bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile One-Pot Preparation of 5-Substituted 4-Iodo-1-tosylpyrazoles from N-Propargyl-N′-tosylhydrazines through Iodocyclization
Authors: Togo Hideo , Saito Aya , Yoshida Kazuhiro
Published: March 2022

Treatment of N-propargyl-N′-tosylhydrazines with molecular iodine (I2) in the presence of NaHCO3 under warming conditions gave efficiently the corresponding 5-substituted 4-iodo-1-tosylpyrazoles in good to moderate yields. In addition, the same reaction in the presence of acetic acid generated the corresponding 5-aryl-4-iodopyrazoles in moderate yields. The reactions are simple and efficient transition-metal-free methods for the preparation of 5-substituted 4-iodo­pyrazole unit.
“Catheter-Locking Device-Assisted” External Ventricular Drain Placement: A New Surgical Technique Preventing Intracranial Drain Displacement—Technical Note with Preliminary Single-Center Results
Authors: Scafa Anthony Kevin , Jiang Tingting , Piccirilli Manolo
Published: March 2022

Background External ventricular drain (EVD) placement is frequently performed in neurosurgical patients to divert cerebrospinal fluid (CSF) and monitor intracranial pressure. The traditional practice is the tunneled EVD technique performed in the operating room. EVD insertion through a bolt in intensive care units has also been reported. We describe here the usage of a novel technique, the “catheter-locking device-assisted” EVD placement, reporting our preliminary, observational single-center results.

Methods From January to October 2021, 15 patients underwent a “catheter-locking device-assisted” EVD placement at our institute. For each of these patients, the following data were evaluated: (1) demographics, (2) etiology, (3) clinical presentation, (4) EVD complications, and (5) final clinical outcomes.

Results Median age of our population was 64 years, with a female/male ratio of 2:1. Average Glasgow Coma Scale score on admission was 8. Each patient maintained the drainage for an average time of 14 days. None of the patients suffered from postoperative intracerebral hemorrhage, CSF leakage, catheter migration, or discontinuation of the drainage system; none developed signs of infection. Nine patients required a permanent CSF diversion system. Outcome was good in 14 patients. One patient died for the underlying disease.

Conclusions The “catheter-locking device-assisted” EVD placement appears to be a safe and accurate alternative to both the standard tunneled and the bolt-assisted EVD insertion techniques. The use of this procedure may significantly reduce the incidence of the commonest EVD complications, though further investigation is required.
Multi-center decomposition of molecular densities: A mathematical perspective
Authors: Benda Robert , Cancès Eric , Ehrlacher Virginie , Stamm Benjamin
Published: March 2022

The aim of this article is to analyze from a mathematical perspective some existing schemes to partition a molecular density into several atomic contributions with a specific focus on Iterative Stockholder Atom (ISA) methods. We provide a unified mathematical framework to describe the latter family of methods and propose a new scheme, named L-ISA (for linear approximation of ISA), which generalizes the so-called additive variational Hirshfeld method. We prove several important mathematical properties of the ISA and L-ISA minimization problems and show that the so-called ISA algorithms can be viewed as alternating minimization schemes, which, in turn, enables us to obtain new convergence results for these numerical methods. Specific mathematical properties of the ISA decomposition for diatomic systems are also presented. Numerical results on diatomic systems illustrate the proven mathematical properties.
Determination of site occupancy of boron in 6H–SiC by multiple-wavelength neutron holography
Authors: Hayashi Kouichi , Lederer Maximilian , Fukumoto Yohei , Goto Masashi , Yamamoto Yuta , Happo Naohisa , Harada Masahide , Inamura Yasuhiro , Oikawa Kenichi , Ohoyama Kenji , Wellmann Peter
Published: March 2022

The local structure around boron doped in 6H-type silicon carbide (SiC) was investigated using neutron holography. Three-dimensional atomic images reconstructed from multiple-wavelength holograms revealed the boron substitution for both silicon and carbon. To determine boron locations accurately, we calculated holograms with varying occupancies of six different sites and fit image intensities with those obtained from experimental holograms by the steepest descent method. As a result, it was found that boron atoms were selectively located at the Si–C-cubic site layer. Furthermore, boundaries right above the boron locations were suggested from the absence of atomic images in the upper region of reconstruction.
Natural range separation of the Coulomb hole
Authors: Via-Nadal Mireia , Rodríguez-Mayorga Mauricio , Ramos-Cordoba Eloy , Matito Eduard
Published: March 2022

A natural range separation of the Coulomb hole into two components, one of them being predominant at long interelectronic separations (hcI) and the other at short distances (hcII), is exhaustively analyzed throughout various examples that put forward the most relevant features of this approach and how they can be used to develop efficient ways to capture electron correlation. We show that hcI, which only depends on the first-order reduced density matrix, can be used to identify molecules with a predominant nondynamic correlation regime and differentiate between two types of nondynamic correlation, types A and B. Through the asymptotic properties of the hole components, we explain how hcI can retrieve the long-range part of electron correlation. We perform an exhaustive analysis of the hydrogen molecule in a minimal basis set, dissecting the hole contributions into spin components. We also analyze the simplest molecule presenting a dispersion interaction and how hcII helps identify it. The study of several atoms in different spin states reveals that the Coulomb hole components distinguish correlation regimes that are not apparent from the entire hole. The results of this work hold out the promise to aid in developing new electronic structure methods that efficiently capture electron correlation.
Electric readout of Bloch sphere spanned by twisted magnon modes
Authors: Yuan Shaohua , Sui Chaowei , Kang Jiyong , Jia Chenglong
Published: March 2022

We present a magnonic type of Bloch sphere based on twisted spin-wave (magnon) eigenmodes with opposite intrinsic orbital angular momentum, which is topology-protected and damping-resistant. Taking advantage of the release of the chiral degeneracy of magnons by dynamic dipolar interactions and/or interfacial Dzyaloshinskii–Moriya interactions in ferromagnetic nanodisks, we show how these magnonic “qubit” states can be precisely launched and electrically detected through combined spin pumping and inverse spin Hall effect. The experimental feasibility is verified using full-edged numerical micromagnetic simulations for FeB nanodisks. Our investigations demonstrate the potential of twisted spin waves for magnonic information encoding in a flexible and realizable approach.
Memristor compact model with oxygen vacancy concentrations as state variables
Authors: Zeumault Andre , Alam Shamiul , Omar Faruk Md , Aziz Ahmedullah
Published: March 2022

We present a unique compact model for oxide memristors based upon the concentration of oxygen vacancies as state variables. In this model, the increase (decrease) in oxygen vacancy concentration is similar in effect to the reduction (expansion) of the tunnel gap used as a state variable in existing compact models, providing a mechanism for the electronic current to increase (decrease) based upon the polarity of the applied voltage. Rate equations defining the dynamics of state variables are obtained from simplifications of a recent paper in which electronic processes (i.e., electron capture/emission) were combined with atomic processes (i.e., Frenkel-pair generation/recombination, diffusion) stemming from the thermochemical model of dielectric breakdown. Central to the proposed model is the effect of the electron occupancy of oxygen vacancy traps on resistive switching dynamics. The electronic current is calculated considering Ohmic, band-to-band, and bound-to-band contributions. The model includes uniform self-heating with Joule heating and conductive loss terms. The model is calibrated using experimental current–voltage characteristics for HfO2 memristors with different electrode materials. Though a general model is presented, a delta-shaped density of states profile for oxygen vacancies is found capable of accurately representing experimental data while providing a minimal description of bound-to-band transitions. The model is implemented in Verilog-A and tested using read/write operations in a 4×4 1T1R nonvolatile memory array to evaluate its ability to perform circuit simulations of practical interest. A particular benefit is that the model does not make strong assumptions regarding filament geometry of which scant experimental-evidence exists to support.
Large rotating magnetocaloric effect of textured polycrystalline HoB2 alloy contributed by anisotropic ferromagnetic susceptibility
Authors: Zhou Xiaoyu , Shang Yafen , Luo Tian , Peng Yifeng , Fu Hao
Published: March 2022

A large rotating magnetocaloric effect (RMCE) was always observed in the materials with anisotropic magnetisms, for example, ferromagnetism vs antiferromagnetism or paramagnetism, at different crystallographic directions. In this work, anisotropic ferromagnetic susceptibility is utilized to implement low-field (≤2 T) large RMCE in the textured polycrystalline HoB2 alloy. The x-ray diffraction and scanning electron microstructure results reveal that the arc-melted HoB2 exhibits preferred grain orientation along the solidification direction. The measured rotating magnetic entropy changes (−ΔSR) and refrigeration capacity are 6.27 J/kg K and 73.7 J/kg, respectively, under the magnetic field change of 1 T. They are comparable with those of other materials contributed by anisotropic magnetisms. Our results suggest that the polycrystal HoB2 alloy is a promising material for practical application of magnetic refrigeration based on RMCE.
Soil salinity indicators and salinity build-up on saline water irrigation in seed spices
Authors: Chandel Sumita , Datta Ashim , Yadav R. K.
Published: March 2022

Context Soil salinity is a major constraint in crop production in arid and semiarid regions where saline water is the main irrigation source affecting soil quality and crop productivity. Aims A pot experiment was conducted to study the impact of alternate application of saline water (electrical conductivity (EC): 6.0 dS m−1) and fresh water on soil salinity indicators and salinity build-up under four seed spices (Anethum graveolens L., Nigella sativa L., Pimpinella anisum L. and Trachyspermum ammi L.). Methods Soil samples were collected from a pot experiment (0–15 cm depth) conducted at ICAR-Central Soil Salinity Research Institute, Karnal, Haryana, and analysed for different physicochemical properties (pH and EC), cationic (Ca2+, Mg2+, Na+ and K+) and anionic (CO32−, HCO3−, Cl−, SO42−) concentration and their contribution to salinity build-up in soil. Key results Soil EC varied between 0.45 and 8.27 dS m−1 (EC1:2) and between 1.20 and 24.90 dS m−1 (ECe) irrespective of the seed spice species. The application of saline water in the early stages of growth followed by fresh-water irrigation resulted in a comparatively low ECe, and cation and anion concentrations over continuous saline-water irrigation irrespective of the seed spice crop. ECe, sodium adsorption ratio, potassium and pHs are the important indicators identified by principal component analysis and better explained soil salinity under this situation. Conclusions Keeping these in view, there is a need for cyclic use of saline and fresh water in growing seed spice crops to prevent soil degradation. Study recommends that these four seed spice crops should be irrigated with fresh water during crop establishment and flowering stage, whereas, in between, saline water can be applied. Implications Such management of saline water irrigation could help to reduce salinity and maintain soil health for sustaining crop productivity, specifically for seed spices, in arid and semiarid regions.
Emergent elastic fields induced by topological phase transitions: Impact of molecular chirality and steric anisotropy
Authors: Takae Kyohei , Kawasaki Takeshi
Published: March 2022

Significance

Chirality, the property of an object that cannot be superimposed on its mirror image, plays an essential role in condensed matter, such as magnetic, electronic, and liquid crystal systems. Topological phases emerge in such chiral materials, wherein helical and vortex-like structures—called skyrmions—are observed. However, the role of elastic fields in these topological phases remains unexplored. Here, we construct a molecular model of two-dimensional crystals incorporating steric anisotropy and chiral interactions to elucidate this problem. The coupling between the elastic fields and phase transitions between uniform, helical, and half-skyrmion phases can be utilized to switch these topological phases by external forces. Our results provide a fundamental physical principle for designing topological materials using chiral molecular and colloidal crystals.
Let-7 underlies metformin-induced inhibition of hepatic glucose production
Authors: Xie Di , Chen Fan , Zhang Yuanyuan , Shi Bei , Song Jiahui , Chaudhari Kiran , Yang Shao-Hua , Zhang Gary J. , Sun Xiaoli , Taylor Hugh S. , Li Da , Huang Yingqun
Published: March 2022

Significance

A clear mechanistic understanding of metformin’s antidiabetic effects is lacking. This is because suprapharmacological concentrations of metformin have been used in most studies. Using mouse models and human primary hepatocytes, we show that metformin, at clinically relevant doses, suppresses hepatic glucose production by activating a conserved regulatory pathway encompassing let-7, TET3, and a fetal isoform of hepatocyte nuclear factor 4 alpha (HNF4α). We demonstrate that metformin no longer has potent antidiabetic actions in a liver-specific let-7 loss-of-function mouse model and that hepatic delivery of let-7 ameliorates hyperglycemia and improves glucose homeostasis. Our results thus reveal an important role of the hepatic let-7/TET3/HNF4α axis in mediating the therapeutic effects of metformin and suggest that targeting this axis may be a potential therapeutic for diabetes.
Nitrox surface discharge used for water activation: the reactive species and their correlation to the bactericidal effect
Authors: Wang Wei , Guo Li , Yao Zhiqian , Xi Wang , Zhao Yan , Lv Jianhua , Zhang Jishen , Liu Zhijie , Liu Dingxin
Published: March 2022

Plasma activated water (PAW) is a promising green antibacterial agent and the bactericidal effect is complicatedly affected by electron bombardment, ultraviolet radiation, interface reaction, and cascade chemical reaction. In this paper, a case of preparing PAW by treating aqueous solutions with afterglow gas is constructed based on surface micro-discharge (SMD), which focuses on the effect of afterglow gas–liquid mass transfer and liquid phase chemistry on PAW sterilization. The correlation of the bactericidal effect of PAW to the reactive species was studied based on the model of methicillin-resistant Staphylococcus aureus. The production of reactive oxygen and nitrogen species (RONS) in PAW with the regulation of N2/O2 ratios in the working gas for SMD. The RONS in both gas and liquid phases and the physicochemical properties of PAW were measured through optical and chemical methods. In addition, the effects of liquid types, liquid conductivity, and storage time on the bactericidal effects of PAW were explored. The key species for bacteria inactivation were identified by equivalent mixed solutions and specific scavengers. The results demonstrated that control of the N2/O2 ratios in the working gas can effectively improve the RONS in plasma and PAW. The bactericidal effect of PAW is correlated with peroxynitrite, superoxide anion, and their synergistic effects in an acidic liquid environment. This study provides a new strategy for insight into the bactericidal mechanism of PAW in biomedical applications.
Measurement algorithm of notch length of plastic parts based on video
Authors: Tao Jiancheng , Wei Haikun , Zhang Kanjian
Published: March 2022

A method for measuring the notch length of plastic parts without stopping the machine in real-time industrial environment is proposed, which can be used to measure the notch length on the assembly line. A camera is used for capturing the live images of plastic images being moving straightly. Firstly, invalid frames, clear and blurred keyframes are preprocessed respectively. Then, for the processed keyframes, the corner extraction algorithm based on contours are used to obtain all corner points and pixel length of notch. Finally, the actual length is calculated by setting constraints on positional parameters. When tested in industrial environment, our algorithm can extract the corner points and calculate the notch length accurately and quickly. The average error of corner extraction is about 0.4%, and the measurement error of notch length is less than 1%. Compared with other methods, the algorithm has the advantages of speed and accuracy in dealing with rectangular plastic notches.
Influence of magnetic property of test plates on magneto-rheological behavior
Authors: Zhang Yanan , Jiang Jile , Wen Gang , Ouyang Chuke , Meng Yonggang , Jia Wenpeng , Tian Yu
Published: March 2022

This paper investigated the behaviors of magnetorheological fluids (MRFs) under shear mode with magnetic iron and non-magnetic titanium upper plates, respectively. Based on the Stribeck curve and friction coefficient normalization methods, the lubrication states at the chain end/plate contacts were more at a boundary lubrication state. The restriction of magnetic plate on the particles ends migrations under high magnetic field enhanced the field induced friction to increase the yield stress. Therefore magnetic plate prevented sliding of particles with plate and resulted in a higher yield stress than the easier sliding of particle chains ends on non-magnetic plate. The magnetic property of the upper test plate should be properly considered during the tests of MRFs to derive accurate description of the properties of MRF to be used in the design of various MR actuators.
Tunable second harmonic generation by an all-dielectric diffractive metasurface embedded in liquid crystals
Authors: Rocco Davide , Zilli Attilio , Ferraro Antonio , Borne Adrien , Vinel Vincent , Leo Giuseppe , Lemaître Aristide , Zucchetti Carlo , Celebrano Michele , Caputo Roberto , De Angelis Costantino , Finazzi Marco
Published: March 2022

We experimentally demonstrate the possibility to modulate the second harmonic (SH) power emitted by nonlinear AlGaAs metasurfaces embedded in a liquid crystal (LC) matrix. This result is obtained by changing the relative in-plane orientation between the LC director and the linear polarization of the light at the excitation wavelength. According to numerical simulations, second-harmonic is efficiently radiated by the metasurfaces thanks to the sizeable second-order susceptibility of the material and the resonant excitation of either electric or magnetic dipole field distributions inside each meta-atom at the illuminating fundamental wavelength. This resonant behavior strongly depends on the geometric parameters, the crystallographic orientation, and the anisotropy of the metasurface, which can be optimized to modulate the emitted SH power by about one order of magnitude. The devised hybrid platforms are therefore appealing in view of enabling the electrical control of flat nonlinear optical devices.
Parallel flow driven by electron cyclotron heating in the helically symmetric experiment
Authors: Yamamoto Y. , Murakami S. , Chang C.C. , Kumar S.T.A. , Talmadge J.N. , Likin K.M. , Anderson D.T.
Published: March 2022

Spontaneous plasma flows have been observed in electron cyclotron heating (ECH) plasmas in the helically symmetric experiment. A smaller parallel flow was observed in the quasi-helically symmetric configuration compared with that observed in the Mirror configuration, although the mirror configuration has a larger neoclassical viscosity. Using the GNET code, we evaluate the electromagnetic and collisional forces induced by ECH. We also evaluate the parallel flow driven by the ECH force, by solving the momentum balance equations and Ampère law. The obtained flows show reasonable agreement with results obtained from experiments. This work indicates that the radial electron current generated by ECH could drive the parallel flow.
Evolutionary history of secondary sexual characters in the most species-rich genus of anurans, the direct-developing frogs of the genusPristimantis(Anura: Strabomantidae)
Authors: García-Gómez Isabella , Pereyra Martín O , Cabra-García Jimmy , Ospina-Sarria Jhon Jairo
Published: March 2022

Ancestral character-state reconstruction is a powerful method in phylogenetics that can be applied to elucidate the evolutionary history of secondary sexual characters. Here, we surveyed the variation and reconstructed the ancestral states of secondary sexual characters (i.e. sexual dichromatism, vocal slits and nuptial pads) for the most species-rich genus of anurans (Pristimantis) using maximum parsimony, maximum-likelihood and Bayesian methods. This study demonstrates that at least five independent transformation series account for the occurrence of sexual dichromatism in Pristimantis: dorsum, throat, venter, groin and posterior surface of thighs. The ancestral reconstructions suggest that the most recent common ancestor of Pristimantis lacks sexual dichromatism on these five body areas. Likewise, the occurrence of vocal slits and the absence of nuptial pads were inferred as ancestral conditions. Morphological synapomorphies were identified for Yunganastes and two infrageneric units within Pristimantis (the Pristimantis devillei and Pristimantis unistrigatus species groups). Our results demonstrate that the evolutionary history of the secondary sexual characters in Pristimantis followed a rather complex pattern of multiple independent gains and losses for which this genus is a promising model to investigate the evolution of secondary sexual characters in the context of the complex interactions between natural and sexual selection.
Numerical modelling of passive electroseismic surveying
Authors: Zyserman F I , Monachesi L B , Thompson A H , D’Biassi T , Jouniaux L , Gauzellino P
Published: March 2022

This work reports numerical modelling of electroseismic conversions when the electric field source originates in the atmosphere. Layered structures of conductivity anomalies yield rotated electric fields at reservoir depths as large as source fields at the surface. Active-source electroseismic field tests imaged reservoirs 1800 m deep. However, the required high-power, dipole sources mediate against these methods finding practical application in hydrocarbon exploration. We extend previous research by considering the potential for using environmental electric fields to create useful electroseismic conversions. World-wide lightning strikes induce time-dependent electric fields in the atmosphere. In the frequency band appropriate for seismic surveying, 1–100 Hz, electromagnetic field pulses occur at a rate of 10–100 pulses per second. These pulses create horizontal electric fields in the earth’s surface that induce electric currents in the subsoil. Those currents preferentially channel through high-conductivity layers. Charge accumulates at the termini of conducting layers. That charge accumulation induces galvanic currents. Vertical galvanic currents propagate to depth where they generate propagating seismic waves at gradients in electrical properties, such as conductivity gradients at reservoirs. We use 2-D numerical simulations on three different, layered-earth models to estimate the seismic amplitudes generated by passive fields. The modelling shows that the transverse magnetic fields can induce potentially useful vertical electric fields at depth. The generated seismic amplitudes at the top of the reservoir are sensitive to the oil content of the reservoir, the frequency of the primary electric field, the geometry of the conducting layers and various material properties. Finally, a hypothetical laterally complex reservoir configuration was tested which confirms the mentioned results and additionally shows the ability of the proposed method to delineate water–oil contacts.
The minimum information required for a glycomics experiment (MIRAGE): reporting guidelines for capillary electrophoresis
Authors: Lageveen-Kammeijer Guinevere S M , Rapp Erdmann , Chang Deborah , Rudd Pauline M , Kettner Carsten , Zaia Joseph
Published: March 2022

The Minimum Information Required for a Glycomics Experiment (MIRAGE) is an initiative to standardize the reporting of glycoanalytical methods and to assess their reproducibility. To date, the MIRAGE Commission has published several reporting guidelines that describe what information should be provided for sample preparation methods, mass spectrometry methods, liquid chromatography analysis, exoglycosidase digestions, glycan microarray methods, and nuclear magnetic resonance methods. Here, we present the first version of reporting guidelines for glyco(proteo)mics analysis by capillary electrophoresis (CE) for standardized and high-quality reporting of experimental conditions in the scientific literature. The guidelines cover all aspects of a glyco(proteo)mics CE experiment including sample preparation, CE operation mode (CZE, CGE, CEC, MEKC, cIEF, cITP), instrument configuration, capillary separation conditions, detection, data analysis, and experimental descriptors. These guidelines are linked to other MIRAGE guidelines and are freely available through the project website https://www.beilstein-institut.de/en/projects/mirage/guidelines/#ce_analysis (doi:10.3762/mirage.7).
Non-linear behaviour of warped discs around a central object with a quadrupole moment
Authors: Deng Hongping , Ogilvie Gordon I
Published: March 2022

The non-linear behaviour of low-viscosity warped discs is poorly understood. We verified a non-linear bending-wave theory, in which fluid columns undergo affine transformations, with direct 3D hydrodynamical simulations. We employed a second-order Godunov-type scheme, meshless finite mass (MFM), and also the smoothed particle hydrodynamics (SPH) method, with up to 128 million particles. For moderate non-linearity, MFM maintains well the steady non-linear warp predicted by the affine model for a tilted inviscid disc around a central object with a quadrupole moment. However, numerical dissipation in SPH is so severe that even a low-amplitude non-linear warp degrades at a resolution where MFM performs well. A low-amplitude arbitrary warp tends to evolve towards a non-linear steady state. However, no such state exists in our thin disc with an angular semithickness H/R = 0.02 when the outer tilt angle is beyond about 14°. The warp breaks tenuously and reconnects in adiabatic simulations, or breaks into distinct annuli in isothermal simulations. The breaking radius lies close to the location with the most extreme non-linear deformation. Parametric instability is captured only in our highest resolution simulation, leading to ring structures that may serve as incubators for planets around binaries.
Notes on a vanishing cosmological constant without Bose–Fermi cancellation
Authors: Satoh Yuji , Sugawara Yuji
Published: March 2022

We discuss how one can systematically construct point particle theories that realize the vanishing one-loop cosmological constant without Bose–Fermi cancellation. Our construction is based on the asymmetric (or non-geometric) orbifolds of supersymmetric string vacua. Using the building blocks of their partition functions and their modular properties, we construct theories which would be naturally identified with certain point particle theories including infinite mass spectra, but not with string vacua. They are obviously non-supersymmetric due to the mismatch of the bosonic and fermionic degrees of freedom at each mass level. Nevertheless, it is found that the one-loop cosmological constant vanishes, after removing the parameter effectively playing the role of the UV cut-off. As concrete examples we demonstrate the construction of models based on toroidal asymmetric orbifolds with Lie algebra lattices (Englert–Neveu lattices) by making use of the analysis given in Satoh and Sugawara (2017)
Effectiveness of Transdermal Buprenorphine for Pain Control in the ICU After Major Surgical Procedures
Authors: Patanwala Asad E. , Moran Benjamin , Johnstone Charlotte , Koelzow Heike , Penm Jonathan
Published: March 2022

OBJECTIVES:

Transdermal buprenorphine (TBUP) may be useful for postoperative pain after major surgery, when pain is expected to be severe and sustained. The objective of this study was to compare pain control and opioid consumption in critically ill postoperative patients who were treated with TBUP or not during ICU admission.

DESIGN:

This was a retrospective, parallel, cohort study.

SETTING:

ICU of a quaternary, urban hospital in Sydney, Australia.

PATIENTS:

Data were obtained for all patients admitted to the ICU from January 2019 to July 2021 after major gastrointestinal (GI) or genitourinary (GU) surgery.

INTERVENTIONS:

TBUP or non-TBUP.

MEASUREMENTS AND MAIN RESULTS:

Pain control was compared between patients who received TBUP and those who did not receive TBUP. The primary outcome was the probability of significant pain. A significant pain score was defined as greater than or equal to 4 on the 0–10 numeric rating scale or greater than or equal to 6 on the behavioral pain scale. Inverse probability of treatment weighting was used to adjust for baseline differences. The cohort included 376 patients, with 224 (60%) in the control group and 152 (40%) in the TBUP group. The mean age was 60 ± 14 years, 202 (54%) were male, mean Acute Physiology and Chronic Health Evaluation III score was 44 ± 13, and 147 (39%) received mechanical ventilation. After adjustment, the median probability of significant pain was 0.25 with control and 0.30 with TBUP (median difference, 0.02; 95% CI, 0.04–0.11; p = 0.44). The median opioid consumption (oral morphine milligram equivalents) per day was 5.7 mg with control and 10.1 mg with TBUP (median difference, 0.4 mg; 95% CI, –0.4 to 3.7 mg; p = 0.31).

CONCLUSIONS:

In patients who are admitted to the ICU after major GI or GU procedures, the use of TBUP in the ICU was not associated with improved pain control or opioid consumption compared with those who did not receive TBUP.
Assessing the Quality, Reliability, and Readability of Online Information on Dry Eye Disease
Authors: Oydanich Marko , Kuklinski Eric , Asbell Penny A.
Published: March 2022

Purpose:

The purpose of this study was to assess the quality, reliability, readability, and technical quality of web sites relating to dry eye disease.

Methods:

A cross-sectional study was conducted that evaluated the first 75 web sites on a Google Search by using the keyword “dry eyes.” Each web site was evaluated by 2 independent reviewers using the DISCERN, HONcode, and JAMA criteria to assess quality and reliability. Interrater reliability was also analyzed. Readability was assessed using the Flesch–Kincaid readability tests and the Gunning fog, Simple Measure of Gobbledygook, Coleman–Liau, and automated readability indices. Technical quality was determined by the presence of 10 specific features. Web sites were further categorized into institutional (academic centers, medical associations, and government institutions) and private (private practices) categories.

Results:

There was no significant difference in scoring observed between the 2 reviewers. The overall mean DISCERN score ± standard error (SE) was 3.2 ± 0.1, the mean HONcode score (±SE) was 9.3 ± 0.3, and the mean JAMA score (±SE) was 1.9 ± 0.1. Institutional web sites had a higher DISCERN score (3.4 ± 0.1 vs. 3.1 ± 0.1; P < 0.05) and HONcode score (10.3 ± 0.5 vs. 8.8 ± 0.4; P < 0.05) than private sites. Technical quality was higher in institutional web sites compared with private web sites (P < 0.05). Readability was poor among all web sites, with most web sites not achieving below a ninth grade reading level.

Conclusions:

Quality, reliability, and readability scores were low for most web sites. Although institutional web sites achieved higher scores than private web sites, revision is warranted to improve their overall quality of information and readability profile.
Using a real-time ABCDEF compliance tool to understand the role of bundle elements in mortality and delirium
Authors: Shampo Jackson C. , Wenszell Kenneth , Luo-Owen Xian , Mukherjee Natalie , Cochran-Yu Meghan , Swentek Lourdes , Burruss Sigrid K. , Markovich Susan , Turay David , Dorotta Ihab R. , Mukherjee Kaushik
Published: March 2022

BACKGROUND

ABC-123, a novel Epic electronic medical record real-time score, assigns 0 to 3 points per bundle element to assess ABCDEF bundle compliance. We sought to determine if maximum daily ABC-123 score (ABC-MAX), individual bundle elements, and mobility were associated with mortality and delirium-free/coma-free intensive care unit (DF/CF-ICU) days in critically injured patients.

METHODS

We reviewed 6 months of single-center data (demographics, Injury Severity Score [ISS], Abbreviated Injury Scale of the head [AIS-Head] score, ventilator and restraint use, Richmond Agitation Sedation Score, Confusion Assessment Method for the ICU, ABC-MAX, ABC-123 subscores, and mobility level). Hospital mortality and likelihood of DF/CF-ICU days were endpoints for logistic regression with ISS, AIS-Head, surgery, penetrating trauma, sex, age, restraint and ventilator use, ABC-MAX or individual ABC-123 subscores, and mobility level or a binary variable representing any improvement in mobility during admission.

RESULTS

We reviewed 172 patients (69.8% male; 16.3% penetrating; median age, 50.0 years [IQR, 32.0–64.8 years]; ISS, 17.0 [11.0–26.0]; AIS-Head, 2.0 [0.0–3.0]). Of all patients, 66.9% had delirium, 48.8% were restrained, 51.7% were ventilated, and 11.0% died. Age, ISS, AIS-Head, and penetrating mechanism were associated with increased mortality. Restraints were associated with more than 70% reduction in odds of DF/CF-ICU days. Maximum daily ABC-123 score and mobility level were associated with decreased odds of death and increased odds of DF/CF-ICU days. Any improvement in mobility during hospitalization was associated with an 83% reduction in mortality odds. A and C subscores were associated with increased mortality, and A was also associated with decreased DF/CF-ICU days. B and D subscores were associated with increased DF/CF-ICU days. D and E subscores were associated with decreased mortality.

CONCLUSION

Maximum daily ABC-123 score is associated with reduced mortality and delirium in critically injured patients, while mobility is associated with dramatic reduction in mortality. B and D subscores have the strongest positive effects on both mortality and delirium.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Engineering a Vaccine Platform using Rotavirus A to Express SARS-CoV-2 Spike Epitopes
Authors: Diebold Ola , Gonzalez Victoria , Venditti Luca , Sharp Colin , Blake Rosemary A. , Stevens Joanne , Caddy Sarah , Digard Paul , Borodavka Alexander , Gaunt Eleanor
Published: March 2022

Human rotavirus (RV) vaccines used worldwide have been developed using live attenuated platforms. The recent development of a reverse genetics system for RVs has delivered the possibility of engineering chimeric viruses expressing heterologous peptides from other virus species to generate polyvalent vaccines. We tested the feasibility of this using two approaches. Firstly, we inserted short SARS-CoV-2 spike peptides into the hypervariable region of the simian SA11 RV strain viral protein (VP) 4. Secondly, we fused the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, or the shorter receptor binding motif (RBM) nested within the RBD, to the C-terminus of non-structural protein (NSP) 3 of the bovine RF strain RV, with or without an intervening T2A peptide. Mutating the hypervariable region of SA11 VP4 impeded viral replication, and for these mutants no cross-reactivity with spike antibodies was detected. To rescue NSP3 mutants, we established a plasmid-based reverse genetics system for the bovine RF strain. Except for the RBD mutant, all NSP3 mutants delivered endpoint titres and replication kinetics comparable to that of the WT virus. In ELISAs, cell lysates of an NSP3 mutant expressing the RBD peptide showed cross reactivity with a SARS-CoV-2 RBD antibody. 3D bovine gut enteroids were susceptible to infection by all NSP3 mutants but only RBM mutant showed cross reactivity with SARS-CoV-2 RBD antibody. The tolerability of large peptide insertions in the NSP3 segment highlights the potential for this approach in the development of vaccine vectors targeting multiple enteric pathogens simultaneously.

IMPORTANCE

We explored the use of rotaviruses (RVs) to express heterologous peptides, using SARS-CoV-2 as an exemplar. Small SARS-CoV-2 peptide insertion (<34 amino acids) into the hypervariable region of the viral protein 4 (VP4) of RV SA11 strain resulted in reduced viral titre and replication, thus limiting its use as a potential vaccine expression platform. To test RF strain for its tolerance for peptide insertions, we constructed a reverse genetics system. NSP3 was C-terminally tagged with SARS-CoV-2 spike peptides of up to 193 amino acids. With a T2A-separated 193 amino acid tag on NSP3, there was little effect on the viral rescue efficiency, titre and replication. Tagged NSP3 elicited cross-reactivity with SARS-CoV-2 spike antibodies in ELISA. This is the first report describing epitope tagging of VP4, and of a reverse genetics system for the RF strain. We highlight the potential for development of RV vaccine vectors targeting multiple enteric pathogens simultaneously.
Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis
Authors: Persson Karl , Stenberg Simon , Tamás Markus J. , Warringer Jonas
Published: March 2022

Adaptive evolution of clonally dividing cells and microbes is the ultimate cause of cancer and infectious diseases. The possibility of constraining the adaptation of cell populations, by inhibiting proteins that enhance their evolvability has therefore attracted substantial interest. However, our current understanding of how individual genes influence the speed of adaptation is limited, partly because accurately tracking adaptation for many experimental cell populations in parallel is challenging. Here we use a high throughput artificial laboratory evolution (ALE) platform to track the adaptation of >18.000 cell populations corresponding to single gene deletion strains in the haploid yeast deletion collection. We report that the fitness of gene knockout near-perfectly (R2=0.91) predicts their adaptation dynamics under arsenic exposure, leaving virtually no role for dedicated evolvability functions in the corresponding proteins. We tracked the adaptation of another >23.000 yeast gene knockout populations to a diverse range of selection pressures and generalised the almost perfect (R2=0.72 to 0.98) capacity of initial fitness to predict the rate of adaptation. Finally, we reconstruct mutations in the genes FPS1, ASK10, and ARR3, which together account for almost all arsenic adaptation in wildtype cells, in gene deletions covering a broad fitness range. We show that the predictability of arsenic adaptation can be understood almost entirely as a global epistasis phenomenon where excluding arsenic from cells, through these mutations, is more beneficial in cells with low arsenic fitness regardless of what causes the arsenic defects. The lack of genes with a meaningful effect on the adaptation dynamics of clonally reproducing cell populations diminishes the prospects of developing adjuvant drugs aiming to slow antimicrobial and chemotherapy resistance.
Identifying transcription factor-bound activators and silencers in the chromatin accessible human genome using ATAC-STARR-seq
Authors: Hansen Tyler J. , Hodges Emily
Published: March 2022

Massively parallel reporter assays test the capacity of putative gene regulatory elements to drive transcription on a genome-wide scale. Most gene regulatory activity occurs within accessible chromatin, and recently described methods have combined assays that capture these regions—such as assay for transposase-accessible chromatin using sequencing (ATAC-seq)—with self-transcribing active regulatory region sequencing (STARR-seq) to selectively assay the regulatory potential of accessible DNA (ATAC-STARR-seq). Here, we report a multi-omic approach that quantifies regulatory activity, chromatin accessibility, and transcription factor (TF) occupancy with one assay using ATAC-STARR-seq. Our strategy, including important updates to the ATAC-STARR-seq assay design and workflow, enabled high-resolution testing of ∼50 million unique DNA fragments tiling ∼101,000 accessible chromatin regions in human lymphoblastoid cells. We discovered that 30% of all accessible regions contain an activator, a silencer or both. We demonstrate that activators and silencers represent distinct functional groups that are enriched for unique sets of TF motifs and are marked by specific combinations of histone modifications. Using Tn5 cut-sites retained by the ATAC-STARR library, we performed TF footprinting and stratified these groups by the presence of specific TF footprints that are supported by chromatin immunoprecipitation data. We found that activators and silencers clustered by distinct TF footprint combinations are enriched for distinct gene regulatory pathways, and thus, represent distinct gene regulatory networks of human lymphoblastoid cell function. Altogether, these data highlight the multi-faceted capabilities of ATAC-STARR-seq to comprehensively investigate the regulatory landscape of the human genome all from a single DNA fragment source.
Bone Morphogenetic Protein (BMP) signaling regulates germline stem cell self-renewal in the newly formed Drosophila testis stem cell niche
Authors: Best Merci N , Fidler Ashley , Jones Marieke K , Wawersik Matthew
Published: March 2022

Bone morphogenetic proteins (BMPs) are a group of multifunctional cytokines and metabologens highly conserved in the transforming growth factor-β (TGF-β) superfamily. BMPs have an established role in controlling cell fate and tissue morphogenesis in a diverse range of organisms and are known to maintain stem cells in adult Drosophila testes. Additional studies in embryonic and larval testes suggest BMP regulates germ cell behavior. However, the roles of BMP signaling in controlling testis stem cell formation have yet to be directly examined. Here, we explore the pattern of BMP activation during embryonic testis niche morphogenesis as well as niche maturation in larval testes. We also assess the impact of altered BMP signaling on these stages of development. Our data suggest that BMP signaling is critical for promoting germ cell identity in primordial germ cells during embryonic niche formation. During niche maturation, we also find that that BMP signaling is both necessary and sufficient for maintenance of a self- renewing germline stem cell (GSC) population, and that newly formed cyst stem cells (CySCs) are a source of BMP activating ligand. As development progresses, however, BMP activation is no longer sufficient to alter GSC self-renewal. Collectively, our work promotes a more thorough understanding of BMP as a key mechanism controlling stem cell development in Drosophila testes that has implications for the development of other organ systems.
Comparison of rule- and ordinary differential equation-based dynamic model of DARPP-32 signalling network
Authors: Wysocka Emilia M. , Page Matthew , Snowden James , Simpson T. Ian
Published: March 2022

Dynamic modelling has considerably improved our understanding of complex molecular mechanisms. Ordinary differential equations (ODEs) are the most detailed and popular approach to modelling the dynamics of molecular systems. However, their application in signalling networks, characterised by multi-state molecular complexes, can be prohibitive. Contemporary modelling methods, such as rule-based (RB) modelling, have addressed these issues. The advantages of RB modelling over ODEs have been presented and discussed in numerous reviews. In this study, we conduct a direct comparison of the time courses of a molecular system founded on the same reaction network but encoded in the two frameworks. To make such a comparison, a set of reactions that underlie an ODE model was manually encoded in the Kappa language, one of the RB implementations. A comparison of the models was performed at the level of model specification and results were acquired through model simulations. Conforming to previous reports, we confirm that the Kappa model recapitulated the general dynamics of its ODE counterpart with minor differences. These differences occur whenever molecules have multiple sites binding the same interactor. Furthermore, activation of these molecules in the RB model is slower than in the ODE one but can be corrected by revision of the rate constants used in the relevant rules. As in previous reports on other molecular systems, we find that, also in the case of the DARPP-32 reaction network, the RB representation offers a more expressive and flexible syntax that facilitates access to fine details of the model, facilitating model reuse. In parallel with these analyses, this manuscript reports a refactored model of the DARPP-32 interaction network that can serve as a canvas for the development of a more complex interaction network to study this important molecular system.
Environmental predictors of electroactive bacterioplankton in small boreal lakes
Authors: Olmsted Charles N. , Ort Roger , Tran Patricia Q. , McDaniel Elizabeth A. , Roden Eric E. , Bond Daniel R. , He Shaomei , McMahon Katherine D.
Published: March 2022

Extracellular electron transfer (EET) by electroactive bacteria in anoxic soils and sediments is an intensively researched subject, but EET’s function in planktonic ecology has been less considered. Following the discovery of an unexpectedly high prevalence of EET genes in a bog lake’s bacterioplankton, we hypothesized that the redox capacities of dissolved organic matter (DOM) enrich for electroactive bacteria by mediating redox chemistry. We developed the bioinformatics pipeline FEET (Find EET) to identify and summarize EET proteins from metagenomics data. We then applied FEET to several bog and thermokarst lakes and correlated EET protein occurrence values with environmental data to test our predictions. Our results provide evidence that DOM participates in EET by bacterioplankton. We found a similarly high prevalence of EET genes in most of these lakes, where oxidative EET strongly correlated with DOM. Numerous novel clusters of multiheme cytochromes that may enable EET were identified. Taxa previously not considered EET-capable were found to carry EET genes. We conclude that EET and DOM interactions are of major ecological importance to bacterioplankton in small boreal lakes, and that EET, particularly by methylotrophs and phototrophs, should be further studied and incorporated into both conceptual and quantitative methane emission models of melting permafrost.