bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insight into the development of deformation texture in face-centered cubic material
Authors: shankar Gyan , Kumar Deepak , Suwas Satyam
Published: April 2021

Despite a tremendous amount of research to understand the evolution of microstructural and texture changes during deformation, there is still a need for further deep insight into it. The most used deformation process underuse in industries is the rolling of material. Stacking fault energy is the most critical material property, which governs the deformation behavior. In the present study, the microstructure and texture changes of a high SFE material (pure nickel) during cold rolling was investigated. The objective is to find criteria for the change of orientation of a particular grain as rolling proceed. Pseudo-in-situ rolling was done through which the shape, orientations, and neighbors of each grain could be tracked as a function of rolling reductions. It was found that orientations of some grains remain stable after a large reduction and do not develop sub-grains within it, whereas orientations of some grains change drastically at a very low deformation level along with the evolution of a large number of sub-grains.
Change in intragranular misorientation during stress relaxation behavior in Cu-Ni-Si alloy subjected to continuous cyclic bending
Authors: Fukutomi Tatsuya , Komei Narumi , Takayama Yoshimasa , Watanabe Hideo
Published: April 2021

Stress relaxation resistance is often required in application of electrical parts for copper and its alloys. The stress relaxation behavior should be influenced by stored strain through manufacturing process. In the present study, a Cu-Ni-Si alloy solution-treated sheet was subjected to continuous cyclic bending (CCB), which was proposed as a useful straining technique to impose higher strain on the surface and lower strain in the center layer of metal sheets. Samples were analyzed by scanning electron microscope / electron back scatter diffraction (SEM/EBSD) technique to investigate stored strain and stress relaxation process. CCB raised up the strength of Cu-Ni-Si alloy sheets at room temperature. The stress relaxation ratios of the CCBent sheets increased with an increment of test exposure time at 423K. The stress relaxation process was accompanied with change in intragranular misorientation of the samples. Change in intragranular misorientation through the stress relaxation test was understood as a result of release of residual and applied stresses with consumption of stored strain.
The influence of the crystallographic texture and phase composition of Ti-Nb-Zr alloys with shape memory and superelasticity on their functional properties
Authors: Zaripova M M , Isaenkova M G , Fesenko V A , Osintsev A V
Published: April 2021

Currently, Ti-Zr-Nb-based biocompatible alloys are considered as prospective for medical applications. In this work, the mechanisms of the formation of the crystallographic texture of five alloys Ti-(17-19)Zr-(14-16)Nb (at.%) have been compared. The presence of martensitic transformations during the rolling process determines the features of the formed texture. At the initial stage of deformation (ε = 50%), the texture {112}<011> is formed in all five alloys. With an increase of the degree of deformation to 92%, the texture dissipates somewhat, which is due to an increase in the fraction of the martensitic phase in the foils. Recrystallization of rolled foils (ε = 92%) at 650°C leads to an exacerbation of the texture component close to {100}<011>, the blurring of which varies in different alloys. Cyclic tensile tests along three directions: the rolling direction (RD), the transverse direction, at an angle of 45° to the RD showed the presence of anisotropy in the samples. It was shown, that the effect of superelasticity is orientation-and structure-depending, and the anisotropy of mechanical properties.
Microstructural study of duplex stainless steel after turning using EBSD and X-ray diffraction analysis
Authors: Capek J , Minarik P , Neslusan M , Trojan K , Ganev N
Published: April 2021

The aim of this research is a microstructural study of duplex stainless steel after turning. The electron backscatter diffraction and X-ray diffraction analyses were applied to analyse the surface and subsurface regions. The gradients of Kernel Average Misorientation as a function of flank wear were investigated. It was found that the concentration of deformation depends on the subsurface depth, individual phases, and flank wear. The similar behaviour but with a different inclination of grain size (determined by electron backscatter diffraction) and crystallite size (determined by X-ray diffraction) depending on flank wear was observed.
Dependence of Thermal Expansion of Zr-Based Products on their Crystallographic Texture
Authors: Stolbov Sergey , Isaenkova Margarita , Perlovich Yuriy , Tenishev Andrey , Krymskaya Olga , Mikhalchik Vladimir , Klyukova Kristina
Published: April 2021

The accident at Fukushima Daiichi in 2011 highlighted the increased interest in predicting the materials properties under extreme conditions. In this work, it is considered the behaviour of cubic samples cut from the wall of channel tubes made of Zr-2.5% Nb alloy during heating and cooling in the temperature range of 20-1200 °C. The anisotropy of changes in the dimensions of cubic samples in different structural states has been studied. Thermal tests were carried out in three mutually perpendicular directions: radial, tangential and axial. The structural state of tubes was estimated from the features of their crystallographic texture. The significant anisotropy of the size change is observed in the Zr-2.5%Nb alloy product with an unstable crystallographic texture of deformation due to the α↔β-phase transformation inhomogeneity. In the case of complete recrystallization and orientation of the <1120> axes along the tube axis, the anisotropy of the dimensions change is minimal, due to uniform nuclei formation of new phases in different orientations.
Evaluation of active slip systems during deformation by Insitu XRD in precipitation hardening Mg Alloys
Authors: Yoshikawa Tomoki , Hirata Masahiro , Okai Daisuke , Adachi Hiroki
Published: April 2021

The effect of precipitates on active slip systems was evaluated in precipitation-hardening Mg Alloys. In a Mg-5% Y-4% Nd (WE54) alloy, the radius and thickness of disc-shaped β“ precipitates were measured by small angle X-ray scattering measurements. The active slip system was then measured during tensile deformation by in situ X-ray diffraction measurements. The average radius and thickness of the precipitates increased with aging time, and approached 19.4 and 3.85 nm, respectively, at a peak aging time of 2160 ks. The uniform elongations of the as-quenched, 1.08 ks aged and 36Q ks aged alloys were determined to be approximately 9.7, 5.5 and 2.3%, respectively. Various slip systems were active in the as-quenched alloy. On the other hand, in the alloy aged for 360 ks, non-basal  slip was found to be dominant.
Influence of parameters of gas-dynamic spraying on substructure of “brass” coating type
Authors: Arkhipov V E , Moskvitin G V , Pugachev M S
Published: April 2021

Investigations of the influence of the parameters of applying a gas-dynamic coating of copper-zinc on its substructure have been carried out. It was found that the coating has a gradient hardness and different phase composition. Increasing the temperature of spraying and coating with 3mm overlap leads to a decrease in the size of the substructures. The structure of the coating, which is gradient in phase composition and hardness, should provide high tribotechnical characteristics of the friction surface in contact.
A method of technological identification of metal-cutting machine
Authors: Sakharov A V
Published: April 2021

The paper demonstrates the disadvantages of formulations of the purposes of metal-cutting machine. The authors suggest to use the modules of the parts surfaces as the subject of machine tool production. The paper presents the method of determination the process capabilities of the machine tool and identifies the process capabilities of a milling machine.
Influence of additional vibration loads on the processes of deformation and fracture of composite tubular samples
Authors: Wildemann Valerii , Staroverov Oleg
Published: April 2021

The work is devoted to an experimental study of the influence of additional vibration torsional effects on the deformation and fracture of composite tubular specimens under quasistatic tensile stress. A series of tests with various parameters of torsional vibration load for thin-walled CFRP tubular samples were performed according to the developed method. As part of the work, the methodological aspects of testing tubular specimens are considered. As a result, experimental data were obtained that reflect the effect of vibration effects on the behaviour of composite specimens during quasi-static tension. Additional vibrations contributed to the implementation of the deformation resources of the composite structural elements.
Exploration of strength characteristics quadrocopter frame structure obtained using 3d printing technology
Authors: Navrotsky R A , Moskvitin G V , Naumov O V , Pugachev M S
Published: April 2021

This article discusses the use of 3D printing technology for manufacturing the frame structure of a quadrocopter. The strength of the plastic frame structure is calculated. The results obtained allow us to draw conclusions about the possibility of using this technology for the production and operation of aircraft of the quadrocopter type.
On the strength of chemical anchors
Authors: Titov O V , Nadezhdin V S , Gruzdev A S , Kuprin A V
Published: April 2021

The work presents the strut attachment unit study of the bridge barrier road rack to the reinforced concrete slab (strength class of concrete B35) using adhesive (chemical) compositions and anchor-studs under the dynamic load. Bench static tests results and virtual experiment results based on study of digital models presented. The required depth of anchor-stud deepening determined.
Solving one dimensional time-space fractional vibration string equation
Authors: Aleroev Temirkhan S. , Elsayed Asmaa M. , Mahmoud Elsayed I.
Published: April 2021

The article presents a solution for the one-dimensional space-time fractional vibration equation (FVE) by the separation of variables method (Fourier method). We describe the fractional derivatives in the sense of Caputo and Riemann-Liouville operators. Our method performs in the extreme well in terms of simplicity and efficiency. A sample of the problem of structural mechanics has been considered. This sample allows the demonstration of some advantages of the application of the suggested approach to solve the fractional vibration equation.
Investigation of the stability of a cantilevered pipeline with a fluid flow compressed at the free end by the tracking force
Authors: Kapitanov D V , Kapitanova O V , Bobylkov A G
Published: April 2021

The paper presents a numerical and analytical investigation of the stability of a cantilevered pipeline transporting an incompressible fluid flow at a constant speed compressed by tracking force at the free end. To solve the problem, a dynamic approach based on the analysis of the behavior of the system’s own characteristics is used. In contrast to the classical research approaches, which are based on the representation of the solution of the problem using a finite number of basic functions, an algorithm that does not require such a restriction is proposed.
Analytical modelling of the influence of temperature and capillary diameter on the sonocapillary effect for liquids with different density
Authors: Mikhailova N , Smirnov I
Published: April 2021

The paper examines an approach to calculating the sonocapillary effect. The proposed model for calculating the initial sonocapillary pressure considers the temperature and density of a liquid, the capillary diameter, and the ultrasound frequency. The calculations are based on the incubation time criterion of cavitation. This approach allows us to find the threshold cavitation amplitude of ultrasound for a given frequency and to estimate the corresponding sonocapillary pressure. The calculation results show that the sonocapillary pressure is directly related to the liquid density, increasing the capillary diameter reduces the intensity of the sonocapillary effect, and a rising temperature increases the sonocapillary pressure. However, minimal experimental data are available at present to verify the obtained theoretical results. Therefore, a wider range of new experimental results should be obtained for further studies of the sonocapillary effect based on the presented results.
Features of the dynamics of walking machines and robots with cycle type of movers and controlled dissipation in the foot joint
Authors: Arykantsev V V , Kalinin Ya V , Chernyshev V V
Published: April 2021

The expediency of introducing an additional damping device (analog of a shock absorber) into the cyclic walking mechanism of a mobile robot, which provides a dissipative connection of a ski-shaped foot with a support link, is discussed. The influence of the damper on the dynamics of the feet changing and the dynamics of the meeting of the foot with an obstacle is considered. It is shown that dissipation in the hinge of the foot leads to a decrease in the intensity of shock processes when changing feet and when meeting an obstacle, provides a decrease in power losses for vertical vibrations of the body, and also expands the propulsion unit’s capabilities for self-adaptation to an unorganized surface.
Automation of robot programming in milling
Authors: Kozlov P , Mikhel S , Klimchik A
Published: April 2021

The paper demonstrates a method of automatic robot programming on the example of milling. The following problems are considered: format of the robot commands, analyze of an obtained trajectory, translation into the robot-specific language. The results confirm the ability of practical application for the proposed technique.
Loading and transport unit with a tripod manipulator and hybrid drive
Authors: Nikolaev M E , Nesmianov I A , Ivanov A G , Dyashkin-Titov V V
Published: April 2021

The analysis of loading and transport operations during the harvesting of vegetables Packed in bags or nets was carried out. The geometric parameters of the pincer grip are justified and analytical and graphical dependences of the required holding force for different bag masses are obtained. The device of a developed and manufactured loading and transport unit with a tripod manipulator is described. The tasks of further research are defined.
Increasing the level of the metrological supply of large-sized windows blades (from 60m) at the production stages
Authors: Sinitsa M O
Published: April 2021

The development of the field of renewable energy sources today is happening at a fairly rapid rate, especially in the field of wind energy. In the last year alone, several large wind farms have been built in Russia. The fast pace of development of wind energy in Russia leads to the fact that in the near future there will be a need to produce our own wind turbines, according to the projects of Russian developers. Also, the development of technologies, the rapid introduction of new production systems, an increase in the share of autonomy of industrial enterprises requires the introduction of new modern approaches in the field of energy, energy efficiency and energy conservation. Against this background, the need for innovative solutions in the field of metrological support and measuring technologies in the energy sector is sharply increasing. The paper presents a complex for carrying out control and measuring procedures, which will improve the quality of metrological support in the production process in Russia. Also, the metrological and economic parameters of the described stand have been calculated.…
Developing of transport airship for delivery oversized cargo to Vostochny Cosmodrome
Authors: Didkovskij A A , Mukhina E D , Chernov A K
Published: April 2021

The analysis of the world experience in the creation of airships has been carried out and the most actual tasks for such devices in the field of rocket and space technology have been revealed. The appearance of a transport airship with a carrying capacity of 100 tons has been developed and its main technical parameters have been defined.
Tobacco and Cannabis Use During Pregnancy
Authors: Hunsaker Joshua J H , La’ulu Sonia L , LaGrave Danielle , Murphy Wendy , Reichman Heather A , Snow Taylor M , McMillin Gwendolyn A , Johnson-Davis Kamisha L , Genzen Jonathan R
Published: April 2021

Objectives

Nicotine (NIC) use during pregnancy can influence markers used in biochemical maternal serum screening. This study was designed to determine prevalence of disclosed tobacco smokers in our patient population and to compare disclosed tobacco smoking status with the presence of serum nicotine and a common tetrahydrocannabinol (THC) metabolite.

Methods

A deidentified dataset of disclosed smoking status for quadruple (Quad) screens was obtained. Residual serum submitted for Quad screens was obtained from frozen storage and analyzed for NIC and THC metabolites.

Results

Of specimens that had corresponding responses to the smoking history question on the patient history form, 7.2% (n = 1,783 of 24,611) specified that the patient was a tobacco smoker. Of the 271 specimens biochemically analyzed for NIC and THC metabolites, disclosed tobacco smokers had the highest prevalence of detectable NIC and THC metabolites. THC product use was most prevalent in patients categorized as probable tobacco smokers based on cotinine concentrations, as well as in younger patients.

Conclusions

Prevalence and concentration of NIC and THC metabolites vary based on disclosed tobacco smoker status. Biochemical testing may increase sensitivity for the identification of NIC and THC status over self-reporting.
Use of failure modes and effects analysis to mitigate potential risks prior to implementation of an intravenous compounding technology
Authors: Feemster Agnes Ann , Augustino Melissa , Duncan Rosemary , Khandoobhai Anand , Rowcliffe Meghan
Published: April 2021

Purpose

The purpose of this study was to identify potential failure points in a new chemotherapy preparation technology and to implement changes that prevent or minimize the consequences of those failures before they occur using the failure modes and effects analysis (FMEA) approach.

Methods

An FMEA was conducted by a team of medication safety pharmacists, oncology pharmacists and technicians, leadership from informatics, investigational drug, and medication safety services, and representatives from the technology vendor. Failure modes were scored using both Risk Priority Number (RPN) and Risk Hazard Index (RHI) scores.

Results

The chemotherapy preparation workflow was defined in a 41-step process with 16 failure modes. The RPN and RHI scores were identical for each failure mode because all failure modes were considered detectable. Five failure modes, all attributable to user error, were deemed to pose the highest risk. Mitigation strategies and system changes were identified for 2 failure modes, with subsequent system modifications resulting in reduced risk.

Conclusion

The FMEA was a useful tool for risk mitigation and workflow optimization prior to implementation of an intravenous compounding technology. The process of conducting this study served as a collaborative and proactive approach to reducing the potential for medication errors upon adoption of new technology into the chemotherapy preparation process.
Pretraining model for biological sequence data
Authors: Song Bosheng , Li Zimeng , Lin Xuan , Wang Jianmin , Wang Tian , Fu Xiangzheng
Published: April 2021

With the development of high-throughput sequencing technology, biological sequence data reflecting life information becomes increasingly accessible. Particularly on the background of the COVID-19 pandemic, biological sequence data play an important role in detecting diseases, analyzing the mechanism and discovering specific drugs. In recent years, pretraining models that have emerged in natural language processing have attracted widespread attention in many research fields not only to decrease training cost but also to improve performance on downstream tasks. Pretraining models are used for embedding biological sequence and extracting feature from large biological sequence corpus to comprehensively understand the biological sequence data. In this survey, we provide a broad review on pretraining models for biological sequence data. Moreover, we first introduce biological sequences and corresponding datasets, including brief description and accessible link. Subsequently, we systematically summarize popular pretraining models for biological sequences based on four categories: CNN, word2vec, LSTM and Transformer. Then, we present some applications with proposed pretraining models on downstream tasks to explain the role of pretraining models. Next, we provide a novel pretraining scheme for protein sequences and a multitask benchmark for protein pretraining models. Finally, we discuss the challenges and future directions in pretraining models for biological sequences.
Capturing dynamic relevance in Boolean networks using graph theoretical measures
Authors: Weidner Felix M , Schwab Julian D , Werle Silke D , Ikonomi Nensi , Lausser Ludwig , Kestler Hans A
Published: April 2021

Motivation

Interaction graphs are able to describe regulatory dependencies between compounds without capturing dynamics. In contrast, mathematical models that are based on interaction graphs allow to investigate the dynamics of biological systems. However, since dynamic complexity of these models grows exponentially with their size, exhaustive analyses of the dynamics and consequently screening all possible interventions eventually becomes infeasible. Thus, we designed an approach to identify dynamically relevant compounds based on the static network topology.

Results

Here, we present a method only based on static properties to identify dynamically influencing nodes. Coupling vertex betweenness and determinative power, we could capture relevant nodes for changing dynamics with an accuracy of 75% in a set of 35 published logical models. Further analyses of the selected compounds’ connectivity unravelled a new class of not highly connected nodes with high impact on the networks’ dynamics, which we call gatekeepers. We validated our method’s working concept on logical models, which can be readily scaled up to complex interaction networks, where dynamic analyses are not even feasible.

Availability and implementation

Code is freely available at https://github.com/sysbio-bioinf/BNStatic.

Supplementary information

Supplementary data are available at Bioinformatics online.
Study on the Pharmacokinetic Profiles of Three Ingredients in Qilong Capsules and Their Potential Interactions in Rats by LC–MS/MS
Authors: Liu Ruichen , Liang Huiliang , Li Zhen , Zang Hengchang
Published: April 2021

Qilong capsule (QLC) is a well-known Traditional Chinese Medicine, and it has a long history for the treatment of ischemic stroke. Its major ingredients are saponins, such as paeoniflorin, amygdalin and calycosin-7-glucoside, contributing to vasodilation function. In this study, a simple, rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method was developed to determine three bioactive ingredients in rat plasma after oral administration of QLC. A simple acetonitrile precipitation method was introduced during the sample preparation. Chromatographic separation was performed on a Shiseido CAPCELL PAC MGIII-C18 column using a gradient elution with acetonitrile and water (0.1% formic acid) as a mobile phase, and the chromatographic separation was 5 min. The methodological evaluation showed that this method had a high sensitivity (the lower limit of quantification was 1 ng/mL for calycosin-7-glucoside, 5 ng/mL for paeoniflorin, 5 ng/mL for amygdalin), satisfactory accuracy (relative error ≤ ±15%) and precision (relative standard deviation ≤15%). Then, the analytical method was applied to the pharmacokinetic study in rats following oral administration of the extracts in QLC. Meanwhile, the pharmacokinetic parameters of complex system in QLC were analyzed and the potential interaction between ingredients was explored. The present quantification method and pharmacokinetic study will provide a meaningful reference for the formulas research of QLC in the treatment of ischemic stroke.

Highlight
Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients Undergoing Serial Laboratory Testing
Authors: Qureshi Adnan I , Baskett William I , Huang Wei , Lobanova Iryna , Hasan Naqvi S , Shyu Chi-Ren
Published: April 2021

Background

A better understanding of reinfection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become one of the healthcare priorities in the current pandemic. We determined the rate of reinfection, associated factors, and mortality during follow-up in a cohort of patients with SARS-CoV-2 infection.

Methods

We analyzed 9119 patients with SARS-CoV-2 infection who received serial tests in total of 62 healthcare facilities in the United States between 1 December 2019 and 13 November 2020. Reinfection was defined by 2 positive tests separated by interval of >90 days and resolution of first infection was confirmed by 2 or more consecutive negative tests. We performed logistic regression analysis to identify demographic and clinical characteristics associated with reinfection.

Results

Reinfection was identified in 0.7% (n = 63, 95% confidence interval [CI]: .5%–.9%) during follow-up of 9119 patients with SARS-CoV-2 infection. The mean period (±standard deviation [SD]) between 2 positive tests was 116 ± 21 days. A logistic regression analysis identified that asthma (odds ratio [OR] 1.9, 95% CI: 1.1–3.2) and nicotine dependence/tobacco use (OR 2.7, 95% CI: 1.6–4.5) were associated with reinfection. There was a significantly lower rate of pneumonia, heart failure, and acute kidney injury observed with reinfection compared with primary infection among the 63 patients with reinfection There were 2 deaths (3.2%) associated with reinfection.

Conclusions

We identified a low rate of reinfection confirmed by laboratory tests in a large cohort of patients with SARS-CoV-2 infection. Although reinfection appeared to be milder than primary infection, there was associated mortality.
Comparative 1-Year Outcomes of Invasive Staphylococcus aureus Infections Among Persons With and Without Drug Use: An Observational Cohort Study
Authors: Appa Ayesha , Adamo Meredith , Le Stephenie , Davis Jennifer , Winston Lisa , Doernberg Sarah B , Chambers Henry , Martin Marlene , Hills Nancy K , Coffin Phillip O , Jain Vivek
Published: April 2021

Background

Persons who use drugs (PWUD) face substantial risk of Staphylococcus aureus infections. Limited data exist describing clinical and substance use characteristics of PWUD with invasive S. aureus infections or comparing treatment and mortality outcomes in PWUD vs non-PWUD. These are needed to inform optimal care for this marginalized population.

Methods

We identified adults hospitalized from 2013 to 2018 at 2 medical centers in San Francisco with S. aureus bacteremia or International Classification of Diseases–coded diagnoses of endocarditis, epidural abscess, or vertebral osteomyelitis with compatible culture. In addition to demographic and clinical characteristic comparison, we constructed multivariate Cox proportional hazards models for 1-year infection-related readmission and mortality, adjusted for age, race/ethnicity, housing, comorbidities, and methicillin-resistant S. aureus (MRSA).

Results

Of 963 hospitalizations for S. aureus infections in 946 patients, 372 of 963 (39%) occurred in PWUD. Among PWUD, heroin (198/372 [53%]) and methamphetamine use (185/372 [50%]) were common. Among 214 individuals using opioids, 98 of 214 (46%) did not receive methadone or buprenorphine. PWUD had lower antibiotic completion than non-PWUD (70% vs 87%; P < .001). While drug use was not associated with increased mortality, 1-year readmission for ongoing or recurrent infection was double in PWUD vs non-PWUD (28% vs 14%; adjusted hazard ratio [aHR], 2.0 [95% confidence interval {CI}: 1.3–2.9]). MRSA was independently associated with 1-year readmission for infection (aHR, 1.5 [95% CI: 1.1–2.2]).

Conclusions

Compared to non-PWUD, PWUD with invasive S. aureus infections had lower rates of antibiotic completion and twice the risk of infection persistence/recurrence at 1 year. Among PWUD, both opioid and stimulant use were common. Models for combined treatment of substance use disorders and infections, particularly MRSA, are needed.
Local Hyperthermia at 44°C Is Effective in Clearing Cervical High-Risk Human Papillomaviruses: A Proof-of-Concept, Randomized Controlled Clinical Trial
Authors: Yang Yang , Zhang Lan , Zhang Yuqing , Huo Wei , Qi Ruiqun , Guo Hao , Li Xiaodong , Wu Xin , Bai Feng , Liu Kuiran , Qiao Youlin , Piguet Vincent , Croitoru David , Chen Hong-Duo , Gao Xing-Hua
Published: April 2021

Background

Persistent infection by high-risk human papillomavirus (HPV) is the leading cause of cervical intraepithelial neoplasia and cervical carcinoma. Local hyperthermia at 44ºC has been proven efficacious to clear cutaneous or anogenital warts caused by HPV infection. This study aims to assess the effect of hyperthermia at 44ºC on the clearance of high-risk HPV.

Methods

A randomized, patient-blind, sham treatment–controlled trial was conducted in 4 medical centers. We enrolled patients with positive high-risk HPVs and normal or insignificant cytological findings (negative/atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion). Participants were randomly assigned (1:1) to receive either hyperthermia at 44ºC or 37ºC, for 30 minutes in each session. Patients in both groups received treatment once a day for 3 consecutive days, plus 2 more sessions 10 ± 3 days later. The primary outcome was clearance rate of HPV 3 months after treatment.

Results

After a 3-month follow-up, hyperthermia treatment at 44ºC and 37ºC achieved HPV clearance rates of 85.19% (23/27) and 50% (13/26), respectively (P = .014). There was no significant difference of treatment response between patients with single and multiple type of HPV by 44ºC hyperthermia treatment. There were no significant adverse events recorded during the treatment period in both groups.

Conclusions

Local hyperthermia at 44ºC safely and significantly aids in clearing cervical high-risk HPVs, the effect of which helps halt the progression of cervical transformation and transmission of the virus.

Clinical Trials Registration

NCT03436251.
Vaccinated and Convalescent Donor–Derived Severe Acute Respiratory Syndrome Coronavirus 2–Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients
Authors: Papayanni Penelope-Georgia , Chasiotis Dimitrios , Koukoulias Kiriakos , Georgakopoulou Aphrodite , Iatrou Anastasia , Gavriilaki Eleni , Giannaki Chrysavgi , Bitzani Militsa , Geka Eleni , Tasioudis Polychronis , Chloros Diamantis , Fylaktou Asimina , Kioumis Ioannis , Triantafyllidou Maria , Dimou-Besikli Sotiria , Karavalakis Georgios , Boutou Afroditi K , Siotou Eleni , Anagnostopoulos Achilles , Papadopoulou Anastasia , Yannaki Evangelia
Published: April 2021

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19).

Methods

We first tested SARS-CoV-2–specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19–infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)–positive subjects, vaccinated individuals, non–intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment.

Results

We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2–specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2–specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity.

Conclusions

Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an “off-the shelf” T-cell immunotherapy for high-risk patients.
The music of Iannis Xenakis’ estrangedKassandra
Authors: Pillinger Emily
Published: April 2021

Iannis Xenakis (1922–2001) was a radically innovative composer. Violently persecuted for his leftist activism in the Greek Civil War that followed the Second World War, he fled Greece to live the rest of his life in Paris. One of the most explicit expressions of his resultant feelings of trauma, guilt, and displacement can be found in the vocal piece he called Kassandra (1987). This demanding work requires its two performers to enact and explore the alienation experienced by the prophet Cassandra in Aeschylus’ Agamemnon. Xenakis’ Kassandra is defined by a symbiotic relationship between percussionist and vocalist, by a simultaneously controlled and improvisatory score based on extracts from Aeschylus’ Agamemnon, and by a striking use of the baritone singer’s falsetto as well as his chest voice. These features of the piece mark out Cassandra as ‘other’ in her origins, her sex, and her language, while also hinting that her characteristics are not entirely foreign, but are in fact understood or even shared by the very communities that initially seemed to exclude her.
Perioperative Venous Thromboembolism in Ulcerative Colitis: A Multicenter Prospective Study in Japan
Authors: Itabashi Michio , Ikeuchi Hiroki , Kimura Hideaki , Fukushima Kohei , Fujii Hisao , Nezu Riichiro , Futami Kitaro , Sugita Akira , Suzuki Yasuo , Hisamatsu Tadakazu
Published: April 2021

Background

Recently, the prevalence of venous thromboembolism (VTE) in Asian patients with inflammatory bowel disease (IBD) is gradually increasing. IBD surgery is a well-recognized risk factor for VTE. However, there are no prospective studies about VTE after surgery for ulcerative colitis (UC) in Asia. This multicenter prospective study aimed to clarify the prevalence and risk factors for perioperative VTE in UC surgery in Japan.

Methods

A total of 134 patients with UC were included from January 1, 2013 to December 31, 2014. Preoperative screening was performed in all patients. In the perioperative period, standard VTE prophylaxis based on risk assessment was administered. The prevalence of pre- and postoperative VTE, its risk factors, and mortality rates were investigated.

Results

Perioperative deep vein thrombosis and pulmonary embolism were diagnosed in 15 (11.1%) and 1 patient (0.7%), respectively. All patients were asymptomatic. No surgery-related deaths were found (mortality rate 0%). Seven patients (5.2%) were diagnosed, and 8 (6.4%) during postoperative follow-up by ultrasonography or computed tomography. Forty-seven percent of VTE cases was developed preoperatively. A preoperative hospital length stay of over 5 days was a significant risk factor [P = 0.04; odds ratio: 8.26 (1.06–64.60)] for preoperative VTE. Postoperative deep vein thrombosis occurred in 8 of the 127 patients (6.4%). Six out of these 8 (75.0%) occurred after postoperative day 14. Perioperative blood transfusion was a significant risk factor [P = 0.04; odds ratio: 8.26 (1.06–64.60)] for postoperative VTE.

Conclusion

A VTE-conscious perioperative management is as necessary in Asia as in Western countries.
Optimizing indices of atrial fibrillation susceptibility and burden to evaluate atrial fibrillation severity, risk and outcomes
Authors: Boriani Giuseppe , Vitolo Marco , Diemberger Igor , Proietti Marco , Valenti Anna Chiara , Malavasi Vincenzo Livio , Lip Gregory Y H
Published: April 2021

Atrial fibrillation (AF) has heterogeneous patterns of presentation concerning symptoms, duration of episodes, AF burden, and the tendency to progress towards the terminal step of permanent AF. AF is associated with a risk of stroke/thromboembolism traditionally considered dependent on patient-level risk factors rather than AF type, AF burden, or other characterizations. However, the time spent in AF appears related to an incremental risk of stroke, as suggested by the higher risk of stroke in patients with clinical AF vs. subclinical episodes and in patients with non-paroxysmal AF vs. paroxysmal AF. In patients with device-detected atrial tachyarrhythmias, AF burden is a dynamic process with potential transitions from a lower to a higher maximum daily arrhythmia burden, thus justifying monitoring its temporal evolution. In clinical terms, the appearance of the first episode of AF, the characterization of the arrhythmia in a specific AF type, the progression of AF, and the response to rhythm control therapies, as well as the clinical outcomes, are all conditioned by underlying heart disease, risk factors, and comorbidities. Improved understanding is needed on how to monitor and modulate the effect of factors that condition AF susceptibility and modulate AF-associated outcomes. The increasing use of wearables and apps in practice and clinical research may be useful to predict and quantify AF burden and assess AF susceptibility at the individual patient level. This may help us reveal why AF stops and starts again, or why AF episodes, or burden, cluster. Additionally, whether the distribution of burden is associated with variations in the propensity to thrombosis or other clinical adverse events. Combining the improved methods for data analysis, clinical and translational science could be the basis for the early identification of the subset of patients at risk of progressing to a longer duration/higher burden of AF and the associated adverse outcomes.
Human IRES Atlas: an integrative platform for studying IRES-driven translational regulation in humans
Authors: Yang Tzu-Hsien , Wang Chung-Yu , Tsai Hsiu-Chun , Liu Cheng-Tse
Published: April 2021

It is now known that cap-independent translation initiation facilitated by internal ribosome entry sites (IRESs) is vital in selective cellular protein synthesis under stress and different physiological conditions. However, three problems make it hard to understand transcriptome-wide cellular IRES-mediated translation initiation mechanisms: (i) complex interplay between IRESs and other translation initiation–related information, (ii) reliability issue of in silico cellular IRES investigation and (iii) labor-intensive in vivo IRES identification. In this research, we constructed the Human IRES Atlas database for a comprehensive understanding of cellular IRESs in humans. First, currently available and suitable IRES prediction tools (IRESfinder, PatSearch and IRESpy) were used to obtain transcriptome-wide human IRESs. Then, we collected eight genres of translation initiation–related features to help study the potential molecular mechanisms of each of the putative IRESs. Three functional tests (conservation, structural RNA–protein scores and conditional translation efficiency) were devised to evaluate the functionality of the identified putative IRESs. Moreover, an easy-to-use interface and an IRES–translation initiation interaction map for each gene transcript were implemented to help understand the interactions between IRESs and translation initiation–related features. Researchers can easily search/browse an IRES of interest using the web interface and deduce testable mechanism hypotheses of human IRES-driven translation initiation based on the integrated results. In summary, Human IRES Atlas integrates putative IRES elements and translation initiation–related experiments for better usage of these data and deduction of mechanism hypotheses.

Database URL: http://cobishss0.im.nuk.edu.tw/Human_IRES_Atlas/
The 12-lead electrocardiogram as a biomarker of biological age
Authors: Ladejobi Adetola O , Medina-Inojosa Jose R , Shelly Cohen Michal , Attia Zachi I , Scott Christopher G , LeBrasseur Nathan K , Gersh Bernard J , Noseworthy Peter A , Friedman Paul A , Kapa Suraj , Lopez-Jimenez Francisco
Published: April 2021

Background

We have demonstrated that a neural network is able to predict a person’s age from the electrocardiogram (ECG) [artificial intelligence (AI) ECG age]. However, some discrepancies were observed between ECG-derived and chronological ages. We assessed whether the difference between AI ECG and chronological age (Age-Gap) represents biological ageing and predicts long-term outcomes.

Methods and results

We previously developed a convolutional neural network to predict chronological age from ECGs. In this study, we used the network to analyse standard digital 12-lead ECGs in a cohort of 25 144 subjects ≥30 years who had primary care outpatient visits from 1997 to 2003. Subjects with coronary artery disease, stroke, and atrial fibrillation were excluded. We tested whether Age-Gap was correlated with total and cardiovascular mortality. Of 25 144 subjects tested (54% females, 95% Caucasian) followed for 12.4 ± 5.3 years, the mean chronological age was 53.7 ± 11.6 years and ECG-derived age was 54.6 ± 11 years (R2 = 0.79, P < 0.0001). The mean Age-Gap was small at 0.88 ± 7.4 years. Compared to those whose ECG-derived age was within 1 standard deviation (SD) of their chronological age, patients with Age-Gap ≥1 SD had higher all-cause and cardiovascular disease (CVD) mortality. Conversely, subjects whose Age-Gap was ≤1 SD had lower all-cause and CVD mortality. Results were unchanged after adjusting for CVD risk factors and other survival influencing factors.

Conclusion

The difference between AI ECG and chronological age is an independent predictor of all-cause and cardiovascular mortality. Discrepancies between these possibly reflect disease independent biological ageing.
Daily rhythms of both host and parasite affect antimalarial drug efficacy
Authors: Owolabi Alíz T Y , Reece Sarah E , Schneider Petra
Published: April 2021

Background and objectives

Circadian rhythms contribute to treatment efficacy in several non-communicable diseases. However, chronotherapy (administering drugs at a particular time-of-day) against infectious diseases has been overlooked. Yet, the daily rhythms of both hosts and disease-causing agents can impact the efficacy of drug treatment. We use the rodent malaria parasite Plasmodium chabaudi, to test whether the daily rhythms of hosts, parasites and their interactions affect sensitivity to the key antimalarial, artemisinin.

Methodology

Asexual malaria parasites develop rhythmically in the host’s blood, in a manner timed to coordinate with host daily rhythms. Our experiments coupled or decoupled the timing of parasite and host rhythms, and we administered artemisinin at different times of day to coincide with when parasites were either at an early (ring) or later (trophozoite) developmental stage. We quantified the impacts of parasite developmental stage, and alignment of parasite and host rhythms, on drug sensitivity.

Results

We find that rings were less sensitive to artemisinin than trophozoites, and this difference was exacerbated when parasite and host rhythms were misaligned, with little direct contribution of host time-of-day on its own. Furthermore, the blood concentration of haem at the point of treatment correlated positively with artemisinin efficacy but only when parasite and host rhythms were aligned.

Conclusions and implications

Parasite rhythms influence drug sensitivity in vivo. The hitherto unknown modulation by alignment between parasite and host daily rhythms suggests that disrupting the timing of parasite development could be a novel chronotherapeutic approach.

Lay Summary

We reveal that chronotherapy (providing medicines at a particular time-of-day) could improve treatment for malaria infections. Specifically, parasites’ developmental stage at the time of treatment and the coordination of timing between parasite and host both affect how well antimalarial drug treatment works.
Underperformance of clinical risk scores in identifying vascular ultrasound-based high cardiovascular risk in systemic lupus erythematosus
Authors: Drosos George C , Konstantonis George , Sfikakis Petros P , Tektonidou Maria G
Published: April 2021

Aims

The aim of this study was to assess the performance of eight clinical risk prediction scores to identify individuals with systemic lupus erythematosus (SLE) at high cardiovascular disease (CVD) risk, as defined by the presence of atherosclerotic plaques.

Methods

CVD risk was estimated in 210 eligible SLE patients without prior CVD or diabetes mellitus (female: 93.3%, mean age: 44.8 ± 12 years) using five generic (Systematic Coronary Risk Evaluation (SCORE), Framingham Risk Score (FRS), Pooled Cohort Risk Equations (ASCVD), Globorisk, Prospective Cardiovascular Münster Study risk calculator (PROCAM)) and three ‘SLE-adapted’ (modified-SCORE, modified-FRS, QRESEARCH risk estimator, version 3 (QRISK3)) CVD risk scores, as well as ultrasound examination of the carotid and femoral arteries. Calibration, discrimination and classification measures to identify high CVD risk based on the presence of atherosclerotic plaques were assessed for all risk models. CVD risk reclassification was applied for all scores by incorporating ultrasound results.

Results

Moderate calibration (p-value range from 0.38 to 0.63) and discrimination (area under the curve 0.73–0.84), and low-to-moderate sensitivity (8.3–71.4%) and classification ability (Matthews correlation coefficient (MCC) 0.25–0.47) were observed for all risk models to identify patients with plaques at any arterial site as high-risk. MCC was improved for modified-FRS versus FRS (0.43 vs 0.36), but not for modified-SCORE versus SCORE (0.25 vs 0.25). Based on plaque presence, CVD risk was upgraded to high-risk in 10%, 16.1%, 20.5%, 21.5%, 24%, 28.2% and 28.6% of cases classified as non-high-risk by QRISK3, modified-FRS, Globorisk, FRS/PROCAM, ASCVD, modified-SCORE and SCORE, respectively.

Conclusions

Most of the five generic and three ‘SLE-adapted’ clinical risk scores underestimated high CVD risk defined by atherosclerotic plaque presence in patients with SLE.