bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge Assessment Among Surgeons About Energy Devices Safe Use: A Multicenter Cross-Sectional Study
Authors: Aljohani Emad , Almadi Fahad , Watanabe Yusuke , Aldawsari Abdullah , Alsuwaigh Mohammed , Alanazi Rakan , Alwadani Salman , Alfayez Talal , Alanazi Ziad
Published: July 2021

Objective

To assess the knowledge of general surgery trainees about the safe use of energy devices in 2 tertiary hospitals in Riyadh, Saudi Arabia.

Background

Electrosurgery (ES) is the use of high-frequency electrical energy to achieve cutting and coagulation. This method has become ubiquitous worldwide for the purpose of achieving rapid hemostasis and rapid dissection of tissues.

Methods

Participants completed a 35-item multiple-choice question examination, testing critical knowledge of ES. The examination was developed according to the objectives and blueprints of Society of American Gastrointestinal Endoscopic Surgeons' Fundamental Use of Surgical Energy curriculum. Sections of the examination included the following: principles of ES, ES-related adverse events, monopolar and bipolar devices, pediatric considerations, and interference with implantable devices. Scores were compared between junior and senior participants.

Results

A total of 51 general surgical trainees from 2 academic hospitals completed the assessment; 15.69% of the participants correctly answered 30 of 35 questions, 39.22% of the participants responded correctly to 20 of 35 questions, and 45.09% responded correctly to fewer than 20 questions. It was found that 52.2% of the individuals with a low level of understanding were junior residents; 87.5% of the participants with the highest level of understanding were senior residents, with a significant P value of 0.04.

Conclusions

Most general surgery residents enrolled in the Saudi Arabian Board of Surgery lack adequate knowledge about the safe and efficient use of surgical energy devices.
Coffee Consumption and Incident Tachyarrhythmias
Authors: Kim Eun-jeong , Hoffmann Thomas J. , Nah Gregory , Vittinghoff Eric , Delling Francesca , Marcus Gregory M.
Published: July 2021

Importance

The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated.

Objective

To assess the association between consumption of common caffeinated products and the risk of arrhythmias.

Design, Setting, and Participants

This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses.

Exposures

Daily coffee intake and genetic polymorphisms that affect caffeine metabolism.

Main Outcomes and Measures

Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes.

Results

A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P < .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P < .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism–related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia.

Conclusions and Relevance

In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.
Burnout and metabolic syndrome among healthcare workers: Is subclinical hypothyroidism a mediator?
Authors: Tsou Meng-Ting , Chen Jau-Yuan
Published: July 2021

Objectives

Evidence suggests that subclinical hypothyroidism (SCH) is associated with burnout and metabolic syndrome (MetS). We examined the relationship between burnout and MetS among healthcare workers (HCWs) and investigated the potential mediation of SCH.

Methods

This cross-sectional study included HCWs from a tertiary medical center; demographic data were obtained using a questionnaire. Burnout was evaluated according to the Chinese version of the Maslach Burnout Inventory–Health Services Survey (MBI–HSS). MetS and thyroid function data were obtained from a physical check-up. Logistic regression models were used to evaluate the adjusted odds ratio (aOR), and mediation analysis was employed to examine the mediation effect.

Results

Among 945 non-doctor/nurse and 1868 doctor/nurse staff, MetS was 30% and 14%, respectively, and the prevalence of burnout was nearly 6.5%. The results showed that burnout induced higher aOR of MetS in the doctor/nurse group (1.27, 95% confidence interval [CI]: 1.05-3.62). Thyroid-stimulating hormone (TSH) showed a positive association factor of MetS in doctor/nurse group-adjusted burnout (aOR = 1.15, 95% CI: 1.01-4.19). A higher TSH level was associated with an increased odds of MetS in younger doctor/nurse staff with burnout syndrome (aOR = 1.74; 95% CI: 1.04-3.22). There was a borderline significant mediation effect of SCH in the association between burnout and MetS in doctor/nurse staff.

Conclusions

The results showed that higher TSH levels were positively associated with burnout and MetS in doctor/nurse professionals, especially in the young cohort. Burnout may rely on the borderline mediation effect of SCH, which is likely to affect MetS.
Tuning the Electrochemical Properties of Polymeric Cobalt Phthalocyanines for Efficient Water Splitting
Authors: Kim Yoonbin , Kim Daekyu , Lee Jeongyeon , Lee Lawrence Yoon Suk , Ng Dennis K. P.
Published: July 2021

Polymeric metal phthalocyanines have great potential as electrocatalysts, yet their incorporation on a current collector without losing the activity of metal centers remains a challenge. Herein, a new strategy for preparing a series of polymeric cobalt phthalocyanines containing S linkers (pCoPc‐1) or SO2 linkers (pCoPc‐2) and their tunable electrochemical properties are reported. The pCoPcs coated on various substrates show favorable electrocatalytic activities toward oxygen and hydrogen evolution reactions (OER and HER). Particularly, the pCoPc‐1 layer on Co3O4 nanosheet arrays exerts a cooperative effect enhancing both the OER and HER performances, and the subsequent phosphorization (P@pCoPc‐1/Co3O4|CC) significantly boosts the HER performance with enhanced hydrophilicity and conductivity. The high permeability and stability reinforcement of the pCoPc‐1 layer allow the phosphorization of underlying Co3O4 to CoP without degradation, which remarkably enhances OER and HER performances as manifested by low overpotentials of 320 and 120 mV at 10 mA cm−2, respectively. When engaged as a bifunctional electrocatalyst for the overall water splitting, the P@pCoPc‐1/Co3O4|CC requires a low cell voltage of 1.672 V at 10 mA cm−2, showing long‐term durability and mechanical robustness. This study demonstrates the collaborative catalytic role of polymeric macrocyclic compounds that offers versatile tunability and stability for various electrocatalytic reactions.
A Field Guide to Azopolymeric Optical Fourier Surfaces and Augmented Reality
Authors: Lim Yongjun , Kang Byungsoo , Hong Seung Jae , Son Heeju , Im Eunji , Bang Joona , Lee Seungwoo
Published: July 2021

Optical Fourier surfaces (OFSs) are used for various applications, from diffractive optics to augmented reality (AR). However, the current methods of fabricating OFSs primarily rely on lithographic photochemical reactions and etching. These methods are likely to fabricate digitalized binary reliefs, which cannot match the ideal surface profile of OFSs. Such a profile is the sum of sinusoidal surfaces with various spatial frequencies. As an exception, scanning probe lithography (SPL) is found to be compatible with OFSs. However, the accessible pattern area of the OFSs created via SPL is relatively small owing to the serial feature of the fabrication, which in turn results in an undesired and complicated Fourier spectrum. In this article, the holographic inscription is redesigned for the low‐cost, large‐area, and rapid prototyping of customized OFSs. To this end, an integrative pipeline is established across numerical design, material optimization, and the pragmatic considerations of optical processing. Then, a soft molding strategy is suggested for optically transparent and flexible OFSs and its use for easy‐to‐craft AR devices. Overall, this intuitive framework not only expands the scope of Fourier optics but also acts as a field guide to azopolymeric OFSs and AR technology for experts and newcomers alike.
Advanced Bioresponsive Multitasking Hydrogels in the New Era of Biomedicine
Authors: Niazi Mostafa , Alizadeh Effat , Zarebkohan Amir , Seidi Khaled , Ayoubi‐Joshaghani Mohammad Hosein , Azizi Mehdi , Dadashi Hamed , Mahmudi Hossein , Javaheri Tahereh , Jaymand Mehdi , Hamblin Michael R. , Jahanban‐Esfahlan Rana , Amoozgar Zohreh
Published: July 2021

Advanced forms of hydrogels have many inherently desirable properties and can be designed with different structures and functions. In particular, bioresponsive multifunctional hydrogels can carry out sophisticated biological functions. These include in situ single‐cell approaches, capturing, analysis, and release of living cells, biomimetics of cell, tissue, and tumor‐specific niches. They can allow in vivo cell manipulation and act as novel drug delivery systems, allowing diagnostic, therapeutic, vaccination, and immunotherapy methods. In the present review of multitasking hydrogels, new approaches and devices classified into point‐of‐care testing (POCT), microarrays, single‐cell/rare cell approaches, artificial membranes, biomimetic modeling systems, nanodoctors, and microneedle patches are summarized. The potentials and application of each format are critically discussed, and some limitations are highlighted. Finally, how hydrogels can enable an “all‐in‐one platform” to play a key role in cancer therapy, regenerative medicine, and the treatment of inflammatory, degenerative, genetic, and metabolic diseases is being looked forward to.
Divalent Ion Selectivity in Capacitive Deionization with Vanadium Hexacyanoferrate: Experiments and Quantum‐Chemical Computations
Authors: Singh Kaustub , Li Guanna , Lee Juhan , Zuilhof Han , Mehdi B. Layla , Zornitta Rafael L. , de Smet Louis C. P. M.
Published: July 2021

Selective removal of ions from water via capacitive deionization (CDI) is relevant for environmental and industrial applications like water purification, softening, and resource recovery. Prussian blue analogs (PBAs) are proposed as an electrode material for selectively removing cations from water, based on their size. So far, PBAs used in CDI are selective toward monovalent ions. Here, vanadium hexacyanoferrate (VHCF), a PBA, is introduced as a new electrode material in a hybrid CDI setup to selectively remove divalent cations from water. These electrodes prefer divalent Ca2+ over monovalent Na+, with a separation factor, βCa/Na ≈3.5. This finding contrasts with the observed monovalent ion selectivity by PBA electrodes. This opposite behavior is understood by density functional theory simulations. Furthermore, coating the VHCF electrodes with a conducting polymer (poly‐pyrrole, doped with poly‐styrenesulphonate) prevents the contamination of the treated water following the degradation of the electrode. This facile and modular coating method can be effortlessly extended to other PBA electrodes, limiting the extent of treated water contamination during repeated cycling. This study paves the way for tunable selectivity while extending the library of electrodes that can be successfully used in (selective) CDI.
Systematic Design and Demonstration of Multi‐Bit Generation in Layered Materials Heterostructures Floating‐Gate Memory
Authors: Gwon Oh Hun , Kim Jong Yun , Kim Han Seul , Kang Seok‐Ju , Byun Hye Ryung , Park Min , Lee Dong Su , Kim Yoon‐jeong , Ahn Seokhoon , Kim Jaekyung , Cho Sang‐Joon , Yu Young‐Jun
Published: July 2021

Van der Waals (vdW) heterostructures with 2D materials have shown that atomically thin non‐volatile memories are advantageous in terms of integration, while offering high performance and excellent stability. The non‐volatile memory behavior of 2D materials has mainly been studied for single‐bit operation, and there is growing interest in expanding to multi‐bit operation to enhance the storage capacities of memory devices. However, the conditions or rules for generating the desired number of bits in 2D‐based multi‐bit memory remain to be identified. In this study, multiple bits are successfully created on non‐volatile memory based on vdW heterostructure floating‐gate memory (FGM) by systematically tuning the dimensions of the 2D materials. In particular, a fingerprint mechanism is established that links the bit number and dimensions of 2D crystals on vdW heterostructures. This approach could enable the precise generation of the desired number of bits in layered‐material‐based vdW FGMs.
A Smartphone‐Enabled Portable Digital Light Processing 3D Printer
Authors: Li Wanlu , Wang Mian , Mille Luis Santiago , Robledo Lara Juan Antonio , Huerta Valentín , Uribe Velázquez Tlalli , Cheng Feng , Li Hongbin , Gong Jiaxing , Ching Terry , Murphy Caroline A. , Lesha Ami , Hassan Shabir , Woodfield Tim B. F. , Lim Khoon S. , Zhang Yu Shrike
Published: July 2021

3D printing has emerged as an enabling approach in a variety of different fields. However, the bulk volume of printing systems limits the expansion of their applications. In this study, a portable 3D Digital Light Processing (DLP) printer is built based on a smartphone‐powered projector and a custom‐written smartphone‐operated app. Constructs with detailed surface architectures, porous features, or hollow structures, as well as sophisticated tissue analogs, are successfully printed using this platform, by utilizing commercial resins as well as a range of hydrogel‐based inks, including poly(ethylene glycol)‐diacrylate, gelatin methacryloyl, or allylated gelatin. Moreover, due to the portability of the unique DLP printer, medical implants can be fabricated for point‐of‐care usage, and cell‐laden tissues can be produced in situ, achieving a new milestone for mobile‐health technologies. Additionally, the all‐in‐one printing system described herein enables the integration of the 3D scanning smartphone app to obtain object‐derived 3D digital models for subsequent printing. Along with further developments, this portable, modular, and easy‐to‐use smartphone‐enabled DLP printer is anticipated to secure exciting opportunities for applications in resource‐limited and point‐of‐care settings not only in biomedicine but also for home and educational purposes.
Plasmon‐Driven Catalytic Chemotherapy Augments Cancer Immunotherapy through Induction of Immunogenic Cell Death and Blockage of IDO Pathway
Authors: Ding Yuan , Sun Zhongquan , Gao Yong , Zhang Sitong , Yang Caixia , Qian Zhefeng , Jin Lulu , Zhang Jiaojiao , Zeng Cheng , Mao Zhengwei , Wang Weilin
Published: July 2021

Clinical trials confirm the combination of indoleamine 2,3‐dioxygenase (IDO) blockade and immunogenic chemotherapy represents a brilliant future in cancer therapy. However, it remains challenging to precisely activate chemo‐immunotherapy in situ to avoid side effects from the systemic administrations and reverse the poor immunogenicity and immunosuppressive microenvironment in tumor sites. Herein, a hybrid nanomedicine (“RPMANB NPs”) to co‐deliver an IDO inhibitor (NLG919) and a chemotherapeutic prodrug to amplify the therapeutic benefits are designed. Attributed to the delicate surface engineering, the RPMANB NPs possess excellent pharmacokinetics and tumor accumulation. The loaded NLG919 are released inside cancer tissues/cells due to the collapse of the metal–organic framework platform triggered by the highly concentrated phosphate, reversing the immunosuppressive tumor microenvironment by suppressing IDO activity. The potent chemotherapeutic drug is precisely activated through a highly efficient plasmon‐driven catalysis in the presence of near‐infrared light, eliciting antitumor immunity by triggering immunogenic cell death and avoiding side effects through in situ activation of chemotherapy. In vivo studies demonstrate that the chemo‐immunotherapy greatly suppresses the tumor growth by promoting intratumoral accumulation of cytotoxic T lymphocytes and downregulating regulatory T cells. This work establishes a robust delivery platform to overcome the current obstacles of tumor treatments by combining precisely activatable chemotherapy with immunotherapy.
Polymer‐Assisted Metallization of Mammalian Cells
Authors: Wang Wenshuo , Gan Qi , Zhang Yuqi , Lu Xi , Wang Huixin , Zhang Yaokang , Hu Hong , Chen Lina , Shi Lianxin , Wang Shutao , Zheng Zijian
Published: July 2021

Developing biotemplating techniques to translate microorganisms and cultured mammalian cells into metallic biocomposites is of great interest for biosensors, electronics, and energy. The metallization of viruses and microbial cells is successfully demonstrated via a genetic engineering strategy or electroless deposition. However, it is difficult to transform mammalian cells into metallic biocomposites because of the complicated genes and the delicate morphological features. Herein, “polymer‐assisted cell metallization” (PACM) is reported as a general method for the transformation of mammalian cells into metallic biocomposites. PACM includes a first step of in situ polymerization of functional polymer on the surface and in the interior of the mammalian cells, and a subsequent electroless deposition of metal to convert the polymer‐functionalized cells into metallic biocomposites, which retain the micro‐ and nanostructures of the mammalian cells. This new biotemplating method is compatible with different cell types and metals to yield a wide variety of metallic biocomposites with controlled structures and properties.
Site‐Specific Biomimicry of Antioxidative Melanin Formation and Its Application for Acute Liver Injury Therapy and Imaging
Authors: Zhao Caiyan , Li Zhi , Chen Jingxiao , Su Lichao , Wang Junqing , Chen Dean Shuailin , Ye Jiamin , Liao Naishun , Yang Huanghao , Song Jibin , Shi Jinjun
Published: July 2021

Biocompatible nano‐antioxidants composed of natural molecules/materials, such as dopamine and melanin, are of great interest for diverse biomedical applications. However, the lack of understanding of the precise structure of these biomaterials and thus the actual dose of effective components impedes their advancement to translation. Herein, a strategy to mimic in situ melanin formation and explore its antioxidative applications is reported, by developing a PEGylated, phenylboronic‐acid‐protected L‐DOPA precursor (PAD) that can self‐assemble into well‐defined nanoparticles (PADN). Exposure to oxidative species leads to deprotection of phenylboronic acids, transforming PADN to PEG‐L‐DOPA, which, similar to the biosynthetic pathway of melanin, can be oxidized and polymerized into an antioxidative melanin‐like structure. With ultrahigh stability and superior antioxidative activity, the PADN shows remarkable efficacy in prevention and treatment of acute liver injury/failure. Moreover, the in situ structure transformation enables PADN to visualize damaged tissue noninvasively by photoacoustic imaging. Overall, a bioinspired antioxidant with precise structure and site‐specific biological activity for theranostics of oxidative stress‐related diseases is described.
Autonomous Off‐Equilibrium Morphing Pathways of a Supramolecular Shape‐Memory Polymer
Authors: Peng Wenjun , Zhang Guogao , Zhao Qian , Xie Tao
Published: July 2021

The diverse morphing behaviors of living creatures arise from their unlimited pathways. In contrast, the equilibrium‐driven morphing pathways of common synthetic shape‐shifting materials are very limited. For a shape‐memory polymer (SMP), its recovery from the temporary shape(s) to the permanent shape typically requires external stimulation and follows a single fixed route. Herein, a covalently crosslinked SMP is designed with ample ureidopyrimidinone (UPy) supramolecular moieties in the network. The UPy units endow the SMP with strong time–temperature dependency, which is explored as a mechanism for spatio‐temporal programming of autonomous shape‐shifting pathways. In particular, the use of digitally controlled photothermal heating provides versatility in control via an off‐equilibrium mechanism. In addition, cooling/heating across its glass transition introduces a locking/unlocking mechanism for its temporal morphing. The benefits of these unique features are demonstrated by multi‐shape‐transformation, an “invisible”‐color‐based clock, a time–temperature indicator, and sequence‐programmable 4D printing.
Copper Promotes Tumorigenesis by Activating the PDK1‐AKT Oncogenic Pathway in a Copper Transporter 1 Dependent Manner
Authors: Guo Jianping , Cheng Ji , Zheng Nana , Zhang Xiaomei , Dai Xiaoming , Zhang Linli , Hu Changjiang , Wu Xueji , Jiang Qiwei , Wu Depei , Okada Hitoshi , Pandolfi Pier Paolo , Wei Wenyi
Published: July 2021

Copper plays pivotal roles in metabolic homoeostasis, but its potential role in human tumorigenesis is not well defined. Here, it is revealed that copper activates the phosphoinositide 3‐kinase (PI3K)‐protein kinase B (PKB, also termed AKT) oncogenic signaling pathway to facilitate tumorigenesis. Mechanistically, copper binds 3‐phosphoinositide dependent protein kinase 1 (PDK1), in turn promotes PDK1 binding and subsequently activates its downstream substrate AKT to facilitate tumorigenesis. Blocking the copper transporter 1 (CTR1)‐copper axis by either depleting CTR1 or through the use of copper chelators diminishes the AKT signaling and reduces tumorigenesis. In support of an oncogenic role for CTR1, the authors find that CTR1 is abnormally elevated in breast cancer, and is subjected by NEDD4 like E3 ubiquitin protein ligase (Nedd4l)‐mediated negative regulation through ubiquitination and subsequent degradation. Accordingly, Nedd4l displays a tumor suppressive function by suppressing the CTR1‐AKT signaling. Thus, the findings identify a novel regulatory crosstalk between the Nedd4l‐CTR1‐copper axis and the PDK1‐AKT oncogenic signaling, and highlight the therapeutic relevance of targeting the CTR1‐copper node for the treatment of hyperactive AKT‐driven cancers.
A comprehensive phylogenomic study of the monocot order Commelinales, with a new classification of Commelinaceae
Authors: Zuntini Alexandre R. , Frankel Lorna P. , Pokorny Lisa , Forest Félix , Baker William J.
Published: July 2021

Premise

Resolving relationships within order Commelinales has posed quite a challenge, as reflected in its unstable infra‐familial classification. Thus, we investigated (1) relationships across families and genera of Commelinales; (2) phylogenetic placement of never‐before sequenced genera; (3) how well off‐target plastid data integrate with other plastid‐based data sets; and (4) how the novel inferences coincide with the infra‐familial classification.

Methods

We generated two large data sets (nuclear and plastome) by means of target sequence capture using the Angiosperms353 probe set, with additional sequences mined from publicly available transcriptomes and full plastomes. A third extended‐plastid data set was considered, including all species with sequences in public repositories. Species trees were inferred under a multispecies coalescent framework from individual gene trees and also using maximum likelihood analyses from concatenated and partitioned data.

Results

The nuclear, plastome, and extended‐plastid data sets include 52, 53, and 58 genera, respectively, and up to 290 species of Commelinales, representing the most comprehensive molecular sampling for the order to date, which includes seven never‐before sequenced genera.

Conclusions

We inferred robust phylogenies supporting the monophyly of Commelinales and its five constituent families, and we recovered the clades Pontederiaceae‐Haemodoraceae and Hanguanaceae‐Commelinaceae, as previously reported. The placement of Philydraceae remains contentious. Relationships within the two largest families, Commelinaceae and Haemodoraceae, are resolved. Based on the latter results, we confirm the subfamilial classification of Haemodoraceae and propose a new classification for Commelinaceae, which includes the synonymization of Tapheocarpa in Commelina.
Technique for ultrasound‐guided radiofrequency denervation of genicular nerves for chronic knee pain
Authors: Merrin Elizabeth , Grimshaw Le‐Anne
Published: July 2021

Genicular nerve radiofrequency denervation (GNRFD), also called radiofrequency ablation or genicular neurotomy, has been demonstrated to be a safe and effective method of treating and managing chronic knee pain caused by osteoarthritis (OA). The genicular nerves have been identified as key sensory nerves that innervate the knee joint. Using ultrasound guidance, the genicular nerves can be heated to temperatures up to 80°C, creating a local neuronal lesion, causing denervation and therefore temporarily alleviating knee pain. GNRFD is an effective treatment for those with chronic knee pain in whom conservative treatment has failed, who are poor candidates for surgery or who are on an extended waiting list for their surgery. This article outlines the technique for introducing the radiofrequency (RF) probes so the tip is in close proximity to the genicular nerves using ultrasound guidance.
Construction of Vicinal Quaternary Carbon Stereocenters Through Diastereo‐ and Enantioselective Oxidative 1,6‐Conjugate Addition
Authors: Liu Xigong , Zhao Changyin , Zhu Rongxiu , Liu Lei
Published: July 2021

The asymmetric construction of vicinal quaternary carbon stereocenters with at least one moiety in acyclic systems is a formidable challenge. We disclose a solution involving diastereo‐ and enantioselective oxidative 1,6‐conjugate addition. The practical asymmetric cross‐dehydrogenative coupling of 2,2‐diarylacetonitriles and diverse α‐substituted cyclic 1,3‐dicarbonyls proceeds, for vicinal quaternary carbon stereocenters with one center in acyclic systems, in excellent yields and stereoselectivities. The generality of the approach is further demonstrated by the stereoselective creation of vicinal quaternary carbon stereocenters with both centers in acyclic systems using acyclic β‐ketoesters as coupling partners. Computational studies elucidate the origins of both diastereo‐ and enantioselectivity.
Exquisite Vesicular Nanomedicine by Paclitaxel Mediated Co‐assembly with Camptothecin Prodrug
Authors: Zhou Zijian , Du Chao , Zhang Qianyu , Yu Guocan , Zhang Fuwu , Chen Xiaoyuan
Published: July 2021

We report that the self‐assembly of drug amphiphiles, Evans blue conjugated camptothecin prodrug (EB‐CPT), can be modulated by another anticancer drug paclitaxel (PTX), resulting in ultrahigh quality of nanovesicles (NVs) with uniform shape and diameters of around 80 nm with the EB‐CPT:PTX weight ratio of 1:1, 1:2, and 1:3, denoted as ECX NVs. Significantly, the co‐assembly of EB‐CPT and PTX without adding other excipients has nearly 100 % drug loading efficiency (DLE) and ultrahigh drug loading content (DLC) of PTX alone of up to 72.3±1.7 wt % which, to our best knowledge, is among the highest level reported in literature. Moreover, the ECX NVs with the EB‐CPT:PTX weight ratio of 1:2 showed remarkable combination index of 0.59 at a level of 50 % efficacy against HCT116 cells in vitro and greatly improved tumor inhibition effect in vivo compared with two clinically approved CPT‐ and PTX‐based anticancer nanomedicines (Onivyde and Abraxane) individually and their combinations.
Molecular Tailoring of an n/p‐type Phenothiazine Organic Scaffold for Zinc Batteries
Authors: Wang Nan , Guo Zhaowei , Ni Zhigang , Xu Jie , Qiu Xuan , Ma Jing , Wei Peng , Wang Yonggang
Published: July 2021

The p‐type or n‐type redox reactions of organics are being used as the reversible electrodes to build the next‐generation rechargeable batteries with sustainable and tunable characteristics. However, the n‐type organics that store cations generally exhibit low potential (<0.8 V vs. Zn/Zn2+), while the p‐type organics that store anions suffer from limited capacity (<100 mAh g−1). Herein, we demonstrate that bis(phenylamino)phenothiazin‐5‐ium iodide (PTD‐1) containing both n‐type and p‐type redox moieties exhibits a hybrid charge storage mechanism (n/p‐type at low potential, p‐type at high potential). Such a hybrid mechanism combines the advantages of n‐ and p‐type reactions and compensates for the associated drawbacks of each. Accordingly, the aqueous Zn//PTD‐1 full cell shows a high voltage (1.8 Vmaximum or 1.1 Vaverage), a high capacity 188.24 mAh gPTD‐1−1 (achieved at 40 mA g−1), a long‐life and a supercapacitor‐like high power. These results shed new light on the design of advanced organic electrodes.
Electrical and mechanical properties of partially bio‐based PP/PBS blends nanocomposites elaborated by twin‐screw extrusion
Authors: Bencharki Mouhja , Rondot Sébastien , Tara Ahmed , Jbara Omar , Berzin Françoise
Published: July 2021

Organically modified montmorillonite (OMMT, Cloisite 20) was used as reinforcing filler to prepare nanocomposites from a blend of polypropylene (PP) and eco‐friendly degradable polybutylene succinate (PBS). A PP grafted with maleic anhydride was also added as a compatibilizer. Scanning electron microscopy observations indicated that the blend morphology was affected by the presence of OMMT, which acted as a compatibilizer between PP and PBS. Rheological measurements showed a significant increase of the complex viscosity when OMMT was added above a certain amount. X‐ray diffraction indicated an intercalated structure for all nanocomposites. The addition of OMMT improved mechanical properties of neat matrices and blends. The electrical insulation properties were preserved for low concentrations of OMMT, up to 2 wt%. Then, to guarantee good mechanical properties without deteriorating electrical ones, while maintaining a sufficient bio‐based composition, the 70/30 (PP/PBS) blend with clay concentrations of less than 2 wt% appeared to be the most satisfactory nanocomposite for applications in the field of electrical insulation.
Hydrophobically modified melamine‐formaldehyde sponge used for conformance control and water shutoff during oil production
Authors: Ou Wen , Luo Xinjie , Feng Yujun
Published: July 2021

Polymer or polymer gels have been widely used to control excessive water during oil production by homogenizing injection profile and reducing water cut in the produced fluids. However, the gels used are generally unable to selectively minimize water production, and face the challenge of syneresis of gels under high temperature and high salinity environment. In this work, melamine‐formaldehyde sponge was modified with AlCl3 solution, rendering a transition from hydrophilic to hydrophobic state with a water contact angle of 130° on the surface of the modified product. Filtration results show that mineral oil and water can be selectively separated with the hydrophobically modified sponge powders. Simulated water shutoff experiments demonstrated the blockage efficiency against water was 30% higher than that against oil, and the oil production was increased 7.4% after blocking. The parallel profile control tests confirmed that the fraction flow of high permeable channel decreased about 75%, accompanied with 60% rise of oil recovery factor. These results indicated that such hydrophobic materials can significantly reduce excessive water production, and this work provided a new idea to offer a low‐cost hydrophobic material for conformance control and water shutoff during oil production.
Risk of Inflammatory Bowel Disease in Patients With Psoriasis and Psoriatic Arthritis/Ankylosing Spondylitis Initiating Interleukin‐17 Inhibitors: A Nationwide Population‐Based Study Using the French National Health Data System
Authors: Penso Laetitia , Bergqvist Christina , Meyer Antoine , Herlemont Philippe , Weill Alain , Zureik Mahmoud , Dray‐Spira Rosemary , Sbidian Emilie
Published: July 2021

Objective

To investigate whether the initiation of treatment with an interleukin‐17 inhibitor (IL‐17i) in real life is associated with a higher risk of inflammatory bowel disease (IBD) in patients who had both psoriasis (PsO) and psoriatic arthritis (PsA)/ankylosing spondylitis (AS).

Methods

This nationwide cohort study was conducted using the French National Health Data System database. All adult patients with PsO and PsA/AS who were identified as having newly initiated treatment with an IL‐17i during 2016–2019 were included. As controls, patients with PsO and PsA/AS who had newly initiated either 1) apremilast or 2) etanercept (ETN) during this period but had not received IL‐17i were included. The follow‐up end date was September 30, 2019. The primary end point was the risk of occurrence of IBD associated with exposure to an IL‐17i compared to exposure to the other treatments, as determined in a time‐to‐event analysis with propensity score–weighted Cox and Fine‐Gray proportional hazards models.

Results

The study included a total of 16,793 new IL‐17i users (mean ± SD age 48.4 ± 13 years, 45% men), 20,556 new apremilast users (age 52.6 ± 15 years, 54% men), and 10,294 new ETN users (age 46.3 ± 15 years, 44% men). New IL‐17i users and new ETN users had received more biologics for their underlying disease compared to new apremilast users. IBD occurred in 132 patients: 72 new IL‐17i users (0.43%), 11 new apremilast users (0.05%), and 49 new ETN users (0.48%). Most IBD cases occurred after 6 months of exposure (82%, 55%, and 76%, respectively). After propensity score weighting, the risk of IBD was significantly greater among patients initiating an IL‐17i compared to those initiating apremilast (weighted hazard ratio [HR] 3.8 [95% confidence interval (95% CI) 2.1–6.8]). No difference in the risk of IBD between new IL‐17i users and new ETN users was observed (weighted HR 0.8 [95% CI 0.5–1.2]).

Conclusion

Patients with PsO and PsA/AS who initiate treatment with an IL‐17i do not have a higher risk of developing IBD when compared to patients initiating ETN who display the same severity of underlying disease. These results need to be confirmed in other large studies of patients with PsO and PsA/AS.
Platelet Phagocytosis via P‐selectin Glycoprotein Ligand 1 and Accumulation of Microparticles in Systemic Sclerosis
Authors: Manfredi Angelo A. , Ramirez Giuseppe A. , Godino Cosmo , Capobianco Annalisa , Monno Antonella , Franchini Stefano , Tombetti Enrico , Corradetti Sara , Distler Jörg H. W. , Bianchi Marco E. , Rovere‐Querini Patrizia , Maugeri Norma
Published: July 2021

Objective

It is unclear why activated platelets and platelet‐derived microparticles (MPs) accumulate in the blood of patients with systemic sclerosis (SSc). This study was undertaken to investigate whether defective phagocytosis might contribute to MP accumulation in the blood of patients with SSc.

Methods

Blood samples were obtained from a total of 81 subjects, including 25 patients with SSc and 26 patients with stable coronary artery disease (CAD). Thirty sex‐ and age‐matched healthy volunteers served as controls. Studies were also conducted in NSG mice, in which the tail vein of the mice was injected with MPs, and samples of the lung parenchyma were obtained for analysis of the pulmonary microvasculature. Tissue samples from human subjects and from mice were assessed by flow cytometry and immunochemical analyses for determination of platelet–neutrophil interactions, phagocytosis, levels and distribution of P‐selectin, P‐selectin glycoprotein ligand 1 (PSGL‐1), and HMGB1 on platelets and MPs, and concentration of byproducts of neutrophil extracellular trap (NET) generation/catabolism.

Results

Activated P‐selectin+ platelets and platelet‐derived HMGB1+ MPs accumulated in the blood of SSc patients but not in the blood of healthy controls. Patients with CAD, a vasculopathy independent of systemic inflammation, had fewer P‐selectin+ platelets and a negligible number of MPs. The expression of the receptor for P‐selectin, PSGL‐1, in neutrophils from SSc patients was significantly decreased, raising the possibility that phagocytes in SSc do not recognize activated platelets, leading to a failure of phagocytosis and continued neutrophil release of MPs. As evidence of this process, activated platelets were not detected in the neutrophils from SSc patients, whereas they were consistently present in the neutrophils from patients with CAD. HMGB1+ MPs elicited generation of NETs, which were only detected in the plasma of SSc patients. In mice, P‐selectin–PSGL‐1 interaction resulted in platelet phagocytosis in vitro and influenced the ability of MPs to elicit NETs, endothelial activation, and migration of leukocytes through the pulmonary microvasculature.

Conclusion

The clearance of activated platelets via PSGL‐1 limits the undesirable effects of MP‐elicited neutrophil activation. This balance is disrupted in patients with SSc. Its reconstitution might curb vascular inflammation and prevent fibrosis.
International Consensus for the Dosing of Corticosteroids in Childhood‐Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis
Authors: Chalhoub Nathalie E. , Wenderfer Scott E. , Levy Deborah M. , Rouster‐Stevens Kelly , Aggarwal Amita , Savani Sonia I. , Ruth Natasha M. , Arkachaisri Thaschawee , Qiu Tingting , Merritt Angela , Onel Karen , Goilav Beatrice , Khubchandani Raju P. , Deng Jianghong , Fonseca Adriana R. , Ardoin Stacy P. , Ciurtin Coziana , Kasapcopur Ozgur , Jelusic Marija , Huber Adam M. , Ozen Seza , Klein‐Gitelman Marisa S. , Appenzeller Simone , Cavalcanti André , Fotis Lampros , Lim Sern Chin , Silva Rodrigo M. , Miramontes Julia Ramírez‐ , Rosenwasser Natalie L. , Saad‐Magalhaes Claudia , Schonenberg‐Meinema Dieneke , Scott Christiaan , Silva Clovis A. , Enciso Sandra , Terreri Maria T. , Torres‐Jimenez Alfonso‐Ragnar , Trachana Maria , Al‐Mayouf Sulaiman M. , Devarajan Prasad , Huang Bin , Brunner Hermine I. ,   for the Childhood Arthritis and Rheumatology Research Alliance Lupus Nephritis Work Group and the Pediatric Rheumatology European Society Lupus Working Party
Published: July 2021

Objective

To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood‐onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology.

Methods

Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood‐onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood‐onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR‐recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%.

Results

Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3–5). Validation of the SSR for up to 6 months post–kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6).

Conclusion

The SSR represents an international consensus on CS dosing for use in patients with childhood‐onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.
Measurements of visual binaries with PISCO2 at the Nice 76‐cm refractor in 2011–2012
Authors: Gili René , Prieur Jean‐Louis , Rivet Jean‐Pierre , Vakili Farrokh , Scardia Marco , Pansecchi Luigi , Argyle Robert W. , Ling Josefina F. , Piccotti Luca , Aristidi Eric , Koechlin Laurent , Bonneau Daniel , Maccarini Luca , Serot Jocelyn
Published: July 2021

We present relative astrometric and photometric measurements of visual binaries made in 2011–2012, with PISCO2 installed at the 76‐cm refractor of Côte d'Azur Observatory in Nice (France). Our observing list contains orbital couples as well as binaries whose motion is still uncertain. Three different techniques have been used for obtaining those measurements: Lucky imaging, speckle interferometry, and the direct vector autocorrelation method. From our observations of 3,136 multiple stars, we obtained 3,568 new measurements with angular separations in the range of 0″.1–10″ and an average accuracy of 0″.016. The mean error on the position angles is 1°.7. Most of the position angles were determined without the usual 180° ambiguity with the application of the direct vector autocorrelation technique and/or by inspection of the Lucky images or the long integration files. We managed to routinely monitor faint systems (mV ≈ 9–11) with large magnitude difference (up to ΔmV ≈ 5). We have thus been able to measure many systems containing red dwarf stars that had been poorly monitored since their discovery. We also measured the magnitude difference of the two components of 326 binaries with an estimated error of 0.2 mag. Except for a few objects that have been discussed, our measurements are in a good agreement with the ephemerides computed with published orbital elements, even for the binaries closer than the diffraction limit. Thanks to good seeing images and with the use of high‐contrast numerical filters, we have also been able to obtain 196 measurements with an angular separation smaller than the diffraction limit of our instrumentation, and consistent with those obtained with larger telescopes. We also obtained new measurements of the 15th magnitude multiple system CON37, and discovered a faint new double star in its vicinity. Finally, we report 47 measurements of 28 new binaries found during our observations.
Discriminant value of repetitive behaviors in families with autism spectrum disorder and obsessional compulsive disorder probands
Authors: Lefebvre Aline , Cohen Alicia , Maruani Anna , Amsellem Fréderique , Beggiato Anita , Amestoy Anouck , Moal Myriam Ly‐Le , Umbricht Daniel , Chatham Christopher , Murtagh Lorraine , Bouvard Manuel , Leboyer Marion , Bourgeron Thomas , Delorme Richard
Published: July 2021

Repetitive behaviors (RB) represent a wide spectrum of symptoms ranging from sensory‐motor stereotypies to complex cognitive rituals, frequently dichotomized as low‐ and high‐order sub‐groups of symptoms. Even though these subgroups are considered as phenomenologically distinct in autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD), brain imaging and genetic studies suggest that they have common mechanisms and pathways. This discrepancy may be explained by the frequent intellectual disability reported in ASD, which blurs the RB expressivity. Given the high heritability of RB, that is, the diversity of symptoms expressed in the relatives are dependent on those expressed in their probands, we hypothesize that if RB expressed in ASD or OCD are two distinct entities, then the RB expressed in relatives will also reflect these two dimensions. We thus conduct a linear discriminant analysis on RB in both the relatives of probands with ASD and OCD and subjects from the general population (n = 1023). The discriminant analysis results in a classification of 81.1% of the controls (p < 10−4), but poorly differentiated the ASD and OCD relatives (≈46%). The stepwise analysis reveals that five symptoms attributed to high‐order RB and two related to low‐order RB (including hypersensitivity) are the most discriminant. Our results support the idea that the difference of RB patterns in the relatives is mild compared with the distribution of symptoms in controls. Our findings reinforce the evidence of a common biological pattern of RB both in ASD and OCD but with minor differences, specific to each of these two neuro‐developmental disorders.

Lay summary

Repetitive behaviors (RB), a key symptom in the classification of both OCD and ASD, are phenomenologically considered as distinct in the two disorders, which is in contrast with brain imaging studies describing a common neural circuit. Intellectual disability, which is frequently associated with ASD, makes RB in ASD more difficult to understand as it affects the expression of the RB symptoms. To avoid this bias, we propose to consider the familial aggregation in ASD and OCD by exploring RB in the first‐degree relatives of ASD and OCD. Our results highlight the existence of RB expressed in relatives compared to the general population, with a common pattern of symptoms in relatives of both ASD and OCD but also minor differences, specific to each of these two neuro‐developmental disorders.
Improving squalene production by blocking the competitive branched pathways and expressing rate‐limiting enzymes in Rhodopseudomonas palustris
Authors: Xu Wen , Wang Danyang , Fan Jinbo , Zhang Lei , Ma Xi , Yao Jia , Wang Yang
Published: July 2021

Squalene is a medically valuable bioactive compound that can be used as a raw material for fuels. Microbial fermentation is the preferred method for the squalene production. In this study, we employed several metabolic engineering strategies to increase squalene yield in Rhodopseudomonas palustris. A 57% increase in squalene titer was achieved by blocking the carotenoid pathway, thus directing more FPP into the squalene biosynthetic pathway. In order to cut down the conversion of squalene to haponoids, a recombinant strain R. palustris [Δshc, ΔcrtB] in which both carotenoid and haponoid pathways were blocked was then constructed, resulting in a 50‐fold increase in squalene titer. Based on the expression of rate‐limiting enzymes involved in the squalene pathway, the final squalene content reached 23.3 mg/g DCW, which was 178‐times higher than that of the wild‐type strain. In this study, several methods effective in improving squalene yield have been described and the potential of R. palustris for producing squalene has been demonstrated.