bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Health Facilities Capacity for the Management of Severe Preeclampsia and Eclampsia in Bayelsa State, Nigeria
Authors: Alabintei O. M. , Alabrah P. W. , Abasi I. J.
Published: April 2021

Background: The lack of properly-stocked facilities with basic and essential equipment and supplies as well as clinical guidelines required to successfully manage Pre-eclampsia/eclampsia (PE/E) has been reported in developing, low-income countries. It is necessary to ensure properly stocked health facilities for effective health care delivery. This study set out to assess the capacity of the health facilities in Bayelsa, Nigeria for the management of cases of eclampsia.

Methods: A descriptive design was used in the conduct of this research in which 155 workers were recruited. A multi-stage sampling technique was employed to select health facilities for the study. The study instruments included a self-administered structured questionnaire, an interview guide, and an inventory checklist. Data entry, cleaning and analysis were done using the Statistical Package for Social Sciences (SPSS) version 22. Descriptive and inferential statistics were generated using the data.

Results: It was found in this study that though MgSO4 was present in one (8.33%) primary and two (66.6%) secondary health facilities visited, no guide on how to administer and monitor the patients was available. The majority of the workforce in the primary health facility were the CHEW/CHO (48%), followed by midwives (16.9%) and then nurses (12.3%).Doctors constituted 7.7% while  pharmacists and pharmacist technicians constituted 6.2% and 9.2% respectively.

Conclusion: In conclusion, this study revealed that facilities assessed lacked most of the basic and essential equipment, supplies and drugs, required for the successful management of PE/E. For effective management of cases of eclampsia, it is very essential that there should be a continuous supply of necessary tools, drugs and functioning equipment needed for the management of PE/E in all health care facilities.
Dipeptidyl Peptidase 4 Inhibitors
Authors: Weber Ann E. , Thornberry Nancy A.
Published: April 2021

Type 2 diabetes (T2DM) is a growing worldwide epidemic. While a number of oral agents have been available to treat T2DM, they suffer from safety and tolerability issues and lack durability. In the 1990s, glucagon‐like peptide 1 (GLP‐1) emerged as a new approach to glucose lowering. Endogenous GLP‐1 is rapidly inactivated through the action of dipeptidyl peptidase 4 (DPP‐4), a serine dipeptidyl aminopeptidase that cleaves its N‐terminal two amino acids. Blocking DPP‐4 with a small molecule inhibitor was shown to increase circulating levels of GLP‐1 in rodent models and humans, leading to improved glucose control. Early DPP‐4 inhibitors were dipeptide mimetics, some of which bound to the DPP‐4 active site serine in a covalent manner. Screening and structure‐based drug design led to the identification of many other structural classes. In 2006, sitagliptin became the first DPP‐4 inhibitor approved by the FDA. Inhibitors now available include two for once‐weekly administration. Over 10 years of clinical experience has shown DPP‐4 inhibition to be safe and effective with a low risk of hypoglycemia, no weight gain, and no increased cardiovascular risk. Used as monotherapy or in combination with other glucose‐lowering medications, DPP‐4 inhibitors have become an important class of oral agents to treat T2DM.
Anti‐DNA Virus Agents
Authors: Herdewijn Piet , Gu Weijie , De Clercq Erik
Published: April 2021

Although most of the drugs that are used to treat deoxyribonucleic acid (DNA) virus infections have been on the market for more than 10 years, anti‐DNA virus drug discovery remains an active field of research. There are still DNA viruses that are important human pathogens for which no therapy is available (i.e. adenovirus), for which the available drugs show considerable toxicity (i.e. cytomegalovirus), or for which the current drug therapy is insufficient to eradicate the virus (i.e. hepatitis B virus). In this article, we have provided an overview of the anti‐DNA virus drugs that are presently on the market together with a description of the new compounds, all active against DNA viruses, covering the literature of the past 10 years. We have focused on the structure of newly discovered compounds, and the mechanism of action and clinical data, when available.

Although the major efforts are still in the nucleotide antimetabolite field, the anti‐DNA virus field of research and development has shifted recently in the direction of the study of more common heterocyclic structures as protein inhibitors.
Enzymes as Drug Targets
Authors: Meek Thomas D.
Published: April 2021

Many drugs commonly used today to treat infectious diseases, cancers, inflammatory, cardiovascular, and metabolic diseases, are enzyme inhibitors or inactivators. Examples exist for all six classes of enzymes, but inhibitors of hydrolases, transferases, and oxidoreductases predominate. Typically, enzyme inhibitors or inactivators that progress to become drugs exert high potency toward their targets at concentrations of 100 nanomolar or less, and attending these potencies is high selectivity for their targets. Drugs that block the activity of enzymes do so by either covalent reaction with nucleophilic enzymatic residues, or by noncovalent binding. Covalent inactivation by affinity agents and mechanism‐based inactivators is generally irreversible, leading to time‐dependent loss of enzyme activity that is normally un‐recoverable. Drugs that are noncovalent enzyme inhibitors, including bi‐substrate analogs, and analogs of enzyme reaction intermediates and transition states, like their covalent counterparts, often display time‐dependent inhibition despite the absence of covalent reaction. This pseudoirreversible inhibition is manifest at nanomolar concentrations of inhibitor, and is due to the isomerization of an initial enzyme–inhibitor complex to a tighter binary complex which reverses very slowly, if at all. Natural‐product enzyme inhibitors have provided the blueprints for many drugs, including the statins, epoxomicin, and inhibitors of HIV protease. We describe herein the aforementioned types of enzyme inhibitors and inactivators that, through the application of medicinal chemistry have rendered new therapies, including case histories of many of the more important drugs that block the action of enzymes.
FDA‐Approved Medicines
Authors: Kinch Michael S.
Published: April 2021

Although medicines have been needed for the entire span of human existence, the age of pharmaceuticals is a relatively recent era. The benefits accompanying the introduction of new medicines meant to combat age‐old maladies have dramatically altered public health and society. Herein, we review the history of drug discovery, demonstrating a constant evolution in both the approaches utilized and the outcomes of technological and scientific advances. These innovations have come with a cost as reflected in the ever‐increasing amounts of resources to develop a medicine. Indeed, we see the industry, as currently configured, is faced with unprecedented challenges that could soon threaten its very existence.
Therapeutic Strategies for the Treatment of Sickle Cell Disease
Authors: Safo Martin K. , Aljahdali Anfal , Burnett James , Abraham Donald J. , Abdulmalik Osheiza
Published: April 2021

There are many important new advances in the development of clinically viable therapeutic options to mitigate the pathophysiology of sickle cell disease (SCD). Some of the most promising new clinical candidates reported herein directly address the primary cause of the disease by allosterically modifying sickle hemoglobin (HbS). In particular, one family of small molecules stabilizes the high oxygen (O
2
)‐affinity R‐state of the protein, which, unlike the low O
2
‐affinity T‐state, does not present the polymerization promoting βVal6 residue. Several compounds employing this mechanism are currently at various stages of preclinical and clinical investigations. Another series of compounds that engage in a covalent bond with the surface‐located residue βCys93 of HbS, and thus destabilize the T‐state to increase Hb affinity for oxygen, is currently under preclinical development. Furthermore, promising new compounds that, similar to hydroxyurea also induce fetal Hb production, are at various stages of clinical development. Finally, compounds that target the secondary pathophysiology of SCD, including those that counter the dehydration of sickle erythrocyte; endothelial adhesion and vasculature damage; nitroxide donors providing vasodilatory and anti‐inflammatory effects; and a myriad of anti‐inflammatory and anticoagulation candidate molecules, are also being investigated in early‐ and/or late‐stage clinical trials.
Bacterial Efflux Pumps and Their Inhibitors
Authors: Zgurskaya Helen I. , Rybenkov Valentin V. , Walker John K. , Parks Jerry M.
Published: April 2021

Bacterial multidrug efflux transporters have distinct molecular features and mechanisms that enable their impressive substrate polyspecificity. These transporters are involved in all physiological processes where nonspecific but active transport across membranes is critical for survival and proliferation. Importantly, efflux pumps contribute to bacterial virulence and pathogenesis, as well as the spread of antibiotic resistance in clinics. Transporters belonging to several protein superfamilies have been selected for polyspecificity by evolution and augmented with accessory proteins that extend and couple transport reactions across the inner and outer membranes of the bacterium. As a result, bacteria are equipped with diverse efflux machines that protect cells from a broad variety of toxic compounds including antibiotics and other small molecule therapeutics. The inhibition of such polyspecific biomolecular machines is a challenging task, which still awaits an efficient solution. Here, we review the molecular mechanisms of efflux pumps from Gram‐negative bacteria and recent advances and challenges associated with the discovery of effective inhibitors of these pumps.
Computational Chemistry Tools
Authors: Metcalf Rainer , Daniel Kenyon , Brooks Wesley , Guida Wayne
Published: April 2021

This article expounds on some of the current computational tools and programs available and the best practices associated with their use. A high‐level introduction, intended for both novices and the semi‐experienced, focusing on the more common programs used in scientific literature is the scope of this article. Both classical and quantum techniques are described. Classical methodologies include molecular dynamics, Monte Carlo, energy minimization methods, molecular docking, low‐mode, and homology modeling. Quantum chemistry techniques are also discussed, encompassing Hartree–Fock, Post‐Hartree–Fock theories, and Density Functional Theory along with associated basis sets. A summary is provided to give a general overview of common modeling software and their functionality.
Genetic Code and Its Variations
Authors: Suzuki Tsutomu , Nagao Asuteka
Published: April 2021

The standard genetic code is a common language used by almost all organisms to translate nucleotide sequences from DNA and RNA into the amino acid sequences of proteins. However, the standard code is not used in all cases, and some organisms and organelles use variant codes.

The genetic code is a basic grammar for translating genetic information into amino acid sequence of protein. Most organisms use the same genetic code, so‐called standard genetic code, assuming that all domains of life evolved from a single organism.

Transfer RNA (tRNA)is an adaptor molecule that links the genetic code with its corresponding amino acid via codon‐anticodon interaction.

A wide variety of chemical modifications in the tRNA anticodons play an important role in accurate protein synthesis by restriction, expansion and alteration of codon recognition.

Natural instances of genetic code variation in several organisms and organelles violated a concept that the genetic code is frozen, but proposed it has continued to evolve.

Recoding is an alternative usage of genetic code in some special biological contexts. including programmed ribosome frameshifting, stop‐codon read‐through, insertion of nonstandard amino acids and translational bypassing.
3D Porous Honeycomb‐Like CoN‐Ni3N/N‐C Nanosheets Integrated Electrode for High‐Energy‐Density Flexible Supercapacitor
Authors: Li Kunzhen , Zhao Bangchuan , Zhang Hui , Lv Hongyan , Bai Jin , Ma Hongyang , Wang Peiyao , Li Wanyun , Si Jianguo , Zhu Xuebin , Sun Yuping
Published: April 2021

Transition metal nitrides (TMNs) are considered as potential electrode materials for high‐performance energy storage devices. However, the structural instability during the electrochemical reaction process severely hinders their wide application. A general strategy to overcome this obstacle is to fabricate nanocomposite TMNs on the conducting substrate. Herein, the honeycomb‐like CoN‐Ni3N/N‐C nanosheets are in situ grown on a flexible carbon cloth (CC) via a mild solvothermal method with post‐nitrogenizing treatment. As an integrated electrode for the supercapacitor, the optimized CoN‐Ni3N/N‐C/CC achieves remarkable electrochemical performance due to the enhanced intrinsic conductivity and increased concentration of the active sites. In particular, the flexible quasi‐solid‐state asymmetric supercapacitor assembled with CoN‐Ni3N/N‐C/CC cathode and VN/CC anode delivers an excellent energy density of 106 μWh cm−2, maximum power density of 40 mW cm−2, along with an outstanding cycle stability. This study provides a neoteric perspective on construction of high‐performance flexible energy storage devices with novel metallic nitrides.
Amorphous Domains in Black Titanium Dioxide
Authors: Kang Jianxin , Zhang Yan , Chai Ziwei , Qiu Xiaoyi , Cao Xingzhong , Zhang Peng , Teobaldi Gilberto , Liu Li‐Min , Guo Lin
Published: April 2021

Although oxygen vacancies (Ovs) play a critical role for many applications of metal oxides, a controllable synthetic strategy for anisotropic Ovs remains a great challenge. Here, a novel strategy is proposed to achieve the regional dual structure with anisotropic Ovs at both the surface and in the interior of TiO2 by constructing amorphous domains. The as‐prepared black TiO2 with amorphous domains exhibits superior activity in degrading rhodamine B (RhB) solutions, which can instantly decompose RhB with just a shake. First‐principle simulations reveal that subsurface Ovs in TiO2 are energetically favored, resulting in the formation of amorphous domains in the interior region via diffusion of surface‐formed Ovs into the subsurface. The stable Ov‐induced amorphous domains in TiO2 with enhanced catalytic performances provide a scalable strategy to practical Ov engineering in functional metal oxides.
MIL‐101‐Derived Mesoporous Carbon Supporting Highly Exposed Fe Single‐Atom Sites as Efficient Oxygen Reduction Reaction Catalysts
Authors: Xie Xiaoying , Peng Lishan , Yang Hongzhou , Waterhouse Geoffrey I. N. , Shang Lu , Zhang Tierui
Published: April 2021

Fe single‐atom catalysts (Fe SACs) with atomic FeNx active sites are very promising alternatives to platinum‐based catalysts for the oxygen reduction reaction (ORR). The pyrolysis of metal–organic frameworks (MOFs) is a common approach for preparing Fe SACs, though most MOF‐derived catalysts reported to date are microporous and thus suffer from poor mass transfer and a high proportion of catalytically inaccessible FeNx active sites. Herein, NH2‐MIL‐101(Al), a MOF possessing a mesoporous cage architecture, is used as the precursor to prepare a series of N‐doped carbon supports (denoted herein as NC‐MIL101‐T) with a well‐defined mesoporous structure at different pyrolysis temperatures. The NC‐MIL101‐T supports are then impregnated with a Fe(II)‐phenanthroline complex, and heated again to yield Fe SAC‐MIL101‐T catalysts rich in accessible FeNx single atom sites. The best performing Fe SAC‐MIL101‐1000 catalyst offers outstanding ORR activity in alkaline media, evidenced by an ORR half‐wave potential of 0.94 V (vs RHE) in 0.1 m KOH, as well as excellent performance in both aqueous primary zinc–air batteries (a near maximum theoretical energy density of 984.2 Wh kgZn−1) and solid‐state zinc–air batteries (a peak power density of 50.6 mW cm−2 and a specific capacity of 724.0 mAh kgZn−1).
Heterophase Interface Dominated Deformation and Mechanical Properties in Al‐Cu‐Li Alloys
Authors: Wang Shuo , Zhang Chi , Li Xin , Wang Junsheng
Published: April 2021

As a common phenomenon in multiphase systems, interfacial deformation has a significant impact on the mechanical properties of materials. By utilizing the brittle cleavage and plastic slip modes, the deformation mechanism is tracked and mechanical properties of precipitate/matrix and precipitate/precipitate heterophase interfaces are induced in third‐generation Al‐Li alloys, including δ'(Al3Li)/α‐Al, θ'(Al2Cu)/α‐Al, and δ'(Al3Li)/θ'(Al2Cu) (depending on the ultrafine δ'/θ'/δ' composite precipitate). Based on bond energy and ideal stress calculations under tensile and shear deformations, it is noted that the universal interface separating the two phases is not the weakest link in these systems. In δ'/θ'/δ', specifically, the defined coherent interface I closing to the δ' may become a weak cracking point under tensile loading. Whereas, the semi‐coherent interface II on the edge of the δ'/θ'/δ' tends to undergo interplanar slip along the [001] direction at relatively low shear stress. By releasing a partial dislocation under shear deformation, the local stable stacking fault can occur in this semi‐coherent interface. And the interface‐mediated plasticity within the ultrafine δ'/θ'/δ' composite precipitate could be expected to solve the origin of the strength‐ductility conflict in modern Al‐Li alloys. Besides, the electronic structures and atomic bonding are performed to reveal the mechanism behind the improved interface strength.
Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects
Authors: Favilla Bianca Pereira , Meloni Vera Ayres , Perez Ana Beatriz , Moretti‐Ferreira Danilo , de Souza Deise Helena , Bellucco Fernanda Teixeira , Melaragno Maria Isabel
Published: April 2021

Patients with unbalanced X‐autosome translocations are rare and usually present a skewed X‐chromosome inactivation (XCI) pattern, with the derivative chromosome being preferentially inactivated, and with a possible spread of XCI into the autosomal regions attached to it, which can inactivate autosomal genes and affect the patients' phenotype. We describe three patients carrying different unbalanced X‐autosome translocations, confirmed by G‐banding karyotype and array techniques. We analyzed their XCI pattern and inactivation spread into autosomal regions, through HUMARA, ZDHHC15 gene assay and the novel 5‐ethynyl‐2′‐deoxyuridine (EdU) incorporation assay, and identified an extremely skewed XCI pattern toward the derivative chromosomes for all the patients, and a variable pattern of late‐replication on the autosomal regions of the derivative chromosomes. All patients showed phenotypical overlap with patients presenting deletions of the autosomal late‐replicating regions, suggesting that the inactivation of autosomal segments may be responsible for their phenotype. Our data highlight the importance of the XCI spread into autosomal regions for establishing the clinical picture in patients carrying unbalanced X‐autosome translocations, and the incorporation of EdU as a novel and precise tool to evaluate the inactivation status in such patients.
Hybrid Electrolyte Engineering Enables Safe and Wide‐Temperature Redox Flow Batteries
Authors: Zhang Leyuan , Yu Guihua
Published: April 2021

Electrolyte is an important component in redox flow batteries (RFBs) that determines the current capability, potential window, and safety, but both aqueous and nonaqueous electrolytes have their intrinsic limits. Here, we develop the proof‐of‐concept hybrid electrolyte chemistry to enable the design of safe and wide‐temperature RFBs. In addition to the non‐flammable characteristics, the hybrid electrolyte also inherits the high electrochemical stability and wide operational temperature range. It can show a potential window of 2.5 V and maintain high ion conductivities at low temperatures. It also enables LiI to achieve high Coulombic efficiencies of >99.9 %, showing long cycling stability over 800 cycles. Moreover, it enables the successful operation of Zn/LiI RFBs at −20 °C for 150 cycles with nearly no capacity loss. This study highlights the great potential of hybrid electrolyte chemistry for the approach of safe and high‐performance large‐scale energy storage systems in wide temperature ranges.
Direct Observation of Metal Oxide Nanoparticles Being Transformed into Metal Single Atoms with Oxygen‐Coordinated Structure and High‐Loadings
Authors: Liu Jian , Cao Changyan , Liu Xiaozhi , Zheng Lirong , Yu Xiaohu , Zhang Qinghua , Gu Lin , Qi Ruilian , Song Weiguo
Published: April 2021

Direct conversion of bulk metal or nanoparticles into metal single atoms under thermal pyrolysis conditions is a highly efficient and promising strategy to fabricate single‐atom catalysts (SACs). Usually, nitrogen‐doped carbon is used as the anchoring substrate to capture the migrating metal ion species at high temperatures, and stable isolated SACs with nitrogen coordination are formed during the process. Herein, we report unexpected oxygen‐coordinated metal single‐atom catalysts (Fe‐, Co‐, Ni‐, Mn‐SACs) with high loadings (above 10 wt %) through direct transformation of metal oxide nanoparticles (Fe‐, Co‐, Ni‐, Mn‐NPs) in an inert atmosphere at 750 °C for 2 h. The atomic dispersion of metal single atoms and their coordinated structures were confirmed by aberration‐corrected scanning transmission electron microscopy and X‐ray absorption fine structures. In addition, the dynamic process of nanoparticles to atoms was directly observed by in situ transmission electron microscopy. The as‐prepared Fe SAC exhibited high activity and superior selectivity for catalytic oxidation of benzene to phenol with hydrogen peroxide.
Monitoring the curing processes of epoxy oligomers with partially substituted polyethoxymetallosiloxanes by IR spectroscopy and thermomechanical analysis
Authors: Parshina Maria S. , Tarasenkov Alexander N. , Aysin Rinat R. , Tebeneva Nadezhda A. , Buzin Michail I. , Afanasyev Egor S. , Serenko Olga A. , Muzafarov Aziz M.
Published: April 2021

In this work, the curing of «ED‐20» epoxy resin with partially siloxy‐substituted aluminum, iron, and zirconium siloxanes that we obtained previously was studied. The initial content of a metallosiloxane in the compositions was 5–50 wt% with respect to the resin. In all the cases, thermal curing was used to obtain a series of samples in the form of solid homogeneous materials. The fact of the epoxy ring opening in the resin was confirmed by IR spectroscopy. The catalytic properties of the metal atom in a metallosiloxane were found to affect the curing process. The samples demonstrate rather a high resistance to thermooxidative destruction, and in most cases, their glass transition temperatures are lower than those obtained upon standard curing of «ED‐20» resin with triethylenetetramine. Partially siloxy‐substituted metalloalkoxysiloxanes can be efficient agents for curing and formation of a hybrid material based on epoxy resins.
Hierarchical consensus problem in hybrid multiagent systems
Authors: Hou Jian , Tang Qingshi , Xiang Gang , Luo Shuyun
Published: April 2021

This paper considers a hierarchical consensus problem in hybrid multiagent systems. By partitioning the agents into several groups, each group contains a value concerning all the state information inside the group, which is called group information. For each single agent, its control input includes not only the inner‐group neighboring agent information but also the group information from its neighboring groups. Moreover, we discuss two kinds of hybrid systems composing of both continuous‐time and discrete‐time dynamic information and propose the corresponding control laws. Finally, simulations are provided to demonstrate the effectiveness of our theoretical results.
Cancer as a prospective sequela of long COVID‐19
Authors: Saini Geetanjali , Aneja Ritu
Published: April 2021

As the spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) continues to surge worldwide, our knowledge of coronavirus disease 2019 (COVID‐19) is rapidly expanding. Although most COVID‐19 patients recover within weeks of symptom onset, some experience lingering symptoms that last for months (“long COVID‐19”). Early reports of COVID‐19 sequelae, including cardiovascular, pulmonary, and neurological conditions, have raised concerns about the long‐term effects of COVID‐19, especially in hard‐hit communities. It is becoming increasingly evident that cancer patients are more susceptible to SARS‐CoV‐2 infection and are at a higher risk of severe COVID‐19 than the general population. Nevertheless, whether long COVID‐19 increases the risk of cancer in those with no prior malignancies, remains unclear. Given, the disproportionate impact of the disease on the African American community, yet another unanswered question is whether racial disparities are to be expected in COVID‐19 sequelae. Herein, we propose that long COVID‐19 may predispose recovered patients to cancer development and accelerate cancer progression. This hypothesis is based on growing evidence of the ability of SARS‐CoV‐2 to modulate oncogenic pathways, promote chronic low‐grade inflammation, and cause tissue damage. Comprehensive studies are urgently required to elucidate the effects of long COVID‐19 on cancer susceptibility.
Successful modeling of long term outcomes in end‐stage renal disease patients undergoing percutaneous coronary intervention with drug‐eluting stents
Authors: Dunn Aaron N. , Huded Chetan , Raymond Russell , Lincoff A. Michael , Bajzer Christopher , Kapadia Samir , Ellis Stephen G.
Published: April 2021

Objectives

The objective of this study is to identify and model risk factors for major adverse cardiac events (MACE) and all‐cause mortality among patients with ESRD treated with PCI using DES.

Background

Patients with end‐stage renal disease (ESRD) have poor long‐term outcomes after percutaneous coronary intervention (PCI) compared with non‐ESRD patients. However, there is a paucity of literature regarding risk factors associated with outcomes of ESRD patients after PCI with drug‐eluding stents (DES).

Methods

This retrospective cohort study includes all patients with ESRD who underwent first‐time PCI with DES at a single, high‐volume hospital between 1/1/2005 and 12/31/2015, with follow‐up through 9/1/2019. Primary outcomes were MACE (cardiac death, myocardial infarction, or unplanned revascularization) and all‐cause mortality.

Results

Five‐year MACE was 83.0% and five‐year morality was 77.9% in patients with ESRD (n = 285). Among ESRD patients, factors independently associated with MACE were C‐reactive peptide level, SYNTAX score, peripheral vascular occlusive disease, hemoglobin, and treatment of a restenotic lesion (c‐index = 0.66). Factors independently associated with mortality in ESRD patients were age, SYNTAX score, non‐use of statins at baseline, insulin‐dependent diabetes, chronic obstructive pulmonary disease (COPD), peripheral vascular occlusive disease, and platelet count (c‐index = 0.65).

Conclusions

Despite relatively poor 1‐and 5‐year outcomes among ESRD patients after PCI, risk of MACE and mortality among this cohort can be successfully modelled, which meaningfully informs clinicians regarding management of ESRD patients with coronary artery disease (CAD). Further investigations are necessary to determine whether or not outcomes might be improved through risk profile modification.
Future culprit detection based on angiography‐derived FFR
Authors: Pagnoni Mattia , Meier David , Candreva Alessandro , Maillard Luc , Adjedj Julien , Collet Carlos , Mahendiran Thabo , Cook Stephane , Mujcinovic Alma , Dupré Marion , Rubimbura Vladimir , Roguelov Christan , Eeckhout Eric , De Bruyne Bernard , Muller Olivier , Fournier Stephane
Published: April 2021

Objectives

We sought to characterize the hemodynamic impact of mild coronary artery disease (CAD) using quantitative flow ratio (QFR, an angiography‐derived fractional flow reserve [FFR]) in a population of patients with only non‐significant CAD at baseline that subsequently experienced a myocardial infarction (MI).

Background

The discriminatory value of FFR in patients with mild CAD remains imperfect.

Methods

We retrospectively included patients who underwent invasive coronary angiography for an MI, in whom another angiogram had been performed within the previous 5 years. Three‐dimensional quantitative coronary angiography, QFR, and lesion length analysis were conducted on lesions responsible for the MI (future culprit lesions, [FCL]) as well as on control lesions (non‐culprit lesions, [NCL]).

Results

Eighty‐three FCL and 117 NCL were analyzed in 83 patients: FCL were more severe (median % diameter of stenosis [DS] 39.1% [29.8; 45.7] vs. 29.8% [25.0; 37.2], p < .001), had lower QFR values (0.94 [0.86; 0.98] vs. 0.98 [0.96; 1.00], p < .001) and tended to be longer (15.2 mm [10.0; 27.3] vs. 12.7 mm [9.3; 22.4], p = .070) than NCL. In lesions with an interval < 2 years between baseline angiography and MI, the difference in QFR was more pronounced compared to the lesions with a longer interval (FCL: 0.92 [0.85; 0.97] vs. NCL: 0.98 [0.94; 1.00], p < .001 and FCL: 0.96 [0.88; 1.00] vs. NCL: 0.98 [0.96;1.00], p = .006 respectively)

Conclusion

Mild coronary stenoses that are subsequently responsible for an MI (FCL) exhibit a higher DS and lower QFR years before the event. Furthermore, FCL with a lower QFR at baseline appear to lead earlier to MI.
Highly Selective Synthesis of Ethanol via CO2 Hydrogenation over CoMoCx Catalysts
Authors: Zhang Huiyu , Han Han , Xiao Linfei , Wu Wei
Published: April 2021

Hydrogenation of CO2 to ethanol is one of the promising and emerging routes for the transformation of CO2 into value‐added chemicals. In the present work, series of CoMoCx catalysts were prepared by using ionic liquids as all‐in‐one precursors and adjusted the proportional and electronic properties of CoMoCx catalysts by modifying carburization temperature, the efficiency of CO2 to ethanol hydrogenation was optimized. Under the optimal reaction conditions (180 °C and 2 MPa), the selectivity of ethanol reached 97.4 %, and the yield of ethanol arrived at 0.528 mmolgcat.−1h−1. In situ DRIFTS results revealed that a nucleophilic attack on the carbon of CH3O* by a formyl to form ethanol.
Excitation of Radical Anions of Naphthalene Diimides in Consecutive‐ and Electro‐Photocatalysis**
Authors: Caby Sofia , Bouchet Lydia M. , Argüello Juan E. , Rossi Roberto A. , Bardagi Javier I.
Published: April 2021

Both photo‐ and electrochemical transformations represent excellent opportunities for the development of environmentally friendly methodologies which, if combined, would result in improved methodologies. Thus, we present here a family of naphthalene diimide photocatalysts comparing a “pure” photochemical and an electro‐photochemical transformation; by means of a C−H substitution in (hetero)aromatic systems with C−C bond formation. We identify a system that has the potential to be applied in both approaches with minor changes in the reaction conditions and recognize the excitation of radical anion of naphthalene diimides as the key event. Both approaches produce similar yields and reaction rates, although a consecutive photoinduced electron transfer (conPET) process shows in principle a simpler setup and more tolerance to a poor catalyst solubility, the electro‐PET process improves selectivity and gives more room for optimization. The more accessible “pure” photochemical approach could be used as an initial assessment for photocatalytic transformation and electro‐photocatalytic transformation.
Distorted Porphyrins with High Stability: Synthesis and Characteristic Electronic Properties of Mono‐ and Di‐Nuclear Tricarbonyl Rhenium Tetraazaporphyrin Complexes
Authors: Wang Mengfei , Murata Kei , Ishii Kazuyuki
Published: April 2021

Mono‐ and di‐nuclear tricarbonyl Re(I) tetraazaporphyrin complexes (Re1TAP and Re2TAP) are investigated and compared with Re(I) phthalocyanine complexes (Re1Pc and Re2Pc). Although Re2Pc is unstable in polar solvents, and easily undergoes demetallation reaction, the coordination of the TAP ligand significantly improves the tolerance toward polar solvents, affording more stability to Re2TAP. Additionally, the incorporation of [Re(CO)3]+ unit(s) and the TAP ligand results in remarkable positive shifts in both oxidation and reduction potentials. Consequently, the more positive oxidation potentials of the ReTAP complexes significantly increase the tolerance toward oxidation, while the reduction potential indicates that Re2TAP is suitable for a soluble electron acceptor. In contrast to Re1Pc and Re2Pc, Re1TAP and Re2TAP show unique broad Q bands, which can be attributed to the admixture of the π‐π* and metal‐to‐ligand charge transfer characters, owing to the lowered π orbital energy in the TAP complexes. This study is useful for controlling electronic properties and realizing high stability in Pc analogues.
Combining data assimilation and machine learning to build data‐driven models for unknown long time dynamics—Applications in cardiovascular modeling
Authors: Regazzoni Francesco , Chapelle Dominique , Moireau Philippe
Published: April 2021

We propose a method to discover differential equations describing the long‐term dynamics of phenomena featuring a multiscale behavior in time, starting from measurements taken at the fast‐scale. Our methodology is based on a synergetic combination of data assimilation (DA), used to estimate the parameters associated with the known fast‐scale dynamics, and machine learning (ML), used to infer the laws underlying the slow‐scale dynamics. Specifically, by exploiting the scale separation between the fast and the slow dynamics, we propose a decoupling of time scales that allows to drastically lower the computational burden. Then, we propose a ML algorithm that learns a parametric mathematical model from a collection of time series coming from the phenomenon to be modeled. Moreover, we study the interpretability of the data‐driven models obtained within the black‐box learning framework proposed in this paper. In particular, we show that every model can be rewritten in infinitely many different equivalent ways, thus making intrinsically ill‐posed the problem of learning a parametric differential equation starting from time series. Hence, we propose a strategy that allows to select a unique representative model in each equivalence class, thus enhancing the interpretability of the results. We demonstrate the effectiveness and noise‐robustness of the proposed methods through several test cases, in which we reconstruct several differential models starting from time series generated through the models themselves. Finally, we show the results obtained for a test case in the cardiovascular modeling context, which sheds light on a promising field of application of the proposed methods.
Towards Carbon‐Neutral Methanol Production from Carbon Dioxide Electroreduction
Authors: Zhang Shuzhen , Jing Xuechen , Wang Yuhang , Li Fengwang
Published: April 2021

Electrochemical conversion of CO2 into liquid fuels and chemicals powered by renewable energy is a promising method to reduce concentration of CO2 in the atmosphere. Methanol, a value‐added fuel and raw industrial material, can potentially derive from CO2 electroreduction. However, this route has been plagued by insufficient selectivity, activity, and efficiency. This review summarizes recent advances of electrochemical CO2‐to‐methanol conversion, highlighting mechanistic studies, materials innovations, and reactor designs that aim for improving selectivity, activity, and efficiency of the reaction. The potential challenges and prospects are discussed to guide future advances of this emerging field.
Synthesis of Snowman‐shaped Photocatalytic Microrotors and Mechanical Micropumps
Authors: Lv Xiaomeng , Du Sinan , Zhou Chao , Wang Wei , Wang Huaguang , Zhang Zexin
Published: April 2021

We synthesize snowman‐shaped microrotors that are composed of TiO2and SiO2particles fused together and half‐coated with Au. The microrotors rotate in the presence of fuel and UV light and the rotation speed is readily modulated by the fuel concentration and the light intensity. Such a microrotor can be transformed into a mechanical micropump that hydrodynamically, rather than electrokinetically, pumps nearby fluids and particles, with a pump power that scales linearly with its rotation speed. This work thereby opens up a new way for the study of microrotors as micropumps.
Memory stem T cells modified with a redesigned CD30‐chimeric antigen receptor show an enhanced antitumor effect in Hodgkin lymphoma
Authors: Alvarez‐Fernández Carmen , Escribà‐Garcia Laura , Caballero AC , Escudero‐López Eva , Ujaldón‐Miró Cristina , Montserrat‐Torres Rosanna , Pujol‐Fernández Paula , Sierra Jorge , Briones Javier
Published: April 2021

Objectives

Adoptive cell therapy (ACT) with mature T cells modified with a chimeric antigen receptor has demonstrated improved outcome for B‐cell malignancies. However, its application for others such as Hodgkin lymphoma remains a clinical challenge. CD30 antigen, expressed in Hodgkin lymphoma cells, is absent in most healthy tissues, representing an ideal target of ACT for this disease. Despite that, efficacy of CD30‐chimeric antigen receptor (CAR) T cells for Hodgkin lymphoma remains modest. Here, we have developed and tested a novel CD30‐CAR T to improve efficacy of CD30‐CAR therapy, using a targeting epitope within the non‐cleavable part of CD30 receptor, and memory stem T cells (TSCM) to improve engraftment, persistence and antitumor activity.

Methods

TSCM‐like cultures were generated and expanded ex vivo and transduced at day 1 or 2 with a lentiviral vector encoding the CD30‐CAR. Therapeutic in vivo experiments were performed using NSG mice injected with L540 (sc) or L428 (iv) and treated with CD30‐CAR T cells when the tumor was established.

Results

CD30‐CAR TSCM‐like cells generated and expanded ex vivo, despite CD30 expression and fratricide killing of CD30+ CAR T cells, were not impaired by soluble CD30 and completely eradicated Hodgkin lymphoma in vivo, showing high persistence and long‐lasting immunity. In addition, highly enriched CD30‐CAR TSCM‐like products confer a survival advantage in vivo, in contrast to more differentiated CAR T cells, with higher tumor infiltration and enhanced antitumor effect.

Conclusion

This study supports the use of a refined CD30‐CAR T cells with highly enriched TSCM‐like products to improve clinical efficacy of CAR T for Hodgkin lymphoma.
Land‐use intensity and biodiversity effects on infiltration capacity and hydraulic conductivity of grassland soils in southern Germany
Authors: Leimer Sophia , Berner Doreen , Birkhofer Klaus , Boeddinghaus Runa S. , Fischer Markus , Kandeler Ellen , Kuka Katrin , Marhan Sven , Prati Daniel , Schäfer Deborah , Schöning Ingo , Solly Emily F. , Wolters Volkmar , Wilcke Wolfgang
Published: April 2021

Evidence from experimental and established grasslands indicates that plant biodiversity can modify the water cycle. One suspected mechanism behind this is a higher infiltration capacity (νB) and hydraulic conductivity (K) of the soil on species‐rich grasslands. However, in established and agriculturally managed grasslands, biodiversity effects cannot be studied independent of land‐use effects. Therefore, we investigated in established grassland systems how land‐use intensity and associated biodiversity of plants and soil animals affect νB and K at and close to saturation. On 50 grassland plots along a land‐use intensity gradient in the Biodiversity Exploratory Schwäbische Alb, Germany, we measured νB with a hood infiltrometer at several matrix potentials and calculated the saturated and unsaturated K. We statistically analysed the relationship between νB or K and land‐use information (e.g., fertilising intensity), abiotic (e.g., soil texture) and biotic data (e.g., plant species richness, earthworm abundance). Land‐use intensity decreased and plant species richness increased νB and K, while the direction of the effects of soil animals was inconsistent. The effect of land‐use intensity on νB and K was mainly attributable to its negative effect on plant species richness. Our results demonstrate that plant species richness was a better predictor of νB and K at and close to saturation than land‐use intensity or soil physical properties in the established grassland systems of the Schwäbische Alb.
Modeling pedestrian group behavior in crowd evacuations
Authors: Turgut Yakup , Bozdag Cafer Erhan
Published: April 2021

Many models have been developed in recent years to describe pedestrian group behavior. Most prior research on group behavior focuses mainly on small groups and does not provide a general approach for grouping pedestrians with respect to different group sizes. They also analyze pedestrian group dynamics in normal circumstances. However, people's reactions who are aware of an emergency are not the same as how they respond to normal or usual situations. The central focus of this paper is to study pedestrian group behavior during evacuation. To accomplish these objectives, a new model is proposed with some extensions of a social force model in its emergency context. The new extensions are intended to simulate the single leader‐centered and group‐centered crowd behavior in emergencies. Besides small pedestrian groups, larger ones are also considered, and extensions are added in this direction. The model is calibrated using the results of an existing experimental study. Then, the model is verified by testing for the occurrence of certain emergent patterns. The results indicate that the proposed model can capture these trends. Additionally, the model is validated by comparing the simulation results with experimental results available in the literature. Also, several different evacuation scenarios are used to evaluate the proposed model. The simulation results show that leader‐centered behavior performs better than group‐centered behavior with respect to the evacuation time for small groups. The number of leaders also affects the evacuation time. Moreover, an increase in the number of leaders positively influences the effect of the width of the door on evacuation time, but the size of this effect depends on the number of leaders. Finally, group‐centered behavior results in less evacuation time than leader‐centered behavior in the presence of multiple exits, and leader‐centered (also called single leader‐centered in this study) behavior causes a more unbalanced use of the exits than group‐centered behavior.
The impact of increased outpatient telehealth during COVID‐19: Retrospective analysis of patient survey and routine activity data from a major healthcare system in England
Authors: Tyler Joshua M.B. , Pratt Adrian C. , Wooster Job , Vasilakis Christos , Wood Richard M.
Published: April 2021

In response to societal restrictions due to the COVID‐19 pandemic, a significant proportion of physical outpatient consultations were replaced with virtual appointments within the Bristol, North Somerset and South Gloucestershire healthcare system. The objective of this study was to assess the impact of this change in informing the potential viability of a longer‐term shift to telehealth in the outpatient setting. A retrospective analysis was performed using data from the first COVID‐19 wave, comprising 2998 telehealth patient surveys and 143,321 distinct outpatient contacts through both the physical and virtual medium. Four in five specialities showed no significant change in the overall number of consultations per patient during the first wave of the pandemic when telehealth services were widely implemented. Of those surveyed following virtual consultation, more respondents ‘preferred’ virtual (36.4%) than physical appointments (26.9%) with seven times as many finding them ‘less stressful’ than ‘more stressful’. In combining both patient survey and routine activity data, this study demonstrates the importance of using data from multiple sources to derive useful insight. The results support the potential for telehealth to be rapidly employed across a range of outpatient specialities without negatively affecting patient experience.
Counterfactual analysis under partial identification using locally robust refinement
Authors: Canen Nathan , Song Kyungchul
Published: April 2021

Structural models that admit multiple reduced forms, such as game‐theoretic models with multiple equilibria, pose challenges in practice, especially when parameters are set identified and the identified set is large. In such cases, researchers often choose to focus on a particular subset of equilibria for counterfactual analysis, but this choice can be hard to justify. This paper shows that some parameter values can be more “desirable” than others for counterfactual analysis, even if they are empirically equivalent given the data. In particular, within the identified set, some counterfactual predictions can exhibit more robustness than others against local perturbations of the reduced forms (e.g., the equilibrium selection rule). We provide a representation of this subset, which can be used to simplify the implementation. We illustrate our message using moment inequality models and provide an empirical application based on a model with top coded data.
Rutin restrains the growth and metastasis of mouse breast cancer cells by regulating the microRNA‐129‐1‐3p‐mediated calcium signaling pathway
Authors: Li Qi , Xu Dongsheng , Gu Zehui , Li Tengteng , Huang Peng , Ren Liqun
Published: April 2021

Breast cancer is a common malignancy that is highly lethal. Due to the poor prognosis, more effective and efficient treatment methods are urgently needed. Rutin (RUT) is a traditional Chinese medicine reported to have a variety of pharmacological properties, including anticancer properties. However, the effects of RUT on breast cancer and its underlying molecular mechanism of action remain unclear. In the present study, we observed a significant downregulation of microRNA (miR)−129‐1‐3p in mouse breast cancer cells (4T1) compared with the expression in mouse normal breast epithelial cells (HC11). We also found that RUT could increase the expression of miR‐129‐1‐3p in 4T1 cells and suppress cell proliferation. To elucidate the molecular mechanism of action of RUT, miR‐129‐1‐3p mimics and its inhibitor were transfected into 4T1 cells. miR‐129‐1‐3p overexpression could inhibit the proliferation, invasion, migration, and calcium overload of mouse breast cancer cells and also enhance apoptosis, whereas miR‐129‐1‐3p knockdown had the opposite effects. Taken together, cell‐based experiments indicated that RUT restrains the growth of mouse breast cancer cells by regulating the miR‐129‐1‐3p/Ca2+ signaling pathway. This study also revealed the inhibitory effect of RUT on breast cancer cells at the noncoding RNA level and provided a theoretical foundation for the application of RUT as a drug to inhibit tumor growth.