bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Electrocatalytic Reduction of Oxygen to Hydroxyl Radicals via 3‐Electron Pathway with FeCo Alloy Encapsulated Carbon Aerogel for Fast and Complete Removing Pollutants
Authors: Xiao Fan , Wang Zining , Fan Jiaqi , Majima Tetsuro , Zhao Hongying , Zhao Guohua
Published: February 2021

We reported the selective electrochemical reduction of oxygen (O2) to hydroxyl radicals (.OH) via 3‐electron pathway with FeCo alloy encapsulated by carbon aerogel (FeCoC). The graphite shell with exposed ‐COOH is conducive to the 2‐electron reduction pathway for H2O2generation stepped by 1‐electron reduction towards to.OH. The electrocatalytic activity can be regulated by tuning the local electronic environment of carbon shell with the electrons coming from the inner FeCo alloy. The new strategy of.OH generation from electrocatalytic reduction O2overcomes the rate‐limiting step over electron transfer initiated by reduction‐/oxidation‐state cycle in Fenton process. Fast and complete removal of ciprofloxacin was achieved within 5 min in this proposed system, the apparent rate constant (kobs) was up to 1.44±0.04 min−1, which is comparable with the state‐of‐the‐art advanced oxidation processes. The degradation rate almost remains the same after 50 successive runs, suggesting the satisfactory stability for practical applications.
Thermal and pH Stabilities of i‐DNA: Confronting in vitro Experiments with Models and In‐Cell NMR Data
Authors: Cheng Mingpan , Qiu Dehui , Tamon Liezel , Ištvánková Eva , Víšková Pavlína , Amrane Samir , Guédin Aurore , Chen Jielin , Lacroix Laurent , Ju Huangxian , Trantírek Lukáš , Sahakyan Aleksandr B. , Zhou Jun , Mergny Jean‐Louis
Published: February 2021

Recent studies indicate that i‐DNA, a four‐stranded cytosine‐rich DNA also known as the i‐motif, is actually formed in vivo; however, a systematic study on sequence effects on stability has been missing. Herein, an unprecedented number of different sequences (271) bearing four runs of 3–6 cytosines with different spacer lengths has been tested. While i‐DNA stability is nearly independent on total spacer length, the central spacer plays a special role on stability. Stability also depends on the length of the C‐tracts at both acidic and neutral pHs. This study provides a global picture on i‐DNA stability thanks to the large size of the introduced data set; it reveals unexpected features and allows to conclude that determinants of i‐DNA stability do not mirror those of G‐quadruplexes. Our results illustrate the structural roles of loops and C‐tracts on i‐DNA stability, confirm its formation in cells, and allow establishing rules to predict its stability.
Catalytic Boration of Alkyl Halides with Borane without Hydrodehalogenation Enabled by Titanium Catalyst
Authors: Wang Xianjin , Cui Penglei , Xia Chungu , Wu Lipeng
Published: February 2021

An unprecedented and general titanium‐catalyzed boration of alkyl (pseudo)halides (alkyl‐X, X=I, Br, Cl, OMs) with borane (HBpin, HBcat) is reported. The use of titanium catalyst can successfully suppress the undesired hydrodehalogenation products that prevail using other transition‐metal catalysts. A series of synthetically useful alkyl boronate esters are readily obtained from various (primary, secondary, and tertiary) alkyl electrophiles, including unactivated alkyl chlorides, with tolerance of other reducing functional groups such as ester, alkene, and carbamate. Preliminary studies on the mechanism revealed a possible radical reaction pathway. Further extension of our strategy to aryl bromides is also demonstrated.
Application of data reconciliation and gross error detection techniques to enhance reliability and consistency of the blast furnace process data
Authors: Hazra Sujan , Abhale Prakash , Nag Samik , Mathew Sam , Narasimhan Shankar
Published: February 2021

Effective control of a blast furnace (BF) process requires accurate estimates of key process indicators (KPIs), namely, productivity, coke rate, direct reduction per cent, adiabatic flame temperature, bosh gas volume and top gas utilization. Some of these KPIs are obtained directly from the measurements, and some are derived by carrying out material and energy balances on measurements of different feeds, their compositions and temperatures. Due to errors in the measurements, the estimates of the KPIs can be inconsistent or misleading, which may result in misinterpretation of the current state of the BF process. Hence, it is necessary to reconcile the measurement data before these are used either for interpreting the current furnace state directly or as an input to other models. In the proposed methodology, data reconciliation and gross error detection techniques are used to improve the accuracy of the estimates of process variables and parameters, by ensuring that they satisfy process constraints such as elemental balances of iron, nitrogen, carbon, oxygen and hydrogen. Since the BF is a fed‐batch process, a customized version of these techniques has been developed and applied real time to an operating BF. The method is shown to be useful in deriving consistent estimates of the hot metal production rate, identifying gross errors in the online gas analyser and for estimating unmeasured parameters, such as top gas flow rate, its moisture concentration and calorific value which are useful for the purpose of stove heating in the downstream process.
The effect of microRNA‐330 replacement on inhibition of growth and migration in renal cancer cells
Authors: Liu Jun , Song Xin , Ren Zhongwei
Published: February 2021

This study was conducted to scrutinize microRNA‐330 (miR‐330) role in growth, migration, and the expression of metastatic genes in renal cell carcinoma (RCC) in vitro. Following transfection of the cells with miR‐330 mimic, cell proliferation using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, cell migration by wound healing assay, and apoptosis by flow cytometry were evaluated. Quantitative real‐time PCR was conducted to assess expression levels of matrix metalloproteinase 2 (MMP2), MMP9, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), Kirsten rat sarcoma virus (K‐Ras), cellular Myc (c‐Myc), and C‐X‐C chemokine receptor type 4 (CXCR‐4) as metastatic genes in the progression of RCC. Results showed that miR‐330 was downregulated in the Caki‐1 cells compared with HK‐2 cells (p < 0.001). Upregulation of miR‐330 obstructed in vitro expansion and migration, while it intensified apoptosis rate in the Caki‐1 cells. Moreover, it was found that miR‐330 transfection negatively modulated the expression of MMP2, MMP9, ADAMTS, K‐Ras, c‐Myc, and CXCR‐4 in the Caki‐1 cells. Our findings revealed that overexpression of miR‐330 might provide an auxiliary treatment approach for overcoming invasion, progression, and metastasis in patients with RCC by enhancing cell apoptosis.
Production of β‐carotene in Saccharomyces cerevisiae through altering yeast lipid metabolism
Authors: Zhao Yijin , Zhang Yueping , Nielsen Jens , Liu Zihe
Published: February 2021

Saccharomyces cerevisiae is a widely used cell factory for the production of fuels and chemicals. However, as a non‐oleaginous yeast, S. cerevisiae has a limited production capacity for lipophilic compounds, such as β‐carotene. To increase its accumulation of β‐carotene, we engineered different lipid metabolic pathways in a β‐carotene producing strain and investigated the relationship between lipid components and the accumulation of β‐carotene. We found that overexpression of sterol ester synthesis genes ARE1 and ARE2 increased β‐carotene yield by 1.5‐fold. Deletion of phosphatidate phosphatase (PAP) genes (PAH1, DPP1, and LPP1) also increased β‐carotene yield by twofold. Combining these two strategies resulted in a 2.4‐fold improvement in β‐carotene production compared with the starting strain. These results demonstrated that regulating lipid metabolism pathways is important for β‐carotene accumulation in S. cerevisiae, and may also shed insights to the accumulation of other lipophilic compounds in yeast.
A novel, rapid and simple UPLC–MS/MS method for quantification of favipiravir in human plasma: Application to a bioequivalence study
Authors: Rezk Mamdouh R. , Badr Kamal A. , Abdel‐Naby Naglaa S. , Ayyad Magy M.
Published: February 2021

A novel, simple and rapid UPLC–MS/MS method was developed and validated for determination of favipiravir (FAV) in human plasma. Lamivudine was used as an internal standard (IS). The Xevo TQD LC–MS/MS was operated under the multiple‐reaction monitoring mode using electrospray ionization. Precipitation with acetonitrile was used in sample preparation as it gives relatively cleaner plasma samples. The prepared samples were chromatographed using an Acquity UPLC® HSS C18 (100 × 2.1 mm, 1.8 μm) column. The mobile phase was composed of ammonium formate and methanol in a gradient mode that was pumped at a flow rate of 0.35 ml/min. The developed method was validated as per the FDA guidelines and linearity was in the range of 0.25–16 μg/ml for FAV. The intra‐ and inter‐day precision and accuracy results were within the acceptable limits. A run time of 4.5 min and a low quantification limit of FAV allowed the application of the developed method for the determination of FAV in a bioequivalence study in healthy human volunteers.
New genetic prognostic biomarkers in primary central nervous system lymphoma (PCNSL)
Authors: Gomes Candido Reis Diego , Levy Débora , Lage Luís Alberto de Pádua Covas , Culler Hebert Fabrício , Rocha Vanderson , Bydlowski Sérgio Paulo , Nogueira Zerbini Maria Cláudia , Pereira Juliana
Published: February 2021

Background

PCNSL is a rare extranodal NHL with poor prognosis. Tumorigenesis has been associated with hyperactivation of BCR downstream and NFkB pathways. We studied the prognosis of the relative expression profile of target genes of NFkB pathway (MYC, BCL2), the essential transcriptional regulator in hematopoiesis LMO2, the checkpoint regulation pathway MGMT, the transcription factor POU2F1, the immune checkpoint gene PDCD1, and the proto‐oncogene and transcriptional repressor gene BCL6 and its proteins in PCNSL.

Methods

This study is a retrospective cohort study; 35 immunocompetent PCNSL‐DLBCL patients had their gene expression (RT‐qPCR) normalized to internal control gene GUSB.

Results

Median patient age was 62 years, median OS was 42.6 months (95% CI: 26.6–58.6), PFS was 41 months (95% CI: 19.7–62.4), and DFS was 59.2 months (95% CI 31.9–86.6). A moderate correlation was found between the gene/protein expressions of MYC (kappa = 0.596, p = .022) and of BCL2 (kappa = 0.426, p = .042). Relative gene expression of MYC ≥ 0.201 (HR 6.117; p = .003) was associated with worse 5‐year OS. Relative gene expression of MYC ≥ 0.201 (HR 3.96; p = .016) and MGMT ≥ 0.335 (HR 3.749; p = .056) was associated with worse PFS. Age > 60 years and IELSG score moderate/high were also associated with worse prognosis.

Conclusions

Overexpression of MYC and overexpression of MGMT were prognostic markers associated with unfavorable clinical outcomes in PCNSL.
Junction plakoglobin regulates and destabilizes HIF2α to inhibit tumorigenesis of renal cell carcinoma
Authors: Chen Ke , Zeng Jin , Sun Yi , Ouyang Wei , Yu Gan , Zhou Hui , Zhang Yangjun , Yao Weimin , Xiao Wei , Hu Junhui , Xing Jinchun , Xiao Kefeng , Wu Lily , Chen Zhiqiang , Ye Zhangqun , Xu Hua
Published: February 2021

Background

Increased hypoxia‐inducible factor 2α (HIF2α) activation is a common event in clear cell renal cell carcinoma (ccRCC) progression. However, the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated. We conducted this study to access the potential link between junction plakoglobin (JUP) and HIF2α in ccRCC.

Methods

Affinity purification and mass spectrometry (AP‐MS) screening, glutathione‐s‐transferase (GST) pull‐down and co‐immunoprecipitation (Co‐IP) assays were performed to detect the interacting proteins of HIF2α. Quantitative PCR (qPCR) and Western blotting were used to detect the expression of JUP in human ccRCC samples. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), cycloheximide chase assays, and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α. Cell Counting Kit‐8 (CCK‐8) assays, colony formation assays, transwell assays, and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells.

Results

We identified JUP as a novel HIF2α‐binding partner and revealed an important role of JUP in recruiting von Hippel‐Lindau (VHL) and histone deacetylases 1/2 (HDAC1/2) to HIF2α to regulate its stability and transactivation. JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo. Importantly, the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes.

Conclusion

Taken together, these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.
A case of insulinoma diagnosed postpartum with hypoglycemic symptoms that were masked during pregnancy
Authors: Abe Tomoe , Takeda Yasutaka , Takiyama Takao , Sasaki Ayaka , Bessho Ryoichi , Sato Mao , Kitsunai Hiroya , Sakagami Hidemitsu , Abiko Atsuko , Imai Koji , Yuzawa Sayaka , Tanino Mishie , Takiyama Yumi
Published: February 2021

The diagnosis of insulinoma in perinatal women can be difficult, as hypoglycemic symptoms may be masked by pregnancy‐associated insulin resistance. In addition, when multiple insulinomas are observed, it is necessary to consider the possibility not only of MEN1, but also of insulinomatosis.
Into the Fray! A Beginner's Guide to Medicinal Chemistry
Authors: Veale Clinton G. L.
Published: February 2021

Modern medicinal chemistry is a complex, multidimensional discipline that operates at the interface of the chemical and biological sciences. The medicinal chemistry contribution to drug discovery is typically described in the context of the well‐recited linear progression of the drug discovery pipeline. However, compound optimization is idiosyncratic to each project, and clear definitions of hit and lead molecules and the subsequent progress along the pipeline becomes easily blurred. In addition, this description lacks insight into the entangled relationship between chemical and pharmacological properties, and thus provides limited guidance on how innovative medicinal chemistry strategies can be applied to solve optimization problems, regardless of the stage in the pipeline. Through discussion and illustrative examples, this article seeks to provide insights into the finesse of medicinal chemistry and the subtlety of balancing chemical properties pharmacology. In so doing, it aims to serve as an accessible and simple‐to‐digest guide for anyone who wishes to learn about the underlying principles of medicinal chemistry, in a context that has been decoupled from the pipeline description.
Use of a clinical trial screening tool to enhance patient accrual
Authors: St. Germain Diane C. , McCaskill‐Stevens Worta
Published: February 2021

Background

Clinical trial patient accrual continues to be challenging despite the identification of multiple physician, patient, and system barriers. Expanded collection of demographic data, including socioeconomic status (employment, income, education) and comorbidities, can enhance our understanding of the identified barriers, inform the development of interventions to overcome these barriers, and recognize their impact on treatment outcomes. A clinical trials screening tool was developed to collect expanded demographic data and barriers to trial enrollment; it has been implemented in the National Cancer Institute Clinical Oncology Research Program. The purpose of this article is to describe the development and implementation of the tool and to share information obtained during the first 43 months of its use.

Methods

There were 19,373 entries collected; 74% of those screened enrolled in a clinical trial. Demographic characteristics were compared between those screened and those enrolled. They varied significantly between the groups.

Results

Reasons for nonenrollment included ineligibility (50%), eligible but declined (47%), eligible but physician declined to offer participation (2%), and eligible but the study was suspended (1%). The most common reasons for ineligibility were failure to meet the protocol‐specific stage of cancer, the presence of comorbidities, and the symptom‐eligibility score was not met. The most common reason for eligible patients declining participation was that they had no desire to participate in research.

Conclusions

The tool provides valuable information about the characteristics of individuals who are screened and enrolled in National Cancer Institute–sponsored trials, as well as about barriers to enrollment in trials. The data also inform protocol development and interventions at the patient, provider, and institutional level.
Photopharmacology on Acetylcholinesterase: Novel Photoswitchable Inhibitors with Improved Pharmacological Profiles
Authors: Scheiner Matthias , Sink Alexandra , Spatz Philipp , Endres Erik , Decker Michael
Published: February 2021

Considerable effort has previously been invested in a light‐controlled inhibition of the enzyme acetylcholinesterase (AChE). We found that a novel azobenzene‐based bistacrine AChE inhibitor switched faster than the known dithienylethene based bistacrine and inverted the photo‐controlled interactions of the photoisomers compared to its dithienylethene congener. Furthermore, we have optimized a previously described light‐controlled tacrine‐based AChE inhibitor. Isomerization upon irradiation with UV light of the novel inhibitor was observed in aqueous medium and showed no fatigue over several cycles. The cis‐enriched form showed an 8.4‐fold higher inhibition of hAChE compared with its trans‐enriched form and was about 30‐fold more active than the reference compound tacrine with a single‐digit nanomolar inhibition. We went beyond proof‐of‐concept to discover photoswitchable AChE inhibitors with pharmacologically desirable nanomolar inhibition, “cis‐on” effect, and pronounces differences between the photoisomers.
Sustainable Access to 5‐Amino‐Oxazoles and Thiazoles via Calcium‐Catalyzed Elimination‐Cyclization with Isocyanides
Authors: Basson Ashley J. , McLaughlin Mark G.
Published: February 2021

Herein, we report a sustainable, modular, rapid and high‐yielding transformation to afford densely functionalized 5‐aminooxazoles and thiazoles. The reaction is tolerant to a wide range of functional groups and is typically complete in under 30 min. Furthermore, the described transformation is inherently green in relation to the catalyst and solvent choice as well as producing environmentally benign alcoholic by‐products.
Partner with housing to provide accommodations for students
Authors: Hope Joan
Published: February 2021

When students need housing accommodations, a strong partnership between housing and disability services can help ensure the best solutions are found. At American University, officials from the two departments working together to meet students’ needs have streamlined processes and enhanced students’ experiences.
Campus recreation websites lack inclusive language, imagery
Authors: Sutton Halley
Published: February 2021

The majority of college recreation program websites had low representation of, and minimal information for, students with disabilities, according to a study published in the Journal of Kinesiology and Wellness.
A “Solvent‐Free” Crystal Structure of [Fe{N(SiMe3)2}3] – Synthesis, Structure and Properties
Authors: Indris Sylvio , Knapp Michael , Schwarz Björn , Eichhöfer Andreas
Published: February 2021

For the synthesis of the ferric bis(trimethylsilyl)amido complex [Fe{N(SiMe3)2}3] literature gives differing synthetic protocols based on crystallization from solution. In this report we present a ‘solvent‐free’ structural phase of [Fe{N(SiMe3)2}3] which was isolated by sublimation of the product obtained from the reaction of 2 eq FeCl3 with 3 eq LiN(SiMe3)2 in benzene. It could be characterized by single crystal as well as powder XRD and elemental analysis. However, 57Fe Mößbauer spectroscopy suggests a contamination of the main product with an Fe(II) species. Also, a part of the solid reaction byproducts from the reactions in solution were identified by powder XRD and 7Li MAS NMR which indicate distinct redox side reactions between oxidizing FeCl3 and reducing LiN(SiMe3)2, a fact which rationalizes the lower than expected yields and the observation of an Fe(II) impurity compound. AC magnetic measurements of [Fe{N(SiMe3)2}3] have been performed in an extended frequency range up to 104 s−1, allowing for a more precise evaluation of the magnetic relaxation parameters when compared to previously published measurements.
Planar and Rigid Pyrazine‐Based TADF Emitter for Deep Blue Bright Organic Light‐Emitting Diodes
Authors: Rajamalli Pachaiyappan , Chen Dongyang , Suresh Subeesh Madayanad , Tsuchiya Youichi , Adachi Chihaya , Zysman‐Colman Eli
Published: February 2021

Two blue thermally activated delayed fluorescence (TADF) emitters bearing di‐tert‐butyl carbazoles as the electron donor groups and pyrazine (DTCz‐Pz) or dipyrazine (DTCz‐Pz) as the electron acceptor are presented. The DFT calculations predict DTCz‐Pz and DTCz‐DPz to possess high S1 energies (3.19 eV and 3.08 eV, respectively), and relatively large ΔEST values (0.52 eV and 0.56 eV, respectively). The closely layered intermediate triplet states between S1 and T1, predicted by DFT calculations, are expected to facilitate the reverse intersystem crossing (RISC) and improve spin‐vibronic coupling efficiency between the excited states, even the relatively larger ΔESTs. The ΔESTs for DTCz‐Pz and DTCz‐DPz are 0.27 eV and 0.38 eV, and both molecules show high photoluminescence quantum yields (65 %, and 70 %, respectively). The decay lifetimes show temperature dependence in a PPT host, which is consistent with the fact that both molecules are TADF emitters in PPT. The OLEDs based on DTCz‐Pz exhibit deep blue emission with λEL of 460 nm and CIE of (0.15, 0.16). The maximum external quantum efficiency (EQEmax) reaches 11.6 %, with a maximum luminance (Lmax) of up to 6892 cd m−2, while the device based on DTCz‐DPz exhibits sky blue emission with λEL of 484 nm and CIE of (0.15, 0.30), an EQEmax of 7.2 %, and Lmax of 8802 cd m−2.
Highly Oriented Nitrogen‐doped Carbon Nanotube Integrated Bimetallic Cobalt Copper Organic Framework for Non‐enzymatic Electrochemical Glucose and Hydrogen Peroxide Sensor
Authors: Kim So eun , Muthurasu Alagan
Published: February 2021

The hierarchical three‐dimensional nitrogen‐doped carbon nanotube anchored bimetallic cobalt copper organic framework (NCNT MOF CoCu) is successfully synthesized by the direct growth approach using the high‐temperature carbonization of bimetallic cobalt copper organic framework (MOF CoCu‐500). The as‐prepared NCNT MOF CoCu nanostructure possesses high‐level activity for both glucose and hydrogen peroxide (H2O2) sensing molecules. The cyclic voltammetry (CV) and chronoamperometry (CA) studies demonstrate excellent electrocatalytic performance for the oxidation of glucose with a linear range of 0.05 to 2.5 mM, high sensitivity of 1027 μA mM−1cm−2, and the lowest detection limit of 0.15 μM. Similarly, the NCNT MOF CoCu nanostructure showed significantly higher H2O2 activity with a linear range of 0.05 to 3.5 mM, high sensitivity of 639.5 μA mM−1cm−2, and the lowest detection limit of 0.206 μM. Thanks to its special hierarchical nanoarchitecture, homogeneous nitrogen‐doped carbon nanotubes, and highly graphitized carbon, which may be increased the synergistic effect between bimetallic CoCu and NCNT in the organic framework. The potentially effective fabricated sensor was also used as a suitable probe for the detection of glucose and H2O2 in the analysis of the real samples.
Mixed Silane‐based Self‐assembled Monolayers Deposited on Fluorine Doped Tin Oxide as Model System for Development of Biosensors for Toxin Detection
Authors: Gabriunaite Inga , Valiūnienė Aušra , Sabirovas Tomas , Valincius Gintaras
Published: February 2021

In this work mixed hybrid phospholipid bilayers (mhBLM) were deposited on fluorine doped tin oxide (FTO) films. Two component silane‐based self‐assembled monolayers (SAMs) formed on FTO surface trigger vesicle fusion and formation of mhBLMs which are stable, can be easily regenerated, and therefore, used for multiple experiments. We found that certain chemical and physical conditions under which mixed SAMs are fabricated translate into functional properties of mhBLMs. In all cases we observed interaction of melittin with mhBLMs demonstrating biological relevance of these biomimetic surface constructs and their possible application in biosensors for toxin detection.
Review predictions about the future of higher education
Authors: Dennis Marguerite J.
Published: February 2021

Higher education administrators expect constant change. Being aware of trends can help you prepare to address them effectively.
Leverage software accessibility features for ADA‐compliant communication
Authors: Taylor Z. W.
Published: February 2021

Communication technologies have made significant advances over the past several decades, including assistive technologies created to help people with disabilities access digital content. In recent years, software developers have updated many common content‐creation software programs to include accessibility options. However, these features are available across several popular software programs only if updates are installed or if users know where to find them, and many of them are tucked away behind several layers of menus. Of the most widely used, affordable, and powerful tools available to content creators working for higher education institutions, the Microsoft Office suite and Adobe Acrobat Pro have the capacity to increase the accessibility of digital content and can help you comply with the Americans with Disabilities Act.
Evaluation of Published Bioconcentration Factor (BCF) and Bioaccumulation Factor (BAF) Data for Per- and Polyfluoroalkyl Substances Across Aquatic Species
Authors: Burkhard Lawrence P.
Published: February 2021

Per- and polyfluoroalkyl substances (PFAS) are a group of man-made chemicals of concern across the globe, and some of the PFAS chemicals are known to be bioaccumulative in aquatic species. A literature search for bioconcentration factors (BCFs) and bioaccumulation factors (BAFs) for PFAS has been done, and data for 22 taxonomic classes were assembled. The assembled data were evaluated for quality, and for gaps and limitations in bioaccumulation information for the PFAS universe of chemicals. In general, carbonyl and sulfonyl PFAS classes are relatively data rich, whereas phosphate, fluorotelomer, and ether PFAS classes are data limited for fish and nonexistent for most other taxonomic classes. Taxonomic classes with the most measurements were, in descending order, Teleostei (fish), Bivalvia, and Malacostraca. For fish, median whole-body log BAFs (L/kg wet wt) for perfluorooctane sulfonic acid and perfluorooctanoic acid were 3.55 (standard deviation [SD] = 0.83, n = 84) and 2.16 (SD = 0.85, n = 48) using all measurements, respectively. In comparison with freshwater species, data are limited for marine species, and further research is needed to determine whether the BAFs for freshwater and marine species should be the same or different. The BAFs for some PFAS appear to be consistent with the BCFs developed with laboratory experiments, in which values decline with increasing concentrations in water. Environ Toxicol Chem 2021;40:1530–1543. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
Association of ficolin‐1 and ficolin‐3 gene variation and pulmonary tuberculosis susceptibility in a Chinese population
Authors: Li Ye , You En‐Qing , Lin Wen‐Hong , Liu Xiao‐Ning , Shen De‐Pei , Zhang Xin‐Li , Ma Dong‐Chun , Li Hong‐Miao
Published: February 2021

Background

The aim of our study was to estimate the association of ficolin‐1 (FCN1) gene (rs10120023, rs1071583) and ficolin‐3 (FCN3) gene (rs3813800, rs10794501) polymorphisms and pulmonary tuberculosis (PTB) susceptibility, as well as their several clinical features, in a Chinese population.

Methods

This study included a cohort of 489 PTB patients and 489 healthy controls, and the four SNPs were genotyped by improved multiple ligase detection reaction (iMLDR).

Results

We found that there were no significant differences regarding the allele and genotype frequencies of FCN1 rs10120023, rs1071583 and FCN3 rs3813800, rs10794501 between PTB patients and healthy controls (all p > 0.05). The association of three main haplotypes (CC, CT, and TC) in FCN1 and three main haplotypes (CT, GA, and GT) in FCN3 with PTB susceptibility was also analyzed, and no significant association was detected (all p > 0.05). In FCN1, the rs1071583 TT genotype was significantly associated with the occurrence of drug resistance in PTB patients (p = 0.040). In addition, the GG genotype and G allele frequencies of rs3813800 in FCN3 gene were significantly higher in PTB patients with pulmonary infection (p = 0.027, p = 0.020, respectively).

Conclusions

FCN1 and FCN3 genetic variation were not contributed to the pathogenesis of PTB in Chinese. While rs1071583 and rs3813800 variant might associate with several clinical characteristics of PTB.
Exosomes derived from vascular endothelial cells antagonize glucocorticoid‐induced osteoporosis by inhibiting ferritinophagy with resultant limited ferroptosis of osteoblasts
Authors: Yang Run‐Ze , Xu Wen‐Ning , Zheng Huo‐Liang , Zheng Xin‐Feng , Li Bo , Jiang Lei‐Sheng , Jiang Sheng‐Dan
Published: February 2021

High dose and long‐term steroid treatment can alter antioxidative ability and decrease the viability and function of osteoblasts, leading to osteoporosis and osteonecrosis. Ferroptosis, a new type of cell death characterized by excessive lipid peroxidation due to the downregulation of GPX4 and system Xc−, is involved in glucocorticoid‐induced osteoporosis. Endothelial cell‐secreted exosomes (EC‐Exos) are important mediators of cell‐to‐cell communication and are involved in many physiological and pathological processes. However, the effect of EC‐Exos on osteoblasts exposed to glucocorticoids has not been reported. Here, we explored the role of EC‐Exos in glucocorticoid‐induced osteoporosis. In vivo and in vitro experiments indicated that EC‐Exos reversed the glucocorticoid‐induced osteogenic inhibition of osteoblasts by inhibiting ferritinophagy‐dependent ferroptosis.
Noninvasive Assessment of O(6)‐Methylguanine‐DNA Methyltransferase Promoter Methylation Status in World Health Organization Grade II–IV Glioma Using Histogram Analysis of Inflow‐Based Vascular‐Space‐Occupancy Combined with Structural Magnetic Resonance Imaging
Authors: He Wenle , Li Xiaodan , Hua Jun , Liao Shukun , Guo Liuji , Xiao Xiang , Liu Xiaomin , Zhou Jun , Wang Wensheng , Xu Yikai , Wu Yuankui
Published: February 2021

Background

O(6)‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation is an important prognostic factor for gliomas and is associated with tumor angiogenesis. Arteriolar cerebral blood volume (CBVa) obtained from inflow‐based vascular‐space‐occupancy (iVASO) magnetic resonance imaging (MRI) is assumed to be an indicator of tumor microvasculature. Its preoperative predictive ability for MGMT promoter methylation remains unclear.

Purpose

To investigate the role of iVASO‐CBVa histogram features in determining MGMT promoter methylation status of grade II–IV gliomas.

Study Type

Retrospective

Subjects

Forty‐six patients consisting of 20 MGMT methylated and 26 unmethylated gliomas.

Field Strength/Sequence

3.0 T magnetic resonance images containing iVASO MRI, T1‐weighted image (T1WI), T2‐weighted image, T2‐weighted fluid attenuated inversion recovery image images, and enhanced T1WI.

Assessment

Sixteen structural imaging features were visually evaluated on structural MRI and 14 CBVa histogram features were extracted from iVASO‐CBVa maps.

Statistical Tests

Imaging features were screened and ranked using Fisher's exact test, Mann–Whitney U‐test, and randomforest algorithm. Features with higher importance were selected to develop logistic regression models to determine MGMT methylation status. Receiver operating characteristics (ROC) curve with the area under the curve (AUC) and leave‐one‐out cross‐validation (LOOCV) were used to assess effectiveness and stability.

Results

The top two CBVa histogram features were root mean squared (RMS) and variance. The top two structural imaging features were contrast‐enhancing component of the tumor (CET) location and tumor location. Both the CBVa model of RMS and variance (ROC, AUC = 0.867; LOOCV, AUC = 0.819) and the model of structural features (ROC, AUC = 0.882; LOOCV, AUC = 0.802) accurately identified MGMT methylation. The fusion model of CBVa RMS and CET location improved diagnostic performance (ROC, AUC = 0.931; LOOCV, AUC =0.906).

Data Conclusion

iVASO‐CBVa has potential in evaluating MGMT methylation status in grade II–IV gliomas.

Level of Evidence

4

Technical Efficacy

Stage 2
An investigation of the potential association between gastrointestinal viral and bacterial infection and development of intestinal acute graft versus host disease following allogeneic hematopoietic stem cell transplantation
Authors: Bueno Felipe , Albert Eliseo , Giménez Estela , Piñana José L. , Pérez Ariadna , Dolores Gómez María , Hernández‐Boluda Juan C. , Gonzalez‐Barberá Eva M. , Montoro Juan , Buesa Javier , Guerreiro Manuel , Balaguer‐Roselló Aitana , Hernani Rafael , Sanz Jaime , Solano Carlos , Navarro David
Published: February 2021

It is uncertain whether gastrointestinal (GI) infection caused by viral and bacterial pathogens may predispose to gastrointestinal acute Graft‐versus‐host disease (aGvHD‐GI) in allogeneic hematopoietic stem cell transplant recipients (allo‐HSCT). We investigated the potential association between detection of enteropathogenic viruses or bacteria in stools and subsequent occurrence of aGvHD‐GI in a cohort of 121 allo‐HSCT patients. Eighty‐six out of 121 patients (71%) had acute diarrhea and underwent screening for primary GI pathogens by molecular diagnostic methods. One or more GI pathogens were detected in 27 out of the 86 patients with diarrhea (31.3%). Specifically, Clostridioides difficile was found in 16 patients (18.6%), enteropathogenic viruses in 11 patients (12.7%) (Astrovirus, n = 4; Norovirus, n = 2; Sapovirus, n = 2; Adenovirus, n = 2; and Rotavirus, n = 1), and Campylobacter spp. in two patients (2.3%). Thirty patients were diagnosed with all grade aGvHD‐GI by histopathology. Detection of primary GI pathogens was achieved in 12 out of 30 patients (Clostridium difficile, n = 5; enteric viruses, n = 8; Campylobacter spp., n = 1) who either subsequently developed (n = 9) or previously had (n = 3) grade I‐IV IaGvHD (n = 9). Neither the detection of these microorganisms (all combined), enteric viruses, nor C. difficile was significantly associated with subsequent aGvHD‐GI development in Cox models (hazard ratio [HR] = 1.11, p = .80; HR = 1.64, p = .62; HR = 0.75, p = .64, respectively). Analogous results were obtained when grade II–IV aGvHD‐GI was selected as the clinical outcome. In summary, data in the current study did not support an association between GI infection and subsequent occurrence of aGvHD‐GI in an unselected cohort of allo‐HSCT recipients.
Developing a framework for neuromuscular ultrasound training and accreditation
Authors: Simon Neil G.
Published: February 2021

See article on pages 651–656 in this issue.
Developing outcome measures of disease activity in pediatric myasthenia
Authors: Prior Devin E. , Cooper Baillee A. , Zhang Bo , Ghosh Partha S.
Published: February 2021

Introduction

Pediatric myasthenia encompasses juvenile myasthenia gravis (JMG) and congenital myasthenic syndrome (CMS), which are chronic disorders with fluctuating symptoms amenable to medical therapy. Disease activity and treatment response may be difficult to assess, but, unlike adults, outcome measures have not been developed in children.

Methods

The study was performed in children (0‐18 years of age) at the neuromuscular center of a pediatric hospital over a 3‐year period. Patients were recruited prospectively as part of their routine clinical care. Demographic data, diagnosis (JMG/CMS), and the following scales were recorded at each visit: Myasthenia Gravis Foundation of America (MGFA) class, Myasthenia Gravis Composite (MGC), and Pediatric Myasthenia–Quality of Life 15 (PM‐QOL15).

Results

Thirty‐three patients (24 JMG, 9 CMS) were included in the study, 22 had two or more visits. We established known‐groups validity of the MGC and PM‐QOL15 scores as compared with the MGFA class. To establish concurrent validity, we constructed a receiver‐operating characteristic curve and calculated threshold values of MGC and PM‐QOL15 with optimal sensitivity and specificity for identifying a patient with more severe (MGFA III or higher) disease. Finally, we demonstrated the concordance between the MGC and PM‐QOL15 by their statistically significant positive Pearson and Spearman correlations.

Discussion

Our study suggests that MGC and PM‐QOL15 are important disease outcome measures in pediatric myasthenia that are easy to administer and provide reliable assessment of disease activity in the clinic setting. Further studies are needed to validate their use for pediatric clinical research trials.
An iterative scheme of flexibility‐based component mode synthesis with higher‐order residual modal compensation
Authors: Chung In Seob , Kim Jin‐Gyun , Chae Soo‐Won , Park K.C.
Published: February 2021

An Iterative Flexibility‐based Component Mode Synthesis (IF‐CMS) is presented for the model reduction of partitioned structural dynamic systems via localized Lagrange multipliers. A distinct IF‐CMS feature is the inclusion of hierarchical residual flexibility at each iteration, resulting in considerably improved accuracy compared with the classical Craig–Bampton (CB) CMS method. The present IF‐CMS method does not increase the number of substructural modes during the hierarchical iteration process. In particular, to alleviate ill‐conditioning during the iteration steps, the proposed IF‐CMS method adopts the so‐called (qd, , ub)‐formulation by condensing Lagrange multipliers from the original F‐CMS method. The performance of the proposed method is evaluated through numerical examples, which illustrates improved accuracy over existing CMS methods.
Estimating the economic impact of a one‐time event: The case of l'Hermione in Yorktown
Authors: Hall Thomas , Shuck Sheri M.
Published: February 2021

In an era of pressure on government resources, nonprofits can serve an important role in the provision of services to the public. However, without clear and quantifiable estimates of their impact, it is difficult for policymakers to justify allocating governmental resources toward these services. This is especially the case for ephemeral opportunities that arise without substantial advance notice or a special program that occurs only once (contrasted to programs that nonprofits provide on a continuing basis). This research note presents economic impact estimates for a unique example of a remarkable effort involving numerous entities from the government, for‐profit, and nonprofit sectors. Our contribution is to exemplify methods that might be used to assess the economic impact of ephemeral or one‐time events. Of course, each situation is unique, so the judgment of the analyst is always a key input. Using three survey‐generated data points per respondent, nonprofits can replicate the methods of this study to assess the economic impact of special events herein. With estimates such as the ones examined herein, policymakers can contrast the benefits of special events with their costs in order to determine if such events are worthwhile investments.
The Insulator–Insulator and the Insulator–Mixed‐Metal–Insulator Transitions in Self‐Heated AlxV1−xO2 Single Crystals and Their Visualization
Authors: Fisher Bertina , Patlagan Larisa , Eyal Anna , Reisner George M.
Published: February 2021

In addition to the well‐known insulator–metal transition above room temperature in pure VO2, AlxV1−xO2 exhibits an insulator–insulator transition at temperatures above room temperature and below the insulator–metal transition temperature, consisting of an increase in resistance by a factor ≤2. The wealth of static and dynamic domain structures discovered in the mixed‐metal‐insulator state of free‐standing, high‐quality, pure VO2 single crystals via optical microscopy synchronous with dc I–V tracing has inspired the use of this technique in these more complex materials. Reported herein are I(V) measurements conducted on crystals of AlxV1−xO2 (0.007≤ × ≤0.02) at various ambient temperatures (To). Prominent features (switching) on the I(V) loops are easily identified with the onset of the insulator–insulator and of the mixed‐metal‐insulator states, both induced by self‐heating (Joule heating). The switching results from instabilities of two different types of negative differential resistance regimes. The applied power at the onset of each switching scales with the excess temperature above ambient. For both transitions, optical microscopy synchronous with dc I–V tracing visualizes the expansion of each phase within the background upon the current increasing, and its contraction upon the current decreasing.
Computation‐driven synthesis of pentothal sodium
Authors: Chen Jitian , Du Tianyu , Gao Liuzhou , Chai Zhongjing , Dong Hao
Published: February 2021

Different reaction conditions or reaction sequences are critical problems to be solved in synthetic chemistry research. Calculating possible reaction paths with quantum chemistry methods could effectively drive the development of chemical synthesis. Here, we take the synthesis of thiopental (or pentothal sodium), an ultra‐short‐acting general anesthetic that induces hypnosis and anesthesia, as an example. Different synthetic routes for this compound have been reported in the literature, but detailed information such as the alkylation sequence is illusive. In this work, we revisited the thiopental synthesis path with combined computational prediction and experimental validation. We explored the reaction mechanism of each putative elementary step with density functional theory (DFT) calculations. Our computations show that two different alkylation paths (with either 2‐bromopentane or bromoethane) are both possible. However, the reaction order has a significant impact on the amount of by‐products in the synthesis product. The subsequent experiments validated the predicted alkylation sequence from DFT calculations. We further showed that EtONa/EtOH is much better than NaH/EtOH to produce thiopental through thiourea's reaction with 2‐ethyl‐2‐(1‐methylbutyl) diethyl malonate with a higher yield of the target product. The proposed synthetic path gives a total yield of 66%, higher than the literature reported. Therefore, the computation‐driven synthesis of drug molecules provides new insight into the synthetic route's appropriate design and optimization of reaction conditions.
Covalently Bonded 2D/0D g‐C3N4/MoS2 Nanocomposites for Enhanced Tribological Properties in Oil
Authors: Min Chunying , Yang Yuzi , Liang Hongyu , He Zengbao , Zhu Jinfeng , Li Qiuying
Published: February 2021

In current work, by an ordinary one‐step hydrothermal strategy, the covalently bonded graphitic carbon nitride/molybdenum disulfide (g‐C3N4/MoS2) nanocomposites were successfully synthesized. SEM, TEM analyses evidenced the well distribution of MoS2 nanoparticles on g‐C3N4. The covalent bond (C−S bond) between two‐dimensional (2D) g‐C3N4 and zero‐dimensional (0D) MoS2 were confirmed by FTIR and XRD. Furthermore, the average friction coefficient and wear rate of g‐C3N4/MoS2 nanocomposites at 0.20 wt % concentration could separately reach up to 27.86 % and 70.87 % reduction by comparing pure oil, benefiting from synergistic lubrication of g‐C3N4 nanosheets plus spherical MoS2. In the work, novel guidance will be provided for the potential application of multi‐dimensional g‐C3N4‐based nanocomposites in lubricating field.
Design and Characterization of Ticagrelor‐Loaded Chitosan Biopolymer to Improve Chemical and Biological Properties of the Drug
Authors: Hosseini‐Ashtiani Nafiseh , Tadjarodi Azadeh
Published: February 2021

The present study aimed at proposing a safe drug delivery system comprising of chitosan, as a natural polymer, and cyanocobalamin (Cbl) in compliance with the biological system to improve oral administration of ticagrelor (TCG). To this end, the drug loading, in‐vitro drug release, and in‐vitro cytotoxicity were assessed after fabricating the drug‐loaded carrier. Drug transfer could be improved due to the inherent features of mucoadhesive chitosan and the existence of a specific receptor for Cbl in the intestine. Given the results, a maximum drug loading efficiency of 80 % was obtained for TCG, and a controlled release profile was achieved for the drug‐loaded carrier in 0.2 % w/v polysorbate 80 in water. Biocompatibility studies of the TCG‐loaded carrier showed similar cytotoxicity compared to the free drug. The proposed safe drug delivery system has the potentials to overcome the constraints that might preclude the use of the TCG formulation in oral dosage forms.
Propylphosphonic Anhydride (T3P®) as Coupling Reagent for Solid‐Phase Peptide Synthesis
Authors: Al Musaimi Othman , Wisdom Richard , Talbiersky Peter , De La Torre Beatriz G. , Albericio Fernando
Published: February 2021

Amidation is the predominant reaction within the pharmaceutical setting, and it is attracting greater attention due to the increased demand for therapeutic peptides. The high therapeutic efficacy and safety profile of peptides have placed these molecules in prime position within the pharmaceutical arena, which is reflected by these molecules receiving several approvals from various regulatory agencies each year. In this context, the demand for developing efficient strategies for peptide synthesis has also risen. Although propylphosphonic anhydride (T3P®), which has been recently proposed as a green coupling reagent, has shown good performance in solution, it has never been applied to solid‐phase peptide synthesis (SPPS). Here we test the use of T3P® for SPPS. Satisfactory yields were achieved with a mild activation protocol. Various green solvents were tested and proved to be compatible with this coupling reagent. Several commonly used reagents cause allergic reactions or are susceptible to explosion under certain conditions. To overcome these issues, we propose T3P® as a potential alternative coupling reagent in SPPS.