bluuebunny/crossref_metadata_2025 huggingface dataset:
How to train a neural network potential
Authors: Tokita Alea Miako , Behler Jörg
Published: September 2023

The introduction of modern Machine Learning Potentials (MLPs) has led to a paradigm change in the development of potential energy surfaces for atomistic simulations. By providing efficient access to energies and forces, they allow us to perform large-scale simulations of extended systems, which are not directly accessible by demanding first-principles methods. In these simulations, MLPs can reach the accuracy of electronic structure calculations, provided that they have been properly trained and validated using a suitable set of reference data. Due to their highly flexible functional form, the construction of MLPs has to be done with great care. In this Tutorial, we describe the necessary key steps for training reliable MLPs, from data generation via training to final validation. The procedure, which is illustrated for the example of a high-dimensional neural network potential, is general and applicable to many types of MLPs.
Enhanced resistive switching characteristics of conductive bridging memory device by a Co–Cu alloy electrode
Authors: Lee Calvin Xiu Xian , Dananjaya Putu Andhita , Chee Mun Yin , Poh Han Yin , Tan Funan , Thong Jia Rui , Liu Lingli , Lim Gerard Joseph , Du Yuanmin , Tan Juan Boon , Lew Wen Siang
Published: September 2023

One of the main challenges in the development of conductive bridging random access memory (CBRAM) is the large stochastic nature of ion movement that ultimately leads to large parameter variability. In this study, the resistive switching variability of CBRAM devices is significantly improved by employing Co–Cu alloy as the active electrode. By comparing with Pt/Ta2O5/Co devices, the Co70Cu30 alloy exhibited lower forming voltage (<2 V), lower SET voltage (<0.70 V), and faster response time (∼70 ns). The filament stability indicated by the distribution of SET/RESET voltage and high resistance state/low resistance state variation was significantly improved. Our experimental results suggest the formation of Co filaments, and the proposed mechanism is governed by the galvanic effect. In addition, a comparison between Co70Cu30 and Co30Cu70 alloys highlights that the relative proportion between Co and Cu plays an essential role in the device performance. A physical model based on different electrochemical activities of the alloys has been proposed to explain the filament formation and the improved switching uniformity in the Co70Cu30 alloy. This study not only develops a CBRAM with enhanced performance but also advances the implementation of suitable alloy systems for the application of such devices.
Mid-wave infrared photoluminescence from low-temperature-grown PbSe epitaxial films on GaAs after rapid thermal annealing
Authors: Meyer Jarod E. , Nordin Leland , Nguyen Tri , Mukherjee Kunal
Published: September 2023

We investigate the beneficial effects of rapid thermal annealing on structure and photoluminescence of PbSe thin films on GaAs (001) grown below 150 °C, with a goal of low temperature integration for infrared optoelectronics. Thin films of PbSe deposited on GaAs by molecular beam epitaxy are epitaxial at these reduced growth temperatures, yet the films are highly defective with a mosaic grain structure with low angle and dendritic boundaries following coalescence. Remarkably, we find that rapid thermal annealing for as short as 180 s at temperatures between 300 and 425 °C in nitrogen ambient leads to extensive re-crystallization and transformation of these grain boundaries. The annealing at the same time dramatically improves the band edge luminescence at 3.7 μm from previously undetectable levels to nearly half as intense as our best conventionally grown PbSe films at 300 °C. We show using an analysis of laser pump-power dependent photoluminescence measurements that this dramatic improvement in the photoluminescence intensity is due to a reduction in the trap-assisted recombination. However, we find it much less correlated with improved structural parameters determined by x-ray diffraction rocking curves, thereby pointing to the importance of eliminating point defects over extended defects. Overall, the success of rapid thermal annealing in improving the luminescent properties of low growth temperature PbSe is a step toward the integration of PbSe infrared optoelectronics in low thermal budget, back end of line compatible fabrication processes.
Rotational energy transfer in the collision of N2O with He atom
Authors: Yang Hanwei , Liu Xinyang , Liu Yuqian , Xu Mohan , Li Zheng
Published: September 2023

The quantum state-to-state rotationally inelastic quenching of N2O by colliding with a He atom is studied on an ab initio potential energy surface with N2O lying on its vibrational ground state. The cross sections for collision energies from 10−6–100 cm−1 and rate constants from 10−5–10 K are calculated employing the fully converged quantum close-coupling method for the quenching of the j = 1–6 rotational states of N2O. Numerous van der Waals shapes or Feshbach resonances are observed; the cross sections of different channels are found to follow the Wigner scaling law in the cold threshold regime and may intersect with each other. In order to interpret the mechanism and estimate the cross sections of the rotational energy transfer, we propose a minimal classical model of collision between an asymmetric double-shell ellipsoid and a point particle. The classical model reproduces the quantum scattering results and points out the attractive interactions and the potential asymmetry can affect the collision process. The resulting insights are expected to expand our interpretations of inelastic scattering and energy transfer in molecular collisions.
High performance and low thermal conductivity in Bi2Se3 induced by the synergistic regulation of a resonant energy level and microstructure prepared by Se slow-release method
Authors: Liu Yaohui , Tang Yu , Tao Yonggui , Shen Lanxian , Ge Wen , Deng Shukang
Published: September 2023

In this study, Bi2Se3 thermoelectric materials with high density, low thermal conductivity, and excellent thermoelectric performance are prepared using a Se slow-release method. It was found that the number of Se defects in the material could be effectively reduced by changing the content of NaCl solvent, and a certain number of Na atoms are introduced into the Bi2Se3 matrix. The carrier concentration of Bi2Se3 is greatly optimized due to the synergistic effect of the two, leading to a gradual increase in the Seebeck coefficient from −94 to −122 μV K−1 at room temperature. Simultaneously, we conducted an in-depth investigation into the effects of Na doping and Se vacancies on the electronic structure of the materials. Our findings indicate that the presence of these two defects gives rise to resonance energy levels and sharpens the density of state peaks near the Fermi level. This discovery further underscores the potential for enhancing thermoelectric performance. Finally, the Bi2Se3(NaCl)10 sample achieved the maximum ZT value of 0.69 at 550 K, and the average ZT within the temperature detection range reached 0.36, increasing the thermoelectric performance of the material.
“
μ
s P-E curve” and reverse phase transition of antiferroelectric ceramics during ultra-fast charge–discharge
Authors: Xu Ran , Li Yingxuan , Qiao Feng , Zhang Lin , Chen Qin , Wang Yingche , Xu Zhuo , Feng Yujun , Wei Xiaoyong
Published: September 2023

Antiferroelectric materials hold great potential for energy storage applications. However, a significant challenge lies in the disparity ΔW between the rapid discharge energy density Wdis and the recoverable energy density Wre. Quantitative analysis is still lacking, and the ultra-fast reverse ferroelectric–antiferroelectric (FE–AFE) transition behavior at the microsecond scale remains unknown. In this study, a pulse technique was employed instead of the Sawyer–Tower method to obtain the “μs P-E loop” during rapid charge–discharge processes. The “μs P-E curve” clearly illustrates the distinct FE–AFE transition behavior during rapid discharge in comparison to low-frequency conditions. Under pulsed conditions, the FE–AFE transition field was observed to decrease, and even a “remanent polarization” was observed, leading to a reduction in discharge energy during fast discharge. Moreover, through the enhancement of relaxor behavior and the increased diffuseness of FE–AFE switching, the μs P-E loop tended to resemble that observed at low frequencies, thereby resulting in more efficient discharge performance. This study introduced a technique for investigating the ultra-fast FE–AFE transition. Furthermore, it unveiled the origin of ΔW and provided an effective method for achieving high discharge energy density.
Nonreciprocal genuine steering of three macroscopic samples in a spinning microwave magnonical system
Authors: Zhong Wenxue , Zheng Qianjun , Cheng Guangling , Chen Aixi
Published: September 2023

Here, we propose to generate the nonreciprocal macroscopic entanglement and steering of magnon modes from three yttrium iron garnet spheres, which are placed in a spinning microwave resonator damped by a squeezed reservoir. Strikingly, the genuine entanglement and steering among three magnons can be achieved due to the correlation transfer from squeezed microwave to three magnons and the steady-state entanglement and steering show strong robustness against temperature. Furthermore, the nonreciprocal tripartite entanglement and steering are simultaneously existent based on Fizeau light-dragging effect by spinning the resonator at the steady state, which provides an alternative way to manipulate nonreciprocal effects in a cavity magnonical system and may have potential applications in manipulating the macroscopic quantum states of the multipartite system.
Electron density-based protocol to recover the interacting quantum atoms components of intermolecular binding energy
Authors: Anisimov Aleksei A. , Ananyev Ivan V.
Published: September 2023

A new approach for obtaining interacting quantum atoms-defined components of binding energy of intermolecular interactions, which bypasses the use of standard six-dimensional integrals and two-particle reduced density matrix (2-RDM) reconstruction, is proposed. To examine this approach, three datasets calculated within the density functional theory framework using the def2-TZVP basis have been explored. The first two, containing 53 weakly bound bimolecular associates and 13 molecular clusters taken from the crystal, were used in protocol refinement, and the third one containing other 20 bimolecular and three cluster systems served as a validation reference. In addition, to verify the performance of the proposed approach on an exact 2-RDM, calculations within the coupled cluster formalism were performed for part of the first set systems using the cc-pVTZ basis set. The process of optimization of the proposed parametric model is considered, and the role of various energy contributions in the formation of non-covalent interactions is discussed with regard to the obtained trends.
Synthesis of high-crystalline ReS2 monolayers by sodium-assisted chemical vapor deposition
Authors: Yang Yunwei , Zhang Xiaodong , Du Zhengwei , Zhao Yibin , Liu Mingyan , Li You , Min Shaolong , Huang Chengxi , Zhan Cheng , Wu Fang , Zeng Hualing , Wan Yi , Kan Erjun
Published: September 2023

Featured with highly structural anisotropy, rhenium-based transition metal dichalcogenides (TMDs) and alloys have attracted significant attention in electronics, optoelectronics, energy storage, and catalysis. The controlled growth of large-area, high-quality anisotropic TMDs is critical for associated applications. However, the Jahn–Teller effect and Peierls distortion of the lattice easily induce out-of-plane growth, making it a challenge to prepare uniform-thickness Re-based TMDs. Here, we report a NaCl-assisted chemical vapor deposition strategy for Re-based TMDs and highlight the essential role of Na+ absorption based on a combination of experiments and density functional theory calculations. We found that Cl has little influence on the intermediate products during the reaction process, while Na is responsible for reducing the highest energy barrier required for the formation of Re–Re chains. The barrier for the rate-determining step is reduced by 0.325 eV compared to that without considering Na+ adsorption. Additionally, the field-effect transistor device based on the sodium-assisted synthesized ReS2 monolayer demonstrates superior electrical properties. Our findings not only provide a reliable experimental scheme for the preparation of Re-based semiconductors but also promote the application of ReS2 in high-performance electronics.
The CN(X 2Σ+) + C2H6 reaction: Dynamics study based on an analytical full-dimensional potential energy surface
Authors: Espinosa-Garcia Joaquin , Rangel Cipriano
Published: September 2023

The hydrogen abstraction reaction of the cyano radical with molecules of ethane presents some interesting points in the chemistry from ultra-cold to combustion environments especially with regard to HCN(v) product vibrational distribution. In order to understand its dynamics, a new analytical full-dimensional potential energy surface was developed, named PES-2023. It uses a combination of valence bond and mechanic molecular terms as the functional form, fitted to high-level ab initio calculations at the explicitly correlated CCSD(T)-F12/aug-cc-pVTZ level on a reduced and selected number of points describing the reactive process. The new surface showed a continuous and smooth behavior, describing reasonably the topology of the reaction: high exothermicity, low barrier, and presence of intermediate complexes in the entrance and exit channels. Using quasi-classical trajectory calculations (QCT) on the new PES-2023, a dynamics study was performed at room temperature with special emphasis on the HCN(v1,v2,v3) product stretching and bending vibrational excitations, and the results were compared with the experimental evidence, which presented discrepancies in the bending excitation. The available energy was mostly deposited as HCN(v) vibrational energy with the vibrational population inverted in the CH stretching mode and not inverted in the CN stretching and bending modes, thus simulating the experimental evidence. Other dynamics properties at room temperature were also analyzed; cold rotational energy distribution was found, associated with a linear and soft transition state, and backward scattering distribution was found, associated with a rebound mechanism.
Efficient photothermal therapy with spatially localized high-temperature generation by refractory absorber
Authors: Li Shuai , Tan Wenyong , Liu Xiaoshan , Liu Guiqiang , Wang Yan , Chen Jing , Tang Chaojun , Du Wei , Liu Zhengqi
Published: September 2023

In this work, we propose a titanium nitride (TiN)-based ultra-broadband perfect absorber from the ultraviolet to near-infrared wavelength ranges with the average absorptivity up to 96.7%. The weighted absorption efficiency of the solar radiation energy reaches 95.6%. In addition, photothermal therapy is conducted on such absorber, showing the effectively confined local high-temperature in the vicinity of the device. The steady-state temperature reaches 327 K at a depth of 3 mm beneath the tissue surface, leading to the efficient optical damage exceeding 90% for the surrounding diseased tissue only by a 3-min illumination. Such moderate photothermal therapy adequately meets the requirements for inactivating tumor cells and hold wide applications in the photo-biomedical science and technology.
Green synthesis of dual-spinneret electrospun polyacrylonitrile–ZnO@β-cyclodextrin–chitosan nanofibrous nanocomposite as a novel nano-biosorbent
Authors: Hajmohammadi Sohrab , Ghazanfari Dadkhoda , Sheikhhosseini Enayatollah , Rastakhiz Nahid , Asadollahzadeh Hamideh
Published: September 2023

A significant range of intriguing nanomaterials includes photocatalytic and antibacterial nanocomposites, which exhibit great efficacy in water treatment. In this work, Euphorbia hebecarpa extract was used as a novel natural reducing agent to investigate the environmentally friendly production of ZnO@β-cyclodextrin (CD) nanoparticles (NPs). In the following, polyacrylonitrile, ZnO@β-CD and chitosan nanofibers were electrospun concurrently using a dual-electrospinning process to create a unique nano-biosorbent made of polyacrylonitrile (PAN)–ZnO@β-CD–chitosan (CS) nanofibrous nanocomposite. Additionally, this nanocomposite’s effectiveness as a novel photocatalyst and antibacterial agent for eliminating organic dyes like methylene blue was evaluated. Field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD) analysis, Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy (RS) were used to analyze the structure of the nanocomposite. The outcomes verified the production of ZnO@β-CD, which had evenly shaped particles with an average size of 45 nm on the nanofibrous matrix. This nanocomposite exhibited removal efficiency of methylene blue of ~90% after 105 min at pH 7 and 2.5 g L−1 nanocomposite concentration. Furthermore, an antibacterial test revealed that PAN–ZnO@β-CD–CS nanofibrous nanocomposite with 6% ZnO showed over 80% reduction in colony-forming units per millilitre against Bacillus cereus, Staphylococcus epidermidis and Streptococcus iniae.
Bacterial SEAL domains undergo autoproteolysis and function in regulated intramembrane proteolysis
Authors: Brogan Anna P. , Habib Cameron , Hobbs Samuel J. , Kranzusch Philip J. , Rudner David Z.
Published: September 2023

Gram-positive bacteria use SigI/RsgI-family sigma factor/anti-sigma factor pairs to sense and respond to cell wall defects and plant polysaccharides. In
Bacillus subtilis,
this signal transduction pathway involves regulated intramembrane proteolysis (RIP) of the membrane-anchored anti-sigma factor RsgI. However, unlike most RIP signaling pathways, site-1 cleavage of RsgI on the extracytoplasmic side of the membrane is constitutive and the cleavage products remain stably associated, preventing intramembrane proteolysis. The regulated step in this pathway is their dissociation, which is hypothesized to involve mechanical force. Release of the ectodomain enables intramembrane cleavage by the RasP site-2 protease and activation of SigI. The constitutive site-1 protease has not been identified for any RsgI homolog. Here, we report that RsgI’s extracytoplasmic domain has structural and functional similarities to eukaryotic SEA domains that undergo autoproteolysis and have been implicated in mechanotransduction. We show that site-1 proteolysis in
B. subtilis
and Clostridial RsgI family members is mediated by enzyme-independent autoproteolysis of these SEA-like domains. Importantly, the site of proteolysis enables retention of the ectodomain through an undisrupted β-sheet that spans the two cleavage products. Autoproteolysis can be abrogated by relief of conformational strain in the scissile loop, in a mechanism analogous to eukaryotic SEA domains. Collectively, our data support the model that RsgI–SigI signaling is mediated by mechanotransduction in a manner that has striking parallels with eukaryotic mechanotransducive signaling pathways.
A passive ‘One Health’ surveillance system to track canine rabies in urban India
Authors: Vanak Abi Tamim , Panchamia Neha , Banerji Indrakshi , Nair Malvika
Published: September 2023

Robust and widely implementable ‘One Health’ surveillance systems are required to detect and control the spread of zoonotic infectious diseases. Using technological tools coupled with a rapid field response and rapid diagnostics can help in the surveillance of deadly diseases such as rabies, even in densely populated urban areas. Here, we describe the use of an animal rescue system (Hawk Data Pro) that was adapted as a passive surveillance tool for rabies in a large metropolis in India. We used a Webline and helpline that reported injured or sick animals to an animal rescue facility to determine possible rabies cases in street animals in Pune city in western India. Suspected rabid animals were tested using lateral flow assays and this information was used to direct awareness materials on rabies as well as in conducting mass dog vaccinations in areas that reported multiple cases. Over a ~4-year period, we received over 90,700 calls or reports, of which 1162 calls were for suspected rabies cases in dogs, and 6 for other animals (cats, goats and cattle). Of these, 749 dogs and 4 other animals tested positive for rabies. Most of the cases were reported from the densely human-populated central Pune region. In response, ~21,000 people were provided with educational materials on post-bite management, and ~23,000 dogs were vaccinated. We show that the adoption of the Hawk Data Pro system as a passive surveillance tool allowed us to document an ongoing outbreak of rabies in a large metropolis in India. Such systems can be modified or adapted to other areas as well to meet the surveillance and reporting requirements of the WHO’s Zeroby30 strategy to eliminate rabies globally.

One Health impact statement

India is a priority country for the action plan for rabies elimination by 2030. Yet, systematic surveillance for rabies in the primary reservoir remains weak. Here, we showcase a collaboration with an animal welfare organization and adaptation of their bespoke animal rescue system for passive surveillance of rabies in dogs and other animals in Pune city in western India. This method allowed us to improve the detection of potentially rabid animals, rapidly ensure post-exposure prophylaxis and provide awareness materials for exposed human victims. To the best of our knowledge, this collaboration between scientists and civil society organizations resulted in the detection of the largest number of rabies cases reported in an urban area anywhere in the world. The use of this system highlights the scope of the problem in urban India and also provides practical guidance on how to improve surveillance using basic technological tools.
IBM achieve quantum advantage without error correction
Authors: Boerkamp Martijn
Published: September 2023

An international team of researchers has used a 127-qubit quantum processor to calculate the magnetic properties of a model 2D material.
John Goodenough: battery pioneer dies aged 100
Authors: Banks Michael
Published: September 2023

The Nobel Prize-winning materials scientist John Goodenough, who pioneered the development of lithium-ion batteries, has died at the age of 100.
Researchers warn of computation’s carbon footprint
Authors: Allen Michael
Published: September 2023

Researchers at the University of Cambridge claim that those involved in computational science should take responsibility for reducing greenhouse-gas emissions.
Oak Ridge lab appoints Stephen Streiffer as director
Authors: Gwynne Peter
Published: September 2023

Stephen Streiffer of the SLAC National Accelerator Laboratory in California has been announced as the next director of the Oak Ridge National Laboratory in Tennessee.
All the fun of the fare
Authors: Randall Ian
Published: September 2023

Ian Randall reviews Taxi From Another Planet: Conversations with Drivers about Life in the Universe by Charles Cockell.
Computing quadratic points on modular curves 𝑋₀(𝑁)
Authors: Adžaga Nikola , Keller Timo , Michaud-Jacobs Philippe , Najman Filip , Ozman Ekin , Vukorepa Borna
Published: September 2023

In this paper we improve on existing methods to compute quadratic points on modular curves and apply them to successfully find all the quadratic points on all modular curves

X
0

(
N
)

X_0(N)

of genus up to

8
8

, and genus up to

10
10

with

N
N

prime, for which they were previously unknown. The values of

N
N

we consider are contained in the set

L

=
{
58
,
68
,
74
,
76
,
80
,
85
,
97
,
98
,
100
,
103
,
107
,
109
,
113
,
121
,
127
}
.

\begin{equation*} \mathcal {L}=\{58, 68, 74, 76, 80, 85, 97, 98, 100, 103, 107, 109, 113, 121, 127 \}. \end{equation*}

We obtain that all the non-cuspidal quadratic points on

X
0

(
N
)

X_0(N)

for

N
∈

L

N\in \mathcal {L}

are complex multiplication (CM) points, except for one pair of Galois conjugate points on

X
0

(
103
)

X_0(103)

defined over

Q

(

2885

)

\mathbb {Q}(\sqrt {2885})

. We also compute the

j
j

-invariants of the elliptic curves parametrised by these points, and for the CM points determine their geometric endomorphism rings.
Empowering African Girls?
Authors: Bellows-Blakely Sarah
Published: September 2023

In the 1980s and 1990s, actors from The African Women’s Development and Communication Network (FEMNET) and the United Nations Children’s Fund (UNICEF) created and internationalized frameworks for girl-focused economic policymaking. They successfully lobbied to include girl-centered programming in the 1995 UN World Conference on Women—the fourth and final event of its kind and one that cemented international norms for the linked UN movements for women’s rights and economic development. Yet this is not a tale of smooth circulation or easy alliances. Within the UNICEF-FEMNET network, ideas about girls and poverty were hotly contested; they did not couple seamlessly. As some frameworks internationalized, others disappeared. Combining histories of knowledge with intersectional and postcolonial methodologies shows how the creation of dominant policy frameworks has involved not only the diffusion of ideas but also their erasure. The article puts forth an alternative methodology that analyzes the interwoven processes of circulation and noncirculation, and of selective amplification and silencing, that have often driven the internationalization of knowledge and the writing of history.
Only CDT values knowledge
Authors: Nielsen Michael
Published: September 2023

Causal decision theory is often motivated as a ‘revision of [decision theory] intended to solve Newcomb’s problem’ (Bacon 2022). In this paper, I give a direct argument for CDT by deriving it from a venerable decision-theoretic principle: the value of knowledge principle. The general framework that I use to deliver this result also supports a new argument for conditionalization.
Reduced gray matter volume in the default-mode network associated with insulin resistance
Authors: Asano Saki , Ogawa Akitoshi , Osada Takahiro , Oka Satoshi , Nakajima Koji , Oshima Yasushi , Tanaka Sakae , Kaga Hideyoshi , Tamura Yoshifumi , Watada Hirotaka , Kawamori Ryuzo , Konishi Seiki
Published: September 2023

Insulin resistance may lead to structural and functional abnormalities of the human brain. However, the mechanism by which insulin resistance impairs the brain remains elusive. In this study, we used two large neuroimaging databases to investigate the brain regions where insulin resistance was associated with the gray matter volume and to examine the resting-state functional connectivity between these brain regions and each hypothalamic nucleus. Insulin resistance was associated with reduced gray matter volume in the regions of the default-mode and limbic networks in the cerebral cortex in older adults. Resting-state functional connectivity was prominent between these networks and the paraventricular nucleus of the hypothalamus, a hypothalamic interface connecting functionally with the cerebral cortex. Furthermore, we found a significant correlation in these networks between insulin resistance-related gray matter volume reduction and network paraventricular nucleus of the hypothalamus resting-state functional connectivity. These results suggest that insulin resistance-related gray matter volume reduction in the default-mode and limbic networks emerged through metabolic homeostasis mechanisms in the hypothalamus.
A-009 Analytical Concordance of High-Sensitivity Cardiac Troponin I and T Assays in Patients From the CONTRAST Trial Presenting to an Emergency Department
Authors: Gunsolus I L , Schulz K M , Sandoval Y , Smith S W , Apple F S
Published: September 2023

Background

There are limited data on the analytical concordance of high-sensitivity cardiac troponin (hs-cTn) T and hs-cTnI assays. The goal of this study was to evaluate the concordance of one hs-cTnT and one hs-cTnI assay relative to each assay’s limit of quantitation (LoQ) and 99th percentile upper reference limit (URL).

Methods

The Comparison of Troponin I and T Assays Trial (CONTRAST) NCT03214029 is an observational study that evaluated the concordance of two FDA-cleared hs-cTn assay concentrations measured at presentation (0 h) and 2 h by the Abbott ARCHITETCT i2000 hs-cTnI (clinically used assay) and Roche cobas 601 Gen 5 hs-cTnT (measured for investigational purposes) from consecutively enrolled patients presenting to an urban US medical center with symptoms suggestive of ischemia. Concordance at presentation (0 h) was assessed relative to each assay’s FDA-cleared reporting concentration (LoQ), and FDA-cleared sex-specific 99th percentile URLs. The incidence of myocardial injury, defined as at least one concentration above the 99th percentile URL over serial sampling, was also evaluated.

Results

At presentation hs-cTn concentrations <LoQs (Abbott 3.5 ng/L, Roche 6 ng/L) were 834/2270 (37%) and 530/2270 (23%), respectively. The concordance of results <LoQ was 81%. The Abbott assay showed a higher percent of concentrations below both female and male URLs than did the Roche assay. For females, concentrations below the sex-specific 99th percentile URLs were 707/945 (75%) for Abbott hs-cTnI (16 ng/L) and 545/945 (58%) for Roche hs-cTnT (14 ng/L, P < 0.03). For males, concentrations below the sex-specific 99th percentile URLs were 1100/1325 (83%) for Abbott hs-cTnI (34 ng/L) and 900/1325 (68%) for Roche hs-cTnT (22 ng/L). The concordance of results below the sex-specific 99th percentile URLs for both assays was 80%. Among males with presentation concentrations URL at 2 h) was approximately two-fold greater for the Roche hs-cTnT (59/900, 6.2%) than Abbott hs-cTnI (31/1110, 2.8%). Females with presentation concentrations <URL showed similar rates of myocardial injury at 2 h for the Roche (24/545 [4.4%]) and Abbott assays (36/707 [5.1%]).

Conclusion

We report a 20% discordance between Abbott hs-cTnI and Roche hs-cTnT assays in detecting myocardial injury at respective 99th percentile URLs and at each assays’ FDA allowed LoQ reporting limit.
A-013 Creation of a Commutable Cardiac Troponin I Reference Material Coined 8121 by the National Institute for Science and Technology and the IFCC Workgroup for Cardiac Troponin I Standardization
Authors: Christenson R H , Duh S , Payne R , Clapshaw S , Lowenthal M S
Published: September 2023

Background

Harmonizing cardiac troponin I (cTnI) is needed because this biomarker is central to defining cardiac injury, and is essential for diagnosis and management of myocardial infarction (MI) and other cardiac conditions. cTnI measurements have evolved through several generations; state-of-the-art assays are coined “high-sensitivity cTnI” tests. We describe development and availability of commutable Reference Material (RM)8121, designed and created by the National institute of Standards and Technology (NIST) and the IFCC workgroup for cTnI standardization for availability to stakeholders.

Methods

RM8121 is a lithium heparinized series of four Levels of increasing cTnI concentration coined Levels A (lowest) to D (highest). Each RM8121 concentration resulted from combining an elevated cTnI pool from sample collections from 58 MI patients with a blending pool comprised of low cTnI samples from 15 healthy females and 15 males, all <40-years old. All subjects donating collections were consented under an IRB-approved protocol at the University of Maryland. All enrolled subjects were confirmed negative for hepatitis A, B, C and HIV infection. Hemolyzed, lipemic and icteric samples were excluded from pooling. RM8121’s Levels A–D were homogenized, and 0.71 mL aliquots pipetted into 2-mL vials. hs-cTnI concentrations were measured at critical points throughout the recruitment, sample collection, blending and final aliquoting processes using the Atellica® IM TnIH assay (Siemens Healthineers).

Results

Approximately 3000 units of RM8121 are available. The table displays the hs-cTnI concentrations of the blending and high pools. Concentrations of RM8121 Levels A and B were designed to bracket the female and male 99th percentile URLs, with RM8121 Levels C and D in the range of 9-fold and 100-fold greater than the female 99th URL, respectively.

Conclusion

Values for FDA cleared hs-cTnI assays will be assigned for RM8121. Availability of this commutable cTnI RM is intended to assist in harmonizing current and future hs-cTnI assays.
A-046 Investigating the Role of RNase L in Metabolic Syndrome
Authors: Zame A A , Liu D , Zhou A
Published: September 2023

Background

Metabolic syndrome is closely associated with the incidence of heart disease, type 2 diabetes, and stroke. Though the exact cause of metabolic syndrome is not known, many features of the metabolic syndrome are caused by insulin resistance. Recent years, accumulating evidence has shown that dysregulation of insulin signaling leads to insulin resistance. Interestingly, we have observed that RNase L affects the insulin signaling pathway by regulating the activation of insulin receptor subtrate-1 (IRS-1) in primary mouse embryonic fibroblasts (MEFs) and primary mouse hepatocyte. RNase L is an enzyme that plays a critical role in interferon function against viral infection and cellular proliferation. How RNase L affects the insulin signaling pathway is still unknown.

Methods

Age-matched C57BL/6 background RNase L wild type (WT) and knockout (KO) mice (n = 6–8) were fed on a chow diet. Metabolic tolerance tests including glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted on mice between 12 and 16 weeks old. Mice were subjected to either a morning (4 h) or an overnight (12 h) fast, then intraperitoneally injected with glucose (1.5 g/kg body weight) in PBS, pH 7.4, for GTT and insulin (1.0I U/kg body weight) for ITT. Blood was collected via tail vein at different time intervals over a span of 2 h and blood glucose was measured using a glucometer.

Results

We found that RNase L KO mice displayed significantly increased glucose tolerance in compared to RNase L WT mice as measured in the intraperitoneal glucose tolerance test. The glucose level in RNase L KO mice was 150% higher than that in RNase L WT mice after IP injection of glucose in 60 min. In the ITT experiment, the glucose level in RNase L KO mice was 130% higher than that in WT mice in 60 min post injection. Taken together, the results in GTT and ITT indicated that RNase L mediates the metabolism of glucose in vivo. Further investigation of molecular mechanisms is currently being conducted.

Conclusion

Our results suggests that RNase L plays a role in insulin sensitivity, which affects glucose metabolism.
A-050 Understanding the Complex Relationship Between TSH and Free Thyroxine
Authors: Lee D J , Che Rahim N S , Aw T C
Published: September 2023

Background

Guidelines suggest screening for thyroid disease using thyroid stimulating hormone (TSH) first before free thyroxine (fT4) since there is an inverse log-linear relationship between them; the signal favors TSH over fT4 in a ratio of >100:2. We reassessed this fT4 to TSH relationship following the improved 3rd generation TSH assay from Roche (since 09/2019).

Methods

Consecutive paired TSH/fT4 (n = 7484) from distinct ambulatory non-hospitalized subjects that were assayed on cobas e801 were retrieved from our laboratory information system and combined with similar data from Kuala Lumpur Hospital (n = 11 369) that were assayed on cobas e601. Reference intervals and measuring limits for the Roche assays were 0.4–4.0 μIU/L and 0.005–100 μIU/L for TSH, and fT4 10–20 pmol/L and 0.3–100 pmol/L for fT4, respectively. Values outside the reportable limits (n = 618) were excluded. Descriptive statistics, linear and nonparametric (kernel) regression were performed using the statistical software packages in R 4.2.0.

Results

Linear regression of logTSH against fT4 (n = 18 235) gave an r = −0.35. Nonparametric regression revealed two negative sigmoid curves merging into the euthyroxinemic region (see Graph). Three different segments can be discerned; hypothyroxinemic (fT4 < 10): logTSH = 1.91–0.136fT4 (n = 422; r = −0.39, P < 0.001), euthyroxinemic (fT4 10–20): logTSH = 0.672–0.028fT4 (n = 15 754, r = −0.13, P < 0.001), and hyperthyroxinemic (fT4>20): logTSH = 1.106–0.055fT4 (n = 2059, r = −0.33, P < 0.001).

Conclusion

The relationship between fT4 and TSH is complex. The widely accepted view of a constant gradient of logTSH against fT4 over the whole range of thyroid test values is inaccurate. Three distinct relationships correspond to each biochemical thyroid status. In the hypothyroxinemic and hyperthyroxinemic range, TSH increases almost 5-fold and 13-fold with a doubling of fT4, respectively. In the euthyroxinemic range, there is no relationship between logTSH and fT4. While a TSH first strategy is applicable in hypo/hyperthyroxinemia, both TSH/fT4 are still required to confirm diagnoses and for baseline assessment prior to commencing therapy.
A-104 Clinical Validation of the VITROS® Immunodiagnostics Products B·R·A·H·M·S PCT Test Medical Decision Points and Prediction of Cumulative 28-Day All-Cause Mortality
Authors: Ogbonna G , Ajongwen P , Alvey S
Published: September 2023

Background

Procalcitonin (PCT) is a biomarker for systemic bacterial infection and sepsis and may be used to aid in decision-making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) and/or sepsis. Procalcitonin medical decision points have been established using the B·R·A·H·M·S PCT sensitive KRYPTOR assay. In this study, we compared the performance of the VITROS® Immunodiagnostic Products B·R·A·H·M·S PCT assay to the performance of the B·R·A·H·M·S PCT sensitive KRYPTOR assay at the established medical decision points. Percent change in PCT level over time can be used to aid in the prediction of cumulative 28-day mortality in patients diagnosed with severe sepsis and septic shock. The 28-day all-cause mortality prediction of the VITROS B·R·A·H·M·S PCT assay was also evaluated in the study.

Methods

Patient sample sets from the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) study conducted in 13 sites in the United States were used in this study. Blood samples were collected on Days 0, 1, 3 and 4 from subjects who were admitted to the ICU with severe sepsis or septic shock. Each patient’s vital status was verified at Day 28. The samples were tested on the VITROS B·R·A·H·M·S PCT assay and the B·R·A·H·M·S PCT sensitive KRYPTOR assay. Concordance analysis between the VITROS B·R·A·H·M·S PCT and the B·R·A·H·M·S PCT sensitive KRYPTOR assays was performed at the established clinical decision points of 0.100 ng/mL, 0.250 ng/mL, 0.500 ng/mL, 2.00 ng/mL and 10.0 ng/mL to determine overall agreement between the two assays. For prediction of cumulative 28-day all-cause mortality using the VITROS B·R·A·H·M·S PCT assay results, the change in PCT values (Δ PCT) from Day 0 to Day 4 and Day 1 to Day 4 was calculated and evaluated against 28-day-all-cause mortality.

Results

Overall agreements of 98.5%, 98.0%, 97.4%, 97.8% and 98.0% were observed at 0.100 ng/mL, 0.250 ng/mL, 0.500 ng/mL, 2.00 ng/mL and 10.0 ng/mL, respectively, with the B·R·A·H·M·S PCT sensitive KRYPTOR assay. Δ PCT decline >80% or ≤80% was significantly associated with 28-day-all-cause mortality (P = 0.006). Univariate Cox proportional hazards regression analysis showed a 1.93-fold increase in risk for mortality in subjects with a Δ PCT change ≤80%.

Conclusion

The VITROS B·R·A·H·M·S PCT assay demonstrated excellent agreement with the B·R·A·H·M·S PCT sensitive KRYPTOR assay at medical decision points used to aid in decision-making on antibiotic therapy for patients with suspected or confirmed LRTI and/or sepsis. Clinical performance shows ΔPCT information can be used to classify patients diagnosed with severe sepsis or septic shock as lower and higher risk for cumulative 28-day all-cause mortality.
A-105 Analytical Performance Evaluation of Four General Chemistry Assays on the Atellica CI 1900 Analyzer Used to Assess Kidney Function
Authors: Lewisch S , Tyler C , Kolewe K , Arrode-Bruses G , Rhea-McManus J , Snyder J
Published: September 2023

Background

The Atellica® CI 1900 Analyzer is an automated, mid-throughput, integrated chemistry and immunoassay analyzer utilizing both Atellica CH and Atellica IM assays. This study was designed to evaluate the analytical performance of the Atellica CH Creatinine (CREA_2)*, Enzymatic Creatinine (ECre_3)*, Urinary/Cerebrospinal Fluid Protein (UCFP)*, and Microalbumin_2 (µALB_2)* assays on the Atellica CI 1900 Analyzer*.

Methods

The Atellica CI 1900 CH CREA_2, ECre_3, UCFP, and µALB_2 assays use the same reagents and calibrators as the Atellica CH assays. Precision and method comparison (MC) were used as performance indicators for the Atellica CI 1900 Analyzer. Precision studies were performed according to CLSI EP05-A3 using native and contrived human urine samples. One aliquot of each sample pool was tested in duplicate in two runs per day >2 h apart on each analyzer for >20 days. MC studies were performed according to CLSI EP09-A3. Individual native and contrived human urine samples were analyzed using the Atellica CH assays on both the Atellica CH and Atellica CI 1900 Analyzers.

Results

Representative precision and MC results observed from one reagent lot across indicated sample ranges are listed for each assay in the table below. Over the four assays tested, repeatability and within-lab %CVs were <5.1% and <6.0%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusion

Evaluation of the Atellica CH CREA_2, ECre_3, UCFP, and µALB_2 assays using the Atellica CI 1900 Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica CH Analyzer.

*The products/features mentioned here are not commercially available in all countries. Their future availability cannot be guaranteed.
A-130 Analytical Performance Evaluation of Assays Measuring Acetaminophen and Ethanol on the Atellica CI 1900 Analyzer
Authors: Freeman J , Morjana N , Singh S , Arrode-Bruses G , Rhea-McManus J , Snyder J
Published: September 2023

Background

The Atellica® CI 1900 Analyzer is an automated, mid-throughput, integrated chemistry and immunoassay analyzer employing both Atellica CH and Atellica IM assays. This study was designed to evaluate the analytical performance of the Atellica CH Ethyl Alcohol (ETOH) and Acetaminophen (Acet) assays on the Atellica CI 1900 Analyzer.

Methods

The Atellica CI 1900 ETOH and Acet assays use the same reagents and calibrators as the comparable Atellica CH assays. Precision and method comparison (MC) were used as performance indicators for the Atellica CI 1900 Analyzer. Precision studies were performed according to CLSI EP05-A3. Native and contrived human serum samples were used. One aliquot of each sample pool was tested in duplicate in two runs per day >2 h apart on each analyzer for >20 days. MC studies were performed according to CLSI EP09-A3. Individual human serum samples were analyzed using the Atellica CH assays on both the Atellica CH and Atellica CI 1900 Analyzers. Precision and MC were evaluated with three reagent lots on one system.

Results

Representative precision and MC results observed for each assay are listed in the table. Over the two assays tested, repeatability and within-lab %CVs were <2.5% and <4.0%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1 for the ETOH and Acet assays.

Conclusion

Evaluation of the Atellica CH ETOH and Acet assays using the Atellica CI 1900 Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica CH Analyzer.

*The products/features mentioned here are not commercially available in all countries. Their future availability cannot be guaranteed.
A-143 Imaging Flow Cytometry: A Novel Method Using ADVIA 2120i System Reagents and Microscopic Image Analysis
Authors: Azhar M , Chakraborty I , Joshi A , Stelling F
Published: September 2023

Background

Flow cytometry based ADVIA 2120i Hematology System reagents are used to modify blood cells. Laser-scattering flow cytometry replaced with digital microscopic image analysis significantly simplifies the complex system to a compact, low-cost microscope. A novel method for imaging flow cytometry is proposed here that simultaneously generates complete blood count (CBC) and high-resolution images of blood cells.

Methods

Image processing algorithms are implemented to process the pixels containing blood cells. RBCs are made isovolumetrically spherical using the RBC reagent (Fig. 1A) and imaged. RBC volumes are easily determined from the diameter of the isovolumetrically spherical RBCs. By illuminating the spherical RBCs with approximately400 nm light, the increasing grayscale values of the pixels corresponds to increasing haemoglobin concentration due to absorption.

WBC nuclei are stained using the Perox reagent (Fig. 1B). The grayscale values of the nuclei pixels can be used to determine the peroxidase stain component, thereby obtaining cell size-to-peroxidase activity scatter plots similar to those on the ADVIA 2120i system. Using the Baso reagent, the cytoplasm of all WBCs are stripped off except for basophils, as shown in Fig. 1C. All the microscopic images have good contrast and high resolution. Image processing techniques can thus provide a 5-part differential using the nuclei/lobular density of WBCs.

Results

Images were obtained under a 20×x Nikon microscope with a Thorlabs DCC1545M monochrome camera. ADVIA reagents were mixed with venous blood and <5 µL of reagent treated sample was spotted between a microscopic slide and coverslip. Image analysis was performed using ImageJ particle analysis tools.

Conclusion

Analysis of digital microscopic images of blood cells acted upon by ADVIA 2120i system reagents can offer a novel, simplified, cost-effective method of hematology analysis. Simultaneous CBC scatter plots and high-resolution images of the blood cells can be obtained using this new approach.Fig. 1.(a) Isovolumetricallly spherical RBCs, (b) peroxidase stain of WBC nuclei, and (c) cytoplasm of WBCs stripped off (except for basophils). Images taken under a 20× Nikon microscope. *Under development and not available for commercial sale.