bluuebunny/crossref_metadata_2025 huggingface dataset:
Bright Luminescence by Combining Chiral [2.2]Paracyclophane with a Boron–Nitrogen‐Doped Polyaromatic Hydrocarbon Building Block
Authors: Rapp Mario R. , Leis Wolfgang , Zinna Francesco , Di Bari Lorenzo , Arnold Tamara , Speiser Bernd , Seitz Michael , Bettinger Holger F.
Published: December 2021

Novel BN‐doped compounds based on chiral, tetrasubstituted [2.2]paracyclophane and NBN‐benzo[f,g]tetracene were synthesized by Sonogashira–Hagihara coupling. Conjugated ethynyl linkers allow electronic communication between the π‐electron systems through‐bond, whereas through‐space interactions are provided by strong π–π overlap between the pairs of NBN‐building blocks. Excellent optical and chiroptical properties in racemic and enantiopure conditions were measured, with molar absorption coefficients up to ϵ=2.04×105 M−1 cm−1, fluorescence quantum yields up to ΦPL=0.70, and intense, mirror‐image electronic circular dichroism and circularly polarized luminescence signals of the magnitude of 10−3 for the absorption and luminescence dissymmetry factors. Computed glum,calcd. values match the experimental ones. Electroanalytical data show both oxidation and reduction of the ethynyl‐linked tetra‐NBN‐substituted paracyclophane, with an overlap of two redox processes for oxidation leading to a diradical dication.
The risk of rupture and abdominal aortic aneurysm morphology: A computational study
Authors: Živić Josip , Virag Lana , Horvat Nino , Smoljkić Marija , Karšaj Igor
Published: December 2021

Prediction of rupture and optimal timing for abdominal aortic aneurysm (AAA) surgical intervention remain wanting even after decades of clinical, histological, and numerical research. Although studies estimating rupture from AAA geometrical features from CT imaging showed some promising results, they are still not being used in practice. Patient‐specific numerical stress analysis introduced too many assumptions about wall structure for the related rupture potential index (RPI) to be considered reliable. Growth and remodeling (G&R) numerical models eliminate some of these assumptions and thus might have the most potential to calculate mural stresses and RPI and increase our understanding of rupture. To recognize numerical models as trustworthy, it is necessary to validate the computed results with results derived from imaging. Elastin degradation function is one of the main factors that determine idealized aneurysm sac shape. Using a hundred different combinations of variables defining AAA geometry or influences AAA stability (elastin degradation function parameters, collagen mechanics, and initial healthy aortic diameters), we investigated the relationship between AAA morphology and RPI and compared numerical results with clinical findings. Good agreement of numerical results with clinical expectations from the literature gives us confidence in the validity of the numerical model. We show that aneurysm morphology significantly influences the stability of aneurysms. Additionally, we propose new parameters, geometrical rupture potential index (GRPI) and normalized aneurysm length (NAL), that might predict rupture of aneurysms without thrombus better than currently used criteria (i.e., maximum diameter and growth rate). These parameters can be computed quickly, without the tedious processing of CT images.
Navier‐Stokes Equations in Gas Dynamics: Green's Function, Singularity, and Well‐Posedness
Authors: Liu Tai‐Ping , Yu Shih‐Hsien
Published: December 2021

The purpose of the present article is to study weak solutions of viscous conservation laws in physics. We are interested in the well‐posedness theory and the propagation of singularity in the weak solutions for the initial value problem. Our approach is to convert the differential equations into integral equations on the level of weak solutions. This depends on exact analysis of the associated linear equations and their Green's functions. We carry out our approach for the Navier‐Stokes equations in gas dynamics. Local in time as well as time‐asymptotic behaviors of weak solutions, and the continuous dependence of the solutions on their initial data are established. © 2022 Wiley Periodicals LLC.
Translation system from Tunisian Dialect to Modern Standard Arabic
Authors: Torjmen Roua , Haddar Kais
Published: December 2021

Nowadays, Tunisian Dialect (TD) is widely used in social media such as Facebook and Twitter to communicate and express opinions. However, the absence of a TD translator prevents comprehension and communication for non‐Tunisian users. Thus, Tunisian translator becomes an important task to overcome these problems. In this article, our main objective is to create a translator from TD to Modern Standard Arabic (MSA). In this context, we are carrying out an in‐depth linguistic study in order to better choose the translation rules which are applicable on the TD sentences. This study guarantees the best quality to obtain MSA sentences. Indeed, our proposed method is based on a linguistic approach. In addition, the method consists of the elaboration of a set of dictionaries and the construction of inflectional, morphological, and syntactic grammars using finite‐state transducers. Then, our method is implemented and tested with new technologies provided by the NooJ linguistic platform. To evaluate our constructed tool, we apply it to two different test corpora containing more than 15,000 words. The obtained results are promising and do highlight our proposed method.
Homo‐ and Heterovalent Neoglycoproteins as Ligands for Bacterial Lectins
Authors: Goyard David , Roubinet Benoît , Vena Federica , Landemarre Ludovic , Renaudet Olivier
Published: December 2021

Click chemistry gives access to unlimited set of multivalent glycoconjugates to explore carbohydrate‐protein interactions and discover high affinity ligands. In this study, we have created supramolecular systems based on a carrier protein that was grafted by Cu(I)‐catalyzed azide‐alkyne cycloaddition with tetravalent glycodendrons presenting αGal, βGal and/or αFuc. Binding studies of the homo‐ (4 a–c) and heterovalent (5) neoglycoproteins (neoGPs) with the LecA and LecB lectins from P. aeruginosa has first confirmed the interest of the multivalent presentation of glycodendrons by the carrier protein (IC50 up to 2.8 nM). Moreover, these studies have shown that the heterovalent display of glycans (5) allows the interaction with both lectins (IC50 of 10 nM) despite the presence of unspecific moieties, and even with similar efficiency for LecB. These results demonstrate the potential of multivalent and multispecific neoGPs as a promising strategy to fight against resistant pathogens.
High Refractive Index Dielectric Nanoparticles for Optically‐Enhanced Activity of Water‐Splitting Photoanodes
Authors: Driencourt Luc , Gallinet Benjamin , Housecroft Catherine E. , Fricke Sören , Constable Edwin C.
Published: December 2021

Metal oxide semiconductors have shown considerable potential for photoelectrochemical water‐splitting. However, no ideal material has emerged which benefit from both an attractive sunlight absorption and efficient charge transport properties. In this work, we show that decorating photoanodes with high refractive index nanoparticles such as amorphous titania can result in reduced reflection losses at the electrolyte/photoanode interface, thereby increasing the performances under illumination from the electrolyte side. A proof of concept is obtained for a bismuth vanadate photoanode including a surface catalyst and a hematite photoanode. The photocurrent density and external quantum efficiency are improved by up to 10 % upon nanoparticle decoration, quantitatively matching the decrease in reflectance. Simulations show that a similar enhancement happens when a thick bismuth vanadate photoanode with optimal charge transport properties is considered, thereby suggesting that this strategy can improve photoanodes suffering from high reflection losses regardless of the bare sample performance.
Assembly of Multiple Full‐Size Genes or Genomic DNA Fragments on Human Artificial Chromosomes Using the Iterative Integration System
Authors: Lee Nicholas C. O. , Petrov Nikolai S. , Larionov Vladimir , Kouprina Natalay
Published: December 2021

Human artificial chromosomes (HACs) are gene delivery vectors that have been used for decades for gene functional studies. HACs have several advantages over viral‐based gene transfer systems, including stable episomal maintenance in a single copy in the cell and the ability to carry up to megabase‐sized genomic DNA segments. We have previously developed the alphoidtetO‐HAC, which has a single gene acceptor loxP site that allows insertion of an individual gene of interest using Chinese hamster ovary (CHO) hybrid cells. The HAC, along with a DNA segment of interest, can then be transferred from donor CHO cells to various recipient cells of interest via microcell‐mediated chromosome transfer (MMCT). Here, we detail a protocol for loading multiple genomic DNA segments or genes into the alphoidtetO‐HAC vector using an iterative integration system (IIS) that utilizes recombinases Cre, ΦC31, and ΦBT. This IIS‐alphoidtetO‐HAC can be used for either serially assembling genomic loci or fragments of a large gene, or for inserting multiple genes into the same artificial chromosome. The insertions are executed iteratively, whereby each round results in the insertion of a new DNA segment of interest. This is accompanied by changes of expression of marker fluorescent proteins, which simplifies screening of correct clones, and changes of selection and counterselection markers, which constitutes an error‐proofing mechanism that removes mis‐incorporated DNA segments. In addition, the IIS‐alphoidtetO‐HAC carrying the genes can be eliminated from the cells, offering the possibility to compare the phenotypes of human cells with and without functional copies of the genes of interest. The resulting HAC molecules may be used to investigate biomedically relevant pathways or the regulation of multiple genes, and to potentially engineer synthetic chromosomes with a specific set of genes of interest. The IIS‐alphoidtetO‐HAC system is expected to be beneficial in creating multiple‐gene humanized models with the purpose of understanding complex multi‐gene genetic disorders. Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Integration of the first DNA segment of interest into the IIS‐alphoidteto‐HAC

Basic Protocol 2: Integration of a second DNA segment of interest into the IIS‐alphoidteto‐HAC

Basic Protocol 3: Integration of a third DNA segment of interest into the IIS‐alphoidteto‐HAC

Support Protocol: Fluorescence in situ hybridization analysis for the circular IIS‐alphoidtetO‐HAC
Drug‐releasing Microspheres for Stem Cell Differentiation
Authors: Sharma Ruchi , Benwood Claire , Willerth Stephanie M.
Published: December 2021

The ability of stem cells to differentiate into specialized cells make them a valuable tool for therapeutic applications. 3D bioprinting, a subset of additive manufacturing, uses bioinks composed of cells and biomaterials to create living tissues. The use of bioactive factors like small molecules and proteins can promote stem cell differentiation into the desired cell phenotypes for tissue regeneration. Small molecules can accelerate the process of regeneration in tissue engineering, maintain bioactivity in a biological environment, and minimize the costs associated with this process. Additionally, they can be encapsulated in specialized drug‐delivery devices called microspheres for controlled release. Microspheres are small (1‐1000 μm) spherical particles usually made from biodegradable and biocompatible polymers that can be loaded with drugs and other bioactive components. They can then be integrated into stem‐cell‐laden bioinks used to form bioprinted tissues, where they will release the encapsulated drug and promote differentiation of stem cells into the desired mature cell type. Microspheres can be widely used to encapsulate a broad range of therapeutic agents, including hydrophilic and hydrophobic small molecule drugs, DNA, and proteins. The release of encapsulated molecules occurs through degradation and erosion of the polymer matrix. This article provides detailed protocols for fabricating and sterilizing drug‐releasing microspheres made from poly‐ε‐caprolactone, a promising biodegradable polymer often used for controlled drug delivery due to its biocompatibility and biodegradation kinetics. Additional protocols describe characterization of the loading and size of microspheres as well as incorporation of microspheres into a fibrin‐based bioink for 3D bioprinting. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Fabrication of drug‐releasing PCL microspheres

Support Protocol 1: Preparation of microspheres for determination of encapsulation efficiency by HPLC

Support Protocol 2: Preparation of microspheres for SEM analysis

Basic Protocol 2: Incorporation of microspheres into fibrin‐based bioink
Perspectives for the Upgrading of Bio‐Based Vicinal Diols within the Developing European Bioeconomy
Authors: Muzyka Claire , Monbaliu Jean‐Christophe M.
Published: December 2021

The previous decade has witnessed a drastic increase of European incentives aimed at pushing forward the transition from an exclusively petro‐based economy toward a strong and homogeneous bio‐based economy. Since 2012, numerous programs have been developed to stimulate and promote research and innovation relying on sustainable and renewable resources. Terrestrial biomass is a virtually infinite reservoir of biomacromolecules, the biorefining of which provides platform molecules of low complexity yet with tremendous industrial potential. Among such bio‐based platform molecules, polyols and, more specifically, molecules featuring vicinal diols have gained tremendous interest and have stimulated an increasing research effort from the chemistry and chemical engineering communities. This Review revolves around the most promising process conditions and technologies reported since 2012 that specifically target bio‐based vicinal diols and promote their transformation into value‐added molecules of wide industrial interest, such as olefins, epoxides, cyclic carbonates, and ketals.
Iodine‐Modified Pd Catalysts Promote the Bifunctional Catalytic Synthesis of 2,5‐Hexanedione from C6 Furan Aldehydes
Authors: Tong Zhikun , Li Xiang , Zhu Jiawei , Chen Shixia , Dai Guiping , Deng Qiang , Wang Jun , Yang Weiran , Zeng Zheling , Zou Ji‐Jun
Published: December 2021

Currently, low intimacy between hydrogenation sites and acidic sites causes unsatisfactory catalytic activity and selectivity for the synthesis of 2,5‐hexanedione from C6 furan aldehydes (5‐methylfurfural, 5‐hydroxymethylfurfural). Herein, iodine(I) modification of Pd‐supported catalysts (such as PdI/Al2O3 and PdI/SiO2) was investigated to modulate the hydrogenation sites and acidic sites. Unlike Pd catalysts that produced 71.4 % yield of 2‐hydroxymethyl‐5‐methyl tetrahydrofuran via an overhydrogenation route of 5‐methylfurfural, PdI catalysts showed a high efficiency for 2,5‐hexanedione with 93.7 % yield by a hydrogenative ring‐opening route. More importantly, the selective synthesis of 2,5‐hexanedione from 5‐hydroxymethylfurfural with a high yield of 50.2 % by the hydrogenolysis and subsequent ring‐opening route was reported for the first time. I‐modified Pd nanoparticles produced in‐situ hydrogen spillover, which promoted the selective C=O hydrogenation and ring‐opening steps by regulating the adsorption configuration of the reactants and the transformation of Lewis to Brønsted acidity, respectively.
A year in heart failure: an update of recent findings
Authors: Stretti Lorenzo , Zippo Dauphine , Coats Andrew J.S. , Anker Markus S. , von Haehling Stephan , Metra Marco , Tomasoni Daniela
Published: December 2021

Major changes have occurred in these last years in heart failure (HF) management. Landmark trials and the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of HF have established four classes of drugs for treatment of HF with reduced ejection fraction: angiotensin‐converting enzyme inhibitors or an angiotensin receptor‐neprilysin inhibitor, beta‐blockers, mineralocorticoid receptor antagonists, and sodium‐glucose co‐transporter 2 inhibitors, namely, dapagliflozin or empagliflozin. These drugs consistently showed benefits on mortality, HF hospitalizations, and quality of life. Correction of iron deficiency is indicated to improve symptoms and reduce HF hospitalizations. AFFIRM‐AHF showed 26% reduction in total HF hospitalizations with ferric carboxymaltose vs. placebo in patients hospitalized for acute HF (P = 0.013). The guanylate cyclase activator vericiguat and the myosin activator omecamtiv mecarbil improved outcomes in randomized placebo‐controlled trials, and vericiguat is now approved for clinical practice. Treatment of HF with preserved ejection fraction (HFpEF) was a major unmet clinical need until this year when the results of EMPEROR‐Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic HFpEF) were issued. Compared with placebo, empagliflozin reduced by 21% (hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.90; P < 0.001), the primary outcome of cardiovascular death or HF hospitalization. Advances in the treatment of specific phenotypes of HF, including atrial fibrillation, valvular heart disease, cardiomyopathies, cardiac amyloidosis, and cancer‐related HF, also occurred. Coronavirus disease 2019 (COVID‐19) pandemic still plays a major role in HF epidemiology and management. All these aspects are highlighted in this review.
Ferrocene Rotary Switches Featuring 2‐Pyridyl‐1,2,3‐triazole “Click” Chelates
Authors: Findlay James A. , Ross Daniel A. W. , Crowley James D.
Published: December 2021

Three ferrocene‐based rotary switches featuring 2‐pyridyl‐1,2,3‐triazole (pytri) “click” chelates have been developed. The rotors can be switched from a folded (syn) to extended (anti) conformation by the addition of [Cu(CH3CN)4](PF6) and 6,6′‐dimesityl‐2,2′‐bipyridine. This extension process could be reversed by the addition of 1,4,8,11‐tetraazacyclotetradecane (cyclam) to sequester the Cu(I) ions. Disappointingly, the weakness of the pytri chelates prevented the development of an electrochemically switchable system.
Design of Metal–Dielectric Multilayer Coatings for Energy‐Efficient Building Glazing
Authors: Garlisi Corrado , Trepci Esra , Azar Elie , Palmisano Giovanni
Published: December 2021

A systematic approach to the design of metal–dielectric multilayer coatings is proposed for energy‐efficient building glazing application. Thirty‐six coatings were modeled with alternating metal (Ag, Au, Cu) and dielectric (TiO2, Ta2O5, ITO, ZrO2, SiO2, Al2O3) thin films in three‐layer (3L) and five‐layer (5L) configurations. It is found that the optical performance is less affected by the bottom dielectric layer compared with the metal and middle/top dielectric layers. The 5L coatings offer a competitive modulation of optical properties, ensuring an optimal balance between luminous transmittance and infrared reflectance. 5L configuration ensures a higher visible transmittance in the whole visible region with peak values close to those of unfunctionalized glass (≈85%), i.e., 3–4% higher compared with the 3L configuration. The optical properties of the optimized multilayers are then used as inputs to building energy models of typical office buildings located in extreme cold and hot weather conditions. The 5L–Ag configurations achieve significant reductions in cooling loads under hot climate conditions (around 15%) without compromising access to daylight (important driver of occupants’ comfort and wellbeing). However, under cold climate conditions, cooling energy savings are outweighed by unintended increases in heating loads, confirming the need for more climate‐driven glazing research efforts.
Advanced microfluidic devices for fabricating multi‐structural hydrogel microsphere
Authors: Chen Zehao , Lv Zhendong , Zhang Zhen , Weitz David A. , Zhang Hongbo , Zhang Yuhui , Cui Wenguo
Published: December 2021

Hydrogel microspheres are a novel functional material, arousing much attention in various fields. Microfluidics, a technology that controls and manipulates fluids at the micron scale, has emerged as a promising method for fabricating hydrogel microspheres due to its ability to generate uniform microspheres with controlled geometry. With the development of microfluidic devices, more complicated hydrogel microspheres with multiple structures can be constructed. This review presents an overview of advances in microfluidics for designing and engineering hydrogel microspheres. It starts with an introduction to the features of hydrogel microspheres and microfluidic techniques, followed by a discussion of material selection for fabricating microfluidic devices. Then the progress of microfluidic devices for single‐component and composite hydrogel microspheres is described, and the method for optimizing microfluidic devices is also given. Finally, this review discusses the key research directions and applications of microfluidics for hydrogel microsphere in the future.
Polycaprolactone usage in additive manufacturing strategies for tissue engineering applications: A review
Authors: Backes Eduardo Henrique , Harb Samarah Vargas , Beatrice Cesar Augusto Gonçalves , Shimomura Kawany Munique Boriolo , Passador Fabio Roberto , Costa Lidiane Cristina , Pessan Luiz Antonio
Published: December 2021

Polycaprolactone (PCL) has been extensively applied on tissue engineering because of its low‐melting temperature, good processability, biodegradability, biocompatibility, mechanical resistance, and relatively low cost. The advance of additive manufacturing (AM) technologies in the past decade have boosted the fabrication of customized PCL products, with shorter processing time and absence of material waste. In this context, this review focuses on the use of AM techniques to produce PCL scaffolds for various tissue engineering applications, including bone, muscle, cartilage, skin, and cardiovascular tissue regeneration. The search for optimized geometry, porosity, interconnectivity, controlled degradation rate, and tailored mechanical properties are explored as a tool for enhancing PCL biocompatibility and bioactivity. In addition, rheological and thermal behavior is discussed in terms of filament and scaffold production. Finally, a roadmap for future research is outlined, including the combination of PCL struts with cell‐laden hydrogels and 4D printing.
Rhenium(VII) extraction from sulfuric aqueous solutions using ionic liquids as diluent and extractant: insights on the extraction stoichiometry and process parameters
Authors: Quijada‐Maldonado Esteban , Román Rodrigo , Merlet Gastón , Pérez Bárbara , Cabezas René , Tapia Ricardo , Olea Felipe , Villarroel Eduardo , Araya‐López Claudio , Romero Julio
Published: December 2021

BACKGROUND

Rhenium(Re) is a highly valuable metal recovered from molybdenite leach liquors by solvent extraction (SX) using toxic organic solvents. This work proposes an extracting phase free of volatile organics composed by the ionic liquid (IL) trioctylmethylammonium benzoate [TOMA][BA] as the extractant, due to its ability to extract Re(VII), and the IL 1‐octyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide [omim][Tf2N] as the diluent, due to its high hydrophobicity where the extraction stoichiometry and process parameters such as the initial pH, the extractant concentration in the diluent and stripping using ammonium hydroxide () and sodium hydroxide () were assessed.

RESULTS

This extracting phase yielded high extraction percentages: 95% with only 3% (v/v) of [TOMA][BA] in [omim][Tf2N]. A detailed study of the SX stoichiometry was carried out through slope analysis, showing that the SX occurs in two steps: first, the extraction of acid; then, the extraction of the metal ion via anion exchange with the transfer of IL‐diluent anion to the aqueous phase. Additionally, the extracting phase was tested in a synthetic molybdenite leached pregnant leach solution, showing selectivity towards Re(VII) over Cu(II) and Fe(III) at very low extractant concentration. The stripping of Re(VII) from the loaded phase was also studied achieving 60% stripping in only one equilibrium step when using .

CONCLUSION

This novel extracting phase, free of volatile organic, shows promising Re(VII) extraction for future industrial applications. © 2021 Society of Chemical Industry (SCI).
A brief history of nearly EV‐erything – The rise and rise of extracellular vesicles
Authors: Couch Yvonne , Buzàs Edit I. , Di Vizio Dolores , Gho Yong Song , Harrison Paul , Hill Andrew F. , Lötvall Jan , Raposo Graça , Stahl Philip D. , Théry Clotilde , Witwer Kenneth W. , Carter David R. F.
Published: December 2021

Extracellular vesicles (EVs) are small cargo‐bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell‐to‐cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes. These small biological particles are also deregulated in disease. As we approach the 75th anniversary of the first experiments in which EVs were unknowingly isolated, it seems right to take stock and look back on how the field started, and has since exploded into its current state. Here we review the early experiments, summarise key findings that have propelled the field, describe the growth of an organised EV community, discuss the current state of the field, and identify key challenges that need to be addressed.
Tissue‐derived extracellular vesicles in cancers and non‐cancer diseases: Present and future
Authors: Li Su‐Ran , Man Qi‐Wen , Gao Xin , Lin Hao , Wang Jing , Su Fu‐Chuan , Wang Han‐Qi , Bu Lin‐Lin , Liu Bing , Chen Gang
Published: December 2021

Extracellular vesicles (EVs) are lipid‐bilayer membrane structures secreted by most cell types. EVs act as messengers via the horizontal transfer of lipids, proteins, and nucleic acids, and influence various pathophysiological processes in both parent and recipient cells. Compared to EVs obtained from body fluids or cell culture supernatants, EVs isolated directly from tissues possess a number of advantages, including tissue specificity, accurate reflection of tissue microenvironment, etc., thus, attention should be paid to tissue‐derived EVs (Ti‐EVs). Ti‐EVs are present in the interstitium of tissues and play pivotal roles in intercellular communication. Moreover, Ti‐EVs provide an excellent snapshot of interactions among various cell types with a common histological background. Thus, Ti‐EVs may be used to gain insights into the development and progression of diseases. To date, extensive investigations have focused on the role of body fluid‐derived EVs or cell culture‐derived EVs; however, the number of studies on Ti‐EVs remains insufficient. Herein, we summarize the latest advances in Ti‐EVs for cancers and non‐cancer diseases. We propose the future application of Ti‐EVs in basic research and clinical practice. Workflows for Ti‐EV isolation and characterization between cancers and non‐cancer diseases are reviewed and compared. Moreover, we discuss current issues associated with Ti‐EVs and provide potential directions.
Comparative study between sorafenib and lenvatinib as the first‐line therapy in the sequential treatment of unresectable hepatocellular carcinoma in a real‐world setting
Authors: Fukushima Taito , Morimoto Manabu , Ueno Makoto , Kubota Kousuke , Uojima Haruki , Hidaka Hisashi , Chuma Makoto , Numata Kazushi , Tsuruya Kota , Hirose Shunji , Kagawa Tatehiro , Hattori Nobuhiro , Watanabe Tsunamasa , Matsunaga Kotaro , Yamamoto Kouji , Tanaka Katsuaki , Maeda Shin
Published: December 2021

Aims

There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real‐world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular‐targeted therapy era.

Methods and Results

We enrolled 386 patients treated with sorafenib or lenvatinib as the first‐line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression‐free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439).

Conclusion

Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first‐line treatment with sorafenib, whereas lenvatinib did not show this effect.
Compressed Sensing in Sodium Magnetic Resonance Imaging: Techniques, Applications, and Future Prospects
Authors: Chen Qingping , Shah N. Jon , Worthoff Wieland A.
Published: December 2021

Sodium (23Na) yields the second strongest nuclear magnetic resonance (NMR) signal in biological tissues and plays a vital role in cell physiology. Sodium magnetic resonance imaging (MRI) can provide insights into cell integrity and tissue viability relative to pathologies without significant anatomical alternations, and thus it is considered to be a potential surrogate biomarker that provides complementary information for standard hydrogen (1H) MRI in a noninvasive and quantitative manner. However, sodium MRI suffers from a relatively low signal‐to‐noise ratio and long acquisition times due to its relatively low NMR sensitivity. Compressed sensing‐based (CS‐based) methods have been shown to accelerate sodium imaging and/or improve sodium image quality significantly. In this manuscript, the basic concepts of CS and how CS might be applied to improve sodium MRI are described, and the historical milestones of CS‐based sodium MRI are briefly presented. Representative advanced techniques and evaluation methods are discussed in detail, followed by an expose of clinical applications in multiple anatomical regions and diseases as well as thoughts and suggestions on potential future research prospects of CS in sodium MRI.

Evidence Level

5

Technical Efficacy

Stage 1
Machine learning in systematic reviews: Comparing automated text clustering with Lingo3G and human researcher categorization in a rapid review
Authors: Muller Ashley Elizabeth , Ames Heather Melanie R. , Jardim Patricia Sofia Jacobsen , Rose Christopher James
Published: December 2021

Systematic reviews are resource‐intensive. The machine learning tools being developed mostly focus on the study identification process, but tools to assist in analysis and categorization are also needed. One possibility is to use unsupervised automatic text clustering, in which each study is automatically assigned to one or more meaningful clusters. Our main aim was to assess the usefulness of an automated clustering method, Lingo3G, in categorizing studies in a simplified rapid review, then compare performance (precision and recall) of this method compared to manual categorization. We randomly assigned all 128 studies in a review to be coded by a human researcher blinded to cluster assignment (mimicking two independent researchers) or by a human researcher non‐blinded to cluster assignment (mimicking one researcher checking another's work). We compared time use, precision and recall of manual categorization versus automated clustering. Automated clustering and manual categorization organized studies by population and intervention/context. Automated clustering failed to identify two manually identified categories but identified one additional category not identified by the human researcher. We estimate that automated clustering has similar precision to both blinded and non‐blinded researchers (e.g., 88% vs. 89%), but higher recall (e.g., 89% vs. 84%). Manual categorization required 49% more time than automated clustering. Using a specific clustering algorithm, automated clustering can be helpful with categorization of and identifying patterns across studies in simpler systematic reviews. We found that the clustering was sensitive enough to group studies according to linguistic differences that often corresponded to the manual categories.
Dupilumab Adverse Events in Nasal Polyp Treatment: Analysis of FDA Adverse Event Reporting System
Authors: Swisher Austin R. , Kshirsagar Rijul S. , Adappa Nithin D. , Liang Jonathan
Published: December 2021

Objectives

Dupilumab was the first biologic approved to treat chronic rhinosinusitis with nasal polyps (CRSwNP). While the risk of adverse events in phase‐III clinical trials was low, dupilumab‐associated adverse reactions (DAR) with real‐world use is unknown and potentially under‐reported. We aimed to evaluate DAR for CRSwNP treatment (CRSwNP‐tx) using the FDA Adverse Event Reporting System (FAERS).

Study Design

Retrospective database study.

Methods

FAERS was queried for DAR from 2019Q1 to 2021Q2. Individual DAR (iDAR) were categorized and quantitatively compared between treatment groups (CRSwNP, asthma, atopic dermatitis). Zero‐truncated Poisson regression was modeled to predict the number of iDAR, and logistic regression was modeled to predict serious DARs.

Results

There were 15,411 DAR observations; 911 for CRSwNP‐tx, of which 121 (13.3%) had serious reactions and 3 died. Common CRSwNP‐tx iDAR were dermatologic (13.9%), generalized (13.3%), and injection‐site (10.8%) symptoms. The number of CRSwNP‐tx iDAR was 2.99 [2.81, 3.17], compared to 3.44 [3.32, 3.56] for asthma and 3.18 [3.13, 3.24] for atopic dermatitis (Kruskal‐Wallis test, P < .001). For CRSwNP‐tx, iDAR reported‐risk‐ratio was 0.84 [0.77, 0.92] among men and 1.12 [1.04, 1.22] among older adults (>50). Serious DAR reported‐odds‐ratio was 1.37 [0.91, 2.04] among men and 1.39 [0.93, 2.08] among older adults.

Conclusions

While there are limitations with FAERS, this analysis suggests CRSwNP‐tx is associated with fewer iDAR compared with other treatment indications. More iDAR are experienced among women and older adults, but men tend to have more serious DAR.

Level of Evidence

3 Laryngoscope, 132:2307–2313, 2022
European Union farming systems: Insights for a more sustainable land use
Authors: Martinho Vítor João Pereira Domingues
Published: December 2021

The diversity of agricultural systems in European Union (EU) regions and countries is vast and vulnerable to the Common Agricultural Policy (CAP) reforms. The CAP instruments have suffered several significant changes over the last decades to take into account the new contexts from the various EU enlargements and problems caused by former measures. This dynamic evolution of the farming system calls for updated assessment to better understand the respective policy impacts and to support the design of new and adjusted instruments. In this context, with this research, the intention is to highlight the most recent characteristics of the EU farming system and to assess the respective impacts from CAP measures. To achieve these aims, we considered statistical information from the Farm Accountancy Data Network (FADN) which was exploited through linear programming models. The main findings reveal that EU subsidies have no implication on the structure of EU farming systems. In other words, the most profitable farming systems are the same whether they were provided with the CAP financial support or not, namely those from the 1st Pillar. On the other hand, the CAP rules condition the farmers' options, sometimes towards adopting a more subsidised production, but with lower margins. These frameworks would not be problematic, if the farming systems were more socially and environmentally sustainable, but this is not always the case. In a future scenario of a farming sector which more regulated by the market and less so by the CAP instruments, the environmental impacts will be more short‐term than medium‐ or long‐term, where the main problem will be with energy consumption.
Scarcity in COVID‐19 vaccine supplies reduces perceived vaccination priority and increases vaccine hesitancy
Authors: Pereira Beatriz , Fehl Amy Greiner , Finkelstein Stacey R. , Jiga‐Boy Gabriela M. , Caserotti Marta
Published: December 2021

In two experimental studies, we tested the effect of COVID‐19 vaccine scarcity on vaccine hesitancy. Based on extensive scarcity literature, we initially predicted that high (vs. low) scarcity would increase demand for vaccines, operationalized as one's willingness to receive a vaccine. Contrary to this prediction, Study 1 showed that scarcity of vaccines reduced participants’ sense of priority which, in turn, also reduced their vaccination intentions. Trust in doctors moderated the effect of perceived vaccination priority on vaccination intentions such that for individuals with high trust in doctors, reduced perceived priority did not reduce their vaccination intentions as much. Study 2 replicated these effects with a more general population sample, which included at‐risk individuals for COVID‐19 complications. At‐risk participants (vs. low‐risk) had higher perceived vaccination priority, but describing vaccine doses as scarce reduced vaccination intentions similarly across both groups. Moreover, Study 2 demonstrated that compassion for others is a boundary condition of the effect of vaccine scarcity on vaccination intentions. For participants with high compassion, scarcity reduces willingness to receive a vaccine; for participants with low compassion, scarcity increases their willingness to be vaccinated. Our results suggest that health policymakers need to deemphasize the scarcity of vaccines to increase vaccine acceptance.
Combination of antiangiogenic treatment with chemotherapy as a multi‐input optimal control problem
Authors: Ledzewicz Urszula , Schättler Heinz
Published: December 2021

We analyze a mathematical model for the combination of chemotherapy with antiangiogenic treatment as a multi‐input optimal control problem. Assuming that the total amounts of both agents to be given have been determined a priori based on a medical assessment of side effects, we consider the problem to minimize a weighted average of tumor volume and the carrying capacity of the tumor vasculature. For medically realistic initial conditions and data, based on a thorough theoretical analysis of the necessary conditions for optimality given by the Pontryagin maximum principle, in this paper, the optimal administration regimen for the antiangiogenic agent is determined.
Novel solution framework for inverse problem considering interval uncertainty
Authors: Tang Jiachang , Mi Chengji , Fu Chunming , Yao Qishui
Published: December 2021

This article proposes a novel solution framework for the inverse problem considering interval uncertainty in structural or systemic responses, which provides an efficient tool for the uncertain inverse problems of nonlinear structures or systems. Interval is used to model and characterize the uncertainty, and the bounds of uncertain structural responses are only required. In each iterative step, the approximate deterministic inverse problem is constructed according to the interval analysis results, and then the identified intervals of inputs are updated by solving the approximate deterministic inverse problem. Therefore, the interval inverse problem is decoupled into a series of interval analyses and deterministic inverse problems that are alternately solved, which dramatically promotes the computational efficiency of the interval inverse problem. Besides, an iterative mechanism is proposed to ensure the convergence of the whole procedure. Finally, two numerical examples and an engineering application are investigated to demonstrate the accuracy and efficiency of the proposed method.
Characterization of interwoven roselle/sisal fiber reinforced epoxy composites
Authors: Kazi Atik Mubarak , D. V. A. Ramasastry , Waddar Sunil
Published: December 2021

The present work deals with the characterization of interwoven roselle/sisal fiber fabric reinforced epoxy composites. All the composites are manufactured using the hand layup technique, and the physical (density), mechanical (tensile, flexural, and impact) and dynamic mechanical characteristics are determined as per ASTM standards. The findings reveal that roselle fabric composite has superior mechanical properties than interwoven roselle/sisal fabric composites. The tensile and impact strengths of the sisal fabric composite are lower than those of the roselle fabric composite. However, the roselle fabric composite and sisal fabric composite have similar flexural properties. The sisal fabric composite yields the highest peak value of the loss factor. The loss factor peak height for the roselle/sisal fabric composites increases with increased sisal fiber content. Morphological analysis revealed proof of yarn pullout and matrix damage near the yarn, indicating inadequate stress transfer between the fabric and epoxy. The property map is presented in comparison with available literature.
Assessing interference in isobaric tag‐based sample multiplexing using an 18‐plex interference standard
Authors: Navarrete‐Perea Jose , Liu Xinyue , Rad Ramin , Gygi Jeremy P. , Gygi Steven P. , Paulo Joao A.
Published: December 2021

Reporter ion interference remains a limitation of isobaric tag‐based sample multiplexing. Advances in instrumentation and data acquisition modes, such as the recently developed real‐time database search (RTS), can reduce interference. However, interference persists as does the need to benchmark upstream sample preparation and data acquisition strategies. Here, we present an updated Triple yeast KnockOut (TKO) standard as well as corresponding upgrades to the TKO viewing tool (TVT2.5, http://tko.hms.harvard.edu/). Specifically, we expand the TKO standard to incorporate the TMTpro18‐plex reagents (TKO18). We also construct a variant thereof which has been digested only with LysC (TKO18L). We compare proteome coverage and interference levels of TKO18 and TKO18L data that are acquired under different data acquisition modes and analyzed using TVT2.5. Our data illustrate that RTS reduces interference while improving proteome coverage and suggest that digesting with LysC alone only modestly reduces interference, albeit at the expense of proteome depth. Collectively, the two new TKO standards coupled with the updated TVT represent a convenient and versatile platform for assessing and developing methods to reduce interference in isobaric tag‐based experiments.
Metopimazine is primarily metabolized by a liver amidase in humans
Authors: Busby Robert W. , Cai Xiaokun , Yang Sihyung , Ramos Luis , Venkatarangan Lata , Shen Helen , Wax Stephen , Sadeque Abu J. M. , De Colle Cyril
Published: December 2021

Metopimazine (MPZ) is a peripherally restricted, dopamine D2 receptor antagonist used for four decades to treat acute nausea and vomiting. MPZ is currently under clinical investigation for the treatment of gastroparesis (GP). MPZ undergoes high first‐pass metabolism that produces metopimazine acid (MPZA), the major circulating metabolite in humans. Despite a long history of use, the enzymes involved in the metabolism of MPZ have not been identified. Here we report a series of studies designed to identify potential MPZ metabolites in vitro, determine their clinical relevance in humans, and elucidate the enzymes responsible for their formation. The findings demonstrated that the formation of MPZA was primarily catalyzed by human liver microsomal amidase. Additionally, human liver cytosolic aldehyde oxidase (AO) catalyzes the formation of MPZA, in vitro, although to a much lesser extent. Neither cytochrome P450 enzymes nor flavin‐monooxygenases (FMO) were involved in the formation MPZA, although two minor oxidative pathways were catalyzed by CYP3A4 and CYP2D6 in vitro. Analysis of plasma samples from subjects dosed 60 mg of MPZ verified that these oxidative pathways are very minor and that CYP enzyme involvement was negligible compared to microsomal amidase/hydrolase in overall MPZ metabolism in humans. The metabolism by liver amidase, an enzyme family not well defined in small molecule drug metabolism, with minimal metabolism by CYPs, differentiates this drug from current D2 antagonists used or in development for the treatment of GP.
Characterization of a Triple Quantum Dot via an On‐chip Microwave Resonator
Authors: Gu Si‐Si , Wang Bao‐Chuan , Chen Ming‐Bo , Lin Ting , Kang Yuan , Li Hai‐Ou , Cao Gang , Guo Guo‐Ping
Published: December 2021

The hybrid circuit quantum electrodynamics architecture integrated quantum dots with a microwave resonator results in the creation of a controllable artificial system and enriches its physics through electron–photon interaction. In this study, a hybrid device is investigated, wherein a triple quantum dot (TQD) is dipole coupled with electric field of a superconducting quantum interference device array resonator. The quantum cellular automata (QCA) process of TQD, related to charge reconfiguration as a result of Coulomb interaction between each dot, is observed by probing reflectance of the resonator. The suppressed cavity reflectance signal of the QCA process may experimentally provide the evidence for the different measurement mechanism of the cavity from external electrometers like quantum point contact. Furthermore, on careful tuning of multiple energy level differences of the TQD to match the cavity photon frequency, four tunneling processes assisted by the absorption of the cavity photons occur simultaneously, contributing to “photon‐assisted” quadruple point. Consequently, these two specific phenomena are found to be closely dependent on the relationship between the various Coulomb energy in TQD and the cavity photon energy. The results are consistent with the theoretical model presented and imply that this hybrid system has the potential for investigating exotic many‐body effects and matter–light interaction.