bluuebunny/crossref_metadata_2025 huggingface dataset:
Activated release of hexanal and salicylaldehyde from imidazolidine precursors encapsulated in electrospun ethylcellulose-poly(ethylene oxide) fibers
Authors: Shi Caihua , Jash Apratim , Lim Loong-Tak
Published: February 2021

Hexanal and salicylaldehyde are naturally-occurring antimicrobial volatiles from edible plants known for their efficacy for post-harvest preservation of fruits and vegetables. Due to their volatility and susceptibility to oxidation, these volatiles must be encapsulated within a carrier to control their release, especially when applied in modified atmnosphere and active packaging applications. In this study, salicylaldehyde precursor (SP; 1,3-dibenzylethane-2-hydroxyphenyl imidazolidine) and hexanal precursor (HP) were synthetized through a Schiff base reaction between these aldehydes and N,N’-dibenzylethane-1,2-diamine. The structure of SP was confirmed using nuclear magnetic resonance and attenuated total reflection-Fourier transform infrared (FTIR) spectroscopies. SP and HP, separately and in combinations, were encapsulated within ethylcellulose–poly(ethylene oxide) (EC–PEO) nonwoven membranes, using a free-surface electrospinning technique. Scanning electron microscopy showed that the morphology of the fibers varied substantially with SP and HP ratio. Specific interactions between SP and HP with the polymers were not detected from the FTIR spectroscopy analysis, suggesting that the precursors were mainly physically entrapped within the EC–PEO fiber matrix. Headspace gas chromatography showed that the release of hexanal and salicylaldehyde could be activated by contacting the precursor-containing electrospun nonwoven with an acidified agarose gel containing 0.003–0.3 M of citric acid. The delivery system can be promising for controlled release of hexanal and salicylaldehyde to extend the shelf-life of fruits and vegetables.
A simple phenomenological approach for myocardial contraction: formulation, parameter sensitivity study and applications in organ level simulations
Authors: Cansız Barış , Woodworth Lucas A. , Kaliske Michael
Published: February 2021

Contraction in myocardial tissue is the result of a complex process through which chemical energy on the cellular level is converted into the mechanical energy needed to circulate blood throughout the body. Due to its vital role for the organism, myocardial contractility is one of the most intensively investigated subjects in medical research. In this contribution, we suggest a novel phenomenological approach for myocardial contraction that is capable of producing realistic intracellular calcium concentration (ICC) and myocyte shortening graphs, can be easily calibrated to capture different ICC and contraction characteristics and, at the same time, is straightforward to implement and ensures efficient computer simulations. This study is inspired by the fact that existing models for myocardial contractility either contain a number of complex equations and material parameters, which reduce their feasibility, or are very simple and cannot accurately mimic reality, which eventually influences the realm of computer simulations. The proposed model in this manuscript considers first the evolution of the ICC through a logarithmic-type ordinary differential equation (ODE) having the normalized transmembrane potential as the argument. The ICC is further put into an exponential-type ODE which determines the shortening of the myocyte (active stretch). The developed approach can be incorporated with phenomenological or biophysically based models of cardiac electrophysiology. Through examples on the material level, we demonstrate that the shape of the ICC and myocardial shortening curves can be easily modified and accurately fitted to experimental data obtained from rat and mouse hearts. Moreover, the performance of the model in organ level simulations is illustrated through several multi-field initial-boundary value problems in which we show variations in volume-time relations, heterogeneous characteristics of myocardial contraction and application of a drug in a virtual left ventricle model.
Sustainability Narratives as Transformative Solution Pathways: Zooming in on the Circular Economy
Authors: D’Amato D.
Published: February 2021

The circular economy can be understood as one of the sustainability narratives (along with, e.g., the bioeconomy, the green economy and the sharing economy), currently relevant in academia, business and policymaking. Sustainability narratives are characterized by a distinctive set of transferable and scalable solutions, addressing resource/services use and distribution in social-ecological-technical systems. Core solutions in the circular economy are technologically-driven improvements towards reductions of inputs/outputs in production and consumption systems. However, the conceptual diversity of the circular economy is such that it can, like other sustainability narratives, serve multiple sustainability discourses (e.g., ecological modernization, sustainable development and degrowth). In order to cater to societal needs within the planet’s biophysical boundaries, the contribution of the circular economy needs to be strengthened in regard to the protection of biodiversity and ecosystems and to the just distribution of resources, opportunities and prosperity. Socio-cultural change should be understood as complementary to technology- and private sector-driven solutions. While circular economy principles are meant to be translated into tailored micro- and macro- level strategies based on context-specific characteristics and needs, the causal connections between units or geographical regions are a crucial issue for sustainability. The overall co-evolution and harmonization of multiple narratives towards coherent sustainability pathways should strive towards decreasing dependence on fossil resources, reversing biodiversity loss and ecosystems degradation and enabling a quality life for all people. The conclusions of this article provide key points that can further guide analyses and implementation of the circular economy in the context of sustainability transformations.
High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
Authors: Zhu Songbiao , Ding Wenxi , Chen Yuling , Wang Weixuan , Xu Renhua , Liu Chongdong , Liu Xiaohui , Deng Haiteng
Published: February 2021

Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. The Von Hippel-Lindau disease tumor suppressor VHL, a known tumor suppressor gene, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL. In the present study, we found that higher expression of VHL was correlated with the better disease-free survival (DFS) in ccRCC patients using The Cancer Genome Atlas (TCGA) datasets. We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition (EMT), sterol regulatory element-binding protein 1 (SREBP1)-regulated triglyceride synthesis, and cell proliferation. Proteomic analysis provided us a global view that VHL regulated four biological processes, including metabolism, immune regulation, apoptosis, and cell movement. Importantly, we found that VHL overexpression led to up-regulated expression of proteins associated with antigen processing and interferon-responsive proteins, thus rendering ccRCC cells more sensitive to interferon treatment. We defined an interferon-responsive signature (IRS) composed of ten interferon-responsive proteins, whose mRNA expression levels were positively correlated with DFS in ccRCC patients. Taken together, our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.
Pathologies of Climate Governance
Authors: Harris Paul G.
Published: February 2021

Earth's climate is in crisis. Climate governance has failed. This book diagnoses climate governance as if it were a sick patient, uncovering the fundamental factors causing the worsening climate crisis. It distils decades of global climate negotiations to reveal the features of international relations that are impeding climate action, and it identifies political obstacles to climate governance across a variety of countries in the Americas, Asia, and Europe. The psychosocial aspects of climate change are explored to show how human nature, overconsumption, and global capitalism conspire to stymy climate action. Remedies are suggested for how to overcome hurdles to effective climate governance internationally and nationally, with ideas provided for individuals to help them align their own interests with those of the global environment. Covering all of the major recent events in climate politics and governance, this is an accessible book for concerned readers who want to understand the climate crisis.
Exploring the Engine and Drivers of Soil Formation
Authors: Hunt Allen , Egli Markus , Faybishenko Boris
Published: February 2021

A new book presents a multidisciplinary perspective on soil, exploring it as a nexus for water flow, near surface (bio)geochemistry, erosion and deposition, and biologically coupled nutrient cycling.
Advances in Satellite Data for Wildfire Smoke Forecasting
Authors: O’Neill Susan , Raffuse Sean
Published: February 2021

Observations from the newest geostationary Earth-observing satellites are offering valuable views of fire progression and smoke plume development and helping simulate impacts from large wildfires.
Metabolomic profiling reveals the effects of early-life lactoferrin intervention on protein synthesis, energy production and antioxidative capacity in the liver of suckling piglets
Authors: Hu Ping , Zhao Fangzhou , Wang Jing , Zhu Weiyun
Published: February 2021

Early-life lactoferrin intervention altered protein synthesis, energy production and antioxidative capacity in the liver of suckling piglets.
Theoretical insight into single Rh atoms anchored on N-doped γ-graphyne as an excellent bifunctional electrocatalyst for the OER and ORR: electronic regulation of graphitic nitrogen
Authors: Qin Youcheng , Yang Miao , Deng Chaofang , Shen Wei , He Rongxing , Li Ming
Published: February 2021

Electronic regulation based on graphitic nitrogen significantly improves the catalytic kinetics and leads to low OER and ORR overpotentials.
The role of visuospatial thinking in students’ predictions of molecular geometry
Authors: Kiernan Nicola A. , Manches Andrew , Seery Michael K.
Published: February 2021

Visuospatial thinking is considered crucial for understanding of three-dimensional spatial concepts in STEM disciplines. Despite their importance, little is known about the underlying cognitive processing required to spatially reason and the varied strategies students may employ to solve visuospatial problems. This study seeks to identify and describe how and when students use imagistic or analytical reasoning when making pen-on-paper predictions about molecular geometry and if particular reasoning strategies are linked to greater accuracy of responses. Student reasoning was evidenced through pen-on-paper responses generated by high attaining, high school students (N = 10) studying Valence Shell Electron Pair Repulsion (VSEPR) Theory in their final year of chemistry. Through analysis and coding of students’ open-ended paper-based responses to an introductory task, results revealed that students employed multiple reasoning strategies, including analytical heuristics and the spontaneous construction of external diagrammatic representations to predict molecular geometry. Importantly, it was observed that despite being instructed on the use of VSEPR theory to find analytical solutions, some students exhibited preference for alternative reasoning strategies drawing on prior knowledge and imagistic reasoning; showing greater accuracy with 3D diagrammatic representations than students who used the algorithmic method of instruction. This has implications for both research and practice as use of specific reasoning strategies are not readily promoted as a pedagogical approach nor are they given credit for in national examinations at school level.
Ruthenium-catalysed meta-selective CAr–H bond alkylation via a deaminative strategy
Authors: Zhu Ze-Fan , Chen Guang-Le , Liu Feng
Published: February 2021

The utilization of readily prepared Katritzky salts as radical precursors for remote meta-CAr–H bond alkylation is described.
Dissection of bicapped octahedral copper hydride cluster to form two chiral tetrahedral copper hydride cluster series exhibiting auto deracemization and photoluminescence
Authors: Xu Han , Han Ying-Zi , OuYang Jie , Chen Zuo-Chang , Chen Hui-Jun , Nie Hong-Hong , Tang Zichao , Yang Shi-Yao , Huang Rong-Bin , Zheng Lan-Sun , Teo Boon K.
Published: February 2021

Synthesis, structures and interconversion of three related classes of copper hydride clusters [Cu8H6(L)6]2+[Cu4HX3(L)3] and [Cu4HX2(L)4]+.
Photoredox-catalyzed hydroxydifluoroacetylation of alkenes with FSO2CF2CO2Me and H2O: simple synthesis of CF2CO2Me-containing alcohols and difluorolactones
Authors: Luo Xuewei , Zhang Bo , Xi Chanjuan
Published: February 2021

Photoredox-catalyzed hydroxydifluoroacetylation of alkenes with FSO2CF2CO2Me and H2O is presented, in which CF2CO2Me-containing alcohols and/or difluorolactones are obtained in high yields with high regioselectivity under mild conditions.
Complexes of divalent europium with dotp and dotpph
Authors: Starynowicz Przemysław
Published: February 2021

Structures, electron spectroscopy and theoretical (DFT and TD DFT) analyses of two complexes of Eu(ii) with phosphonate and phosphinate ligands based on cyclen ring are presented.
Plasma-engineered bifunctional cobalt–metal organic framework derivatives for high-performance complete water electrolysis
Authors: Chen Wenxia , Wei Wei , Wang Kefeng , Zhang Nan , Chen Guangliang , Hu Yingjie , Ostrikov Kostya (Ken)
Published: February 2021

A MOF-derived CoPO hollow polyhedron structure is designed by simultaneous oxidation/phosphatization processes during Ar–N2 RF plasma discharge.
Photodynamic antitumor activity of aggregation-induced emission luminogens as chemosensitizers for paclitaxel by concurrent induction of apoptosis and autophagic cell death
Authors: Wang Jia , Zhang Wenling , Wu Ting , Wu Haisi , Zhang Yuan , Wang Siwan , Ji You , Jiang Hui , Zhang Ziting , Tang Chunming , Tang Qiyun , Li Xiaolin , Xu Huae
Published: February 2021

TPE-Py inhibits the growth of tumor cells by inducing apoptotic and autophagic cell death, and the effect could be enhanced by white light irradiation. TPE-Py enhances the anticancer activity of Ptx by inducing apoptosis by white light irradiation.
Superassembly of NiCoOx solid solution hybrids with a 2D/3D porous polyhedron-on-sheet structure for multi-functional electrocatalytic oxidation
Authors: Hao Pin , Wen Houguang , Wang Qian , Li Liyi , Zhao Zhenhuan , Xu Ruirui , Xie Junfeng , Cui Guanwei , Tang Bo
Published: February 2021

NiCoOx solid solution hybrids with a hierarchical architecture and high porosity present excellent electrocatalytic performances in the UOR and electro-oxidation of organic molecules.
Local blackout and global power system wide blackout are caused by non‐linear negative damping
Authors: Ooi Boon Teck , Guo Jinpeng , Wang Xiaozhe
Published: February 2021

Local blackout occurs when the transient stability limit is exceeded after a transmission line fault. As to global blackout, a recording of the 10 August 1996‐WECC blackout shows that it was accompanied negative damping. A turbine‐generator swinging against an infinite bus is used to approximate the dynamics leading to the WECC blackout. There is no analytic solution when non‐linearity is included. Small‐signal linearisation shows that negative damping can occur but cannot produce the waveform recorded in the WECC blackout. Therefore, the graphical phase‐plane method, which is easy to use, is resorted to. The study shows that the kernel of non‐linearity consists of the gradients which produce limit cycles. Positive or negative damping is produced by shifting the gradients of the limit cycles to the right or left in the direction of the trajectory. The study makes a contribution by showing that phase plane can be used to study the impact of multiple independent controllers. A worked example shows when transient stability limit is exceeded, local blackout occurs. The swing equation of local blackout is applied to the WECC blackout. As proof that negative damping was due to non‐linearity, a waveform having the frequency of the recorded WECC blackout is presented.
Simple accurate model‐based phase diversity phase retrieval algorithm for wavefront sensing in high‐resolution optical imaging systems
Authors: Qin Shun , Zhang Yongbing , Wang Haoqian , Chan Wai Kin
Published: February 2021

In optical imaging systems, the aberration is an important factor that impedes realising diffraction‐limited imaging. Accurate wavefront sensing and control play important role in modern high‐resolution optical imaging systems nowadays. In this study, a simple model‐based phase retrieval algorithm is proposed for accurate efficient wavefront sensing with high dynamic range. In the authors’ algorithm, a wavefront is represented by the Zernike polynomials, and the Zernike coefficients are solved by the least‐squares‐based non‐linear optimisation method, i.e. the Lederberg–Marquardt algorithm, with multiple phase‐diversity images. The numerical results show that the proposed algorithm is capable of retrieving wavefront with a large dynamic range up to seven wavelength and robust to noise. In comparison, the proposed algorithm is more efficient than the existing model‐based technique and more accurate than existing Fourier ‐ transformation‐based iterative techniques.
A low‐light image enhancement method based on bright channel prior and maximum colour channel
Authors: Sandoub Ghada , Atta Randa , Ali Hesham Arafat , Abdel‐Kader Rabab Farouk
Published: February 2021

Low‐light image enhancement algorithms have been introduced to improve the visual quality of low‐light images that may degrade the performance of many computer vision and multimedia systems designed for high‐quality images. However, the existing bright channel prior and maximum colour channel enhancement algorithms introduce halo artifacts and colour distortions while enhancing the images. To overcome these limitations, in this paper, an effective fusion‐based low‐light image enhancement algorithm is proposed. In the proposed algorithm, the illumination of the low‐light image is estimated from both the bright and maximum colour channels to overcome the halo artifacts and colour distortion problems. Further, an effective refinement method is utilized to improve the sharpness of the initial enhanced image representing the scene reflectance. Experiment results show that the proposed algorithm outperforms the state‐of‐the‐art algorithms qualitatively and quantitatively. Moreover, the proposed algorithm reduces the halo artifacts and colour distortion and enhances the details while preserving the naturalness.
Discovery of new globular clusters in the Sagittarius dwarf galaxy
Authors: Minniti D. , Ripepi V. , Fernández-Trincado J. G. , Alonso-García J. , Smith L. C. , Lucas P. W. , Gómez M. , Pullen J. B. , Garro E. R. , Vivanco Cádiz F. , Hempel M. , Rejkuba M. , Saito R. K. , Palma T. , Clariá J. J. , Gregg M. , Majaess D.
Published: February 2021

Context. Globular clusters (GCs) are witnesses of the past accretion events onto the Milky Way. In particular, the GCs of the Sagittarius (Sgr) dwarf galaxy are important probes of an on-going merger.

Aims. Our main goal is to search for new GC members of this dwarf galaxy using the VISTA Variables in the Via Lactea Extended Survey (VVVX) near-infrared database combined with the Gaia Early Data Release 3 (EDR3) optical database.

Methods. We investigated all VVVX-enabled discoveries of GC candidates in a region covering about 180 sq. deg. toward the bulge and the Sgr dwarf galaxy. We used multiband point-spread function photometry to obtain deep color-magnitude diagrams (CMDs) and luminosity functions (LFs) for all GC candidates, complemented by accurate Gaia-EDR3 proper motions (PMs) to select Sgr members and variability information to select RR Lyrae which are potential GC members.

Results. After applying a strict PM cut to discard foreground bulge and disk stars, the CMDs and LFs for some of the GC candidates exhibit well defined red giant branches and red clump giant star peaks. We selected the best Sgr GCs, estimating their distances, reddenings, and associated RR Lyrae.

Conclusions. We discover 12 new Sgr GC members, more than doubling the number of GCs known in this dwarf galaxy. In addition, there are 11 other GC candidates identified that are uncertain, awaiting better data for confirmation.
Diagnose und Differenzialdiagnose von peripheren und zentralen Schwindelsyndromen
Authors: Strupp Michael , Feil Katharina , Zwergal Andreas
Published: February 2021

Die Diagnose der verschiedenen peripheren und zentralen Schwindelsyndrome basiert auf einer systematischen Anamnese und kombinierten klinischen Untersuchung der vestibulären, okulomotorischen und zerebellären Systeme. Die wichtigsten apparativen diagnostischen Verfahren sind der Video-Kopfimpulstest und die kalorische Testung. Die Diagnosestellung ist durch die neuen Diagnosekriterien der Bárány-Society vereinfacht worden (www.jvr-web.org/ICVD.html).
Primäre Rekonstruktion der ableitenden Tränenwege nach Trauma – bikanalikulonasale Schienung mit autostabilen Silikonverweilsonden
Authors: Heichel Jens , Struck Hans-Gert , Viestenz Arne
Published: February 2021

Verletzungen des medialen Lidwinkels können alle Abschnitte der ableitenden Tränenwege (TNW) involvieren. Je nach Alter der Patienten finden sich typische Verletzungsmuster. Die chirurgische Tränenwegsrekonstruktion durch 2 autostabile („selbsthaltende“) monokanalikulonasale Silikonverweilsonden soll anhand von 2 Fallberichten beschrieben werden. Ein 6 Jahre altes Mädchen zeigte infolge eines Hundebisses (Rottweiler) neben schwerwiegenden Kopfverletzungen eine tiefe periokuläre Weichteilwunde mit Tränenwegsbeteiligung. Der Canaliculus lacrimalis inferior war durchtrennt und der Canaliculus lacrimalis communis war vom Tränensack abgerissen. Schwerste Weichteilverletzungen ausgehend vom Unterlid erstreckten sich bis zur Wange und Nase. Mittels nahtfixierten monokanalikulonasalen Silikonverweilsonden und Kanalikulusnähten sowie einer schichtweisen Weichteilrekonstruktion wurden die TNW und das Lid rekonstruiert. 18 Monate postoperativ zeigt sich eine diskrete Depression der medialen Unterlidkante bei sonst guter Funktion. Der 2. Fall berichtet von einem 43 Jahre alten Fleischereifachangestellten, der sich mit einem Messer eine tiefe Wunde des medialen Lidwinkels zuzog. Bei dem erwachsenen Patienten waren beide Tränenröhrchen weit proximal (sakkusnah) sowie das mediale Lidbändchen und der M. orbicularis oculi durchtrennt. Nach Einbringen zweier monokanalikulonasaler Silikonverweilsonden wurde eine mikrochirurgische Rekonstruktion vorgenommen. Das Follow-up bei diesem Patienten beträgt 6 Monate. Klinisch und funktionell bestand abschließend bei beiden Patienten kein Anhalt für eine Tränenabflussstörung. Zeitgleich können mehrere Abschnitte der TNW verletzt sein. Das Erkennen und das korrekte Zuordnen des Verletzungsmusters in Hinblick auf Schädigungsart, ‑grad und die anatomische Lokalisation sind grundlegend für eine adäquate Rekonstruktion der TNW. Ein schichtweiser Wundverschluss von innen nach außen unter Berücksichtigung der topografischen Anatomie ist obligat. Die Wiederherstellung der funktionellen Einheit von Lidern und TNW ist hierbei anzustreben. Autostabile monokanalikulonasale Silikonverweilsonden können nach Trauma zur Schienung beider Tränenröhrchen sowohl bei Kindern als auch Erwachsenen zur Anwendung kommen.
Akuter ischämischer Schlaganfall und Troponinerhöhung: Diagnostische Abklärung und therapeutische Konsequenzen
Authors: Grassl Niklas , Baumann Stefan , Kruska Mathieu , Fatar Marc , Akin Ibrahim , Platten Michael , Borggrefe Martin , Alonso Angelika , Szabo Kristina , Fastner Christian
Published: February 2021

Erhöhte Troponinwerte beim akuten ischämischen Schlaganfall sind ein häufiges klinisches Szenario, das vor dem Hintergrund der hohen kardialen Mortalität nach Schlaganfall eine angemessene diagnostische Aufarbeitung erfordert. Zur Vermeidung sekundärer intrazerebraler Hämorrhagien durch duale Thrombozytenaggregationshemmung sollte die Indikation zur Koronarintervention streng gestellt werden. Anhand dreier Fallbeispiele stellt diese Arbeit auf Grundlage der vorhandenen Evidenz einen diagnostischen Algorithmus vor.
Double Diabetes: A Growing Problem Requiring Solutions
Authors: Popovic Djordje S. , Papanas Nikolaos
Published: February 2021

The growing proportion of type 1 diabetes mellitus (T1DM) patients with clinical features of insulin resistance (IR) has led to the description of a distinctive T1DM subgroup, still unrecognised by current guidelines, called double diabetes, assumingly associated with poorer metabolic phenotype and increased risk of micro- and macrovascular complications. The main goal of identifying double diabetes, estimated to be present in up to half of T1DM patients, is timely implementation of appropriate therapeutic interventions to reduce the increased risk of chronic complications and other adverse metabolic traits associated with this condition. Proposed diagnostic criteria are largely divided into three different groups: family history of type 2 diabetes mellitus (T2DM), obesity/metabolic syndrome, and IR. Estimated glucose disposal rate may prove the most reliable marker of double diabetes. In addition to general measures (diet, physical activity, antihypertensive, and lipid-lowering medications, etc.) and development of new insulin preparations with more hepatic action, double diabetes patients may derive more benefit from agents developed for T2DM. Indeed, such potentially promising agents include glucagon-like peptide-1 receptor agonists, sodium-glucose contrasporter-2 inhibitors, and their combination. We are now awaiting long-term trials assessing metabolic and vascular benefits of these medications in double diabetes.
Evidence that GPVI is Expressed as a Mixture of Monomers and Dimers, and that the D2 Domain is not Essential for GPVI Activation
Authors: Clark Joanne C. , Neagoe Raluca A. I. , Zuidscherwoude Malou , Kavanagh Deirdre M. , Slater Alexandre , Martin Eleyna M. , Soave Mark , Stegner David , Nieswandt Bernhard , Poulter Natalie S. , Hummert Johan , Herten Dirk-Peter , Tomlinson Michael G. , Hill Stephen J. , Watson Steve P.
Published: February 2021

Collagen has been proposed to bind to a unique epitope in dimeric glycoprotein VI (GPVI) and the number of GPVI dimers has been reported to increase upon platelet activation. However, in contrast, the crystal structure of GPVI in complex with collagen-related peptide (CRP) showed binding distinct from the site of dimerization. Further fibrinogen has been reported to bind to monomeric but not dimeric GPVI. In the present study, we have used the advanced fluorescence microscopy techniques of single-molecule microscopy, fluorescence correlation spectroscopy (FCS) and bioluminescence resonance energy transfer (BRET), and mutagenesis studies in a transfected cell line model to show that GPVI is expressed as a mixture of monomers and dimers and that dimerization through the D2 domain is not critical for activation. As many of these techniques cannot be applied to platelets to resolve this issue, due to the high density of GPVI and its anucleate nature, we used Förster resonance energy transfer (FRET) to show that endogenous GPVI is at least partially expressed as a dimer on resting and activated platelet membranes. We propose that GPVI may be expressed as a monomer on the cell surface and it forms dimers in the membrane through diffusion, giving rise to a mixture of monomers and dimers. We speculate that the formation of dimers facilitates ligand binding through avidity.
Copper(I) Iodide Catalyzed Tandem Reactions of N-Propargyl-N-(2-iodoaryl)amides with Sodium Azide: An Efficient Synthesis of [1,2,3]Triazolo[1,5-a]quinoxalines
Authors: Zhu Yinghong , Chen Wanli , Tu Xiangtu , Xu Mingxia , Chu Youqun
Published: February 2021

Copper-catalyzed reactions of N-propargyl-N-(2-iodoaryl)amides with sodium azide have been developed, providing a novel and efficient method for the synthesis of [1,2,3]triazolo[1,5-a]quinoxaline compounds under mild conditions in moderate yields by tandem copper-catalyzed azide-alkyne cycloaddition and Ullmann-type coupling.
Gene Therapy for Inherited Bleeding Disorders
Authors: Arruda Valder R. , Weber Jesse , Samelson-Jones Benjamin J.
Published: February 2021

Decades of preclinical and clinical studies developing gene therapy for hemophilia are poised to bear fruit with current promising pivotal studies likely to lead to regulatory approval. However, this recent success should not obscure the multiple challenges that were overcome to reach this destination. Gene therapy for hemophilia A and B benefited from advancements in the general gene therapy field, such as the development of adeno-associated viral vectors, as well as disease-specific breakthroughs, like the identification of B-domain deleted factor VIII and hyperactive factor IX Padua. The gene therapy field has also benefited from hemophilia B clinical studies, which revealed for the first time critical safety concerns related to immune responses to the vector capsid not anticipated in preclinical models. Preclinical studies have also investigated gene transfer approaches for other rare inherited bleeding disorders, including factor VII deficiency, von Willebrand disease, and Glanzmann thrombasthenia. Here we review the successful gene therapy journey for hemophilia and pose some unanswered questions. We then discuss the current state of gene therapy for these other rare inherited bleeding disorders and how the lessons of hemophilia gene therapy may guide clinical development.
Advances in the Management of Cancer-Associated Thrombosis
Authors: Dhami Sukhraj Pal Singh , Patmore Sean , O'Sullivan Jamie M.
Published: February 2021

The association between cancer and venous thromboembolism (VTE) has been established for more than 150 years. Nevertheless, cancer-associated thrombosis still remains a major clinical challenge and is associated with significant morbidity and mortality for patients with cancer. The clinical presentation of cancer-associated thrombosis can be distinct from that of a patient without an underlying malignancy. Moreover, specific cancer types, including pancreatic cancer and hematological malignancies, as well as advanced stage disease can confer a significant thrombotic risk. This risk is further augmented by specific anticancer treatment modalities. The pathophysiology of cancer-associated thrombosis is complex and multifactorial. However, understanding the biological mechanisms underpinning VTE risk may provide insight into novel targeted prophylaxis in cancer patients. Over the last decade, low-molecular-weight heparin has been the preferred anticoagulant agent for patients with cancer-associated thrombosis due to improved efficacy compared with vitamin K antagonists. However, the advent of direct oral anticoagulants (DOACs) has added to the repertoire of ammunition now at the disposal of clinicians to aid in the management of cancer-associated thrombosis. Several randomized controlled trials have now been published, demonstrating DOAC as a noninferior alternative for both the treatment and prevention of cancer-associated thrombosis. Notwithstanding this, limitations for their widespread use remain, with the potential for increased bleeding risk, drug interactions, and poor DOAC metabolism. This review discusses the evidence base for the incidence and risk factors associated with VTE in cancer, development, and refinement of risk prediction models and novel advances in the therapeutic management of cancer-associated thrombosis.
Leadership Development in Ophthalmology: Current Impact and Future Needs
Authors: Berkowitz Sean T. , Law Janice C. , Sternberg Paul , Patel Shriji
Published: February 2021

Importance There is a lack of peer-reviewed literature on leadership development programs (LDP) in ophthalmology. Research into LDP demographics, outcomes, and methodology is needed.

Objective The aim of the study is to evaluate the extent to which LDPs targeting ophthalmologists meet the needs of emerging leaders.

Design The design type of the study is cross-sectional analysis.

Setting This study involves international setting.

Participants The participants involved were ophthalmologists at any career level.

Methods Routine internet search was used to identify LDPs targeting ophthalmologists. LDPs identified were categorized by the outcome data available into four levels based on prior literature. Participants were assessed using previously validated software for gender (Gender-API, 2020) and race or ethnicity (NamSor, 2020)

Results Nine programs were identified which were classified into LDP generations. The first LDP in ophthalmology was the American Academy of Ophthalmology (AAO) LDP, which served as the nidus for the formation of four multinational LDPs, together forming the Global LDP. These LDPs were similar in size and scope; program size ranging from nine to 30 participants; a length of 1 to 2 years; with similar curricular offerings; with funding primarily derived from cost-sharing with a nominating society. The second generation of ophthalmology LDPs in the United States has targeted female scientists or faculty (Women's LDP by ARVO) and academic ophthalmology leaders (Academic LDP by Association of University Professors of Ophthalmology).

The AAO's LDP appears increasingly diverse with approximately 13% women at inception, gradually increasing from 40 to 65% women in the last 5 years (n = 389). There has also been a notable increase in ethnic diversity.

Conclusion and Relevance AAO LDP is the preeminent leadership training program for ophthalmologists, and it has influenced the creation of a new generation of LDP offerings. There remains a paucity of LDP evaluation metrics and reported outcomes. Newer iterations are successfully targeting academic leadership and attempting to address known disparities in gender and race or ethnicity. Further expansion of LDPs and related research can ensure equity and diversity in the pipeline.
Optimization of the Soft Tissue Envelope of the Nose in Rhinoplasty Utilizing Fat Transfer Combined with Platelet-Rich Fibrin
Authors: Kovacevic Milos , Kosins Aaron M. , Göksel Abdülkadir , Riedel Frank , Bran Gregor , Veit Johannes A.
Published: February 2021

A thin or damaged skin soft tissue envelope may cause concerns in primary and secondary rhinoplasty. During postoperative healing, unpredictable scarring and contraction may occur and lead to significant aesthetic and trophic sequelae. Besides a meticulous surgical technique, there are no reliable techniques to prevent long-term skin damage and shrinkage. Fat transfer with addition of platelet-rich fibrin (PRF) harbors the possibility of local soft tissue regeneration and skin rejuvenation through growth factors and mesenchymal stem cells. It may also facilitate the creation of a thin fat layer on the dorsum to prevent shrink-wrap forces and conceal small irregularities. The goal is to provide evidence for the feasibility, durability, and beneficial effect of diced macrofat transfer bonded with PRF on the nasal dorsum. We present the technique of fat transfer conjugated with PRF as a nasal dorsal graft. Clinical endpoints were the prevention of trophic disturbances and atrophy at a 1-year postoperative follow-up. We present the skin mobility test as a clinical indicator of a healthy soft tissue envelope. The presented case series consists of 107 rhinoplasties. Fat was harvested in the umbilical or costal region. PRF was created by centrifugation of autologous whole blood samples. Macrofat was diced, cleaned, and bonded with PRF. The compound transplants were transferred to the nasal dorsum. There were no perioperative complications or wound-healing issues. Mean follow-up was 14 months. Clinical inspection showed good skin quality and no signs of shrinkage, marked scarring, or color changes with positive skin mobility test in all patients. Survival of fat was confirmed by ultrasonography and magnetic resonance imaging. Diced macrofat transfer in conjunction with PRF to the nasal dorsum is a feasible and safe method. A beneficial effect on the soft tissue envelope is demonstrated as well as the prevention of shrink-wrap forces.
Current Challenges in the Peripartum Management of Women with von Willebrand Disease
Authors: Byrne Bridgette , Ryan Kevin , Lavin Michelle
Published: February 2021

For many women, pregnancy and childbirth represent their first major hemostatic challenges. Despite advancements in obstetric care, up to 2 to 5% of all deliveries are complicated by postpartum hemorrhage (PPH). To mitigate bleeding risk, physiological changes occur in pregnancy, including increases in plasma von Willebrand factor (VWF) and factor VIII levels. For women with von Willebrand disease (VWD), these physiological alterations are blunted or absent. As a result, women with VWD have a heightened risk of PPH, both primary (in the first 24 hours) and secondary (>24 hours to 6 to 12 weeks postpartum). Pregnancy and delivery management for women with VWD should therefore be carefully coordinated as part of a multidisciplinary team approach. In the absence of large-scale clinical trials, the management of women with VWD during pregnancy is guided by expert consensus guidelines. Clinical practices internationally are not uniform, and areas of considerable clinical uncertainty exist. Traditional peripartum plasma VWF thresholds for hemostatic cover and therapeutic targets are currently under scrutiny, as PPH is not eliminated in women with VWD who receive replacement therapy. The benefit and optimal duration of postpartum tranexamic acid have yet to be defined, and standardized methods of quantification of blood loss at the time of delivery are currently lacking. In this article, we review the evidence base to date and explore the current clinical challenges in the management of pregnant women with VWD.
The Effect of Joint Line Elevation on In Vivo Knee Kinematics in Bicruciate Retaining Total Knee Arthroplasty
Authors: Klemt Christian , Padmanabha Anand , Tirumala Venkatsaiakhil , Smith Evan J. , Kwon Young-Min
Published: February 2021

Prior studies have reported a negative effect on both clinical outcomes and patient-reported outcome measures (PROMS) following joint line elevation (JLE) in cruciate-retaining (CR) total knee arthroplasty (TKA) and posterior stabilized (PS) TKA designs. This experimental study was aimed to quantify the effect of JLE on in vivo knee kinematics in patients with bicruciate retaining (BCR) TKA during strenuous activities. Thirty unilateral BCR TKA patients were evaluated during single-leg deep lunge and sit-to-stand using a validated combined computer tomography and dual fluoroscopic imaging system. Correlation analysis was performed to quantify any correlations between JLE and in vivo kinematics, as well as PROMS. There was a significant negative correlation between JLE and maximum flexion angle during single-leg deep lunge (ρ = −0.34, p = 0.02), maximum varus joint angles during single-leg deep lunge (ρ = −0.37, p = 0.04), and sit-to-stand (ρ = −0.29, p = 0.05). There was a significant negative correlation between JLE and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (ρ = −0.39, p = 0.01) and knee disability and osteoarthritis outcome score physical function (KOOS-PS; ρ = −0.33, p = 0.03). The JLE that yields a significant loss in PROMS and maximum flexion angles were 2.6 and 2.3 mm, respectively. There was a linear negative correlation of JLE with both in vivo knee kinematics and PROMS, with changes in JLE of greater than 2.6 and 2.3 mm, leading to a clinically significant loss in PROMS and maximum flexion angles, respectively, suggesting an increased need to improve surgical precision to optimize patient outcomes following BCR TKA.
Outcomes of Femtosecond Laser Assisted Cataract Surgery Performed by Resident and Attending Surgeons
Authors: Cleland Spencer C. , Knoch Daniel W. , Larson Jennifer C.
Published: February 2021

Objective The study aimed to evaluate the safety and efficacy of resident surgeons performing femtosecond laser assisted cataract surgery (FLACS).

Methods A retrospective chart review was conducted at the University of Wisconsin-Madison from postgraduate year four residents performing FLACS between 2017 and 2019. Data were also collected from residents performing manual cataract surgery, and attending surgeons performing FLACS for comparison. Recorded data included patient demographics, pre- and postoperative visual acuity, pre- and postoperative spherical equivalent, nuclear sclerotic cataract grade, ocular and systemic comorbidities, intraocular lens, duration of surgery, cumulative dissipated energy (CDE), and intraoperative and postoperative complications.

Results A total of 90 cases were reviewed with 30 resident manual cases, 30 resident FLACS cases, and 30 attending FLACS cases. Resident manual (25.5 ± 6.8 minutes) and resident FLACS (17.5 ± 7.1 minutes) cases took a significantly longer time to complete compared with attending FLACS cases (13.6 ± 4.4 minutes; p < 0.001). There was higher CDE in resident FLACS and resident manual cases compared with attending FLACS cases, but the difference was not statistically significant (p = 0.06). Postoperative visual acuity was not statistically different at 1-day and 1-month after surgery among the three groups. Resident FLACS complications, which included one case requiring an intraoperative suture to close the wound, two cases with intraoperative corneal abrasions, two cases with postoperative ocular hypertension, and one case with cystoid macular edema, were not significantly greater than attending FLACS complications (p = 0.30).

Conclusion The FLACS performed by resident surgeons had comparable visual acuity outcomes to FLACS performed by attending surgeons, and to manual cataract surgery performed by resident surgeons. However, resident FLACS cases took significantly longer time to complete, and they were associated with a higher CDE and minor complication rate compared with attending FLACS cases. Introducing advanced technologies into surgical training curricula improves resident preparedness for independent practice, and this study suggests FLACS can be incorporated safely and effectively into resident education.
On the tensor rank of multiplication in finite extensions of finite fields and related issues in algebraic geometry
Authors: Ballet S. , Pieltant J. , Rambaud M. , Randriambololona H. , Rolland R. , Chaumine J.
Published: February 2021

In this paper, we give a survey of the known results concerning the tensor rank of multiplication in finite extensions of finite fields, enriched with some unpublished recent results, and we analyze these to enhance the qualitative understanding of the research area. In particular, we identify and clarify certain partially proved results and emphasise links with open problems in number theory, algebraic geometry, and coding theory.

Bibliography: 92 titles.
Newton polytopes and tropical geometry
Authors: Kazarnovskii B. Ya. , Khovanskii A. G. , Esterov A. I.
Published: February 2021

The practice of bringing together the concepts of ‘Newton polytopes’, ‘toric varieties’, ‘tropical geometry’, and ‘Gröbner bases’ has led to the formation of stable and mutually beneficial connections between algebraic geometry and convex geometry. This survey is devoted to the current state of the area of mathematics that describes the interaction and applications of these concepts.

Bibliography: 68 titles.
Delayed consequences of the influence of hypomagnetic field on roach (
Authors: Krylov Viacheslav V. , Chebotareva Yulia V. , Izyumov Yuri G.
Published: February 2021

The absence of magnetic fields can affect fish embryogenesis. The influence of hypomagnetic field on the survival of roach (Rutilus rutilus) embryos was estimated. Delayed consequences of R. rutilus embryos and prelarvae exposure to these magnetic conditions were also studied. Hypomagnetic field during embryogenesis led to an increased mortality of embryos. The juveniles developed from the exposed embryos were characterised by reduced vertebral phenotypic diversity. The influence of hypomagnetic field on roach prelarvae led to changes in the size–mass indices of juvenile fish. Present results differ from those that were previously obtained in experiments with simulated geomagnetic storms and artificial low-frequency magnetic fields and emphasise the importance of the magnetic environment for the fish embryogenesis. Possible mechanisms of the described effects are discussed.
Physical activity, screen time and the COVID‐19 school closures in Europe – An observational study in 10 countries
Authors: Kovacs Viktoria A. , Starc Gregor , Brandes Mirko , Kaj Monika , Blagus Rok , Leskošek Bojan , Suesse Thomas , Dinya Elek , Guinhouya Benjamin C. , Zito Viviana , Rocha Paulo M. , Gonzalez Benito Perez , Kontsevaya Anna , Brzezinski Michal , Bidiugan Radu , Kiraly Anita , Csányi Tamás , Okely Anthony D.
Published: February 2021

To date, few data on how the COVID‐19 pandemic and restrictions affected children's physical activity in Europe have been published. This study examined the prevalence and correlates of physical activity and screen time from a large sample of European children during the COVID‐19 pandemic to inform strategies and provide adequate mitigation measures. An online survey was conducted using convenience sampling from 15 May to 22 June, 2020. Parents were eligible if they resided in one of the survey countries and their children aged 6–18 years. 8395 children were included (median age [IQR], 13 [10–15] years; 47% boys; 57.6% urban residents; 15.5% in self‐isolation). Approximately two‐thirds followed structured routines (66.4% [95%CI, 65.4–67.4]), and more than half were active during online P.E. (56.6% [95%CI, 55.5–57.6]). 19.0% (95%CI, 18.2–19.9) met the WHO Global physical activity recommendation. Total screen time in excess of 2 h/day was highly prevalent (weekdays: 69.5% [95%CI, 68.5–70.5]; weekend: 63.8% [95%CI, 62.7–64.8]). Playing outdoors more than 2 h/day, following a daily routine and being active in online P.E. increased the odds of healthy levels of physical activity and screen time, particularly in mildly affected countries. In severely affected countries, online P.E. contributed most to meet screen time recommendation, whereas outdoor play was most important for adequate physical activity. Promoting safe and responsible outdoor activities, safeguarding P.E. lessons during distance learning and setting pre‐planned, consistent daily routines are important in helping children maintain healthy active lifestyle in pandemic situation. These factors should be prioritised by policymakers, schools and parents.

Highlights

To our knowledge, our data provide the first multi‐national estimates on physical activity and total screen time in European children roughly two months after COVID‐19 was declared a global pandemic.

Only 1 in 5 children met the WHO Global physical activity recommendations.

Under pandemic conditions, parents should set pre‐planned, consistent daily routines and integrate at least 2‐hours outdoor activities into the daily schedule, preferable on each day. Schools should make P.E. lessons a priority. Decision makers should mandate online P.E. be delivered by schools during distance learning. Closing outdoor facilities for PA should be considered only as the last resort during lockdowns.