bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic Approaches to N‐Methoxy‐N‐methylamides
Authors: Lee Jae In , Park Hyun
Published: May 2021

N‐Methoxy‐N‐methylamides were prepared by the acylation of acid halides, acyl cyanides, esters, lactones, activated amides, and mesyl carboxylates with N,O‐dimethylhydroxylamine hydrochloride. The reaction of carboxylic acids with alkyl chloroformates, phosphonate reagents, or coupling agents afforded the activated esters, which were converted to N‐methoxy‐N‐methylamides by (CH3O)NHCH3. N‐Methoxy‐N‐methylamides were also prepared by the oxidative amidation of benzyl alcohols and palladium‐catalyzed aminocarbonylation of organoboronic acids or aryl halides with (CH3O)NHCH3 under CO equivalents. Furthermore, N‐methoxy‐N‐methylamides were produced by the selective substitution of N,O‐dimethylcarbamoylation agents with organometallic reagents.
Comparative analysis of excretion of six major compounds of Polygonum orientale L. extract in urine, feces and bile under physiological and myocardial ischemia conditions in rats using UPLC–MS/MS
Authors: Lu Yuan , Li Na , Zhu Xiaoqin , Pan Jie , Wang Yonglin , Lan Yanyu , Li Yongjun , Wang Aimin , Sun Jia , Liu Chunhua
Published: May 2021

Polygonum orientale L. is a traditional Chinese medicine having extensive pharmacological activities including antimyocardial ischemia (MI) injury properties. Isoorientin, orientin, vitexin, quercitrin, astragalin and protocatechuic acid are the main compounds in P. orientale extract. The aim of this study was to establish an ultra‐performance liquid chromatography–tandem mass spectrometry method for the determination of the content of these compounds in urine, feces and bile samples simultaneously and application of the method in a comparative excretion study in normal and MI model rats after oral administration of P. orientale extract. Chromatographic seperation was conducted on an Agilent Eclipse Plus C18 column with the mobile phase consisting of 0.1% formic acid–acetonitrile and 0.1% formic acid–water. Negative ion multiple reaction monitoring mode was used for quantification. The six compounds had good linearity (r ≥ 0.9921) and acceptable accuracy ranging from 10.10 to −5.82% The relative standard deviations of within‐day precision and inter‐day precision were <10.45 and 13.44%, respectively. The extraction recovery of the six analytes ranged from 80.31 to 101.47% and the matrix effect was 82.56–102.88%, indicating that the preparations of sample collected form urine, feces and bile were stable throughout analysis. The excretion amount of the six analytes increased in both normal and MI model rats’ urine, feces and bile in a 24 h period and became stable between 36 and 48 h after administration. The total excretion rate of six compounds was <5% in urine, feces and bile of normal and MI model rats. The excretion peak period for all compounds in MI rats was slower than that in normal rats. This excretion study provides insights for further application and research on P. orientale.
Toward sustainable development: Board characteristics, country governance quality, and environmental performance
Authors: Orazalin Nurlan , Mahmood Monowar
Published: May 2021

The objective of this study is to examine the effects of board characteristics and country governance quality on both individual aspects and the overall level of environmental performance through the lens of agency, resource dependency, and institutional theories. The study is based on a sample of 3023 firm‐year observations from European companies operating in 22 countries between 2009 and 2016. Data on the resources, emissions, and innovation dimensions of environmental performance and board governance data were collected from the Refinitiv database, whereas financial data were extracted from the Worldscope database. The study employs a multilevel modeling analysis and the generalized method of moments (GMM) estimation technique to analyze the data. The findings suggest that board gender diversity and the presence of a corporate social responsibility and sustainability committee have a positive impact on environmental performance. The results also show that country governance quality is positively related to environmental performance. The findings have important implications for practitioners, regulators, and policymakers with respect to the effectiveness of corporate governance mechanisms and country governance systems in determining corporate environmental practices.
Cost‐effectiveness of multiparametric magnetic resonance imaging and MRI‐guided biopsy in a population‐based prostate cancer screening setting using a micro‐simulation model
Authors: Getaneh Abraham M. , Heijnsdijk Eveline AM , de Koning Harry J.
Published: May 2021

Background

The introduction of multiparametric magnetic resonance imaging (mpMRI) and MRI‐guided biopsy has improved the diagnosis of prostate cancer. However, it remains uncertain whether it is cost‐effective, especially in a population‐based screening strategy.

Methods

We used a micro‐simulation model to assess the cost‐effectiveness of an MRI‐based prostate cancer screening in comparison to the classical prostate‐specific antigen (PSA) screening, at a population level. The test sensitivity parameters for the mpMRI and MRI‐guided biopsy, grade misclassification rates, utility estimates, and the unit costs of different interventions were obtained from literature. We assumed the same screening attendance rate and biopsy compliance rate for both strategies. A probabilistic sensitivity analysis, consisting of 1000 model runs, was performed to estimate a mean incremental cost‐effectiveness ratio (ICER) and assess uncertainty. A €20,000 willingness‐to‐pay (WTP) threshold per quality‐adjusted life year (QALY) gained, and a discounting rate of 3.5% was considered in the analysis.

Results

The MRI‐based screening improved the life‐years (LY) and QALYs gained by 3.5 and 3, respectively, in comparison to the classical screening pathway. Based on the probabilistic sensitivity analyses, the MRI screening pathway leads to total discounted mean incremental costs of €15,413 (95% confidence interval (CI) of €14,556–€16,272) compared to the classical screening pathway. The corresponding discounted mean incremental QALYs gained was 1.36 (95% CI of 1.31–1.40), resulting in a mean ICER of €11,355 per QALY gained. At a WTP threshold of €20,000, the MRI screening pathway has about 84% chance to be more cost‐effective than the classical screening pathway.

Conclusions

For triennial screening from age 55–64, incorporation of mpMRI as a reflex test after a positive PSA test result with a subsequent MRI‐guided biopsy has a high probability to be more cost‐effective as compared with the classical prostate cancer screening pathway.
The Therapeutic Effects and Mechanisms of Salidroside on Cardiovascular and Metabolic Diseases: An Updated Review
Authors: Zhao Cheng‐Cheng , Wu Xin‐Yue , Yi Huan , Chen Rong , Fan Gang
Published: May 2021

The increasing incidence of metabolic and cardiovascular diseases has severely affected global human health and life safety. In recent years, some effective drugs with remarkable curative effects and few side effects found in natural compounds have attracted attention. Salidroside (SAL), a phenylpropane glycoside, is the main active ingredient of the plateau plant Rhodiola. So far, many animal experiments proved that SAL has good biological activity against some metabolic and cardiovascular diseases. However, most of these reports are scattered. This review systematically summarizes the pharmacological progress of SAL in the treatment of several metabolic (e. g., diabetes and non‐alcoholic fatty liver disease) and cardiovascular (e. g., atherosclerosis) diseases in a timely manner to promote the clinical application and basic research of SAL. Accumulating evidence proves that SAL has beneficial effects on these diseases. It can improve glucose tolerance, insulin sensitivity, and β‐cell and liver functions, and inhibit adipogenesis, inflammation and oxidative stress. Overall, SAL may be a valuable and potential drug candidate for the treatment of metabolic and cardiovascular diseases. However, more studies especially clinical trials are needed to further confirm its therapeutic effects and molecular mechanisms.
Chemoproteomics for Plasmodium Parasite Drug Target Discovery
Authors: Lu Kuan‐Yi , Mansfield Christopher R. , Fitzgerald Michael C. , Derbyshire Emily R.
Published: May 2021

Emerging Plasmodium parasite drug resistance is threatening progress towards malaria control and elimination. While recent efforts in cell‐based, high‐throughput drug screening have produced first‐in‐class drugs with promising activities against different Plasmodium life cycle stages, most of these antimalarial agents have elusive mechanisms of action. Though challenging to address, target identification can provide valuable information to facilitate lead optimization and preclinical drug prioritization. Recently, proteome‐wide methods for direct assessment of drug‐protein interactions have emerged as powerful tools in a number of systems, including Plasmodium. In this review, we will discuss current chemoproteomic strategies that have been adapted to antimalarial drug target discovery, including affinity‐ and activity‐based protein profiling and the energetics‐based techniques thermal proteome profiling and stability of proteins from rates of oxidation. The successful application of chemoproteomics to the Plasmodium blood stage highlights the potential of these methods to link inhibitors to their molecular targets in more elusive Plasmodium life stages and intracellular pathogens in the future.
Design and Hybridization Properties of Acyclic Xeno Nucleic Acid Oligomers
Authors: Murayama Keiji , Asanuma Hiroyuki
Published: May 2021

Xeno nucleic acids (XNAs) are analogues of DNA and RNA that have a non‐ribose artificial scaffold. XNAs are possible prebiotic genetic carriers as well as alternative genetic systems in artificial life. In addition, XNA oligomers can be used as biological tools. Acyclic XNAs, which do not have cyclic scaffolds, are attractive due to facile their synthesis and remarkably high nuclease resistance. To maximize the performance of XNAs, a negatively charged backbone is preferable to provide sufficient water solubility; however, acyclic XNAs containing polyanionic backbones suffer from high entropy cost upon duplex formation, because of the high flexibility of the acyclic nature. Herein, we review the relationships between the structure and duplex hybridization properties of various acyclic XNA oligomers with polyanion backbones.
Per‐glycosylation of the Surface‐Accessible Lysines: One‐Pot Aqueous Route to Stabilized Proteins with Native Activity
Authors: Walther Raoul , Monge Pere , Pedersen Andreas Bøtker , Benderoth Anja , Pedersen Jannik Nedergaard , Farzadfard Azad , Mandrup Ole A. , Howard Kenneth A. , Otzen Daniel E. , Zelikin Alexander N.
Published: May 2021

Chemical glycosylation of proteins is a powerful tool applied widely in biomedicine and biotechnology. However, it is a challenging undertaking and typically relies on recombinant proteins and site‐specific conjugations. The scope and utility of this nature‐inspired methodology would be broadened tremendously by the advent of facile, scalable techniques in glycosylation, which are currently missing. In this work, we investigated a one‐pot aqueous protocol to achieve indiscriminate, surface‐wide glycosylation of the surface accessible amines (lysines and/or N‐terminus). We reveal that this approach afforded minimal if any change in the protein activity and recognition events in biochemical and cell culture assays, but at the same time provided a significant benefit of stabilizing proteins against aggregation and fibrillation ‐ as demonstrated on serum proteins (albumins and immunoglobulin G, IgG), an enzyme (uricase), and proteins involved in neurodegenerative disease (α‐synuclein) and diabetes (insulin). Most importantly, this highly advantageous result was achieved via a one‐pot aqueous protocol performed on native proteins, bypassing the use of complex chemical methodologies and recombinant proteins.
Mental distress in a clinical nurse due to a false‐positive COVID‐19 antibody test result during the COVID‐19 epidemic in Japan: A case report
Authors: Shimazu Yuzo , Kobashi Yurie , Zhao Tianchen , Nishikawa Yositaka , Sawano Toyoaki , Ozaki Akihiko , Obara Daiji , Tsubokura Masaharu
Published: May 2021

This study suggests the importance of instituting accompanying measures to prevent potential negative mental and social impacts on people receiving false‐positive results.
Treatment of Pipkin type I fracture using safe surgical hip dislocation: A case report
Authors: Baidoo Paa Kwesi , Twumasi Baah Jnr Kwasi , Abu Anning , Assim Alex Osei , Ayodeji Emmanuel Kafui , Gudugbe Senyo
Published: May 2021

We report the clinical and radiological outcomes of a 30‐year‐old female with femoral head fracture following a posterior hip dislocation. The patient was managed using safe surgical hip dislocation. She had a pain free range of motion of the hip at 1 year postinjury.
Successful surgical treatment approach for mitral valve vegetation of infective endocarditis after severe soft tissue infection with mediastinitis
Authors: Uchida Kenichiro , Takahashi Yosuke , Shibata Toshihiko , Mizobata Yasumitsu
Published: May 2021

Transesophageal echocardiography is mandatory if you do suspect infective endocarditis. By approaching via a small right thoracotomy, vegetectomy and mitral valvuloplasty following severe mediastinitis were successfully accomplished without any complications.
Right atrial mass in a patient with COVID‐19 pneumonia: A case report
Authors: Othman Fahmi , Abid Abdul Rehman , Abdulkarim Sabir , Khatib Mohamad Y. , Nashwan Abdulqadir J. , Alkuwari Maryam , AlMulla Abdulwahid , Alqahtani Awad
Published: May 2021

Lipomatous hypertrophy of the interatrial septum can have an atypical appearance by transthoracic echocardiography. The authors emphasize on the importance of the multimodality imaging approach to reach the appropriate diagnosis in such cases.
Exacerbation of atrial fibrillation related to dulaglutide use
Authors: Lee Jayden , Umana Idopise E. , Nguyen Judy
Published: May 2021

Dulaglutide is associated with sinus tachycardia, increased PR interval, and 1st degree AV block. These conduction abnormalities can increase the risk of arrhythmia. Dulaglutide should be used with caution in patients with pre‐existing arrhythmia.
HPV32‐related Heck’s disease in a chronic graft‐versus‐host disease patient with long‐term successful KTP laser treatment: A rare case report
Authors: Nguyen Joe Truong , Allen Clint T. , Dodge Joshua T. , Van Doorslaer Koenraad , McBride Alison A. , Pavletic Steven Z. , Mays Jacqueline W.
Published: May 2021

We recently identified and treated a rare case of oral focal epithelial hyperplasia (FEH) in an adult patient with chronic graft‐vs‐host disease. This is the first report linking KTP laser therapy to successful long‐term treatment HPV32 FEH.
Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice‐site mutations: Two case reports and a literature review
Authors: Cardoso Leila , Galán‐Gómez Víctor , Corral‐Sánchez María Dolores , Pérez‐Martínez Antonio , Riesco Susana , Isidoro‐García María , Escudero Adela
Published: May 2021

The clinical and laboratory criteria for hemophagocytic lymphohistiocytosis should be taken into account during the juvenile myelomonocytic leukemia diagnosis, specifically in CBL syndrome, to reveal the presence of primary rather than secondary associated hemophagocytosis.
Cobalt Carbonyl Clusters Enable Independent Control of Two Proton Transfer Rates in the Mechanism for Hydrogen Evolution
Authors: Pattanayak Santanu , Berben Louise A.
Published: May 2021

Metal carbonyl clusters (MCC's) are atomically defined nanomaterials which can be characterized using the precise tools of molecular (electro)chemistry. HER mechanisms involve two proton transfer (PT) steps in the catalytic cycle. For HER catalyzed by [Co11C2(CO)23]3− (13−), cyclic voltammetry measurements were used to determine the rate for PT1 as kPT1=3×108 M−1 s−1, whereas the rate for PT2 is kPT2=3.7×103 M−1 s−1. The fast, diffusion‐limited rate for PT1 is consistent with a previous report describing [Co13C2(CO)24]4− (24−), with PT=2.9×109 M−1 s−1. In both cases rate enhancement in PT1 is promoted by the many Co−Co bonds on the surface of the MCC that serve as PT sites: a statistical enhancement of rate akin to the effects of proton relays. In contrast, kPT2 varies and is five orders of magnitude slower for 12− compared with 24−. Thus, MCC's and nanomaterials offer an opportunity to enhance the rate for PT1 while maintaining thermochemical or kinetic control of PT2.
Theoretical Insight into the Effect of Fluorine‐Functionalized Metal‐Organic Framework Supported Palladium Single‐Site Catalyst in the Ethylene Dimerization Reaction
Authors: Ortega Daniela E.
Published: May 2021

Ethylene dimerization reaction is one of the most common mechanisms for the production of 1‐butene. Recently, metal–organic frameworks (MOFs) have received extensive attention in this area since they combine all the advantages of homogeneous and heterogeneous catalysts in a single compound. Here a computational mechanistic study of MOF‐supported palladium single‐site catalyst for ethylene dimerization reaction is reported. Catalytic systems with both biphenyl‐type backbone as organic ligand and its fluorine‐functionalization have been investigated to reveal the origin of ligand effects on the catalytic activity and selectivity. The calculations revealed that the nonfluorinated palladium MOF catalyst undergoes dimerization over isomerization reaction. Then the influence of the fluorine‐functionalized organic ligand was compared in the dimerization catalytic cycle, which was strongly favored in terms of activity and selectivity. Catalyst‐substrate interactions were analyzed by energy decomposition analysis revealing the critical role of ligand backbone functionalization on the activity. This theoretical analysis identified three chemically meaningful dominant effects on these catalysts; steric, electrostatic and charge transfer effects. The steric effects promote nonfluorinated MOF catalyst, whereas the electrostatic effects are the dominant factor that promotes its fluorinated counterpart. This theoretical study provides feedback with future experimental studies about the role of fluorine ligand functionalization in palladium MOF catalysts for ethylene dimerization reaction.
Design and Application of Mini‐libraries of miRNA Probes for an Efficient and Versatile miRNA‐mRNA Cross‐linking
Authors: Malinowska Anna L. , Laski Artur , Hall Jonathan
Published: May 2021

MicroRNAs constitute a class of endogenous, non‐coding RNAs that influence various processes within the cell. By base‐pairing to partially‐complementary sites located in the 3’ untranslated region of target messenger RNAs, microRNAs participate in post‐transcriptional regulation of the majority of human protein‐coding genes. Their dysregulation has been related to many pathological processes and diseases. Thus, an in‐depth understanding of the microRNA mechanisms of action is crucial. Here, we present a new concept of probe design to achieve an efficient and sequence‐independent miRNA‐mRNA cross‐linking. The new strategy is based on the utilization of a controlled mixture of probes for a chosen miRNA, in which a trioxsalen moiety is introduced at the N4‐position of a selected cytidine through short oligoethylene glycol‐based linkers. In vitro photo‐cross‐linking experiments with mini‐libraries of probes for microRNAs of interest showed variable cross‐linking efficiencies, demonstrating a general applicability of the presented approach.
The reporting rates of high‐grade squamous intraepithelial lesions and their human papillomavirus testing and histologic follow‐up results: A comparison between ThinPrep and SurePath preparations
Authors: Sinclair William David , Gibbons‐Fideler I‐sanna , Shen Rulong , Li Zaibo
Published: May 2021

Background

Liquid‐based cytology (LBC) tests SurePath (SP) and ThinPrep (TP) have largely replaced conventional Papanicolaou (Pap) tests for cervical cytology screening due to higher sensitivity. However, comparison between SP and TP test sensitivity and efficacy in detecting squamous abnormalities is lacking. Our study aims to compare high‐grade squamous intraepithelial lesion (HSIL) reporting rates, human papillomavirus (HPV) positivity rates, and histologic outcome between these two LBC methods.

Materials and Methods

We performed a retrospective search of the period between January 2014 and June 2017, when both TP and SP were utilized at our institution, to identify HSIL cases and collect the HPV testing and histologic follow‐up results for those cases.

Results

One hundred twenty‐five HSILs were identified from the 15 382 TP specimens (0.81%) and 93 HSILs were identified from the 25 105 SP specimens (0.37%), a statistically significant difference (P < .0001). The corresponding HPV positivity rates were 95.6% and 89.7% in TP‐HSILs and SP‐HSILs, respectively, a statistically non‐significant difference. Histologic follow‐up showed HSILs or carcinomas were identified in 78% (49/63) of TP‐HSILs and 79% (45/57) of SP‐HSILs, with no statistically significant difference.

Conclusion

TP demonstrated a higher HSIL detection rate than SP with no significant difference in follow‐up HPV or histologic results.
Associations of adverse childhood experiences with stress physiology and insulin resistance in adolescents at risk for adult obesity
Authors: Jimenez Virginia , Sanchez Natalia , Clark Emma L. M. , Miller Reagan L. , Casamassima Milena , Verros Megan , Conte Isabella , Ruiz‐Jaquez Metztli , Gulley Lauren D. , Johnson Sarah A. , Melby Christopher , Lucas‐Thompson Rachel G. , Shomaker Lauren B.
Published: May 2021

Adverse childhood experiences (ACEs) heighten the risk for adult obesity and cardiometabolic disease, but physiological factors underlying this connection are not well understood. We determined if ACEs were associated with physiological stress response and insulin resistance in adolescents at risk for adult obesity. Participants were 90 adolescents 12.0–17.5 years (50% female, 30% Hispanic/Latinx), at risk for adult obesity by virtue of above‐average body mass index (BMI; kg/m2 ≥ 70th percentile) or parental obesity (BMI ≥ 30 kg/m2). ACEs were determined as presence (vs. absence) based upon the Schedule for Affective Disorders and Schizophrenia for School‐Aged Children. Physiological stress response was measured as heart rate/blood pressure response to the Trier Social Stress Test. Homeostatic model assessment of insulin resistance was determined from fasting glucose/insulin. Sixty‐one percent of adolescents reported positive ACE history. The presence of ACEs predicted greater heart rate (p < .001) and diastolic blood pressure (p = .02) response to stress, controlling for age, sex, race/ethnicity, puberty, and BMI standard score. Systolic blood pressure and insulin resistance did not differ by ACE history (p‐values > .08). Findings suggest heightened sympathetic stress response in adolescence could be explanatory in how ACEs increase the risk for later cardiometabolic disease. Future studies should characterize ACEs in relationship to day‐to‐day variations in adolescents’ stress physiology and glucose homeostasis.
Detection of γ‐hydroxybutyric acid‐related acids in blood plasma and urine: Extending the detection window of an exogenous γ‐hydroxybutyric acid intake?
Authors: Küting Theresa , Schneider Bianca , Heidbreder Anna , Krämer Michael , Jarsiah Pouria , Madea Burkhard , Hess Cornelius
Published: May 2021

In crimes facilitated by γ‐hydroxybutyric acid (GHB) administration, the frequent occurrence of anterograde amnesia of the victims as well as the short detection window and variations of endogenous GHB concentrations complicate obtaining analytical proof of GHB administration. Because elevated endogenous organic acid concentrations have been found in the urine of patients with succinic semialdehyde deficiency (leading to accumulation of GHB in human specimens) and after GHB ingestion, we searched for an alternative way to prove GHB administration via detection of elevated organic acid concentrations in blood plasma and urine. We collected blood and urine samples from narcolepsy patients (n = 5) treated with pharmaceuticals containing GHB sodium salt (1.86–3.72 g GHB as free acid per dose). Although GHB was detectable only up to 4 h in concentrations greater than the commonly used cutoff levels in blood plasma, 3,4‐dihydroxybutyric acid (3,4‐DHB) could be detected up to 12 h in blood plasma in concentrations exceeding initial concentrations of the same patient before GHB ingestion. Furthermore, four of the five patients showed an increase above endogenous levels described in the scientific literature. In urine, GHB concentrations above commonly used cutoff levels could be observed 4.5–9.5 h after GHB intake. Creatinine standardized initial concentrations were reached again for glycolic acid (GA), 3,4‐DHB, and 2,4‐dihydroxybutyric (2,4‐DHB) acid at 6.5–22, 11.5–22, and 8.5–70 h after GHB intake, respectively. Therefore, 2,4‐DHB, 3,4‐DHB, and GA are promising and should be further investigated as potential biomarkers to prolong the detection window of GHB intake.
Eligibility of outpatients with chronic heart failure for sodium–glucose co‐transporter‐2 inhibitors
Authors: Angelini Gianmarco , Albanese Miriam , Ursi Raffaella , Lisi Francesco , Bellino Maria Consiglia , Amato Luca , Gioia Margherita Ilaria , Parisi Giuseppe , Brunetti Natale Daniele , Piazzolla Giuseppina , Ciccone Marco Matteo , Iacoviello Massimo
Published: May 2021

Aims

Sodium–glucose co‐transporter‐2 inhibitors (SGLT2i) have been shown to have a relevant role in the prevention of hospitalizations for heart failure and improvement in the life expectancy of patients with diabetes and outpatients with chronic heart failure (CHF) with reduced left ventricular ejection fraction, independently from the presence of type 2 diabetes mellitus (T2DM). The aim of our study was to evaluate in a real‐world population the number of outpatients with CHF who meet the enrolment criteria of the main randomized controlled trials (RCT) published in the last 5 years and consequently identify the percentage of patients who could potential benefit from SGLT2i therapy.

Methods and results

We retrospectively evaluated all consecutive outpatients referred for CHF. The diagnosis of T2DM was according to the latest European Society of Cardiology Guidelines. Clinical characteristics considered for the enrolment in the RCTs were recorded. We enrolled 515 patients, 384 (75%) of whom had a left ventricular ejection fraction (LVEF) ≤ 40%, 82 (16%) had pre‐diabetes, and 187 (36%) had diabetes. Most of the patients with LVEF ≤ 40% met the criteria for the DAPA‐HF trial (65%), and this percentage was even higher if the serum level of N‐terminal pro‐brain natriuretic peptide was not considered. A high percentage of patients with diabetes and LVEF > 40% met the criteria for the DECLARE (39%), CANVAS (47%), and EMPA‐REG (30%) trials. Patients meeting the enrolment criteria of RCTs evaluating SGLT2i were also characterized by a high risk of heart failure events during follow‐up.

Conclusions

In spite of a low number of patients actually treated with SGLT2i, we observed that a high prevalence of patients with CHF met the clinical characteristics of RCTs that have demonstrated a beneficial effect of SGLT2i.
Ruthenium‐based Conjugated Polymer and Metal‐organic Framework Nanocomposites for Glucose Sensing
Authors: Jin Xiaofeng , Li Guanhua , Xu Tailin , Su Lei , Yan Dan , Zhang Xueji
Published: May 2021

Many studies have focused on effective ways to exploit enzyme immobilization on an electrode surface to help improve the performance of enzymatic electrochemical biosensors. Herein, a novel glucose sensor was fabricated by immobilizing glucose oxidase (GOx) onruthenium‐based conjugated polymer (CP) and metal‐organic framework (MOF) nanocomposites. This has not only reduced the applied potential to 0.2 V (vs. Ag/AgCl), but also improved the effective surface area for enzyme immobilization.PPG@Ru@UiO‐66‐NH2 was tailored by controlled chemical synthesis from a pre‐synthesized water‐soluble conjugated polymer (poly(N‐phenylglycine)) and metal‐organic framework (UiO‐66‐NH2). The resulting nanocomposites were characterized using Fourier transform infrared spectroscopy, X‐ray fluorescence, scanning electron microscopy, and cyclic voltammetry. The PPG@Ru@UiO‐66‐NH2/GOx coated electrodedisplayed a linear measurementrange for glucose from 1 mM to 10 mM, with a sensitivity of 45.92 μA ⋅ mM−1cm−1 and limit of detection of5 μM(
). Furthermore, the practical application of the fabricatedglucosesensor was tested in simulative blood samples with satisfactoryaccuracy. This approach alsoopens a new door for applications regarding both enzymatic electrochemical biosensors and enzymatic biofuel cells (EBFCs).
Numerical simulations of paper‐based electrophoretic separations with open‐source tools
Authors: Gerlero Gabriel S. , Márquez Damián Santiago , Schaumburg Federico , Franck Nicolás , Kler Pablo A.
Published: May 2021

A new tool for the solution of electromigrative separations in paper‐based microfluidics devices is presented. The implementation is based on a recently published complete mathematical model for describing these types of separations, and was developed on top of the open‐source toolbox electroMicroTransport, based on OpenFOAM®, inheriting all its features as native 3D problem handling, support for parallel computation, and a GNU GPL license. The presented tool includes full support for paper‐based electromigrative separations (including EOF and the novel mechanical and electrical dispersion effects), compatibility with a well‐recognized electrolyte database, and a novel algorithm for computing and controlling the electric current in arbitrary geometries. Additionally, the installation on any operating system is available due to its novel installation option in the form of a Docker image. A validation example with data from literature is included, and two extra application examples are provided, including a 2D free‐flow IEF problem, which demonstrates the capabilities of the toolbox for dealing with computational and physicochemical modeling challenges simultaneously. This tool will enable efficient and reliable numerical prototypes of paper‐based electrophoretic devices to accompany the contemporary fast growth in paper‐based microfluidics.
Quantitative characterization of human oncogene promoter G‐quadruplex DNA‐ligand interactions using a combination of mass spectrometry and capillary electrophoresis
Authors: Wang Shuangshuang , Yang Yang , Yang Yunhe , Li Huihui , Chen David D.Y.
Published: May 2021

Human c‐KIT oncogene is known to regulate cell growth and proliferation, and thus, acts as a probable target in the treatment of gastrointestinal tumors (GIST). To identify small molecule ligands which can specifically bind with the G‐quadruplex (G4) in the c‐KIT promoter region as potential antitumor agents, we propose the combination of electrospray ionization–mass spectrometry (ESI‐MS), capillary electrophoresis frontal analysis (CE‐FA), and Taylor dispersion analysis (TDA) to accurately investigate the G4/ligands binding properties. First, ESI–MS was used for initial screening of natural products (NPs). CE‐FA was then used to calculate specific binding constants and the stoichiometry of the native state binding pair in solution. Next, TDA, a micro‐capillary flow technique was used to examine the effect of the ligand binding on the diffusivity and particle size of the c‐KIT G4. Two of the screened NPs, scopolamine butylbromide (L1) and isorhamnetin‐3‐O‐neohesperidoside (L3), were found to specifically bind to the c‐KIT G4 with binding constants of around 104 M–1 and 1:1 stoichiometry in a free solution. TDA data showed that ligand binding (both L1 and L3) induced the c‐KIT strands to fold into a tightly structured G4 with a decreased hydrodynamic radius. These ligands have the potential to be drug candidates for the regulation of c‐KIT gene transcription by stabilizing the G4 structure. This methodology not only increased the speed of analysis but also improved its accuracy and specificity compared with the conventional binding approaches.
Review of nonlinear electrokinetic flows in insulator‐based dielectrophoresis: From induced charge to Joule heating effects
Authors: Xuan Xiangchun
Published: May 2021

Insulator‐based dielectrophoresis (iDEP) has been increasingly used for particle manipulation in various microfluidic applications. It exploits insulating structures to constrict and/or curve electric field lines to generate field gradients for particle dielectrophoresis. However, the presence of these insulators, especially those with sharp edges, causes two nonlinear electrokinetic flows, which, if sufficiently strong, may disturb the otherwise linear electrokinetic motion of particles and affect the iDEP performance. One is induced charge electroosmotic (ICEO) flow because of the polarization of the insulators, and the other is electrothermal flow because of the amplified Joule heating in the fluid around the insulators. Both flows vary nonlinearly with the applied electric field (either DC or AC) and exhibit in the form of fluid vortices, which have been utilized to promote some applications while being suppressed in others. The effectiveness of iDEP benefits from a comprehensive understanding of the nonlinear electrokinetic flows, which is complicated by the involvement of the entire iDEP device into electric polarization and thermal diffusion. This article is aimed to review the works on both the fundamentals and applications of ICEO and electrothermal flows in iDEP microdevices. A personal perspective of some future research directions in the field is also given.
Optimizing Catalyst Loading Ratio between the Anode and Cathode for Ultralow Catalyst Usage in Polymer Electrolyte Membrane Fuel Cell
Authors: Lee Jinwon , Seol Changwook , Kim Joondong , Jang Segeun , Kim Sang Moon
Published: May 2021

With increasing demand for high‐efficiency and clean energy sources, the polymer electrolyte membrane fuel cell (PEMFC) has received attention in a wide range of fields including transportation and back‐up power. For securing the economic viability of PEMFC, the U.S. Department of Energy (DOE) provides the target of the total Pt catalyst loading as 0.125 mgPt cm−2 on both cathode and anode, which is much less than that currently used (>0.25 mgPt cm−2 for cathode). An optimized ratio of catalyst loading between the anode and cathode with a fixed Pt catalyst loading according to the DOE target is figured out by conducting diverse electrochemical measurements with varying the catalyst loading ratio in single‐cells. Among the experimental set, the membrane electrode assembly (MEA) with 70% catalyst loading on the cathode side shows the highest performance with the maximum power density of 643 mW cm−2, while the MEA with 90% catalyst loading on the cathode side exhibits inferior performance. Experimental results are validated by suggesting the theoretical model, which was established based on considering both the electrochemical kinetics of hydrogen oxidation and oxygen reduction reaction.
Evaluation of saliva as a source of accurate whole‐genome and microbiome sequencing data
Authors: Herzig Anthony F. , Velo‐Suárez Lourdes , Le Folgoc Gaëlle , Boland Anne , Blanché Hélène , Olaso Robert , Le Roux Liana , Delmas Christelle , Goldberg Marcel , Zins Marie , Lethimonnier Franck , Deleuze Jean‐François , Génin Emmanuelle
Published: May 2021

This study sets out to establish the suitability of saliva‐based whole‐genome sequencing (WGS) through a comparison against blood‐based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo‐replication. We also investigated the potential of characterizing individual salivary microbiomes from non‐human DNA fragments found in saliva.

We observed that the majority of discordant genotype calls between blood and saliva fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo‐replication demonstrated that the levels of discordance between blood‐ and saliva‐derived WGS data were entirely similar to what one would expect between technical replicates if an individual's blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project.
A novel Mendelian randomization method with binary risk factor and outcome
Authors: Allman Philip H. , Aban Inmaculada , Long Dustin M. , Bridges S Louis , Srinivasasainagendra Vinodh , MacKenzie Todd , Cutter Gary , Tiwari Hemant K.
Published: May 2021

Background

Mendelian randomization (MR) applies instrumental variable (IV) methods to observational data using a genetic variant as an IV. Several Monte‐Carlo studies investigate the performance of MR methods with binary outcomes, but few consider them in conjunction with binary risk factors.

Objective

To develop a novel MR estimator for scenarios with a binary risk factor and outcome; and compare to existing MR estimators via simulations and real data analysis.

Methods

A bivariate Bernoulli distribution is adapted to the IV setting. Empirical bias and asymptotic coverage probabilities are estimated via simulations. The proposed method is compared to the Wald method, two‐stage predictor substitution (2SPS), two‐stage residual inclusion (2SRI), and the generalized method of moments (GMM). An analysis is performed using existing data from the CLEAR study to estimate the potential causal effect of smoking on rheumatoid arthritis risk in African Americans.

Results

Bias was low for the proposed method and comparable to 2SPS. The Wald method was often biased towards the null. Coverage was adequate for the proposed method, 2SPS, and 2SRI. Coverage for the Wald and GMM methods was poor in several scenarios. The causal effect of ever smoking on rheumatoid arthritis risk was not statistically significant using a variety of genetic instruments.

Conclusions

Simulations suggest the proposed MR method is sound with binary risk factors and outcomes, and comparable to 2SPS and 2SRI in terms of bias. The proposed method also provides more natural framework for hypothesis testing compared to 2SPS or 2SRI, which require ad‐hoc variance adjustments.
Locomotor action sequences impact the scale of representation in hippocampus and posterior parietal cortex
Authors: Shelley Laura E. , Nitz Douglas A.
Published: May 2021

The hippocampus and posterior parietal cortex are implicated in both episodic memory and encoding of position in an environment. In the present study, we examine the impact of locomotor behaviors associated with movement in both the horizontal and vertical dimensions on population activity patterns in these two brain structures. We utilized a five‐looped, squared spiral track containing stair segments, ramp segments, and flat segments. In addition to encoding locations along the full route, posterior parietal cortex population activity demonstrates strong pattern recurrence for similar action types at different locations in the environment. Additionally, posterior parietal and hippocampal neurons exhibit parallel modulation in the scale of representation that follows behavioral dynamics required for track traversal. These findings build on prior work examining spatial mapping in the vertical dimension and provide a better understanding of how a series of actions and visited locations can be coordinated in the generation of episodic memory.
Causal Bayesian networks in assessments of wildfire risks: Opportunities for ecological risk assessment and management
Authors: Carriger John F. , Thompson Matthew , Barron Mace G.
Published: May 2021

Wildfire risks and losses have increased over the last 100 years, associated with population expansion, land use and management practices, and global climate change. While there have been extensive efforts at modeling the probability and severity of wildfires, there have been fewer efforts to examine causal linkages from wildfires to impacts on ecological receptors and critical habitats. Bayesian networks are probabilistic tools for graphing and evaluating causal knowledge and uncertainties in complex systems that have seen only limited application to the quantitative assessment of ecological risks and impacts of wildfires. Here, we explore opportunities for using Bayesian networks for assessing wildfire impacts to ecological systems through levels of causal representation and scenario examination. Ultimately, Bayesian networks may facilitate understanding the factors contributing to ecological impacts, and the prediction and assessment of wildfire risks to ecosystems. Integr Environ Assess Manag 2021;17:1168–1178. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

KEY POINTS

The ladder of causation has broad implications for understanding the role of models in supporting assessment and decision-making goals. Each of the rungs of the ladder is examined in terms of environmental assessment and decision models. Our case studies focus on managing wildfire risks for ecological endpoints but will be broadly applicable to other environmental issues. Establishing a causal hierarchy for environmental models will benefit future environmental assessment and management endeavors.
Coastal resilience surges as living shorelines reduce lateral erosion of salt marshes
Authors: Polk Mariko A. , Gittman Rachel K. , Smith Carter S. , Eulie Devon O.
Published: May 2021

A growing suite of research has demonstrated that nature-based shoreline stabilization methods can increase resilience of coastal ecosystems by improving their capacity to return to predisturbance states. Previous work suggests that during hurricanes, living shorelines promote vertical accretion and experience less damage than traditional shoreline stabilization alternatives. Nevertheless, there is limited research looking at the impacts of major storm events on living shorelines and most studies have investigated a small number of sites. This study used in situ real-time kinematic (RTK)-GPS surveys to quantify the resilience (via the lateral change in shore position) of 17 living shoreline sites before and after a Category 1 hurricane event (Hurricane Florence, 2018). By doing so, this study seeks to understand the capacity of living shorelines (marsh with seaward breakwater or sill) to provide storm protection as compared to unaltered natural fringing salt marshes. After Hurricane Florence, living shorelines on average experienced significantly less lateral erosion compared to unprotected control segments (shoreline change rates of 0.015 and −0.31 m year−1, respectively). This study also explores how environmental siting variables (i.e., scarp presence, fetch, and bottom sediment) and sill design variables (i.e., sill material, width, and height) influence short- and long-term erosion. living shorelines were found to reduce erosion of fringing marsh edge among projects with a range of installation ages, structural materials, sill widths, and sill heights, and they were able to provide protection from erosion across a range of fetch, scarp, and bottom sediment conditions. Living shoreline siting and sill design may be suitable for broader environmental conditions than previously known. This study shows that living shorelines can increase resilience by reducing erosion of fringing salt marshes, promoting lateral building up of shoreline zones during short-term disturbance events, and from their long-term presence. Integr Environ Assess Manag 2022;18:82–98. © 2021 SETAC

KEY POINTS

The long-term efficacy of sill living shorelines and short-term performance encompassing major storm events, support lateral growth of the shoreline and, in contrast, unprotected control shorelines continued to see long-term and short-term lateral loss of salt marsh. Our results provide evidence to suggest that living shorelines reduce erosion and, in many instances, promote lateral building of shore zones during short-term periods that include Category 1 hurricane events. living shorelines were found to reduce erosion of fringing marsh edge among projects with a range of installation ages, structural materials, sill widths, and sill heights, and they were able to provide protection from erosion across a range of fetch, scarp, and bottom sediment conditions. Living shoreline siting and sill design may be suitable for broader environmental conditions than previously known.
Colorectal cancer incidence and mortality after negative fecal immunochemical tests by age 70: A prospective observational study
Authors: Zorzi Manuel , Battagello Jessica , Fiore Anna Rita , Memo Laura , Senore Carlo , Rugge Massimo
Published: May 2021

Limited endoscopy capacity usually represents the main barrier to the extension of screening to subjects older than 70, given the high positivity rate in this age group. We assessed CRC incidence and mortality by number of previous negative fecal immunochemical tests (FIT) among subjects turning 70. We selected persons aged 70 years who had received their last screening invitation when they were 68 or 69 years old within the population‐based screening program in the Veneto region of Italy. Subjects with a positive FIT were excluded. We calculated 10‐year cumulative CRC incidence and mortality in cohorts of subjects having performed zero, one, two or three negative FITs over the last three screening rounds before turning 70. Out of 117 858 subjects included in the study (46.4% men), 33.7% had never participated in screening (zero negative FITs), 23.3% had had one‐negative FIT, 20.1% two‐negative FITs and 22.9% three negative FITs. The 10‐year cumulative CRC incidence was 29.7 per 1000 subjects with zero FITs, and respectively, 14.5, 11.7 and 9.6 per 1000 subjects with one, two and three negative FITs. The corresponding figures for 10‐year cumulative mortality were 9.3, 3.5, 2.2 and 2.1 per 1000 in the four study cohorts. Figures were roughly double for men than for women for all the study cohorts. In order to use more efficiently limited endoscopy resources, and to minimize the potential harms related to false positive results in the elderly, screening among people aged 70 to 74 might be restricted to those with zero previous negative FITs.
A systematic review of biomarkers associated with maternal infection in pregnant and postpartum women
Authors: Oben Ayamo G. , Johnson Brittany M. , Tita Alan T. N. , Andrews William W. , Hibberd Patricia L. , Subramaniam Akila , Sinkey Rachel G.
Published: May 2021

Background

Serum biomarkers are commonly used to support the diagnosis of infection in non‐pregnant patients whose clinical presentation suggests infection. The utility of serum biomarkers for infection in pregnant and postpartum women is uncertain.

Search strategy

PubMed, CINAHL, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL, and SCOPUS were searched from inception to February 2020.

Selection criteria

Full‐text manuscripts in English were included if they reported the measurement of maternal serum biomarkers—and included a control group—to identify infection in pregnant and postpartum women. Data collection and analysis: two authors independently screened manuscripts, extracted data, and assessed methodologic quality.

Main results

Interleukin‐6 (IL‐6), C‐reactive protein, procalcitonin, insulin‐like growth factor binding protein 1, tumor necrosis factor‐α, calgranulin B, neopterin, and interferon‐γ inducible protein 10 reliably indicated infection. Intercellular adhesion molecule 1, monocyte chemotactic and activating factor, soluble IL‐6 receptor, and IL‐8 were not useful markers in pregnant and postpartum women.

Conclusions

Findings suggest that certain biomarkers have diagnostic value when maternal infection is suspected, but also confirms limitations in this population.