bluuebunny/crossref_metadata_2025 huggingface dataset:
Macroscopic trends of linear tearing stability in cylindrical current profiles
Authors: Benjamin S , Clauser C , Rea C , Sweeney R , Kumar A , Marmar E
Published: May 2024

The likelihood of realising tokamak power-plants will be greatly improved by the discovery of high-gain equilibria that resist the formation of small islands and hence avoid the disruptive neoclassical tearing mode. We propose a series of studies to understand how simple tokamak design can leverage aspects of tearing onset physics to maximise passive resistance to island formation. Here we investigate the variation that current profiles can bring about in preventing tearing onset through the cylindrical linear tearing stability parameterΔ′. A database of 159148 realistic pilot-plant current profiles was generated with Monte Carlo sampling, and the distribution ofΔ′values was linked with interpretable profile characteristics. In agreement with prior theoretical and experimental studies,Δ′was found to be strongly correlated with the existence and steepness of a local toroidal current well or hill, with the former destabilising and the latter stabilising. In the absence of these two cases, the remainingΔ′values were linearly bounded by the toroidal current gradient at the rational surface.
Spontaneous and tunable valley polarization in two-dimensional single-layer LaCl2
Authors: Liu Hengbo , Li Jia , Tian Jianke , Li Yan , Shi Junjie
Published: May 2024

Applying the valley contrasting properties of valleytronic materials to logical operations is the foundation of valleytronic device manufacturing. It is predicted that single-layer (SL) LaCl2 is an ferrovalley material with intrinsic and tunable valley polarization through first-principles calculations. It is a ferromagnetic semiconductor (bandgap 0.767 eV) with roughly 1.0 μ
B per unit cell as well as out of plane magnetization, and the Curie temperature is about 149 K. The tight-binding model considering five orbitals as well as next nearest neighboring hopping get a consistent band structure with the first-principles calculation. The valley polarization changes from 40.49 to 98.51 meV under the biaxial strain of 5% ∼ −5%. Therefore, the biaxial strain can be a means to tune the valley polarization. In addition, the valley polarization of the double-layer (DL) structure (∼80 meV) is much greater than that of the SL structure (∼59 meV) due to the increased magnetic moment of the DL structure, indicating the potential tunable character by stacking few layers. We believe that SL LaCl2 has great potential for device manufacturing and application in the field of valley electronics.
Design on thermal-mechanism coordination for binding reinforcing mesh based on shape memory polymer
Authors: Gu Xilong , Yin Haibin , Liu Bei , Chen Xi , Chen Weiping , Zhang Haiquan
Published: May 2024

The traditional rebar binding devices require complex drive and transmission mechanisms, which leads to large volume and complex structure. In this paper, a cylindrical thermoplastic shape memory polymer (SMP) fixture is proposed to verify the rebar binding method of thermal-mechanism coordination. The SMP fixture is manufactured by the injection molding technology through selecting suitable-ratio Polylactic acid and Polycaprolactone (PCL) blend materials. Besides, an additional auxiliary device is presented to overcome the incomplete recovery disadvantage existing in the thermoplastic SMP and completely achieve binding the rebar. On this base, two different binding methods are proposed to compare the mechanical performance after fixing the rebar, and the external force/thermal contributions are tested and discussed in detail. The tested results show that the binding contribution of heat could reach 70% while the binding contribution of external force could reach 30% above the transition temperature (Tg
). The maximum tensile force that the binding rebar can withstand under the thermal-mechanism coordination action could reach up to 657.7 N, which is higher than the maximum tensile force of the wire binding. In addition, the maximum friction force between rebar and notches of fixture could reach up to 94.1 N, which further verifies the feasibility of thermal-mechanism coordination for binding reinforcing mesh based on SMP fixture.
Estimation of magnetic levitation and lateral forces in MgB2 superconducting bulks with various dimensional sizes using artificial intelligence techniques
Authors: Alipour Bonab Shahin , Xing Yiteng , Russo Giacomo , Fabbri Massimo , Morandi Antonio , Bernstein Pierre , Noudem Jacques , Yazdani-Asrami Mohammad
Published: May 2024

The advent of superconducting bulks, due to their compactness and performance, offers new perspectives and opportunities in many applications and sectors, such as magnetic field shielding, motors/generators, NMR/MRI, magnetic bearings, flywheel energy storage, Maglev trains, among others. The investigation and characterization of bulks typically relies on time-consuming and expensive experimental campaigns; hence the development of effective surrogate models would considerably speed up the research progress around them. In this study, we first produced an experimental dataset containing the levitation and lateral forces between different MgB2 bulks and one permanent magnet under different operating conditions. Next, we have exploited the dataset to develop surrogate models based on Artificial Intelligence (AI) techniques, namely Extremely Gradient Boosting, Support Vector Regressor (SVR), and Kernel Ridge Regression. After the tuning of the hyperparameters of the AI models, the results demonstrated that SVR is the superior technique and can predict levitation and lateral forces with a worst-case accuracy scenario 99.86% in terms of goodness of fit to experimental data. Moreover, the response time of these models for the estimation of new datapoints is ultra-fast.
Anomalous diffusion, prethermalization, and particle binding in an interacting flat band system
Authors: Daumann Mirko , Dahm Thomas
Published: May 2024

We study the broadening of initially localized wave packets in a quasi one-dimensional diamond ladder with interacting, spinless fermions. The lattice possesses a flat band causing localization. We place special focus on the transition away from the flat band many-body localized case by adding very weak dispersion. By doing so, we allow propagation of the wave packet on significantly different timescales which causes anomalous diffusion. Due to the temporal separation of dynamic processes, an interaction-induced, prethermal equilibrium becomes apparent. A physical picture of light and heavy modes for this prethermal behavior can be obtained within Born–Oppenheimer approximation via basis transformation of the original Hamiltonian. This reveals a detachment between light, symmetric and heavy, anti-symmetric particle species. We show that the prethermal state is characterized by heavy particles binding together mediated by the light particles.
Inferring to cooperate: Evolutionary games with Bayesian inferential strategies
Authors: Patra Arunava , Sengupta Supratim , Paul Ayan , Chakraborty Sagar
Published: May 2024

Strategies for sustaining cooperation and preventing exploitation by selfish agents in repeated games have mostly been restricted to Markovian strategies where the response of an agent depends on the actions in the previous round. Such strategies are characterized by lack of learning. However, learning from accumulated evidence over time and using the evidence to dynamically update our response is a key feature of living organisms. Bayesian inference provides a framework for such evidence-based learning mechanisms. It is therefore imperative to understand how strategies based on Bayesian learning fare in repeated games with Markovian strategies. Here, we consider a scenario where the Bayesian player uses the accumulated evidence of the opponent’s actions over several rounds to continuously update her belief about the reactive opponent’s strategy. The Bayesian player can then act on her inferred belief in different ways. By studying repeated Prisoner’s dilemma games with such Bayesian inferential strategies, both in infinite and finite populations, we identify the conditions under which such strategies can be evolutionarily stable. We find that a Bayesian strategy that is less altruistic than the inferred belief about the opponent’s strategy can outperform a larger set of reactive strategies, whereas one that is more generous than the inferred belief is more successful when the benefit-to-cost ratio of mutual cooperation is high. Our analysis reveals how learning the opponent’s strategy through Bayesian inference, as opposed to utility maximization, can be beneficial in the long run, in preventing exploitation and eventual invasion by reactive strategies.
Effect of Baculovirus oryctes concentration on mortality of Oryctes rhinoceros L.
Authors: Fauzana H , Rahman A
Published: May 2024

One of the key plantation crops in Indonesia, particularly in the expanding Riau region, is oil palm (Elaeis guineensis Jacq.). The frequent attacks by Rhinoceros beetles (Oryctes rhinoceros), are the greatest barrier to oil palm development in Riau region. Integrated Pest Management (IPM), which puts an emphasis on ecologically friendly controls one of which uses the entomopathogen Baculovirus oryctes, is the preferred control strategy. This study sought to determine the optimal suspension concentration of Baculovirus oryctes infected larvae on the mortality of the Oryctes rhinoceros beetle. The treatment given was concentration of Baculovirus oryctes suspension of, 0 ml.500 ml−1 water (0 x 106 PIBs.ml−1), 40 ml.500 ml−1 water (6 x 106 PIBs.ml−1), 50 ml.500 ml−1 water (7.6 x 106 PIBs.ml−1), 60 ml.500 ml−1 water (9.3 x 106 PIBs.ml−1) and 70 ml.500 ml−1 water (9.6 x 106 PIBs.ml−1). The results showed that the suspension concentration of 70 ml.500 ml−1 water (9.6 x 106 PIBs/ml) is the best trend concentration because it generates the fastest initial time of death which is 180 hours, lethal time 50 for 288 hours after application and total mortality of 70.83%. The conclusion is that Baculovirus oryctes can be used to kill rhinoceros beetle Oryctes rhinoceros best at a concentration of 70 ml.500 ml−1 water (9.6 x 106 PIBs ml−1).
On the minimality condition for caustics of pseudo-spherical surfaces
Authors: Jikumaru Yoshiki , Teramoto Keisuke
Published: May 2024

We show that only pseudo-spherical surface whose caustic becomes a minimal surface is Dini surface family. Moreover, we give the Weierstrass data for corresponding minimal surface to the caustic.
Development and Validation of a Composite Skin Quality Scale
Authors: Gold Michael , Lorenc Z Paul , Bass Lawrence S , Bank David , Downie Jeanine , Bellia Gilberto , Giori Andrea , Grimolizzi Franco
Published: May 2024

Background

The increasing demand for skin quality interventions in aesthetic medicine underscores the necessity for objective, evidence-based assessment tools that may be used to evaluate novel interventions or devices.

Objectives

To develop and validate a 5-point photonumeric rating scale for assessing overall skin quality, including radiance, color evenness, and smoothness.

Methods

The IBSA (Institut Biochimique SA) Composite Skin Quality Scale was developed and underwent live validation with 88 real-world patients, chosen to encompass a broad spectrum of skin qualities and Fitzpatrick skin types. Scale validation was performed by board-certified plastic surgeons and dermatologists over 2 rounds, 2 weeks apart. Reliability was assessed through intrarater and interrater agreements, utilizing weighted kappa statistics and intraclass correlation coefficient (ICC). The scale’s ability to discern a clinically relevant 1-grade difference was evaluated with 72 photo pairs.

Results

Combined intrarater reliability results showed weighted kappa values of 0.812 (right side) and 0.815 (left side) and an ICC of 0.903 for both sides, indicating an almost perfect agreement. Interrater reliability ranged from substantial to almost perfect, with kappa coefficients between 0.654 and 0.853 and ICCs between 0.657 and 0.855 across all rater pairs in both rounds. The ability to detect a clinically relevant 1-point difference using the scale was established.

Conclusions

Integrating various key aspects of skin quality, the IBSA Composite Skin Quality Scale is a clinically relevant and highly reliable tool, suitable for skin assessment in clinical studies of new aesthetic technologies and products.

Level of Evidence: 3
Semaglutide for weight loss in people with obesity as an adjunctive treatment for hidradenitis suppurativa: its impact on disease control and quality of life
Authors: Lyons Daniel , Louly Nathan Anusha , Pender Emily , Murray Gregg , Smith Conor , Kirby Brian , Hughes Rosalind
Published: May 2024

Hidradenitis suppurativa (HS) has a significant impact on patients’ quality of life (QoL) and mortality. We report the use of semaglutide and its impact on disease control and QoL in 30 patients with obesity attending an HS specialty clinic. These retrospective data suggest that the addition of semaglutide to standard HS treatments results in improvement in QoL and fewer HS flares. The retrospective nature of the study is a limitation. Placebo-controlled randomized clinical trials should be done in HS to assess the efficacy of semaglutide in this debilitating condition.
Tracing conflict-induced cognitive-control adjustments over time using aperiodic EEG activity
Authors: Jia Shiwei , Liu Dandan , Song Wenqi , Beste Christian , Colzato Lorenza , Hommel Bernhard
Published: May 2024

Cognitive-control theories assume that the experience of response conflict can trigger control adjustments. However, while some approaches focus on adjustments that impact the selection of the present response (in trial N), other approaches focus on adjustments in the next upcoming trial  (N + 1). We aimed to trace control adjustments over time by quantifying cortical noise by means of the fitting oscillations and one over f algorithm, a measure of aperiodic activity. As predicted, conflict trials increased the aperiodic exponent in a large sample of 171 healthy adults, thus indicating noise reduction. While this adjustment was visible in trial N already, it did not affect response selection before the next trial. This suggests that control adjustments do not affect ongoing response-selection processes but prepare the system for tighter control in the next trial. We interpret the findings in terms of a conflict-induced switch from metacontrol flexibility to metacontrol persistence, accompanied or even implemented by a reduction of cortical noise.
Stimulating prefrontal cortex facilitates training transfer by increasing representational overlap
Authors: Wards Yohan , Ehrhardt Shane E , Garner Kelly G , Mattingley Jason B , Filmer Hannah L , Dux Paul E
Published: May 2024

A recent hypothesis characterizes difficulties in multitasking as being the price humans pay for our ability to generalize learning across tasks. The mitigation of these costs through training has been associated with reduced overlap of constituent task representations within frontal, parietal, and subcortical regions. Transcranial direct current stimulation, which can modulate functional brain activity, has shown promise in generalizing performance gains when combined with multitasking training. However, the relationship between combined transcranial direct current stimulation and training protocols with task-associated representational overlap in the brain remains unexplored. Here, we paired prefrontal cortex transcranial direct current stimulation with multitasking training in 178 individuals and collected functional magnetic resonance imaging data pre- and post-training. We found that 1 mA transcranial direct current stimulation applied to the prefrontal cortex paired with multitasking training enhanced training transfer to spatial attention, as assessed via a visual search task. Using machine learning to assess the overlap of neural activity related to the training task in task-relevant brain regions, we found that visual search gains were predicted by changes in classification accuracy in frontal, parietal, and cerebellar regions for participants that received left prefrontal cortex stimulation. These findings demonstrate that prefrontal cortex transcranial direct current stimulation may interact with training-related changes to task representations, facilitating the generalization of learning.
Test–retest reliability and time-of-day variations of perfusion imaging at rest and during a vigilance task
Authors: Guo Bowen , Mao Tianxin , Tao Ruiwen , Fu Shanna , Deng Yao , Liu Zhihui , Wang Mengmeng , Wang Ruosi , Zhao Weiwei , Chai Ya , Jiang Caihong , Rao Hengyi
Published: May 2024

Arterial spin-labeled perfusion and blood oxygenation level–dependent functional MRI are indispensable tools for noninvasive human brain imaging in clinical and cognitive neuroscience, yet concerns persist regarding the reliability and reproducibility of functional MRI findings. The circadian rhythm is known to play a significant role in physiological and psychological responses, leading to variability in brain function at different times of the day. Despite this, test–retest reliability of brain function across different times of the day remains poorly understood. This study examined the test–retest reliability of six repeated cerebral blood flow measurements using arterial spin-labeled perfusion imaging both at resting-state and during the psychomotor vigilance test, as well as task-induced cerebral blood flow changes in a cohort of 38 healthy participants over a full day. The results demonstrated excellent test–retest reliability for absolute cerebral blood flow measurements at rest and during the psychomotor vigilance test throughout the day. However, task-induced cerebral blood flow changes exhibited poor reliability across various brain regions and networks. Furthermore, reliability declined over longer time intervals within the day, particularly during nighttime scans compared to daytime scans. These findings highlight the superior reliability of absolute cerebral blood flow compared to task-induced cerebral blood flow changes and emphasize the importance of controlling time-of-day effects to enhance the reliability and reproducibility of future brain imaging studies.
Risk of heart failure in inflammatory bowel disease: a Swedish population-based study
Authors: Sun Jiangwei , Yao Jialu , Olén Ola , Halfvarson Jonas , Bergman David , Ebrahimi Fahim , Rosengren Annika , Sundström Johan , Ludvigsson Jonas F
Published: May 2024

Background and Aims

Dysregulation of inflammatory and immune responses has been implicated in the pathogenesis of heart failure (HF). But even if inflammation is a prerequisite for inflammatory bowel disease (IBD), little is known about HF risk in IBD.

Methods

In this Swedish nationwide cohort, patients with biopsy-confirmed IBD were identified between 1969 and 2017 [n = 81 749, Crohn’s disease (CD, n = 24 303), ulcerative colitis (UC, n = 45 709), and IBD-unclassified (IBD-U, n = 11 737)]. Each patient was matched with up to five general population reference individuals (n = 382 190) and IBD-free full siblings (n = 95 239) and followed until 31 December 2019. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) and standardized cumulative incidence for HF, with 95% confidence intervals (CI).

Results

There were 5582 incident HF identified in IBD patients (incidence rate [IR]: 50.3/10 000 person-years) and 20 343 in reference individuals (IR: 37.9) during a median follow-up of 12.4 years. IBD patients had a higher risk of HF than reference individuals (aHR 1.19, 95% CI 1.15–1.23). This increased risk remained significant ≥20 years after IBD diagnosis, leading to one extra HF case per 130 IBD patients until then. The increased risk was also observed across IBD subtypes: CD (IR: 46.9 vs. 34.4; aHR 1.28 [1.20–1.36]), UC (IR: 50.1 vs. 39.7; aHR 1.14 [1.09–1.19]), and IBD-U (IR: 60.9 vs. 39.0; aHR 1.28 [1.16–1.42]). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10 [1.03–1.19]).

Conclusions

Patients with IBD had a moderately higher risk of developing HF for ≥20 years after IBD diagnosis than the general population.
Evolutionary mechanism for diversity dynamics in technology using a phylogenetic tree approach: directional suggestions for photovoltaic technology
Authors: Park Hayoung , Jeong Dawoon , Lee Jeong-Dong
Published: May 2024

This study investigates the dynamics of diversity within photovoltaic technology by considering the spatial information of technological change. We introduce a phylogenetic tree methodology using an evolutionary perspective for validation at the level of technology genes and functional modules. Our findings show that the photovoltaic technology phylogenetic tree fully describes the technological and industrial histories of photovoltaics. Furthermore, the results imply that diversity is necessary for the evolutionary mechanism to operate and technology integration is the correct direction to pursue.
A non-stressful vision-based method for weighing live lambs
Authors: Riego del Castillo Virginia , Sánchez-González Lidia , Fernández Laura , Rebollar Ruben , Samperio Enrique
Published: May 2024

Accurate measurement of livestock weight is a primary indicator in the meat industry to increase the economic gain. In lambs, the weight of a live animal is still usually estimated manually using traditional scales, resulting in a tedious process for the experienced assessor and stressful for the animal. In this paper, we propose a solution to this problem using computer vision techniques; thus, the proposed procedure estimates the weight of a lamb by analysing its zenithal image without interacting with the animal, which speeds up the process and reduces weighing costs. It is based on a data-driven decision support system that uses RGB-D machine vision techniques and regression models. Unlike existing methods, it does not require walk-over-weighing platforms or special and expensive infrastructures. The proposed method includes a decision support system that automatically rejects those images that are not appropriate to estimate the lamb weight. After determining the body contour of the lamb, we compute several features that feed different regression models. Best results were achieved with Extra Tree Regression ($R^{2}$=91.94%), outperforming the existing techniques. Using only an image, the proposed approach can identify with a minimum error the optimal weight of a lamb to be slaughtered, so as to maximise the economic profit.
Varying primordial state fractions in exo- and endothermic SIDM simulations of Milky Way-mass haloes
Authors: Leonard Aidan , O’Neil Stephanie , Shen Xuejian , Vogelsberger Mark , Rosenstein Olivia , Shangguan Haotian , Teng Yuanhong , Hu Jiayi
Published: May 2024

Self-interacting dark matter (SIDM) is increasingly studied as a potential solution to small-scale discrepancies between simulations of cold dark matter (CDM) and observations. We examine a physically motivated two-state SIDM model with both elastic and inelastic scatterings. In particular, endothermic, exothermic, and elastic scattering have equal transfer cross-sections at high relative velocities ($v_{\rm rel}\gtrsim 400~{\rm km\, s}^{-1})$. In a suite of cosmological zoom-in simulation of Milky Way-size haloes, we vary the primordial state fractions to understand the impact of inelastic dark matter self-interactions on halo structure and evolution. In particular, we test how the initial conditions impact the present-day properties of dark matter haloes. Depending on the primordial state fraction, scattering reactions will be dominated by either exothermic or endothermic effects for high and low initial excited state fractions, respectively. We find that increasing the initial excited fraction reduces the mass of the main halo, as well as the number of subhaloes on all mass scales. The main haloes are cored, with lower inner densities and higher outer densities compared with CDM. Additionally, we find that the shape of the main halo becomes more spherical the higher the initial excited state fraction is. Finally, we show that the number of satellites steadily decreases with initial excited state fraction across all satellite masses.
Stellar atmospheric parameters from Gaia BP/RP spectra using uncertain neural networks
Authors: Fallows Connor P , Sanders Jason L
Published: May 2024

With the plentiful information available in the Gaia BP/RP spectra, there is significant scope for applying discriminative models to extract stellar atmospheric parameters and abundances. We describe an approach to leverage an ‘Uncertain Neural Network’ model trained on APOGEE data to provide high-quality predictions with robust estimates for per-prediction uncertainty. We report median formal uncertainties of 0.068 dex, 69.1 K, 0.14 dex, 0.031 dex, 0.040 dex, and 0.029 dex for [Fe/H], Teff, log g, [C/Fe], [N/Fe], and [α/M], respectively. We validate these predictions against our APOGEE training data, LAMOST, and Gaia GSP-phot stellar parameters, and see a strong correlation between our predicted parameters and those derived from these surveys. We investigate the information content of the spectra by considering the ‘attention’ our model pays to different spectral features compared to expectations from synthetic spectra calculations. Our model’s predictions are applied to the Gaia data set, and we produce a publicly available catalogue of our model’s predictions.
Quantum refraction effects in pulsar emission
Authors: Kim Dong-Hoon , Kim Chul Min , Kim Sang Pyo
Published: May 2024

Highly magnetized neutron stars exhibit the vacuum non-linear electrodynamics effects, which can be well-described using the one-loop effective action for quantum electrodynamics. In this context, we study the propagation and polarization of pulsar radiation, based on the post-Maxwellian Lagrangian from the Heisenberg–Euler–Schwinger action. Given the refractive index obtained from this Lagrangian, we determine the leading-order corrections to both the propagation and polarization vectors due to quantum refraction via perturbation analysis. In addition, the effects on the orthogonality between the propagation and polarization vectors and the Faraday rotation angle, all due to quantum refraction are investigated. Furthermore, from the dual refractive index and the associated polarization modes, we discuss quantum birefringence, with the optical phenomenology analogous to its classical counterpart.
Spectral study of star-forming rings in S0 galaxies of Dorado group – NGC 1533 and NGC 1543
Authors: Proshina Irina S , Sil’chenko Olga K , Kniazev Alexei Yu
Published: May 2024

We have fulfilled a detailed long-slit spectroscopic analysis for two SB0 galaxies – NGC 1533 and NGC 1543, – belonging to the Dorado group. Our spectral data reveal asymmetric decoupled kinematics of the stars and ionized gas in these barred lenticular galaxies that give evidences for external origin of the gas in the rings. We have calculated the star formation rates in the rings by using the ultraviolet fluxes of the rings corrected for the foreground and intrinsic absorption; and we have estimated parameters of the stellar populations in the inner parts of the galaxies confirming that they are old – except the nucleus of NGC 1543, which demonstrates signatures of rejuvenation less than 5 Gyr ago.
REEV: review, evaluate and explain variants
Authors: Hramyka Dzmitry , Sczakiel Henrike Lisa , Zhao Max Xiaohang , Stolpe Oliver , Nieminen Mikko , Adam Ronja , Danyel Magdalena , Einicke Lara , Hägerling René , Knaus Alexej , Mundlos Stefan , Schwartzmann Sarina , Seelow Dominik , Ehmke Nadja , Mensah Martin Atta , Boschann Felix , Beule Dieter , Holtgrewe Manuel
Published: May 2024

In the era of high throughput sequencing, special software is required for the clinical evaluation of genetic variants. We developed REEV (Review, Evaluate and Explain Variants), a user-friendly platform for clinicians and researchers in the field of rare disease genetics. Supporting data was aggregated from public data sources. We compared REEV with seven other tools for clinical variant evaluation. REEV (semi-)automatically fills individual ACMG criteria facilitating variant interpretation. REEV can store disease and phenotype data related to a case to use these for phenotype similarity measures. Users can create public permanent links for individual variants that can be saved as browser bookmarks and shared. REEV may help in the fast diagnostic assessment of genetic variants in a clinical as well as in a research context. REEV (https://reev.bihealth.org/) is free and open to all users and there is no login requirement.
REME: an integrated platform for reaction enzyme mining and evaluation
Authors: Shi Zhenkun , Wang Dehang , Li Yang , Deng Rui , Lin Jiawei , Liu Cui , Li Haoran , Wang Ruoyu , Zhao Muqiang , Mao Zhitao , Yuan Qianqian , Liao Xiaoping , Ma Hongwu
Published: May 2024

A key challenge in pathway design is finding proper enzymes that can be engineered to catalyze a non-natural reaction. Although existing tools can identify potential enzymes based on similar reactions, these tools encounter several issues. Firstly, the calculated similar reactions may not even have the same reaction type. Secondly, the associated enzymes are often numerous and identifying the most promising candidate enzymes is difficult due to the lack of data for evaluation. Thirdly, existing web tools do not provide interactive functions that enable users to fine-tune results based on their expertise. Here, we present REME (https://reme.biodesign.ac.cn/), the first integrated web platform for reaction enzyme mining and evaluation. Combining atom-to-atom mapping, atom type change identification, and reaction similarity calculation enables quick ranking and visualization of reactions similar to an objective non-natural reaction. Additional functionality enables users to filter similar reactions by their specified functional groups and candidate enzymes can be further filtered (e.g. by organisms) or expanded by Enzyme Commission number (EC) or sequence homology. Afterward, enzyme attributes (such as kcat, Km, optimal temperature and pH) can be assessed with deep learning-based methods, facilitating the swift identification of potential enzymes that can catalyze the non-natural reaction.
Proscan: a structure-based proline design web server
Authors: Felbinger Nathaniel , Ribeiro-Filho Helder V , Pierce Brian G
Published: May 2024

The ability to control protein conformations and dynamics through structure-based design has been useful in various scenarios, including engineering of viral antigens for vaccines. One effective design strategy is the substitution of residues to proline amino acids, which due to its unique cyclic side chain can favor and rigidify key backbone conformations. To provide the community with a means to readily identify and explore proline designs for target proteins of interest, we developed the Proscan web server. Proscan provides assessment of backbone angles, energetic and deep learning-based favorability scores, and other parameters for proline substitutions at each position of an input structure, along with interactive visualization of backbone angles and candidate substitution sites on structures. It identifies known favorable proline substitutions for viral antigens, and was benchmarked against datasets of proline substitution stability effects from deep mutational scanning and thermodynamic measurements. This tool can enable researchers to identify and prioritize designs for prospective vaccine antigen targets, or other designs to favor stability of key protein conformations. Proscan is available at: https://proscan.ibbr.umd.edu.
Comparing evidence use in parliaments: the interplay of beliefs, traditions, and practices in the UK and Germany
Authors: Geddes Marc
Published: May 2024

This article draws on rich qualitative data from two national parliaments—the UK House of Commons and the German Bundestag—to examine knowledge practices in political institutions. This is an important topic, not only because parliaments play a significant role in democratic decision-making, but because it sheds light on debates about how such decision-making is based on and interacts with knowledge and evidence. By adopting an interpretive analytical approach, I analyze the ways in which those practices are shaped by the beliefs and values of parliamentary actors. Indeed, in better understanding everyday practices, beliefs, and ideational traditions, it also contributes to better explaining how components of political and parliamentary cultures contribute to knowledge use more broadly. In the House of Commons, MPs draw on a highly trusted and independent parliamentary administration; meanwhile, committees have become fruitful avenues for MPs to develop policy expertise and engage with knowledge and evidence in a non-partisan way. In the German Bundestag, MPs also develop policy expertise—in fact, they interpret their role as specialists in a “working” parliament—but their knowledge practices are more openly partisan through the structuring role of parliamentary party groups and the skepticism of “neutral” advice from research services. Consequently, committees tend to be sites of political bargaining and conflict, rather than evidence-gathering. In both cases, parliaments’ knowledge practices are shaped by wider webs of beliefs about the role of MPs within the institutions. This suggests that knowledge use in political and policy settings is shaped by broader cultural factors.
Religious Leaders’ Compliance with State Authority: Experimental Evidence from COVID-19 in Pakistan
Authors: Vyborny Kate
Published: May 2024

A randomized controlled trial in Pakistan tests whether one-on-one engagement with community religious leaders can encourage them to instruct congregants to follow government regulations. Treated religious leaders are 25 percent more likely to comply with government requirements to tell congregants they should wear a mask to prevent COVID transmission when attending prayers. Treatment effects do not depend on the religious content of the message. Effects are driven by respondents who already understand the mechanics of COVID transmission at baseline, suggesting the treatment does not work by correcting basic knowledge about the disease, but rather through a mechanism of persuasion.
Safety and Efficacy of 177Lu-DOTATATE in Children and Young Adult Population
Authors: Aggarwal Piyush , Satapathy Swayamjeet , Sood Ashwani , Singh Harmandeep , Mittal Bhagwant Rai , Lal Sadhna , Gupta Rajesh , Das Chandan Krushna , Yadav Thakur Deen , Walia Rama
Published: May 2024

Purpose

This single-center retrospective study explores the safety and efficacy of 177Lu-DOTATATE in children and young adult population with metastatic/inoperable neuroendocrine tumors (NETs).

Patients and Methods

This study is a retrospective analysis of all children and young adult patients (≤29 years) with advanced inoperable/metastatic epithelial or nonepithelial NETs who were administered a median of 4 cycles of 177Lu-DOTATATE therapy and low-dose oral capecitabine as a radiosensitizer every 8–12 weeks, except 2 patients who received CAPTEM chemotherapy. The radiological response was assessed using RECIST 1.1 on interim and end-of-treatment 68Ga-DOTANOC PET/CT. The primary endpoint was objective response rate, whereas disease control rate, toxicity profile, progression-free survival, and overall survival were secondary endpoints.

Results

Nineteen biopsy-proven NET patients (median age, 22 ± 10 years) with 8 of them adolescents (10–18 years) and the remaining young adults (19–29 years) were included. Fourteen patients had gastroenteropancreatic neuroendocrine tumor (pancreas being most common primary site), whereas the rest had non–gastroenteropancreatic neuroendocrine tumor. A total of 65 cycles of 177Lu-DOTATATE (range, 1–6 cycles) were administered with a median cumulative activity of 600 mCi (range, 100–1000 mCi). The objective response rate and disease control rate were 41% and 94%, respectively. Grade 1 and 2 adverse events were observed in 14 (74%) and 5 (26%) of 19 patients, respectively. In a total of 8 events (42%), 4 events each of disease progression and death occurred during a median follow-up of 80.1 months with an estimated 5-year progression-free survival and overall survival of 54% (95% confidence interval, 30–78) and 63% (95% confidence interval, 39–87), respectively.

Conclusions

177Lu-DOTATATE appears safe and effective in children and young adults with metastatic/inoperable NETs. Large prospective trials are required to validate these results.
225Ac-PSMA-617 Augmentation in High-Risk mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy
Authors: Rosar Florian , Burgard Caroline , Rohloff Luna Vanessa , Blickle Arne , Bartholomä Mark , Maus Stephan , Petto Sven , Schaefer-Schuler Andrea , Ezziddin Samer
Published: May 2024

Purpose

This pilot study investigates the efficacy and safety profile as well as predictive biomarkers of 225Ac-PSMA-617–augmented 177Lu-PSMA-617 radioligand therapy (RLT) in a cohort of high-risk patients with metastatic castration-resistant prostate cancer (mCRPC), enrolled in a prospective registry (NCT 04833517).

Patients and Methods

A group of n = 33 high-risk mCRPC patients received 177Lu-PSMA-617 RLT, augmented by 1 or more cycles of 225Ac-PSMA-617. Response was assessed by prostate-specific antigen (PSA) serum value after 2 cycles of treatment. Overall survival (OS) and PSA-based progression-free survival were evaluated using Kaplan-Meier analysis. To assess the side effect profile, Common Terminology Criteria for Adverse Events were applied. In total, 12 potential pretherapeutic biomarkers were tested for association with OS.

Results

The median decrease in serum PSA value was −49.1%, and 16/33 (48.5%) patients experienced a partial response after 2 cycles RLT. The median PSA-based progression-free survival and median OS was 7.2 and 14.8 months, respectively. Alkaline phosphatase (P < 0.001), lactate dehydrogenase (P = 0.035), Eastern European Oncology Group Performance Score (P = 0.037), and the presence of visceral metastases (P = 0.029) revealed significant association with OS in Kaplan-Meier analysis (log-rank test). Most of the recorded adverse events were rated as mild or moderate. Higher-grade adverse events were very limited with only 1 case (3.0%) of grade 3 anemia. Treatment-related mild xerostomia was recorded in 6/33 (18.2%) patients.

Conclusions

225Ac-PSMA-617 augmentation in high-risk mCRPC undergoing 177Lu-PSMA-617 RLT appears to be an effective treatment option with a favorable safety profile. The pretherapeutic values of alkaline phosphatase, lactate dehydrogenase, the Eastern European Oncology Group Performance Score, and the presence of visceral metastases may be appropriate biomarkers predicting survival outcome of this treatment regimen.
Peritoneal tuberculosis, an underestimated diagnosis: a case report
Authors: Laamara Leila , Benaissa Elmostafa , Achemlal Amine , Bounakhla Amal , Bssaibis Fatna , BenLahlou Yassine , Maleb Adil , Chadli Mariama , Elouennass Mostafa
Published: May 2024

Tuberculosis is an infectious disease that most often affects the lungs, caused by human-to-human transmission of Mycobacterium tuberculosis. Peritoneal tuberculosis is an extra-pulmonary form of the disease that usually manifests as an ascitic syndrome, with or without fever, in a context of altered general condition, often in endemic areas. The diagnosis of peritoneal tuberculosis is not always easy, as the clinical signs are often insidious and unspecific. We report a case of peritoneal tuberculosis in an 18-year-old female, who had presented for 10 days with a progressive increase in abdominal volume associated with vomiting and diarrhoea.
Drop-by-drop Addition of Reagents to a Double Emulsion
Authors: Cowell Thomas W. , Jing Wenyang , Han Hee-Sun
Published: May 2024

Developments in droplet microfluidic assays have facilitated an era of high-throughput, sensitive single-cell, or single-molecule measurements capable of tackling the heterogeneity present in biological systems. Relying on single emulsion (SE) compartments, droplet assays achieve absolute quantification of nucleic acids, massively parallel single-cell profiling, identification of rare variants, and more. Double emulsions (DEs) have seen new interest in recent years for their potential to enable new droplet assays and build upon SE techniques. DEs are compatible with flow cytometry enabling high-throughput multi-parameter drop screening and eliminate content mixing due to coalescence during lengthy workflows, addressing inherent limitations of SEs. Despite these strengths, DEs lack important technical functions that exist in SEs such as picoinjection or any other method for adding reagents to droplets on demand. Consequently, DEs cannot be used for multistep workflows which has limited their adoption in assay development. Here, we report a simple device achieving picoinjection of DEs. We developed strategies to enable active manipulations on DEs by converting DE inputs to SEs on chip. The released aqueous cores of the DE can be manipulated using existing SE techniques, such as reagent addition, before reforming a DE at the outlet. We identified device designs and operation conditions achieving drop-by-drop reagent addition to DEs and used it as part of a muti-step aptamer screening assay performed entirely in DE drops. This work enables the further development of multistep DE droplet assays.
Pattern of Alcohol tolerance and Adh gene Frequencies in Northern and Southern Populations of two Drosophila species from India
Authors: Shamina
Published: May 2024

In this study, we collected four geographical populations of Drosophila melanogaster and Drosophila ananassae from the southern and northern axes of India, spanning latitudes ranging from 13.04°N to 29.58°N. We observed significant clinal variation at the alcohol dehydrogenase (Adh) locus, with the frequency of the Adh F allele increasing by 3% and 1.5% per degree latitude in D. melanogaster and D. ananassae, respectively.

Adult populations of D. melanogaster were found to tolerate ethanol concentrations ranging from 10% to 14.75%, while D. ananassae exhibited tolerance levels between 2.4% and 4.0%. These patterns of interspecific divergence in ethanol tolerance levels corresponded with their natural habitats: D. ananassae primarily utilizes fermented organic matter and fruits in the wild, while D. melanogaster exploits ethanol-rich resources found indoors. Ethanol serves as a resource at low concentrations but becomes a stressor at higher concentrations for D. ananassae. Both traits exhibited a clinal pattern that is increase in ethanol tolerance and of the frequency of Adh-F allele with latitude.

Our observations suggest that D. ananassae exhibits adaptive characteristics for ethanol utilization, while D. melanogaster populations demonstrate both ethanol utilization and detoxification abilities. The observed latitudinal variation in Adh F frequency and ethanol tolerance in these two Drosophilids may be maintained by the interplay of balancing natural selection and climatic factors that vary spatially along the south-north axis of the Indian subcontinent.
Coarse-graining the recognition of a glycolipid by the C-type lectin Mincle receptor
Authors: Noriega Maxime , Corey Robin A. , Haanappel Evert , Demange Pascal , Czaplicki Georges , Atkinson R. Andrew , Chavent Matthieu
Published: May 2024

Macrophage inducible Ca2+-dependent lectin (Mincle) receptor recognizesMycobacterium tuberculosisglycolipids to trigger an immune response. This host membrane receptor is thus a key player in the modulation of the immune response to infection byM. tuberculosis, and has emerged as a promising target for the development of new vaccines for tuberculosis. The recent development of the Martini 3 force field for coarse-grained (CG) molecular modeling allow the study of interactions of soluble proteins with small ligands but its use for the study of interactions with lipids remains less explored. Here, we present a refined approach detailing a protocol for modeling such interactions at a CG level using the Martini 3 force field. Using this approach, we studied Mincle and identified critical parameters governing ligand recognition, such as loop flexibility and the regulation of hydrophobic groove formation by calcium ions. In addition, we assessed ligand affinity using free energy perturbation calculations. Our results offer mechanistic insight into the interactions between Mincle and glycolipids, providing a basis for rational design of molecules targeting this type of membrane receptors.
Mechanical state of pre-tumoral epithelia dictates subsequent tumour aggressiveness
Authors: Montemurro Marianne , Monier Bruno , Suzanne Magali
Published: May 2024

Tumours evolve through the acquisition of increasingly aggressive traits associated with dysplasia. This progression is accompanied by the alteration of tumour mechanical properties, especially through extracellular matrix remodelling. However, the contribution of intrinsic tumour cells mechanics to tumour aggressiveness remains unknownin vivo.

Here we show that adherens junction tension in pre-tumoral tissues dictates subsequent tumour evolution. Increased cell contractility, observed in aggressive tumours before any sign of tissue overgrowth, proved sufficient to trigger dysplasia in normally hyperplastic tumours. Unexpectedly, high contractility contributes to tumour evolution through cell death induction which favours cell-cell junctions weakening. Overall, our results highlight the need to re-evaluate the roles of tumoral cell death, and identify pre-tumour cell mechanics as an unsuspected early marker and key trigger of tumour aggressiveness.

GRAPHICAL ABSTRACT
Cholestasis alters polarization and suppressor function of hepatic regulatory T cells.
Authors: Kudira Ramesh , Yang Zi F , Osuji Immaculeta , Karns Rebekah , Bariya Priya , Pfuhler Liva , Mullen Mary , Taylor Amy , Ji Hong , Lages Celine S , Yang vom Hofe Annika , Shi Tiffany , Pasula Srikar , Wayman Joseph A , Bernieh Anas , Zhang Wujuan , Chougnet Claire A , Hildeman David , Tiao Gregory M , Huppert Stacey S , Subramanian Sajay , Salomonis Nathan , Miraldi Emily , Miethke Alexander Gerhard
Published: May 2024

Fibrosing cholangiopathies, including biliary atresia and primary sclerosing cholangitis, involve immune-mediated bile duct epithelial injury and hepatic bile acid (BA) retention (cholestasis). Regulatory T-cells (Tregs) can prevent auto-reactive lymphocyte activation, yet the effects of BA on this CD4 lymphocyte subset are unknown. Gene regulatory networks for hepatic CD4 lymphocytes in a murine cholestasis model revealed Tregs are polarized to Th17 during cholestasis. Following bile duct ligation, Stat3 deletion in CD4 lymphocytes preserved hepatic Treg responses. While pharmacological reduction of hepatic BA in MDR2-/- mice prompted Treg expansion and diminished liver injury, this improvement subsided with Treg depletion. A cluster of patients diagnosed with biliary atresia showed both increased hepatic Treg responses and improved 2-year native liver survival, supporting that Tregs might protect against neonatal bile duct obstruction. Together, these findings suggest liver BA determine Treg function and should be considered as a therapeutic target to restore protective hepatic immune responses.