bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractMost 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

AbstractPhotoactive 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

AbstractZeolitic 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

AbstractIm 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

AbstractDensity 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

AbstractThe 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

AbstractShort‐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

BACKGROUNDBile 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.METHODSA 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.RESULTSThe 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.CONCLUSIONSEZH2 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

AbstractThe 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

AbstractBackgroundPolycyclic 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.AimThe aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure.Methods and ResultsWe 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].ConclusionThe 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

AbstractLong‐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

AbstractThanks 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.
Explorative study on Lactobacillus species and their acid‐producing capacity and anti‐microbial activity in head and neck cancer patients
Authors: Rahne Matilda , Basic Amina , Almståhl Annica 
Published: March 2021

AbstractObjectiveTo determine acid‐producing capacity and anti‐microbial activity of Lactobacillus species collected pretreatment and post treatment in head and neck cancer patients.Material and MethodsLactobacillus isolates from 21 patients pretreatment and post treatment were identified using molecular methods. The patients' stimulated salivary secretion was determined pretreatment, and 6 and 12 months post treatment and caries lesions/new filled surfaces registered at 24 months post treatment. The acid‐producing capacity of the Lactobacillus isolate was analyzed using a colorimetric fermentation test in microtiter plates. The anti‐microbial activity of the isolates against Streptococcus mutans associated with caries, and against the mucosal pathogens Staphylococcus aureus, Candida albicans, and Enterococcus faecalis was analyzed by determining inhibitory zones on agar plates.ResultsThe most frequent species were L. paracasei (n = 21), L. casei/rhamnosus (n = 17) and L. fermentum (n = 10). Sixty‐seven percent of the patients harbored L. paracasei either at 6 or 12 months post radiotherapy. The corresponding figures for L. casei/rhamnosus and L. fermentum were 62% and 33%. L. paracasei strains showed the best acid‐producing capacity and L. fermentum strains the lowest. Strong acid‐producing capacity was most common among isolates collected at 6 months post treatment. Seventy‐two percent of the strains showed an anti‐microbial activity against S. mutans, one strain against S. aureus and none against C. albicans or E. faecalis.ConclusionThe most frequent species isolated from head and neck cancer patients both pretreatment and post treatment were L. paracasei, L. casei/rhamnosus, and L. fermentum. L. paracasei showed the best acid‐producing capacity and the highest proportion with anti‐microbial activity against S. mutans.
Systematic evaluation of a panel of 30 synthetic cannabinoid receptor agonists structurally related to MMB‐4en‐PICA, MDMB‐4en‐PINACA, ADB‐4en‐PINACA, and MMB‐4CN‐BUTINACA using a combination of binding and different CB1 receptor activation assays: Part I—Synthesis, analytical characterization, and binding affinity for human CB1 receptors
Authors: Pike Edward , Grafinger Katharina Elisabeth , Cannaert Annelies , Ametovski Adam , Luo Jia Lin , Sparkes Eric , Cairns Elizabeth A. , Ellison Ross , Gerona Roy , Stove Christophe P. , Auwärter Volker , Banister Samuel D. 
Published: March 2021

AbstractSynthetic cannabinoid receptor agonists (SCRAs) are one of the largest and most structurally diverse classes of new psychoactive substances (NPS). Despite this, pharmacological data are often lacking following the identification of a new SCRA in drug markets. In this first of a three‐part series, we describe the synthesis, analytical characterization, and binding affinity of a proactively generated, systematic library of 30 indole, indazole, and 7‐azaindole SCRAs related to MMB‐4en‐PICA, MDMB‐4en‐PINACA, ADB‐4en‐PINACA, and MMB‐4CN‐BUTINACA featuring a 4‐pentenyl (4en‐P), butyl (B/BUT), or 4‐cyanobutyl (4CN‐B/BUT) tail and a methyl l‐valinate (MMB), methyl l‐tert‐leucinate (MDMB), methyl l‐phenylalaninate (MPP), l‐valinamide (AB), l‐tert‐leucinamide (ADB), l‐phenylalaninamide (APP), adamantyl (A), or cumyl head group. Competitive radioligand binding assays demonstrated that the indazole core conferred the highest CB1 binding affinity (Ki = 0.17–39 nM), followed by indole‐ (Ki = 0.95–160 nM) and then 7‐azaindole‐derived SCRAs (Ki = 5.4–271 nM). Variation of the head group had the greatest effect on binding, with tert‐leucine amides and methyl esters (Ki = 0.17–14 nM) generally showing the greatest affinities, followed by valine derivatives (Ki = 0.72–180 nM), and then phenylalanine derivatives (Ki = 2.5–271 nM). Adamantyl head groups (Ki = 8.8–59 nM) were suboptimal for binding, whereas the cumyl analogues consistently conferred high affinity (Ki = 0.62–36 nM). Finally, both butyl (Ki = 3.1–163 nM) and 4‐cyanobutyl (Ki = 5.5–44 nM) tail groups were less favorable for CB1 binding than their corresponding 4‐pentenyl counterparts (Ki = 0.72–25 nM).