bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic computing with voltage-controlled dynamics in magnetic tunnel junctions
Authors: Shao Yixin , Duffee Christian , Raimondo Eleonora , Davila Noraica , Lopez-Dominguez Victor , Katine Jordan A , Finocchio Giovanni , Khalili Amiri Pedram
Published: September 2023

Probabilistic (p-) computing is a physics-based approach to addressing computational problems which are difficult to solve by conventional von Neumann computers. A key requirement for p-computing is the realization of fast, compact, and energy-efficient probabilistic bits. Stochastic magnetic tunnel junctions (MTJs) with low energy barriers, where the relative dwell time in each state is controlled by current, have been proposed as a candidate to implement p-bits. This approach presents challenges due to the need for precise control of a small energy barrier across large numbers of MTJs, and due to the need for an analog control signal. Here we demonstrate an alternative p-bit design based on perpendicular MTJs that uses the voltage-controlled magnetic anisotropy (VCMA) effect to create the random state of a p-bit on demand. The MTJs are stable (i.e. have large energy barriers) in the absence of voltage, and VCMA-induced dynamics are used to generate random numbers in less than 10 ns/bit. We then show a compact method of implementing p-bits by using VC-MTJs without a bias current. As a demonstration of the feasibility of the proposed p-bits and high quality of the generated random numbers, we solve up to 40 bit integer factorization problems using experimental bit-streams generated by VC-MTJs. Our proposal can impact the development of p-computers, both by supporting a fully spintronic implementation of a p-bit, and alternatively, by enabling true random number generation at low cost for ultralow-power and compact p-computers implemented in complementary metal-oxide semiconductor chips.
Solar light induced photocatalytic degradation of textile dyes using solvothermally synthesized SnO2 impregnated pumice stone
Authors: Rajput Rekha B , Salunkhe Abhaysinh , Kale Rohidas B
Published: September 2023

In this study, a facile solvothermal route was utilized to immobilize SnO2 on the surface of pumice stone and used as a photocatalyst to remove methyl orange (MO) and crystal violet (CV). Based on the SEM findings, the SnO2 particles were successfully immobilized on the surface of the pumice without aggregation. Also, the immobilization of SnO2 was identified using XRD, EDS, XRF and FTIR analysis. The UV–vis spectroscopy measurement revealed the energy bandgap of pristine pumice and SnO2/pumice composite was found to be 2.71 and 2.55 eV, respectively. The BET surface area of SnO2/pumice is about 29.08 m2 g−1, with pore volume and pore radius of up to 0.045 cm3 g−1 and 30.97 Ả, respectively. The photocatalytic activity of SnO2/pumice under sunlight irradiation shows the degradation of MO and CV by about 85 and 70% within 40 and 60 min, respectively. Moreover, the radical scavengers test discovered that h+ and OH ̇ radicals play a crucial role, whereas
·
O2
− radicals also exhibited a minor role in the degradation process. In addition, the XRD, FTIR, EDX and XRF analysis of the fresh and used SnO2/pumice sample was carried out to detect a minimal change in sample peaks even after the photocatalytic experiment. As a future aspect, after SnO2/pumice reusability, it can be again reused as a bare substrate in the same synthesis process.
Development of 3D printed nanomaterials for restoration of exterior artworks
Authors: Mansi E. , Terranova G. , Linardi D. , Marfia S. , Monaldo E. , Ricci M. , Imbimbo M. , Pelliccio A. , Brunetin A. , D’Amato R.
Published: September 2023

Despite the great potential of 3D printing technologies coupled with nanotechnologies, just few studies are present in the scientific literature. Application of nanocomposites materials for 3D printing in the field of cultural heritage restoration, is a promising approach to obtain novel and functionalized materials for the artworks element to be recreated. In this context, the present work aims to study innovative nanocomposites materials suitable for the considered application. A commercial PLA filament was additivated with SiC, SiO2 and TiO2 nanoparticles, synthetized by CO2 laser pyrolysis. Nanocomposite filaments were produced by a co-rotating twin-screw extruder and specimens were produced by 3D printing and analysed against their mechanical and hydrophobic properties by means of tensile tests and water absorption and contact angle measurements, respectively.
Functionalized gold nanorods as drug carriers: a promising antiviral system
Authors: Olivieri Elena , Amatori Simone , Marsotto Martina , Iucci Giovanna , Battocchio Chiara , Pellei Maura , Santini Carlo , Cara Andrea , Michelini Zuleika , Colone Marisa , Calcabrini Annarica , Paladini Alessandra , Toschi Francesco , Venditti Iole , Stringaro Annarita
Published: September 2023

Functionalized gold nanorods (AuNRs) are innovative tools useful in theranostics, combining diagnostics and therapy and allowing optimal and personal treatment of patients. Moreover, AuNRs are studied for use in photothermal therapy and imaging thanks to the peculiar phenomenon of Localised Surface Plasmon Resonance (LSPR), which allows them to be identified through spectroscopic techniques in the energy range in which biological tissues are not active. Their functionalization can involve a variety of molecules, including specific drugs or peptides, allowing a controlled transport and release of desired drugs. In this framework, AuNRs were synthesised and characterised through spectroscopic (UV–Vis-NIR, XPS) and microscopic techniques (TEM, FE-SEM). Furthermore, their cytotoxic activity was evaluated on Vero E6 cell line by MTT assay. The data obtained confirm the AuNRs are promising carriers for antiviral drugs, opening new possibilities of application for biomedical field.
A SP-ICP-MS protocol for the detection of metal nanoparticles composition and size in tattooed ex vivo human skin explants
Authors: Bocca B , Caimi S , Failla CM , Dellambra E , Lulli D , Carbone ML , Scatozza F , De Angelis I , Battistini B
Published: September 2023

We developed and validated a protocol based on Single Particle Inductively Coupled Plasma Mass Spectrometry (SP ICP-MS) to detect composition and size of metal nanoparticles (MNPs) in tattoo inks end ex vivo tattooed human skin explants. The explants were tattooed with different inks using an ordinary tattoo machine. Then, 72 hours after tattooing, skin explants were subjected to alkaline extraction by tetramethylammonium hydroxide solution and MNPs of Ag, Al2O3, Au, Cr2O3, CuO, Fe2O3, TiO2 and ZnO were analysed for particle composition and size by SP ICP-MS. The method was validated by assessing the limit of detection, accuracy, precision, and size stability over 72 hours. Particles of Al2O3, Cr2O3, CuO, Fe2O3, TiO2 and ZnO were observed in human skin in the range from 27 nm to 153 nm, and from 26 nm to 228 nm in tattoo inks. Ag and Au NPs were not found neither in inks nor in the skin. Advantages of the protocol were the ability to simultaneously detect the composition of particles and their size, the straightforward sample preparation, the high sensitivity and precision, and the speed of execution of the analysis. The developed methodology can be applied to skin exposed to other consumer products topically applied, such as sunscreens, cosmetics, personal care products and medical devices, which can be all sources of MNPs, in order to improve knowledge and support the human exposure assessment process.
Study on tool wear morphology and mechanism of coated tool on turning austenitic stainless steel
Authors: Zhu Zhenguo , Yang Haidong
Published: September 2023

The dry cutting test of austenitic stainless steel 06Cr19Ni10 workpiece material was carried out with YBG205 coated tool. By scanning electron scanning microscope (SEM) and energy dispersive spectrum (EDS), the wear morphology and wear mechanism of the tool were analysed. The results showed that when cutting the stainless steel 06Cr19Ni10 with YBG205 coated tool, the main wear morphologies of the tool were flank wear, boundary wear, and tip damage. The wear mechanism were mainly adhesive wear and diffusion wear.
Neural network structure optimization for Hefei Light Source II β function correction
Authors: Yu Y.B. , Ni W.B. , Xuan K. , Li W.M. , Xu W. , Li C. , Liu G.F.
Published: September 2023

In this study, we address the design challenges related to hyperparameters, such as the number of layers and nodes in deep neural networks, by introducing an Improved Genetic Algorithm-based method for optimizing neural network structures (IGA-DNN). We apply this method to the practical problem of β function correction in particle accelerators and develop a storage ring β function correction scheme based on IGA-DNN. We compare our approach with traditional genetic algorithm-optimized neural networks to evaluate its performance.
Our results reveal that the neural network optimized by the improved genetic algorithm reduces the number of layers by three and decreases training time by a factor of three, leading to a more efficient model. Moreover, the accuracy of β function simulation correction is enhanced using the IGA-DNN method. This approach can also be extended to optimize other optical parameters and tackle multi-parameter optimization problems, showcasing its versatility and potential for broader applications across various fields.
Design and thermal analysis of the BPM-bellows assembly front-end photon block for Hefei Advanced Light Facility
Authors: Bian Baoyuan , Wang Sihui , Hong Yuanzhi , Fan Le , Ge Xiaoqin , Fang Jianwei , Zhang Wenli , Ma Wenjing , Wang Yong
Published: September 2023

The BPM-bellows front-end photon block with ellipse
cross-sections has been designed for Hefei Advanced Light Facility
(HALF). Such structure has lower longitudinal coupling impedances
than the photon block with commonly-used circle cross-sections. In
addition, two types of cooling structures have been designed, which
are shared water-cooling pipe (cooling structure 1, CS1) and
independent water-cooling tank (cooling structure 1, CS2),
respectively. The CS1 is simple and space-saving, while the CS2 has
better heat dissipation capability. In order to calculate power
density on complex light-receiving surfaces, the Monte Carlo
simulation tool, Synrad, was applied. By building finite element
models and importing power density data from Syrand, the temperature
and thermal stress distributions of photon blocks with two different
cooling structures were calculated. The thermal analysis indicates
that the maximum temperature (37.73°C) is located at CS1, but
the maximum stress (16.28 MPa) is on CS2 due to the difference in
structure and heat dissipation capability. Moreover, the maximum
temperature and thermal stress values are far below the material
criteria of CuCrZr. Therefore, the simple and space-saving CS1 is
more suitable for HALF, which can reduce manufacturing costs and
better satisfy the compact layout in the storage ring.
Wind-modulated groundwater discharge along a microtidal Arctic coastline
Authors: Guimond Julia A , Demir Cansu , Kurylyk Barret L , Walvoord Michelle A , McClelland James W , Cardenas M Bayani
Published: September 2023

Groundwater discharge transports dissolved constituents to the ocean, affecting coastal carbon budgets and water quality. However, the magnitude and mechanisms of groundwater exchange along rapidly transitioning Arctic coastlines are largely unknown due to limited observations. Here, using first-of-its-kind coastal Arctic groundwater timeseries data, we evaluate the magnitude and drivers of groundwater discharge to Alaska’s Beaufort Sea coast. Darcy flux calculations reveal temporally variable groundwater fluxes, ranging from −6.5 cm d−1 (recharge) to 14.1 cm d−1 (discharge), with fluctuations in groundwater discharge or aquifer recharge over diurnal and multiday timescales during the open-water season. The average flux during the monitoring period of 4.9 cm d−1 is in line with previous estimates, but the maximum discharge exceeds previous estimates by over an order-of-magnitude. While the diurnal fluctuations are small due to the microtidal conditions, multiday variability is large and drives sustained periods of aquifer recharge and groundwater discharge. Results show that wind-driven lagoon water level changes are the dominant mechanism of fluctuations in land–sea hydraulic head gradients and, in turn, groundwater discharge. Given the microtidal conditions, low topographic relief, and limited rainfall along the Beaufort Sea coast, we identify wind as an important forcing mechanism of coastal groundwater discharge and aquifer recharge with implications for nearshore biogeochemistry. This study provides insights into groundwater flux dynamics along this coastline over time and highlights an oft overlooked discharge and circulation mechanism with implications towards refining solute export estimates to coastal Arctic waters.
Experimental and numerical study on unsteady entrainment behaviour of ventilated air mass in underwater vehicles
Authors: Qu Zhaoyu , Yang Nana , Yao Xiongliang , Wu Wenhua , Ma Guihui
Published: September 2023

The hydrodynamic characteristics of underwater vehicles are significantly affected by the ventilated cavity covered by the vehicle surface. In this paper, the unsteady flow characteristics of this ventilated cavity are studied using experimental and numerical methods, and the unsteady entrainment behaviour of the ventilated air mass is emphasised. The flow pattern of the ventilated air mass is recorded using a high-speed camera. The large eddy simulation turbulence model is employed for the numerical simulations, and a good agreement is observed between the experimental and numerical results. In the early stage of the formation of the ventilated air mass, the internal structure exhibits a symmetric kidney vortex system, while the ventilated cavity below the vent hole has a continuous hairpin vortex structure. The ventilated air mass experiences a growth stage, an entrainment stage, and a shedding stage. The entrainment behaviour enables the ventilated air mass to quickly fill the ventilated cavity and modifies the surface pressure distribution of the vehicle. As the cavitation number decreases, the radial size of the ventilated cavity increases, and the contact area between the cavity and the water body increases, thus enhancing the vertical drag coefficient of the vehicle.
Mechanical properties of polyamide 12 manufactured by means of SLS: Influence of wall thickness and build direction
Authors: Rodríguez Alejandro Garcia , Mora Edgar Espejo , Velasco Marco Antonio , Tovar Carlos Alberto Narváez
Published: September 2023

The wall thickness and build direction of PA 12 parts manufactured via SLS are currently being investigated for applications requiring low weight and good mechanical properties (ultimate tensile strength, elongation at break, elastic modulus, and hardness). Current design guidelines for the SLS process include recommendations about the influence of build direction on the mechanical properties of the part; however, the recommended minimum wall thickness only considers the process's manufacturability, so this study aims to determine the wall thickness and build orientation conditions that present the slightest difference in mechanical properties, considering different conditions as vertical, horizontal, and transverse build directions and wall thicknesses of 2.0, 2.5 and 3.0 mm. Statistical differences were found between build direction, ultimate tensile stress, and elongation at break and hardness. It was observed that the significant differences in the direction of impression were between the vertical direction versus the transverse and horizontal directions. The differences were between the values of 2.0 mm versus 2.5 and 3.0 mm for the wall thickness. The mechanical properties between these last two thicknesses do not present significant differences, so it is suggested that parts manufactured with PA 12 by SLS with thicknesses of 2.5 mm could have the same tensile mechanical properties as those of 3.0 mm. The horizontal and transverse directions with a 2.5–3.0 mm thickness showed the highest mechanical properties with an ultimate tensile stress of ≈ 43 MPa, a modulus of elasticity of 2.2 GPa, and an elongation at break of 16%–18% and a hardness of ≈ 75 Shore D.
Editorial: ‘Bioinspired Adaptive Intelligent Robots’
Authors: Donati E , Laschi C , Mazzolai B , Bartolozzi C
Published: September 2023

The NCE Focus Issue on Bioinspired Adaptive Intelligent Robots aims at collecting evidence of the different forms of biomimicry in robotics, from soft robotics and embodiment to neuromorphic sensing, computation and control, as enabling approaches to intelligent and adaptive robots.
Defining the single base importance of human mRNAs and lncRNAs
Authors: Fan Rui , Ji Xiangwen , Li Jianwei , Cui Qinghua , Cui Chunmei
Published: September 2023

As the fundamental unit of a gene and its transcripts, nucleotides have enormous impacts on the gene function and evolution, and thus on phenotypes and diseases. In order to identify the key nucleotides of one specific gene, it is quite crucial to quantitatively measure the importance of each base on the gene. However, there are still no sequence-based methods of doing that. Here, we proposed Base Importance Calculator (BIC), an algorithm to calculate the importance score of each single base based on sequence information of human mRNAs and long noncoding RNAs (lncRNAs). We then confirmed its power by applying BIC to three different tasks. Firstly, we revealed that BIC can effectively evaluate the pathogenicity of both genes and single bases through single nucleotide variations. Moreover, the BIC score in The Cancer Genome Atlas somatic mutations is able to predict the prognosis of some cancers. Finally, we show that BIC can also precisely predict the transmissibility of SARS-CoV-2. The above results indicate that BIC is a useful tool for evaluating the single base importance of human mRNAs and lncRNAs.
Multimodal learning of noncoding variant effects using genome sequence and chromatin structure
Authors: Tan Wuwei , Shen Yang
Published: September 2023

Motivation

A growing amount of noncoding genetic variants, including single-nucleotide polymorphisms, are found to be associated with complex human traits and diseases. Their mechanistic interpretation is relatively limited and can use the help from computational prediction of their effects on epigenetic profiles. However, current models often focus on local, 1D genome sequence determinants and disregard global, 3D chromatin structure that critically affects epigenetic events.

Results

We find that noncoding variants of unexpected high similarity in epigenetic profiles, with regards to their relatively low similarity in local sequences, can be largely attributed to their proximity in chromatin structure. Accordingly, we have developed a multimodal deep learning scheme that incorporates both data of 1D genome sequence and 3D chromatin structure for predicting noncoding variant effects. Specifically, we have integrated convolutional and recurrent neural networks for sequence embedding and graph neural networks for structure embedding despite the resolution gap between the two types of data, while utilizing recent DNA language models. Numerical results show that our models outperform competing sequence-only models in predicting epigenetic profiles and their use of long-range interactions complement sequence-only models in extracting regulatory motifs. They prove to be excellent predictors for noncoding variant effects in gene expression and pathogenicity, whether in unsupervised “zero-shot” learning or supervised “few-shot” learning.

Availability and implementation

Codes and data can be accessed at https://github.com/Shen-Lab/ncVarPred-1D3D and https://zenodo.org/record/7975777.
Phylogenetic inference using generative adversarial networks
Authors: Smith Megan L , Hahn Matthew W
Published: September 2023

Motivation

The application of machine learning approaches in phylogenetics has been impeded by the vast model space associated with inference. Supervised machine learning approaches require data from across this space to train models. Because of this, previous approaches have typically been limited to inferring relationships among unrooted quartets of taxa, where there are only three possible topologies. Here, we explore the potential of generative adversarial networks (GANs) to address this limitation. GANs consist of a generator and a discriminator: at each step, the generator aims to create data that is similar to real data, while the discriminator attempts to distinguish generated and real data. By using an evolutionary model as the generator, we use GANs to make evolutionary inferences. Since a new model can be considered at each iteration, heuristic searches of complex model spaces are possible. Thus, GANs offer a potential solution to the challenges of applying machine learning in phylogenetics.

Results

We developed phyloGAN, a GAN that infers phylogenetic relationships among species. phyloGAN takes as input a concatenated alignment, or a set of gene alignments, and infers a phylogenetic tree either considering or ignoring gene tree heterogeneity. We explored the performance of phyloGAN for up to 15 taxa in the concatenation case and 6 taxa when considering gene tree heterogeneity. Error rates are relatively low in these simple cases. However, run times are slow and performance metrics suggest issues during training. Future work should explore novel architectures that may result in more stable and efficient GANs for phylogenetics.

Availability and implementation

phyloGAN is available on github: https://github.com/meganlsmith/phyloGAN/.
Automated machine learning for genome wide association studies
Authors: Lakiotaki Kleanthi , Papadovasilakis Zaharias , Lagani Vincenzo , Fafalios Stefanos , Charonyktakis Paulos , Tsagris Michail , Tsamardinos Ioannis
Published: September 2023

Motivation

Genome-wide association studies (GWAS) present several computational and statistical challenges for their data analysis, including knowledge discovery, interpretability, and translation to clinical practice.

Results

We develop, apply, and comparatively evaluate an automated machine learning (AutoML) approach, customized for genomic data that delivers reliable predictive and diagnostic models, the set of genetic variants that are important for predictions (called a biosignature), and an estimate of the out-of-sample predictive power. This AutoML approach discovers variants with higher predictive performance compared to standard GWAS methods, computes an individual risk prediction score, generalizes to new, unseen data, is shown to better differentiate causal variants from other highly correlated variants, and enhances knowledge discovery and interpretability by reporting multiple equivalent biosignatures.

Availability and implementation

Code for this study is available at: https://github.com/mensxmachina/autoML-GWAS. JADBio offers a free version at: https://jadbio.com/sign-up/. SNP data can be downloaded from the EGA repository (https://ega-archive.org/). PRS data are found at: https://www.aicrowd.com/challenges/opensnp-height-prediction. Simulation data to study population structure can be found at: https://easygwas.ethz.ch/data/public/dataset/view/1/.
Novel progestogenic androgens for male contraception: design, synthesis, and activity of C7 α-substituted testosterone
Authors: Lee Min S , Bunin Deborah I , Furimsky Anna M , Nguyen Donna , Parman Toufan , Kim Kyuri , Rausch Linda , Lin Ming-Teh , Gupta Pranab , Brown Jill E , Kroopnick Jeffrey M , Blithe Diana L
Published: September 2023

Male contraceptive development has included use of testosterone (T) with or without a progestin or the use of a single molecule such as progestogenic androgens (PA) for suppression of testicular T production. Expanding upon the vast amount of data accumulated from nortestosterone (NT), NT analogs, and their prodrugs, a new series of PA, the C7 methyl, and ethyl α-substituted T analogs 7α-Methyltestosterone (7α-MT) and 7α-Ethyltestosterone (7α-ET), respectively, were hypothesized and designed to have superior androgenic and progestogenic activities when compared with parent T. Results from androgen receptor and progesterone receptor competitive binding and transcriptional activation assays showed favorable activities for these T analogs. Additionally, 7α-MT and 7α-ET were shown to be active substrates for aromatase in vitro, mitigating a potential negative impact on bone mineral density with long-term use. In conjunction with this observation, the diminished metabolism of these T analogs by 5α-reductase may reduce potential concerns for prostatic growth. In the Hershberger in vivo rat bioassay, 7α-MT and 7α-ET showed superior androgenic and anabolic activities as compared with T. These C7 α-substituted T analogs also showed clear progestogenic activity in the McPhail bioassay which evaluated endometrial glandular arborization in a rabbit model. The discovery of aromatizable molecules with reduced metabolism by 5α-reductase that have androgenic, anabolic, and progestogenic properties indicates that the core and/or prodrugs of 7α-MT and 7α-ET are promising molecules for further development as male contraceptive PAs.
Novel variant in CADM3 causes Charcot–Marie–Tooth disease
Authors: Yalcouyé Abdoulaye , Rebelo Adriana P , Cissé Lassana , Rives Lynette , Bamba Salia , Cogan Joy , Esoh Kevin , Diarra Salimata , Ezell Kimberly M , Taméga Abdoulaye , Guinto Cheick O , Dohrn Maike F , Hamid Rizwan , Fischbeck Kenneth H , Zuchner Stephan , Landouré Guida
Published: September 2023

CADM3 has been recently reported causing a rare axonal Charcot–Marie–Tooth disease in three independent Caucasian families carrying a recurrent change. We describe the first alternative causative mutation in CADM3 in a family from black African and also observed de novo in a patient of Caucasian ancestry. The disease inheritance was consistent with autosomal dominant and sporadic patterns, respectively. Eight patients and their relatives were enroled from both families. The mean age at diagnosis was 33.9 years, and walking difficulty was commonly the first symptom. Neurological examination showed distal muscle weakness and atrophy, sensory loss and foot and hand deformities. A high clinical variability was noted, but as seen in CADM3-associated neuropathy, symptoms were more pronounced in the arms in some patients. Nerve conduction studies showed no response in most of the examined nerves, and an axonal type of neuropathy, where recorded. Whole exome sequencing revealed a novel missense variant (c.1102G>T; Gly368Cys) in CADM3, segregating with the disease. Functional analyses showed a significant decrease in CADM3-Gly368Cys protein levels in the membrane and major structural changes in its predicted secondary structure. Therefore, we extend the genotype spectrum of CADM3, underlining the need for genetic studies in underrepresented populations like in Africa.
Analysis of quantile graphs in EGC data from elderly and young individuals using machine learning and deep learning
Authors: Pineda Aruane M , Alves Caroline L , Möckel Michael , Toutain Thaise G L de O , Moura Porto Joel Augusto , Rodrigues Francisco A
Published: September 2023

Heart disease, also known as cardiovascular disease, encompasses a variety of heart conditions that can result in sudden death for many people. Examples include high blood pressure, ischaemia, irregular heartbeats and pericardial effusion. Electrocardiogram (ECG) signal analysis is frequently used to diagnose heart diseases, providing crucial information on how the heart functions. To analyse ECG signals, quantile graphs (QGs) is a method that maps a time series into a network based on the time-series fluctuation proprieties. Here, we demonstrate that the QG methodology can differentiate younger and older patients. Furthermore, we construct networks from the QG method and use machine-learning algorithms to perform the automatic diagnosis, obtaining high accuracy. Indeed, we verify that this method can automatically detect changes in the ECG of elderly and young subjects, with the highest classification performance for the adjacency matrix with a mean area under the receiver operating characteristic curve close to one. The findings reported here confirm the QG method’s utility in deciphering intricate, nonlinear signals like those produced by patient ECGs. Furthermore, we find a more significant, more connected and lower distribution of information networks associated with the networks from ECG data of the elderly compared with younger subjects. Finally, this methodology can be applied to other ECG data related to other diseases, such as ischaemia.
What is the diagnosis?
Authors: Almasri Murad , Salim Hamza , Orcutt Jeffrey
Published: September 2023

In this manuscript, we present an ECG that is diagnostic of congenitally corrected transposition of great arteries (ccTGA) and ask about the arrhythmias associated as well as the management options.
Digest: Urbanization shapes selection altering food webs
Authors: Williams Magie
Published: September 2023

How has urbanization altered the relationships between species and selection on phenotypes? To address this question, Palacio and Ordano measured trait and frugivore selection in blue passionflower (Passiflora caerulea) in three different localities. Their analysis revealed changes in avian selection with urbanization, which altered population phenotypes.
Quantifying assays: inhibition of signalling pathways of cancer
Authors: Anguelov Roumen , Manjunath G , Phiri Avulundiah E , Nyakudya Trevor T , Bipath Priyesh , C. Serem June , N. Hlophe Yvette
Published: September 2023

Inhibiting a signalling pathway concerns controlling the cellular processes of a cancer cell’s viability, cell division and death. Assay protocols created to see if the molecular structures of the drugs being tested have the desired inhibition qualities often show great variability across experiments, and it is imperative to diminish the effects of such variability while inferences are drawn. In this paper, we propose the study of experimental data through the lenses of a mathematical model depicting the inhibition mechanism and the activation-inhibition dynamics. The method is exemplified through assay data obtained from an experimental study of the inhibition of the chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) signalling pathway of melanoma cells. The quantitative analysis is conducted as a two step process: (i) deriving theoretically from the model the cell viability as a function of time depending on several parameters; (ii) estimating the values of the parameters by using the experimental data. The cell viability is obtained as a function of concentration of the inhibitor and time, thus providing a comprehensive characterization of the potential therapeutic effect of the considered inhibitor, e.g. $IC_{50}$ can be computed for any time point.
Interspecific Variation in the Inner Ear Maculae of Sharks
Authors: Sauer Derek J , Yopak Kara E , Radford Craig A
Published: September 2023

Synopsis

There is well-documented diversity in the organization of inner ear hair cells in fishes; this variation is thought to reflect the differing functional requirements of species across a range of ecological niches. However, relatively little is known about interspecific variation (and its potential ecological implications) in the number and density of inner ear hair cells in elasmobranchs (sharks, skates, and rays). In this study, we quantified inner ear hair cells in the saccule, lagena, utricle, and macula neglecta of 9 taxonomically and ecologically distinct shark species. Using phylogenetically informed comparative approaches, sharks that feed in the water column had significantly greater hair cell density and total number of hair cells in the lagena and macula neglecta (i.e., vertically oriented maculae) compared to species that feed primarily on the seafloor. In addition, sharks within Carcharhinidae seemingly possess a specialized macula neglecta compared to other shark species. Overall, findings suggest that, similar to bony fishes, there is considerable variation in hair cell organization of shark inner ears, which may be tied to variation in ecology and/or specialized behaviors between different species.
Food Insecurity and Unrest Participation: Evidence from Johannesburg, South Africa
Authors: Rudolfsen Ida
Published: September 2023

This study assesses the claim that food insecurity leads to participation in unrest. I argue that insecure access to food can provide a motivational force to engage in urban unrest. But individuals must also have the capacity to partake in collective action, and acute food insecurity may undermine mobilization potential. Further, food insecurity is a mundane and widespread grievance often seen as an apolitical issue. I therefore suggest that organizational networks could facilitate the occurrence of unrest, as they provide both an existing mobilizing structure and the potential to politicize an individual-level grievance. The article explores the relationship between food access and unrest participation on the individual level in the context of Johannesburg, South Africa. I find that food insecurity increases the likelihood of unrest participation and that some types of organizational networks are catalysts of such effects.
The 2023 Impact of Inflammatory Bowel Disease in Canada: The Influence of Sex and Gender on Canadians Living With Inflammatory Bowel Disease
Authors: Targownik Laura E , Bollegala Natasha , Huang Vivian W , Windsor Joseph W , Kuenzig M Ellen , Benchimol Eric I , Kaplan Gilaad G , Murthy Sanjay K , Bitton Alain , Bernstein Charles N , Jones Jennifer L , Lee Kate , Peña-Sánchez Juan-Nicolás , Rohatinsky Noelle , Ghandeharian Sara , Davis Tal , Weinstein Jake , Im James H B , Jannati Nazanin , Khan Rabia , Matthews Priscilla , Jones May Tyrel , Tabatabavakili Sahar , Jogendran Rohit , Hazan Elias , Browne Mira , Meka Saketh , Vukovic Sonya , Jogendran Manisha , Hu Malini , Osei Jessica Amankwah , Wang Grace Y , Sheekha Tasbeen Akhtar , Dahlwi Ghaida , Goddard Quinn , Gorospe Julia , Nisbett Cyanne , Gertsman Shira , Sousa James , Morganstein Taylor , Stocks Taylor , Weber Ann , Seow Cynthia H
Published: September 2023

Sex (the physical and physiologic effects resulting from having specific combinations of sex chromosomes) and gender (sex-associated behaviours, expectations, identities, and roles) significantly affect the course of inflammatory bowel disease (IBD) and the experience of living with IBD. Sex-influenced physiologic states, like puberty, the menstrual cycle, pregnancy, and andropause/menopause may also impact and be impacted by IBD.

While neither Crohn’s disease nor ulcerative colitis is commonly considered sex-determined illnesses, the relative incidence of Crohn’s disease and ulcerative colitis between males and females varies over the life cycle. In terms of gender, women tend to use healthcare resources at slightly higher rates than men and are more likely to have fragmented care. Women are more commonly prescribed opioid medications and are less likely than men to undergo colectomy. Women tend to report lower quality of life and have higher indirect costs due to higher rates of disability. Women are also more likely to take on caregiver roles for children with IBD. Women with IBD are more commonly burdened with adverse mental health concerns and having poor mental health has a more profound impact on women than men.

Pregnant people with active IBD have higher rates of adverse outcomes in pregnancy, made worse in regions with poor access to IBD specialist care. The majority of individuals with IBD in Canada do not have access to a pregnancy-in-IBD specialist; access to this type of care has been shown to allay fears and increase knowledge among pregnant people with IBD.
The 2023 Impact of Inflammatory Bowel Disease in Canada: Treatment Landscape
Authors: Murthy Sanjay K , Weizman Adam V , Kuenzig M Ellen , Windsor Joseph W , Kaplan Gilaad G , Benchimol Eric I , Bernstein Charles N , Bitton Alain , Coward Stephanie , Jones Jennifer L , Lee Kate , Peña-Sánchez Juan-Nicolás , Rohatinsky Noelle , Ghandeharian Sara , Sabrie Nasruddin , Gupta Sarang , Brar Gurmun , Khan Rabia , Im James H B , Davis Tal , Weinstein Jake , St-Pierre Joëlle , Chis Roxana , Meka Saketh , Cheah Eric , Goddard Quinn , Gorospe Julia , Kerr Jack , Beaudion Kayla D , Patel Ashley , Russo Sophia , Blyth Jonathan , Blyth Stephanie , Charron-Bishop Diane , Targownik Laura E
Published: September 2023

The therapeutic landscape for inflammatory bowel disease (IBD) has changed considerably over the past two decades, owing to the development and widespread penetration of targeted therapies, including biologics and small molecules. While some conventional treatments continue to have an important role in the management of IBD, treatment of IBD is increasingly moving towards targeted therapies given their greater efficacy and safety in comparison to conventional agents. Early introduction of these therapies—particularly in persons with Crohn’s disease—combining targeted therapies with traditional anti-metabolite immunomodulators and targeting objective markers of disease activity (in addition to symptoms), have been shown to improve health outcomes and will be increasingly adopted over time. The substantially increased costs associated with targeted therapies has led to a ballooning of healthcare expenditure to treat IBD over the past 15 years. The introduction of less expensive biosimilar anti-tumour necrosis factor therapies may bend this cost curve downwards, potentially allowing for more widespread access to these medications. Newer therapies targeting different inflammatory pathways and complementary and alternative therapies (including novel diets) will continue to shape the IBD treatment landscape. More precise use of a growing number of targeted therapies in the right individuals at the right time will help minimize the development of expensive and disabling complications, which has the potential to further reduce costs and improve outcomes.
The 2023 Impact of Inflammatory Bowel Disease in Canada: COVID-19 and IBD
Authors: Kaplan Gilaad G , Kuenzig M Ellen , Windsor Joseph W , Bernstein Charles N , Bitton Alain , Coward Stephanie , Jones Jennifer L , Lee Kate , Murthy Sanjay K , Targownik Laura E , Peña-Sánchez Juan-Nicolás , Ghandeharian Sara , Rohatinsky Noelle , Weinstein Jake , Jones May Tyrel , Browne Mira , Jannati Nazanin , Tabatabavakili Sahar , Im James H B , Meka Saketh , Vukovic Sonya , Davis Tal , Goddard Quinn , Gorospe Julia , Stocks Taylor , Caplan Léa , Kanaan Najla , Stuart Daniel , Ramsay Tesa , Robinson Kelly J , Charron-Bishop Diane , Benchimol Eric I
Published: September 2023

The COVID-19 pandemic had a monumental impact on the inflammatory bowel disease (IBD) community. At the beginning of the pandemic, knowledge on the effect of SARS-CoV-2 on IBD was lacking, especially in those with medication-suppressed immune systems. Throughout the pandemic, scientific literature exponentially expanded, resulting in clinical guidance and vaccine recommendations for individuals with IBD. Crohn’s and Colitis Canada established the COVID-19 and IBD Taskforce to process and communicate rapidly transforming knowledge into guidance for individuals with IBD and their caregivers, healthcare providers, and policy makers. Recommendations at the onset of the pandemic were based on conjecture from experience of prior viruses, with a precautionary principle in mind. We now know that the risk of acquiring COVID-19 in those with IBD is the same as the general population. As with healthy populations, advanced age and comorbidities increase the risk for severe COVID-19. Individuals with IBD who are actively flaring and/or who require high doses of prednisone are susceptible to severe COVID-19 outcomes. Consequently, sustaining maintenance therapies (e.g., biologics) is recommended. A three-dose mRNA COVID-19 vaccine regimen in those with IBD produces a robust antibody response with a similar adverse event profile as the general population. Breakthrough infections following vaccine have been observed, particularly as the virus continues to evolve, which supports receiving a bivalent vaccine booster. Limited data exist on the impact of IBD and its therapies on long-term outcomes following COVID-19. Ongoing research is necessary to address new concerns manifesting in those with IBD throughout the evolving pandemic.
Algorithmic Personalized Pricing with the Right to Explanation
Authors: Zhao Zeyu
Published: September 2023

Personalized pricing by algorithms has been widely deployed by digital platforms. Although this strategy provides economic efficiencies and benefits consumers, it precipitates discriminatory, exploitative, and exclusionary effects on the market. If massive market power and certain information asymmetry exist, this pricing behavior could be illegal as the negatives could outweigh the positives. The negatives could nevertheless not be fully addressed by current ex-post and ex-ante antitrust, consumer protection, and anti-discrimination approaches because the sloping pricing information between platforms and consumers based on data will not be effectively rebalanced considering these approaches. Data protection measures should be underlined, despite the flaws of some data rights. This article shows how the right to explanation as a synthetic right of data protection mitigates the damaging effects by providing consumers with the access to the result of algorithmic decision-making to optimize the information distribution, despite the application limits due to technological and cognitive immatureness of ‘explanation’.
The Ready-To-Go Questionnaire predicts health outcomes during travel: a smartphone application-based analysis
Authors: Maier Julian D , Anagnostopoulos Alexia , Gazzotti Anna , Bühler Silja , Baroutsou Vasiliki , Hatz Christoph , Puhan Milo A , Fehr Jan , Farnham Andrea
Published: September 2023

Background

The Ready-To-Go (R2G) Questionnaire is a tool for rapid assessment of health risks for travel consultation. This study aims to assess the utility of the R2G Questionnaire in identifying high-risk travellers and predicting health events and behaviour during travel in the TOURIST2 prospective cohort.

Methods

TOURIST2 data were used to calculate the R2G medical and travel risk scores and categorize each participant based on their risk. The TOURIST2 study enrolled 1000 participants from Switzerland’s largest travel clinics between 2017 and 2019. Participants completed daily smartphone application surveys before, during and after travel on health events and behaviours. We used regression models to analyse incidence of overall health events and of similar health events grouped into health domains (e.g. respiratory, gastrointestinal, accident/injury). Incidence rate ratios (IRR) are displayed with 95% confidence intervals (95% CI).

Results

R2G high-risk travellers experienced significantly greater incidence of health events compared to lower-risk travellers (IRR = 1.27, 95% CI: 1.22–1.33). Both the medical and travel scores showed significant positive associations with incidence of health events during travel (IRR = 1.11, 95% CI: 1.07–1.16; IRR = 1.07, 95% CI: 1.03–1.12, respectively), with significant increases in all health domains except skin disorders. Medical and travel risk scores were associated with different patterns in behaviour. Travellers with chronic health conditions accessed medical care during travel more often (IRR = 1.16, 95% CI: 1.03–1.31), had greater difficulty in carrying out planned activities (IRR = –0.04, 95% CI: –0.05, –0.02), and rated their travel experience lower (IRR = –0.04, 95% CI: –0.06, –0.02). Travellers with increased travel-related risks due to planned travel itinerary had more frequent animal contact (IRR = 1.09, 95% CI: 1.01–1.18) and accidents/injuries (IRR = 1.28, 95% CI: 1.15–1.44).

Conclusions

The R2G Questionnaire is a promising risk assessment tool that offers a timesaving and reliable means to identify high-risk travellers. Incorporated into travel medicine websites, it could serve as a pre-consultation triage to help travellers self-identify their risk level, direct them to the appropriate medical provider(s), and help practitioners in giving more tailored advice.
A nomogram predicting the histologic activity of lupus nephritis from clinical parameters
Authors: Gao Cui , Bian Xueyan , Wu Longlong , Zhan Qian , Yu Fengfei , Pan Hong , Han Fei , Wang Yong-Fei , Yang Yi
Published: September 2023

Background

The 2021 clinical guidelines of the Kidney Disease: Improving Global Outcomes emphasize the importance of the histological activity index (AI) in the management of lupus nephritis (LN). Patients with LN and a high AI have poor renal outcomes and high rates of nephritic relapse. In this study we constructed prediction models for the AI in LN.

Methods

The study population comprised 337 patients diagnosed with LN using kidney biopsy. The participants were randomly divided into training and testing cohorts. They were further divided into high-activity (AI >2) and low-activity (AI ≤2) groups. This study developed two clinical prediction models using logistic regression and least absolute shrinkage and selection operator (LASSO) analyses with laboratory test results collected at the time of kidney biopsy. The performance of models was assessed using 5-fold cross-validation and validated in the testing cohort. A nomogram for individual assessment was constructed based on the preferable model.

Results

Multivariate analysis showed that higher mean arterial pressure, lower estimated glomerular filtration rate, lower complement 3 level, higher urinary erythrocytes count and anti-double-stranded DNA seropositivity were independent risk factors for high histologic activity in LN. Both models performed well in the testing cohort regarding the discriminatory ability to identify patients with an AI >2. The average area under the curve of 5-fold cross-validation was 0.855 in the logistic model and 0.896 in the LASSO model. A webtool based on the LASSO model was created for clinicians to enter baseline clinical parameters to produce a probability score of an AI >2.

Conclusions

The established nomogram provides a quantitative auxiliary tool for distinguishing LN patients with a high AI and helps physicians make clinical decisions in their comprehensive assessment.
Arabidopsis MCTP family member QUIRKY regulates the formation of the STRUBBELIG receptor kinase complex
Authors: Chen Xia , Leśniewska Barbara , Boikine Rodion , Yun Nicole , Mody Tejasvinee Atul , Vaddepalli Prasad , Schneitz Kay
Published: September 2023

Intercellular communication plays a central role in organogenesis. Tissue morphogenesis in Arabidopsis (Arabidopsis thaliana) requires signaling mediated by a cell surface complex containing the atypical receptor kinase STRUBBELIG (SUB) and the multiple C2 domains and transmembrane region protein QUIRKY (QKY). QKY is required to stabilize SUB at the plasma membrane. However, it is unclear what the in vivo architecture of the QKY/SUB signaling complex is, how it is controlled, and how it relates to the maintenance of SUB at the cell surface. We addressed these questions using a combination of genetics, yeast 2-hybrid assays, and Förster resonance energy transfer (FRET)/fluorescence lifetime imaging microscopy (FLIM) in epidermal cells of seedling roots. We found that QKY promotes the formation of SUB homooligomers in vivo. Homooligomerization of SUB appeared to involve its extracellular domain. We also showed that QKY and SUB physically interact and form a complex at the cell surface in vivo. In addition, the data showed that the N-terminal C2A-B region of QKY interacts with the intracellular domain of SUB. They further revealed that this interaction is essential to maintain SUB levels at the cell surface. Finally, we provided evidence that QKY forms homomultimers in vivo in a SUB-independent manner. We suggest a model in which the physical interaction of QKY with SUB mediates the oligomerization of SUB and attenuates its internalization, thereby maintaining sufficiently high levels of SUB at the cell surface required for the control of tissue morphogenesis.