bluuebunny/crossref_metadata_2025 huggingface dataset:
Reinvestigating the environmental Kuznets curve (EKC) of carbon emissions and ecological footprint in 147 countries: a matter of trade protectionism
Authors: Wang Qiang , Wang Xiaowei , Li Rongrong , Jiang Xueting
Published: January 2024

Environmental degradation has profoundly impacted both human society and ecosystems. The environmental Kuznets curve (EKC) illuminates the intricate relationship between economic growth and environmental decline. However, the recent surge in trade protectionism has heightened global economic uncertainties, posing a severe threat to global environmental sustainability. This research aims to investigate the intricate pathways through which trade protection, assessed by available trade openness data, influences the nexus between economic growth and environmental degradation. Leveraging comprehensive global panel data spanning 147 countries from 1995 to 2018, this study meticulously examines the non-linear dynamics among trade, economy, and the environment, with a particular emphasis on validating the EKC hypothesis. This study encompasses exhaustive global and panel data regressions categorized across four income groups. The research substantiates the validity of the EKC hypothesis within the confines of this investigation. As income levels rise, the impact of economic growth on environmental degradation initially intensifies before displaying a diminishing trend. Additionally, trade protection manifests as a detriment to improving global environmental quality. The ramifications of trade protectionism display nuanced variations across income strata. In high-income nations, trade protection appears to contribute to mitigating environmental degradation. Conversely, within other income brackets, the stimulating effect of trade protection on environmental pressure is more conspicuous. In other words, trade protectionism exacerbates environmental degradation, particularly affecting lower-income countries, aligning with the concept of pollution havens. The study’s results illuminate nuanced thresholds in the relationship between trade, economic growth, and environmental degradation across income groups, emphasizing the heterogeneous impact and underlying mechanisms. These findings provide valuable insights for policymakers, urging collaborative efforts among nations to achieve a harmonious balance between economic advancement and environmental preservation on a global scale.
Two-dimensional electronic spectroscopy from first principles
Authors: Krumland Jannis , Guerrini Michele , De Sio Antonietta , Lienau Christoph , Cocchi Caterina
Published: January 2024

The recent development of multidimensional ultrafast spectroscopy techniques calls for the introduction of computational schemes that allow for the simulation of such experiments and the interpretation of the corresponding results from a microscopic point of view. In this work, we present a general and efficient first-principles scheme to compute two-dimensional electronic spectroscopy maps based on real-time time-dependent density-functional theory. The interface of this approach with the Ehrenfest scheme for molecular dynamics enables the inclusion of vibronic effects in the calculations based on a classical treatment of the nuclei. The computational complexity of the simulations is reduced by the application of numerical advances such as branching techniques, undersampling, and a novel reduced phase cycling scheme, applicable for systems with inversion symmetry. We demonstrate the effectiveness of this method by applying it to prototypical molecules such as benzene, pyridine, and pyrene. We discuss the role of the approximations that inevitably enter the adopted theoretical framework and set the stage for further extensions of the proposed method to more realistic systems.
Noise tailoring, noise annealing, and external perturbation injection strategies in memristive Hopfield neural networks
Authors: Fehérvári János Gergő , Balogh Zoltán , Török Tímea Nóra , Halbritter András
Published: January 2024

The commercial introduction of a novel electronic device is often preceded by a lengthy material optimization phase devoted to the suppression of device noise as much as possible. The emergence of novel computing architectures, however, triggers a paradigm shift in noise engineering, demonstrating that non-suppressed but properly tailored noise can be harvested as a computational resource in probabilistic computing schemes. Such a strategy was recently realized on the hardware level in memristive Hopfield neural networks, delivering fast and highly energy efficient optimization performance. Inspired by these achievements, we perform a thorough analysis of simulated memristive Hopfield neural networks relying on realistic noise characteristics acquired on various memristive devices. These characteristics highlight the possibility of orders of magnitude variations in the noise level depending on the material choice as well as on the resistance state (and the corresponding active region volume) of the devices. Our simulations separate the effects of various device non-idealities on the operation of the Hopfield neural network by investigating the role of the programming accuracy as well as the noise-type and noise amplitude of the ON and OFF states. Relying on these results, we propose optimized noise tailoring and noise annealing strategies, comparing the impact of internal noise to the effect of external perturbation injection schemes.
Crystal-liquid duality driven ultralow two-channel thermal conductivity in α-MgAgSb
Authors: Li Jingyu , Li Xiyang , Zhang Yongsheng , Zhu Jianbo , Zhao Enyue , Kofu Maiko , Nakajima Kenji , Avdeev Maxim , Liu Peng-Fei , Sui Jiehe , Zhao Huaizhou , Wang Fangwei , Zhang Junrong
Published: January 2024

The desire for intrinsically low lattice thermal conductivity (κL) in thermoelectrics motivates numerous efforts on understanding the microscopic mechanisms of heat transport in solids. Here, based on theoretical calculations, we demonstrate that α-MgAgSb hosts low-energy localized phonon bands and avoided crossing of the rattler modes, which coincides with the inelastic neutron scattering result. Using the two-channel lattice dynamical approach, we find, besides the conventional contribution (∼70% at 300 K) from particlelike phonons propagating, the coherence contribution dominated by the wavelike tunneling of phonons accounts for ∼30% of the total κL at 300 K. By considering dual contributions, our calculated room-temperature κL of 0.64 W m−1 K−1 well agrees with the experimental value of 0.63 W m−1 K−1. More importantly, our computations give a nonstandard κL ∝ T−0.61 dependence, perfectly explaining the abnormal temperature-trend of ∼T−0.57 in experiment for α-MgAgSb. By molecular dynamics simulation, we reveal that the structure simultaneously has soft crystalline sublattices with the metavalent bonding and fluctuating liquid-like sublattices with thermally induced large amplitude vibrations. These diverse forms of chemical bonding arouse mixed part-crystal part-liquid state, scatter strongly heat-carrying phonons, and finally produce extremely low κL. The fundamental research from this study will accelerate the design of ultralow-κL materials for energy-conversion applications.
Solar photovoltaic cell model optimal parameter identification by using an improved chimp optimization algorithm
Authors: Yang Shipin , He Zongxin , Mei Xue , Li Lijuan , Zhang Qing , Jiao Wenhua
Published: January 2024

Identifying the parameters of solar photovoltaic (PV) cell models accurately and reliably is crucial for simulating, evaluating, and controlling PV systems. For this reason, we present an improved chimp optimization algorithm (IChOA) for the generation of precise and reliable solar PV cell models. As a new and improved version of the standard chimp optimization algorithm (ChOA), IChOA embeds two mutation rules in ChOA that include the elite opposition-based learning and visual search mechanism. The first rule is applied to strengthen global exploration capacity of ChOA, and the second one is utilized to enhance ChOA’s local exploitation ability (convergence accuracy). Based on the six benchmark test functions with different characteristics, the effectiveness of IChOA is evaluated by comparing to other five well-known optimization algorithms. The results suggest that IChOA offers superior performance over other competing algorithms. Finally, IChOA’s performance is confirmed through optimizing parameters for three widely employed mathematical models, specifically the single diode model, the double diode model, and the multi-cell PV modules. The findings prove the excellent performance of the suggested approach.
White emission metal halides for flexible and transparent x-ray scintillators
Authors: Zhao Shuangyi , Zhao Jinrong , Qaid Saif M. H. , Liang Dehai , An Kang , Cai Wensi , Qian Qingkai , Zang Zhigang
Published: January 2024

Flat-panel x-ray scintillators with a high spatial resolution at a low radiation dose rate are desirable for efficient imaging applications in medical diagnostics, security inspection, and nondestructive inspection. To promote the progress of x-ray imaging technologies, it is of great interest to explore transparent scintillators with reduced light scattering, high light yields, and uniform radioluminescence. Herein, we design and prepare a novel lead-free (C12H28N)2Cu2I4 metal halide featuring a high luminescent efficiency and white emission benefiting from the double self-trapped exciton mechanism, which enable to not only match the response of semiconductor-based sensors but also enhance light yields and decrease exposed doses to objects. Furthermore, transparent, and flexible scintillators with large areas of 20.25 cm2 demonstrate an outstanding scintillation performance including a high spatial resolution of 19.8 lp mm−1 and an ultralow detection limit of 28.39 nGyair s−1, which are ∼4 times higher and 194 times lower than typical values for medical imaging, respectively. This work provides not only a new route to explore promising alternatives with broadband emission but also a novel opportunity to develop flexible x-ray imaging technology.
Label-free and non-destructive histology of unprocessed biological tissues with ultraviolet single-plane illumination microscopy
Authors: Zhang Yan , Huang Bingxin , Dai Weixing , Kang Lei , Tsang Victor T. C. , Wu Jiajie , Lo Claudia T. K. , Wong Terence T. W.
Published: January 2024

Histopathology has remained the gold standard for surgical margin assessment for decades. However, routine pathological examination based on formalin-fixed and paraffin-embedded (FFPE) tissues is laborious and time-consuming, failing to guide surgeons intraoperatively. Here, we propose a rapid, label-free, and non-destructive histological imaging method, termed microscopy with ultraviolet single-plane illumination (MUSI). With intrinsic fluorescence from deep ultraviolet excitation, MUSI enables both ex vivo and in vivo imaging of fresh and unprocessed tissues at the subcellular level with an imaging speed of 0.5 mm2/s, generating high-quality optically sectioned surface images from irregular surgical tissues with a long depth-of-field. We demonstrate that MUSI could differentiate between different subtypes of human lung adenocarcinomas (e.g., lepidic, acinar, papillary, and micropapillary), revealing diagnostically important features that are comparable to the gold standard FFPE histology. As an assistive imaging platform, MUSI can provide immediate feedback to surgeons and pathologists for intraoperative decision-making, holding great promise to revolutionize the current clinical practice in surgical pathology.
Wearable temperature sensor with moisture resistance based on MXene-embedded fiber
Authors: Yang Jonguk , Lee Jeong Hui , Lim Taekyung , Seo Hee Sung , Seo Keumyoung , Jeong Sang-Mi , Ju Sanghyun
Published: January 2024

As climate change intensifies, summer temperatures are gradually rising, resulting in an increase in heat-related illnesses among individuals exposed to heatwaves. Consequently, wearable sensors for external environmental monitoring are gaining prominence as personal healthcare and safety diagnosis systems. Wearable temperature sensors must provide stable sensing even when subjected to various external environmental changes, such as repetitive movement, humidity, and water contact. In this study, a fiber-type temperature sensor with an embedded MXene (Ti3C2Tx) was fabricated. MXene was synthesized by etching aluminum (Al) from Ti3AlC2 (MAX phase powder) using a mixture of Li salt and hydrochloric acid (HCl) and then prepared as an aqueous dispersion. Subsequently, conductive fibers were fabricated by embedding MXene into polyester fibers via a dipping–drying process. To mitigate susceptibility to moisture, hydrophobic 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecylphosphonic acid (HDF-PA) was applied to the surface of the MXene embedded in the fiber, providing hydrophobicity. The temperature range of 0–50 °C was monitored by measuring the resistance change in the fabricated HDF-PA-coated MXene-embedded fiber. Furthermore, sensing characteristics remained robust even under a bending radius of 15–3 mm. In addition, the sensor was confirmed to operate stably despite physical deformation from repeated bending up to 1000 times, as well as exposure to 50%–90% RH and 1 h of immersion in water, demonstrating excellent durability and water resistance.
Extraordinary transmission of intense short laser pulse through thin foil with near- and sub-wavelength slits
Authors: Lu Sidailuo , Zhang Xiaohai , Sheng Zhengmao , Yu Ming-Young
Published: January 2024

To supplement our earlier study [Lu et al., AIP Adv. 10, 015209 (2020)] on the propagation of intense short laser pulse through foils with multiple sub-wavelength sized slits, here, we consider the effects of the interaction parameters on the occurrence of extremums in the light transmission. Our results suggest that for periodic slit distribution, maximum and minimum transmissions occur for L ± d = κλ and L = κλ, respectively, where L and d are the period and width of the slits, respectively, λ is the laser wavelength, and κ is a positive integer or a rational number.
Harmonic response of Gd-doped Mn-ferrite nanoparticles under AC magnetic field and optimization of Gd doping for MPI applications
Authors: Sakamoto T. , Nii K. , Fujita Y. , Moriwaki T. , Amano H. , Abe R. , Ichiyanagi Y.
Published: January 2024

This study synthesized Gd-doped Mn-ferrite nanoparticles for magnetic particle imaging (MPI) applications with doping levels (x) of 0, 0.05, 0.07, and 0.10. Analyses using X-ray diffraction measurements unequivocally confirmed the presence of a spinel-type crystal structure in the synthesized particles and X-ray absorption fine-structure spectroscopy confirmed the incorporation of Gd atoms in place of Mn within the crystal lattice. Magnetization and harmonic measurements under an AC magnetic field revealed that particles with a high initial permeability and low coercivity showed a high response intensity. Notably, particles possessing a Gd doping level of x = 0.07 displayed the highest response and were considered promising as MPI materials.
An economic evaluation of point-of-care ultrasound for children presenting to the emergency department with suspected septic arthritis of the hip
Authors: Bailey Cate , Deane Heather , O’Brien Adam , Dalziel Kim
Published: January 2024

Objective Diagnosing septic arthritis of the hip in children is time-sensitive, with earlier diagnosis improving outcomes. Point-of-care ultrasound (POCUS) requires specialised training and resources in emergency departments (ED) to potentially lower costs through reducing patient time in ED. We aimed to compare the costs of using POCUS for suspected septic arthritis of the hip to current practice. Methods This study is embedded in a retrospective review of 190 cases of suspected cases of septic hip joint collected over 5 years to investigate patient length of stay and time to perform ultrasound. We multiplied time use by cost per bed hour comparing current practice with POCUS. The POCUS arm included training and equipment costs. Scenario, sensitivity, and threshold analyses were conducted. Costs were calculated in Australian dollars for 2022. Results The current practice arm took 507 min from initial patient assessment to ultrasound examination, compared with 96 min for the POCUS arm. Cost per bed hour was estimated at $207 from hospital data. Total cost savings for POCUS compared to current practice were $35 821 per year assuming 38 cases of suspected arthritis of the hip per year, saving 228 bed hours per year. All scenario and sensitivity analyses were cost saving. Threshold analysis indicated that if the cost of a paediatric ED bed was higher than $51 per hour, POCUS would be cost saving. Conclusion There was significant cost saving potential for hospitals by switching to POCUS for suspected septic arthritis of the hip.
Laser-driven noncontact bubble transfer printing via a hydrogel composite stamp
Authors: Li Chenglong , Luo Hongyu , Lin Xinyi , Zhang Shun , Song Jizhou
Published: January 2024

Transfer printing that enables heterogeneous integration of materials into spatially organized, functional arrangements is essential for developing unconventional electronic systems. Here, we report a laser-driven noncontact bubble transfer printing via a hydrogel composite stamp, which features a circular reservoir filled with hydrogel inside a stamp body and encapsulated by a laser absorption layer and an adhesion layer. This composite structure of stamp provides a reversible thermal controlled adhesion in a rapid manner through the liquid–gas phase transition of water in the hydrogel. The ultrasoft nature of hydrogel minimizes the influence of preload on the pick-up performance, which offers a strong interfacial adhesion under a small preload for a reliable damage-free pick-up. The strong light-matter interaction at the interface induces a liquid–gas phase transition to form a bulge on the stamp surface, which eliminates the interfacial adhesion for a successful noncontact printing. Demonstrations of noncontact transfer printing of microscale Si platelets onto various challenging nonadhesive surfaces (e.g., glass, key, wrench, steel sphere, dry petal, droplet) in two-dimensional or three-dimensional layouts illustrate the unusual capabilities for deterministic assembly to develop unconventional electronic systems such as flexible inorganic electronics, curved electronics, and micro-LED display.
Reverse effects of pre-deformation and traverse speed on the mechanical properties of friction stir processed pure copper
Authors: Mazaheri Hoora , Aval Hamed Jamshidi , Jamaati Roohollah
Published: January 2024

In the present work, the effects of pre-strain and traverse speed on the microstructural evolution and tensile behavior of friction stir processed (FSPed) pure copper were investigated. In the samples without pre-deformation (0% samples), with the increment of the traverse speed from 100 mm min−1 to 200 mm min−1, the grain size decreased from 5.2 to 2.5 μm due to heat input domination. In the 60% pre-rolled samples (60% samples), interestingly, with an increase in the traverse speed (from 100 mm min−1 to 200 mm min−1), the average grain size increased from 2.4 to 6.8 μm owing to the domination of deformation degree. With the increment of speed from 100 mm min−1 to 200 mm min−1 in the 0% samples, the YS and UTS increased from 158.6 and 244.6 MPa to 190.7 and 253.9 MPa, respectively, due to decrement in the mean grain size. In addition, the increment of speed from 100 mm min−1 to 200 mm min−1 in the 60% samples reduced the YS and UTS from 177.9 and 261.7 MPa to 138.9 and 234.8 MPa, respectively, due to the increase in the mean grain size. In the 0% FSPed copper, by increasing the speed, the depth and size of dimples reduced, while, in the 60% FSPed samples, when the traverse speed increased, the dimples became larger.
Low power CNTFET-based ternary multiplier for digital signal processing applications
Authors: Chauhan Katyayani , Bansal Deepika
Published: January 2024

Multiplication is a fundamental arithmetic process, although it necessitates more hardware resources. Researchers in advanced technology attempted to boost the speed and lower the power in digital signal processing applications by utilizing multipliers. The majority of digital signal processing applications demanded increased speed. In addition, ternary logic based on CNTFETs is a feasible alternative for Si-MOSFETs. The article proposes a ternary multiplier, which is designed using proposed ternary logical and combinational circuits that includes STI, TNAND, TNOR, and ternary decoder. The proposed and existing designs are simulated, compared, and analysed on the parameters of delay, average power, and noise using the HSPICE simulator. Therefore, the results show 10%, 81% and 81% improvement in delay, average power, and PDP respectively for proposed TMUL. The noise margin of the proposed TMUL is increased up to 54% over existing circuits. The proposed TDecoder, STI, TNAND, and TNOR are 95%, 97%, 81%, and 95% more energy efficient than existing designs, respectively.
The effects of resourcefulness-based instrumental reminiscence therapy on psychological adjustment in nursing home residents: a randomised controlled trial
Authors: Pan Xiaohui , Huang Qiyuan , Zhang Zhefu , Liu Huangqin , Xiao Huimin
Published: January 2024

Background

Older adults do not always adapt successfully to nursing homes. Learning resourcefulness and instrumental reminiscence may contribute to the psychological adjustment made by nursing home residents. How both attributes can be combined to enhance residents’ adjustment remains unclear.

Objectives

This study examined the effects of resourcefulness-based instrumental reminiscence therapy (RBIRT) on psychological adjustment, learned resourcefulness, self-efficacy, social support and quality of life (QoL) of nursing home residents.

Methods

A randomised, controlled, assessor-blinded, parallel-arm trial was conducted between January 2022 and February 2023 in Fujian, China, with 120 participants (intervention = 60, comparison = 60) from two separate nursing homes. The intervention group participants received a 6-week RBIRT, involving Reminiscence Interview, Emotional Venting, Reconstruction Strategies, Planning for the Future and Strengthening Support. The control group participants received routine institutional care. Participants were assessed using the Nursing Home Adjustment Scale, Resourcefulness Scale, General Self-efficacy Scale, Perceived Social Support Scale and the 12-item Short-Form Health Survey. Outcomes were evaluated at baseline (T0), immediately post intervention (T1) and at 1-month (T2) and 3-months (T3) post-intervention.

Results

Participants in the intervention group showed significant improvement in ‘psychological adjustment,’ ‘learned resourcefulness,’ ‘self-efficacy,’ ‘social support’ and ‘QoL-mental health dimension’ compared to the control group (P < 0.001). These effects were sustained at the 1- and 3-month follow-ups.

Conclusions

Innovative RBIRT improved psychological adjustment, learned resourcefulness, self-efficacy, social support and mental health-related QoL among nursing home residents.
Baclofen in the treatment of alcohol use disorder: tailored doses matter
Authors: de Beaurepaire Renaud , Jaury Philippe
Published: January 2024

Aims

To address the question of tailored baclofen prescribing in alcohol use disorder (AUD) in relation to dose-dependent efficacy and the potential danger of high doses and to provide suggestions for the use of high doses of baclofen in the treatment of AUD. The context is the approvement in France of baclofen in the treatment of AUD without dose limitation, making French physicians, who usually prescribe baclofen in a tailored manner, often use high or very high doses.

Methods

A narrative review of the results of randomized controlled trials (RCTs) and observational studies that used tailored baclofen prescribing and of the severe adverse effects of baclofen that have been reported in the literature.

Results

The results show that RCTs using tailored doses of baclofen in AUD are not completely demonstrative, though they are encouraging according to certain meta-analyses, while observational studies that used tailored doses constantly show a good effectiveness of baclofen treatment. The results suggest that many severe adverse effects of baclofen could be related to a nonrespect by physicians of prescription rules and appropriate treatment monitoring.

Conclusions

The use of tailored doses shows that the dose required to suppress cravings is highly variable, low or high, depending on each case. Analysis of the circumstances in which severe adverse effects occur suggest that a careful monitoring of baclofen prescribing might prevent a large majority of severe adverse effects. We propose that the education of the patients and the prescription skills, seriousness, and availability of the prescribing physicians are of major importance in the managing of tailored baclofen treatment of AUD.
SPREd: a simulation-supervised neural network tool for gene regulatory network reconstruction
Authors: Wu Zijun , Sinha Saurabh
Published: January 2024

Reconstruction of gene regulatory networks (GRNs) from expression data is a significant open problem. Common approaches train a machine learning (ML) model to predict a gene’s expression using transcription factors’ (TFs’) expression as features and designate important features/TFs as regulators of the gene. Here, we present an entirely different paradigm, where GRN edges are directly predicted by the ML model. The new approach, named “SPREd,” is a simulation-supervised neural network for GRN inference. Its inputs comprise expression relationships (e.g. correlation, mutual information) between the target gene and each TF and between pairs of TFs. The output includes binary labels indicating whether each TF regulates the target gene. We train the neural network model using synthetic expression data generated by a biophysics-inspired simulation model that incorporates linear as well as non-linear TF–gene relationships and diverse GRN configurations. We show SPREd to outperform state-of-the-art GRN reconstruction tools GENIE3, ENNET, PORTIA, and TIGRESS on synthetic datasets with high co-expression among TFs, similar to that seen in real data. A key advantage of the new approach is its robustness to relatively small numbers of conditions (columns) in the expression matrix, which is a common problem faced by existing methods. Finally, we evaluate SPREd on real data sets in yeast that represent gold-standard benchmarks of GRN reconstruction and show it to perform significantly better than or comparably to existing methods. In addition to its high accuracy and speed, SPREd marks a first step toward incorporating biophysics principles of gene regulation into ML-based approaches to GRN reconstruction.

Availability and implementation

Data and code are available from https://github.com/iiiime/SPREd.
The predictive capacity of polygenic risk scores for disease risk is only moderately influenced by imputation panels tailored to the target population
Authors: Levi Hagai , Elkon Ran , Shamir Ron
Published: January 2024

Motivation

Polygenic risk scores (PRSs) predict individuals’ genetic risk of developing complex diseases. They summarize the effect of many variants discovered in genome-wide association studies (GWASs). However, to date, large GWASs exist primarily for the European population and the quality of PRS prediction declines when applied to other ethnicities. Genetic profiling of individuals in the discovery set (on which the GWAS was performed) and target set (on which the PRS is applied) is typically done by SNP arrays that genotype a fraction of common SNPs. Therefore, a key step in GWAS analysis and PRS calculation is imputing untyped SNPs using a panel of fully sequenced individuals. The imputation results depend on the ethnic composition of the imputation panel. Imputing genotypes with a panel of individuals of the same ethnicity as the genotyped individuals typically improves imputation accuracy. However, there has been no systematic investigation into the influence of the ethnic composition of imputation panels on the accuracy of PRS predictions when applied to ethnic groups that differ from the population used in the GWAS.

Results

We estimated the effect of imputation of the target set on prediction accuracy of PRS when the discovery and the target sets come from different ethnic groups. We analyzed binary phenotypes on ethnically distinct sets from the UK Biobank and other resources. We generated ethnically homogenous panels, imputed the target sets, and generated PRSs. Then, we assessed the prediction accuracy obtained from each imputation panel. Our analysis indicates that using an imputation panel matched to the ethnicity of the target population yields only a marginal improvement and only under specific conditions.

Availability and implementation

The source code used for executing the analyses is this paper is available at https://github.com/Shamir-Lab/PRS-imputation-panels.
3D Optical Coherence Tomography image processing in BISCAP: characterization of biofilm structure and properties
Authors: Narciso Diogo A C , Pereira Ana , Dias Nuno O , Monteiro Manuel , Melo Luis F , Martins Fernando G
Published: January 2024

Motivation

BISCAP is a state-of-the-art tool for automatically characterizing biofilm images obtained from Optical Coherence Tomography. Limited availability of other software tools is reported in the field. BISCAP’s first version processes 2D images only. Processing 3D images is a problem of greater scientific relevance since it deals with the entire structure of biofilms instead of their 2D slices.

Results

Building on the image-processing principles and algorithms proposed earlier for 2D images, these were adapted to the 3D case, and a more general implementation of BISCAP was developed. The primary goal concerns the extension of the initial methodology to incorporate the depth axis in 3D images; multiple improvements were also made to boost computational performance. The calculation of structural properties and visual outputs was extended to offer new insights into the 3D structure of biofilms. BISCAP was tested using 3D images of biofilms with different morphologies, consistently delivering accurate characterizations of 3D structures in a few minutes using standard laptop machines. Low user dependency is required for image analysis.

Availability and implementation

BISCAP is available from https://github.com/diogonarciso/BISCAP. All images used in the tutorials and the validation examples are available from https://web.fe.up.pt/∼fgm/biscap3d.
Post-stroke upper limb recovery is correlated with dynamic resting-state network connectivity
Authors: Tang Chih-Wei , Zich Catharina , Quinn Andrew J , Woolrich Mark W , Hsu Shih-Pin , Juan Chi-Hung , Lee I Hui , Stagg Charlotte J
Published: January 2024

Motor recovery is still limited for people with stroke especially those with greater functional impairments. In order to improve outcome, we need to understand more about the mechanisms underpinning recovery. Task-unbiased, blood flow–independent post-stroke neural activity can be acquired from resting brain electrophysiological recordings and offers substantial promise to investigate physiological mechanisms, but behaviourally relevant features of resting-state sensorimotor network dynamics have not yet been identified. Thirty-seven people with subcortical ischaemic stroke and unilateral hand paresis of any degree were longitudinally evaluated at 3 weeks (early subacute) and 12 weeks (late subacute) after stroke. Resting-state magnetoencephalography and clinical scores of motor function were recorded and compared with matched controls. Magnetoencephalography data were decomposed using a data-driven hidden Markov model into 10 time-varying resting-state networks. People with stroke showed statistically significantly improved Action Research Arm Test and Fugl-Meyer upper extremity scores between 3 weeks and 12 weeks after stroke (both P < 0.001). Hidden Markov model analysis revealed a primarily alpha-band ipsilesional resting-state sensorimotor network which had a significantly increased life-time (the average time elapsed between entering and exiting the network) and fractional occupancy (the occupied percentage among all networks) at 3 weeks after stroke when compared with controls. The life-time of the ipsilesional resting-state sensorimotor network positively correlated with concurrent motor scores in people with stroke who had not fully recovered. Specifically, this relationship was observed only in ipsilesional rather in contralesional sensorimotor network, default mode network or visual network. The ipsilesional sensorimotor network metrics were not significantly different from controls at 12 weeks after stroke. The increased recruitment of alpha-band ipsilesional resting-state sensorimotor network at subacute stroke served as functionally correlated biomarkers exclusively in people with stroke with not fully recovered hand paresis, plausibly reflecting functional motor recovery processes.
Modification of Huntington’s disease by short tandem repeats
Authors: Hong Eun Pyo , Ramos Eliana Marisa , Aziz N Ahmad , Massey Thomas H , McAllister Branduff , Lobanov Sergey , Jones Lesley , Holmans Peter , Kwak Seung , Orth Michael , Ciosi Marc , Lomeikaite Vilija , Monckton Darren G , Long Jeffrey D , Lucente Diane , Wheeler Vanessa C , Gillis Tammy , MacDonald Marcy E , Sequeiros Jorge , Gusella James F , Lee Jong-Min
Published: January 2024

Expansions of glutamine-coding CAG trinucleotide repeats cause a number of neurodegenerative diseases, including Huntington’s disease and several of spinocerebellar ataxias. In general, age-at-onset of the polyglutamine diseases is inversely correlated with the size of the respective inherited expanded CAG repeat. Expanded CAG repeats are also somatically unstable in certain tissues, and age-at-onset of Huntington’s disease corrected for individual HTT CAG repeat length (i.e. residual age-at-onset), is modified by repeat instability-related DNA maintenance/repair genes as demonstrated by recent genome-wide association studies. Modification of one polyglutamine disease (e.g. Huntington’s disease) by the repeat length of another (e.g. ATXN3, CAG expansions in which cause spinocerebellar ataxia 3) has also been hypothesized. Consequently, we determined whether age-at-onset in Huntington’s disease is modified by the CAG repeats of other polyglutamine disease genes. We found that the CAG measured repeat sizes of other polyglutamine disease genes that were polymorphic in Huntington’s disease participants but did not influence Huntington’s disease age-at-onset. Additional analysis focusing specifically on ATXN3 in a larger sample set (n = 1388) confirmed the lack of association between Huntington’s disease residual age-at-onset and ATXN3 CAG repeat length. Additionally, neither our Huntington’s disease onset modifier genome-wide association studies single nucleotide polymorphism data nor imputed short tandem repeat data supported the involvement of other polyglutamine disease genes in modifying Huntington’s disease. By contrast, our genome-wide association studies based on imputed short tandem repeats revealed significant modification signals for other genomic regions. Together, our short tandem repeat genome-wide association studies show that modification of Huntington’s disease is associated with short tandem repeats that do not involve other polyglutamine disease-causing genes, refining the landscape of Huntington’s disease modification and highlighting the importance of rigorous data analysis, especially in genetic studies testing candidate modifiers.
OP03 Efficacy and safety of the oral selective sphingosine-1-phosphate-1 receptor modulator VTX002 in moderately to severely active Ulcerative Colitis: results from a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Sands B E , Panaccione R , D'Haens G , Schreiber S , DuVall A , Kierkus J , Naik S , Gilder K , Yun C , Sandborn W J , Walczak M , Vermeire S , Rubin D T , Peyrin-Biroulet L , Danese S
Published: January 2024

Background

VTX002 is a novel oral selective sphingosine-1-phosphate-1 (S1P1) receptor modulator in development for the treatment of ulcerative colitis (UC). The efficacy and safety of VTX002 in patients with ulcerative colitis (UC) was assessed in a phase 2, multicentre, randomised, double-blind, placebo-controlled study (NCT05156125).

Methods

Adults (N=213) with moderately to severely active UC (modified Mayo score [MMS] 4-9) and inadequate response/intolerance to conventional and/or advanced (approved biologics or Janus kinase inhibitor) therapies were randomised 1:1:1 to once daily treatment with placebo (n=70), 30 mg (n=73) or 60 mg (n=70) VTX002 tablets for 13 weeks. Patients underwent a 6–8-day dose titration up to the assigned treatment dose. The primary endpoint was clinical remission (MMS stool frequency subscore ≤ 1, rectal bleeding subscore=0, and endoscopic subscore [ES] ≤ 1) at week 13. A protocol amendment limiting eligibility to patients with baseline MMS 5-9 resulted in 213 and 209 patients in the safety and efficacy populations, respectively. Key secondary endpoints were endoscopic improvement, symptomatic remission, histologic remission, and endoscopic improvement-histologic remission. Endoscopic remission and histologic-endoscopic mucosal improvement (HEMI) were also assessed (see Table 1 for outcome definitions). Adverse events (AEs) and laboratory abnormalities were assessed for safety.

Results

The primary endpoint of clinical remission at week 13 was achieved (27.9% of patients who received VTX002 60 mg vs 11.4% of patients who received placebo, ∆=16.5%, p=0.0184). Both doses of VTX002 achieved nominal statistical significance for all key secondary endpoints (Table 1).

Significantly greater proportions of patients who received VTX002 60 mg achieved endoscopic remission and HEMI compared to patients who received placebo (29.4% VTX002 60 mg vs 7.1% placebo, ∆=22.3%, p=0.0012, and 32.4% VTX002 60 mg vs 10.0% placebo, ∆=22.4%, p=0.0026, respectively). A dose-dependent decrease of 67.7% and 53.9% in mean absolute lymphocyte count (ALC) from baseline was observed at week 8 for patients who received VTX002 60 mg and 30 mg, respectively. Most AEs were mild to moderate (Table 2). No AEs of bradycardia, atrioventricular block, serious infections, macular oedema, or deaths were reported.

Conclusion

The S1P1 receptor modulator VTX002 was well-tolerated and statistically superior to placebo for induction of clinical, endoscopic, histologic, HEMI, and symptomatic remission/response at week 13. These positive findings, including a dose-dependent pharmacodynamic reduction in ALC, support phase 3 development of VTX002 for treatment of UC.
OP04 Endoscopic healing in paediatric IBD perpetuates a persistent signature characterized by pathogenic Th17 cells and tissue-associated molecular and microbial drivers of disease
Authors: Siebert K , Köhler N , Faro T , Matchado M , Hölz H , Jarosch S , Koletzko S , Ohnmacht C , List M , Busch D , Haller D , Schwerd T
Published: January 2024

Background

Endoscopic healing (EH) is the major long-term treatment target for inflammatory bowel diseases (IBD) in adults and paediatric patients. However, EH may not represent disease clearance. Hence, risk of relapse remains high and treatment discontinuation after reaching EH often results in disease exacerbation. We aimed to identify persistent cellular, molecular and microbial drivers of IBD under EH and longitudinally collected endoscopic biopsies from paediatric patients for analysis of single T-cell and bulk transcriptomics as well as mucosa-associated microbiota.

Methods

We followed disease trajectories of paediatric IBD patients treated according to international guidelines and collected mucosal biopsies from the terminal ileum (TI) and sigmoid colon (SC) at baseline (T1) and after approximately 3-12 months (T2) to assess EH. Non-IBD controls showed no macroscopic or histologic signs of inflammation. Host RNA and bacterial DNA were simultaneously extracted from single biopsies for bulk RNA-seq, and 16S rRNA seq. A second biopsy was used for isolation of lamina propria mononuclear cells (LPMCs), followed by CD45+, CD3+ cell sorting and single T-cell analysis (10X Genomics). Data were quality controlled and integrated.

Results

217 biopsies (135 simultaneous extraction of host RNA and bacterial DNA; 82 single T-cell analysis) from 32 paediatric IBD patients (mean age 13 ± 3.5 years, 21 Crohn’s disease [CD], 11 ulcerative colitis [UC]; T1 = 32, T2 = 32, T > 2 = 6) and 5 non-IBD controls were analysed. Time between T1 and T2 averages 40 ± 22 weeks. At baseline, 15 patients (14 CD, 1 UC) were newly diagnosed and 31/32 patients had active mucosal inflammation. Twenty-two patients (71%) achieved EH at T2 (SES-CED ≤2 and absence of ulcerations), mostly on anti-TNF therapy. One patient (EH at T1) experienced relapsing disease within 10 weeks after discontinuing medication. In the bulk RNA-seq, we identified 299 differential expressed genes (DEGs; corrected p-value <0.05, FC >2.0), such as DUOX2, SAA2-SAA4, FCGR3B and NOS2, that are associated with active IBD and remained upregulated in EH in contrast to non-IBD controls. In addition single cell analysis revealed an IBD-specific pathogenic Th17 cluster that continued to exist in EH and showed high correlation with top DEGs after data integration. 16S rRNA gene seq highlighted highly individual mucosa-associated bacterial profiles and a reduced α-diversity in active and EH compared to non-IBD controls.

Conclusion

A persisting IBD signature in EH reflects ongoing cellular, molecular and microbial activity in comparison to non-IBD controls despite EH and mucosal regeneration. These markers may provide targets for future or sequential therapies.
OP16 A novel artificial intelligence-assisted Image Enhanced Endoscopy assesses accurately “vascular-healing” and predicts long-term clinical relapse in patients with ulcerative colitis: a prospective cohort study
Authors: Maeda Y , Kudo S E , Kuroki T , Masashi M , Ogata N , Miyachi H , Baba T , Nemoto T , Ohtsuka K , Iacucci M
Published: January 2024

Background

Ulcerative colitis (UC) is a chronic specific inflammatory bowel disease that alternates between remission and relapse statuses. Microvascular finding observed in image-enhanced endoscopy (IEE) has been attracting attention to detect inflammation and predict outcomes in patients with UC; however, this requires specialist endoscopists. Artificial intelligence (AI)-assisted IEE may help to overcome this problem. We developed a novel AI-based narrow-band imaging (NBI) system, using 8853 images from 167 patients, that can be adapted to commercially available various endoscopes and determined if AI-identified ‘vascular-healing’ could predict relapse and guide treatment in patients with UC.

Methods

This prospective cohort study analyzed data from 100 patients with UC in clinical remission. The endoscopists performed colonoscopy using the AI system, which outputs identified the target mucosa as vascular-active or vascular-healing. The Mayo endoscopic subscore (MES), AI outputs, and histological assessment were recorded for six colorectal segments of each patient. Patients were then followed up for 12 months. Clinical relapse was defined as a partial Mayo score >2.

Results

The clinical relapse rate was significantly higher in the AI-based vascular-active group [23.9% (16/67)] compared with the AI-based vascular-healing group [3.0% (1/33)] (P=0.01). In a sub-analysis predicting clinical relapse in patients with MES ≤1, the area under the curve for the combination of complete endoscopic remission and vascular healing (0.70) was increased compared with that for complete endoscopic remission (MES=0) alone (0.65). Colonoscopy by a total of 27 endoscopists, comprising 11 experts and 16 trainees, evaluated 35 and 65 patients, respectively. The sensitivity, specificity, and accuracy for predicting clinical relapse did not differ significantly according to the endoscopist’s experience: 100%, 39.3%, and 51.4%, respectively, for experts and 90.0%, 38.2%, and 46.2%, respectively, for trainees (P>0.95, P>0.95, and P=0.84, respectively).

Conclusion

Colonoscopy using the AI-based NBI system for diagnosing “vascular-healing” identifies patients with UC at high risk of relapse and thus aids future disease management.
DOP61 Up-regulated Gremlin 1 in fibroblasts from Crohn’s Disease fibrotic strictures: A potential therapeutic target
Authors: Acharjee A , Shivaji U N , Santacroce G , Jeffery L , Reynolds G , Majumder S , Akiror S , Zardo D , Gkoutos G V , Iacucci M , Amamou A , Ghosh S
Published: January 2024

Background

Fibrosis is a common complication in Crohn’s disease (CD), often leading to intestinal strictures that are refractory to available biologic drugs and require surgery. Addressing this complication remains a significant unmet need. This study aims to explore the transcriptomic signature of fibrostenotic ileal CD to identify novel therapeutic targets.

Methods

9 CD patients undergoing surgery for fibrotic strictures were prospectively recruited. All patients underwent magnetic resonance enterography, ileoscopy, and assessment of C-reactive protein and faecal calprotectin. A multidisciplinary team adjudicated the presence of fibrotic strictures, warranting surgical resection. Resected specimens were harvested directly from the operating theatre and delivered fresh to pathologists, who dissected samples from the strictured area, and the proximal and distal non-strictured regions. RNA was extracted from all samples for bulk-transcriptomic and single-cell RNA sequencing (scRNAseq) analysis, using the 10x Chromium Controller® platform. Differentially expressed genes (adj. p-value <0.05) were identified. Machine learning analyses, including PCA and PLS-DA, were employed to compare gene expression patterns among different tissue segments. Pathway enrichment analysis pinpointed relevant pathways. Further, the random forest model was constructed to evaluate the predictive significance of genes in relation to strictures, and the resulting ranked list of genes was subsequently validated through qPCR, confirming the significance of selected genes.

Results

Bulk-transcriptomic analysis revealed 64 significantly up-regulated genes in strictures, associated with inflammation, matrix remodeling, adipogenesis and cellular stress. Furthermore, 17 down-regulated genes were linked to epithelial barrier integrity. Normalised gene expression of GREM1, SERPINE1, FGF2, HDAC1 AND LY96 showed high predictive value for strictures compared to distal and proximal segments. Notably, qPCR confirmed the significant up-regulation of GREM1 expression exclusively in the ileal stricture samples (non-stricture vs. stricture: AUC 0.88, 95% CI 0.77-0.95). scRNAseq linked up-regulated GREM1 exclusively to the fibroblast cell population (THY1+, COL1A1+,ACTA2+).

Conclusion

Bulk and single-cell transcriptomics, along with qPCR validation of resected CD ileal strictures, showed the up-regulation of GREM1 in fibroblasts within stricture compared to adjacent proximal and distal intestinal samples. These findings confirmed in ileal CD previous reports from animal models, highlighting the role of GREM1 in promoting intestinal fibrosis. Therefore, GREM1 emerges an attractive target for the treatment of fibrotic strictures in CD.