bluuebunny/crossref_metadata_2025 huggingface dataset:
Usage of In Vitro Metabolism Data for Drug‐Drug Interaction in Physiologically Based Pharmacokinetic Analysis Submissions to the US Food and Drug Administration
Authors: Lee Jieon , Yang Yuching , Zhang Xinyuan , Fan Jianghong , Grimstein Manuela , Zhu Hao , Wang Yaning
Published: January 2021

The key parameters necessary to predict drug‐drug interactions (DDIs) are intrinsic clearance (CLint) and fractional contribution of the metabolizing enzyme toward total metabolism (fm). Herein, we summarize the accumulated knowledge from 53 approved new drug applications submitted to the Office of Clinical Pharmacology, US Food and Drug Administration, from 2016 to 2018 that contained physiologically based pharmacokinetic (PBPK) models to understand how in vitro data are used in PBPK models to assess drug metabolism and predict DDIs. For evaluation of CLint and fm, 29 and 20 new drug applications were included for evaluation, respectively. For CLint, 86.2% of the PBPK models used modified values based on in vivo data with modifications ranging from –82.5% to 2752.5%. For fm, 45.0% of the models used modified values with modifications ranging from –28% to 178.6%. When values for CLint were used from in vitro testing without modification, the model resulted in up to a 14.3‐fold overprediction of the area under the concentration‐time curve of the substrate. When values for fm from in vitro testing were used directly, the model resulted in up to a 2.9‐fold underprediction of its DDI magnitude with an inducer, and up to a 1.7‐fold overprediction of its DDI magnitude with an inhibitor. Our analyses suggested that the in vitro system usually provides a reasonable estimation of fm when the drug metabolism by a given CYP pathway is more than 70% of the total clearance. In vitro experiments provide important information about basic PK properties of new drugs and can serve as a starting point for building a PBPK model. However, key PBPK parameters such as CLint and fm still need to be optimized based on in vivo data.
Process of cytoplasm elimination during spermiogenesis in Octopus tankahkeei: Polarized development of the spermatid and discarding of the residual body
Authors: Gao Xinming , Du Chen , Zheng Xuebin , Zhu Junquan , Jin Shan
Published: January 2021

The elimination of the spermatid cytoplasm during spermiogenesis enables the sperm to acquire a streamlined architecture, which allows for unhindered swimming. While this process has been well described in vertebrates, it has rarely been reported in invertebrates. In this study, we observed the process of cytoplasm elimination during spermiogenesis in Octopus tankahkeei (Mollusca, Cephalopoda) using light microscopy, transmission electron microscopy, and immunofluorescence. In the early spermatid, the cell is circular, and the nucleus is centrally located. With spermatid development, the cell becomes polarized. The nucleus gradually elongates and moves toward the end of the cell where the tail is forming. As a result, the cytoplasm moves past the nucleus at the anterior region of the future sperm head (the foreside of the acrosome). Following this, during the late stage of spermiogenesis, the cytoplasm condenses and collects on the foreside of the acrosome until finally the residual body is discarded from the top of the sperm head. This represents a distinct directionality for the development of cytoplasmic polarity and discarding of residual body compared with that reported for vertebrates (in which the cytoplasm of the elongating spermatids is polarized toward the caudal region). The fact that the cytoplasm also becomes concentrated suggests that water pumps may be involved in the elimination of water from the cytoplasm before the residual body is discarded. Furthermore, we found that microtubules, forming a manchette‐like structure, are involved not only in reshaping of the nucleus but also in the transport of mitochondria and vesicles to the foreside of the acrosome, subsequently allowing them to be discarded with the residual body. This study broadens our understanding of the development of polarization and elimination of cytoplasm from spermatids in animals.
World‐wide tracking of major SARS‐CoV‐2 genome haplotypes in sequences of June 1 to November 15, 2020 and discovery of rapid expansion of a new haplotype
Authors: Safari Iman , InanlooRahatloo Kolsoum , Elahi Elahe
Published: January 2021

Earlier, 13 haplotype groups defined by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) genome sequence variations were identified in 2790 sequences available in March 2020. Also, 23403A>G that causes p. Asp614Gly in the spike protein and is one of the defining variations of the haplotype group H1, was becoming increasingly prevalent. As a follow‐up, 74922 SARS‐CoV‐2 sequences retrieved from individuals infected in June 1 to November 15 were analyzed. Consistent with the reports on 23403A>G, H1 haplotype frequency increased world‐wide; among August to November sequences, only 0.3% were associated with non‐H1 haplotypes. This finding prompted assessment of H1 sub‐haplotypes among the sequences of the later stage of the coronavirus disease 2019 pandemic. The distribution of the sub‐haplotypes differed in different regions, but 98.4% of the sequences were associated with five H1 sub‐haplotypes. One of these had not been previously observed and had emerged in Europe by June 2020. The most important finding of the present study is identification of this new sub‐haplotype (H1r) and finding evidence that suggest it may have a high potential for expansion. Its frequency had reached 10%–90% in various countries/territories of Europe by the end of September. The new sub‐haplotype is defined by seven sequence variations, one of which causes Ala222Val in the spike protein.
Part 2. Review and meta‐analysis of studies on modulation of longitudinal bone growth and growth plate activity: A micro‐scale perspective
Authors: D'Andrea Christian R. , Alfraihat Ausilah , Singh Anita , Anari Jason B. , Cahill Patrick J. , Schaer Thomas , Snyder Brian D. , Elliott Dawn , Balasubramanian Sriram
Published: January 2021

Macro‐scale changes in longitudinal bone growth resulting from mechanical loading were shown in Part 1 of this review to depend on load magnitude, anatomical location, and species. While no significant effect on longitudinal growth was observed by varying frequency and amplitude of cyclic loading, such variations, in addition to loading duration and species, were shown to affect the morphology, viability, and gene and protein expression within the growth plate. Intermittent compression regimens were shown to preserve or increase growth plate height while stimulating increased chondrocyte presence in the hypertrophic zone relative to persistent and static loading regimens. Gene and protein expressions related to matrix synthesis and degradation, as well as regulation of chondrocyte apoptosis were shown to exhibit magnitude‐, frequency‐, and duration‐dependent responses to loading regimen. Chondrocyte viability was shown to be largely preserved within physiological bounds of magnitude, frequency, amplitude, and duration. Persistent static loading was shown to be associated with overall growth plate height in tension only, reducing it in compression, while affecting growth plate zone heights differently across species and encouraging mineralization relative to intermittent cyclic loading. Lateral loading of the growth plate, as well as microfluidic approaches are relatively understudied, and age, anatomical location, and species effects within these approaches are undefined. Understanding the micro‐scale effects of varied loading regimes can assist in the development of growth modulation methods and device designs optimized for growth plate viability preservation or mineralization stimulation based on patient age and anatomical location.
Effect of Lateral Crural Procedures on Nasal Wall Stability and Tip Aesthetics in Rhinoplasty
Authors: Abdelwahab Mohamed , Patel Priyesh , Kandathil Cherian K. , Wadhwa Harsh , Most Sam P.
Published: January 2021

Objectives/Hypothesis

To evaluate the lateral nasal wall stability, nasal function, and cosmesis when creating an aesthetically pleasing nasal tip subunit utilizing lateral crus (LC) altering procedures.

Study design

Retrospective cohort.

Methods

In this retrospective cohort study, cosmetic rhinoplasty patients undergoing LC procedures with available lateral wall insufficiency (LWI) scores were included. An LWI grading system was used to evaluate internal (zone 1) and external (zone 2) nasal valves objectively. Secondarily, Nasal Obstruction Symptom Evaluation (NOSE) Score, Visual Analog Scale (VAS) and Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) results were evaluated. Based on the LC intervention, the cohort was divided into six groups: lateral cural strut graft (LCSG), mini‐LCSG, lateral crural overlay (LCO) with and without additional support, cephalic trimming, and cephalic turn‐in flaps.

Results

Subjects undergoing LCO with and without support, LCSG, and mini‐LCSG showed significant improvement in zone 1 LWI (P = .042, P = .041, P < .001, and P < .001, respectively), while cephalic trimming and turn‐in/hinged flaps had no effect. Subjects undergoing LCO with support and LCSG showed significant improvement in zone 2 LWI (P = .022, P = .004), while LCO without support, mini‐LCSG, cephalic trimming, and turn‐in flaps showed no effect on LWI. The SCHNOS‐C and VAS‐C showed significant improvement in all subgroups (P < .05) when comparing pre‐ to postoperative values. Alar‐spanning sutures did not significantly change zone 1 scores but did conceal zone 2 improvements in LCSG and LCO with support groups.

Conclusions

Selected LC procedures are robust techniques for improving tip cosmesis independently without compromising nasal lateral wall stability. Some LC procedures can improve nasal valves patency in tip surgery. Laryngoscope, 131:E1830–E1837, 2021
Drug Delivery Systems‐Based Dendrimers and Polymer Micelles for Nuclear Diagnosis and Therapy
Authors: Aranda‐Lara Liliana , García Blanca Eli Ocampo , Isaac‐Olivé Keila , Ferro‐Flores Guillermina , Meléndez‐Alafort Laura , Morales‐Avila Enrique
Published: January 2021

Polymeric nanoparticles encompass micelles and dendrimers. They are used for improving or controlling the action of the loaded therapy or imaging agent, including radionuclides. Some radionuclides possess properties appropriate for simultaneous imaging and therapy of a disease and are therefore called theranostic. The diversity in core materials and surface modification, as well as radiolabeling strategies, offers multiples possibilities for preparing polymeric nanoparticles using radionuclides. The present review describes different strategies in the preparation of such nanoparticles and their applications in nuclear nanomedicine.
What is effective transfinite recursion in reverse mathematics?
Authors: Freund Anton
Published: January 2021

In the context of reverse mathematics, effective transfinite recursion refers to a principle that allows us to construct sequences of sets by recursion along arbitrary well orders, provided that each set is ‐definable relative to the previous stages of the recursion. It is known that this principle is provable in . In the present note, we argue that a common formulation of effective transfinite recursion is too restrictive. We then propose a more liberal formulation, which appears very natural and is still provable in .
Characteristics of DNA polymerase I from an extreme thermophile, Thermus scotoductus strain K1
Authors: Saghatelyan Ani , Panosyan Hovik , Trchounian Armen , Birkeland Nils‐Kåre
Published: January 2021

Several native and engineered heat‐stable DNA polymerases from a variety of sources are used as powerful tools in different molecular techniques, including polymerase chain reaction, medical diagnostics, DNA sequencing, biological diversity assessments, and in vitro mutagenesis. The DNA polymerase from the extreme thermophile, Thermus scotoductus strain K1, (TsK1) was expressed in Escherichia coli, purified, and characterized. This enzyme belongs to a distinct phylogenetic clade, different from the commonly used DNA polymerase I enzymes, including those from Thermus aquaticus and Thermus thermophilus. The enzyme demonstrated an optimal temperature and pH value of 72–74°C and 9.0, respectively, and could efficiently amplify 2.5 kb DNA products. TsK1 DNA polymerase did not require additional K+ ions but it did need Mg2+ at 3–5 mM for optimal activity. It was stable for at least 1 h at 80°C, and its half‐life at 88 and 95°C was 30 and 15 min, respectively. Analysis of the mutation frequency in the amplified products demonstrated that the base insertion fidelity for this enzyme was significantly better than that of Taq DNA polymerase. These results suggest that TsK1 DNA polymerase could be useful in various molecular applications, including high‐temperature DNA polymerization.
Western Diet Aggravated Carbon Tetrachloride‐Induced Chronic Liver Injury by Disturbing Gut Microbiota and Bile Acid Metabolism
Authors: Yang Liya , Li Yating , Wang Shuting , Bian Xiaoyuan , Jiang Xianwan , Wu Jingjing , Wang Kaicen , Wang Qiangqiang , Xia Jiafeng , Jiang Shiman , Zhuge Aoxiang , Yuan Yin , Li Shenjie , Li Lanjuan
Published: January 2021

Scope

The high‐fat, high‐sucrose, and low‐fiber Western diet (WD) is popular in many countries and affects the onset and progression of many diseases. This study is aimed to explore the influence of the WD on chronic liver disease (CLD) and its possible mechanism.

Methods and results

C57BL/6 mice are given a control diet (CD) or WD and CLD is induced by intraperitoneally injecting carbon tetrachloride (CCL4) twice a week for 8 weeks. The WD aggravated CCL4‐induced chronic liver injury, as evidenced by increased serum transaminase levels, worsened hepatic inflammatory response, and fibrosis. Gut microbiota is disturbed in mice treated with CCL4+WD (WC group), manifested as the accumulation of Fusobacteria, Streptococcaceae, Streptococcus, Fusobacterium, and Prevotella and the depletion of Firmicutes, Lachnospiraceae, and Roseburia. Additionally, increased hepatic taurocholic acid in the WC group activated sphingosine‐1‐phosphate receptor 2, which is positively correlated with hepatic fibrosis and inflammation parameters. Mice in the WC group have higher fecal primary bile acid (BA) levels and lower fecal secondary/primary BA ratios. Serum FGF15 levels are also elevated in the WC group, which is positively correlated with hepatic inflammation.

Conclusion

WD accelerates the progression of CLD which is associated with changes in the gut microbiota and BA metabolism.
Single cell temperature probed by Eu+3 doped TiO2 nanoparticles luminescence
Authors: Garvas Maja , Acosta Selene , Urbančič Iztok , Koklič Tilen , Štrancar Janez , Nunes Luiz A. O. , Guttmann Peter , Umek Polona , Bittencourt Carla
Published: January 2021

Temperature is a critical parameter in biology, affecting the speed of reactions that occur in living systems. Nevertheless, measuring temperature with subcellular resolution (micrometric scale) and reliability remains a challenge to overcome. In this perspective, luminescence nanothermometry is a non‐contact technique which aims to measure temperature with a sub‐micrometric spatial resolution through the use of nanomaterials whose luminescence is affected solely by changes in temperature. Here, TiO2 nanoparticles doped with Eu+3 ions (Eu+3‐TiO2) are used for sensing temperature differences within single living cells. XRD, XPS, SEM, TEM and NEXAFS analysis allow the determination of the physicochemical characteristics of the Eu+3‐TiO2 nanoparticles and, the variation of the luminescence intensity of the Eu+3‐TiO2 nanoparticles with their temperature is investigated. The successful internalization of Eu+3‐TiO2 nanoparticles in different types of cells is observed. The luminescence of nanoparticles internalized in L929 fibroblast cells is measured when the system is heated in a biological relevant temperature range. Making use of an appropriate calibration curve the temperature variation inside the cells is determined with sensitivity of 0.5 K per 1% of luminosity change when heated.
Toward high thermal conductive aramid nanofiber papers: Incorporating hexagonal boron nitride bridged by silver nanoparticles
Authors: Zhuo Longhai , Chen Shanshan , Xie Fan , Qin Panliang , Lu Zhaoqing
Published: January 2021

In this work, a novel thermal conductive and electrical insulation h‐BN@AgNPs/ANFs composite paper was fabricated by vacuum‐assisted filtration approach. Specifically, hexagonal boron nitride (h‐BN) was incorporated via polydopamine pretreatment and subsequent decoration by silver nanoparticles, which served as bridges to link neighboring h‐BN sheets. The results revealed that the thermal conductivity of as‐prepared composite paper increased to 1.032 W/m K with 40 wt% filler loading, about 464% higher than the pure ANFs paper, which was attributed to the efficient thermal conductive networks within the paper and strong interfacial combination through hydrogen bonding. Besides, the as‐prepared composite paper exhibited excellent mechanical property with the maximum tensile strength over 90 MPa, and good electrical insulation performance. More importantly, this work provided a promising strategy to achieve high thermal conductivity ANFs based composite paper by constructing efficient thermal conductive networks, which had potential to be used in the field of electronic packaging.
Mass spectrometric investigations of caloric restriction mimetics
Authors: Bibyk Michael J. , Campbell Melanie J. , Hummon Amanda B.
Published: January 2021

Caloric restriction (CR) is an innovative therapy used in tumor tissue and tumor model studies to promote cell death and decrease cell viability. Caloric restriction mimetics (CRMs) are a class of drugs that induce CR and starvation conditions within a cell. When used simultaneously with other chemotherapy agents, the effects are synergistic and effective at promoting tumor cell death. In this review, we discuss CRMs and their potential as cancer therapeutics. Firstly, we establish an overview of CR and its impacts on healthy and tumor cells. CR and CRM drugs have shown to decrease age‐related diseases and can act as an anti‐cancer agent. As it can be challenging for an individual to diligently stick to a diet that would induce CR, CRMs are even more desirable. Then, we discuss the drug class by highlighting three CRMs: resveratrol, (‐)‐hydroxycitric acid, and rapamycin. These CRMs are commonly known for their dietary effects, but the underlying mechanisms that drive cellular metabolic and proteomic changes show promise as a cancer therapeutic. Lastly, we highlight the use of mass spectrometry and proteomic techniques on experiments utilizing CRM drugs to understand the cellular pathways impacted by this drug class, leading to a better understanding of the anti‐cancer properties and potentials of CRM.
Tuning the Oxygen Balance of Energetic Composites: Crystallization of ADN/Secondary Explosives Mixtures by Spray Flash Evaporation
Authors: Lobry Emeline , Berthe Jean‐Edouard , Hübner Jakob , Schnell Fabien , Spitzer Denis
Published: January 2021

New energetic composites with enhanced reactive performances while allowing the safe handling according to their sensitivity thresholds are presented. This paper combines different approaches: the intimate contact between the compounds, the particle size reduction and the processing of composite materials to maintain the oxygen balance close to zero. The Spray Flash Evaporation process enables the fast crystallization at the submicron scale by combining an oxidizer, ammonium dinitramide ADN and two secondary explosives (RDX and HMX). The morphologies of the particles were analyzed and compared with slow evaporation tests. An intimate mixing between the two components (crystallized by SFE) is highlighted and core‐shell structure is evidenced by advanced techniques such as 2D and 3D confocal Raman microscopy. The composites offer outstanding energetic performances compared to sole explosives. It paves the way to new energetic compositions based on current materials.
Effects of Micro‐Encapsulation Treatment on the Thermal Safety of High Energy Emulsion Explosives with Boron Powders
Authors: Yao Yu‐le , Cheng Yang‐fan , Liu Rong , Hu Fang‐fang , Zhang Qi‐wei , Xia Yu , Chen Yuan
Published: January 2021

The effects of micro‐encapsulation technology on the thermal safety of boron‐containing emulsion explosives were experimentally studied. Micro‐structures of additives, demulsification states and thermal characteristics of boron‐containing emulsion explosives were characterized by the laser particle size analyzer, scanning electron microscope and thermal analysis equipment, respectively. The storage experiments showed that emulsion explosives with boron powders would be demulsified in a short time, while those with micro‐encapsulated boron powders were not demulsified and had good surface morphologies and structures. The results of TG‐DSC experiments showed that the thermal stability of emulsion explosive with polymethyl methacrylate (PMMA) micro‐encapsulated boron powders was higher than that of other samples with boron powders, and the order of thermal stability was as follows: PMMA/Boron sensitized emulsion explosive > Paraffin/Boron‐Glass microspheres (GMs) sensitized emulsion explosive > Boron‐GMs sensitized emulsion explosive. The experimental data of accelerating rate calorimeter (ARC) tests showed that the addition of boron powders would significantly increase the risk of thermal explosion of emulsion explosives under the adiabatic condition, and PMMA micro‐encapsulation for boron powders could largely reduce the thermal explosion risk of boron‐containing emulsion explosives compared with paraffin coating. The coating effect of micro‐encapsulation technology was much better than that of traditional paraffin coating method, and the compatibility and thermal safety of boron‐containing emulsion explosives were also improved.
Spatio‐temporal distribution of sexual calling behaviour in domesticated, sterile and wild Queensland fruit fly males under field cage conditions
Authors: Inskeep Jess R , Taylor Phillip W , Mainali Bishwo , Rempoulakis Polychronis , Weldon Christopher W
Published: January 2021

BACKGROUND

The sterile insect technique (SIT) is used in Australia to contain and eradicate outbreaks of Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) in fruit‐fly‐free regions, and to manage populations in some endemic regions. To assess the likely impact of SIT on wild B. tryoni populations it is important to assess the colocation and synchrony of male calling between sterile and wild flies. We observed the location and timing of calling behaviours of marked mass‐reared (fertile and sterile) and wild B. tryoni males in walk‐in field cages.

RESULTS

We found that wild males called further from the canopy centre than mass‐reared (fertile or sterile) males. Mass‐reared (fertile or sterile) males called earlier in the evening than wild males and, consequently, mass‐reared males called when temperature and light intensity were higher than when wild males called.

CONCLUSION

Male calling is a prerequisite to mating among dacine fruit flies. Therefore, our observations of spatio‐temporal divergence in male calling behaviour may lead to assortative mating between mass‐reared and wild B. tryoni in SIT applications. The importance of these spatio‐temporal differences warrants further inquiry, with particular focus on how environmental conditions modify calling behaviour and avenues to ameliorate differences between sterile and wild flies. © 2021 Society of Chemical Industry
Microfluidic Evolution‐On‐A‐Chip Reveals New Mutations that Cause Antibiotic Resistance
Authors: Zoheir Ahmed E. , Späth Georg P. , Niemeyer Christof M. , Rabe Kersten S.
Published: January 2021

Microfluidic devices can mimic naturally occurring microenvironments and create microbial population heterogeneities ranging from planktonic cells to biofilm states. The exposure of such populations to spatially organized stress gradients can promote their adaptation into complex phenotypes, which are otherwise difficult to achieve with conventional experimental setups. Here a microfluidic chip that employs precise chemical gradients in consecutive microcompartments to perform microbial adaptive laboratory evolution (ALE), a key tool to study evolution in fundamental and applied contexts is described. In the chip developed here, microbial cells can be exposed to a defined profile of stressors such as antibiotics. By modulating this profile, stress adaptation in the chip through resistance or persistence can be specifically controlled. Importantly, chip‐based ALE leads to the discovery of previously unknown mutations in Escherichia coli that confer resistance to nalidixic acid. The microfluidic device presented here can enhance the occurrence of mutations employing defined micro‐environmental conditions to generate data to better understand the parameters that influence the mechanisms of antibiotic resistance.
A Durable, Flexible, Large‐Area, Flame‐Retardant, Early Fire Warning Sensor with Built‐In Patterned Electrodes
Authors: Khan Fawad , Wang Shanchi , Ma Zhewen , Ahmed Adnan , Song Pingan , Xu Zhiguang , Liu Riping , Chi Huanjie , Gu Jiayi , Tang Long‐Cheng , Zhao Yan
Published: January 2021

Fire has been giving rise to enormous loss of life and property worldwide annually. Early fire warning represents an active and effective means to avoid potential fire hazards before huge losses occur. Despite encouraging advances in early fire warning systems, to date there remains an urgent lack of the design of a durable, flexible, and universal early fire warning sensor for large‐area practical applications. Herein, facile fabrication of a durable, flexible, large‐scale early fire‐warning sensor is demonstrated through constructing a hierarchical flame retardant nanocoating, composed of graphene oxide, poly(dimethylaminoethyl methacrylate), and hexagonal boron nitride, on cotton fabric in combination with the parallelly patterned conductive ink as built‐in electrodes. As‐designed large‐scale sensor (>33 cm and extendable) exhibits a short alarming time of <3 s in response to external abnormal high temperature, heat, or fire. In addition to high washability, flexibility, resistance to abrasion and wear, this hierarchical nanocoating can self‐extinguish, thus enabling the sensor to continue warning during fire. This work offers an inventive concept to develop a universal and large‐scale very early fire‐monitoring platform, which opens up new opportunities for their practical applications in effectively reducing fire‐related casualties and economic losses.
Nonhalogenated Solvent‐Processed Thick‐Film Ternary Nonfullerene Organic Solar Cells with Power Conversion Efficiency >13% Enabled by a New Wide‐Bandgap Polymer
Authors: Gokulnath Thavamani , Reddy Saripally Sudhaker , Park Ho-Yeol , Kim Junyoung , Kim Jehan , Song Myungkwan , Yoon Jinhwan , Jin Sung-Ho
Published: January 2021

Although several donor polymers have been synthesized for use in nonfullerene organic solar cells (NFOSCs), the number of efficient π‐conjugated donor polymers compatible with nonhalogenated solvent‐processed thick active layer NFOSCs is limited. Two wide‐bandgap π‐conjugated donor polymers functionalized with a siloxane side chain, P1 (chlorine‐free) and P2 (chlorinated), are designed and synthesized. The siloxane‐functionalized side chains and/or Cl π‐conjugated donor polymers increase the absorption coefficients, reduce the energy losses, increase the charge‐carrier mobility, and suppress the bimolecular recombination, which are beneficial to achieve high‐performance thick‐film ternary NFOSCs. Toluene‐processed devices based on P2:IT‐4F:BTP‐4Cl, and P2:IT‐4F:BTP‐4F exhibit high power conversion efficiencies (PCEs) of 13.25% and 11.02% with fill factors (FFs) of 70.03% and 71.60%, respectively. A P2:IT‐4F binary NFOSC exhibits a PCE of 10.38% with an FF of 69.78%, lower than that of the ternary NFOSC. The ternary device PCE of 13.25% is achieved using a 300 nm‐thick active layer, indicating that the siloxane‐functionalized side‐chain π‐conjugated polymer easily controls the bulk heterojunction blend film thickness of the NFOSC. The findings may potentially aid the development of nonhalogenated solvent‐processed thick‐film ternary NFOSCs that can satisfy future production requirements.
The Role of Dynorphin and the Kappa Opioid Receptor in Schizophrenia and Major Depressive Disorder: A Translational Approach
Authors: Clark Samuel David
Published: January 2021

The kappa opioid receptor (KOR) and its endogenous ligands dynorphins (DYN) have been implicated in the development or symptomatology of a variety of neuropsychiatric disorders. This review covers a brief history of the development of KOR agonists and antagonists, their effects in healthy volunteers, and the potential role of DYN/KOR dysfunction in schizophrenia and major depressive disorder from a translational perspective. The potential role of DYN/KOR dysfunction in schizophrenia is based on several lines of evidence. Selective KOR agonists induce affective states in healthy volunteers with similarities to the symptoms of schizophrenia. Studies have shown increased DYN in patients with schizophrenia, although the data have been mixed. Finally, meta-analytic data have shown that opioid antagonists are associated with reductions in the symptoms of schizophrenia. The potential role of DYN/KOR dysfunction in major depressive disorder is also based on a combination of preclinical and clinical data. Selective KOR agonists have shown pro-depressive effects in human volunteers, while selective KOR antagonists have shown robust efficacy in several preclinical models of antidepressant activity. Small studies have shown that nonselective KOR antagonists may have efficacy in treatment-resistant depression. Additionally, recent clinical data have shown that the KOR may be an effective target for treating anhedonia, a finding relevant to both schizophrenia and depression. Finally, recommendations are provided for translating preclinical models for schizophrenia and major depressive disorder into the clinic.
Embedded Security-Critical Device Resource Isolation
Authors: Wang Xuguo , Kan Shengzhe , Xu Yeli
Published: January 2021

At present, embedded devices have been widely used in people’s daily life, which makes more convenience for the public. However, embedded devices still have security problems, such as automatic driving accidents that may cause casualties. In the field of embedded device security, there are many studies, for instance, OPENTEE for ARM handheld devices, providing a secure execution environment for payment devices, and SGX for Intel desk top devices, for security-critical applications, such as bank teller systems, build a safe operating environment. But it is a lack of correlation between these new and existing technologies. In our opinion, through the combination of mature technology accumulation and embedded devices, the antivirus industry can create a more secure user environment. In this paper, we propose a source isolation method to make the resources used by key processes exclusive. This method uses antivirus software and builds a more comprehensive embedded security system in critical security applications. The experimental results show that the proposed method is effective and safe.
Practical DDoS Attack Group Discovery and Tracking with Complex Graph-Based Network
Authors: Rao Yu , Liu Weixin , Zhu Tian , Yan Hanbin , Zhou Hao , Bai Jinghua
Published: January 2021

In recent years, a large number of users continuously suffer from DDoS attacks. DDoS attack volume is on the rise and the scale of botnets is also getting larger. Many security organizations began to use data-driven approaches to investigate gangs and groups beneath DDoS attack behaviors, trying to unveil the facts and intentions of DDoS gangs. In this paper, DDoSAGD - a DDoS Attack Group Discovery framework is proposed to help gang recognition and situation awareness. A heterogeneous graph is constructed from botnet control message and relative threat intelligence data, and a meta path-based similarity measurement is set up to calculate relevance between C2 servers. Then two graph mining measures are combined to build up our hierarchical attack group discovery workflow, which can output attack groups with both behavior-based similarity and evidence-based relevance. Finally, the experimental results demonstrate that the designed models are promising in terms of recognition of attack groups, and evolution process of different attack groups is also illustrated.
Di-lepton production from a single photon in strong magnetic fields: vacuum dichroism
Authors: Hattori Koichi , Taya Hidetoshi , Yoshida Shinsuke
Published: January 2021

Abstract

We study di-lepton production from a single photon in the presence of a strong constant magnetic field. By the use of the Ritus-basis formalism, we analytically evaluate the photon-to-di-lepton conversion vertex with fully taking into account the non-perturbative interactions between the produced fermions and the strong magnetic field. We show that the di-lepton spectrum becomes anisotropic with respect to the magnetic-field direction and depends on the photon polarization as a manifestation of the vacuum dichroism in a strong magnetic field. According to the energy conservation in the presence of the Landau quantization, not only the transverse momentum of the produced fermions but also the longitudinal momentum is discretized, and the di-lepton spectrum exhibits spike structures as functions of the incident photon energy and the magnetic field strength. We also show that the di-lepton production is strictly prohibited for massless fermions in the lowest Landau levels as an analogue of the so-called helicity suppression.
The special Galileon as Goldstone of diffeomorphisms
Authors: Roest Diederik
Published: January 2021

Abstract

The special Galileon stands out amongst scalar field theories due to its soft limits, non-linear symmetries and scattering amplitudes. This prompts the question what the origin of its underlying symmetry is. We show that it is intimately connected to general relativity: the special Galileon is the Goldstone mode of the affine group, consisting of linear coordinate transformations, analogous to the dilaton for conformal symmetries. We construct the corresponding metric, and discuss various relations to gravity, Yang-Mills and the non-linear sigma-model.
Chirurgie bei Patienten mit Leberzirrhose
Authors: Pantea Roxana , Meister Phil , Neuhaus Jan P. , Nowak Knut , Paul Andreas , Saner Fuat H.
Published: January 2021

Hintergrund und Ziel der Arbeit

Patienten mit einer Leberzirrhose, die eine operative Behandlung benötigen, weisen eine hohe Krankenhausmortalität auf. Die vorliegende Studie untersucht die postoperative Morbidität sowie Krankenhausmortalität nach stattgehabter Operation von Patienten mit einer Leberzirrhose.

Material und Methode

Retrospektiv wurden im Zeitraum von 01/2010 bis 12/2017 321 Patienten mit einer Leberzirrhose in unserer Klinik operativ behandelt. Erfasst wurden leberspezifische Scoringsysteme wie MELD(Model of End Stage Liver Disease)- und Child-Pugh-Score (CPS), die Krankenhausletalität und die postoperative Morbidität wurden mittels der Dindo-Clavien-Klassifikation erhoben.

Ergebnisse

Von den 321 Patienten (68 % männlich) wurden 21,2 % als Notfall versorgt. Die Letalität der Notfallpatienten war mit 60 % signifikant höher als die der elektiv operierten Patienten (12 %, p < 0,0001). Komplexe Eingriffe zeigen insgesamt eine Letalität von 41 %, kleinere Eingriffe immer noch 20,5 % (p = 0,0001). Die postoperativen Komplikationsrate und Mortalität zeigten sich nach CPS signifikant unterschiedlich bei 11,8 % bzw. 6,3 % in der CPS-A-Kategorie im Vergleich zu 84 % bzw. 73 % in der CPS-C-Kategorie (p = 0,001). Statistisch steigt die Krankenhausletalität um etwa 20 % mit jedem MELD-Anstieg um einen Punkt (OR 1,23, p = 0,0001). Am schwerwiegendsten ist das Vorliegen einer hepatischen Dekompensation.

Diskussion

Operative Eingriffe von Patienten mit Leberzirrhose sind mit einer hohen Komplikationsrate und Krankenhausletalität verbunden. CPS und MELD können bei der objektiven Risikoeinschätzung helfen, während auch die klinische Untersuchung auf Zeichen einer hepatischen Dekompensation von Bedeutung ist. Natrium, Kreatinin und andere Laborwerte können diese Einschätzung ergänzen.
Is body-contouring surgery a right for massive weight loss patients? A survey through the European Union National Health Systems
Authors: Lo Torto Federico , Frattaroli Jacopo M. , Kaciulyte Juste , Redi Ugo , Marcasciano Marco , Casella Donato , Ribuffo Diego
Published: January 2021

Background

Obesity is pandemic nowadays, and hanging skin with consequent functional and psychological impairments is a common price to pay for massive weight loss. Plastic surgery in postbariatric patients represents a fundamental step to regain possession of a positive self-image. The authors aimed to investigate how EU countries’ National Health System (NHS) behaves regarding reimbursements for body-contouring procedures after massive weight loss.

Methods

A 1-item survey was sent to contacts found on the NHS official Web sites of 27 EU countries. The question focused on postbariatric surgery practice and investigated the accessibility criteria for NHS coverage concerning body-contouring procedures after massive weight loss.

Results

Responses were collected between January 2020 and February 2020. Response rate was 65%, and access criteria to NHS coverage for postbariatric surgery presented great variation across EU countries. Only one country presented an NHS with no coverage for postbariatric surgeries.

Conclusions

Despite the conspicuous variability found among the EU NHS, none of them admit reimbursement in cases of merely aesthetic procedures: postbariatric patients need to display functional or health impairments due to the extensive weight loss. The results of the current study describe a complex situation among EU countries, but a common lead towards postbariatric patients’ care shows off. The ultimate goal of bariatric patient’s healing should be full restoration of physical and psychological well-being. NHS of EU countries are facing this increasing request in various ways, and more studies should be performed in order to understand which is the best approach.

Level of evidence: Not ratable.
Ultrasound features help identify patients who can undergo noninvasive management for suspected retained products of conception: a single institutional experience
Authors: Vyas Shrilakshmi , Choi Hailey H. , Whetstone Sara , Jha Priyanka , Poder Liina , Shum Dorothy J.
Published: January 2021

Objectives

To evaluate ultrasound (US) features associated with successful noninvasive management for suspected retained products of conception (RPOC).

Methods

In this IRB-approved retrospective study, the radiology report database was queried for pelvic US with keywords of postpartum hemorrhage (PPH) and/or RPOC over a 2-year period. Follow-up exams, US exams without clinical follow-up, suboptimal image quality, and > 1 year from delivery or pregnancy termination were excluded. Charts were reviewed for clinical presentation and management. Two radiologists reviewed images for endometrial thickness, endometrial echogenicity, endometrial vascularity, and enhanced myometrial vascularity (EMV), as well as inner myometrial peak systolic velocity (PSV) and resistive index (RI) where available. Features were assessed for associations with management approach, and test characteristics were calculated.

Results

Initial query yielded 196 exams, and 48 were excluded. A total of 148 patients were included. Mean age was 34.2 years (21–47), and mean time from delivery or pregnancy termination was 40.4 days (0–223). 81 (55%) underwent noninvasive management: 72 (48%) expectant and 9 (6%) medical. 67 (45%) underwent invasive management: 60 (41%) surgical and 7 (5%) uterine artery embolization. There was substantial inter-reader agreement for assessment of EMV (K = 0.78) and endometrial vascularity (K = 0.72). Thin endometrial stripe, avascular endometrium, and absence of EMV were associated with successful noninvasive management (p < 0.05). Thin endometrium (< 10 mm) had specificity (90%), PPV (88%), and likelihood ratio (5.91) in predicting successful noninvasive management.

Conclusion

Endometrial thickness < 10 mm, avascular endometrium, and absence of EMV are the sonographic features associated with successful noninvasive management for PPH or suspected RPOC.
Aplication of Soil Productivity Index after Eight Years of Soil Reclamation with Sewage Sludge Amendments
Authors: Halecki Wiktor , Klatka Sławomir
Published: January 2021

Remediation methods are gaining acceptance as effective and inexpensive techniques used in the reclamation of degraded areas. The reclamation of post-mining sites has become important for the conservation of soil and vegetation. An assessment of potential productivity of plants based on the depth of their root zone is crucial for the validation of properties of post-mining soils. Our aim was to present soil productivity parameters that would facilitate assessment of various post-mining objects. Soil productivity index (SPI) was calculated to assess soil quality, mainly in areas degraded by hard coal mining. It is based on an equation determining the relationship between the productivity index and the physical, chemical, and hydrological properties of soil. Our study demonstrated the positive effects of enriched sewage sludge with amendments on newly formed soil and plants. The soil productivity index was 0.81, demonstrating the suitable condition of the initial soil resulting from reclamation. This parameter might be important for post-industrial reclamation, such as wasteland intended to be transformed into woodland. Considering the composition of sewage sludge amendments, it can be successfully used as an effective method of restoring and improving both the physical and chemical properties of soils, thus effectively replacing mineral fertilisers. The use of sewage sludge in soil reclamation will be an important method of managing this waste material in post-mining areas.
Five-Card AND Computations in Committed Format Using Only Uniform Cyclic Shuffles
Authors: Abe Yuta , Hayashi Yu-ichi , Mizuki Takaaki , Sone Hideaki
Published: January 2021

In card-based cryptography, designing AND protocols in committed format is a major research topic. The state-of-the-art AND protocol proposed by Koch, Walzer, and Härtel in ASIACRYPT 2015 uses only four cards, which is the minimum permissible number. The minimality of their protocol relies on somewhat
complicated shuffles having non-uniform probabilities of possible outcomes. Restricting the allowed shuffles to uniform closed ones entails that, to the best of our knowledge, six cards are sufficient: the six-card AND protocol proposed by Mizuki and Sone in 2009 utilizes the random bisection cut, which is a uniform and cyclic (and hence, closed) shuffle. Thus, a question has arisen: “Can we improve upon this six-card protocol using only uniform closed shuffles?” In other words, the existence or otherwise of a five-card AND protocol in committed format using only uniform closed shuffles has been one of the most important open questions in this field. In this paper, we answer the question affirmatively by designing five-card committed-format AND protocols using only uniform cyclic shuffles. The shuffles that our protocols use are the random cut and random bisection cut, both of which are uniform cyclic shuffles and can be easily implemented by humans.
Scope for predicting seasonal variation of the SPCZ with ACCESS-S1
Authors: Beischer Thomas A. , Gregory Paul , Dayal Kavina , Brown Josephine R. , Charles Andrew N. , Wang William X. D. , Brown Jaclyn N.
Published: January 2021

Regional seasonal forecasting requires accurate simulation of the variability of local climate drivers. The South Pacific Convergence Zone (SPCZ) is a large region of low-level convergence, clouds and precipitation in the South Pacific, whose effects extend as far as northeast Australia (NEA). The location of the SPCZ is modulated by the El Niño-Southern Oscillation (ENSO) which causes rainfall variability in the region. Correctly simulating the ENSO-SPCZ teleconnection and its interplay with local conditions is essential for improving seasonal rainfall forecasts. Here we analyse the ability of the ACCESS-S1 seasonal forecast system to predict the SPCZ’s relationship with ENSO including its latitudinal shifts, zonal slope and rainfall magnitude between 1990 and 2012 for the December–January–February (DJF) season. We found improvements in ACCESS-S1’s SPCZ prediction capability compared to its predecessor (POAMA), although prediction of the slope is still limited. The inability of ACCESS-S1 to replicate seasons with a strong anti-zonal SPCZ slope is attributed to its atmospheric model. This has implications for accurate seasonal rainfall forecasts for NEA and South Pacific Islands. Future challenges in seasonal prediction facing regional communities and developers of coupled ocean–atmosphere forecast models are discussed.
No implant, no solution, lost cases to surgery: orthopedic trauma triage for surgery in an NGO hospital in Sierra Leone
Authors: Wichlas F. , Hofmann V. , Moursy M. , Strada G. , Deininger C.
Published: January 2021

Introduction

In low-income countries (LIC), international surgeons face the fact that there are patients they cannot treat. The goal of this study was to identify and analyze patients lost to treatment.

Material and methods

We analyzed retrospectively the data of 282 trauma victims from a non-governmental organizational (NGO) hospital in Sierra Leone, Africa. During a 3-month period (10.10.2015–08.01.2016), these patients had 367 injuries and underwent 263 orthopedic surgeries. Despite a clear indication, some patients did not receive surgical treatment. We identified these injuries and the reason why they could not be operated. The anatomic region of the injury was evaluated and if they had a bone or soft tissue defect or were infected.

Results

We identified 95 (25.89%) injuries in 70 patients (47 males; 23 females) that were not be operated. The reasons were lack of specific implants (no implant group; N = 33), no treatment strategy for the injury (no solution group; N = 29), and patients that were lost (lost patient group; N = 33), almost equally distributed by 1/3. In the no implant group were mainly closed fractures and fractures of the pelvis and the proximal femur. The implants needed were locking plates (N = 19), proximal femoral nails (N = 8), and implants for pelvic surgery (N = 6). In the no solution group were nearly all bone (P < 0.0000), soft tissue defects (P < 0.00001) and infections (P = 0.00003) compared to the rest and more open fractures (P < 0.00001). In the lost patients group, most fractures were closed (24 out of 33, P = 0.033). These fractures were mostly not urgent and were postponed repeatedly.

Conclusion

One quarter of the patients did not receive the surgical treatment needed. Besides acquisition of implants, surgical skills and expertise could be a solution for this issue. Nevertheless, these skills must be passed to local surgeons.