bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesizing external aggregated information in the penalized Cox regression under population heterogeneity
Authors: Sheng Ying , Sun Yifei , Huang Chiung‐Yu , Kim Mi‐Ok
Published: June 2021

Synthesizing external aggregated information has been proven useful in improving estimation efficiency when conducting statistical analysis using a limited amount of data. In this paper, we develop a unified framework for combining information from high‐dimensional individual‐level data and potentially low‐dimensional external aggregate data under the Cox model. We summarize various forms of external aggregated information by population estimating equations and propose a penalized empirical likelihood approach to borrow information from these estimating equations. The proposed methods possess the flexibility to handle the case where individual‐level data and external aggregate data are from heterogeneous populations. Specifically, a penalized empirical likelihood ratio test is developed to check for the potential heterogeneity, and a semiparametric density ratio model is postulated to account for the heterogeneity. Moreover, we study the impact of uncertainty in the auxiliary information on the efficiency gain and propose a modified variance estimator to adjust for the uncertainty. The proposed estimators enjoy the oracle property and are asymptotically more efficient than the penalized partial likelihood estimator that does not exploit the external aggregated information. Simulation studies show improvement in both estimation efficiency and variable selection over the competitors. The proposed approaches are applied to the analysis of a pediatric kidney transplant study for illustration.
Merkel Cell Carcinoma
Authors: Mistry K. , Levell N. J. , Craig P. , Steven N. M. , Venables Z. C.
Published: June 2021

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma. The cellular origin of MCC may include Merkel cell precursors. The incidence of MCC has increased significantly however trends may have been confounded by evolving diagnostic criteria. The two key aetiologies of MCC are ultraviolet radiation and Merkel cell polyoma virus (MCPyV). Both have unique mechanisms of carcinogenesis. MCC presents non-specifically as a rapidly growing, red-to-violet nodule on sun-exposed areas. Diagnostic accuracy has improved through immunohistochemical markers such as CK-20. Lymph nodes should be evaluated in MCC through examination and sentinel biopsy. USS, CT, MRI and CT-PET may be useful in staging. Management depends on tumour location, stage and comorbidities. MCPyV status may guide treatment strategy in the future. Treatment for the primary MCC is commonly wide local excision followed by radiotherapy, guided by anatomical constraints. There is uncertainty about surgical margins. Treatments for nodal disease have not been determined through trials. They include nodal dissection or radiotherapy for clinically or radiologically apparent disease, and adjuvant nodal irradiation for negative nodes, microscopic disease or following nodal dissection for definite disease. Patients with loco-regional advanced inoperable disease should be considered for combination therapy including chemotherapy, radiotherapy, surgery and immunotherapy. Systemic therapy for advanced disease includes immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway. Avelumab can improve survival in metastatic MCC. Immunotherapy may result in longer disease control. Various other immunotherapeutic and molecular agents are undergoing trials. MCC continues to have a high mortality characterized by high recurrence and early metastases.
Synthesis and Optimization of a Highly Stable and Efficient BN/TiO2 Nanocomposite for Phenol Degradation: A Photocatalytic, Mechanistic and Environmental Impact Study
Authors: Al‐Kandari Shekhah A. , Mohamed Ahmed M. , Abdullah Aboubakr M. , AlMarzouq Douaa S. , Nasrallah Gheyath K. , Sharaf Mohammed A. , Younes Nadine , Hamdan Munia M. , Altahtamouni Talal , Al‐Kandari Halema A.
Published: June 2021

Different BN/TiO2 nanocomposites were prepared hydrothermally, and their ratio was optimized to get the best photocatalytic performance towards phenol degradation. They were characterized by x‐ray photoelectron spectroscopy, x‐ray diffraction, Fourier transform infrared spectroscopy, thermal gravimetric analysis, scanning and transmission electron microscopies coupled with energy dispersive x‐ray units, BET surface area, and UV‐Vis diffuse reflectance. The bandgap energy was reduced from 3.35 to 2.95 eV due to the formation of the B−O−Ti bond. This allowed the exploitation of the visible light and inhibited the TiO2 e−/h+ recombination, and consequently, the photocatalytic activity of TiO2 was dramatically improved. Almost 90 % mineralization of 20 ppm phenol solution was achieved within 30 min under simulated sunlight. The as‐prepared composite showed excellent stability and reusability. Mechanistic analysis indicated that
and h+ played a crucial role in phenol degradation. The nanocomposite′s biocompatibility and environmental impact were evaluated by analyzing its potential toxicity in vivo using the zebrafish embryos. 96‐hpf acute toxicity assays, including the mortality rate assay (to obtain the LC50 values) and teratogenic assays (to obtain the No Observed Effect Concentration, NOEC) was conducted. The LC50 value for BN/TiO2 was 482.5 mg L−1, and the NOEC was 100 mg L−1. Based on LC50 value and according to the Fish and Wildlife Service (FWS) acute toxicity rating scale, the photocatalyst is “practically not toxic.”
Claisen‐Schmidt Condensation and Domino Claisen‐Schmidt Condensation ‐ Michael Addition of 16‐Formyl Steroids in the Presence of Switchable Polarity Solvents
Authors: Ispán Dávid , Varga Bence , Balogh Szabolcs , Zsirka Balázs , Gömöry Ágnes , Skoda‐Földes Rita
Published: June 2021

Switchable polarity solvents (reversible ionic liquids) have been used to replace conventional catalysts and solvents in Claisen‐Schmidt condensation reactions of 16‐formyl steroids and aromatic ketones. The primarily formed α,β‐unsaturated ketones may undergo a Michael addition with the aromatic ketone reaction partner. By the proper choice of the reaction conditions, either the α,β‐unsaturated ketone or the products of the domino Claisen‐Schmidt condensation ‐ Michael addition could be obtained with good selectivity. The catalyst could successfully be recovered and reused. The steroidal products with androstane and estrane skeleton were characterized by different spectroscopic methods (NMR, IR, MS).
Synthesis and Application of (S)‐Nicotine‐Based Chiral Ionic Liquids in Enantiomeric Recognition by Using Fluorescence Spectroscopy
Authors: Kaur Nirmaljeet , Rahim Junaid Ur , Rai Rajkishore , Chopra Harish Kumar
Published: June 2021

The present report discusses the synthesis, characterization and application of novel chiral ionic liquids (CILs) derived from an enantiopure alkaloid (S)‐nicotine. The synthesis of the CILs was initiated by the preparation of (−)‐bornyl chloroacetate from (−)‐borneol and monochloroacetic acid and then used for the quaternization of (S)‐nicotine. The derivatives of the parent CIL were obtained via anion‐metathesis reactions with sodium salts of dicyanamide and dioctyl sulfosuccinate. The synthesis of the respective compounds was confirmed through NMR (1H,13C) spectroscopy, mass spectrometry, and FTIR. The thermal stability and optical activity of the CILs were analysed through TGA, DTG and polarimetry. All the CILs obtained were liquid at room temperature and exhibited thermal stability up to 150 °C. The potential of chiral ionic liquids as enantiomeric recognizing agents for six amino acids (phenylalanine, proline, valine, alanine, leucine, histidine) was determined through fluorescence spectroscopy. CILs performed well against enantiomers of all amino‐acid with maximum selectivity 1.22 (phenylalanine) and fluorescence enhancement 24.90 : 23.79 (ID/Io : IL/Io) for enantiomers of leucine.
Recent Anti‐angiogenic Drug Discovery Efforts To Combat Cancer
Authors: Upadhyay Neha , Tilekar Kalpana , Safuan Sabreena , Kumar Alan P. , Stalin Jimmy , Ruegg Curzio , Ramaa C S
Published: June 2021

The process of angiogenesis promotes tumor growth and metastatic spreading and angiogenesis inhibition has therapeutic efficacy in many preclinical models. The discovery of pathways mediating tumor angiogenesis, in particular VEGFs and their receptors, paved the way to the development of anti‐angiogenic drugs to translate into clinic as anti‐cancer agents. However, dozens of anti‐angiogenic drugs have been approved and routinely used under clinical practice. However, with the compelling preclinical evidence demonstrating anti‐cancer activity, therapeutic benefits in patients remained modest. Recent progress in understanding the biology of tumor angiogenesis and their molecular mechanisms opened a new prospect for improving therapeutic strategies. An emergent approach to improve efficacy and avoid resistance is to hit multiple angiogenesis pathways and or administration in combination with other anticancer agents. In this review, we have highlighted some of the emerging aspects and discussed new antiangiogenic drug discovery in the past five years.
Image Encoding Using Multi‐Level DNA Barcodes with Nanopore Readout
Authors: Zhu Jinbo , Ermann Niklas , Chen Kaikai , Keyser Ulrich F.
Published: June 2021

Deoxyribonucleic acid (DNA) nanostructure‐based data encoding is an emerging information storage mode, offering rewritable, editable, and secure data storage. Herein, a DNA nanostructure‐based storage method established on a solid‐state nanopore sensing platform to save and encrypt a 2D grayscale image is proposed. DNA multi‐way junctions of different sizes are attached to a double strand of DNA carriers, resulting in distinct levels of current blockades when passing through a glass nanopore with diameters around 14 nm. The resulting quaternary encoding doubles the capacity relative to a classical binary system. Through toehold‐mediated strand displacement reactions, the DNA nanostructures can be precisely added to and removed from the DNA carrier. By encoding the image into 16 DNA carriers using the quaternary barcodes and reading them in one simultaneous measurement, the image is successfully saved, encrypted, and recovered. Avoiding any proteins or enzymatic reactions, the authors thus realize a pure DNA storage system on a nanopore platform with increased capacity and programmability.
3D‐Printed, High‐Porosity, High‐Strength Graphite Aerogel
Authors: Liu Dapeng , Chen Chaoji , Zhou Yubing , Bao Yinhua , Wang Ruiliu , Liu Yu , He Shuaiming , Huang Hao , Zhang Clark , Foster Bob , Li Teng , Hu Liangbing
Published: June 2021

The global demand for plastic foam materials is enormous (annual worth of ≈$341.3 billion) and still surging with an annual growth rate of 4.8%, driven by increasing modern societal needs. The majority of existing foam materials are made of plastics, which take hundreds of years to degrade, leading to severe global pollution issues. Here, a degradable, recyclable, and cost‐effective solution to foam materials based on 3D graphite‐cellulose nanofibers (G‐CNF) foam fabricated from resource‐abundant graphite and cellulose via advanced 3D printing is reported. The CNFs can directly disperse the graphite under physical sonication without the need for any chemical reactions. The interaction of the CNFs with graphite through the function of hydrophilic and hydrophobic faces in CNFs renders the dispersion polymer‐like rheological properties and good processability with tunable viscosity for 3D printing. A robust, degradable, and recyclable G‐CNF foam with designed shapes can be printed in a large scale, demonstrating higher mechanical strength (3.72 MPa versus 0.28 MPa in tensile strength and 2.34 MPa versus 1.11 MPa in compressive stiffness), better fire resistance, degradability, and recyclability than commercial polystyrene foam material. The demonstrated G‐CNF foam can potentially replace the commercial plastic foam materials, representing a sustainable solution toward white pollution.
Heterogeneous Interface Design for Enhanced Sodium Storage: Sb Quantum Dots Confined by Functional Carbon
Authors: Qiu Tianyun , Yang Li , Xiang Yinger , Ye Yu , Zou Guoqiang , Hou Hongshuai , Ji Xiaobo
Published: June 2021

Antimony (Sb) is considered a promising anode material for sodium‐ion batteries due to its high specific capacity and moderate working potential. However, the non‐negligible volume variation leads to the rapid decay of capacity, which hinders the practical application of Sb anode materials. Here, an economical and scalable route with high yield is proposed to obtain Sb ultrafine nanocrystals embedded in a porous carbon skeleton. Notably, the synergetic effect of the heterogeneous structure is maximized by inducing the interfacial coupling SbOC and creating buffering space for the volume effect of Sb. The high‐entropy phase interface creates the doping site breaking the periodicity of atoms and alters the electronic structure, also bridging the slip of intergranular defects. Thus, the electronic conductivity and phase interface structural stability are reinforced. The mechanism of accelerating electron migration at the heterogeneous phase interface is visualized through the density functional theory method, and the mass/charge‐transfer kinetics is analyzed via the calculation of surface‐induced capacitive contribution.
Perspectives of business process ethics in data‐driven marketing management
Authors: Shamsuzzoha Ahm , Raappana Heli
Published: June 2021

In today's digitalized world, people leave trails of data about themselves when operating online. While marketers are eagerly utilizing this data for marketing insights, many consumers have a growing fear of their personal data ending up in the wrong hands and losing their privacy. The aim of this study was to understand the role of ethics in current marketing based on consumer data and to examine how data could be used ethically in marketing. The empirical research was conducted by analyzing secondary data from a 2018 survey about the use of digital services in Europe. The main conclusions that can be drawn from study findings are that the need for ethics is even more apparent in marketing than ever before, because of the broad access to personal data. Giving the consumers the ability to opt‐out from data use and data selling without it affecting the use of services can create an enormous competitive advantage for organizations in the future.
Nonenzymatic, Template‐Free Polymerization of 3’,5’ Cyclic Guanosine Monophosphate on Mineral Surfaces
Authors: Šponer Judit E. , Šponer Jiří , Výravský Jakub , Šedo Ondrej , Zdráhal Zbyněk , Costanzo Giovanna , Di Mauro Ernesto , Wunnava Sreekar , Braun Dieter , Matyášek Roman , Kovařík Aleš
Published: June 2021

Previous studies on the polymerization of 3’,5’ cyclic guanosine monophosphate (cGMP) demonstrated the potential of the compound in the abiotic generation of the first oligonucleotide sequences on the early Earth. These experiments were conducted under idealized laboratory conditions, which logically raises the question whether the same chemistry could take place in the harsh environment present on our planet in its earliest days. In the current study, we focus on the mineralogical context of this chemistry and show that numerous, but not all, common minerals assumed to be present on the early Earth could host the polymerization of H‐form 3’,5’ cGMP. In particular, we have found that quartz varieties are especially suitable for this purpose, similar to andalusite, amphibole or micas. On the contrary, olivine, calcite, and serpentine‐group minerals interfere with the studied polymerization chemistry. Our results show that crystallization on mineral surfaces, which is mainly a diffusion controlled process, determines the ability of 3’,5’ cGMP to polymerize. The observation that numerous amorphous and crystalline SiO2 forms are compatible with the oligomerization chemistry suggests that the process could commonly occur in a wide range of primordial environments allowing for crystallization of the cyclic monomers from a dropping solution.
Organo‐Cobalt Complexes in Reversible‐Deactivation Radical Polymerization
Authors: Benchaphanthawee Wachara , Peng Chi‐How
Published: June 2021

Cobalt complexes have played an essential role in different chemical reactions. One of them that has attracted substantial attention in polymer science is cobalt mediated radical polymerization (CMRP), which is famous for its remarkable efficiency in controlling the radical polymerization of vinyl acetate (VAc) and other less active monomers (LAMs). Two pathways, reversible termination (RT) and degenerative transfer (DT), were recognized to control the polymerization in CMRP and could be further used to rationalize the mechanism of other RDRP methods. These control mechanisms were then found to be correlated to the redox potential of cobalt complexes and thus could be judged more quantitatively. The control of polymer composition and tacticity could also be achieved by using CMRP. The hybridization of CMRP and atom transfer radical polymerization (ATRP) could directly synthesize the vinyl acetate/methyl methacrylate and vinyl acetate/styrene block copolymers in one pot. The copolymer of acrylates and 1‐octene could be obtained by visible‐light‐induced CMRP. With the addition of bulky Lewis acid, CMRP of N,N‐dimethylacrylamide (DMA) showed high isotacticities with the contents of meso dyads (m) and meso triads (mm) up to 94 % and 87 %, respectively, and generated the crystalline PDMA with Tm as high as 276 °C. This personal account reviewed the development of CMRP with the mechanistic understanding, the control of composition and stereoselectivity of the polymeric products, and its perspective.
Present Status and Future Prospects of Jute in Nanotechnology: A Review
Authors: Shah Syed Shaheen , Shaikh M. Nasiruzzaman , Khan Mohd Yusuf , Alfasane Md. Almujaddade , Rahman Mohammad Mizanur , Aziz Md. Abdul
Published: June 2021

Nanotechnology has transformed the world with its diverse applications, ranging from industrial developments to impacting our daily lives. It has multiple applications throughout financial sectors and enables the development of facilitating scientific endeavors with extensive commercial potentials. Nanomaterials, especially the ones which have shown biomedical and other health‐related properties, have added new dimensions to the field of nanotechnology. Recently, the use of bioresources in nanotechnology has gained significant attention from the scientific community due to its 100 % eco‐friendly features, availability, and low costs. In this context, jute offers a considerable potential. Globally, its plant produces the second most common natural cellulose fibers and a large amount of jute sticks as a byproduct. The main chemical compositions of jute fibers and sticks, which have a trace amount of ash content, are cellulose, hemicellulose, and lignin. This makes jute as an ideal source of pure nanocellulose, nano‐lignin, and nanocarbon preparation. It has also been used as a source in the evolution of nanomaterials used in various applications. In addition, hemicellulose and lignin, which are extractable from jute fibers and sticks, could be utilized as a reductant/stabilizer for preparing other nanomaterials. This review highlights the status and prospects of jute in nanotechnology. Different research areas in which jute can be applied, such as in nanocellulose preparation, as scaffolds for other nanomaterials, catalysis, carbon preparation, life sciences, coatings, polymers, energy storage, drug delivery, fertilizer delivery, electrochemistry, reductant, and stabilizer for synthesizing other nanomaterials, petroleum industry, paper industry, polymeric nanocomposites, sensors, coatings, and electronics, have been summarized in detail. We hope that these prospects will serve as a precursor of jute‐based nanotechnology research in the future.
Engaging students with team‐based learning in courses taught at two campuses synchronously: Two case studies in health sciences
Authors: Bender Holly S. , Garrett Kennon M. , Hostetter Shannon Jones
Published: June 2021

This chapter describes two case studies that highlight how courses can be taught simultaneously in classrooms across partnering university campuses using the effective, evidence‐based team‐based learning (TBL) method. The objective is to assist faculty in effectively using TBL in a synchronous virtual collaborative space.
Application of the gamma‐interferon assay to determine the prevalence of bovine tuberculosis in slaughter livestock at abattoirs in Gauteng, South Africa
Authors: Mareledwane Vuyokazi E. , Adesiyun Abiodun A. , Thompson Peter N. , Hlokwe Tiny M.
Published: June 2021

Background

Bovine tuberculosis (bTB) is a zoonotic disease with great economic impact estimated at billions of dollars annually worldwide. Meat inspection represents a long‐standing form of disease surveillance that serves both food safety and animal health. The objective of this study was to determine the prevalence of bTB in livestock at abattoirs using a cell‐mediated immune (CMI) assay, the gamma interferon (IFN‐γ) assay. This cross‐sectional study was conducted at selected abattoirs (low‐throughput, high‐throughput and rural/informal) in Gauteng province, where animals were also subjected to routine meat inspection.

Results

A total of 410 fresh blood samples were collected from slaughter livestock (369 cattle and 41 sheep) from 15 abattoirs, and analysed using Bovigam® test kit with bovine, avian and Fortuitum purified protein derivatives (PPD) as blood stimulating antigens. The estimated prevalence of bTB in cattle was 4.4% (95% CI: 2.4%–7.3%). The prevalence of bTB in cattle varied between abattoirs (p = .005), ranging from 0% to 23%; however, there were no significant differences among genders, breeds, municipality, districts, origins of animals (feedlot, auction or farm) or throughput of abattoirs. The prevalence of avian reactors was 6.0% (95% CI: 3.6%–9.2%) in cattle, varying between abattoirs (p = .004) and ranging from 0% to 20.7%. None of the sheep with valid test results was positive for bTB and none was avian reactors (95% CI: 0%–15%).

Conclusion

The detection of bTB reactor cattle in our study clearly shows the limitation of disease surveillance using a meat inspection approach, as all the 410 slaughter animals sampled had passed visual abattoir inspection and been classified as bTB‐free. Our findings therefore emphasize the risk of zoonotic transmission of bTB to abattoir workers and potential food safety hazard to consumers. Furthermore, our study highlights the potential for the use of the IFN‐γ assay to reduce this risk.
Integration schemes for hybrid and polygeneration concentrated solar power plants
Authors: Cardemil José M. , Starke Allan R. , Zurita Adriana , Mata‐Torres Carlos , Escobar Rodrigo
Published: June 2021

Concentrated solar power (CSP) technologies have been developed over the past four decades for commercial operation, establishing them as reliable power generation sources in regions with high direct solar irradiance. The sizing of the solar field, thermal energy storage systems, and power block enables CSP plants to operate under various operating conditions, while also exhibiting capabilities to generate multiple products such as electricity, heat, desalination, and cooling. The limitations of CSP systems can be reduced by utilizing the positive traits of other technologies, thus resulting in hybrid plant configurations that can fully exploit different technology strengths while minimizing their individual weaknesses. This review presents the state of the art on CSP stand‐alone plants for both power generation and combined generation of different products. Subsequently, the characteristics of CSP plants hybridized with photovoltaics, wind, fossil fuels, and biomass systems are discussed for both power multiple‐product generation. The review of assessment methodologies provides suggestions for both assessment and performance analysis and comparison with other generation technologies. This review shows that hybrid CSP plants have clear advantages in terms of cost, flexibility of operation, adaptability, and capability for the multigeneration of different products compared with stand‐alone plants used to generate each product individually. Hybrid CSP plants have advantages and can be designed to satisfy multiple demands on a case‐by‐case basis and are valid alternatives to combinations of stand‐alone plants.

This article is categorized under:

Concentrating Solar Power > Systems and Infrastructure
High-energy operator product expansion at sub-eikonal level
Authors: Chirilli Giovanni Antonio
Published: June 2021

Abstract

The high energy Operator Product Expansion for the product of two electromagnetic currents is extended to the sub-eikonal level in a rigorous way. I calculate the impact factors for polarized and unpolarized structure functions, define new distribution functions, and derive the evolution equations for unpolarized and polarized structure functions in the flavor singlet and non-singlet case.
An update on the two singlet dark matter model
Authors: Basak Tanushree , Coleppa Baradhwaj , Loho Kousik
Published: June 2021

Abstract

We revisit the two real singlet extension of the Standard Model with a $$ {Z}_2\times {Z}_2^{\prime } $$

Z
2

×

Z
2
′

symmetry. One of the singlet scalars S2, by virtue of an unbroken $$ {Z}_2^{\prime } $$

Z
2
′

symmetry, plays the role of a stable dark matter candidate. The other scalar S1, with spontaneously broken Z2-symmetry, mixes with the SM Higgs boson and acts as the scalar mediator. We analyze the model by putting in the entire set of theoretical and recent experimental constraints. The latest bounds from direct detection Xenon1T experiment severely restricts the allowed region of parameter space of couplings. To ensure the dark matter satisfies the relic abundance criterion, we rely on the Breit-Wigner enhanced annihilation cross-section. Further, we study the viability of explaining the observed gamma-ray excess in the galactic center in this model with a dark matter of mass in the ∼ 36 − 51 GeV window and present our conclusions.
Ergebnisse des Limberg-Plastik-Verfahrens bei akuten und chronischen Pilonidalabszessen
Authors: Driouch Jamal , Braumann C. , Dehnst J. , Ikram M. , Alnammous G. , Bausch D. , Glatz T.
Published: June 2021

Hintergrund

In der Behandlung des Sinus pilonidalis werden unterschiedliche Therapiealgorithmen für den akuten sowie den chronischen Sinus pilonidalis empfohlen. Während sich beim chronischen Sinus pilonidalis ein einzeitiges Vorgehen als Exzision oder plastische Rekonstruktion nach Limberg oder Karydakis anbietet, ist die empfohlene Vorgehensweise beim akuten Pilonidalabszess zweizeitig. Ziel dieser Studie war es, die Ergebnisse der einzeitigen Operation mit Limberg-Plastik bei akutem Pilonidalabszess und chronischem Sinus pilonidalis bezogen auf Rezidive, Wundheilungsstörungen, stationärer Liegedauer sowie Patientenzufriedenheit zu vergleichen.

Methoden

Von 2009 bis 2014 wurden 39 Patienten in die prospektive Beobachtungsstudie eingeschlossen. 21 Patienten mit akutem Pilonidalabszess, 18 mit chronischem Sinus pilonidalis. Alle Patienten wurden einzeitig mittels Limberg-Rautenplastik operativ behandelt. Die Gruppen wurden in Bezug auf postoperative Komplikationsrate und Rezidivhäufigkeit miteinander verglichen.

Ergebnisse

Beide Gruppen waren im Wesentlichen vergleichbar. Die Analyse der postoperativen Ergebnisse zeigte eine vergleichbare Rate an Wundheilungsstörungen (10 % vs. 17 %, p = 0,647). In der Gruppe des akut abszedierten Sinus trat kein Rezidiv im Beobachtungszeitraum auf, während sich in der chronischen Gruppe 2 (11 %) Rezidive zeigten (p = 0,206).

Diskussion

Die Ergebnisse der Limberg-Plastik als einzeitige Therapie des Pilonidalabszesses sind mit denen beim chronischen Sinus pilonidalis vergleichbar. Es zeigt sich ein Trend zu einem geringeren Rezidivrisiko. Der Einsatz der Limberg-Plastik scheint daher auch in der akuten Infektsituation eine adäquate Therapieoption.
Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes
Authors: Sjögren Rasmus J. O. , Rizo-Roca David , Chibalin Alexander V. , Chorell Elin , Furrer Regula , Katayama Shintaro , Harada Jun , Karlsson Håkan K. R. , Handschin Christoph , Moritz Thomas , Krook Anna , Näslund Erik , Zierath Juleen R.
Published: June 2021

Aims/hypothesis

Increased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified.

Methods

Plasma and vastus lateralis muscle biopsies were obtained from individuals with NGT or type 2 diabetes before and after an OGTT. Plasma and quadriceps muscles were harvested from skeletal muscle-specific Ppargc1a knockout and transgenic mice. BCAA-related metabolites and genes were assessed by LC-MS/MS and quantitative RT-PCR, respectively. Small interfering RNA and adenovirus-mediated overexpression techniques were used in primary human skeletal muscle cells to study the role of PPARGC1A and ESRRA in the expression of the BCAA gene set. Radiolabelled leucine was used to analyse the impact of oestrogen-related receptor α (ERRα) knockdown on leucine oxidation.

Results

Impairments in BCAA catabolism in people with type 2 diabetes under fasting conditions were exacerbated after a glucose load. Branched-chain keto acids were reduced 37–56% after an OGTT in the NGT group, whereas no changes were detected in individuals with type 2 diabetes. These changes were concomitant with a stronger correlation with glucose homeostasis biomarkers and downregulated expression of branched-chain amino acid transaminase 2, branched-chain keto acid dehydrogenase complex subunits and 69% of downstream BCAA-related genes in skeletal muscle. In primary human myotubes overexpressing peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, encoded by PPARGC1A), 61% of the analysed BCAA genes were upregulated, while 67% were downregulated in the quadriceps of skeletal muscle-specific Ppargc1a knockout mice. ESRRA (encoding ERRα) silencing completely abrogated the PGC-1α-induced upregulation of BCAA-related genes in primary human myotubes.

Conclusions/interpretation

Metabolic inflexibility in type 2 diabetes impacts BCAA homeostasis and attenuates the decrease in circulating and skeletal muscle BCAA-related metabolites after a glucose challenge. Transcriptional regulation of BCAA genes in primary human myotubes via PGC-1α is ERRα-dependent.

Graphical abstract
Natural microbial polysaccharides as effective factors for modification of the catalytic properties of fungal cellobiose dehydrogenase
Authors: Sulej Justyna , Jaszek Magdalena , Osińska-Jaroszuk Monika , Matuszewska Anna , Bancerz Renata , Janczarek Monika
Published: June 2021

Polysaccharides are biopolymers composed of simple sugars like glucose, galactose, mannose, fructose, etc. The major natural sources for the production of polysaccharides include plants and microorganisms. In the present work, four bacterial and two fungal polysaccharides (PS or EPS) were used for the modification and preservation of Pycnoporus sanguineus cellobiose dehydrogenase (CDH) activity. It was found that the presence of polysaccharide preparations clearly enhanced the stability of cellobiose dehydrogenase compared to the control value (4 °C). The highest stabilization effect was observed for CDH modified with Rh110EPS. Changes in the optimum pH in the samples of CDH incubated with the chosen polysaccharide modifiers were evidenced as well. The most significant effect was observed for Rh24EPS and Cu139PS (pH 3.5). Cyclic voltammetry used for the analysis of electrochemical parameters of modified CDH showed the highest peak values after 30 days of incubation with polysaccharides at 4 °C. In summary, natural polysaccharides seem to be an effective biotechnological tool for the modification of CDH activity to increase the possibilities of its practical applications in many fields of industry.
Prospective assessment of diagnostic efficacy and safety of SonazoidTM and SonoVue® ultrasound contrast agents in patients with focal liver lesions
Authors: Lv Ke , Zhai Hongyan , Jiang Yuxin , Liang Ping , Xu Hui-Xiong , Du Lianfang , Chou Yi-Hong , Xie Xiaoyan , Luo YuKun , Lee Young Joon , Lee Jae Young , Hu Bing , Luo Baoming , Wang Yi , Luan Ying , Kalli Christina , Chen Kun , Wang Wenping , Liang Ja-Der
Published: June 2021

Objectives

To assess the respective diagnostic value of Sonazoid™ and SonoVue® for characterizing FLLs as benign or malignant and the corresponding safety.

Methods

This prospective Phase 3 study was conducted at 17 centres in China and Korea (May 2014 to April 2015); 424 patients (20 to 80 years) with at least 1 untreated focal liver lesion (FLL) (< 10 cm in diameter) underwent a contrast-enhanced ultrasound (CEUS) examination (218 received Sonazoid of 0.12 μL microbubbles/kg; 206 received SonoVue of 2.4 mL). Three independent blinded readers evaluated pre- and post-contrast images characterising the FLLs as benign or malignant.

Results

Sonazoid-enhanced and SonoVue-enhanced ultrasound provided a statistically significant improvement in specificity for all 3 readers comparing to unenhanced ultrasound (for Sonazoid: p = 0.0093, < 0.0001, 0.0011; for SonoVue: p = 0.002, 0.03, 0.12, respectively). Difference in accuracy improvement between the 2 groups was within the pre-specified non-inferiority margin of 20% for all 3 readers (6.1%, 95% CI: − 5.0 to 17.2; − 7.5%, 95% CI: − 18.4 to 3.5; − 0.3%, 95% CI: − 11.3 to 10.7).

The diagnostic confidence level for all 3 readers increased with post-contrast images relative to pre-contrast images. Both contrast agents were well tolerated.

Conclusion

Results showed a similar efficacy for Sonazoid™ and SonoVue® in diagnosing FLLs as benign or malignant, and underlined the benefit of CEUS imaging over unenhanced ultrasound imaging in reaching a confident diagnosis without having to refer patients for additional imaging exams.
DEtection of ProxImal Coronary stenosis in the work-up for Transcatheter aortic valve implantation using CTA (from the DEPICT CTA collaboration)
Authors: van den Boogert Thomas P. W. , Claessen Bimmer E. P. M. , Opolski Maksymilian P. , Kim Won-Keun , Hamdan Ashraf , Andreini Daniele , Pugliese Francesca , Möllmann Helge , Delewi Ronak , Baan Jan , Vis M. Marije , van Randen Adrienne , van Schuppen Joost , Stoker Jaap , Henriques José P. , Planken R. Nils
Published: June 2021

Objectives

Computed tomography angiography (CTA) is performed routinely in the work-up for transcatheter aortic valve implantation (TAVI), and could potentially replace invasive coronary angiography (ICA) to rule out left main (LM) and proximal coronary stenosis. The objectives were to assess the diagnostic yield and accuracy of pre-TAVI CTA to detect LM and proximal coronary stenosis of ≥ 50% and ≥ 70% diameter stenosis (DS).

Methods

The DEPICT CTA database consists of individual patient data from four studies with a retrospective design that analyzed the diagnostic accuracy of pre-TAVI CTA to detect coronary stenosis, as compared with ICA. Pooled data were used to assess diagnostic accuracy to detect coronary stenosis in the left main and the three proximal coronary segments on a per-patient and a per-segment level. We included 1060 patients (mean age: 81.5 years, 42.7% male).

Results

On ICA, the prevalence of proximal stenosis was 29.0% (≥ 50% DS) and 15.7% (≥ 70% DS). Pre-TAVI CTA ruled out ≥ 50% DS in 51.6% of patients with a sensitivity of 96.4%, specificity of 71.2%, PPV of 57.7%, and NPV of 98.0%. For ≥ 70% DS, pre-TAVI CTA ruled out stenosis in 70.0% of patients with a sensitivity of 96.7%, specificity of 87.5%, PPV of 66.9%, and NPV of 99.0%.

Conclusion

CTA provides high diagnostic accuracy to rule out LM and proximal coronary stenosis in patients undergoing work-up for TAVI. Clinical application of CTA as a gatekeeper for ICA would reduce the need for ICA in 52% or 70% of patients, using a threshold of ≥ 50% or ≥ 70% DS, respectively.

Key Points

• Clinical application of CTA as a gatekeeper for ICA would reduce the need for ICA in 52% or 70% of TAVI patients, using a threshold of ≥ 50% or ≥ 70% diameter stenosis.

• The diagnostic accuracy of CTA to exclude proximal coronary stenosis in these patients is high, with a sensitivity of 96.4% and NPV of 98.0% for a threshold of ≥ 50%, and a sensitivity of 96.7% and NPV of 99.0% for a threshold of ≥ 70% diameter stenosis.

• Atrial fibrillation and heart rate did not significantly affect sensitivity and NPV. However, a heart rate of < 70 b/min during CTA was associated with a significantly improved specificity and PPV.
Hamiltonian Aspects of Three-Layer Stratified Fluids
Authors: Camassa R. , Falqui G. , Ortenzi G. , Pedroni M. , Ho T. T. Vu
Published: June 2021

The theory of three-layer density-stratified ideal fluids is examined with a view toward its generalization to then-layer case. The focus is on structural properties, especially for the case of a rigid upper lid constraint. We show that the long-wave dispersionless limit is a system of quasi-linear equations that do not admit Riemann invariants. We equip the layer-averaged one-dimensional model with a natural Hamiltonian structure, obtained with a suitable reduction process from the continuous density stratification structure of the full two-dimensional equations proposed by Benjamin. For a laterally unbounded fluid between horizontal rigid boundaries, the paradox about the non-conservation of horizontal total momentum is revisited, and it is shown that the pressure imbalances causing it can be intensified by three-layer setups with respect to their two-layer counterparts. The generator of thex-translational symmetry in then-layer setup is also identified by the appropriate Hamiltonian formalism. The Boussinesq limit and a family of special solutions recently introduced by de Melo Viríssimo and Milewski are also discussed.
The effect of exercise and nutrition interventions on physical functioning in patients undergoing haematopoietic stem cell transplantation: a systematic review and meta-analysis
Authors: Prins Marianne C. , van Hinte Gerben , Koenders Niek , Rondel Anne Lieke , Blijlevens Nicole M. A. , van den Berg Manon G. A.
Published: June 2021

Purpose

Haematopoietic stem cell transplantation (HSCT) is potentially lifesaving. However, it comes with negative consequences such as impaired physical functioning, fatigue and poor quality of life. The aim of this systematic review and meta-analysis is to determine the effect of exercise and nutrition interventions to counteract negative consequences of treatment and improve physical functioning in patients receiving HSCT.

Methods

This systematic review and meta-analysis included randomised controlled trials from three electronic databases between 2009 and 2020. The trials included adult patients receiving HSCT and an exercise or nutrition intervention. Study selection, bias assessment and data extraction were independently performed by two reviewers. Physical functioning outcomes were meta-analysed with a random-effects model.

Results

Thirteen studies were included using exercise interventions (n = 11) and nutrition interventions (n = 2); no study used a combined intervention. Meta-analysis of the trials using exercise intervention showed statistically significant effects on 6-min walking distance (standardised mean difference (SMD) 0.41, 95% CI: 0.14–0.68), lower extremity strength (SMD 0.37, 95% CI 0.12–0.62) and global quality of life (SMD 0.27, 95% CI: 0.08–0.46).

Conclusion

Our physical functioning outcomes indicate positive effects of exercise interventions for patients receiving HSCT. Heterogeneity of the exercise interventions and absence of high-quality nutrition studies call for new studies comparing different types of exercise studies and high quality studies on nutrition in patients with HSCT.
Reducing pain in children with cancer at home: a feasibility study of the KLIK pain monitor app
Authors: Simon Julia D. H. P. , Schepers Sasja A. , Grootenhuis Martha A. , Mensink Maarten , Huitema Angelique D. , Tissing Wim J. E. , Michiels Erna M. C.
Published: June 2021

Purpose

This study assessed adherence to, feasibility of, and barriers and facilitators of implementation of an app developed to monitor and follow-up with pain in children with cancer at home.

Methods

Children (8–18 years) receiving cancer treatment (all diagnoses) or their parents (of children aged 0–7 years) used the KLIK Pain Monitor app for 3 weeks. Pain was assessed twice daily using an 11-point numeric rating scale (NRS-11) (ranging from 0 to 10). Healthcare professionals (HCP’s) from the hospital’s Pediatric Pain Service were instructed to follow-up with clinically significant pain scores (≥ 4) within 120 min (scores 4–6) or 30 min (scores 7–10). Adherence, feasibility, and implementation outcomes were assessed using questionnaires, app log data, and interviews.

Results

Twenty-seven children (M age = 7.3 years, 51.8% male) and six HCP’s participated. Sixty-three percent (N = 17) of families used the app on a daily basis during three weeks, and 18.5% (N = 5) reported pain scores twice daily during that time (family adherence). Twelve out of 27 children (44.4%) reported a clinically significant pain score at least once. In 70% (14/20) of clinically significant pain scores, HCP’s followed-up with families within the set timeframe (HCP adherence). Outcomes reveal feasibility for the majority of app functions (i.e., positive evaluation by ≥ 70% families/HCP’s), and non-feasible aspects could be resolved. Identified barriers and facilitators were used to improve future implementation efforts.

Conclusion

Use of the KLIK Pain Monitor app seems feasible. Future research will determine its effectiveness in reducing pain in children with cancer at home.
Alternative Magnetflussführung in Elektromotoren
Authors: Schauerte Benedikt , Gilch Ines , Neuwirth Tobias , Sebold Simon , Leuning Nora , Schulz Michael , Volk Wolfram , Hameyer Kay
Published: June 2021

Nicht-kornorientiertes Elektroblech ist eine Kernkomponente im Aufbau rotierender elektrischer Maschinen. Es dient der gezielten Führung und Verstärkung des magnetischen Flusses. Eine möglichst starke magnetische Kopplung zwischen Rotor- und Statorfluss ist hierbei entscheidend für die Effizienz und Leistungsdichte des elektrischen Antriebs.

Zu diesem Zweck werden in permanentmagneterregten Synchron-Maschinen und Synchron-Reluktanzmaschinen Flussbarrieren eingebracht, um Streuflüsse zu unterdrücken und eine gezielte Führung des magnetischen Flusses zu gewährleisten. Die Flussbarrieren werden typischerweise durch Aussparungen im Rotorquerschnitt realisiert. Die resultierenden filigranen Strukturen des Elektroblechs führen zu einer mechanischen Schwächung des Rotors und somit zu geringeren erreichbaren Drehzahlen und Leistungsdichten.

In dieser Arbeit wird ein alternativer Ansatz zur Führung des magnetischen Flusses auf Basis des Villari-Effekts vorgestellt. Lokal veränderte magnetische Werkstoffeigenschaften werden durch erhöhte Eigenspannungen in geprägten Werkstoffbereichen erzielt. Der Zusammenhang zwischen umformtechnisch eingebrachten Eigenspannungen und der reduzierten magnetischen Leitfähigkeit des Elektroblechs wird anhand homogen geprägter Proben untersucht. Höhere Umformkräfte, die mit gesteigerten mechanischen Spannungen einhergehen, führen zu einer stärkeren Reduktion der magnetischen Permeabilität. Die Funktionsweise dieser alternativen magnetischen Flusssperren wird anhand kreisförmiger Prägemuster gezeigt. Neben der Darstellung des Einflusses variierender Prägeparameter auf die magnetischen Eigenschaften des Elektroblechs wird vor allem die Reproduzierbarkeit der veränderten magnetischen Eigenschaften durch umformtechnisch hervorgerufene Eigenspannungen nachgewiesen.
Differential expression of miRNAs and functional role of mir-200a in high and low productivity CHO cells expressing an Fc fusion protein
Authors: Bryan Laura , Henry Michael , Barron Niall , Gallagher Clair , Kelly Ronan M. , Frye Christopher C. , Osborne Matthew D. , Clynes Martin , Meleady Paula
Published: June 2021

Objectives

We used miRNA and proteomic profiling to understand intracellular pathways that contribute to high and low specific productivity (Qp) phenotypes in CHO clonally derived cell lines (CDCLs) from the same cell line generation project.

Results

Differentially expressed (DE) miRNAs were identified which are predicted to target several proteins associated with protein folding. MiR-200a was found to have a number of predicted targets associated with the unfolded protein response (UPR) which were shown to have decreased expression in high Qp CDCLs and have no detected change at the mRNA level. MiR-200a overexpression in a CHO CDCL was found to increase recombinant protein titer by 1.2 fold and Qp by 1.8 fold.

Conclusion

These results may suggest a role for miR-200a in post-transcriptional regulation of the UPR, presenting miR-200a as a potential target for engineering industrially attractive CHO cell phenotypes.