bluuebunny/crossref_metadata_2025 huggingface dataset:
Discordance of Tracer Transport and Particulate Matter Fate in a Baffled Clarification System
Authors: Li Haochen , Balachandar S. , Sansalone John
Published: January 2021

Large eddy simulation (LES) and coupled physical laboratory-scale modeling are performed to elucidate tracer transport and particulate matter (PM) fate in a baffled clarification system. Such baffled systems are common for urban water unit operations and processes. Flow hydrodynamic indices of these systems such as short-circuiting are often examined with measurement of inert tracer transport as a surrogate for chemical or PM transport and fate. Results of this study illustrate complex interactions between turbulent flow, tracer, and various PM diameters at the system scale. PM preferential accumulation and the discordance of PM transport with respect to flow hydrodynamics are observed based on the modeling results; otherwise not practical with physical model testing. Results demonstrate that baffling can promote system tracer mixing and improve volumetric utilization by extending the mean flow path through flow separation and bifurcation. The baffle tested produced high turbulence kinetic energy near the sedimentation floor and reduced PM separation (clarification) as compared to the unbaffled system used as a control. The unbaffled system in this study yields the highest PM separation, even though significant short-circuiting occurs during the residence time distribution (RTD) of the tracer. Further analysis demonstrates the mechanistic difference between the tracer transport and the finer suspended PM as compared to larger settleable and sediment PM diameters. Results illustrate that the tracer RTD, residence time (RT) and hydraulic efficiency indices are not reliable surrogates for PM or PM-bound chemical/pathogen separation. In addition, simulations suggest a site, system or condition-specific design approach given the coupled dependence on flow and design geometry.
Computational Fluid Dynamics Study of a Nonpremixed Turbulent Flame Using openfoam: Effect of Chemical Mechanisms and Turbulence Models
Authors: Noume Hermann Chopkap , Bomba Valentin , Obounou Marcel , Fouda Henri Ekobena , Sapnken Flavian Emmanuel
Published: January 2021

This article presents a study of the influence of chemical mechanisms and turbulence models on Reynolds-averaged Navier–Stokes (RANS) simulations of the CH4/H2/N2-air turbulent diffusion flame, i.e., the so-called DLR-A flame. The first part of this study is focused on the assessment of the influence of four chemical models on predicted profiles of the DLR-A flame. The chemical mechanisms considered are as follows: (i) a C2 compact skeletal mechanism, which is derived from the GRI3.0 mechanism using an improved multistage reduction method, (ii) a C1 skeletal mechanism containing 41 elementary reactions amongst 16 species, (iii) the global mechanism by Jones and Lindstedt, (iv) and a global scheme consisting of the overall reactions of methane and dihydrogen. RANS numerical results (e.g., velocities, temperature, species, or the heat production rate profiles) obtained running the reactingFOAM solver with the four chemical mechanisms as well as the standard k − ɛ model, the partially stirred reactor (PaSR) combustion model, and the P − 1 radiation model indicate that the C2 skeletal mechanism yields the best agreement with measurements. In the second part of this study, four turbulence models, namely, the standard k − ɛ model, the renormalization group (RNG) k − ɛ model, realizable k − ɛ model, and the k − ω shear stress transport (SST) model, are considered to evaluate their effects on the DLR-A flame simulation results obtained with the C2 skeletal mechanism. Results reveal that the predictions obtained with the standard k − ɛ and the RNG k − ɛ models are in very good agreement with the experimental data. Hence, for simple jet flame with moderately high Reynolds number such as the DLR-A flame, the standard k-epsilon can model the turbulence with a very good accuracy.
Design and Analysis of a Water-Cooling System in a New Yokeless and Segmented Armature Axial In-Wheel Motor for Electric Vehicles
Authors: Luo Liang , Chang Jiujian , Wu Jinglai , Zhu Bo , Zheng Minyi , Zhang Nong
Published: January 2021

An in-wheel motor, as a key part of an in-wheel driving system, needs to satisfy strict restrictions on thermal balance for increasingly high-power density in limited space and weight. Therefore, a new in-wheel motor with an innovative water-cooling system for one newly developed electric vehicle was developed. Based on the mechanical structure of the motor, all potential water-cooling layouts were first designed with consideration of mechanical strength and manufacturability. A thermal conjugate simulation model of the developed in-wheel motor was then built, and its thermally fluid–solid interactions were investigated in this study. All potential water-path layouts of the motor were compared regarding the cooling effect and fluid resistance, which impact the performance of the motor. Fluid flow velocity and fluid state, determined by the water-path layout, significantly impact the cooling effect of the motor. The well-designed water-cooling system significantly reduces the motor’s temperature at a low cost on required coolant-driven pressure which benefits the efficiency of the developed motor. A prototype of the developed motor with the optimal water-path layout was built and tested on the test rig. The developed motor provides outstanding thermal performance.
Science could benefit as Democrats take power
Authors: Malakoff David , Mervis Jeffrey
Published: January 2021

Major shifts on climate and science policy expected, but political obstacles abound.
The language of a virus
Authors: Kim Yoo-Ah , Przytycka Teresa M.
Published: January 2021

Viral fitness and its immune escape can be modeled by using concepts of natural language
Herd immunity by infection is not an option
Authors: Sridhar Devi , Gurdasani Deepti
Published: January 2021

Difficult lessons are learned from a largely uncontrolled COVID-19 epidemic in Manaus, Brazil
Mechanisms and Consequences of Newcastle Disease Virus W Protein Subcellular Localization in the Nucleus or Mitochondria
Authors: Yang Yanling , Xue Jia , Teng Qingyuan , Li Xiao , Bu Yawen , Zhang Guozhong
Published: January 2021

In Newcastle disease virus (NDV), the W protein, like the V protein, is a nonstructural protein encoded by the P gene via RNA editing. Compared with the V protein, the W protein has a common N-terminal domain but a unique C-terminal domain.
Cross-Reactive Anti-Nucleocapsid Protein Immunity against Crimean-Congo Hemorrhagic Fever Virus and Hazara Virus in Multiple Species
Authors: Kalkan-Yazıcı Merve , Karaaslan Elif , Çetin Nesibe Selma , Hasanoğlu Sevde , Güney Filiz , Zeybek Ümit , Doymaz Mehmet Z.
Published: January 2021

Crimean-Congo hemorrhagic fever virus (CCHFV) and Hazara virus (HAZV), members of theNairoviridaefamily, are transmitted to mammals by tick bites. CCHFV is considered a severe threat to public health and causes hemorrhagic diseases with a high mortality rate, and there are neither preventative nor therapeutic medications against CCHFV disease.
Quantitative reconstruction of pore-pressure history in sedimentary basins using fluid escape pipes
Authors: Cartwright Joe , Kirkham Chris , Foschi Martino , Hodgson Neil , Rodriguez Karyna , James David
Published: January 2021

We present a novel method to reconstruct the pressure conditions responsible for the formation of fluid escape pipes in sedimentary basins. We analyzed the episodic venting of high-pressure fluids from the crests of a large anticlinal structure that formed off the coast of Lebanon in the past 1.7 m.y. In total, 21 fluid escape pipes formed at intervals of 50–100 k.y. and transected over 3 km of claystone and evaporite sealing units to reach the seabed. From fracture criteria obtained from nearby drilling, we calculated that overpressures in excess of 30 MPa were required for their formation, with pressure recharge of up to 2 MPa occurring after each pipe-forming event, resulting in a sawtooth pressure-time evolution. This pressure-time evolution is most easily explained by tectonic overpressuring due to active folding of the main source aquifer while in a confined geometry.
Agglomeration-Based Node Importance Analysis in Wheel-Type Networks
Authors: Berberler Zeynep Nihan , Yildirim Halil İbrahim , İltüzer Tolga , Tunç İzzet
Published: January 2021

Evaluating the importance of nodes for complex networks is an important part of invulnerability research. In this paper, node importance analysis is conducted in wheel-related networks by a method of evaluating node importance by node contraction based on network agglomeration in communication networks. Both degrees and positions of nodes are considered with this method. This method was also proved to be feasible and effective measure to identify influential nodes in a network.
SIGACT News Online Algorithms Column 36
Authors: Höhne Felix , Schmitt Sören , van Stee Rob
Published: January 2021

In this column, we will discuss some papers in online algorithms that appeared in 2020. As usual, we make no claim at complete coverage here, and have instead made a selection. If we have unaccountably missed your favorite paper and you would like to write about it or about any other topic in online algorithms, please don't hesitate to contact us!
PI(4,5)P2 Clustering and Its Impact on Biological Functions
Authors: Wen Yi , Vogt Volker M. , Feigenson Gerald W.
Published: January 2021

Located at the inner leaflet of the plasma membrane (PM), phosphatidyl-inositol 4,5-bisphosphate [PI(4,5)P2] composes only 1–2 mol% of total PM lipids. With its synthesis and turnover both spatially and temporally regulated, PI(4,5)P2 recruits and interacts with hundreds of cellular proteins to support a broad spectrum of cellular functions. Several factors contribute to the versatile and dynamic distribution of PI(4,5)P2 in membranes. Physiological multivalent cations such as Ca2+ and Mg2+ can bridge between PI(4,5)P2 headgroups, forming nanoscopic PI(4,5)P2–cation clusters. The distinct lipid environment surrounding PI(4,5)P2 affects the degree of PI(4,5)P2 clustering. In addition, diverse cellular proteins interacting with PI(4,5)P2 can further regulate PI(4,5)P2 lateral distribution and accessibility. This review summarizes the current understanding of PI(4,5)P2 behavior in both cells and model membranes, with emphasis on both multivalent cation– and protein-induced PI(4,5)P2 clustering. Understanding the nature of spatially separated pools of PI(4,5)P2 is fundamental to cell biology.
Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding
Authors: Liu Yi , Yang Qian , Zhao Fangzhou
Published: January 2021

Codon usage bias, the preference for certain synonymous codons, is found in all genomes. Although synonymous mutations were previously thought to be silent, a large body of evidence has demonstrated that codon usage can play major roles in determining gene expression levels and protein structures. Codon usage influences translation elongation speed and regulates translation efficiency and accuracy. Adaptation of codon usage to tRNA expression determines the proteome landscape. In addition, codon usage biases result in nonuniform ribosome decoding rates on mRNAs, which in turn influence the cotranslational protein folding process that is critical for protein function in diverse biological processes. Conserved genome-wide correlations have also been found between codon usage and protein structures. Furthermore, codon usage is a major determinant of mRNA levels through translation-dependent effects on mRNA decay and translation-independent effects on transcriptional and posttranscriptional processes. Here, we discuss the multifaceted roles and mechanisms of codon usage in different gene regulatory processes.
Quantitative Mass Spectrometry Imaging of Biological Systems
Authors: Unsihuay Daisy , Mesa Sanchez Daniela , Laskin Julia
Published: January 2021

Mass spectrometry imaging (MSI) is a powerful, label-free technique that provides detailed maps of hundreds of molecules in complex samples with high sensitivity and subcellular spatial resolution. Accurate quantification in MSI relies on a detailed understanding of matrix effects associated with the ionization process along with evaluation of the extraction efficiency and mass-dependent ion losses occurring in the analysis step. We present a critical summary of approaches developed for quantitative MSI of metabolites, lipids, and proteins in biological tissues and discuss their current and future applications.
Characterization of the Particle-Polymer Interface in Dual-Phase Electrolytes by Kelvin Probe Force Microscopy
Authors: Buchheit Annika , Hoffmeyer Marija , Teßmer Britta , Neuhaus Kerstin
Published: January 2021

In this study, the possibility to characterize the electrochemical characteristics of the particle-polymer interface in dual-phase electrolytes by measuring the contact potential difference with high local resolution is demonstrated. Two different polymer electrolytes, polyethylene oxide (PEO) and poly[bis-2-(2-methoxyethoxy)-ethoxyphosphazene] (MEEP), were investigated in combination with lithium ion conductive Li7La3Zr2O12 (LLZ) particles and two different mixed ionic-electronic conductive ceramic particles: uncoated and carbon coated LiFePO4 (LFP) as typical cathode material and uncoated Li4Ti5O12 as typical anode material. A distinct Volta potential gradient between the particles and the polymer was observable in all cases, except when no lithium salt was present within the polymer matrix. The measured potential gradients can be explained in terms of a contact potential between the polymer electrolyte and the ceramic electrolyte. A more negatively charged space charge layer around LFP particles in PEO matrix and around LLZ particles in MEEP can be explained by enrichment of salt anions in direct vicinity of the particle. Electrochemical characterization with impedance spectroscopy showed an increased conductivity for addition of LFP for PEO while the addition of various particles in different concentrations showed no effect on the conductivity of MEEP. The lithium transference number was unaffected by particle addition for all samples.
Negligible influence of moderate to severe hyperthermia on blood-brain barrier permeability and neuronal parenchymal integrity in healthy men
Authors: Shepley Brooke R. , Ainslie Philip N. , Hoiland Ryan L. , Donnelly Joseph , Sekhon Mypinder S. , Zetterberg Henrik , Blennow Kaj , Bain Anthony R.
Published: January 2021

The acute effects of passive whole-body hyperthermia on the integrity of the neurovascular unit (NVU) in humans have remained unclear. We demonstrate that passive heating for ∼1 h until an increase of +2°C esophageal temperature in healthy men does not increase the cerebral release of neuronal parenchymal stress biomarkers, suggesting the NVU integrity is maintained. This preliminary study indicates passive heating is safe for the brain, at least in young healthy men.
Markers of branched-chain amino acid catabolism are not affected by exercise training in pregnant women with obesity
Authors: Allman Brittany R. , Spray Beverly J. , Mercer Kelly E. , Andres Aline , Børsheim Elisabet
Published: January 2021

This research showed an increase in insulin resistance (IR) and decrease in branched-chain amino acid catabolism throughout gestation in women with obesity, and addition of a moderate exercise intervention (known to attenuate IR in nonpregnant populations) did not alter these shifts. Findings provide support for metabolic safety of exercise during pregnancy.
Reduced skeletal muscle endurance and ventilatory efficiency during exercise in adult smokers without airflow obstruction
Authors: Sadaka Ahmed S. , Faisal Azmy , Khalil Yehia M. , Mourad Sahar M. , Zidan Mohamed H. , Polkey Michael I. , Hopkinson Nicholas S.
Published: January 2021

In adult smokers without airflow obstruction, the contributions of pulmonary and skeletal muscle functions to reduced exercise capacity are unclear. We found that non-COPD smokers had decreased exercise capacity and muscle endurance although strength was preserved compared with never-smoking controls. Exercise endurance was associated with quadriceps endurance and CO transfer factor. Despite similar physical activity levels, smokers developed leg fatigue, breathlessness, and displayed increased ventilation with reduced ventilatory efficiency at lower workloads, without exhibiting ventilatory constraint.
An Improved Dual‐Kurtogram‐Based T2 Control Chart for Condition Monitoring and Compound Fault Diagnosis of Rolling Bearings
Authors: Jiao Zhiyuan , Fan Wei , Xu Zhenying
Published: January 2021

Condition monitoring and compound fault diagnosis are crucial key points for ensuring the normal operation of rotating machinery. A novel method for condition monitoring and compound fault diagnosis based on the dual‐kurtogram algorithm and multivariate statistical process control is established in this study. The core idea of this method is the capability of the dual‐kurtogram in extracting subbands. Vibration data under normal conditions are decomposed by the dual‐kurtogram into two subbands. Then, the spectral kurtosis (SK) of Subband I and the envelope spectral kurtosis (ESK) of Subband II are formulated to construct a control limit based on kernel density estimation. Similarly, vibration data that need to be monitored are constructed into two subbands by the dual‐kurtogram. The SK of Subband I and the ESK of Subband II are calculated to derive T2 statistics based on the covariance determinant. An alarm will be triggered when the T2 statistics exceed the control limit and suitable subbands for square envelope analysis are adopted to obtain the characteristic frequency. Simulation and experimental data are used to verify the feasibility of the proposed method. Results confirm that the proposed method can effectively perform condition monitoring and fault diagnosis. Furthermore, comparison studies show that the proposed method outperforms the traditional T2 control chart, envelope analysis, and empirical mode decomposition.
Analysis of Sensitive Parameters Affecting Unlocking Force of Finger Lock in Landing Gear
Authors: Hou Yu , Zhang Ming , Nie Hong
Published: January 2021

The mechanical characteristics of the unlocking force of the landing gear finger lock were studied in this paper, the influence of its diameter, fingertip angle, wear, and other factors on the unlocking force in one complete working cycle was analyzed, and the sensitive parameters that affect the unlocking force were obtained. Firstly, the unlocking force and wear of finger lock were calculated theoretically, and the changing rule of the unlocking force and wear with each parameter was obtained. Then, the validity of the correlation coefficient and model was verified by experiment. Finally, combined with the effective coefficient obtained from the experiment, the Archard wear model was used to simulate the change rule of lock force. The results show that in one complete working cycle, the inner surface diameter is negatively related to the unlocking force, fingertip diameter has little effect on the unlocking force, fingertip angle is negatively related to the unlocking force, and wear is positively related to the unlocking force; friction coefficient and fingertip angle are high sensitive parameters that affect the unlocking force, which have obvious effect on the unlocking force. The inner surface diameter, fingertip diameter of finger lock, and wear are the low sensitive parameters that affect the unlocking force, and the influence on the unlocking force is weak.
Magnetohydrodynamic Control of Hypersonic Separation Flows
Authors: Luo Shichao , Liu Jun , Jiang Hao , Wang Junyuan
Published: January 2021

Magnetohydrodynamic (MHD) control of hypersonic laminar separation flows is investigated in this paper. A series of numerical simulations over various geometry configurations, namely, a compression corner and a double wedge ramp hypersonic inlet, have been conducted by application of an external electromagnetic field. Results show that the performance of MHD separation flow control is mainly determined by flow acceleration of the Lorentz force directed in the streamwise direction. The Joule heating term always brings negative effects on the MHD separation flow control and increased the static pressure locally, where the electromagnetic field is applied. With an external electromagnetic field applied, the low velocity fluid in the boundary layer can be accelerated. Moreover, there exists a best location for the MHD zone to be applied and completely eliminate the separation of the flow from the surface.
Event-Sensitive Network: A Construction Algorithm of Agricultural Sensor Network Driven by Environmental Change
Authors: Xu Shipu , Liu Yong , Hu WenWen , Wu Yingjing , Liu Sijia , Wang Yunsheng , Liu Chang
Published: January 2021

In a wireless sensor network, the sensor nodes transmit the acquired information to the server through the data transmission link. On the serverside, the data are processed, fused, and expressed to serve the user. Sensor deployment is a key factor related to the stability and security of wireless networks. This article uses environmental changes to drive related technologies to deploy wireless sensors. In this article, environmental change-driven means that through certain deployment cost model assumptions and problem descriptions, network deployment is artificially divided into two stages: initial deployment and redeployment. In the deployment phase, by referring to the idea of virtual force, a new sensor deployment algorithm is proposed in the redeployment phase, which can well solve the stability- and security-related issues encountered in agricultural wireless sensor networks. In this algorithm, the moving distance of the mobile receiver and the average coverage of the network are calculated based on the virtual force, the direction, and the number of adjacent clusters. Finally, the algorithm model was simulated in MATLAB, and the feasibility of the algorithm was verified by analyzing the event coverage and the moving distance of nodes. The final simulation results show that the algorithm proposed in this paper can achieve better performance than existing algorithms in terms of average coverage and moving distance.
Material Sputtering with a Multi‐Ion Species Plasma Focused Ion Beam
Authors: Brogden Valerie , Johnson Cameron , Rue Chad , Graham Jeremy , Langworthy Kurt , Golledge Stephen , McMorran Ben
Published: January 2021

Focused ion beams are an essential tool for cross‐sectional material analysis at the microscale, preparing TEM samples, and much more. New plasma ion sources allow for higher beam currents and options to use unconventional ion species, resulting in increased versatility over a broader range of substrate materials. In this paper, we present the results of a four‐material study from five different ion species at varying beam energies. This, of course, is a small sampling of the enormous variety of potential specimen and ion species combinations. We show that milling rates and texturing artifacts are quite varied. Therefore, there is a need for a systematic exploration of how different ion species mill different materials. There is so much to be done that it should be a community effort. Here, we present a publicly available automation script used to both measure sputter rates and characterize texturing artifacts as well as a collaborative database to which anyone may contribute. We also put forth some ideas for new applications of focused ion beams with novel ion species.
Polygonatum sibiricum Polysaccharides Protect against MPP‐Induced Neurotoxicity via the Akt/mTOR and Nrf2 Pathways
Authors: Huang Si , Yuan Haiyan , Li Wenqun , Liu Xinyi , Zhang Xiaojie , Xiang Daxiong , Luo Shilin
Published: January 2021

Polygonatum sibiricum, a well‐known life‐prolonging tonic in Chinese medicine, has been widely used for nourishing nerves in the orient, but the underlying molecular mechanisms remain unclear. In this study, we found that P. sibiricum polysaccharides (PSP) ameliorated 1‐methyl‐4‐phenyl‐1,2.3,6‐tetrahydropyridine‐ (MPTP‐) induced locomotor activity deficiency and dopaminergic neuronal loss in an in vivo Parkinson’s disease (PD) mouse model. Additionally, PSP pretreatment inhibited N‐methyl‐4‐phenylpyridine (MPP+) induced the production of reactive oxygen species, increasing the ratio of reduced glutathione/oxidized glutathione. In vitro experiments showed that PSP promoted the proliferation of N2a cells in a dose‐dependent manner, while exhibiting effects against oxidative stress and neuronal apoptosis elicited by MPP+. These effects were found to be associated with the activation of Akt/mTOR‐mediated p70S6K and 4E‐BP1 signaling pathways, as well as nuclear factor erythroid 2‐related factor 2‐ (Nrf2‐) mediated NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase‐1 (HO‐1), glutamate‐cysteine ligase catalytic subunit (Gclc), and glutamate‐cysteine ligase modulatory subunit (Gclm), resulting in antiapoptotic and antioxidative effects. Meanwhile, PSP exhibited no chronic toxicity in C57BJ/6 mice. Together, our results suggest that PSP can serve as a promising therapeutic candidate with neuroprotective properties in preventing PD.
A Novel Self-Tuning Fuzzy Logic-Based PID Controllers for Two-Axis Gimbal Stabilization in a Missile Seeker
Authors: Senthil Kumar S. , Anitha G.
Published: January 2021

Tracking a target is an essential function of a seeker for missiles. The target tracking mechanism of a seeker consists of gimbals, mounted with gyroscopes, and an antenna or some other energy receiving devices such as radar, infrared (IR), or laser. Stabilization of such a gimbal is necessary for any guided missile to maintain the tracking device always pointing towards the target. For the stabilization of the gimbal system, several control methods have been employed for making the gimbal to follow an input rate command by eliminating all the gimbal disturbances. Here, a new self-tuning fuzzy logic-based proportional, integral, derivative (PID) controller is introduced for the stabilization of a two-axis gimbal for a manoeuvring guided missile. The proposed control method involves tuning the gains of the PID controller based on the fuzzy logic rule bases considering the missile body rotation. The performance of the stabilization loops has been verified through MATLAB simulations for fuzzy logic-based PID controller compared with the conventional PID controller. The simulation results show the response of the gimbal system with stabilization loops met the control requirements with fuzzy PID controllers but not with conventional PID controllers.
Roles of the BAP1 Tumor Suppressor in Cell Metabolism
Authors: Han Anna , Purwin Timothy J. , Aplin Andrew E.
Published: January 2021

BRCA1-associated protein 1 (BAP1) is emerging as an intensively studied cancer-associated gene. Germline mutations in BAP1 lead to a cancer syndrome, and somatic loss is found in several cancer types. BAP1 encodes a deubiquitinase enzyme, which plays key roles in cell-cycle regulation, cell death, and differentiation. Recent studies have demonstrated that BAP1 is also involved in several aspects of cellular metabolism, including metabolic homeostasis, glucose utilization, control of ferroptosis, and stress response. A better knowledge of the metabolic roles of cancer-associated genes is important to understanding tumor initiation and progression, as well as highlighting potential therapeutic avenues. With this review, we summarize the current knowledge regarding BAP1-mediated regulation of metabolic activities that may support new strategies to treat BAP1-mutated cancers.
Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score ≥10
Authors: Wainberg Zev A. , Fuchs Charles S. , Tabernero Josep , Shitara Kohei , Muro Kei , Van Cutsem Eric , Bang Yung-Jue , Chung Hyun Cheol , Yamaguchi Kensei , Varga Eniko , Chen Jen-Shi , Hochhauser Daniel , Thuss-Patience Peter , Al-Batran Salah-Eddin , Garrido Marcelo , Kher Uma , Shih Chie-Schin , Shah Sukrut , Bhagia Pooja , Chao Joseph
Published: January 2021

Purpose:

Pembrolizumab demonstrated efficacy in PD-L1–positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (G/GEJ) cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively. To better delineate the specificity of CPS as a predictor of clinical outcomes, we analyzed pembrolizumab efficacy in patients with CPS ≥ 10 in these trials.

Patients and Methods:

Included were patients with CPS ≥ 10 tumors from KEYNOTE-059 cohort 1 (pembrolizumab, n = 46; post hoc), KEYNOTE-061 (pembrolizumab, n = 53; chemotherapy, n = 55; post hoc), and KEYNOTE-062 (pembrolizumab, n = 92; chemotherapy, n = 90; primary). Efficacy outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).

Results:

In KEYNOTE-059, median follow-up was 6 months, median OS was 8 months [95% confidence interval (CI), 5.8–11.1], ORR was 17%, and median (range) DOR was 21 months (3+ to 35+). In KEYNOTE-061, median follow-up was 9 months, median OS (pembrolizumab vs. chemotherapy) was 10 versus 8 months (HR, 0.64; 95% CI, 0.41–1.02), median PFS was 3 months versus 3 months (HR, 0.86; 95% CI, 0.56–1.33), ORR was 25% versus 9%, and median (range) DOR was not reached (4 to 26+ months) versus 7 months (3–7). In KEYNOTE-062, median follow-up was 11 months, median OS (pembrolizumab vs. chemotherapy) was 17 months versus 11 months (HR, 0.69; 95% CI, 0.49–0.97), median PFS was 3 months versus 6 months (HR, 1.09, 95% CI; 0.79–1.49), ORR was 25% versus 38%, and median (range) DOR was 19 months (1+ to 34+) versus 7 months (2+ to 30+).

Conclusions:

This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS ≥ 10 G/GEJ cancer.
A Case Report of Pediatric Geniculate Neuralgia Treated with Sectioning of the Nervus Intermedius and Microvascular Decompression of Cranial Nerves IX and X
Authors: Zenonos Georgios , McDowell Michael M. , Abou-Al-Shaar Hussam , Alkhalili Kenan , Gardner Paul A.
Published: January 2021

Background: Classic geniculate neuralgia (GN) is a rare condition characterized by lancinating pain centered in the ear and not involving the throat. To the best of our knowledge, no case of pediatric GN has been reported in the English literature. Case Presentation: We present the first reported case of successfully treated GN in a child via an endoscopic approach. The patient was a 9-year-old boy who presented with a 1-year history of lancinating right ear pain. Neuroleptics resulted in a short-lived improvement in symptoms, but with significant side effects. Extensive evaluation by multiple specialties did not reveal a cause for his pain. Imaging disclosed a tortuous loop of the right posterior inferior cerebellar artery abutting cranial nerves IX and X but no other abnormalities. The patient underwent an endoscopic microvascular decompression of cranial nerves IX and X, and sectioning of the nervus intermedius through a right retromastoid craniotomy. Postoperatively, the patient reported complete resolution of his symptoms that persisted at 3 months of follow-up. At the 5-year follow-up, the patient maintained pain relief and was developing normally. Conclusion: GN can affect the pediatric population. In carefully selected patients with consistent clinical and radiographic presentation, sectioning of the nervus intermedius and microvascular decompression of the lower cranial nerves can be an effective treatment.
Impact of Previous Genetic Counseling and Objective Numeracy on Accurate Interpretation of a Pharmacogenetics Test Report
Authors: Drelles Kelly , Pilarski Robert , Manickam Kandamurugu , Shoben Abigail B. , Toland Amanda Ewart
Published: January 2021

Introduction: Pharmacogenetic (PGx) testing can be useful for providing information about a patient’s drug response by increasing drug efficacy and decreasing the incidence of adverse drug events. While PGx tests were previously only offered to patients under healthcare provider supervision, they are now available as direct to consumer (DTC) tests. This study aimed to assess how accurately individuals from the general population were able to interpret a sample PGx test report and if accuracy differed based on individuals’ numeracy or prior genetic counseling (GC). Methods: We surveyed 293 individuals from the general population, ascertained through ResearchMatch. The survey included questions about PGx test interpretation, numeracy, and genetic literacy. Results: In our cohort, numeracy level impacted PGx result interpretation, with those of high numeracy performing statistically significantly better on both the table format and graphical format (p value = 0.002 and p value <0.001, respectively) and genetic knowledge questions (p value <0.001) than those with low/average numeracy. In addition, previous GC did not impact test interpretation or genetic knowledge, but the number of individuals with prior GC was small (n = 26). Discussion/Conclusion: We found that numeracy had a significant impact on correct interpretation of PGx test reports. Because many individuals in the USA have low numeracy levels, it is extremely important that patients do not make their own medication management decision based on the test results and that they consult with their physicians about their PGx testing. The importance of consultation and discussion with providers about results should be emphasized on the test report.
Coagulation under Mild Hypothermia Assessed by Thromboelastometry
Authors: Nitschke Tobias , Groene Philipp , Acevedo Alice-Christin , Kammerer Tobias , Schäfer Simon T.
Published: January 2021

Introduction: While previous studies have shown a significant impact of extreme hypo- and hyperthermia on coagulation, effects of much more frequently occurring perioperative mild hypothermia are largely unknown. This study therefore aimed to analyze the effects of mild hypothermia using rotational thromboelastometry in vitro. Materials and Methods: Twelve healthy volunteers were included in this study. Standard thromboelastometric tests (EXTEM, INTEM, FIBTEM) were used to evaluate coagulation in vitro at 39, 37, 35.5, 35, and 33°C. Beyond standard thromboelastometric tests, we also evaluated the effects of mild hypothermia on the TPA-test (ClotPro, Enicor GmbH, Munich, Germany), a new test which aims to detect fibrinolytic capacity by adding tissue plasminogen activator to the sample. Data are presented as the median with 25/75th percentiles. Results: Extrinsically activated coagulation (measured by EXTEM) showed a significant increase in clot formation time (CFT; 37°C: 90 s [81/105] vs. 35°C: 109 s [99/126]; p = 0.0002), while maximum clot firmness (MCF) was not significantly reduced. Intrinsically activated coagulation (measured by INTEM) also showed a significant increase in CFT (37°C: 80 s [72/88] vs. 35°C: 94 s [86/109]; p = 0.0002) without significant effects on MCF. Mild hypothermia significantly increased both the lysis onset time (136 s [132/151; 37°C] vs. 162 s [141/228; 35°C], p = 0.0223) and lysis time (208 s [184/297; 37°C] vs. 249 s [215/358; 35°C]; p = 0.0259). Conclusion: This demonstrates that even under mild hypothermia coagulation is significantly altered in vitro. Perioperative temperature monitoring and management are greatly important and can help to prevent mild hypothermia and its adverse effects. Further investigation and in vivo testing of coagulation under mild hypothermia is needed.
Diversity of Diptera species associated with pig carcasses in a Brazilian city exposed to high rates of homicide
Authors: Cruz Tadeu Morais , Barbosa Taciano Moura , Thyssen Patrícia Jacqueline , Vasconcelos Simão Dias
Published: January 2021

Cities in northeastern Brazil experience extreme rates of unsolved homicides, a situation that stimulates innovative procedures in the police work, such as forensic entomology. We surveyed necrophagous insects associated with carrion in a city exposed to high rates of homicides in Northeastern Brazil. The experiments were carried out in a rainforest fragment located in Recife, State of Pernambuco. Two pig carcasses were used as models, one in the dry and the other in the rainy season. The collection of adults was performed daily until the complete skeletonization of the carcasses. At least 32 Diptera species from the families Calliphoridae, Muscidae, Sarcophagidae, Fanniidae, Phoridae, Anthomyiidae, Piophilidae, and Stratiomyidae were registered, some of which have been previously documented on cadavers. A high richness of Diptera species was registered in all stages of decomposition. A strong overlap in the occurrence of most species was observed, which invalidates a defined entomological succession on the carcasses. Two species stood out in terms of abundance: Ophyra chalcogaster (Muscidae) and Chrysomya albiceps (Calliphoridae). The ubiquity of Hemilucilia semidiaphana (Calliphoridae) seems to confirm its preference for forest fragments exposed to low anthropogenic action. Our data contribute to expand the knowledge on the geographical distribution of forensically relevant species in the region and confirm the rapid dissemination of invasive Chrysomya species in forested areas.
Reliability of heart rate variability in futsal players
Authors: Paludo Ana Carolina , Peçanha Tiago , Rabelo Felipe N. , Bartels Rhenan , Fecchio Rafael Y. , Simões Antonio Carlos , Nakamura Fábio Y.
Published: January 2021

The main aim the present study was evaluated the reliability of the heart rate variability (HRV) indices in futsal players. Additionally the study verifi ed the reliability of different approaches for 5 min interval selection of recording. Eighteen under-20 futsal players underwent 15 min of pre-training RR interval recordings in two different day. Time and frequency domain and Poincaré Plot indices were tested. The indices were calculated using: 1) fi nal 5 min of recording; 2) 5 min of lower variance of recording, by a mathematical algorithm; 3) 5 min segment of lower variance, by an experienced operator. The HRV indices presented a wide range reliability [e.g. RRmean (ICC=0.96, SEM=3.4ms, CV=2.6%), lnRMSSD (ICC=0.88, SEM=5.9ms, CV=4.3%), lnHF (ICC=0.89, SEM=7.5ms, CV=5.9%), LFnu (ICC=0.84, SEM=13ms, CV=9.4%), LF (ICC=0.47, SEM=65.2ms,CV=38.5%) and LF/HF (ICC=0.63, SEM=83.7ms, CV=54.5%)]. The fi nal 5 min of recording was the most reliable. The results suggest that most of HRV indices presented acceptable reliability, however the RRmean, lnRMSSD, lnHF and LFnu were the most reliable.
Imprescindíveis e silenciados: desvalorização dos professores e destituição da participação nas decisões políticas
Authors: Costa Áurea de Carvalho , Rodrigues Robson da Silva
Published: January 2021

Este texto analisa a destituição do direito à participação dos professores nas deliberações políticas educacionais, agravada na conjuntura da pandemia, indagando se se trata de uma dimensão da desvalorização do professor na condição de trabalhador assalariado, tendo como ponto de partida a contradição: ao mesmo tempo em que sofrem prescrições e controle sobre o trabalho e destituição da participação deliberativa, os professores, na conjuntura atual, revelam-se imprescindíveis. Buscamos discutir as dimensões econômica, social e política da retórica da valorização do professor, o que, na realidade, se impõe como controle, destituição de direitos e, enfim, desvalorização.
E17241 as a Novel ABCA1 (ATP-Binding Cassette Transporter A1) Upregulator Ameliorates Atherosclerosis in Mice
Authors: Xu Yanni , Liu Chang , Han Xiaowan , Jia Xiaojian , Li Yongzhen , Liu Chao , Li Ni , Liu Lunming , Liu Peng , Jiang Xinhai , Wang Weizhi , Wang Xiao , Li Yining , Chen Mingzhu , Luo Jinque , Zuo Xuan , Han Jiangxue , Wang Li , Du Yu , Xu Yang , Jiang Jian-Dong , Hong Bin , Si Shuyi
Published: January 2021

Objective:

Reverse cholesterol transport, removing excess cholesterol from peripheral tissues, is an important therapeutic target for atherosclerosis treatment. In this study, we propose a new small molecule, E17241, that may be used to treat atherosclerosis by promoting reverse cholesterol transport via ABCA1 (ATP-binding cassette transporter A1) upregulation.

Approach and Results:

E17241 (4-(1,3-dithiolan-2-yl)-N-(3-hydroxypyridin-2-yl)benzamide) was first identified as an ABCA1 upregulator using a cell-based reporter assay. E17241 significantly increases the mRNA and protein expression levels of ABCA1 in both hepatic cells and macrophages. It promotes cholesterol efflux to apo AI in macrophage cells, and this effect depends on ABCA1. It also decreases total cholesterol content in Ox-LDL (oxidized low-density lipoprotein) loading macrophage cells. E17241 treatment increases the content of
3
H-labeled cholesterol in the feces of male C57BL/6J mice intraperitoneally injected with
3
H-cholesterol-labeled macrophage J774 cells, indicating that it could promote in vivo macrophage reverse cholesterol transport. Compared with the western diet group (western diet–fed male ApoE
−/−
mice), the E17241 group (western diet+E17241 treatment) shows decreased plasma cholesterol, liver cholesterol, and triglyceride levels, with increased fecal cholesterol content. Importantly, E17241 reduces atherosclerotic lesion areas in the en face aorta and aortic sinus while increasing ABCA1 protein levels in both liver and macrophages. Human proteome microarray, coimmunoprecipitation, and other assays demonstrate that PKCζ (protein kinase C zeta) is a binding target of E17241, and this small molecule increases ABCA1 expression in macrophages via the PKCζ-NR (nuclear receptor) pathway.

Conclusions:

E17241 may be developed as a new lead or drug candidate for the treatment of atherosclerosis by upregulating ABCA1.
Aortic Regurgitation Is Associated With Ascending Aortic Remodeling in the Nondilated Aorta
Authors: Balint Brittany , Federspiel Jan M. , Schwab Tanja , Ehrlich Tristan , Ramsthaler Frank , Schäfers Hans-Joachim
Published: January 2021

Objective:

The probability of aortic complications in patients with bicuspid aortic valve is higher in association with aortic regurgitation (AR) compared with aortic stenosis (AS) or normally functioning valves. The objective of this study was to determine whether this is related to the specific characteristics of aneurysmatic dilatation that includes AR or whether AR itself has a negative impact on the aortic wall, independent of aneurysmatic dilatation.

Approach and Results:

Nondilated aortic specimens were harvested intraoperatively from individuals with tricuspid aortic valves and either AS (n=10) or AR (n=16). For controls, nondilated aortas were harvested during autopsies from individuals with tricuspid aortic valves and no evidence of aortic valve disease (n=10). Histological and immunohistochemical analyses revealed that compared with control aortas, overall medial degeneration was more severe in AR-aortas (
P
=0.005) but not AS-aortas (
P
=0.23). This pathological remodeling included mucoid extracellular matrix accumulation (
P
=0.005), elastin loss (
P
=0.003), elastin fragmentation (
P
=0.008), and decreased expression of fibrillin (
P
=0.003) and collagen (
P
=0.008). Furthermore, eNOS (endothelial nitric oxide synthase) expression was decreased in the intima (
P
=0.0008) and in vasa vasorum (
P
=0.004) of AR-aortas but not AS-aortas (all
P
>0.05). Likewise, subendothelial apoptosis was increased in AR-aortas (
P
=0.03) but not AS-aortas (
P
=0.50).

Conclusions:

AR has a negative effect on the nondilated ascending aortic wall. Accordingly, our results support the need for more detailed studies of the aortic wall in relation to aortic valve disease and may ultimately lead to more aggressive clinical monitoring and/or surgical criteria for patients with relevant AR.

Graphic Abstract:

A graphic abstract is available for this article.
Time Delay, Infarct Size, and Microvascular Obstruction After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction
Authors: Redfors Björn , Mohebi Reza , Giustino Gennaro , Chen Shmuel , Selker Harry P. , Thiele Holger , Patel Manesh R. , Udelson James E. , Ohman E. Magnus , Eitel Ingo , Granger Christopher B. , Maehara Akiko , Ali Ziad A. , Ben-Yehuda Ori , Stone Gregg W.
Published: January 2021

Background:

Symptom-to-balloon time (SBT) and door-to-balloon time (DBT) are both considered important metrics in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment–elevation myocardial infarction (STEMI). We sought to assess the relationship of SBT and DBT with infarct size and microvascular obstruction (MVO) after pPCI.

Methods:

Individual patient data for 3115 ST-segment–elevation myocardial infarction patients undergoing pPCI in 10 randomized trials were pooled. Infarct size (% left ventricular mass) was assessed within 1 month after randomization by technetium-99 m sestamibi single-photon emission computerized tomography (3 studies) or cardiac magnetic resonance imaging (7 studies). MVO was assessed by cardiac magnetic resonance. Patients were stratified by short (≤2 hours), intermediate (2–4 hours), or long (>4 hours) SBTs, and by short (≤45 minutes), intermediate (45–90 minutes), or long (>90 minutes) DBTs.

Results:

Median [interquartile range] SBT and DBT were 185 [130–269] and 46 [28–83] minutes, respectively. Median [interquartile range] time to infarct size assessment after pPCI was 5 [3–12] days. There was a stepwise increase in infarct size according to SBT category (adjusted difference, 2.0% [95% CI, 0.4–3.5] for intermediate versus short SBT and 4.4% [95% CI, 2.7–6.1] for long versus short SBT) but not according to DBT category (adjusted difference, 0.4% [95% CI, −1.2 to 1.9] for intermediate versus short DBT and −0.1% [95% CI, −1.0 to 3.0] for long versus short SBT). MVO was greater in patients with long versus short SBT (adjusted difference, 0.9% [95% CI, 0.3–1.4]) but was not different between patients with intermediate versus short SBT (adjusted difference, 0.1 [95% CI, −0.4 to 0.6]). There was no difference in MVO according to DBT. Results were similar in multivariable analysis with SBT and DBT included as continuous variables.

Conclusions:

Among 3115 patients with ST-segment–elevation myocardial infarction undergoing infarct size assessment after pPCI, SBT was more strongly correlated with infarct size and MVO than DBT.