bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban mobility trends and climate change: sustainability policies in the parking industry
Authors: Fernández-González Raquel , Puime-Guillén Félix , Moutinho Victor Manuel Ferreira , de Oliveira Helena Maria Santos
Published: May 2023

The concern to create cleaner and more ecosystem-friendly production processes has extended to the parking sector in Spain. Since the creation of the multi-level institutional framework for sustainable mobility management (mainly composed of the Infrastructure, Transport and Housing Plan 2012–2024, the Sustainable Urban Mobility Plans, Law 9/2006, and Law 9/2017), environmental considerations, including sustainable management certificates, have occupied a privileged place in public procedures for the management of parking structures and regulated surface parking facilities. Although there have been previous academic studies on the design and implementation of SUMPs and the growth of the parking sector, this article is novel in that it analyzes the market concentration of the parking sector in a scenario where climate change policies are crucial and the importance of sustainability certificates takes on a new meaning. Therefore, the objective of this article is to analyze whether the growing importance of environmental aspects has led to an increase in the concentration level of the parking sector in Spain. For this purpose, several concentration and stability indices are calculated. The results show that, although there are additional factors, the certification of a cleaner activity is relevant in the process of public tenders in the sector, which has served to strengthen the dominance of the most prominent companies in the sector that are in possession of environmental certificates. This shows that environmental policies can also have negative effects on the market, so the results of this analysis are of great value to policymakers.
Behavioural Markers of Harm and Their Potential in Identifying Product Risk in Online Gambling
Authors: Delfabbro Paul , Parke Jonathan , Catania Maris , Chikh Karim
Published: May 2023

Many studies have been conducted to identify potentially useful behavioural markers of harmful behaviour using online gambling data sourced from operators. However, less is known about how such markers could be used to identify higher risk products. The study examined whether certain categories and subcategories of product are more strongly associated with behavioural markers of harm than others. Analyses were based on 6 months of data (N = 100,000 individual gamblers) drawn from the population of UK users of an online gambling website in 2022. Measures included individual-level expenditure data across multiple forms of gambling and a series of literature-informed behavioural markers of harm including declined deposits, easing/removing responsible gambling settings, within-session repeat deposits (or ‘top-ups’), bonus-seeking behaviour and gambling at unusual hours. Negative binomial models examined how well the number of active days playing different products predicted behavioural markers of harm. All markers apart from easing/removing responsible gambling settings appeared to covary with the number of active days engaging in specific product types, most notably slots, in-playing betting and some most forms of combination bets on sports. These findings highlight the potential value of using measurable markers to differentiate the risk and potential harm associated with different online products.
Fast iterative reverse filters using fixed-point acceleration
Authors: Deng Guang , Galetto Fernando
Published: May 2023

Iterative reverse filters have been recently developed to address the problem of removing effects of a black box image filter. Because numerous iterations are usually required to achieve the desired result, the processing speed is slow. In this paper, we propose to use fixed-point acceleration techniques to tackle this problem. We present an interpretation of existing reverse filters as fixed-point iterations and discuss their relationship with gradient descent. We then present extensive experimental results to demonstrate the performance of fixed-point acceleration techniques named after: Anderson, Chebyshev, Irons, and Wynn. We also compare the performance of these techniques with that of gradient descent acceleration. Key findings of this work include: (1) Anderson acceleration can make a non-convergent reverse filter convergent, (2) the T-method with an acceleration technique is highly efficient and effective, and (3) in terms of processing speed, all reverse filters can benefit from one of the acceleration techniques.
Fundamentals of Green Steel Production: On the Role of Gas Pressure During Hydrogen Reduction of Iron Ores
Authors: Souza Filho I. R. , Ma Y. , Raabe D. , Springer H.
Published: May 2023

Out of the multitude of researched processing routes for sustainable ironmaking, hydrogen-based direct reduction and hydrogen plasma smelting reduction (HyPSR) are currently the most promising candidates for a successful industrial application. Both processes operate under gaseous atmospheres, which turn the partial and absolute pressure of hydrogen into a relevant process parameter. Here, we present first insights into the influence of total pressure and concentration of hydrogen on the reduction of hematite, focusing on the more pressure-sensitive route (HyPSR). The effect of pressure on the dissociation of H2 molecules into metastable H atoms or H+ ions,- and the overall hydrogen utilization is discussed using a thermodynamic approach. Validation experiments were conducted to testify the practical feasibility of adjusting these parameters. A decrease in the total pressure of the system from 900 mbar to 450 mbar resulted in an improved hydrogen utilization, thus suggesting that a larger population of H atoms can exist in the plasma arcs ignited under 450 mbar. An increase in the hydrogen concentration to 20 vol.% lead to undesired evaporation, likely because of a parallel increase in plasma temperature. Possibilities and challenges for exploiting these pressure-related phenomena for the industrial production of green steel are outlined and discussed.
The Potential of Fibroblast Activation Protein-Targeted Imaging as a Biomarker of Cardiac Remodeling and Injury
Authors: Mayola Maday Fernandez , Thackeray James T.
Published: May 2023

Purpose of Review

Cardiovascular disease features adverse fibrotic processes within the myocardium, leading to contractile dysfunction. Activated cardiac fibroblasts play a pivotal role in the remodeling and progression of heart failure, but conventional diagnostics struggle to identify early changes in cardiac fibroblast dynamics. Emerging imaging methods visualize fibroblast activation protein (FAP) as a marker of activated fibroblasts, enabling non-invasive quantitative measurement of early cardiac remodeling.

Recent Findings

Retrospective analysis of oncology patient cohorts has identified cardiac uptake of FAP radioligands in response to various cardiovascular conditions. Small scale studies in dedicated cardiac populations have revealed FAP upregulation in injured myocardium, wherein the area of upregulation predicts subsequent ventricle dysfunction. Recent studies have demonstrated that silencing of FAP-expressing fibroblasts can reverse cardiac fibrosis in disease models.

The parallel growth of FAP-targeted imaging and therapy provides the opportunity for imaging-based monitoring and refinement of treatments targeting cardiac fibroblast activation.
Comparative Analysis of Clinical Practice Guidelines for the Pharmacological Treatment of Type 2 Diabetes Mellitus in Latin America
Authors: Taborda Restrepo Paula Andrea , Acosta-Reyes Jorge , Estupiñan-Bohorquez Andrés , Barrios-Mercado María Alejandra , Correa Gonzalez Nestor Fabián , Taborda Restrepo Alejandra , Barengo Noël C. , Gabriel Rafael
Published: May 2023

Purpose of Review

Type 2 diabetes mellitus (T2DM) is one of the leading causes of death and disability in the world. The majority of diabetes deaths (> 80%) occur in low- and middle-income countries, which are predominant in Latin America. Therefore, the purpose of this article is to compare the clinical practice guideline (CPG) for the pharmacological management of T2DM in Latin America (LA) with international reference guidelines.

Recent Findings

Several LA countries have recently developed CPGs. However, the quality of these guidelines is unknown according to the AGREE II tool and taking as reference three CPGs of international impact: American Diabetes Association (ADA), European Diabetes Association (EASD), and Latin American Diabetes Association (ALAD).

Ten CPGs were selected for analysis. The ADA scored > 80% on the AGREE II domains and was selected as the main comparator. Eighty percent of LA CPGs were developed before 2018. Only one was not recommended (all domains < 60%). The CPGs in LA have good quality but are outdated. They have significant gaps compared to the reference. There is a need for improvement, as proposing updates every three years to maintain the best available clinical evidence in all guidelines.
Structural and Functional Imaging Correlates of Visual Hallucinations in Parkinson’s Disease
Authors: Bhome Rohan , Thomas George Edward Calver , Zarkali Angeliki , Weil Rimona Sharon
Published: May 2023

Purpose of Review

To review recent structural and functional MRI studies of visual hallucinations in Parkinson’s disease.

Recent Findings

Previously, neuroimaging had shown inconsistent findings in patients with Parkinson’s hallucinations, especially in studies examining grey matter volume. However, recent advances in structural and functional MRI techniques allow better estimates of structural connections, as well as the direction of connectivity in functional MRI. These provide more sensitive measures of changes in structural connectivity and allow models of the changes in directional functional connectivity to be tested.

We identified 27 relevant studies and found that grey matter imaging continues to show heterogeneous findings in Parkinson’s patients with visual hallucinations. Newer approaches in diffusion imaging and functional MRI are consistent with emerging models of Parkinson’s hallucinations, suggesting shifts in attentional networks. In particular, reduced bottom-up, incoming sensory information, and over-weighting of top-down signals appear to be important drivers of visual hallucinations in Parkinson’s disease.
African Urban Sexualities After Queer Visibilities
Authors: Tucker Andrew
Published: May 2023

This article outlines why there exist important opportunities to think through what research on African urban sexualities—and specifically non-heteronormative sexualities—may mean moving forward. By looking back at the text Queer Visibilities that largely focused on articulating some of the relationships between the urban and sexuality over a decade ago in Cape Town, this article suggests at least three key opportunities in which future scholarship may wish to explore African urban sexualities in the current moment. These opportunities circulate around new theoretical insights that emerge from the South that may speak to but are not beholden to theories from the North, the urgent need for further empirical work on the ways sexuality interfaces with urbanisation dynamics on the continent, and to think through and give space to broader approaches to document the relationship between sexuality and the urban that include but also extend beyond more ‘traditional’ social science methods. This article then explores these opportunities in relation to the interventions that follow in this special issue.
Thermodynamic properties of heavy mesons in strongly coupled quark gluon plasma using the fractional of non-relativistic quark model
Authors: Abu-Shady M. , Ezz-Alarab Sh. Y.
Published: May 2023

A generalized fractional derivative of the analytical exact iteration method is used, in which the two-body potential in strongly coupled quark–gluon plasma is devoted to solve theN-dimensional radial Schrödinger equation. The energy eigenvalues for any state (n,l) and mass spectra in theN-dimensional space have been investigated. The dissociation temperatures were computed in theN-dimensional space for different states of quarkonia. The effect of fractional-order parameter is investigated on the dissociation temperatures of heavy quarkonium masses such as charmonium and bottomonium and thermodynamic properties such as entropy, free energy, internal energy, and specific heat in the 3D and the higher-dimensional space. Also, the effect of dimensionality number on dissociation temperatures is discussed. A comparison with other recent works is displayed. We deduce that the fractional-order plays an essential role in 3D and higher-dimensional space.
Automated detection, delineation and quantification of whole-body bone metastasis using FDG-PET/CT images
Authors: Nigam R. , Field M. , Harris G. , Barton M. , Carolan M. , Metcalfe P. , Holloway L.
Published: May 2023

Non-small cell lung cancer (NSCLC) patients with the metastatic spread of disease to the bone have high morbidity and mortality. Stereotactic ablative body radiotherapy increases the progression free survival and overall survival of these patients with oligometastases. FDG-PET/CT, a functional imaging technique combining positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) and computer tomography (CT) provides improved staging and identification of treatment response. It is also associated with reduction in size of the radiotherapy tumour volume delineation compared with CT based contouring in radiotherapy, thus allowing for dose escalation to the target volume with lower doses to the surrounding organs at risk. FDG-PET/CT is increasingly being used for the clinical management of NSCLC patients undergoing radiotherapy and has shown high sensitivity and specificity for the detection of bone metastases in these patients. Here, we present a software tool for detection, delineation and quantification of bone metastases using FDG-PET/CT images. The tool extracts standardised uptake values (SUV) from FDG-PET images for auto-segmentation of bone lesions and calculates volume of each lesion and associated mean and maximum SUV. The tool also allows automatic statistical validation of the auto-segmented bone lesions against the manual contours of a radiation oncologist. A retrospective review of FDG-PET/CT scans of more than 30 candidate NSCLC patients was performed and nine patients with one or more metastatic bone lesions were selected for the present study. The SUV threshold prediction model was designed by splitting the cohort of patients into a subset of ‘development’ and ‘validation’ cohorts. The development cohort yielded an optimum SUV threshold of 3.0 for automatic detection of bone metastases using FDG-PET/CT images. The validity of the derived optimum SUV threshold on the validation cohort demonstrated that auto-segmented and manually contoured bone lesions showed strong concordance for volume of bone lesion (r = 0.993) and number of detected lesions (r = 0.996). The tool has various applications in radiotherapy, including but not limited to studies determining optimum SUV threshold for accurate and standardised delineation of bone lesions and in scientific studies utilising large patient populations for instance for investigation of the number of metastatic lesions that can be treated safety with an ablative dose of radiotherapy without exceeding the normal tissue toxicity.
Phase Regulation and Defect Passivation Enabled by Phosphoryl Chloride Molecules for Efficient Quasi-2D Perovskite Light-Emitting Diodes
Authors: Li Mingliang , Zhao Yaping , Guo Jia , Qin Xiangqian , Zhang Qin , Tian Chengbo , Xu Peng , Li Yuqing , Tian Wanjia , Zheng Xiaojia , Xing Guichuan , Zhang Wen-Hua , Wei Zhanhua
Published: May 2023

Highlights

The modification of perovskite precursor by a series of phosphoryl chloride molecules can indeed improve the performance of perovskite LEDs (Pero-LEDs).

The bis(2-oxo-3-oxazolidinyl) phosphinic chloride can not only regulate the phase distribution by controlling the crystallization rate but also passivate the defects of the quasi-2D perovskite.

Highly efficient and reproducible Pero-LEDs are achieved with an maximum external quantum efficiency (EQEmax) of 20.82% and an average EQE (EQEave) of around 20% on 50 devices.

Quasi-2D perovskites have attracted tremendous interest for application as light-emission layers in light-emitting diodes (LEDs). However, the heterogeneous n phase and non-uniform distribution still severely limit the further development of quasi-2D perovskite LEDs (Pero-LEDs). Meanwhile, the increased defect density caused by the reduced dimension and grain size induces non-radiative recombination and further deteriorates the device performance. Here, we found that a series of molecules containing phosphoryl chloride functional groups have noticeable enhancement effects on the device performance of quasi-2D Pero-LEDs. Then, we studied the modification mechanism by focusing on the bis(2-oxo-3-oxazolidinyl) phosphinic chloride (BOPCl). It is concluded that the BOPCl can not only regulate the phase distribution by decreasing the crystallization rate but also remain in the grain boundaries and passivate the defects. As a result, the corresponding quasi-2D Pero-LEDs obtained a maximum external quantum efficiency (EQEmax) of 20.82% and an average EQE (EQEave) of around 20% on the optimal 50 devices, proving excellent reproducibility. Our work provides a new selection of molecular types for regulating the crystallization and passivating the defects of quasi-2D perovskite films.
Measuring Physiological Responses to Visualizations of Urban Planning Scenarios in Immersive Virtual Reality
Authors: Keil Julian , Weißmann Marco , Korte Annika , Edler Dennis , Dickmann Frank
Published: May 2023

Stakeholder participation is an important component of modern urban planning processes. It can provide information about potential social conflicts related to specific urban planning scenarios. However, acquiring feedback from stakeholders is usually limited to explicit response types such as interviews or questionnaires. Such explicit response types are not suitable for the assessment of unconscious responses to specific parameters of an urban planning scenario. To address this limitation, we propose an approach for the assessment of affective and stress responses using implicit measures. Using a measure for electrodermal activity (EDA) and a virtual reality (VR)-based 3D urban model, we demonstrate how implicit physiological measurements can be visualized and temporally matched to specific parameters in an immersive representation of an urban planning scenario. Since this approach is supposed to support conventional stakeholder participation processes in urban planning, we designed it to be simple, cost-effective and with as little task interference as possible. Based on the additional insights gained from measuring physiological responses to urban planning scenarios, urban planners can further optimize planning scenarios by adjusting them to the derived implicitly expressed needs of stakeholders. To support simple implementation of the suggested approach, we provide sample scripts for visualization of EDA data. Limitations concerning the evaluation of raw EDA data and potentials for extending the described approach with additional physiological measures and real-time data evaluation are discussed.
Why Is It so Difficult to Investigate Violent Radicalization?
Authors: Gómez Ángel , Vázquez Alexandra , Chinchilla Juana , Blanco Laura , Alba Beatriz , Chiclana Sandra , González-Álvarez José Luis
Published: May 2023

Imagine that you are a researcher interested in disentangling the underlying mechanisms that motivate certain individuals to self-sacrifice for a group or an ideology. Now, visualize that you are one of a few privileged that have the possibility of interviewing people who have been involved in some of the most dramatic terrorist attacks in history. What should you do? Most investigations focused on terrorism do not include empirical data and just a handful of fortunate have made face-to-face interviews with these individuals. Therefore, we might conclude that most experts in the field have not directly met the challenge of experiencing studying violent radicalization in person. As members of a research team who have talked with individuals under risk of radicalization, current, and former terrorists, our main goal with this manuscript is to synopsize a series of ten potential barriers that those interested in the subject might find when making fieldwork, and alternatives to solve them. If all the efforts made by investigators could save the life of a potential victim, prevent an individual from becoming radicalized, or make him/her decide to abandon the violence associated with terrorism, all our work will have been worthwhile.
Verification and Model Configuration Sensitivity of Simulated ABI Radiance Forecasts With the FV3‐LAM Model
Authors: Johnson Aaron , Wang Xuguang , Blake Benjamin T. , Rogers Eric , Wang Yunheng , Carley Jacob R. , Clark Adam , Beck Jeffrey , Alexander Curtis
Published: May 2023

This study evaluates simulated radiance forecasts from a series of controlled experiments consisting of FV3‐LAM forecasts with different configurations of model physics and vertical resolution. The forecasts were produced during the 2020 Hazardous Weather Testbed Spring Forecasting Experiments on the same forecast cases. The evaluation includes grid‐point, neighborhood‐based and object‐based verification. The experiments include forecasts that were identical except for the physics (EMC‐LAM vs. EMC‐LAMx), vertical resolution (EMC‐LAMx vs. NSSL‐LAM), or combined initial conditions, physics and vertical resolution (GSL‐LAM). It is found that the EMC‐LAM generally provided better simulated radiance forecasts than the other three configurations at most forecast lead times, due to its unique physics configuration. All configurations generally over‐forecasted high level clouds. EMC‐LAM reduced the over‐forecasting of high clouds, but also under‐forecasted the coverage of mid‐level clouds. In contrast, at early lead times the EMC‐LAM had relatively poor performance relative to the other forecasts. Furthermore, EMC‐LAM was an outlier in terms of the vertical structure of clouds. It is also found that the NSSL‐LAM consistently improved upon the EMC‐LAMx, which had fewer vertical levels than NSSL‐LAM. Compared to EMC‐LAMx, NSSL‐LAM had less cloud over‐forecasting bias, especially with small cloud objects, and less overall error. The differences between EMC‐LAMx and GSL‐LAM were generally much smaller than the differences between EMC‐LAMx and EMC‐LAM/NSSL‐LAM. Finally, it is found that a non‐linear bias correction conditioned on symmetric brightness temperature reduced the overall root‐mean‐square error by about a factor of 2 while improving the unrealistic vertical structure of clouds in the EMC‐LAM.
Seamount Subduction and Megathrust Seismicity: The Interplay Between Geometry and Friction
Authors: Menichelli I. , Corbi F. , Brizzi S. , van Rijsingen E. , Lallemand S. , Funiciello F.
Published: May 2023

Subducting seamounts are recognized as one of the key features influencing megathrust earthquakes. However, whether they trigger or arrest ruptures remains debated. Here, we use analog models to study the influence of a single seamount on megathrust earthquakes, separating the effect of topography from that of friction. Four different model configurations have been developed (i.e., flat interface, high and low friction seamount, low friction patch). In our models, the seamount reduces recurrence time, interseismic coupling, and fault strength, suggesting that it acts as a barrier: 80% of the ruptures concentrate in flat regions that surround the seamount and only smaller magnitude earthquakes nucleate above it. The low‐friction zone, which mimics the fluid accumulation or the establishment of fracture systems in natural cases, seems to be the most efficient in arresting rupture propagation in our experimental setting.
The Role of a Strong Out‐Of‐Plane Magnetic Field at the X‐Line in Antiparallel Magnetic Reconnection as a Guide Field
Authors: Zhang Y. C. , Wang C. , Dai L. , Tang S. Y. , Burch J. L.
Published: May 2023

The magnetic reconnection process substantially changes the configuration of the magnetic field in plasma and explosively releases magnetic energy. The asymptotic magnetic field lines during magnetic reconnection events can be strictly antiparallel or only have one antiparallel component, and the magnetic reconnection features are distinct under different asymptotic magnetic fields. Here, we provide the first observational evidence demonstrating the existence of a strong out‐of‐plane magnetic field at the X‐line in antiparallel reconnection. The analyses described herein show that this strong out‐of‐plane magnetic field significantly changes the structure of the diffusion region, thereby altering the reconnection features in terms of particle dynamics and energy dissipation by way of a guide field. A new pattern of the normal electric field near the X‐line is responsible for producing this out‐of‐plane magnetic field. Our findings suggest that, in addition to asymptotic conditions, local processes inside the diffusion region can also determine whether magnetic reconnection events develop as antiparallel reconnection or component reconnection.
Glia maturation factor beta deficiency protects against diabetic osteoporosis by suppressing osteoclast hyperactivity
Authors: Shi Si , Gu Huijie , Xu Jinyuan , Sun Wan , Liu Caiyin , Zhu Tong , Wang Juan , Gao Furong , Zhang Jieping , Ou Qingjian , Jin Caixia , Xu Jingying , Chen Hao , Li Jiao , Xu Guotong , Tian Haibin , Lu Lixia
Published: May 2023

Excessive osteoclast activation, which depends on dramatic changes in actin dynamics, causes osteoporosis (OP). The molecular mechanism of osteoclast activation in OP related to type 1 diabetes (T1D) remains unclear. Glia maturation factor beta (GMFB) is considered a growth and differentiation factor for both glia and neurons. Here, we demonstrated that Gmfb deficiency effectively ameliorated the phenotype of T1D-OP in rats by inhibiting osteoclast hyperactivity. In vitro assays showed that GMFB participated in osteoclast activation rather than proliferation. Gmfb deficiency did not affect osteoclast sealing zone (SZ) formation but effectively decreased the SZ area by decreasing actin depolymerization. When GMFB was overexpressed in Gmfb-deficient osteoclasts, the size of the SZ area was enlarged in a dose-dependent manner. Moreover, decreased actin depolymerization led to a decrease in nuclear G-actin, which activated MKL1/SRF-dependent gene transcription. We found that pro-osteoclastogenic factors (Mmp9 and Mmp14) were downregulated, while anti-osteoclastogenic factors (Cftr and Fhl2) were upregulated in Gmfb KO osteoclasts. A GMFB inhibitor, DS-30, targeting the binding site of GMFB and Arp2/3, was obtained. Biocore analysis revealed a high affinity between DS-30 and GMFB in a dose-dependent manner. As expected, DS-30 strongly suppressed osteoclast hyperactivity in vivo and in vitro. In conclusion, our work identified a new therapeutic strategy for T1D-OP treatment. The discovery of GMFB inhibitors will contribute to translational research on T1D-OP.
The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy
Authors: Wang Hui-Ching , Moi Sin-Hua , Chan Leong-Perng , Wu Chun-Chieh , Du Jeng-Shiun , Liu Pei-Lin , Chou Meng-Chun , Wu Che-Wei , Huang Chih-Jen , Hsiao Hui-Hua , Pan Mei-Ren , Chen Li-Tzong
Published: May 2023

Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.
Mesenchymal stem cell-derived extracellular vesicles protect against abdominal aortic aneurysm formation by inhibiting NET-induced ferroptosis
Authors: Chen Liang , Liu Yuting , Wang Zheyu , Zhang Leiyang , Xu Yi , Li Yinan , Zhang Lan , Wang Guiming , Yang Shuofei , Xue Guanhua
Published: May 2023

Neutrophil extracellular traps (NETs) play an important role in abdominal aortic aneurysm (AAA) formation; however, the underlying molecular mechanisms remain unclear. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may exert therapeutic effects on AAA through their immunomodulatory and regenerative abilities. This study aimed to examine the role and mechanism of MSC-EVs in regulating the development of NET-mediated AAA. Excessive release of NETs was observed in patients with AAA, and the levels of NET components were associated with the clinical outcomes of the patients. Datasets from the Gene Expression Omnibus database were analyzed and revealed that the PI3K/AKT pathway and ferroptosis were strongly associated with NETosis during AAA formation. Further experiments verified that NETs promoted AAA formation by inducing ferroptosis in smooth muscle cells (SMCs) by inhibiting the PI3K/AKT pathway. The PI3K agonist 740 Y-P, the ferroptosis inhibitor ferrostatin-1, and Padi4 deficiency significantly prevented AAA formation. MSC-EVs attenuated AAA formation by reducing NET release in an angiotensin II-induced AAA mouse model. In vitro experiments revealed that MSC-EVs reduced the release of NETs by shifting NETosis to apoptosis. Our study indicates an important role for NET-induced SMC ferroptosis in AAA formation and provides several potential targets for AAA treatment.
Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis
Authors: Kim Kwangho , Ryu Tae Young , Jung Eunsun , Han Tae-Su , Lee Jinkwon , Kim Seon-Kyu , Roh Yu Na , Lee Moo-Seung , Jung Cho-Rok , Lim Jung Hwa , Hamamoto Ryuji , Lee Hye Won , Hur Keun , Son Mi-Young , Kim Dae-Soo , Cho Hyun-Soo
Published: May 2023

Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone methyltransferase SMYD2 is overexpressed in lung cancer and that knockdown of SMYD2 could reduce the rates of cell migration and invasion in lung cancer cell lines via direct downregulation of SMAD3 via SMYD2-mediated epigenetic regulation. Furthermore, using an in vitro epithelial-mesenchymal transition (EMT) system with a Transwell system, we generated highly invasive H1299 (In-H1299) cell lines and observed the suppression of metastatic features by SMYD2 knockdown. Finally, two types of in vivo studies revealed that the formation of metastatic tumors by shSMYD2 was significantly suppressed. Thus, we suggest that SMYD2 is a potential metastasis regulator and that the development of SMYD2-specific inhibitors may help to increase the efficacy of lung cancer treatment.
Clinical molecular subtyping reveals intrinsic mesenchymal reprogramming in gastric cancer cells
Authors: Jang Eunji , Shin Min-Kyue , Kim Hyunki , Lim Joo Yeon , Lee Jae Eun , Park Jungmin , Kim Jungeun , Kim Hyeseon , Shin Youngmin , Son Hye-Young , Choi Yoon Young , Hyung Woo Jin , Noh Sung Hoon , Suh Jin-Suck , Sung Ji-Yong , Huh Yong-Min , Cheong Jae-Ho
Published: May 2023

The mesenchymal cancer phenotype is known to be clinically related to treatment resistance and a poor prognosis. We identified gene signature-based molecular subtypes of gastric cancer (GC,n = 547) based on transcriptome data and validated their prognostic and predictive utility in multiple external cohorts. We subsequently examined their associations with tumor microenvironment (TME) features by employing cellular deconvolution methods and sequencing isolated GC populations. We further performed spatial transcriptomics analysis and immunohistochemistry, demonstrating the presence of GC cells in a partial epithelial-mesenchymal transition state. We performed network and pharmacogenomic database analyses to identify TGF-β signaling as a driver pathway and, thus, a therapeutic target. We further validated its expression in tumor cells in preclinical models and a single-cell dataset. Finally, we demonstrated that inhibition of TGF-β signaling negated mesenchymal/stem-like behavior and therapy resistance in GC cell lines and mouse xenograft models. In summary, we show that the mesenchymal GC phenotype could be driven by epithelial cancer cell-intrinsic TGF-β signaling and propose therapeutic strategies based on targeting the tumor-intrinsic mesenchymal reprogramming of medically intractable GC.
Crystal structure of LRG1 and the functional significance of LRG1 glycan for LPHN2 activation
Authors: Yang Jimin , Yin Guo Nan , Kim Do-Kyun , Han Ah-reum , Lee Dong Sun , Min Kwang Wook , Fu Yaoyao , Yun Jeongwon , Suh Jun-Kyu , Ryu Ji-Kan , Kim Ho Min
Published: May 2023

The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1), primarily produced by hepatocytes and neutrophils, is a multifunctional protein that modulates various signaling cascades, mainly TGFβ signaling. Serum LRG1 and neutrophil-derived LRG1 have different molecular weights due to differences in glycosylation, but the impact of the differential glycan composition in LRG1 on its cellular function is largely unknown. We previously reported that LRG1 can promote both angiogenic and neurotrophic processes under hyperglycemic conditions by interacting with LPHN2. Here, we determined the crystal structure of LRG1, identifying the horseshoe-like solenoid structure of LRG1 and its four N-glycosylation sites. In addition, our biochemical and cell-biological analyses found that the deglycosylation of LRG1, particularly the removal of glycans on N325, is critical for the high-affinity binding of LRG1 to LPHN2 and thus promotes LRG1/LPHN2-mediated angiogenic and neurotrophic processes in mouse tissue explants, even under normal glucose conditions. Moreover, the intracavernous administration of deglycosylated LRG1 in a diabetic mouse model ameliorated vascular and neurological abnormalities and restored erectile function. Collectively, these data indicate a novel role of LRG1 glycans as molecular switches that can tune the range of LRG1’s cellular functions, particularly the LRG1/LPHN2 signaling axis.
Steady-state memory-phenotype conventional CD4+ T cells exacerbate autoimmune neuroinflammation in a bystander manner via the Bhlhe40/GM-CSF axis
Authors: Cho Min-Ji , Lee Hong-Gyun , Yoon Jae-Won , Kim Gil-Ran , Koo Ja-Hyun , Taneja Reshma , Edelson Brian T. , Lee You Jeong , Choi Je-Min
Published: May 2023

Memory-phenotype (MP) CD4+ T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4+ T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4+ T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure. Distinct subpopulations of MP CD4+ T cells were specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells exerted TCR-independent bystander effector functions similar to innate lymphoid cells. In particular, CCR6high subpopulation of MP CD4+ T cells were major responders to IL-23 and IL-1β without MOG35-55 antigen reactivity, which gave them pathogenic Th17 characteristics and allowed them to contribute to autoimmune encephalomyelitis. We identified that Bhlhe40 in CCR6high MP CD4+ T cells as a key regulator of GM-CSF expression through IL-23 and IL-1β signaling, contributing to central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal the clearly distinct effector-like heterogeneity of MP CD4+ T cells in the steady state and indicate that CCR6high MP CD4+ T cells exacerbate autoimmune neuroinflammation via the Bhlhe40/GM-CSF axis in a bystander manner.
Integrative multi-omics and drug–response characterization of patient-derived prostate cancer primary cells
Authors: Wang Ziruoyu , Li Yanan , Zhao Wensi , Jiang Shuai , Huang Yuqi , Hou Jun , Zhang Xuelu , Zhai Zhaoyu , Yang Chen , Wang Jiaqi , Zhu Jiying , Pan Jianbo , Jiang Wei , Li Zengxia , Ye Mingliang , Tan Minjia , Jiang Haowen , Dang Yongjun
Published: May 2023

Prostate cancer (PCa) is the second most prevalent malignancy in males across the world. A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa. Herein, we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients, including gene mutations, mRNA/protein/surface protein distributions, and pharmaceutical responses. The multi-omics analyses identify Anterior Gradient 2 (AGR2) as a pre-operative prognostic biomarker in PCa. Through the drug library screening, we describe crizotinib as a selective compound for malignant PCa primary cells. We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations. Surprisingly, the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model. Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses, allowing for more precise diagnosis and therapies.
Vascular endothelium is the basic way for stem cells to treat erectile dysfunction: a bibliometric study
Authors: Zou Hede , Zhang Xuesong , Chen Wenkang , Tao Yi , Li Bolin , Liu Hanfei , Wang Ruikun , Zhao Jiayou
Published: May 2023

Vascular endothelial is considered to be a key factor in the pathogenesis of erectile dysfunction (ED). The purpose is to reveal the research trend of the field of ED and vascular endothelium. In addition, the goal is to discover the role and mechanism of vascular endothelium in ED. Bibliometrics and visualization methods based on CiteSpace were selected. We conducted the co-authorship analysis of countries, institutions and authors, co-occurrence analysis of keywords, and co-citation analysis of literature and authors through CiteSpace 6.1.R3. 1431 articles from Web of Science Core Collection (WOSCC) were included in the analysis from 1991 to 2022. We found some influential and cutting-edge nodes in each map, including countries, institutions, authors, articles, etc. Stem cell, therapy, oxidative stress, cavernous nerve injury, radical prostatectomy, fibrosis, erectile function, mesenchymal stem cell, and apoptosis may be hot keywords. In conclusion, the efficacy and mechanisms of stem cells and their derivatives in the treatment of diabetes (DM) ED and cavernous nerve injury (CNI) ED are the future research trends. Stem cells therapy for ED is a hot spot in this field, which side notes that stem cells may work mainly through improving endothelial function. Vascular endothelial cells and VEGF may repair nerve and cavernous smooth muscle directly or indirectly, and finally polish up erectile function.
Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids
Authors: Papsdorf Katharina , Miklas Jason W. , Hosseini Amir , Cabruja Matias , Morrow Christopher S. , Savini Marzia , Yu Yong , Silva-García Carlos G. , Haseley Nicole R. , Murphy Luke Meraz , Yao Pallas , de Launoit Elisa , Dixon Scott J. , Snyder Michael P. , Wang Meng C. , Mair William B. , Brunet Anne
Published: May 2023

Dietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced longevity in Caenorhabditis elegans. MUFAs upregulate the number of lipid droplets in fat storage tissues. Increased lipid droplet number is necessary for MUFA-induced longevity and predicts remaining lifespan. Lipidomics datasets reveal that MUFAs also modify the ratio of membrane lipids and ether lipids—a signature associated with decreased lipid oxidation. In agreement with this, MUFAs decrease lipid oxidation in middle-aged individuals. Intriguingly, MUFAs upregulate not only lipid droplet number but also peroxisome number. A targeted screen identifies genes involved in the co-regulation of lipid droplets and peroxisomes, and reveals that induction of both organelles is optimal for longevity. Our study uncovers an organelle network involved in lipid homeostasis and lifespan regulation, opening new avenues for interventions to delay aging.
Positive correlation between wet-day frequency and intensity linked to universal precipitation drivers
Authors: McErlich Cameron , McDonald Adrian , Schuddeboom Alex , Vishwanathan Gokul , Renwick James , Rana Sapna
Published: May 2023

Understanding precipitation is essential for quantifying weather and climate-related risks. Changes in precipitation climatology are typically based on independent analysis of precipitation frequency and intensity. Here we show that where it rains more often, it also rains harder. When grouping global precipitation reanalysis data and observations from the past 40 years into regions of similar wet-day frequency, regardless of geographical separation, there is a strong correlation with wet-day intensity distributions. These wet-day-frequency regions are also more physically coherent than regions based on geographical location. We find the coherent relationship between wet-day frequency and intensity distributions is partially explained by wet-day-frequency regions having similar vertical velocity and convective available potential energy distributions, once polar regions are excluded. These represent dynamic and thermodynamic processes that indicate how conducive wet-day-frequency regions are to large-scale and convective precipitation. This suggests that the main drivers of precipitation are universal. We also show that extreme-precipitation metrics are dependent on wet-day frequency within our framework. Our results imply that wet-day frequency could be used to derive estimates of extreme-precipitation climate indices and corresponding uncertainties, these uncertainties being related to local processes.
Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits
Authors: Zhang Brian C. , Biddanda Arjun , Gunnarsson Árni Freyr , Cooper Fergus , Palamara Pier Francesco
Published: May 2023

Genome-wide genealogies compactly represent the evolutionary history of a set of genomes and inferring them from genetic data has the potential to facilitate a wide range of analyses. We introduce a method, ARG-Needle, for accurately inferring biobank-scale genealogies from sequencing or genotyping array data, as well as strategies to utilize genealogies to perform association and other complex trait analyses. We use these methods to build genome-wide genealogies using genotyping data for 337,464 UK Biobank individuals and test for association across seven complex traits. Genealogy-based association detects more rare and ultra-rare signals (N = 134, frequency range 0.0007−0.1%) than genotype imputation using ~65,000 sequenced haplotypes (N = 64). In a subset of 138,039 exome sequencing samples, these associations strongly tag (average r = 0.72) underlying sequencing variants enriched (4.8×) for loss-of-function variation. These results demonstrate that inferred genome-wide genealogies may be leveraged in the analysis of complex traits, complementing approaches that require the availability of large, population-specific sequencing panels.
Dynamic epistasis analysis reveals how chromatin remodeling regulates transcriptional bursting
Authors: Brouwer Ineke , Kerklingh Emma , van Leeuwen Fred , Lenstra Tineke L.
Published: May 2023

Transcriptional bursting has been linked to the stochastic positioning of nucleosomes. However, how bursting is regulated by the remodeling of promoter nucleosomes is unknown. Here, we use single-molecule live-cell imaging of GAL10 transcription in Saccharomyces cerevisiae to measure how bursting changes upon combined perturbations of chromatin remodelers, the transcription factor Gal4 and preinitiation complex components. Using dynamic epistasis analysis, we reveal how the remodeling of different nucleosomes regulates transcriptional bursting parameters. At the nucleosome covering the Gal4 binding sites, RSC and Gal4 binding synergistically facilitate each burst. Conversely, nucleosome remodeling at the TATA box controls only the first burst upon galactose induction. At canonical TATA boxes, the nucleosomes are displaced by TBP binding to allow for transcription activation even in the absence of remodelers. Overall, our results reveal how promoter nucleosome remodeling together with Gal4 and preinitiation complex binding regulates transcriptional bursting.
Personality traits and dimensions of mental health
Authors: Kang Weixi , Steffens Francois , Pineda Sònia , Widuch Kaya , Malvaso Antonio
Published: May 2023

Individuals are different in a relatively constant pattern of thoughts, feeling, and behaviors, which are called personality traits. Mental health is a condition of well-being in which people may reach their full potential and deal effectively with stress, work efficiently, and contribute to their communities. Indeed, the link between personality and mental health as indicated by the 12-item version of the general health questionnaires (GHQ-12) has been well-established according to evidence found by decades of research. However, the GHQ-12 comprises many questions asking about different dimensions of mental health. It is unclear how personality traits relate to these dimensions of mental health. In this paper, we try to address this question. We analyzed data from 12,007 participants from the British Household Panel Study (BHPS) using a confirmatory factor analysis (CFA) and generalized linear models. We replicated the factor structure of GHQ-12 labeled as GHQ-12A (social dysfunction & anhedonia; 6 items), GHQ-12B (depression & anxiety; 4 items), and GHQ-12C (loss of confidence; 2 items). Moreover, Neuroticism was positively related to all dimensions of mental health issues, Extraversion was negatively related to GHQ-12A (social dysfunction & anhedonia) and GHQ-12B (depression & anxiety), Agreeableness and Conscientiousness were negatively related to GHQ-12A (social dysfunction & anhedonia) and GHQ-12C (loss of confidence), and Openness was negatively related to GHQ-12B (depression & anxiety). These results contribute to theories including the predisposition/vulnerability model, complication/scar model, pathoplasty/exacerbation model, and the spectrum model, which propose that personality traits are linked to mental health and explained possible reasons. Psychologists may use results from this study to identify individuals who may be at high risk of developing various non-psychiatric mental health issues and intervene to avoid negative outcomes.