bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetics of cardiovascular drugs
Authors: Saleh Ateka , Al-Abcha Abdullah , Pereira Naveen 
Published: April 2023

Purpose of review
Advances in pharmacogenomics have paved the way for personalized medicine. The purpose of this review is to summarize the background, rationale, and evidence for pharmacogenomics in cardiovascular medicine.

Recent findings
Randomized clinical trials have supported the role of a genotype-guided approach for antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary interventions. Additionally, there is increasing evidence supporting the association of certain genetic variants and risk of statin associated muscle symptoms. Furthermore, germline genetic variation is being used as a biomarker to target patients with specific therapy.

Summary
Pharmacogenomics has the potential to improve patient care by providing the right drug to the right patient and could guide the identification of novel drug therapies for cardiovascular disease.
Can ex-situ normothermic perfusion improve graft survival compared to static cold storage among donation after circulatory death liver allografts?
Authors: Ibeabuchi Tobenna , Li Eric , Bittermann Therese , Mahmud Nadim , Abt Peter L. 
Published: April 2023

Limited data suggest that ex-situ normothermic liver perfusion (ENLP) may improve the outcomes of donation after circulatory death (DCD) liver transplants compared to static cold storage (SCS). All adult DCD liver transplants performed between 2016 and 2021 were identified in the United Network of Organ Sharing database. ENLP liver transplants were compared to SCS using inverse probability of treatment weighting to balance clinical and demographic confounders. The primary analysis simulated intention-to-treat with inverse probability of treatment weighting-adjusted Cox models. Compared to SCS DCDs (N = 3,079), recipients of ENLP DCDs (N = 65) had lower Model of End Stage Liver Disease scores at transplant (16.5 v. 18.8, p = 0.033), longer wait times (468 ± 720 vs. 246 ± 467 d; p < 0.001), and received livers from donors with a greater BMI (29.2 vs. 27.5; p = 0.008). ENLP preservation was associated with a lower risk of graft failure (HR 0.31 vs. SCS, 95% CI:0.12–0.86, p = 0.023) and a lower incidence of retransplantation. A sub-analysis restricted to the 20 centers performing ENLP, encompassing 946 SCS DCDs, demonstrated similar results: (HR 0.33 vs. SCS, 95% CI: 0.13–0.94, p = 0.021). Among 111 patients who required retransplantation and where the etiology of graft failure was identified, graft failure due to ischemic cholangiopathy was noted in 1 ENLP and 46 SCS. In this retrospective analysis of the early US DCD ENLP experience, there may exist a graft survival benefit to transplants performed with ENLP compared to SCS.
A positive feedback loop between ZEB2 and ACSL4 regulates lipid metabolism to promote breast cancer metastasis
Authors: Lin Jiamin , Zhang Pingping , Liu Wei , Liu Guorong , Zhang Juan , Yan Min , Duan Yuyou , Yang Na 
Published: April 2023

AbstractLipid metabolism plays a critical role in cancer metastasis. However, the mechanisms through which metastatic genes regulate lipid metabolism remain unclear. Here, we describe a new oncogenic-metabolic feedback loop between the epithelial-mesenchymal transition (EMT) transcription factor ZEB2 and the key lipid enzyme ACSL4 (long-chain acyl-CoA synthetase 4), resulting in enhanced cellular lipid storage and fatty acid oxidation to drive breast cancer metastasis. Functionally, Depletion of ZEB2 or ACSL4 significantly reduced lipid droplets (LD) abundance and cell migration. ACSL4 overexpression rescued the invasive capabilities of the ZEB2 knockdown cells, suggesting that ACSL4 is crucial for ZEB2-mediated metastasis. Mechanistically, ZEB2 activated ACSL4 expression by directly binding to the ACSL4 promoter. ACSL4 binds to and stabilizes ZEB2 by reducing ZEB2 ubiquitination. Notably, ACSL4 not only promotes the intracellular lipogenesis and lipid droplet accumulation but also enhances fatty acid oxidation (FAO) and ATP production by upregulating the FAO rate-limiting enzyme CPT1A (carnitine palmitoyltransferase 1 isoform A). Finally, we demonstrated that ACSL4 knockdown significantly reduced metastatic lung nodes in vivo. In conclusion, we reveal a novel positive regulatory loop between ZEB2 and ACSL4, which promotes LD storage to meet the energy needs of breast cancer metastasis, and identify the ZEB2-ACSL4 signaling axis as an attractive therapeutic target for overcoming breast cancer metastasis.HighlightsZEB2 activates FAO through transcription of ACSL4ACSL4 regulates lipid metabolism through FAO, promoting breast cancer metastasis Targeting ZEB2-ACSL4 signaling axis inhibits breast cancer metastasisSignificanceWe describe a novel positive feedback loop between ZEB2 and ACSL4 that results in enhanced cellular lipid storage and FA oxidation to drive breast cancer metastasis.
Deterministic and stochastic processes generating alternative states of microbiomes
Authors: Hayashi Ibuki , Fujita Hiroaki , Toju Hirokazu 
Published: April 2023

AbstractThe structure of microbial communities is often classified into discrete or semi-discrete compositions of taxa as represented by “enterotypes” of human gut microbiomes. Elucidating mechanisms that generate such “alternative states” of microbiome compositions has been one of the major challenges in ecology and microbiology. In a time-series analysis of experimental microbiomes, we here show that both deterministic and stochastic ecological processes drive divergence of alternative microbiome states. We introduced species-rich soil-derived microbiomes into eight types of culture media with 48 replicates, monitoring shifts in community compositions at six time points (8 media × 48 replicates × 6 time points = 2,304 community samples). We then confirmed that microbial community structure diverged into a few discrete states in each of the eight medium conditions as predicted in the presence of both deterministic and stochastic community processes. In other words, microbiome structure was differentiated into a small number of reproducible compositions under the same environment. This fact indicates not only the presence of selective forces leading to specific equilibria of community-scale resource use but also the influence of demographic drift (fluctuations) across basins of such equilibria. A reference-genome analysis further suggested that the observed alternative states differed in ecosystem-level functions. These findings will help us examine how microbiome structure and functions can be controlled by changing the “stability landscapes” of ecological community compositions.
ST3Gal1 synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer
Authors: Garnham Rebecca , Geh Daniel , Nelson Ryan , Ramon-Gill Erik , Wilson Laura , Schmidt Edward N , Walker Laura , Adamson Beth , Buskin Adriana , Hepburn Anastasia , Hodgson Kirsty , Kendall Hannah , Frame Fiona M , Maitland Norman , Coffey Kelly , Robson Craig N , Elliott David J , Heer Rakesh , Macauley Matthew , Munkley Jennifer , Gaughan Luke , Leslie Jack , Scott Emma 
Published: April 2023

AbstractImmune checkpoint blockade trials have yet to produce a robust anti-cancer response in prostate cancer patients as a monotherapy due to the immunosuppressed prostate cancer tumour immune microenvironment. ST3Gal1 and other sialyltransferases are implicated in cancer and immune suppression by synthesizing sialoglycans, which act as ligands for Siglec receptors. These checkpoints are important for the immune response. However, it’s unclear how the synthesis of Siglec ligands is regulated, and little is known about the role of sialoglycan-Siglec-axis in prostate cancer’s evasion of anti-tumour immunity. We report that ST3Gal1 levels negatively correlate with androgen signalling in prostate tumours. Utilising syngeneic mouse models, we demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion. Using mouse models, patient samples andin vitromodels we show that ST3Gal1 synthesises sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. For the first time we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. Importantly, we show that these interactions can be modulated by enzalutamide and may maintain immune suppression in enzalutamide treated tumours. We conclude that the activity of ST3Gal1 is critical to prostate cancer anti-tumour immunity and provide rationale for the use of glyco-immune checkpoint targeting therapies in advanced prostate cancer.
Genetic associations among internalizing and externalizing traits with polysubstance use among young adults
Authors: Brick Leslie A , Benca-Bachman Chelsie E , Johnson Emma C , Gustavson Daniel E. , Carper Matthew , Palmer Rohan HC 
Published: April 2023

AbstractThough most genetic studies of substance use focus on specific substances in isolation or generalized vulnerability across multiple substances, few studies to date focus on the concurrent use of two or more substances within a specified time frame (i.e., polysubstance use; PSU). We evaluated whether distinct genetic factors underlying internalizing and externalizing traits were associated with past 30-day PSU above variance shared across general psychopathology and substance use (SU). Using Genomic Structural Equation Modeling, we constructed theory-driven, multivariate genetic factors of 16 internalizing, externalizing, and SU traits using genome-wide association studies (GWAS) summary statistics. Next, we fit a model with a higher order SU-related psychopathology factor as well as genetic variance specific to externalizing and internalizing (i.e., residual genetic variance not explained by SU or general psychopathology). GWAS-by-subtraction was used to obtain single nucleotide polymorphism effects on each of these factors. Polygenic scores (PGS) were then created in an independent target sample with data on PSU, the National Longitudinal Study of Adolescent to Adult Health. To evaluate the effect of genetic variance due to internalizing and externalizing traits independent of variance related to SU, we regressed PSU on the PGSs, controlling for sex, age, and genetic principal components. PGSs for SU-related psychopathology and non-SU externalizing traits were associated with higher PSU factor scores, while the non-SU internalizing PGS was not significantly associated with PSU. In total, the three PGSs accounted for an additional 4% of the variance in PSU above and beyond a null model with only age, sex, and genetic principal components as predictors. These findings suggest that there may be unique genetic variance in externalizing traits contributing to liability for PSU that is independent of the genetic variance shared with SU.
Passive exposure to task-relevant stimuli enhances categorization learning
Authors: Schmid Christian , Haziq Muhammad , Baese-Berk Melissa M. , Murray James M. , Jaramillo Santiago 
Published: April 2023

AbstractLearning to perform a perceptual decision task is generally achieved through sessions of effortful practice with feedback. Here, we investigated how passive exposure to task-relevant stimuli, which is relatively effortless and does not require feedback, influences active learning. First, we trained mice in a sound-categorization task with various schedules combining passive exposure and active training. Mice that received passive exposure exhibited faster learning, regardless of whether this exposure occurred entirely before active training or was interleaved between active sessions. We next trained neural-network models with different architectures and learning rules to perform the task. Networks that use the statistical properties of stimuli to enhance separability of the data via unsupervised learning during passive exposure provided the best account of the behavioral observations. We further found that, during interleaved schedules, there is an increased alignment between weight updates from passive exposure and active training, such that a few interleaved sessions can be as effective as schedules with long periods of passive exposure before active training, consistent with our behavioral observations. These results provide key insights for the design of efficient training schedules that combine active learning and passive exposure in both natural and artificial systems.
Activation mechanism and activity of globupain, a thermostable C11 protease from the Arctic Mid-Ocean Ridge hydrothermal system
Authors: Røyseth Victoria , Hurysz Brianna M , Kaczorowska Anna , Dorawa Sebastian , Fedøy Anita-Elin , Arsin Hasan , Serafim Mateus , Werbowy Olesia , Kaczorowski Tadeusz , Stokke Runar , O’Donoghue Anthony J , Steen Ida Helene 
Published: April 2023

AbstractDeep-sea hydrothermal vent systems with prevailing extreme thermal conditions for life offer unique habitats to source heat tolearant enzymes with potential new enzymatic properties. Here, we present the novel C11 proteaseglobupain, prospected from a metagenome-assembled genome of uncultivatedArchaeoglobalessampled from the Soria Moria hydrothermal vent system located on the Arctic Mid- Ocean Ridges. By sequence comparisons against the MEROPS-MPRO database, globupain showed highest sequence identity to C11-like proteases present in human gut and intestinal bacteria,. Successful recombinant expression inEscherichia coliof the active zymogen and 13 mutant substitution variants allowed assesment of residues involved in maturation and activity of the enzyme. For activation, globupain required the addition of DTT and Ca²⁺. When activated, the 52 kDa proenzyme was processed at Lys137and Lys144into a 12 kDa light- and 32 kDa heavy chain heterodimer. A structurally conserved His132/Cys185catalytic dyad was responsible for the proteolytic activity, and the enzyme demonstrated the ability to activatein-trans. Globupain exhibited caseinolytic activity and showed a strong preference for arginine in the P1 position, with Boc-QAR- aminomethylcoumarin (AMC) as the best substrate out of a total of 17 fluorogenic AMC substrates tested. Globupain was thermostable (Tm activated enzyme= 94.51 ± 0.09°C) with optimal activity at 75 °C and pH 7.1. By characterizing globupain, our knowledge of the catalytic properties and activation mechanisms of temperature tolerant marine C11 proteases have been expanded. The unique combination of features such as elevated thermostability, activity at relatively low pH values, and ability to operate under high reducing conditions makes globupain a potential intriguing candidate for use in diverse industrial and biotechnology sectors.
Super-resolution mapping of anisotropic tissue structure with diffusion MRI and deep learning
Authors: Abramian David , Eklund Anders , Özarslan Evren 
Published: April 2023

ABSTRACTDiffusion magnetic resonance imaging (diffusion MRI) is widely employed to probe the diffusive motion of water molecules within the tissue. Numerous diseases and processes affecting the central nervous system can be detected and monitored via diffusion MRI thanks to its sensitivity to microstructural alterations in tissue. The latter has prompted interest in quantitative mapping of the microstructural parameters, such as the fiber orientation distribution function (fODF), which is instrumental for noninvasively mapping the underlying axonal fiber tracts in white matter through a procedure known as tractography. However, such applications demand repeated acquisitions of MRI volumes with varied experimental parameters demanding long acquisition times and/or limited spatial resolution. In this work, we present a deep-learning-based approach for increasing the spatial resolution of diffusion MRI data in the form of fODFs obtained through constrained spherical deconvolution. The proposed approach is evaluated on high quality data from the Human Connectome Project, and is shown to generate upsampled results with a greater correspondence to ground truth high-resolution data than can be achieved with ordinary spline interpolation methods.
Resilient evacuation infrastructure; an assessment of resilience toward natural hazards
Authors: Fathianpour Azin , Babaeian Jelodar Mostafa , Wilkinson Suzanne , Evans Barry 
Published: April 2023

Purpose
As evacuation is one of the most used response actions to such disasters, it is essential to understand correctly what a resilient evacuation would mean. One critical factor in evacuation resilience is the resilience level of evacuation infrastructures. Also, UN sustainable development has a goal to build resilient infrastructures. This study aims to investigate the characteristics of resilient evacuation infrastructures.

Design/methodology/approach
A systematic methodology for reviewing articles has been implemented to understand how vulnerable cities can be more prepared, especially for pedestrian evacuation.

Findings
This study has developed an evacuation scoring system framework for pedestrians to investigate evacuation infrastructure in terms of different resilience features, such as redundancy, safe-to-fail, readiness and capacity. The most practical evacuation system will be estimated. The output of this study can provide insight into a final output to provide the features of a successful pedestrian evacuation system for future policy drafting for infrastructure strategy decision-makers.

Practical implications
Climate change has made the risks of natural hazards such as tsunamis more intense for humans. Many people in the world live in hazardous environments and are susceptible to disasters. A community must be prepared to mitigate the destructive event and quickly respond to be called resilient.

Originality/value
This is an original work. The researcher has gone through a deep literature review and developed a cluster showing the features a resilient evacuation infrastructure should have.
Laser 3D tightly coupled mapping method based on visual information
Authors: Liu Sixing , Chai Yan , Yuan Rui , Miao Hong 
Published: April 2023

Purpose
Simultaneous localization and map building (SLAM), as a state estimation problem, is a prerequisite for solving the problem of autonomous vehicle motion in unknown environments. Existing algorithms are based on laser or visual odometry; however, the lidar sensing range is small, the amount of data features is small, the camera is vulnerable to external conditions and the localization and map building cannot be performed stably and accurately using a single sensor. This paper aims to propose a laser three dimensions tightly coupled map building method that incorporates visual information, and uses laser point cloud information and image information to complement each other to improve the overall performance of the algorithm.

Design/methodology/approach
The visual feature points are first matched at the front end of the method, and the mismatched point pairs are removed using the bidirectional random sample consensus (RANSAC) algorithm. The laser point cloud is then used to obtain its depth information, while the two types of feature points are fed into the pose estimation module for a tightly coupled local bundle adjustment solution using a heuristic simulated annealing algorithm. Finally, the visual bag-of-words model is fused in the laser point cloud information to establish a threshold to construct a loopback framework to further reduce the cumulative drift error of the system over time.

Findings
Experiments on publicly available data sets show that the proposed method in this paper can match its real trajectory well. For various scenes, the map can be constructed by using the complementary laser and vision sensors, with high accuracy and robustness. At the same time, the method is verified in a real environment using an autonomous walking acquisition platform, and the system loaded with the method can run well for a long time and take into account the environmental adaptability of multiple scenes.

Originality/value
A multi-sensor data tight coupling method is proposed to fuse laser and vision information for optimal solution of the positional attitude. A bidirectional RANSAC algorithm is used for the removal of visual mismatched point pairs. Further, oriented fast and rotated brief feature points are used to build a bag-of-words model and construct a real-time loopback framework to reduce error accumulation. According to the experimental validation results, the accuracy and robustness of the single-sensor SLAM algorithm can be improved.
Investigating consumer ethical beliefs: role of moral philosophies and personality traits
Authors: Gala Prachi , Chauhan Rahul , King Robert , Vitell Scott 
Published: April 2023

Purpose
This research looks at the main effect of individuals’ moral philosophies, idealism and relativism, and its impact on the four dimensions of the consumer ethics beliefs – active benefit, passive benefit, no harm and doing good. The moderating impact of two dominant personalities – Machiavellianism and narcissism – was also analyzed. Based on Hunt–Vitell theory of ethics, this study aims to propose that there is a positive and significant impact of more relativistic and less idealistic moral philosophies on the decreased consumer ethical perceptions and that the narcissistic/Machiavellian personality traits drive that effect.

Design/methodology/approach
A total of 497 survey respondents were recruited via an online platform. All respondents were asked to answer questions, which were divided into four major parts. The first part consisted of scales related to both moral philosophies, the second part had both dark personality scales, the third part questioned about their consumer ethical beliefs and the final part was related to consumer demographics.

Findings
Relativists had higher scores in three consumer unethical belief dimensions. Idealists were not supportive of the active and passive illegal activities, as did their positive relation with doing good aspect of the ethical beliefs. Machiavellians strengthen the positive relativism relationship. The idealistic relation of narcissists, compared to relativistic relation, is stronger on unethical decision-making for consumers.

Originality/value
This study contributes to the current knowledge of individual’s moral philosophies and their impact on consumer ethical beliefs. It further demonstrates how the dark personalities of narcissism and Machiavellianism drive the relationship.