bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences Sustained Between Diffuse and Limited Forms of Juvenile Systemic Sclerosis in an Expanded International Cohort
Authors: Foeldvari Ivan , Klotsche Jens , Kasapcopur Ozgur , Adrovic Amra , Terreri Maria Teresa , Sakamoto Ana Paula , Stanevicha Valda , Sztajnbok Flavio , Anton Jordi , Feldman Brian , Alexeeva Ekaterina , Katsicas Maria , Smith Vanessa , Avcin Tadej , Marrani Edoardo , Kostik Mikhail , Lehman Thomas , Sifuentes‐Giraldo Walter‐Alberto , Vasquez‐Canizares Natalia , Appenzeller Simone , Janarthanan Mahesh , Moll Monika , Nemcova Dana , Patwardhan Anjali , Santos Maria Jose , Sawhney Sujata , Schonenberg‐Meinema Dieneke , Battagliotti Cristina , Berntson Lillemor , Bica Blanca , Brunner Jürgen , Costa‐Reis Patricia , Eleftheriou Despina , Harel Liora , Horneff Gerd , Kaiser Daniela , Kallinich Tilmann , Lazarevic Dragana , Minden Kirsten , Nielsen Susan , Nuruzzaman Farzana , Uziel Yosef , Helmus Nicola , Torok Kathryn S.
Published: March 2021

Objective

To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features.

Methods

A cross‐sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient‐ and physician‐reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi‐square and Mann‐Whitney U tests.

Results

At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6‐minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician‐rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features.

Conclusion

Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.
Improvement in the Mechanical Properties of Additively Manufactured Ni–Co‐Based Superalloy by Tailoring Microstructures
Authors: Lee Jung-Uk , Kim Young-Kyun , Kim Seong-Soo , Lee Kee-Ahn
Published: March 2021

Herein, a Ni‐Co‐based superalloy is manufactured using selective laser melting (SLM), and the effects of heat treatment (direct aging [DA] and solution treatment + aging [STA]) on the microstructure and mechanical properties of an SLM‐built Ni–Co‐based superalloy are investigated. An electron channeling contrast (ECC) image of the as‐built alloy shows a substructure where nm‐sized carbides are present along with a dislocation network. In the DA alloy, the basic characteristics of the substructure do not change, but the dislocation density decreases, the carbide fraction increases, and a large number of γ′ phases are formed. On the other hand, the STA alloy has very low dislocation density and exhibits γ′ phases with a size and fraction similar to those of the DA alloy. Room temperature compression tests are conducted, and the yield strengths of the as‐built, DA and STA alloys are 480, 837.5, and 750 MPa, respectively. The main underlying mechanism of improvement in the mechanical properties after heat treatment can be explained by the change of dislocation density and the fraction of carbide and γ′ phase. Based on the abovementioned findings, this study discusses the relationship between the microstructure and mechanical properties of the SLM‐built Ni–Co‐based superalloy.
Charge‐Conversion Strategies for Nucleic Acid Delivery
Authors: Dutta Kingshuk , Das Ritam , Medeiros Jewel , Kanjilal Pintu , Thayumanavan S.
Published: March 2021

Nucleic acids are considered as one of the most potent therapeutic modalities, as their roles go beyond storing genetic information and chemical energy or as signal transducers. Attenuation or expression of desired genes through nucleic acids have profound implications in gene therapy, gene editing, and even in vaccine development. Although nucleic acid therapeutics bring in overwhelming possibilities toward the development of molecular medicines, there are significant loopholes in their effective clinical translation. One of the major pitfalls lies in the traditional design concepts of nucleic acid drug carriers, namely, cationic charge induced cytotoxicity. Targeting this bottleneck, several innovative carrier designs have been proposed accommodating charge‐conversion approaches, whereby built‐in functionalities convert from cationic to neutral or anionic, or even from anionic to cationic enabling the carrier to overcome several critical barriers for therapeutics delivery, such as serum deactivation, instability in circulation, low transfection, and poor endosomal escape. This review will critically analyze various molecular designs of charge‐converting nanocarriers in a classified approach for the successful delivery of nucleic acids. Accompanied by the narrative on recent clinical nucleic acid candidates, the review concludes with a discussion on the pitfalls and scope of these emerging approaches.
Poly(ionic liquid)/Ce‐Based Antimicrobial Nanofibrous Membrane for Blocking Drug‐Resistance Dissemination from MRSA‐Infected Wounds
Authors: Luo Zhenhong , Cui Hengqing , Guo Jiangna , Yao Jieran , Fang Xia , Yan Feng , Wang Bin , Mao Hailei
Published: March 2021

Resistant bacteria have become a global threat. Even if bacteria are killed, their carried drug‐resistant genes can remain in the environment and spread to other microbes via horizontal gene transfer. Development of antimicrobial materials with intrinsic gene break down activity can prevent the dissemination of released drug‐resistant genes from the dead bacteria. Herein, imidazolium type poly(ionic liquid) (PIL)/cerium (IV) ion‐based electrospun nanofibrous membranes (PIL‐Ce) are synthesized. The effects of PIL and Ce moieties on the antimicrobial properties against Gram‐negative Escherichia coli and kanamycin‐resistant E. coli, and Gram‐positive Staphylococcus aureus and methicillin‐resistant S. aureus (MRSA), as well as deoxyribonuclease‐mimic activities to the drug‐resistant genes of KanR (E. coli) and mecA (MRSA) are investigated. The Ce‐containing PIL membranes show the high efficiencies to eradicate bacteria and disintegrate drug‐resistant genes. A wound treatment test using MRSA infected mice as the model further demonstrate that PIL‐Ce membranes combine both antibacterial and DNase‐mimic properties, and may have the potential application as a new “green” wound dressing to block the drug resistance spread in a clinical setting.
Biocompatible Light Guide‐Assisted Wearable Devices for Enhanced UV Light Delivery in Deep Skin
Authors: Zhang Hao , Zhao Hangbo , Zhao Xingyue , Xu Chenkai , Franklin Daniel , Vázquez‐Guardado Abraham , Bai Wubin , Zhao Jeffrey , Li Kan , Monti Giuditta , Lu Wei , Kobeissi Aya , Tian Limei , Ning Xin , Yu Xinge , Mehta Sunita , Chanda Debashis , Huang Yonggang , Xu Shuai , Perez White Bethany E. , Rogers John A.
Published: March 2021

Phototherapy represents an attractive route for treating a range of challenging dermatological diseases. Existing skin phototherapy modalities rely on direct UV illumination, although with limited efficacy in addressing disorders of deeper tissue and with requirements for specialized illumination equipment and masks to shield unaffected regions of the skin. This work introduces a skin‐integrated optoelectronic device that incorporates an array of UVA (360 nm) light emitting diodes in layouts that match those of typical lesional plaques and in designs that couple to biocompatible, penetrating polymer microneedle light waveguides to provide optical access to deep skin. Monte Carlo simulations and experimental results in phantom skin suggest that these waveguides significantly enhance light delivery to deep skin, with a >4‐fold increase for depths of >500 µm. In ex vivo human skin, the devices show reduced measures of phototoxicity compared to direct illumination and enhanced modulation of gene expression relevant to sclerosing skin diseases. These systems are also compatible with design principles in soft, skin‐compatible electronics and battery‐powered wireless operation. Collectively, the favorable mechanical and light delivery properties of these devices expand possibilities in targeting of deep skin lesions beyond those attainable with clinical‐standard UV light therapy approaches.
A Review of Magnesium Aluminum Chloride Complex Electrolytes for Mg Batteries
Authors: Li Yaqi , Guan Shaoliang , Huo Hua , Ma Yulin , Gao Yunzhi , Zuo Pengjian , Yin Geping
Published: March 2021

Developing suitable electrolytes with high oxidation decomposition potential, low cost, and good compatibility with electrode materials has been a critical challenge in realizing practical magnesium batteries. The emerging magnesium aluminum chloride complex (MACC) electrolytes based on inorganic chloride salts exhibit high Coulombic efficiencies for magnesium batteries. This review summarizes recent studies of MACC electrolytes, focusing on the synthesis, characterization, and chemical environment of Mg species, electrolytic conditioning of electrolytes, and their application in typical magnesium batteries. The electrolyte evolution and influencing factor of electrolytic conditioning are discussed, and several kinds of conditioning‐free MACC electrolytes are further introduced. Finally, future trends and perspectives in this field are discussed.
Fast and High‐Resolution Ultrasound Pressure Field Mapping Using Luminescent Membranes
Authors: Michels Simon E. , Kersemans Mathias , Versluis Michel , Lajoinie Guillaume , Smet Philippe F.
Published: March 2021

Ultrasound is used extensively in medical imaging and therapy, non‐destructive testing, flow sensing, underwater range assessment, and acoustic microscopy. To ensure the accuracy of these techniques, detailed knowledge of the acoustic pressure field produced by the ultrasonic transducer is required. This paper proposes a functional polymer membrane loaded with ultrasound‐activated luminescent microparticles. The semitransparent membrane makes use of the luminescent properties of BaSi2O2N2:Eu2+ to convert ultrasonic pressure into visible light in a fast and straightforward way, through a process termed acoustically produced luminescence (APL). APL is shown to work within a wide range of acoustic frequencies (1–25 MHz) and pressures (50 kPa–4.5 MPa), and enables a quantitative characterization of ultrasound fields with a lateral spatial resolution below 200 µm. At the investigated pressures and frequencies, the light generation mechanism is essentially related to ultrasonic heating rather than mechanical stimulation. These membranes offer effective field mapping possibilities, much faster than conventional time consuming point‐by‐point hydrophone scanning.
Decarboxylation‐Initiated Intermolecular Carbon‐Heteroatom Bond Formation
Authors: Zeng Zhongyi , Feceu Abigail , Sivendran Nardana , Gooßen Lukas J.
Published: March 2021

Carboxylic acids are among the most used feedstock chemicals due to their great structural diversity and easy handling. The use of carboxylic acids and their derivatives in decarboxylative couplings has proven to be a valuable tool for the construction of C−C and C‐heteroatom bonds. This synthetic strategy provides a complementary bond disconnection to traditional cross‐coupling methods. In this review, we provide a comprehensive overview of decarboxylation‐initiated intermolecular C‐heteroatom bond formation, outlining several main mechanistic concepts combined with early examples and highlighting the achievements made in the past decade until January 2021. In these reactions, carboxylic acids and their derivatives undergo initial decarboxylation and then react with other heteroatom electrophiles and nucleophiles, thus replacing the carboxylate group with a valuable and prevalent heteroatom functionality.

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Dynamic model of beer pricing and buyouts
Authors: Richards Timothy J. , Rickard Bradley J.
Published: March 2021

The beer industry in the United States is in a period of dramatic transformation. Major breweries are acquiring much smaller craft breweries in an attempt to purchase growth, but it is not clear whether these acquisitions are economically viable. In this paper, we study the impact of craft brewery acquisitions on retail beer prices, and firm profitability in a dynamic, Markov‐perfect equilibrium pricing framework. We find that the estimated impact of mergers, or buyouts, is critically dependent upon estimates of the extent of state‐dependence in demand and is, in fact, negatively correlated with the initial shock to demand. That is, if the demand shock is positive, the effect of a buyout will be under‐estimated by not accounting for state‐dependence in demand, while it is over‐estimated if the demand shock is negative. This finding is intuitive as the static model will not properly account for the long‐term positive effects of a demand shock that is initially positive, or the long‐term negative effects that are initially negative. Ultimately, we show that not all the craft‐beer buyouts in 2015 made economic sense from the acquirer's perspective. [EconLit Citations: D43, L13, M31].
The Effects of Flow Disruptions on RN Circulators
Authors: Cohen Tara N. , Boquet Albert J.
Published: March 2021

The RN circulator role includes maintaining situational awareness and mitigating risks to patient safety in the OR. Flow disruptions—deviations that threaten the safe and efficient flow of surgery—may contribute to the occurrence of errors and negatively affect safety for patients and health care providers. We used an existing data set to explore the effects of flow disruptions on the RN circulator. To create the data set, doctoral‐level human factors students observed 24 cardiac surgery procedures and recorded the types and durations of disruptions. We used a human factors taxonomy to classify the flow disruptions. Of the 1,470 events observed, interruptions were most prevalent (66.67%), followed by coordination issues (15.37%) and communication breakdowns (8.37%). Layout (7.21%), equipment (1.77%), and usability (0.61%) issues accounted for the remainder of the disruptions. Perioperative leaders should work with staff members to minimize workflow disruptions and provide support for identifying and documenting flow disruptions.
Tribo‐material based on a UHMWPE/RGOC biocomposite for using in artificial joints
Authors: Mindivan Ferda , Çolak Alime
Published: March 2021

Reduced graphene oxide (RGOC) filler that was green synthesized by vitamin C had been included in the ultrahigh molecular weight polyethylene (UHMWPE) matrix to produce biocomposite possessing improved properties especially against wear. The biocomposites filled with different loading (0.1, 0.3, 1.0, and 2.0 wt%) of RGOC was produced by a method of liquid phase ultrasonic mixing and then hot press molding. The structural analysis results of biocomposites showed that RGOC well‐dispersed in polymer matrix and confirmed that there was interaction between the RGOC‐UHMWPE. The biocomposite containing 2.0 wt% RGOC (UHMWPE/RGOC‐2) gave the maximum microhardness and the value increased by 22. 5% compared with unfilled polymer. At the same RGOC content, the biocomposite had the highest thermal stability with residue content at 2.42%. The wear and friction behavior of biocomposites were carried out in a reciprocating friction testing machine under distilled water lubricating conditions. The UHMWPE/RGOC‐2 biocomposite had the lowest friction coefficient value (0.034) and the wear rate of the biocomposite decreased by 44%, compared with that of unfilled UHMWPE. Furthermore, fatigue wear tracks were significantly reduced. This study suggests the use of this composite that had excellent tribological behavior as biomaterial instead of UHMWPE.
Physicochemical modification of hydroxylated polymers to develop thermosensitive double network hydrogels
Authors: Abdolmaleki Amir , Gharibi Hamidreza , Molavian Mohammad Reza , Norouzi Mohammad‐Reza , Asefifeyzabadi Narges
Published: March 2021

Due to the unique biophysicochemical characteristics of synthesized superhydrophilic poly[N‐[tris(hydroxymethyl)methyl] acrylamide] (PTHMMA) and poly(vinyl alcohol) (PVA), in this study, we investigated the preparation of physically and chemically crosslinked thermosensitive double network (DN) hydrogels with superior mechanical properties. The effect of the combination of PTHMMA with PVA was further explored experimentally and theoretically. Moreover, adjusting the lower critical solution temperature (LCST) of PTHMMA/PVA DN hydrogels in the phosphate buffer was achieved by chemical alteration and crosslinking of water‐soluble polymers. Changing the composition and the extent of ether/acetal linkages altered the LCST based on hydrophilic/hydrophobic composition, which decreased the complexity of adjusting hydrogels' temperature sensitivity. PTHMMA‐comprising hydrogels were found to have non‐Fickian and super case ΙΙ transport characters. Moreover, the construction of shrunken PVA at high temperature was tailored by introducing PTHMMA into the network to permit a relaxed drug release of indomethacin (IND) at 37°C and pH 7.4. Finally, the tensile strength, the equilibrium water content, thermo‐sensitivity, and cell viability behaviors suggest that these materials can be tailored for potential applications as biomaterials.
Data‐driven generalized predictive control for car‐like mobile robots using interval type‐2 T‐S fuzzy neural network
Authors: Shui Yi , Zhao Tao , Dian Songyi , Hu Yi , Guo Rui , Li Shengchuan
Published: March 2021

In this paper, for the nonlinear influencing factors such as uncertainty and external disturbance existing in the actual driving process of the car‐like mobile robot (CLMR), a data‐driven generalized predictive control (GPC) method based on interval type‐2 T‐S fuzzy neural network (IT2TSFNN) is proposed for the trajectory tracking of CLMR. The controlled auto‐regressive integrated moving average (CARIMA) model of the mobile robot is established by analyzing data samples and using IT2TSFNN. Then, a generalized predictive controller is designed for the CARIMA model. Also, the global convergence of IT2TSFNN is verified by the Stone‐Weirstrass theorem. Unlike most previous results, the proposed method does not rely on the mathematical model of the mobile robot but only on the historical data of its operation. Finally, the simulation results show that the proposed method can avoid repeatedly debugging parameters, deal with the influence of uncertain factors, and obtain higher tracking accuracy.
A 30‐year review of copper pitting corrosion and pinhole leaks: Achievements and research gaps
Authors: Gibson John , Karney Bryan
Published: March 2021

Despite decades of research, the pitting of copper pipes is poorly understood. This article summarizes the key research findings from 1990 to the present and identifies research gaps. Several lines of evidence suggest that, for soft waters, additional alkalinity or maintaining a pH <8.5 may reduce copper pitting. Phosphate corrosion inhibitors, used to prevent lead corrosion, may also moderate copper pitting in low‐alkalinity waters. However, such inhibitors could also exacerbate pitting due to insufficient coverage or could increase biological growth. Biological processes are likely involved in pitting corrosion, and practices to reduce biological growth may be beneficial. The research gaps identified include a need for better benchmarking, the effects of chemical transients (e.g., chlorine burns) and of hydraulic transients (e.g., water hammer), and changing the residual disinfectant from chlorine to chloramine.

Article Impact Statement

Approximately 750,000 pinhole leaks are estimated to occur in the United States each year, but we do not really know why.
Under hypoxic conditions, MSCs affect the expression and methylation level of survival‐related genes in ALL independent of apoptosis pathways in vitro
Authors: Marofi Faroogh , Shomali Navid , Younus Laith A. , Hassanzadeh Ali , Vahedi Ghasem , Kuznetsova Mariya Yurievna , Solali Saeed , Gharibi Tohid , Hosseini Arezoo , Mohammed Rebar N. , Mohammadi Hamed , Tamjidifar Rozita , Firouzi‐Amandi Akram , Farshdousti Hagh Majid
Published: March 2021

Mesenchymal stem cells (MSCs) are one of the most prominent cells in the bone marrow. MSCs can affect acute lymphocytic leukemia (ALL) cells under hypoxic conditions. With this aim, we used MOLT‐4 cells as simulators of ALL cells cocultured with bone marrow mesenchymal stem cells (BMMSCs) under hypoxic conditions in vitro. Then, mRNA and protein expression of the MAT2A, PDK1, and HK2 genes were evaluated by real‐time PCR and Western blot which was also followed by apoptosis measurement by a flow‐cytometric method. Next, the methylation status of the target genes was investigated by MS‐qPCR. Additionally, candidate gene expressions were examined after treatment with rapamycin using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. We found that the mRNA expression of the candidate genes was augmented under the hypoxic condition in which MAT2A was upregulated in cocultured cells compared to MOLT‐4, while HK2 and PDK1 were downregulated. Moreover, we found an association between gene expression and promoter methylation levels of target genes. Besides, expressions of the candidate genes were decreased, while their methylation levels were promoted following treatment with rapamycin. Our results suggest an important role for the BMMSC in regulating the methylation of genes involved in cell survival in hypoxia conditions; however, we found no evidence to prove the MSCs' effect on directing malignant lymphoblastic cells to apoptosis.
Zeichnest du noch oder modellierst du schon?
Authors: Breinig Werner , Bard Madeline , Gonzalez‐Hernandez Abril , Irngartinger Andreas , Rahm Tobias , Siegert Stephan
Published: March 2021

Planungsbeschleunigung, Kosten‐ und Terminsicherheit sowie Transparenz dominieren inzwischen als Projektziele die Planung und Realisierung von Verkehrsinfrastrukturprojekten. Konventionelle Methoden stoßen hier regelmäßig an ihre Grenzen. Deshalb werden neue, digitale Methoden benötigt, um die genannten Ziele zu erreichen. Die Digitalisierung der Planung, der baulichen Realisierung, aber auch des Betriebs bietet dazu eine große Chance. Ein wesentlicher Aspekt dieser Digitalisierung wird durch die BIM‐Methode adressiert, die u. a. althergebrachte Strukturen hinterfragt. Die DEGES unterstützt aktiv diesen Transformationsprozess durch Wissensteilung mit Dritten, aber auch mit der Implementierung von BIM in Projekten sowie im Unternehmen. Die Projektmanagementgesellschaft DEGES verfolgt dabei den Ansatz der Kategorisierung nach konkreten Handlungsfeldern, zu denen u. a. eine eigene Lernplattform zur BIM‐Kompetenzvermittlung entwickelt wurde. Im Aufsatz werden nach einer eingehenden Einleitung diese Handlungsfelder vorgestellt und so ein Einblick in die BIM‐Maßnahmen bei der DEGES gewährt. Dabei wird immer wieder auf die kulturellen Herausforderungen eingegangen, denn die Digitalisierung verändert nicht nur die Arbeitsmethoden, sondern auch die Form der Zusammenarbeit im Projektteam.
Synthesis of novel oligomeric anionic alkyl glycosides using laccase/TEMPO oxidation and cyclodextrin glucanotransferase (CGTase)‐catalyzed transglycosylation
Authors: Ngo Ngoc T. N. , Linares‐Pastén Javier A. , Grey Carl , Adlercreutz Patrick
Published: March 2021

Modification of alkyl glycosides, to alter their properties and widen the scope of potential applications, is of considerable interest. Here, we report the synthesis of new anionic alkyl glycosides with long carbohydrate chains, using two different approaches: laccase/2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) oxidation of a long‐carbohydrate‐chain alkyl glycoside and cyclodextrin glucanotransferase (CGTase)‐catalyzed elongation of anionic alkyl glycosides. The laccase/TEMPO oxidation of dodecyl β‐
d‐maltooctaoside proceeded efficiently with the formation of aldehyde and acid products. However, depolymerization occurred to a large extent, limiting the product yield and purity. On the other hand, CGTase‐catalyzed coupling/disproportionation reactions with α‐cyclodextrin and dodecyl β‐
d‐maltoside diuronic acid (DDM‐2COOH) or octyl β‐
d‐glucuronic acid (OG‐COOH) as substrates gave high conversions, especially when the CGTase Toruzyme was used. It was found that pH had a strong influence on both the enzyme activity and the acceptor specificity. With non‐ionic substrates (dodecyl β‐
d‐maltoside and octyl β‐
d‐glucoside), Toruzyme exhibited high catalytic activity at pH 5–6, but for the acidic substrates (DDM‐2COOH and OG‐COOH) the activity was highest at pH 4. This is most likely due to the enzyme favoring the protonated forms of DDM‐2COOH and OG‐COOH, which exist at lower pH (pKa about 3).
A review of new adsorbents for separation of BTEX biomarkers
Authors: Bahrami Mohammadreza , Pirmohammadi Zahra , Bahrami Abdulrahman
Published: March 2021

The biomarker analysis of benzene, toluene, ethylbenzene and xylene (BTEXs) in biological samples is the primary technique for evaluating these compounds in occupational and environmental exposures. The BTEX biomarkers are widely used to study the BTEX distribution in the environment and workplaces. Liquid–liquid extraction and solid‐phase liquid extraction are among the most commonly used conventional methods to analyze biological indices of BTEXs. New methods have been proposed to analyze BTEX biomarkers using novel adsorbents such as sol–gel composite nanotubes, molecularly imprinted polymers and metal–organic frameworks, which are based on the application of needle trap devices, microextraction by packed sorbent, and solid‐phase microextraction techniques. This paper provides an overview of new methods since 2015 regarding applying microextraction methods based on new adsorbents and analyzing BTEX biomarker compounds for occupational and environmental exposures. The results were compared with the liquid‐phase microextraction methods recommended for urinary BTEX biomarkers.
Nitidine chloride suppresses epithelial‐mesenchymal transition and stem cell‐like properties in glioblastoma by regulating JAK2/STAT3 signaling
Authors: Jia Mingbo , Wang Ying , Guo Yingxue , Yu Pengyue , Sun Ying , Song Yanke , Zhao Liyan
Published: March 2021

Glioblastoma is the most aggressive and common intracranial malignant tumor, and the prognosis is still poor after various treatments. Based on the poor prognosis of glioma, new drugs that suppress the rapid progression and aggressive growth of glioma are urgently needed. It has been reported that nitidine chloride (NC) can inhibit tumor growth and epithelial‐mesenchymal transition (EMT), and EMT is associated with cancer stem cell properties. The present study aimed to investigate the inhibitory effect of NC on the EMT process and stem cell‐like properties in glioma cells. The results showed that the migration and invasion abilities in U87 and LN18 glioma cells were significantly increased after the induction of EMT and these effects were inhibited by NC in a concentration‐dependent manner. NC treatment decreased the expression of EMT markers in glioma cells and self‐renewal capacity of glioma stem‐like cells. We demonstrated that these effects of NC were achieved via JAK2/STAT3 signaling. Taken together, these results indicate that NC inhibits the EMT process and glioma stem‐like properties via JAK2/STAT3 signaling pathway, suggesting that NC may be a potential anti‐glioma drug.
Phase I study of ADI‐PEG20 plus low‐dose cytarabine for the treatment of acute myeloid leukemia
Authors: Tsai Hui‐Jen , Hsiao Hui‐Hua , Hsu Ya‐Ting , Liu Yi‐Chang , Kao Hsiao‐Wen , Liu Ta‐Chih , Cho Shih‐Feng , Feng Xiaoxing , Johnston Amanda , Bomalaski John S. , Kuo Ming‐Chung , Chen Tsai‐Yun
Published: March 2021

Most acute myeloid leukemia (AML) cells are argininosuccinate synthetase‐deficient. Pegylated arginine deiminase (ADI‐PEG20) monotherapy depletes circulating arginine, thereby selectively inducing tumor cell death. ADI‐PEG20 was shown to induce complete responses in ~10% of relapsed/refractory or poor‐risk AML patients. We conducted a phase I, dose‐escalation study combining ADI‐PEG20 and low‐dose cytarabine (LDC) in AML patients. Patients received 20 mg LDC subcutaneously twice daily for 10 days every 28 days and ADI‐PEG20 at 18 or 36 mg/m2 (dose levels 1 and 2) intramuscularly weekly. An expansion cohort for the maximal tolerated dose of ADI‐PEG20 was planned to further estimate the toxicity and preliminary response of this regimen. The primary endpoints were safety and tolerability. The secondary endpoints were time on treatment, overall survival (OS), overall response rate (ORR), and biomarkers (pharmacodynamics and immunogenicity detection). Twenty‐three patients were included in the study, and seventeen patients were in the expansion cohort (dose level 2). No patients developed dose‐limiting toxicities. The most common grade III/IV toxicities were thrombocytopenia (61%), anemia (52%), and neutropenia (30%). One had an allergic reaction to ADI‐PEG20. The ORR in 18 evaluable patients was 44.4%, with a median OS of 8.0 (4.5‐not reached) months. In seven treatment‐naïve patients, the ORR was 71.4% and the complete remission rate was 57.1%. The ADI‐PEG20 and LDC combination was well‐tolerated and resulted in an encouraging ORR. Further combination studies are warranted. (This trial was registered in ClinicalTrials.gov as a Ph1 Study of ADI‐PEG20 Plus Low‐Dose Cytarabine in Older Patients With AML, NCT02875093).
Covalent Organic Frameworks toward Diverse Photocatalytic Aerobic Oxidations
Authors: Liu Shuyang , Tian Miao , Bu Xiubin , Tian Hua , Yang Xiaobo
Published: March 2021

Photoactive two‐dimensional covalent organic frameworks (2D‐COFs) have become promising heterogenous photocatalysts in visible‐light‐driven organic transformations. Herein, a visible‐light‐driven selective aerobic oxidation of various small organic molecules by using 2D‐COFs as the photocatalyst was developed. In this protocol, due to the remarkable photocatalytic capability of hydrazone‐based 2D‐COF‐1 on molecular oxygen activation, a wide range of amides, quinolones, heterocyclic compounds, and sulfoxides were obtained with high efficiency and excellent functional group tolerance under very mild reaction conditions. Furthermore, benefiting from the inherent advantage of heterogenous photocatalysis, prominent sustainability and easy photocatalyst recyclability, a drug molecule (modafinil) and an oxidized mustard gas simulant (2‐chloroethyl ethyl sulfoxide) were selectively and easily obtained in scale‐up reactions. Mechanistic investigations were conducted using radical quenching experiments and in situ ESR spectroscopy, all corroborating the proposed role of 2D‐COF‐1 in photocatalytic cycle.
Tailored Mobility in a Zeolite Imidazolate Framework (ZIF) Antibody Conjugate**
Authors: Chapartegui‐Arias Ander , Raysyan Anna , Belenguer Ana M. , Jaeger Carsten , Tchipilov Teodor , Prinz Carsten , Abad Carlos , Beyer Sebastian , Schneider Rudolf J. , Emmerling Franziska
Published: March 2021

Zeolitic imidazolate framework (ZIF) hybrid fluorescent nanoparticles and ZIF antibody conjugates have been synthesized, characterized, and employed in lateral‐flow immunoassay (LFIA). The bright fluorescence of the conjugates and the possibility to tailor their mobility gives a huge potential for diagnostic assays. An enzyme‐linked immunosorbent assay (ELISA) with horseradish peroxidase (HRP) as label, proved the integrity, stability, and dispersibility of the antibody conjugates, LC‐MS/MS provided evidence that a covalent link was established between these metal‐organic frameworks and lysine residues in IgG antibodies.
Experimentelle Untersuchungen zum Tropfenmitriss im Feedeinleitbereich von Destillationskolonnen
Authors: Fasel Henrik , Darvishsefat Novin , Riese Julia , Grünewald Marcus
Published: March 2021

Im Rahmen dieses Beitrags werden experimentelle Untersuchungen zur Tropfenabscheidung im Einleitbereich eines Stoffaustauschapparates für zweiphasige Strömungen vorgestellt. Dafür wurde in einem Versuchsstand im Pilotmaßstab der qualitative Tropfenmitriss für unterschiedliche Tropfenabscheider eines Stoffaustauschapparates vermessen. Die daraus resultierenden Ergebnisse werden in diesem Beitrag hinsichtlich ihrer Aussagekraft zur Vermeidung von Tropfenmitriss diskutiert und bewertet. Darüber hinaus wird ein kurzer Ausblick über simulative Arbeiten zur Bestimmung des Tropfenmitriss gegeben.
Experimental methods in chemical engineering: Density functional theory
Authors: Al‐Mahayni Hasan , Wang Xiao , Harvey Jean‐Philippe , Patience Gregory S. , Seifitokaldani Ali
Published: March 2021

Density functional theory (DFT) computations apply to physics, chemistry, material science, and engineering. In chemical engineering, DFT identifies material structure and properties, and mechanisms for phenomena such as chemical reaction and phase transformation that are otherwise impossible to measure experimentally. Even though its practical application dates back only a decade or two, it is already a standard tool for materials modelling. Many textbooks and articles describe the theoretical basis of DFT, but it remains difficult for researchers to autonomously learn the steps to accurately calculate system properties. Here, we first explain the foundations of DFT in a way accessible to chemical engineers with little background in quantum mechanics or solid‐state physics. Then, we introduce the basics of the computations and, for most of the rest of the article, we show how to derive physical characteristics of interest to chemical engineers: elastic, thermodynamic, and surface properties, electronic structure, and surface and chemical reaction energy. Finally, we highlight some limitations of DFT; since these calculations are approximations to the Schrödinger equation, their accuracy relies on choosing adequate exchange‐correlation functions and basis sets. Since 1991, the number of articles WoS has indexed related to DFT has increased quadratically with respect to time and now numbers 15 000. A bibliometric analysis of the top 10 000 cited articles in 2018 and 2019 classifies them into four clusters: adsorption, graphene, and nanoparticles; ab initio molecular dynamics and crystal structure; electronic structure and optical properties; and total energy calculations and wave basis sets.
Generalization of the integral and differential method for analysis of rate data by means of the fractional calculus
Authors: Ströher Gylles Ricardo , Ströher Gisely Luzia
Published: March 2021

The kinetic study of chemical reactions is usually carried out by means of analysis of experimental rate data obtained during the evolution of a reaction in a batch reactor. The methods for analysis of rate data obtained in a batch reactor include the classical integral methods (CIM) and classical differential methods (CDM), which use temporal derivatives of the unit‐order concentration, dCA/dt, in the mass balance equation. The present study proposes these two methods of analysis in a generalized formulation that makes use of non‐integer order temporal derivatives, dαCA/dtα, 0<α ≤ 1, called generalized integral method (GIM) and generalized differential method (GDM) in the present work. The solutions of the fractional ordinary differential equations (FODE) of GIM are presented using the Laplace transform technique and numerical fractional derivative evaluation methods for GDM application. The proposed generalized methods allow for the determination of the order and the specific reaction rate in the same way as the classical methods, that is, of integer order (α = 1); however, generalized methods have the additional advantage of determining the fractional order of the temporal derivative.
Synthesis, Characterization, and in vivo Distribution of Intracellular Delivered Macrolide Short‐Chain Fatty Acid Derivatives
Authors: Straß Simon , Schwamborn Anna , Keppler Manuel , Cloos Natascha , Guezguez Jamil , Guse Jan‐Hinrich , Burnet Michael , Laufer Stefan
Published: March 2021

Short‐chain fatty acids (SCFAs) have a range of effects in metabolism and immune regulation. We have observed that delivery of SCFAs to lysosomes has potent immune regulatory effects, possibly as a surrogate signal for the presence of anaerobic organisms. To better understand the pharmacology of lysosomal SCFA donors, we investigated the distribution and metabolism of propionate and butyrate donors. Each analog (1 a and 2 a) can donate three SCFA equivalents via ester hydrolysis through six intermediate metabolites. The compounds are stabilized by low pH, and stability in cells is usually higher than in medium, but is cell‐type specific. Butyrate derivatives were found to be more stable than propionates. Tri‐esters were more stable than di‐ or mono‐esters. The donors were surprisingly stable in vivo, and hydrolysis of each position was organ specific. Jejunum and liver caused rapid loss of 4’’ esters. The gut metabolite pattern by i. v. differed from that of p.o. application, suggesting luminal and apical enzyme effects in the gut epithelium. Central organs could de‐esterify the 11‐position. Levels in lung relative to other organs were higher by p.o. than via i. v., suggesting that delivery route can influence the observed pharmacology and that gut metabolites distribute differently. The donors were largely eliminated by 24 h, following near linear decline in organs. The observed levels and distribution were found to be consistent with pharmacodynamic effects, particularly in the gut.
Application of enhancer of zeste homolog 2 immunocytochemistry to bile cytology
Authors: Tone Kiyoshi , Ohno Sachiyo , Honda Masatake , Notsu Akifumi , Sasaki Keiko , Sugino Takashi
Published: March 2021

BACKGROUND

Bile cytology has low diagnostic sensitivity and requires ancillary techniques. This study assessed the utility of enhancer of zeste homolog 2 (EZH2) immunocytochemistry (ICC) in bile cytology.

METHODS

A total of 141 bile cytology specimens from 141 patients were evaluated retrospectively. Papanicolaou‐stained slides were immunostained with an antibody to EZH2. After calculation of the EZH2 labeling index (LI), the cutoff value was determined via receiver operating characteristic curve analysis. Cytological performance with and without EZH2 ICC was evaluated with reference to the final diagnosis.

RESULTS

The area under the curve for the EZH2 LI was 0.955, and the cutoff value for identifying benign bile samples versus malignant ones was 24.0%. The sensitivity and specificity values for malignancy were 53.4% and 100% for routine cytology only, 89.0% and 95.7% for EZH2 ICC only, and 89.8% and 95.7% for a combination of routine cytology and EZH2 ICC. The sensitivities of EZH2 ICC only and a combination of routine cytology and EZH2 ICC were significantly improved in comparison with routine cytology only (P < .001). EZH2 ICC alone had a sensitivity of 68.0% and a specificity of 85.7% in bile samples with atypical cytology, a sensitivity of 87.0% in samples that were suspicious for malignancy, and a sensitivity of 85.7% and a specificity of 100% in samples that were negative for malignancy.

CONCLUSIONS

EZH2 ICC improved the diagnostic sensitivity for pancreatobiliary adenocarcinoma in bile cytology. This method is particularly meaningful in samples of indeterminate cytology and may be useful as an initial assessment to ensure that no cancer cells are missed.
The Lbx1 lineage differentially contributes to inhibitory cell types of the dorsal cochlear nucleus, a cerebellum‐like structure, and the cerebellum
Authors: Schinzel Friedrich , Seyfer Hannah , Ebbers Lena , Nothwang Hans Gerd
Published: March 2021

The dorsal cochlear nucleus (DCN) is a mammalian‐specific nucleus of the auditory system. Anatomically, it is classified as a cerebellum‐like structure. These structures are proposed to share genetic programs with the cerebellum. Previous analyses demonstrated that inhibitory serial sister cell types (SCTs) of the DCN and cerebellum are derived from the pancreatic transcription factor 1a (Ptf1a) lineage. Postmitotic neurons of the Ptf1a lineage often express the transcription factor Ladybird homeobox protein homolog 1 (Lbx1) which is involved in neuronal cell fate determination. Lbx1 is therefore an attractive candidate for a further component of the genetic program shared between the DCN and cerebellum. Here, we used cell‐type specific marker analysis in combination with an Lbx1 reporter mouse line to analyze in both tissues which cell types of the Ptf1a lineage express Lbx1. In the DCN, stellate cells and Purkinje‐like cartwheel cells were part of the Lbx1 lineage and Golgi cells were not, as determined by cell counts. In contrast, in the cerebellum, stellate cells and Golgi cells were part of the Lbx1 lineage and Purkinje cells were not. Hence, two out of three phenotypically similar cell types differed with respect to their Lbx1 expression. Our study demonstrates that Lbx1 is differentially recruited to the developmental genetic program of inhibitory neurons both within a given tissue and between the DCN and cerebellum. The differential expression of Lbx1 within the DCN and the cerebellum might contribute to the genetic individuation of the inhibitory SCTs to adapt to circuit specific tasks.
Genetic polymorphisms of metabolic enzyme genes associated with leukocyte mitochondrial DNA copy number in PAHs exposure workers
Authors: Li Xinling , Duan Xiaoran , Zhang Hui , Ding Mingcui , Wang Yanbin , Yang Yongli , Yao Wu , Zhou Xiaoshan , Wang Wei
Published: March 2021

Background

Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure workers has not been fully evaluated.

Aim

The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure.

Methods and Results

We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real‐time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1‐OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs‐exposure [β (95% CI) = −0.420 (−0.469, −0.372), p < .001], male [β (95% CI) = −0.058 (−0.103, −0.012), p = .013], and AA genotype for GSTP1 rs1695 [β (95% CI) = −0.051 (−0.095, −0.008), p = .020].

Conclusion

The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs.
The Pharmacokinetics of Triheptanoin and Its Metabolites in Healthy Subjects and Patients With Long‐Chain Fatty Acid Oxidation Disorders
Authors: Lee Sun Ku , Gupta Manju , Shi Jack , McKeever Kathleen
Published: March 2021

Long‐chain fatty acid oxidation disorders (LC‐FAODs) are a group of life‐threatening autosomal recessive disorders caused by defects in nuclear genes encoding mitochondrial enzymes involved in the conversion of dietary long‐chain fatty acids into energy. Triheptanoin is an odd‐carbon, medium‐chain triglyceride consisting of 3 fatty acids with 7 carbons each on a glycerol backbone developed to treat adult and pediatric patients with LC‐FAODs. The pharmacokinetics of triheptanoin and circulating metabolites were explored in healthy subjects and patients with LC‐FAODs using noncompartmental analyses. Systemic exposure to triheptanoin following an oral administration was negligible, as triheptanoin is extensively hydrolyzed to glycerol and heptanoate in the gastrointestinal tract. Multiple peaks for triheptanoin metabolites were observed in the plasma following oral administration of triheptanoin, generally coinciding with the time that meals were served. Heptanoate, the pharmacologically active metabolite of triheptanoin supplementing energy sources in patients with LC‐FAODs, showed the greatest exposure among the metabolites of triheptanoin in human plasma following oral administration of triheptanoin. The exposure of heptanoate was approximately 10‐fold greater than that of beta‐hydroxypentoate, a downstream metabolite of heptanoate. Exposure to triheptanoin metabolites appeared to increase following multiple doses as compared with the single dose, and with the increase in triheptanoin dose levels.
EPA: The effective pipeline architecture for CNN accelerator with high performance and computing efficiency based on FPGA
Authors: Zhang Junjie , Yin Qiao , Hu Weicheng , Li Yunfeng , Li Hu , Ye Nan , Cao Bingyao
Published: March 2021

Thanks to the great developments of the latest Field Programmable Gate Array (FPGA), the performance bottleneck of Deep Learning hardware accelerators has been converted to computing ability. In this paper, a novel FPGA‐based Convolutional Neural Network (CNN) Accelerator architecture, named the Effective Pipeline Architecture (EPA) is proposed to optimize the resource usage for the implementation of the CNN calculation. As the unique storage strategies, which contain many creative designing details, are adopted and optimized for different CNN models and layers, great DSP computing efficiency can be achieved in the fine‐grained pipeline. Moreover, compared with the traditional architectures, through the kernel combination and data scheduling, twice throughput for the general matrix multiplication is realized in a great many parallel DSP48E resources. As a result, the realization of Yolov2‐Tiny achieves 873 Giga Operations Per Second (GOPS) by 902 DSPs with 67 Frames Per Second (FPS), and the computing efficiency in most layers can even reach more than 90%, which improves the calculation performance and efficiency comparing with the previous designs, and is significant to meet the increasing computing requirement.