bluuebunny/crossref_metadata_2025 huggingface dataset:
Full-field deformation reconstruction for large-scale cryogenic composite tanks with limited strain monitoring data
Authors: Li Tengteng , Liu Minjing , Li Jianle , Xu Hao , Wu Zhanjun
Published: September 2023

Online deformation monitoring, while of paramount importance in safety evaluation for aerospace composite tanks, is highly challenging due to the complex strain distributions in the composite tank and the strict restrictions of sensor placement. In this study, full-field deformation of large-scale cryogenic composite tanks were reconstructed under thermo-mechanical coupling conditions. In essence, the inner surface strains in the junction area of the head and cylindrical shell of the tank, defined as the ‘H-C portion’, was derived theoretically based on outer-surface strain measurement. The inverse finite element method (iFEM) was then applied using the measured and derived strains to reconstruct the full-field deformed shape of the tank. A systematic and efficient parametric discussion was conducted using an orthotropic model equivalent with composite laminated models with different lay-ups. The influences of various factors relevant to the material and geometries of the tank on the accuracy of deformation reconstruction were unveiled. Finally, a numerical experiment was carried out to reconstruct the full-field deformation of a large-scale aerospace composite tank with a specific lay-up, where limited strain data analogous to those sparely measured using distributed optical fiber sensors was used. It was found that the sensor placement strategy markedly affects the accuracy of deformation reconstruction.
Interaction-motif-based classification of self-organizing metabolic cycles
Authors: Ouazan-Reboul Vincent , Golestanian Ramin , Agudo-Canalejo Jaime
Published: September 2023

Particles that are catalytically-active and chemotactic can interact through the concentration fields upon which they act, which in turn may lead to wide-scale spatial self-organization. When these active particles interact through several fields, these interactions gain an additional structure, which can result in new forms of collective behavior. Here, we study a mixture of active species which catalyze the conversion of a substrate chemical into a product chemical, and chemotax in concentration gradients of both substrate and product. Such species develop non-reciprocal, specific interactions that we coarse-grain into attractive and repulsive, which can lead to a potentially complex interaction network. We consider the particular case of a metabolic cycle of three species, each of which interacts with itself and both other species in the cycle. We find that the stability of a cycle of species that only chemotax in gradients of their substrate is piloted by a set of two parameter-free conditions, which we use to classify the low number of corresponding interaction networks. In the more general case of substrate- and product-chemotactic species, we can derive a set of two high-dimensional stability conditions, which can be used to classify the stability of all the possible interaction networks based on the self- and pair-interaction motifs they contain. The classification scheme that we introduce can help guide future studies on the dynamics of complex interaction networks and explorations of the corresponding large parameter spaces in such metabolically active complex systems.
Dark-probe scanning near-field microscopy
Authors: Parsamyan Henrik , Yezekyan Torgom , Nerkararyan Khachatur , Bozhevolnyi Sergey I
Published: September 2023

Scanning near-field optical microscopy (SNOM) is a well-known powerful optical technique for visualization of surface nanostructures and fields far beyond the diffraction limit and thus indispensable in material- and nanoscience. While the SNOM resolution is theoretically unlimited, the SNOM performance is in practice constrained by the signal-to-background ratio, simply because of light scattering scaling down as the sixth power of a nanoparticle size and useful signals rapidly drowning in the background for very small objects. In modern instruments, this problem is usually ameliorated through advanced post-processing techniques. Here, we suggest using, instead or in parallel, a ‘dark’ SNOM probe designed to suppress the background light scattering, so that the scattering occurs only when the probe is very close to a nanoscopic object. We argue and demonstrate with simulations that the dark-probe SNOM imaging is much more sensitive to the presence of tiny nanoparticles or any other nanoscale features, allowing thereby for superior resolution and sensing capabilities that are invaluable for nano-optical characterization.
∂¯ -dressing method for the complex modified KdV equation
Authors: Yang Shuxin , Li Biao
Published: September 2023

The dressing method based on the 2 × 2 matrix∂¯-problem is generalized to study the complex modified KdV equation (cmKdV). Through two linear constraint equations, the spatial and time spectral problems related to the cmKdV equation are derived. The gauge equivalence between the cmKdV equation and the Heisenberg chain equation is obtained. Using a recursive operator, a hierarchy of cmKdV with source is proposed. On the basis of the∂¯-equation, theN-solition solutions of the cmKdV equation are obtained by selecting the appropriate spectral transformation matrix. Furthermore, we get explicit one-soliton and two-soliton solutions.
Data-driven fusion and fission solutions in the Hirota–Satsuma–Ito equation via the physics-informed neural networks method
Authors: Sun Jianlong , Xing Kaijie , An Hongli
Published: September 2023

Fusion and fission are two important phenomena that have been experimentally observed in many real physical models. In this paper, we investigate the two phenomena in the (2+1)-dimensional Hirota–Satsuma–Ito equation via the physics-informed neural networks (PINN) method. By choosing suitable physically constrained initial boundary conditions, the data-driven fusion and fission solutions are obtained for the first time. Dynamical behaviors and error analysis of these solutions are investigated via illustratively numerical figures, which show that good results are achieved. It is pointed out that the PINN method adopted here can be effectively used to construct the data-driven fusion and fission solutions for other nonlinear integrable equations. Based on the powerful predictive capability of the PINN method and wide applications of fusion and fission in many physical areas, it is hoped that the data-driven solutions obtained here will be helpful for experts to predict or explain related physical phenomena.
Advances in mobility enhancement of ITZO thin-film transistors: a review
Authors: Chen Feilian , Zhang Meng , Wan Yunhao , Xu Xindi , Wong Man , Kwok Hoi-Sing
Published: September 2023

Indium-tin-zinc oxide (ITZO) thin-film transistor (TFT) technology holds promise for achieving high mobility and offers significant opportunities for commercialization. This paper provides a review of progress made in improving the mobility of ITZO TFTs. This paper begins by describing the development and current status of metal-oxide TFTs, and then goes on to explain the advantages of selecting ITZO as the TFT channel layer. The evaluation criteria for TFTs are subsequently introduced, and the reasons and significance of enhancing mobility are clarified. This paper then explores the development of high-mobility ITZO TFTs from five perspectives: active layer optimization, gate dielectric optimization, electrode optimization, interface optimization, and device structure optimization. Finally, a summary and outlook of the research field are presented.
Low-temperature conformal vacuum deposition of OLED devices using close-space sublimation
Authors: Tam Bryan Siu Ting , Dong Shou-Cheng , Tang Ching W.
Published: September 2023

Close-space sublimation (CSS) has been demonstrated as an alternative vacuum deposition technique for fabricating organic light-emitting diodes (OLEDs). CSS utilizes a planar donor plate pre-coated with organic thin films as an area source to rapidly transfer the donor film to a device substrate at temperatures below 200 °C. CSS is also conformal and capable of depositing on odd-shaped substrates using flexible donor media. The evaporation behaviors of organic donor films under CSS were fully characterized using model OLED materials and CSS-deposited films exhibited comparable device performances in an OLED stack to films deposited by conventional point sources. The low temperature and conformal nature of CSS, along with its high material utilization and short process time, make it a promising method for fabricating flexible OLED displays.
Enhancing performance of inverted quantum-dot light-emitting diodes based on a solution-processed hole transport layer via ligand treatment
Authors: Li Depeng , Ma Jingrui , Liu Wenbo , Xiang Guohong , Qu Xiangwei , Jia Siqi , Gu Mi , Wei Jiahao , Liu Pai , Wang Kai , Sun Xiaowei
Published: September 2023

The performance of inverted quantum-dot light-emitting diodes (QLEDs) based on solution-processed hole transport layers (HTLs) has been limited by the solvent-induced damage to the quantum dot (QD) layer during the spin-coating of the HTL. The lack of compatibility between the HTL's solvent and the QD layer results in an uneven surface, which negatively impacts the overall device performance. In this work, we develop a novel method to solve this problem by modifying the QD film with 1,8-diaminooctane to improve the resistance of the QD layer for the HTL’s solvent. The uniform QD layer leads the inverted red QLED device to achieve a low turn-on voltage of 1.8 V, a high maximum luminance of 105 500 cd/m2, and a remarkable maximum external quantum efficiency of 13.34%. This approach releases the considerable potential of HTL materials selection and offers a promising avenue for the development of high-performance inverted QLEDs.
Investigating the roles of reflexes and central pattern generators in the control and modulation of human locomotion using a physiologically plausible neuromechanical model
Authors: Di Russo Andrea , Stanev Dimitar , Sabnis Anushree , Danner Simon M , Ausborn Jessica , Armand Stéphane , Ijspeert Auke
Published: September 2023

Objective. Studying the neural components regulating movement in human locomotion is obstructed by the inability to perform invasive experimental recording in the human neural circuits. Neuromechanical simulations can provide insights by modeling the locomotor circuits. Past neuromechanical models proposed control of locomotion either driven by central pattern generators (CPGs) with simple sensory commands or by a purely reflex-based network regulated by state-machine mechanisms, which activate and deactivate reflexes depending on the detected gait cycle phases. However, the physiological interpretation of these state machines remains unclear. Here, we present a physiologically plausible model to investigate spinal control and modulation of human locomotion. Approach. We propose a bio-inspired controller composed of two coupled CPGs that produce the rhythm and pattern, and a reflex-based network simulating low-level reflex pathways and Renshaw cells. This reflex network is based on leaky-integration neurons, and the whole system does not rely on changing reflex gains according to the gait cycle state. The musculoskeletal model is composed of a skeletal structure and nine muscles per leg generating movement in sagittal plane. Main results. Optimizing the open parameters for effort minimization and stability, human kinematics and muscle activation naturally emerged. Furthermore, when CPGs were not activated, periodic motion could not be achieved through optimization, suggesting the necessity of this component to generate rhythmic behavior without a state machine mechanism regulating reflex activation. The controller could reproduce ranges of speeds from 0.3 to 1.9 m s−1. The results showed that the net influence of feedback on motoneurons (MNs) during perturbed locomotion is predominantly inhibitory and that the CPGs provide the timing of MNs’ activation by exciting or inhibiting muscles in specific gait phases. Significance. The proposed bio-inspired controller could contribute to our understanding of locomotor circuits of the intact spinal cord and could be used to study neuromotor disorders.
A multivariate physiological model of vagus nerve signalling during metabolic challenges in anaesthetised rats for diabetes treatment
Authors: Güemes Gonzalez Amparo , Carnicer-Lombarte Alejandro , Hilton Sam , Malliaras George
Published: September 2023

Objective. This study aims to develop a comprehensive decoding framework to create a multivariate physiological model of vagus nerve transmission that reveals the complex interactions between the nervous and metabolic systems. Approach. Vagus nerve activity was recorded in female Sprague-Dawley rats using gold hook microwires implanted around the left cervical vagus nerve. The rats were divided into three experimental cohorts (intact nerve, ligation nerve for recording afferent activation, and ligation for recording efferent activation) and metabolic challenges were administered to change glucose levels while recording the nerve activity. The decoding methodology involved various techniques, including continuous wavelet transformation, extraction of breathing rate (BR), and correlation of neural metrics with physiological signals. Main results. Decrease in glucose level was consistently negatively correlated with an increase in the firing activity of the intact vagus nerve that was found to be conveyed by both afferent and efferent pathways, with the afferent response being more similar to the one on the intact nerve. A larger variability was observed in the sensory and motor responses to hyperglycaemia. A novel strategy to extract the BR over time based on inter-burst-interval is also presented. The vagus afferent was found to encode breathing information through amplitude and firing rate modulation. Modulations of the signal amplitude were also observed due to changes in heart rate in the intact and efferent recordings, highlighting the parasympathetic control of the heart. Significance. The analytical framework presented in this study provides an integrative understanding that considers the relationship between metabolic, cardiac, and breathing signals and contributes to the development of a multivariable physiological model for the transmission of vagus nerve signals. This work progresses toward the development of closed-loop neuro-metabolic therapeutic systems for diabetes.
Impact of fusion reactor neutronics modeling for transmutation and thermal feedback
*
Authors: Bae Jin Whan , Borowiec Katarzyna , Sircar Arpan , Badalassi Vittorio
Published: September 2023

Fusion neutronics calculations provide important metrics pertinent to fusion device operations, such as tritium breeding ratios (TBRs) and data on heat deposition, material activation, and damage. Because of the high computational burden required to generate a high-fidelity Monte Carlo simulation of a 3D fusion device, various assumptions are made to reduce computational time by simplifying the reactor model or the calculation iteration. This paper explores the impact of fusion neutronics metrics such as the TBR and decay heat of structural materials based on assumptions of material composition in the fusion reactor and temperature modeling of materials. Results show that for compact tokamaks with high power and long operational cycles, the transmutation of structural materials is significant enough to cause a substantial change in the flux spectrum and decrease the TBR by 1.68% after 2 years of full power operation. Additionally, assuming a constant temperature and material density can impact the TBR calculations up to 3%.
Separating internal and forced contributions to near term SST predictability in the CESM2-LE
Authors: Gordon E M , Barnes E A , Davenport F V
Published: September 2023

An open question in the study of climate prediction is whether internal variability will continue to contribute to prediction skill in the coming decades, or whether predictable signals will be overwhelmed by rising temperatures driven by anthropogenic forcing. We design a neural network that is interpretable such that its predictions can be decomposed to examine the relative contributions of external forcing and internal variability to future regional sea surface temperature (SST) trend predictions in the near-term climate (2020–2050). We show that there is additional prediction skill to be garnered from internal variability in the Community Earth System Model version 2 Large Ensemble, even in a relatively high forcing future scenario. This predictability is especially apparent in the North Atlantic, North Pacific and Tropical Pacific Oceans as well as in the Southern Ocean. We further investigate how prediction skill covaries across the ocean and find three regions with distinct coherent prediction skill driven by internal variability. SST trend predictability is found to be associated with consistent patterns of decadal variability for the grid points within each region.
On the convex characterisation of the set of unital quantum channels
Authors: Rodriguez-Ramos Constantino , Wilmott Colin M
Published: September 2023

In this paper, we consider the convex structure of the set of unital quantum channels. To do this, we introduce a novel framework to construct and characterise different families of low-rank unital quantum maps. In this framework, unital quantum maps are represented as a set of complex parameters on which we impose a set of constraints. The different families of unital maps are obtained by mapping those parameters into the operator representation of a quantum map. For these families, we also introduce a scalar measuring their distance to the set of mixed-unitary maps. We consider the particular case of qutrit channels which is the smallest set of maps for which the existence of non-unitary extremal maps is known. In this setting, we show how our framework generalises the description of well-known maps such as the antisymmetric Werner–Holevo map but also novel families of qutrit maps.
Enhancing Post-Mining Lands’ Value through Sustainable Melon Cultivation: A Hydroponic Approach
Authors: Nursanto E , Widowati I , Kaswidjanti W , Supriyanta B
Published: September 2023

This study investigates the potential of utilizing post-mining areas for sustainable melon (Cucurbitales, Cucurbitaceae, Cucumis) cultivation, focusing on premium melon production by PT. Indominco Mandiri within its Community Development and Empowerment program. A hydroponic system, which involves the cultivation of plants in a soilless medium with a nutrient solution, was employed due to its advantages in improving plant quality and yield. Findings demonstrate that melon thrives in ex-mining conditions, reaching harvesting maturity within 2.5 months, with fruits noted for their sweetness. Additionally, melons were found to be a rich source of vitamins A, K, C, B-6, E, niacin, and essential minerals including calcium, potassium, ferum, magnesium, phosphorus, sodium, and zinc, with low sodium and no fat content. This research underscores the hydroponic system’s potential in reclaiming post-mining lands, enhancing economic viability and fostering community development and empowerment. The implications of these findings extend to environmental rehabilitation and sustainable agriculture practices, offering a feasible and productive use of post-mining land globally.
Optimal EC Value and Pruning Strategy for Enhanced Growth in Hydroponic Watermelon Cultivation
Authors: Irawati E B , Sasmita E R , Padmini O S
Published: September 2023

This study investigated the impact of electrical conductivity (EC) values and pruning methods on the growth and yield of hydroponic watermelon plants (Citrullus lanatus) at the Wedomartani experimental station, Sleman DIY, from May to August 2022. Using a field experiment in a split plot design, the effects of varying EC values during different plant growth phases and differing pruning practices were evaluated. EC values (in mS/cm) for the vegetative I, vegetative II, and generative phases were manipulated at 1.2;2.0;2.8, 1.5;2.1;3.1, and 1.8;2.6;3.4 respectively, while pruning involved maintaining 2 branches and 1 fruit, 3 branches and 1 fruit, and 3 branches and 2 fruits respectively. Analyses of variance (ANOVA) and Duncan’s Multiple Range Test (DMRT) at a 5% level revealed that EC significantly impacted plant height at 14, 21, and 28 days after planting (DAP), stem diameter at 28 DAP, and leaf area at 14 DAP, but not fruit weight per plant. Pruning had a significant effect on plant height at 14 DAP, with the best results obtained from maintaining 2 branches and 1 fruit. No interaction was found between EC value and pruning on watermelon plant growth and yield. These findings offer potential strategies for improving yield in hydroponic watermelon cultivation.
ITS2 Isolation in Endemic Loka Pere Banana: A New Potential DNA Barcode Marker
Authors: Rahmah Mufti Hatur , Dwivany Fenny Martha , Esyanthi Rizkita R
Published: September 2023

The present research aimed to investigate Loka Pere banana (Musa sp.), an endemic species with distinct characteristics, but currently underrepresented in scientific literature. Our primary goal was to isolate the Internal Transcribed Spacer (ITS2) region from the leaf and corm samples of this unique banana variant. As a methodological approach, we utilized a modified CTAB protocol to extract DNA and amplified the ITS2 region via polymerase chain reaction (PCR) using ITS-S2F and ITS-S3R primers, achieving an amplicon size approximately 500 bp long. The results showed successful isolation of the ITS2 sequences from both leaf and corm samples of Loka Pere Banana. This finding signifies the potential of the ITS2 region of the Loka Pere banana as a novel and reliable DNA barcode marker. Future research can leverage this data for more accurate molecular identification and phylogenetic analyses, enhancing our understanding of the genetic diversity among the Musa genus.
Exploration and Inhibition Test of Penicillium sp. In Vitro by Trichoderma
Authors: Yuliantoro I D , Prihatiningrum A E , Sutarman
Published: September 2023

Penicillium is an entomopathogenic fungus which can be used as a bio-bactericidal. Its existence in nature can be found together with other microbes including Trichoderma, a biocontrol agent that has the ability to damage the cell walls of other fungi due to the activity of the extracellular enzyme chitinase it produces. This study aims to obtain potential isolates of Penicillium biocontrol agents from vegetable growing fields and to determine their response to inhibition by Trichoderma esperellum in vitro. On PDA-chloramphenicol media, a suspension of 104 dilution was inoculated containing sample soil from vegetable crops to be isolated and purified and identified as to its species. The entomopathogenic isolates obtained were grown together with T. esperellum in dual culture and also grown in monoculture as a comparison. The isolation results obtained Penicillium sp. Pc-02. The in vitro test results showed that Trichoderma isolates could inhibit Penicillium sp. by 35.5 ± 1.9% and supported the growth of this entomopagen fungus by 15.7% at 24 and 72 hours after inoculation, respectively.
Unlocking Agricultural Potential: Soil Structure and Analysis in a Limestone Mining Site Using Artificial Intelligence and USDA Classification
Authors: Oktaviani R , Trides T , Respati L L , Pangestu I E , Ferdyan R , Simatupang N
Published: September 2023

This study aimed to investigate the soil structure and agricultural potential of a research area located within a limestone mining site. The sampling process was conducted using sieve analysis and hydrometer tests on soil samples collected from six points within a 1-hectare area. The results revealed that the soil structure was Silt Loam, with 48%-64% consisting of Silt, 30%-50% sand, and 1%-6% clay. The data were then classified using USDA classification to identify the potential agricultural uses of the soil. Additionally, artificial intelligence was used through ArcGIS software to prepare a regional map and analyze soil properties. The study findings can serve as a valuable reference for agro-industry activities and land-use planning in the area.
Optimizing turning parameters for improved surface quality and productivity of Al-MMC under dry, wet, and MQL conditions
Authors: Khandey Umesh , Chandra Vaibhav , Arya Vedpal , Kumar Praveen
Published: September 2023

The machining of Aluminum-based Metal Matrix Composites (Al-MMCs) is challenging due to their inhomogeneity, anisotropic nature, and dynamic cutting forces. In this paper, the effect of machining parameters, including cutting speed, feed rate, and depth of cut, on surface quality (Ra) and main (Normal) cutting forces (Fc) during turning of Al-MMCs under different cutting conditions (DRY, WET, and MQL) was investigated. Statistical analysis tools were used to analyze the experimental results, and ANOVA and RSM techniques were used to model the relationships between machining parameters and responses. The results showed that feed rate significantly affected both Ra and Fc for all machining conditions. The DRY machining mode was optimal for surface finish, and the MQL mode was effective in reducing cutting forces due to its cooling and lubrication properties. A feed rate of 0.03 mm rev−1 was found to be the most favourable for all cutting environments as it resulted in lower Ra and Fc values. Turning in the WET condition also produced lower Ra due to the effective flushing of chips and cleaning of the cutting zone. In contrast, turning in the MQL condition reduced cutting forces by 17% and 50% as compared with dry and Wet conditions respectively under optimal conditions. Similarly, surface roughness improves under dry conditions by 33% and 3% compared to Wet and MQL conditions.
The minimal number of critical points of a smooth function on a closed manifold and the ball category
Authors: Sadykov Rustam , Trunov Stanislav
Published: September 2023

Introduced by Seifert and Threlfall [Variationsrechnung im Grossen, Hamburger Math Einzelschr., Heft 24, Teubner, Leipzig-Berlin, 1938], cylindrical neighborhoods of isolated critical points of smooth functions is an essential tool in the Lusternik-Schnirelmann theory. We conjecture that every isolated critical point of a smooth function admits a cylindrical ball neighborhood. We show that the conjecture is true for cone-like critical points, Cornea reasonable critical points, and critical points that satisfy the Rothe

H
H

hypothesis. In particular, the conjecture holds true at least for those critical points that are not infinitely degenerate.

If, contrary to the assertion of the conjecture, there are isolated critical points that do not admit cylindrical ball neighborhoods, then we say that such critical points are exotic. We prove a Lusternik-Schnirelmann type theorem asserting that the minimal number of critical points of smooth functions without exotic critical points on a closed manifold of dimension at least

6
6

is the same as the minimal number of elements in a Singhof-Takens filling of

M
M

by smooth balls with corners.
A solution operator for the \overline∂ equation in Sobolev spaces of negative index
Authors: Shi Ziming , Yao Liding
Published: September 2023

Let

Ω
\Omega

be a strictly pseudoconvex domain in

C

n

\mathbb {C}^n

with

C

k
+
2

C^{k+2}

boundary,

k
≥
1

k \geq 1

. We construct a

∂
¯

\overline \partial

solution operator (depending on

k
k

) that gains

1
2

\frac 12

derivative in the Sobolev space

H

s
,
p

(
Ω
)

H^{s,p} (\Omega )

for any

1
>
p
>
∞

1>p>\infty

and

s
>

1
p

−
k

s>\frac {1}{p} -k

. If the domain is

C

∞

C^{\infty }

, then there exists a

∂
¯

\overline \partial

solution operator that gains

1
2

\frac 12

derivative in

H

s
,
p

(
Ω
)

H^{s,p}(\Omega )

for all

s
∈

R

s \in \mathbb {R}

. We obtain our solution operators via the method of homotopy formula. A novel technique is the construction of “anti-derivative operators” for distributions defined on bounded Lipschitz domains.
Recent Methodological Trends in Epidemiology: No Need for Data-Driven Variable Selection?
Authors: Staerk Christian , Byrd Alliyah , Mayr Andreas
Published: September 2023

Variable selection in regression models is a particularly important issue in epidemiology, where one usually encounters observational studies. In contrast to randomized trials or experiments, confounding is often not controlled by the study design, but has to be accounted for by suitable statistical methods. For instance, when risk factors should be identified with unconfounded effect estimates, multivariable regression techniques can help to adjust for confounders. We investigated the current practice of variable selection in 4 major epidemiologic journals in 2019 and found that the majority of articles used subject-matter knowledge to determine a priori the set of included variables. In comparison with previous reviews from 2008 and 2015, fewer articles applied data-driven variable selection. Furthermore, for most articles the main aim of analysis was hypothesis-driven effect estimation in rather low-dimensional data situations (i.e., large sample size compared with the number of variables). Based on our results, we discuss the role of data-driven variable selection in epidemiology.
3D-SMGE: a pipeline for scaffold-based molecular generation and evaluation
Authors: Xu Chao , Liu Runduo , Huang Shuheng , Li Wenchao , Li Zhe , Luo Hai-Bin
Published: September 2023

In the process of drug discovery, one of the key problems is how to improve the biological activity and ADMET properties starting from a specific structure, which is also called structural optimization. Based on a starting scaffold, the use of deep generative model to generate molecules with desired drug-like properties will provide a powerful tool to accelerate the structural optimization process. However, the existing generative models remain challenging in extracting molecular features efficiently in 3D space to generate drug-like 3D molecules. Moreover, most of the existing ADMET prediction models made predictions of different properties through a single model, which can result in reduced prediction accuracy on some datasets. To effectively generate molecules from a specific scaffold and provide basis for the structural optimization, the 3D-SMGE (3-Dimensional Scaffold-based Molecular Generation and Evaluation) work consisting of molecular generation and prediction of ADMET properties is presented. For the molecular generation, we proposed 3D-SMG, a novel deep generative model for the end-to-end design of 3D molecules. In the 3D-SMG model, we designed the cross-aggregated continuous-filter convolution (ca-cfconv), which is used to achieve efficient and low-cost 3D spatial feature extraction while ensuring the invariance of atomic space rotation. 3D-SMG was proved to generate valid, unique and novel molecules with high drug-likeness. Besides, the proposed data-adaptive multi-model ADMET prediction method outperformed or maintained the best evaluation metrics on 24 out of 27 ADMET benchmark datasets. 3D-SMGE is anticipated to emerge as a powerful tool for hit-to-lead structural optimizations and accelerate the drug discovery process.
Clinical severity in Parkinson’s disease is determined by decline in cortical compensation
Authors: Johansson Martin E , Toni Ivan , Kessels Roy P C , Bloem Bastiaan R , Helmich Rick C
Published: September 2023

Dopaminergic dysfunction in the basal ganglia, particularly in the posterior putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e. bradykinesia) in Parkinson’s disease. However, striatal dopamine loss fails to account for interindividual differences in motor phenotype and rate of decline, implying that the expression of motor symptoms depends on additional mechanisms, some of which may be compensatory in nature. Building on observations of increased motor-related activity in the parieto-premotor cortex of Parkinson patients, we tested the hypothesis that interindividual differences in clinical severity are determined by compensatory cortical mechanisms and not just by basal ganglia dysfunction.

Using functional MRI, we measured variability in motor- and selection-related brain activity during a visuomotor task in 353 patients with Parkinson’s disease (≤5 years disease duration) and 60 healthy controls. In this task, we manipulated action selection demand by varying the number of possible actions that individuals could choose from. Clinical variability was characterized in two ways. First, patients were categorized into three previously validated, discrete clinical subtypes that are hypothesized to reflect distinct routes of α-synuclein propagation: diffuse-malignant (n = 42), intermediate (n = 128) or mild motor-predominant (n = 150). Second, we used the scores of bradykinesia severity and cognitive performance across the entire sample as continuous measures.

Patients showed motor slowing (longer response times) and reduced motor-related activity in the basal ganglia compared with controls. However, basal ganglia activity did not differ between clinical subtypes and was not associated with clinical scores. This indicates a limited role for striatal dysfunction in shaping interindividual differences in clinical severity. Consistent with our hypothesis, we observed enhanced action selection-related activity in the parieto-premotor cortex of patients with a mild-motor predominant subtype, both compared to patients with a diffuse-malignant subtype and controls. Furthermore, increased parieto-premotor activity was related to lower bradykinesia severity and better cognitive performance, which points to a compensatory role.

We conclude that parieto-premotor compensation, rather than basal ganglia dysfunction, shapes interindividual variability in symptom severity in Parkinson’s disease. Future interventions may focus on maintaining and enhancing compensatory cortical mechanisms, rather than only attempting to normalize basal ganglia dysfunction.
Regional activity and effective connectivity within the frontoparietal network during precision walking with visual cueing: an fNIRS study
Authors: Le Duc Trung , Tsuyuhara Masato , Kuwamura Hiroki , Kitano Kento , Nguyen Thu Dang , Duc Nguyen Thuan , Fujita Naoto , Watanabe Tatsunori , Nishijo Hisao , Mihara Masahito , Urakawa Susumu
Published: September 2023

Precision walking (PW) incorporates precise step adjustments into regular walking patterns to navigate challenging surroundings. However, the brain processes involved in PW control, which encompass cortical regions and interregional interactions, are not fully understood. This study aimed to investigate the changes in regional activity and effective connectivity within the frontoparietal network associated with PW. Functional near-infrared spectroscopy data were recorded from adult subjects during treadmill walking tasks, including normal walking (NOR) and PW with visual cues, wherein the intercue distance was either fixed (FIX) or randomly varied (VAR) across steps. The superior parietal lobule (SPL), dorsal premotor area (PMd), supplementary motor area (SMA), and dorsolateral prefrontal cortex (dlPFC) were specifically targeted. The results revealed higher activities in SMA and left PMd, as well as left-to-right SPL connectivity, in VAR than in FIX. Activities in SMA and right dlPFC, along with dlPFC-to-SPL connectivity, were higher in VAR than in NOR. Overall, these findings provide insights into the roles of different brain regions and connectivity patterns within the frontoparietal network in facilitating gait control during PW, providing a useful baseline for further investigations into brain networks involved in locomotion.
Oral and Intravenous Amoxicillin Dosing Recommendations in Neonates: A Pooled Population Pharmacokinetic Study
Authors: Keij Fleur M , Schouwenburg Stef , Kornelisse René F , Preijers Tim , Mir Fatima , Degraeuwe Pieter , Stolk Leo M , van Driel Arianne , Kenter Sandra , van der Sluijs Jacqueline , Heidema Jojanneke , den Butter Paul C P , Reiss Irwin K M , Allegaert Karel , Tramper-Stranders Gerdien A , Koch Birgit C P , Flint Robert B
Published: September 2023

Background

There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI.

Methods

In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used.

Results

The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9–42.4) and bodyweight of 2.6 kg (range, 0.5–5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks’ gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration.

Conclusions

This pooled population pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwide.
Study of the association between serum levels of kynurenine and cardiovascular outcomes and overall mortality in chronic kidney disease
Authors: El Chamieh Carolla , Larabi Islam Amine , Alencar De Pinho Natalia , Lambert Oriane , Combe Christian , Fouque Denis , Frimat Luc , Jacquelinet Christian , Laville Maurice , Laville Solène , Lange Céline , Alvarez Jean-Claude , Massy Ziad A , Liabeuf Sophie ,   the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group, Hannedouche T , Moulin B , Klein A , Combe C , Bourdenx J P , Keller A , Delclaux C , Vendrely B , Deroure B , Lacraz A , Lobbedez T , Landru I , Massy Z , Lang P , Belenfant X , Thervet E , Urena P , Delahousse M , Vela C , Essig M , Clément D , Sekhri H , Smati M , Jamali M , Hacq B , Panescu V , Bellou M , Frimat Luc , Kamar N , Noël C , Glowacki F , Maisonneuve N , Azar R , Hoffmann M , Hourmant M , Testa A , Besnier D , Choukroun G , Lambrey G , Burtey S , Lebrun G , Magnant E , Laville M , Fouque D , Juillard L , Chazot C , Zaoui P , Kuentz F
Published: September 2023

Background

Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate an association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality in CKD patients.

Methods

The CKD-REIN study is a prospective cohort of people with CKD having an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m². Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome.

Results

Of the 2406 included patients (median age: 68 years; median eGFR: 25 ml/min/1.73 m2), 52% had a history of cardiovascular disease. A doubling of serum-free kynurenine levels was associated with an 18% increased hazard of cardiovascular events [466 events, HR (95%CI):1.18(1.02,1.33)], independently of eGFR, serum-free tryptophan level or other uremic toxins, cardioprotective drugs, and traditional cardiovascular risk factors. Serum-free kynurenine was significantly associated with non-atheromatous cardiovascular events [HR(95%CI):1.26(1.03,1.50)], but not with atheromatous cardiovascular events [HR(95%CI):1.15(0.89,1.50)]. The association of serum-free kynurenine with cardiovascular mortality was also independently significant [87 events; adjusted HR(95%CI):1.64(1.10,2.40)]. However, the association of serum-free kynurenine with all-cause mortality was no more significant after adjustment on serum-free tryptophan [311 events, HR(95%CI):1.12(0.90, 1.40)].

Conclusions

Our findings imply that serum-free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events; in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies.
A-192 Cause and Departmental Origin of Errors—An Investigation of Questionable Patient Test Results
Authors: Brady A L , Hayden M , Elkins M B , Nasr M R , Reyes A , Cao Z T
Published: September 2023

Introduction

Reliable patient test results are crucial for quality patient care, involving pre-, post- and analytical phases. Questionable Patient test Results (QPRs), either not matching patient clinical presentation or apparent outliers for the patient population, are often encountered. We aimed to investigate the source and nature of possible errors that cause QPRs.

Methods

960 QPRs were identified during July-December 2022 at our institution. We examined the nature of the QPRs, the corresponding patient clinical records, the procedures involved in pre-, post- and analytical phases, and quality control systems.

Results

The QPRs were found to be originated from 31 departments and medical specialty units. Of those, 5 departments/units had >50 QPRs (accounting for 64% of total QPRs) and are listed in the table provided. The table also lists the information on 7 types of errors identified by our analysis. Of all errors, 78% occurred at pre-analytical phase, with the majority of errors occurring during sample collection.

Discussion

The most common types of errors were either diluted or contaminated samples accounting for 38% and 34%, respectively. Such errors often occur during sample drawing from an existing I.V. access port if not adequately flushed after saline solution infusion (causing sample dilution) or dextrose solution (causing glucose contamination). Many errors were due to samples drawn in the wrong collection tube type. Sample integrity issues included hemolysis, lack of sufficient sample volume, or clotting. For those QPRs that we did not find apparent errors, they were either due to random errors or the results fit the patient’s true medical condition.

Conclusions

Our findings highlight the importance of pre-analytical quality control measures and the need for regular staff education/training. This study pinpointed the errors that require targeted education materials, as well as the hospital units that would benefit most from this focus on error prevention.
Phenology of Leucotaraxis argenticollis, a specialist predator of the invasive hemlock woolly adelgid, in the eastern United States
Authors: Preston Carrie E , Dietschler Nicholas J , Whitmore Mark C , Salom Scott M
Published: September 2023

In hemlock stands within eastern US forests, classical biological control has been one of the main strategies used to manage the hemlock woolly adelgid, Adelges tsugae Annand. Specialist predator species may offer a management solution to help regulate A. tsugae populations. In the Pacific Northwest, a suite of specialist predators has been a focus of research and includes 2 species of silver fly, Leucotaraxis argenticollis (Zetterstedt) and Leucotaraxis piniperda (Malloch) (Diptera: Chamaemyiidae). Leucotaraxis spp. phenology has been documented in the Pacific Northwest, but the phenology of either western Leucotaraxis species is unknown in the eastern United States. This study sought to document the phenology of Le. argenticollis in NY in 2021 and in VA in 2021 and 2022. Nylon mesh cages were applied over eastern hemlock branches infested with A. tsugae to contain Le. argenticollis adults. Biweekly and monthly branch samples were taken in 2021 and 2022, documenting all life stages of A. tsugae and of Le. argenticollis that were observed. In 2021 and 2022, Le. argenticollis adults and eggs were present during the oviposition stage of the 2 generations of A. tsugae. In addition, Le. argenticollis larvae were present when A. tsugae ovisacs had eggs and while A. tsugae nymphs of both generations were present. These observations indicate that Le. argenticollis phenology is well synchronized with A. tsugae in the eastern United States.
Sequential transplantation of the liver–kidney–heart from different donors: a case report
Authors: Wang Liaoran , Zhang Yu , Yu Hang , Song Jiangping , Wang Yi
Published: September 2023

Background

Multi-organ transplantation has emerged as a viable treatment strategy for patients afflicted with multiple organ failure or significant organ dysfunctions. Despite the promising therapeutic outcomes, this approach also amplifies the risk of organ rejection, infection, or neoplastic growth. We present a unique case of a patient who sequentially underwent liver, kidney, and heart transplantation, all sourced from different donors. This case brings forth intriguing possibilities about the interplay between cardiovascular diseases and complications arising post-transplantation, thereby enriching our understanding of comprehensive transplant immunomodulation and cardiovascular disease prevention.

Case summary

A 59-year-old male with chronic alcohol misuse developed liver cirrhosis in 2012 and subsequent kidney failure in 2018 due to alcoholic liver disease, type II diabetes, hyperlipidaemia, and severe hypertension. Subsequently, an incident of extensive transmural myocardial infarction (Killip III) warranted a heart transplant in 2022. Post-transplant, the patient was maintained on a standard immunosuppression regimen with regular post-operative follow-ups. No signs of rejection were noted 1-year post-final transplantation under standard immunosuppression.

Discussion

The presented case exemplifies the potential and feasibility of sequential multi-organ transplantation. The multifaceted interplay between the transplanted organs and the immunosuppressive pharmaceuticals likely exert distinct influences on transplantation immune regulation, possibly diverging from the dynamics observed in single-organ transplantation. A comprehensive exploration of the mechanisms governing immune responses in the context of multi-organ transplantation could yield valuable insights for mitigating graft dysfunction. Furthermore, the rapid progression of atherosclerosis observed after liver and kidney transplantation necessitates further scrutiny to elucidate potential correlations with the post-transplantation state.