bluuebunny/crossref_metadata_2025 huggingface dataset:
A measure of local uniqueness to identify linchpins in a social network with node attributes
Authors: Nemesure Matthew D. , Schwedhelm Thomas M. , Sacerdote Sofia , O’Malley A. James , Rozema Luke R. , Moen Erika L.
Published: July 2021

Network centrality measures assign importance to influential or key nodes in a network based on the topological structure of the underlying adjacency matrix. In this work, we define the importance of a node in a network as being dependent on whether it is the only one of its kind among its neighbors’ ties. We introduce linchpin score, a measure of local uniqueness used to identify important nodes by assessing both network structure and a node attribute. We explore linchpin score by attribute type and examine relationships between linchpin score and other established network centrality measures (degree, betweenness, closeness, and eigenvector centrality). To assess the utility of this measure in a real-world application, we measured the linchpin score of physicians in patient-sharing networks to identify and characterize important physicians based on being locally unique for their specialty. We hypothesized that linchpin score would identify indispensable physicians who would not be easily replaced by another physician of their specialty type if they were to be removed from the network. We explored differences in rural and urban physicians by linchpin score compared with other network centrality measures in patient-sharing networks representing the 306 hospital referral regions in the United States. We show that linchpin score is uniquely able to make the distinction that rural specialists, but not rural general practitioners, are indispensable for rural patient care. Linchpin score reveals a novel aspect of network importance that can provide important insight into the vulnerability of health care provider networks. More broadly, applications of linchpin score may be relevant for the analysis of social networks where interdisciplinary collaboration is important.
DNA structural and physical properties reveal peculiarities in promoter sequences of the bacterium Escherichia coli K-12
Authors: Martinez Gustavo Sganzerla , de Ávila e Silva Scheila , Kumar Aditya , Pérez-Rueda Ernesto
Published: July 2021

The gene transcription of bacteria starts with a promoter sequence being recognized by a transcription factor found in the RNAP enzyme, this process is assisted through the conservation of nucleotides as well as other factors governing these intergenic regions. Faced with this, the coding of genetic information into physical aspects of the DNA such as enthalpy, stability, and base-pair stacking could suggest promoter activity as well as protrude differentiation of promoter and non-promoter data. In this work, a total of 3131 promoter sequences associated to six different sigma factors in the bacterium E. coli were converted into numeric attributes, a strong set of control sequences referring to a shuffled version of the original sequences as well as coding regions is provided. Then, the parameterized genetic information was normalized, exhaustively analyzed through statistical tests. The results suggest that strong signals in the promoter sequences match the binding site of transcription factor proteins, indicating that promoter activity is well represented by its conversion into physical attributes. Moreover, the features tested in this report conveyed significant variances between promoter and control data, enabling these features to be employed in bacterial promoter classification. The results produced here may aid in bacterial promoter recognition by providing a robust set of biological inferences.
Comparative spatial–temporal analysis and predictive modeling of climate change-induced malaria vectors’ invasion in new hotspots in Kenya
Authors: Kimuyu J. S.
Published: July 2021

Climate change/variability is a major driving factor among others that contribute to the spread of suitable malaria vectors’ geographical extent. The current study employed comparative spatial–temporal analysis using bioclimatic envelope modeling to predict and quantify the possible surge of suitable malaria vectors’ habitats in new hotspots in Kenya. BIOCLIM and BIOCLIM True/False models were run with model data from HADCM3, CCCMA and SCIRO IPCC future climatic projections under A2a scenario. Prediction and projection of the malaria vectors’ prevalence and distribution were done for the whole country. Spatial–temporal models were generated for the baseline climate, and projections were done to depict how the vectors are likely to be distributed by the years 2020, 2050 and 2080 under the influence of climate change. The results showed that the highest suitable malaria vectors’ habitats by area was 227, 092 km2obtained when prediction was done with HADCM3 future climate by the year 2050. The least suitable habitats by area was 80, 060 km2which was predicted with CCCMA projection by the year 2050. Ecological niche prediction from HADCM3 and CSIRO showed a similar trend although at different magnitudes. The prediction results portrayed high likelihood of shift in some suitable habitats that could turn unsuitable, while new hotspots are likely to emerge. The BIOCLIM prediction with the three future climate models showed that the current endemic zones of the lake region and south coastal strip of the Indian Ocean will still remain suitable habitats but with a decline shift in spatial extent by the year 2020, then start to expand by the years 2050–2080. Predictions from HADCM3 by the year 2050 has shown possible wide spread of malaria spatial extents in counties like Narok, Kajiado, Kitui, Makueni, Machakos, Meru, Marsabit, Isiolo, Samburu, Baringo, West Pokot, Turkana and Mandera, while a few others of lower extent might have some emerging isolated hotspots. Laikipia County might become unsuitable habitat for malaria vectors by the year 2050, and the case may remain the same by the year 2080. The malaria burden is likely to shift from Laikipia to the neighboring counties of Baringo, Isiolo, Meru and Turkana. In conclusion, malaria vectors are likely to spread in new continuous and isolated hotspots with future likely increase in malaria prevalence hence possible epidemic upsurge by the year 2050. Consequently, evidence-based scientific research can be utilized to guide policy for sustainable development in the health agenda.
Demand and growth regimes in finance-dominated capitalism and the role of the macroeconomic policy regime: a post-Keynesian comparative study on France, Germany, Italy and Spain before and after the Great Financial Crisis and the Great Recession
Authors: Hein Eckhard , Martschin Judith
Published: July 2021

We contribute to the recent debates on demand and growth regimes in modern finance-dominated capitalism linking them to the post-Keynesian research on macroeconomic policy regimes. We examine the demand and growth regimes, as well as the macroeconomic policy regimes for the big four Eurozone countries, France, Germany, Italy and Spain, for the periods 2001–2009 and 2010–2019. First, our approach supports the usefulness of the identification of demand and growth regimes according to growth contributions of the main demand components and financial balances of the macroeconomic sectors. This allows for an understanding of the demand sources of growth, or stagnation, if there is a lack of demand, of how these sources are financed and of potential financial instabilities and fragilities. Second, when it comes to the macroeconomic policy drivers of demand and growth regimes, as well as their respective changes, we show that the exclusive focus on fiscal policies, as in the previous literature, is too limited and that it is the macroeconomic policy regime which matters here, i.e. the combination of monetary, fiscal and wage policies, as well as the open economy conditions.
Aerosol-based antimicrobial photoinactivation in the lungs: an action spectrum study
Authors: Treghini Chiara , Dell’Accio Alfonso , Fusi Franco , Romano Giovanni
Published: July 2021

Chronic lung infections are among the most diffused human infections, being often associated with multidrug-resistant bacteria. In this framework, the European project “Light4Lungs” aims at synthesizing and testing an inhalable light source to control lung infections by antimicrobial photoinactivation (aPDI), addressing endogenous photosensitizers only (porphyrins) in the representative case of S. aureus and P. aeruginosa. In the search for the best emission characteristics for the aerosolized light source, this work defines and calculates the photo-killing action spectrum for lung aPDI in the exemplary case of cystic fibrosis. This was obtained by applying a semi-theoretical modelling with Monte Carlo simulations, according to previously published methodology related to stomach infections and applied to the infected trachea, bronchi, bronchioles and alveoli. In each of these regions, the two low and high oxygen concentration cases were considered to account for the variability of in vivo conditions, together with the presence of endogenous porphyrins and other relevant absorbers/diffusers inside the illuminated biofilm/mucous layer. Furthermore, an a priori method to obtain the “best illumination wavelengths” was defined, starting from maximizing porphyrin and light absorption at any depth. The obtained action spectrum is peaked at 394 nm and mostly follows porphyrin extinction coefficient behavior. This is confirmed by the results from the best illumination wavelengths, which reinforces the robustness of our approach. These results can offer important indications for the synthesis of the aerosolized light source and definition of its most effective emission spectrum, suggesting a flexible platform to be considered in further applications.
BrcaSeg: A Deep Learning Approach for Tissue Quantification and Genomic Correlations of Histopathological Images
Authors: Lu Zixiao , Zhan Xiaohui , Wu Yi , Cheng Jun , Shao Wei , Ni Dong , Han Zhi , Zhang Jie , Feng Qianjin , Huang Kun
Published: July 2021

Epithelial and stromal tissues are components of the tumor microenvironment and play a major role in tumor initiation and progression. Distinguishing stroma from epithelial tissues is critically important for spatial characterization of the tumor microenvironment. Here, we propose BrcaSeg, an image analysis pipeline based on a convolutional neural network (CNN) model to classify epithelial and stromal regions in whole-slide hematoxylin and eosin (H&E) stained histopathological images. The CNN model is trained using well-annotated breast cancer tissue microarrays and validated with images from The Cancer Genome Atlas (TCGA) Program. BrcaSeg achieves a classification accuracy of 91.02%, which outperforms other state-of-the-art methods. Using this model, we generate pixel-level epithelial/stromal tissue maps for 1000 TCGA breast cancer slide images that are paired with gene expression data. We subsequently estimate the epithelial and stromal ratios and perform correlation analysis to model the relationship between gene expression and tissue ratios. Gene Ontology (GO) enrichment analyses of genes that are highly correlated with tissue ratios suggest that the same tissue is associated with similar biological processes in different breast cancer subtypes, whereas each subtype also has its own idiosyncratic biological processes governing the development of these tissues. Taken all together, our approach can lead to new insights in exploring relationships between image-based phenotypes and their underlying genomic events and biological processes for all types of solid tumors. BrcaSeg can be accessed at https://github.com/Serian1992/ImgBio.
i2dash: Creation of Flexible, Interactive, and Web-Based Dashboards for Visualization of Omics Data
Authors: Ustjanzew Arsenij , Preussner Jens , Bentsen Mette , Kuenne Carsten , Looso Carsten
Published: July 2021

Data visualization and interactive data exploration are important aspects of illustrating complex concepts and results from analyses of omics data. A suitable visualization has to be intuitive and accessible. Web-based dashboards have become popular tools for the arrangement, consolidation, and display of such visualizations. However, the combination of automated data processing pipelines handling omics data and dynamically generated, interactive dashboards is poorly solved. Here, we present i2dash, an R package intended to encapsulate functionality for the programmatic creation of customized dashboards. It supports interactive and responsive (linked) visualizations across a set of predefined graphical layouts. i2dash addresses the needs of data analysts/software developers for a tool that is compatible and attachable to any R-based analysis pipeline, thereby fostering the separation of data visualization on one hand and data analysis tasks on the other hand. In addition, the generic design of i2dash enables the development of modular extensions for specific needs. As a proof of principle, we provide an extension of i2dash optimized for single-cell RNA sequencing analysis, supporting the creation of dashboards for the visualization needs of such experiments. Equipped with these features, i2dash is suitable for extensive use in large-scale sequencing/bioinformatics facilities. Along this line, we provide i2dash as a containerized solution, enabling a straightforward large-scale deployment and sharing of dashboards using cloud services. i2dash is freely available via the R package archive CRAN (https://CRAN.R-project.org/package=i2dash).
scDPN for High-Throughput Single-Cell CNV Detection to Uncover Clonal Evolution During HCC Recurrence
Authors: Wu Liang , Jiang Miaomiao , Wang Yuzhou , Zhou Biaofeng , Sun Yunfan , Zhou Kaiqian , Xie Jiarui , Zhong Yu , Zhao Zhikun , Dean Michael , Hou Yong , Liu Shiping
Published: July 2021

Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution. Unfortunately, classical DNA amplification-based methods have low throughput and introduce coverage bias during sample preamplification. We developed a single-cell DNA library preparation method without preamplification in nanolitre scale (scDPN) to address these issues. The method achieved a throughput of up to 1800 cells per run for copy number variation (CNV) detection. Also, our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification (MDA) method and showed high sensitivity and accuracy for cell line and tumor tissue evaluation. We used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepatocellular carcinoma (HCC). We identified three clonal subpopulations with a multitude of aneuploid alterations across the genome. Furthermore, we observed that a minor clone of the primary tumor containing additional alterations in chromosomes 1q, 10q, and 14q developed into the dominant clone in the recurrent tumor, indicating clonal selection during recurrence in HCC. Overall, this approach provides a comprehensive and scalable solution to understand genome heterogeneity and evolution
Oxaliplatin, an Anticancer Agent, Causes Erectile Dysfunction in Rats due to Endothelial Dysfunction
Authors: Kataoka Tomoya , Mori Taiki , Suzuki Jun , Kawaki Yuto , Kito Yohei , Hotta Yuji , Kawade Yoshihiro , Maeda Yasuhiro , Kimura Kazunori
Published: July 2021

Background

Chemotherapeutics, one of the standard treatment options for cancer worldwide, have various adverse effects, including erectile dysfunction (ED).

Aim

To investigate erectile function in an animal model after administration of the anticancer agent oxaliplatin (L-OHP).

Methods

Male Wistar/ST rats were divided into 2 groups: L-OHP rats (n = 21), which were intravenously administered L-OHP (4 mg/kg; twice a week for 4 weeks), and Control rats (n = 21), which were injected with the same volume of 5% glucose solution, using the same dosing schedule. At the end of the study period, erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation (n = 9–10). Endothelial function was evaluated with an isometric tension study using corpus cavernosum strips (n = 11). Western blot analysis was used to assess neuronal nitric oxide (nNOS) and endothelial NO synthase (eNOS) protein levels (n = 7). Real-time quantitative polymerase chain reaction (qRT-PCR) was used to assess the expression of inflammation- and oxidative stress-related markers (nicotinamide adenine dinucleotide phosphate oxidase-1, p22phox, interleukin [IL]-6, and nuclear factor-kappa B) (n = 6). Statistical significance was determined using the Student’s t-test.

Outcomes

The L-OHP group had a significantly lower ICP:MAP ratio than the control group (P < .05). Compared to the Control group, the L-OHP group exhibited significantly lower responses to ACh and eNOS protein levels and significantly higher inflammatory biomarker levels.

Clinical Translation

The results based on this animal model indicate that use of the anticancer agent L-OHP should be considered as a risk factor for ED occurring via reduction of NO bioavailability in humans; our results provide possible treatment strategies for maintaining the erectile function of cancer survivors.

Strengths and limitations

Our study showed that the anticancer agent L-OHP has the propensity to cause ED in rats. A major limitation of this study is the lack of an established cure for ED associated with L-OHP and the lack of clinical evidence.

CONCLUSIONS

L-OHP causes ED in rats via reduction of NO bioavailability caused by endothelial dysfunction.
Aggression-Related Sexual Fantasies: Prevalence Rates, Sex Differences, and Links with Personality, Attitudes, and Behavior
Authors: Bondü Rebecca , Birke Joseph B.
Published: July 2021

Background

Aggression-related sexual fantasies (ASF) are considered an important risk factor for sexual aggression, but empirical knowledge is limited, in part because previous research has been based on predominantly male, North-American college samples, and limited numbers of questions.

Aim

The present study aimed to foster the knowledge about the frequency and correlates of ASF, while including a large sample of women and a broad range of ASF.

Method

A convenience sample of N = 664 participants from Germany including 508 (77%) women and 156 (23%) men with a median age of 25 (21–27) years answered an online questionnaire. Participants were mainly recruited via social networks (online and in person) and were mainly students. We examined the frequencies of (aggression-related) sexual fantasies and their expected factor structure (factors reflecting affective, experimental, masochistic, and aggression-related contents) via exploratory factor analysis. We investigated potential correlates (eg, psychopathic traits, attitudes towards sexual fantasies) as predictors of ASF using multiple regression analyses. Finally, we examined whether ASF would positively predict sexual aggression beyond other pertinent risk factors using multiple regression analysis.

Outcomes

The participants rated the frequency of a broad set of 56 aggression-related and other sexual fantasies, attitudes towards sexual fantasies, the Big Five (ie, broad personality dimensions including neuroticism and extraversion), sexual aggression, and other risk factors for sexual aggression.

RESULTS

All participants reported non-aggression-related sexual fantasies and 77% reported at least one ASF in their lives. Being male, frequent sexual fantasies, psychopathic traits, and negative attitudes towards sexual fantasies predicted more frequent ASF. ASF were the strongest predictor of sexual aggression beyond other risk factors, including general aggression, psychopathic traits, rape myth acceptance, and violent pornography consumption.

Clinical Translation

ASF may be an important risk factor for sexual aggression and should be more strongly considered in prevention and intervention efforts.

Strengths and Limitations

The strengths of the present study include using a large item pool and a large sample with a large proportion of women in order to examine ASF as a predictor of sexual aggression beyond important control variables. Its weaknesses include the reliance on cross-sectional data, that preclude causal inferences, and not continuously distinguishing between consensual and non-consensual acts.

CONCLUSION

ASF are a frequent phenomenon even in in the general population and among women and show strong associations with sexual aggression. Thus, they require more attention by research on sexual aggression and its prevention.
Neuro‐Fuzzy Kinematic Finite‐Fault Inversion: 1. Methodology
Authors: Kheirdast Navid , Ansari Anooshiravan , Custódio Susana
Published: July 2021

Kinematic finite‐fault source inversions aim at resolving the spatio‐temporal evolution of slip on a fault given ground motion recorded on the Earth's surface. This type of inverse problem is inherently ill posed due to two main factors. First, the number of model parameters is typically greater than the number of independent observed data. Second, small singular values are generated by the discretization of the physical rupture process and amplify the effect of noise in the inversion. As a result, one can find different slip distributions that fit the data equally well. This ill posedness can be mitigated by decreasing the number of model parameters, hence improving their relationship to the observed data. In this study, we propose a fuzzy function approximation approach to describe the spatial slip function. In particular, we use an Adaptive Network‐based Fuzzy Inference System (ANFIS) to find the most adequate discretization for the spatial variation of slip on the fault. The fuzzy basis functions and their respective amplitudes are optimized through hybrid learning. We solve this earthquake source problem in the frequency domain, searching for optimal spatial slip distribution independently for each frequency. The approximated frequency‐dependent spatial slip functions are then used to compute the forward relationship between slip on the fault and ground motion. The method is constrained through Tikhonov regularization, requiring a smooth spatial slip variation. We discuss how the number of model parameters can be decreased, while keeping the inversion stable and achieving an adequate resolution. The proposed inversion method is tested using the SIV1‐benchmark exercise.
The Impacts of Global Warming on Climate Zone Changes Over Asia Based on CMIP6 Projections
Authors: Kim Jeong‐Bae , Bae Deg‐Hyo
Published: July 2021

It is challenging to estimate how the regional climate will be shifted under future global warming. To reduce the potential risk of regional climate shift under future climates, examining the change in climate features over Asia is important, as approximately 60% of the world's population resides there. In this study, climate shifts are assessed over the Asian monsoon region under global mean temperature warming targets from 1.5°C to 5.0°C above preindustrial (PI) levels based on different shared socioeconomic pathway (SSP) scenarios. Global warming impacts the individual climate variables, and consequently, it impacts the regional climate features across the Asian region. Temperature change patterns are more dominant contributors to the spatial extent and magnitude of climate shifts than precipitation change patterns. Changes in regional climates show different behaviors according to the degree of global warming rather than the type of SSP scenario. Climate shifts are intensified under a higher level of global warming that is above the PI levels. The largest climate shifts in this region are shown under global warming of 5.0°C based on the SSP5‐8.5 scenario, especially in current polar climate zones. Future change patterns in individual climate zone can differ. Regions with tropical climates and arid climates are likely to be expanded, whereas some regions with warm temperate climates, cold climates, and polar climates are likely to shrink under global warming conditions. Therefore, this study supports the necessity of mitigating greenhouse gas (GHG) emissions and establishing an adaptation plan for future global warming conditions.
Astronomers for Planet Earth
Authors: Japelj Jure
Published: July 2021

A volunteer network of astronomers is using a unique astronomical perspective to educate people about the climate crisis while at the same time striving for sustainability in academia.
Constraining the Timespan of Fluvial Activity From the Intermittency of Sediment Transport on Earth and Mars
Authors: Hayden A. T. , Lamb M. P. , McElroy B. J.
Published: July 2021

The timespan recorded in deposits from fluvial activity is a key gap in our understanding of ancient environments on Earth and Mars. Because riverine sediment transport occurs under time‐variable water discharge, common models that represent sediment transport with a single bankfull discharge require an intermittency factor. For this reason, the ability to predict intermittency factor values based on environmental factors would improve estimates of time from fluvial deposits. To address this knowledge gap, we calculated intermittency factors from 201 modern rivers and six fans and deltas with depositional timespans of months to millions of years. Intermittency factors range from 0.0064–0.73; they are uncorrelated with averaging timescale, bed‐material grainsize, or climate aridity, but are larger in river catchments with greater rates of denudation relative to precipitation. Application to ancient fluvial systems on Mars indicates long‐lived depositional river systems for up to 104–106 years.
Shallow Crustal Shear Velocity and Vp/Vs Across Southern California: Joint Inversion of Short‐Period Rayleigh Wave Ellipticity, Phase Velocity, and Teleseismic Receiver Functions
Authors: Berg Elizabeth M. , Lin Fan‐Chi , Schulte‐Pelkum Vera , Allam Amir , Qiu Hongrui , Gkogkas Konstantinos
Published: July 2021

Near‐surface seismic velocity structure plays a critical role in ground motion amplification during large earthquakes. In particular, the local Vp/Vs ratio strongly influences the amplitude of Rayleigh waves. Previous studies have separately imaged 3D seismic velocity and Vp/Vs ratio at seismogenic depth, but lack regional coverage and/or fail to constrain the shallowest structure. Here, we combine three datasets with complementary sensitivity in a Bayesian joint inversion for shallow crustal shear velocity and near‐surface Vp/Vs ratio across Southern California. Receiver functions–including with an apparent delayed initial peak in sedimentary basins, and long considered a nuisance in receiver function imaging studies–highly correlate with short‐period Rayleigh wave ellipticity measurements and require the inclusion of a Vp/Vs parameter. The updated model includes near‐surface low shear velocity more in line with geotechnical layer estimates, and generally lower than expected Vp/Vs outside the basins suggesting widespread shallow fracturing and/or groundwater undersaturation.
Inferring the Shallow Layered Structure at the Chang’E‐4 Landing Site: A Novel Interpretation Approach Using Lunar Penetrating Radar
Authors: Giannakis Iraklis , Zhou Feng , Warren Craig , Giannopoulos Antonios
Published: July 2021

The current paper investigates the shallow layers of the lunar regolith at the Chang’E‐4 landing site. Four layers between 0 and 10 m were identified using lunar penetrating radar. Based on these outputs, a revised stratigraphic model is suggested for the post‐Imbrian ejecta at the Von Kármán crater. The layers were previously unseen due to the smooth boundaries between them. The revised model was inferred using an advanced hyperbola‐fitting scheme. Applying conventional hyperbola‐fitting to non‐homogeneous media results in errors and inaccuracies that are often wrongly assumed to be negligible. We propose a novel hyperbola‐fitting scheme that is, not constrained to homogeneous media and can be applied subject to any arbitrary one‐dimensional permittivity distribution. Via this approach, we can estimate the permittivity profile of an investigated area and detect layered structures that were previously transparent to electromagnetic waves due to the gradational dielectric properties at their interfaces.
On the Generation of Pi2 Pulsations due to Plasma Flow Patterns Around Magnetosheath Jets
Authors: Katsavrias C. , Raptis S. , Daglis I. A. , Karlsson T. , Georgiou M. , Balasis G.
Published: July 2021

We report observations of a magnetosheath jet followed by a period of decelerated background plasma. During this period, THEMIS‐A magnetometer showed abrupt disturbances which, in the wavelet spectrum, appeared as prominent and irregular pulsations in two frequency bands (7.6–9.2 and 12–17 mHz) within the Pi2 range. The observations suggest—for the first time to our knowledge—that these pulsations were locally generated by the abrupt magnetic field changes driven by the jet’s interaction with the ambient magnetosheath plasma. Furthermore, similar pulsations, detected by THEMIS‐D inside the magnetosphere with a 140 s time‐lag (which corresponds to the propagation time of a disturbance traveling with Alfvénic speed), are shown to be directly associated with the ones in the magnetosheath, which raises the question of how exactly these pulsations are propagated through the magnetopause.
Linking Large‐Scale Circulation Descriptors to Precipitation Variability in the Northern French Alps
Authors: Blanc Antoine , Blanchet Juliette , Creutin Jean‐Dominique
Published: July 2021

This work analyses the link between Western Europe large‐scale circulation and precipitation variability in the Northern French Alps from 1950 to 2017. We consider simple descriptors characterizing the daily 500 hPa geopotential height fields. They are the maximum pressure difference (MPD)—representing the range of geopotential heights over Western Europe, and the singularity—representing the mean distance between a geopotential shape and its closest analogs, that is, the way this geopotential shape is reproduced in climatology. We show that the MPD and the singularity of geopotential shapes explain a significant part of precipitation variability in the Isère River catchment () from 10 days to 10 years, especially in winter (correlations of 0.7). These simple descriptors ‐ that are easy to implement—provide as much information as weather pattern classification and much better performance than North Atlantic Oscillation to explain precipitation variability over a medium size mountainous catchment.
Aquifer Permeability Decreases Before Local Earthquakes Inferred From Water Level Response to Period Loading
Authors: Sun Xiaolong , Xiang Yang
Published: July 2021

Changes of permeability caused by dynamic stress induced by distant earthquakes have been widely reported. Permeability decreases before local earthquakes have been less commonly reported. In this study, we document pre‐earthquake aquifer permeability decreases in a well named X11 in northwest China. The response of the water level to barometric pressure and Earth tides was used to calculate relative changes in permeability between July 2014 and February 2020. The results revealed that there was a decrease in the permeability of the aquifer prior to four local earthquakes between 2015 and 2020. We infer that crack clogging caused by particle deposition causes the permeability decreases before earthquakes.
Stratigraphic Evidence for Early Martian Explosive Volcanism in Arabia Terra
Authors: Whelley Patrick , Matiella Novak Alexandra , Richardson Jacob , Bleacher Jacob , Mach Kelsey , Smith Reagan N.
Published: July 2021

Several large paterae in Arabia Terra are suggested to be calderas that produced colossal explosive eruptions (i.e., supereruptions). If these features are indeed explosive calderas, dispersion modeling suggests extensive ash deposits should be common throughout the region. However, such deposits have not previously been linked with the suggested calderas. Here, we describe layered deposits containing minerals both consistent with and diagnostic of altered volcanic ash throughout Arabia Terra. These deposits include Al‐dominant minerals such as montmorillonite, imogolite, and allophane among others. Altered ash deposits are found to thin (from 1‐km to 100‐m thickness) away from the suggested calderas. We estimate that the volcanic ash observed in Arabia Terra is the result of between 1,000 and 2,000 individual explosive eruptions over 500‐million years. Our observations support the hypothesis that Arabia Terra hosted supereruptions in the late Noachian‐early Hesperian that repeatedly blanketed the region with layers of ash.
Reorganized Atmospheric Circulation During the Little Ice Age Leads to Rapid Southern California Deoxygenation
Authors: Wang Yi , Hendy Ingrid L.
Published: July 2021

The magnitude of natural oceanic dissolved oxygen (DO) variability remains poorly understood due to the short duration of the observational record. Here we present a high‐resolution (4–9 years) reconstruction of the Southern California oxygen minimum zone (OMZ) through the Common Era using redox‐sensitive metals. Rapid OMZ intensification on multidecadal timescales reveals greater DO variability than observed in instrumental records. An anomalous interval of intensified OMZ between 1600–1750 CE contradicts the expectation of better‐ventilated mid‐depth North Pacific during cool climates. Although the influence of low‐DO Equatorial Pacific Intermediate Water on the Southern California Margin was likely weaker during this interval, we attribute the observed rapid deoxygenation to reduced North Pacific Intermediate Water (NPIW) ventilation. NPIW ventilation thus appears very sensitive to atmospheric circulation reorganization (e.g., a weakened Siberian High and Aleutian Low). In addition to temperature‐induced gas solubility, atmospheric forcing under future anthropogenic influences could amplify OMZ variability.
The ELF3-regulated lncRNA UBE2CP3 is over-stabilized by RNA–RNA interactions and drives gastric cancer metastasis via miR-138-5p/ITGA2 axis
Authors: Li Dandan , She Jiajun , Hu Xinhui , Zhang Meixin , Sun Ruonan , Qin Shanshan
Published: July 2021

LncRNAs play essential roles in tumorigenesis and tumor progression. Pseudogene UBE2CP3 is an antisense intronic lncRNA. However, the biological function of UBE2CP3 in gastric cancer (GC) remains unknown. In this study, we revealed that lncRNA UBE2CP3 was aberrantly upregulated in multiple independent gastric cancer cohorts, and its overexpression was clinically associated with poor prognosis in GC. UBE2CP3 was mainly located in cytoplasm and promoted migratory and invasive capacities of GC cells in vitro and in vivo. Mechanismly, a novel dysregulated ceRNA network UB2CP3/miR-138-5p/ITGA2 was identified in GC by transcriptome sequencing. Furthermore, rescue assay further confirmed that UBE2CP3 mainly promoted GC progression through miR-138-5p/ITGA2 axis. More importantly, our data proved that UBE2CP3/IGFBP7 could form an RNA duplex, thereby directly interacting with the ILF3 protein. In turn, this RNA-RNA interaction between IGFBP7 mRNA and UBE2CP3 mediated by ILF3 protein plays an essential role in protecting the mRNA stability of UBE2CP3. In addition, transcription factor ELF3 was identified to be a direct repressor of lncRNA UBE2CP3 in GC. Taken together, overexpression of UBE2CP3 promotes tumor progression via cascade amplification of ITGA2 upregulation in GC. Our finding has revealed that the dysregulation of UBE2CP3 is probably due to the downregulation of ELF3 and/or the overexpression of IGFBP7 mRNA in GC. Our findings reveal, for the first time, that UBE2CP3 plays crucial a role in GC progression by modulating miR-138-5p/ITGA2 axis, suggesting that UBE2CP3 may serve as a potential therapeutic target in GC.
Articaine in dentistry: an overview of the evidence and meta-analysis of the latest randomised controlled trials on articaine safety and efficacy compared to lidocaine for routine dental treatment
Authors: Martin Erica , Nimmo Alan , Lee Andrew , Jennings Ernest
Published: July 2021

Objectives

To comprehensively review the existing studies of articaine in dentistry and conduct a systematic review and meta-analysis to answer the following Population, Intervention, Comparison and Outcome question: “Is articaine a safe and efficacious local anaesthetic for routine dental treatment compared to lidocaine?”

Methods

Database searches were conducted in Medline Ovid, Medline Pubmed, Scopus, Emcare, Proquest and the Cochrane Central register of Controlled Trials. Inclusion criteria were all existing English, human, randomised controlled trials of interventions involving 4% articaine and 2% lidocaine in routine dental treatment. Twelve studies were included for meta-analysis using Cochrane Review Manager 5 software. Anaesthetic success odds ratios were calculated using a random-effects model.

Results

Articaine had a higher likelihood of achieving anaesthetic success than lidocaine overall and in all subgroup analyses with varying degrees of significance. Overall (OR: 2.17, 95% CI: 1.50, 3.15,I2 = 62%) articaine had 2.17 times the likelihood of anaesthetic success of lidocaine (P < 0.0001). For mandibular blocks (OR: 1.50, 95% CI: 1.14, 1.98,I2 = 0%) articaine had 1.5 times the likelihood of anaesthetic success of lidocaine (P = 0.004). For all infiltrations, maxillary and mandibular (OR: 2.78, 95% CI: 1.61, 4.79,I2 = 66%) articaine had 2.78 times the likelihood of anaesthetic success of lidocaine (P = 0.0002). None of the studies reported any major local anaesthetic-related adverse effects as a result of the interventions.

Conclusions

Articaine is a safe and efficacious local anaesthetic for all routine dental procedures in patients of all ages, and more likely to achieve successful anaesthesia than lidocaine in routine dental treatment. Neither anaesthetic has a higher association with anaesthetic-related adverse effects.
Patterns of therapy initiation during the first decade for patients with follicular lymphoma who were observed at diagnosis in the rituximab era
Authors: Arushi Khurana  , Mwangi Raphael , Ansell Stephen M. , Habermann Thomas M. , Cerhan James R. , Strouse Christopher , Link Brian K. , Wang Yucai , King Rebecca L. , Macon William R. , Villasboas J. C. , Witzig Thomas E. , Maurer Matthew J. , Nowakowski Grzegorz S.
Published: July 2021

Immediate treatment for asymptomatic, low-tumor burden follicular lymphoma (FL) has not shown an overall survival benefit over “watch and wait” (W/W) strategy. We estimated incidence of treatment initiation at specific time points and assessed its association with the presence of any criteria such as GELF, BNLI, GITMO at diagnosis. FL patients managed by W/W strategy were identified from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE between 2002 and 2015. Cumulative incidence estimates of treatment initiation were calculated using transformation (as the first event) and death as competing risks. 401 FL patients were identified on W/W strategy. At a median follow-up of 8 years, 256 (64%) initiated treatment. For patients on the W/W strategy for 5 years, the likelihood of treatment initiation in the next 5 years was 12% compared to 43% at diagnosis unlike transformation rates which remained steady. Patients with any of popular treatment criteria at diagnosis did not have increased therapy initiation rates (44% vs. 42%) during the first 5 years or lymphoma-related death rates at 10 years (6% vs. 7%). Identifying biological differences in patients with early vs. late or no progression is a critical next step in understanding outcomes in W/W patients.
Metabolic syndrome and cardiovascular disease after haematopoietic cell transplantation (HCT) in adults: an EBMT cross-sectional non-interventional study
Authors: Greenfield D. M. , Salooja N. , Peczynski C. , van der Werf S. , Schoemans H. , Hill K. , Cortelezzi A. , Lupo-Stangellini M. , Özkurt Z. N. , Arat M. , Metzner B. , Turlure P. , Rovo A. , Socié G. , Mohty M. , Nagler A. , Kröger N. , Dreger P. , Labopin M. , Han T. S. , Tichelli A. , Duarte R. , Basak G. , Snowden J. A.
Published: July 2021

Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09–6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.
DJ-1 inhibits microglial activation and protects dopaminergic neurons in vitro and in vivo through interacting with microglial p65
Authors: Lin Zixuan , Chen Chen , Yang Dongqin , Ding Jianqing , Wang Guanghui , Ren Haigang
Published: July 2021

Parkinson’s disease (PD), one of the most common neurodegenerative disorders, is characterized by progressive neurodegeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). DJ-1 acts essential roles in neuronal protection and anti-neuroinflammatory response, and its loss of function is tightly associated with a familial recessive form of PD. However, the molecular mechanism of DJ-1 involved in neuroinflammation is largely unclear. Here, we found that wild-type DJ-1, rather than the pathogenic L166P mutant DJ-1, directly binds to the subunit p65 of nuclear factor-κB (NF-κB) in the cytoplasm, and loss of DJ-1 promotes p65 nuclear translocation by facilitating the dissociation between p65 and NF-κB inhibitor α (IκBα).DJ-1knockout (DJ-1−/−) mice exhibit more microglial activation compared with wild-type littermate controls, especially in response to lipopolysaccharide (LPS) treatment. In cellular models, knockdown of DJ-1 significantly upregulates the gene expression and increases the release of LPS-treated inflammatory cytokines in primary microglia and BV2 cells. Furthermore,DJ-1deficiency in microglia significantly enhances the neuronal toxicity in response to LPS stimulus. In addition, pharmacological blockage of NF-κB nuclear translocation by SN-50 prevents microglial activation and alleviates the damage of DA neurons induced by microglialDJ-1deficiency in vivo and in vitro. Thus, our data illustrate a novel mechanism by which DJ-1 facilitates the interaction between IκBα and p65 by binding to p65 in microglia, and thus repressing microglial activation and exhibiting the protection of DA neurons from neuroinflammation-mediated injury in PD.
Genetically engineered MAPT 10+16 mutation causes pathophysiological excitability of human iPSC-derived neurons related to 4R tau-induced dementia
Authors: Kopach Olga , Esteras Noemí , Wray Selina , Abramov Andrey Y. , Rusakov Dmitri A.
Published: July 2021

Human iPSC lines represent a powerful translational model of tauopathies. We have recently described a pathophysiological phenotype of neuronal excitability of human cells derived from the patients with familial frontotemporal dementia and parkinsonism (FTDP-17) caused by theMAPT10+16 splice-site mutation. This mutation leads to the increased splicing of 4R tau isoforms. However, the role of different isoforms of tau protein in initiating neuronal dementia-related dysfunction, and the causality between theMAPT10+16 mutation and altered neuronal activity have remained unclear. Here, we employed genetically engineered cells, in which the IVS10+16 mutation was introduced into healthy donor iPSCs to increase the expression of 4R tau isoform in exon 10, aiming to explore key physiological traits of iPSC-derivedMAPTIVS10+16 neurons using patch-clamp electrophysiology and multiphoton fluorescent imaging techniques. We found that during late in vitro neurogenesis (from ~180 to 230 days) iPSC-derived cortical neurons of the control group (parental wild-type tau) exhibited membrane properties compatible with “mature” neurons. In contrast,MAPTIVS10+16 neurons displayed impaired excitability, as reflected by a depolarized resting membrane potential, an increased input resistance, and reduced voltage-gated Na+- and K+-channel-mediated currents. The mutation changed the channel properties of fast-inactivating Navand decreased the Nav1.6 protein level.MAPTIVS10+16 neurons exhibited reduced firing accompanied by a changed action potential waveform and severely disturbed intracellular Ca2+dynamics, both in the soma and dendrites, upon neuronal depolarization. These results unveil a causal link between theMAPT10+16 mutation, hence overproduction of 4R tau, and a dysfunction of human cells, identifying a biophysical basis of changed neuronal activity in 4R tau-triggered dementia. Our study lends further support to using iPSC lines as a suitable platform for modelling tau-induced human neuropathology in vitro.
Transgenic and genome-edited fruits: background, constraints, benefits, and commercial opportunities
Authors: Lobato-Gómez Maria , Hewitt Seanna , Capell Teresa , Christou Paul , Dhingra Amit , Girón-Calva Patricia Sarai
Published: July 2021

Breeding has been used successfully for many years in the fruit industry, giving rise to most of today’s commercial fruit cultivars. More recently, new molecular breeding techniques have addressed some of the constraints of conventional breeding. However, the development and commercial introduction of such novel fruits has been slow and limited with only five genetically engineered fruits currently produced as commercial varieties—virus-resistant papaya and squash were commercialized 25 years ago, whereas insect-resistant eggplant, non-browning apple, and pink-fleshed pineapple have been approved for commercialization within the last 6 years and production continues to increase every year. Advances in molecular genetics, particularly the new wave of genome editing technologies, provide opportunities to develop new fruit cultivars more rapidly. Our review, emphasizes the socioeconomic impact of current commercial fruit cultivars developed by genetic engineering and the potential impact of genome editing on the development of improved cultivars at an accelerated rate.
Recognition of hydrophilic molecules in deep cavitand hosts with water-mediated hydrogen bonds
Authors: Guan Hua-Wei , Zhu Yu-Jie , Peters Joannes , Brea Oriana , Himo Fahmi , Rebek Julius , Yu Yang
Published: July 2021

A new supramolecular system was constructed based on water-mediated hydrogen bonding between a benzimidazole functionalized host, water and guest. Intriguingly, these hosts can recognize small hydrophilic guests in water through the synergistic action of water-mediated hydrogen bonding and hydrophobic effects.
The effect of a micro-crystalline ZnO with columnar structure on the crystallization behavior and mechanical properties of poly(ethylene 2,6-naphthalate)
Authors: Yao Jianqi , Li Xuzhao , Lu Jing , Ma Qing , Liu Yongdong , Luo Faliang
Published: July 2021

Polarized optical micrographs of PEN/H-ZnOc blends: (a) 0 wt%, (b) 0.4 wt%, (c) 0.6 wt%, (d) 1.0 wt%, (e) 1.5 wt% isothermally crystallized at 200 °C for 40 min.