in the levels of these glycoproteins suggest involvement in circuit dismantling, whereas postacute levels may indicate a restorative or regenerative response associated with recovery from TBI.
Bombyx mori kynurenine 3‐monooxygenase gene editing and insect molecular breeding using the clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 system
Authors: Hong Jeong Won , Jeong Chan Young , Yu Jeong Hee , Kim Su‐Bae , Kang Sang Kuk , Kim Seong‐Wan , Kim Nam‐Suk , Kim Kee Young , Park Jong Woo
Published: July 2020

Genome editing by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated protein (Cas)9, a third‐generation gene scissors, and molecular breeding at the genome level are attracting considerable attention as future breeding techniques. In the present study, genetic and phenotypic analyses were conducted to examine the molecular breeding of Bombyx mori through CRISPR/Cas9‐mediated editing of the kynurenine 3‐monooxygenase (KMO) gene. The synthesized guide RNAs (gRNAs) were analyzed using T7 endonuclease I after introduction into the BM‐N silkworm cell line. To edit the silkworm gene, K1P gRNA, and Cas9 complexes were microinjected into silkworm embryos. After microinjection, the hatching rate and the incidence of mutation were determined as 18.1% and 60%, respectively. Gene mutation was verified in the heterozygous G0 generation, but no phenotypic change was observed; however, certain embryos and moths produced through sib‐mating had significant differences compared to the wild‐type. In successive generations, a distinct phenotypic change was also observed by continuous mating. Thus, although there are limitations in the phenotypic expression in breeding through the induction of deletion mutations, as in the present study, the process is believed to yield successful results within a shorter period compared to traditional breeding and is safer than transgenic technology.
Regimen‐intensity per count‐recovery and hospitalization index: A new tool to assign regimen intensity for AML
Authors: Sorror Mohamed L. , Agarwal Shirali , Othus Megan , Lynch Ylinne , Nyland Jennifer E. , Percival Mary‐Elizabeth , Becker Pamela S. , Appelbaum Frederick R. , Estey Elihu H.
Published: July 2020

Background

Low‐intensity regimens have been increasingly used to treat older patients with acute myeloid leukemia (AML). Recent studies, however, suggest older patients can tolerate and potentially benefit from intensive chemotherapeutic regimens. The ability to compare the utility of varying regimen intensities in AML is hindered by the lack of a standardized definition of “regimen intensity.”

Methods

We conducted a survey asking AML physicians which of 38 regimens they would consider intensive vs less‐intensive. Electronic medical records of 592 patients receiving many of these regimens were used to design a model characterizing regimens as intensive vs less‐intensive as identified by ≥75% physician consensus. Variables included frequency and length of hospitalizations, intensive care unit admissions, severe gastrointestinal toxicities, time to nadir, and recovery of neutrophil/platelet count.

Results

Physicians agreed at a rate of 75%‐100% on the assignment of degree of intensity to the majority (n = 28) of these regimens, while the level of agreement was <75% for the remaining 10 regimens (26%). Logistic regression analyses identified number and length of hospitalizations to be significantly associated with intensive regimens and count recovery with less‐intensive regimens. We created the “regimen‐intensity per count‐recovery and hospitalization” (RICH) index with an AUC of 0.87. Independent model validation yielded an AUC of 0.75.

Conclusions

We were able to generate a novel model that defines regimen intensity for many therapies used to treat AML. Results facilitate a future randomized study comparing intensive vs less‐intensive regimens.
Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge
Authors: Scheurlen Katharina M. , Billeter Adrian T. , O'Brien Stephen J. , Galandiuk Susan
Published: July 2020

Background

The incidence of colorectal cancer (CRC) among patients <50 years of age has increased dramatically over the last decades. At the same time, the growing proportion of obese children and adolescents and the increasing proportion of young and obese patients with CRC suggests an association between metabolic dysfunction and carcinogenesis. Tumor‐associated macrophages (TAMs) are able to orchestrate tumor promoting and suppressing mechanisms in CRC. The aim of this review was to discuss the different roles of TAMs in CRC and their phenotype‐specific metabolic pathways to identify potential new targets for CRC treatment.

Methods

A literature search was performed using PubMed, Cochrane and Embase to identify studies on TAMs and their metabolism in CRC. The following search terms were used in various combinations: (obesity OR adiposity OR obese) AND (macrophage OR polarization OR macrophage metabolism) AND ((colon cancer*) OR (colon carcinoma) OR (colonic tumor*) OR (colonic neoplasm[MeSH]) OR (rectal cancer*) OR (rectal carcinoma) OR (rectal tumor*) OR (rectal neoplasm[MeSH]) OR (colorectal cancer*) OR (colorectal carcinoma) OR (colorectal tumor*) OR (colorectal neoplasm[MeSH])). Studies including data on the phenotype and metabolism of TAMs in CRC were analyzed.

Results

Evidence for the prognostic utility of macrophage markers in CRC is currently evolving, with a particular role of stage‐dependent cellular metabolism profiles of TAMs. Itaconate is one of the metabolites produced by proinflammatory subtypes of TAMs and it is known to have tumor promoting effects. Metabolic pathways that are involved in macrophage activation and reprogramming play a role in a chronic inflammatory setting, consequently affecting the onset and development of CRC.

Conclusions

Tumor‐promoting metabolites, such as itaconate, are directly regulating these mechanisms, thereby triggering carcinogenesis. Metabolic reprogramming in TAMs can build a bridge between metabolic dysfunction and the onset and progression of CRC through inflammatory pathways, particularly in younger patients with early‐onset CRC.
Towards Efficient Nonenzymatic DNA Ligation: Comparing Key Parameters for Maximizing Ligation Rates and Yields with Carbodiimide Activation**
Authors: Obianyor Chiamaka , Newnam Gary , Clifton Bryce E. , Grover Martha A. , Hud Nicholas V.
Published: July 2020

Chemical ligation is an important tool for the generation of synthetic DNA structures, which are used for a wide range of applications. Surprisingly, reported chemical ligation yields can range from 30 to 95 % for the same chemical activating agent and comparable DNA structures. We report a systematic study of DNA ligation by using a well‐defined bimolecular test system and a water‐soluble carbodiimide (EDC) as a phosphate‐activating agent. Our results emphasize the interplay between template‐substrate complex stability and the rates of the chemical steps of ligation, with 3′ phosphate substrates providing yields near 100 % after 24 hours for particularly favorable reaction conditions. Ligation rates are also shown to be sensitive to the identity of the base pairs flanking a nick site, with as much as threefold variation. Finally, the observation that DNA substrates are modified by EDC at rates that can be comparable with ligation rates emphasizes the importance of considering side reactions when designing protocols to maximize ligation yields.
DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells
Authors: Nie Xuekun , Chen Huajiao , Niu Peiguang , Zhu Yanting , Zhou Jintuo , Jiang Li , Li Danyun , Lin Minhua , Chen Zichun , Shi Daohua
Published: July 2020

Autophagy is closely related to the formation and development of multiple human tumors including ovarian cancer. As a major regulator of this process, the role of mTOR (mammalian target of rapamycin) has been well proven. Cardamonin, a kind of flavonoid from plants, has effects on induction of autophagy and thus antiproliferation of cancer cells. However, the detailed mechanism remains unclear. DAP1 (death‐associated protein 1) is a proline‐rich protein, which is involved in the regulation of cellular growth and programmed cell death including autophagy and apoptosis. The aim of this study was to investigate whether DAP1 is involved in proliferation inhibition and autophagy induced by cardamonin in tumor cells. Using online bioinformatics tools, we found that DAP1 expression is closely related to the survival of patients with ovarian cancer. Our study showed that autophagy induced by cardamonin was associated with mTOR inhibition, and DAP1 was involved in this process. Silence of DAP1 decreased cell proliferation but enhanced the antiproliferative effect of cardamonin in SKOV3 cells. The level of autophagy was elevated by DAP1 silencing in SKOV3 cells. Notably, cardamonin showed higher autophagy flux in the DAP1 small interfering RNA group. Taken together, our results implied that DAP1 negatively regulates autophagy induced by cardamonin, and it may be a potential target for ovarian cancer therapy.
Full Thermal Switching of Enzymes by Thermoresponsive Poly(2‐oxazoline)‐Based Enzyme Inhibitors
Authors: Hijazi Montasser , Türkmen Esra , Tiller Joerg C.
Published: July 2020

Controlling the activity of enzymes is an important feature for many processes in medicine, bioanalytics, and biotechnology. So far, it has not been possible to fully switch biocatalysts on and off by thermoresponsive enzyme inhibitors. Herein, we present poly(2‐oxazoline)s with iminodiacetic acid end groups (POx‐IDA) that are lower critical solution temperature (LCST) polymers and thus thermosensitive. They are capable of reversibly inhibiting the activity of horse radish peroxidase and laccase by more than 99 %. Increasing the temperature makes the POx‐IDA precipitate, which leads to 100 % recovery of the enzyme activity. This switching cycle is fully reversible. The LCST of the POx‐IDA can be tuned by varying the polymer composition to generate a wide range of switching windows.
Environmentally Benign, Intrinsically Coordinated, Lithium‐Based Solid Electrolyte with a Modified Purine as Supporting Ligand
Authors: Avasthi Ilesha , Gaganjot  , Katiyar Monica , Verma Sandeep
Published: July 2020

Bioinspired materials have become increasingly competitive for electronic applications in recent years owing to the environment‐friendly alternatives they offer. The notion of biocompatible solid organic electrolytes addresses the issues concerning potential leakage of corrosive liquids, volatility and flammability of electrolyte solvents. This study presents a new intrinsically coordinated LiI adenine complex that exhibits electrical conductivity as a solid electrolyte capable of self‐sustained supply of LiI ions. It exhibits conductivity through moisture‐assisted LiI ion motion up to 373 K, and possibly by an ion‐hopping mechanism beyond 373 K. This purine‐derived solid electrolyte shows enhanced conductivity and transference number demonstrating the potential of purine‐based ligands and their coordination complexes in interesting materials applications.
Hierarchical Synthesis, Structure, and Photophysical Properties of Gallium‐ and Ruthenium‐Porphyrins with Axially Bonded Azo Ligands
Authors: Gao Yueze , Walter Vroni , Ferguson Michael J. , Tykwinski Rik R.
Published: July 2020

The hierarchical synthesis of three porphyrin and four bisporphyrin derivatives is presented. This strategy relies on the incorporation of linkers based on azo moieties appended with pyridyl and/or acetylenic groups that facilitate axial coordination to Ga‐ and Ru‐metalloporphyrins. These porphyrinic systems allow for a quantitative analysis of the effects of diamagnetic anisotropy (DA) by using 1H NMR spectroscopic and X‐ray crystallographic analyses. A simple power‐law relationship between the proton chemical shift and the distance from the porphyrin core is experimentally outlined, which confirms previous theoretical predictions and shows that the limit of DA is about 2 nm. Photophysical properties of the azo‐linked porphyrins are analyzed by UV/Vis spectroscopy, showing that significant cis–trans isomerization is not observed for azo ligands bound only to Ga‐porphyrins. Incorporation of Ru‐porphyrins to an azo ligand facilitates photoswitching behavior, but the process faces competition from decarbonylation of the Ru‐porphyrin, and appreciable switching is only documented for GaL1Ru.
Understanding the Catalytic Sites of Metal–Nitrogen–Carbon Oxygen Reduction Electrocatalysts
Authors: Chen Ming‐Xi , Tong Lei , Liang Hai‐Wei
Published: July 2020

The development of low‐cost catalysts containing earth‐abundant elements as alternatives to Pt‐based catalysts for the oxygen reduction reaction (ORR) is crucial for the large‐scale commercial application of proton exchange membrane fuel cells (PEMFCs). Nonprecious metal–nitrogen–carbon (M‐N‐C) materials represent the most promising candidates to replace Pt‐based catalysts for PEMFCs applications. However, the high‐temperature pyrolysis process for the preparation of M‐N‐C catalysts frequently leads to high structural heterogeneity, that is, the coexistence of various metal‐containing sites and N‐doped carbon structures. Unfortunately, this impedes the identification of the predominant catalytic active structure, and thus, the further development of highly efficient M‐N‐C catalysts for the ORR. This Minireview, after a brief introduction to the development of M‐N‐C ORR catalysts, focuses on the commonly accepted views of predominant catalytic active structures in M‐N‐C catalysts, including atomically dispersed metal–Nx sites, metal nanoparticles encapsulated with nitrogen‐doped carbon structures, synergistic action between metal–Nx sites and encapsulated metal nanoparticles, and metal‐free nitrogen‐doped carbon structures.
Transition‐Metal‐Catalyzed Cycloaddition Reactions to Access Seven‐Membered Rings
Authors: Trost Barry M. , Zuo Zhijun , Schultz Johnathan E.
Published: July 2020

The efficient and selective synthesis of functionalized seven‐membered rings remains an important pursuit within synthetic organic chemistry, as this motif appears in numerous drug‐like molecules and natural products. Use of cycloaddition reactions remains an attractive approach for their construction within the perspective of atom and step economy. Additionally, the ability to combine multiple components in a single reaction has the potential to allow for efficient combinatorial strategies of diversity‐oriented synthesis. The inherent entropic penalty associated with achieving these transformations has impressively been overcome with development of catalysis, whereby the reaction components can be pre‐organized through activation by transition‐metal‐catalysis. The fine‐tuning of metal/ligand combinations as well as reaction conditions allows for achieving chemo‐, regio‐, diastereo‐ and enantioselectivity in these transformations. Herein, we discuss recent advances in transition‐metal‐catalyzed construction of seven‐membered rings via combination of 2–4 components mediated by a variety of metals. An emphasis is placed on the mechanistic aspects of these transformations to both illustrate the state of the science and to highlight the unique application of novel processes of transition‐metals in these transformations.
Functional Rotaxanes in Catalysis
Authors: Kwamen Carel , Niemeyer Jochen
Published: July 2020

Mechanically interlocked molecules (MIMs) have gained attention in the field of catalysis due to their unique molecular properties. Central to MIMs, rotaxanes are highly promising and attractive supramolecular catalysts due to their unique three‐dimensional structures and the flexibility of their subcomponents. This Minireview discusses the use of rotaxanes in organocatalysis and transition‐metal catalysis.
Kiss1R Identification and Biodistribution Analysis Employing a Western Ligand Blot and Ligand‐Derivative Stain with a FITC‐Kisspeptin Derivative
Authors: Hasegawa Koki , Maedomari Rika , Sato Younosuke , Gotoh Kumiko , Kudoh Shinji , Kojima Akihiro , Okada Seiji , Ito Takaaki
Published: July 2020

It is not always easy to establish specific antibodies against receptors. Most receptors are hydrophobic and have complicated three‐dimensional structures, making them difficult to use as immunogens. Thus, we developed receptor detection methods with a fluorescein‐labeled ligand as an antibody alternative, which we referred to as a western ligand blot (WLB) and ligand derivative stain (LDS). Kisspeptin receptor (Kiss1R) was detected by its ligand. Kiss1R expression was confirmed in eight human cell lines by the WLB and in four pathological tissues by the LDS. Next, Kiss1R was stained by LDS in organs, revealing Kiss1R expression by [67Ga]Ga‐DOTA‐kisspeptin 10 accumulation. As a result, Kiss1R‐expressing cells in each organ could be stained with fluorescein‐labeled kisspeptin 14 instead of an antibody and observed by light microscopy. The combination of the WLB and LDS allows identification of receptors in tissues, which can be readily applied to target receptor detection by a synthetic ligand derivative.
Why does the CIELAB a* axis point toward magenta instead of red?
Authors: Seymour John
Published: July 2020

Red is a basic color. The work of Kay and Berlin on the evolution of color names in languages shows that, after white and black, red is the most basic of color terms. Red plays a key part in Hering's color opponent theory, and is one of the elementary colors in both the Munsell Color system and in the Natural Colour System (NCS). The CIELAB color system has an axis which is sometimes referred to as the red‐green axis. But unique red is about 25° degrees counterclockwise from the positive a* axis. This article answers the question of why this is.
Evaluation of Absolute Oral Bioavailability and Bioequivalence of Ribociclib, a Cyclin‐Dependent Kinase 4/6 Inhibitor, in Healthy Subjects
Authors: Ji Yan , Abdelhady Ahmed M. , Samant Tanay S. , Yang Shu , Rodriguez Lorenc Karen
Published: July 2020

Ribociclib, a selective and potent cyclin‐dependent kinase 4/6 inhibitor, has demonstrated safety and efficacy in combination with endocrine therapy in hormone receptor‐positive, human epidermal growth factor receptor‐2‐negative advanced breast cancer. In 2 open‐label crossover studies in healthy participants, the absolute bioavailability of a single oral dose of a ribociclib 600‐mg tablet (n = 16) was compared with a single intravenous ribociclib infusion of 150 mg (n = 16), and the bioequivalence of a ribociclib 600‐mg tablet (n = 31) and a ribociclib 600‐mg capsule (n = 31) was evaluated. The pharmacokinetics of ribociclib and its major metabolite, LEQ803, were assessed in both studies. The oral bioavailability of the 600‐mg ribociclib tablet was 65.8% (90% confidence interval [CI], 59.1‐73.2%). The geometric mean systemic clearance of ribociclib was moderate (40.2 L/h; 27.4% intersubject variability [CV%]) compared with hepatic blood flow, and the geometric mean volume of distribution was high (979 L; 25.2 CV%). LEQ803‐to‐ribociclib metabolic ratios were 0.198 for the oral administration and 0.125 for intravenous infusion. Bioequivalence of the tablet and capsule formulations was demonstrated for ribociclib. The geometric mean ratios of maximum concentration and area under the curve from time 0 to last quantifiable concentration and to infinity were 1.01, 1.00, and 0.937, respectively, within the predefined bioequivalence range of 0.80 to 1.25. The median time to reach maximum concentration was 3 hours with both formulations. No serious adverse events were observed in either study.
In Vitro Dissolution and In Vivo Bioequivalence Evaluation of Two Metformin Extended‐Release Tablets
Authors: Zhou Ziye , Wang Chenxiang , Li Min , Lan Qin , Yu Chao , Yu Guoxin , Xia Yan , Chen Huafang , Zhang Xiuhua
Published: July 2020

The objective of the present study was to evaluate the bioequivalence between generic and branded metformin extended‐release (ER) tablets in Chinese subjects. We tested bioequivalence in vitro and in vivo using a comparative dissolution study and a comparative pharmacokinetic trial. Safety assessments were conducted throughout the entire trial period. The dissolution profiles of the generic formulation expressed obvious extended‐release properties, similar to those of the branded formulation (f2 > 60.0%). Consistent with the result of the in vitro study, no remarkable differences were found in terms of pharmacokinetic profiles between generic and branded formulations. The 90% confidence intervals of Ln AUC0‐36 h, Ln AUC0‐∞, and Ln Cmax from generic formulation versus branded formulation were 91.4% to 105.0%, 91.3% to 104.7%, and 101.2% to 119.4%, respectively. During the entire trial period, 4 subjects experienced 11 adverse events. All these were mild and spontaneously resolved. The results obtained from the present study suggest that the generic and branded metformin ER tablets were bioequivalent in Chinese subjects.
Polyanionic Lattice Modifications Leading to High‐Entropy Sodium Ion Conductors: Mathematical Solution of Accessible Compositions
Authors: Tietz Frank , Fronia Carsten
Published: July 2020

Sodium zirconium double phosphate NaZr2(PO4)3 can be used as a starting point for investigations of high‐entropy materials. Apart from the frequently used approach of partial substitution with four or more different transition metal cations, this class of materials also allows multiple substitutions of the phosphate groups. Herein modifications of the polyanionic lattice are considered and high‐entropy compositions are numerically determined with up to eight elements on the central tetrahedral lattice site of the so‐called NaSICON structure. For this study, the chemical formula was fixed as Na3Zr2(EO4)3 with E=B, Al, Si, P, As, Sb, S, Se and Te. The number of compositions increases exponentially with the increasing number of elements involved and with decreasing equal step size for each element. The maximum number of 237258 compositions is found for Na3Zr2([B,Al,Si,P,As,Sb,S,Se]O4)3 with a step size of 0.1 mol/formula unit. Of this compositional landscape, 143744 compositions fulfil the definitions of high‐entropy materials. The highest entropy factor of ΔSconfig/R=‐2.0405 is attributed to the compositions Na3Zr2(B0.5Al0.6Si0.4P0.3As0.3Sb0.3S0.3Se0.3)O12 and Na3Zr2(B0.6Al0.5Si0.4P0.3As0.3Sb0.3S0.3Se0.3)O12.