bluuebunny/crossref_metadata_2025 huggingface dataset:
From Fluid Flow to Coupled Processes in Fractured Rock: Recent Advances and New Frontiers
Authors: Viswanathan H. S. , Ajo‐Franklin J. , Birkholzer J. T. , Carey J. W. , Guglielmi Y. , Hyman J. D. , Karra S. , Pyrak‐Nolte L. J. , Rajaram H. , Srinivasan G. , Tartakovsky D. M.
Published: February 2022

Quantitative predictions of natural and induced phenomena in fractured rock is one of the great challenges in the Earth and Energy Sciences with far‐reaching economic and environmental impacts. Fractures occupy a very small volume of a subsurface formation but often dominate fluid flow, solute transport and mechanical deformation behavior. They play a central role in CO2 sequestration, nuclear waste disposal, hydrogen storage, geothermal energy production, nuclear nonproliferation, and hydrocarbon extraction. These applications require predictions of fracture‐dependent quantities of interest such as CO2 leakage rate, hydrocarbon production, radionuclide plume migration, and seismicity; to be useful, these predictions must account for uncertainty inherent in subsurface systems. Here, we review recent advances in fractured rock research covering field‐ and laboratory‐scale experimentation, numerical simulations, and uncertainty quantification. We discuss how these have greatly improved the fundamental understanding of fractures and one's ability to predict flow and transport in fractured systems. Dedicated field sites provide quantitative measurements of fracture flow that can be used to identify dominant coupled processes and to validate models. Laboratory‐scale experiments fill critical knowledge gaps by providing direct observations and measurements of fracture geometry and flow under controlled conditions that cannot be obtained in the field. Physics‐based simulation of flow and transport provide a bridge in understanding between controlled simple laboratory experiments and the massively complex field‐scale fracture systems. Finally, we review the use of machine learning‐based emulators to rapidly investigate different fracture property scenarios and accelerate physics‐based models by orders of magnitude to enable uncertainty quantification and near real‐time analysis.
Packing Fraction, Tortuosity, and Permeability of Granular‐Porous Media With Densely Packed Spheroidal Particles: Monodisperse and Polydisperse Systems
Authors: Xu Wenxiang , Zhang Kaixing , Zhang Yufeng , Jiang Jinyang
Published: February 2022

The geometrical and topological configurations of particles have great influences on their surrounding pore tortuosity and the permeability of granular‐porous media. In this work, we develop a relaxation iteration scheme to create random dense packings of different anisotropic‐shaped spheroidal particles with monodispersity and polydispersity in sizes, which manifest the effects of particle shape, fineness, and size distribution on the random packing fraction of particles. Subsequently, we propose a direction‐guided rapidly exploring random tree (DGRRT) algorithm to probe the geometrical tortuosity of complex pore space interstitial to spheroidal particles. A non‐linear pore tortuosity prediction model that relies on the specific surface area and packing fraction of particles, is developed to suit for polydisperse and monodisperse spheroidal particle systems. We further investigate the permeability of granular‐porous media through the lattice Boltzmann method (LBM) of fluid flow. These proposed methods can accurately predict the tortuosity and permeability by comparing against available experimental, theoretical, and numerical results reported in literature. Moreover, the effects of particle packing fraction (i.e., porosity), shape, fineness, and size distribution on the pore tortuosity and permeability of granular‐porous media are evaluated. The results reveal that these microstructural configurations have important influences on the permeability and tortuosity. Our results give an intrinsic interplay between the geometrical tortuosity and permeability of monodisperse and polydisperse particle systems, which have implications for a broad range of scientific disciplines, including the properties of rocks, sandstones and soils, and the design of ultra‐high performance concrete.
Absence of a sexual dimorphism in postprandial glucose metabolism after administration of a balanced mixed meal in healthy young volunteers
Authors: Leone Alessandro , De Amicis Ramona , Bertoli Simona , Spadafranca Angela , De Carlo Giulia , Battezzati Alberto
Published: February 2022

Background/Objectives

A different ability to regulate glucose homeostasis between men and women may contribute to their difference in diabetes prevalence and in its predisposing conditions. Data on this issue are controversial because of heterogeneous protocols and insufficient control of confounders affecting glucose metabolism like age, body composition, and physical activity level. To clarify this issue, we compared among sexes the postprandial glucose metabolism after the administration of a balanced mixed meal normalized to daily energy expenditure.

Subjects/Methods

Thirty-six healthy young volunteers (18 men and 18 women; age, 23.9 ± 2.8 years; BMI, 21.9 ± 1.7 kg/m2) were recruited for the experiment. After overnight fast, subjects consumed a mixed meal providing 40% of daily energy expenditure (60% carbohydrates, 25% lipids, 15% proteins) estimated multiplying resting energy expenditure, obtained by Harris & Benedict equation, for the corresponding physical activity level. Blood was sampled at 0, 10, 20, 30, 45, 60, 90, 120, and 180 min and serum concentrations of glucose, insulin, and C-peptide were measured.

Results

Fasting serum glucose concentrations were lower in women than in men, while fasting insulin and C-peptide concentrations did not differ between sexes. Linear mixed models did not show any significant effect of sex and sex # time interaction on postprandial serum glucose, insulin, and C-peptide concentrations. The comparison of areas under the curve between the sexes revealed similar glycemic, insulinemic, and C-peptide postprandial responses between men and women.

Conclusions

Our results do not support the hypothesis of a sexual dimorphism in the regulation of carbohydrate metabolism in young when a mixed meal normalized on individual daily energy expenditure is ingested.
EPHA2 mediates PDGFA activity and functions together with PDGFRA as prognostic marker and therapeutic target in glioblastoma
Authors: Gai Qu-Jing , Fu Zhen , He Jiang , Mao Min , Yao Xiao-Xue , Qin Yan , Lan Xi , Zhang Lin , Miao Jing-Ya , Wang Yan-Xia , Zhu Jiang , Yang Fei-Cheng , Lu Hui-Min , Yan Ze-Xuan , Chen Fang-Lin , Shi Yu , Ping Yi-Fang , Cui You-Hong , Zhang Xia , Liu Xindong , Yao Xiao-Hong , Lv Sheng-Qing , Bian Xiu-Wu , Wang Yan
Published: February 2022

Platelet-derived growth subunit A (PDGFA) plays critical roles in development of glioblastoma (GBM) with substantial evidence from TCGA database analyses and in vivo mouse models. So far, only platelet-derived growth receptor α (PDGFRA) has been identified as receptor for PDGFA. However, PDGFA and PDGFRA are categorized into different molecular subtypes of GBM in TCGA_GBM database. Our data herein further showed that activity or expression deficiency of PDGFRA did not effectively block PDGFA activity. Therefore, PDGFRA might be not necessary for PDGFA function.To profile proteins involved in PDGFA function, we performed co-immunoprecipitation (Co-IP) and Mass Spectrum (MS) and delineated the network of PDGFA-associated proteins for the first time. Unexpectedly, the data showed that EPHA2 could be temporally activated by PDGFA even without activation of PDGFRA and AKT. Furthermore, MS, Co-IP, in vitro binding thermodynamics, and proximity ligation assay consistently proved the interaction of EPHA2 and PDGFA. In addition, we observed that high expression of EPHA2 leaded to upregulation of PDGF signaling targets in TCGA_GBM database and clinical GBM samples. Co-upregulation of PDGFRA and EPHA2 leaded to worse patient prognosis and poorer therapeutic effects than other contexts, which might arise from expression elevation of genes related with malignant molecular subtypes and invasive growth. Due to PDGFA-induced EPHA2 activation, blocking PDGFRA by inhibitor could not effectively suppress proliferation of GBM cells, but simultaneous inhibition of both EPHA2 and PDGFRA showed synergetic inhibitory effects on GBM cells in vitro and in vivo. Taken together, our study provided new insights on PDGFA function and revealed EPHA2 as a potential receptor of PDGFA. EPHA2 might contribute to PDGFA signaling transduction in combination with PDGFRA and mediate the resistance of GBM cells to PDGFRA inhibitor. Therefore, combination of inhibitors targeting PDGFRA and EHA2 represented a promising therapeutic strategy for GBM treatment.
Cultivation and biogeochemical analyses reveal insights into methanogenesis in deep subseafloor sediment at a biogenic gas hydrate site
Authors: Katayama Taiki , Yoshioka Hideyoshi , Kaneko Masanori , Amo Miki , Fujii Tetsuya , Takahashi Hiroshi A , Yoshida Satoshi , Sakata Susumu
Published: February 2022

Gas hydrates deposited in subseafloor sediments are considered to primarily consist of biogenic methane. However, little evidence for the occurrence of living methanogens in subseafloor sediments has been provided. This study investigated viable methanogen diversity, population, physiology and potential activity in hydrate-bearing sediments (1–307 m below the seafloor) from the eastern Nankai Trough. Radiotracer experiments, the quantification of coenzyme F430 and molecular sequencing analysis indicated the occurrence of potential methanogenic activity and living methanogens in the sediments and the predominance of hydrogenotrophic methanogens followed by methylotrophic methanogens. Ten isolates and nine representative culture clones of hydrogenotrophic, methylotrophic and acetoclastic methanogens were obtained from the batch incubation of sediments and accounted for 0.5–76% of the total methanogenic sequences directly recovered from each sediment. The hydrogenotrophic methanogen isolates of Methanocalculus and Methanoculleus that dominated the sediment methanogen communities produced methane at temperatures from 4 to 55 °C, with an abrupt decline in the methane production rate at temperatures above 40 °C, which is consistent with the depth profiles of potential methanogenic activity in the Nankai Trough sediments in this and previous studies. Our results reveal the previously overlooked phylogenetic and metabolic diversity of living methanogens, including methylotrophic methanogenesis.
Hypoxia-induced lncRNA RBM5-AS1 promotes tumorigenesis via activating Wnt/β-catenin signaling in breast cancer
Authors: Li Xinping , Yang Jingyan , Ni Ruiqi , Chen Jintian , Zhou Yanhao , Song Hao , Jin Liang , Pan Yi
Published: February 2022

Breast cancer is the most common malignancy among women across the globe. Recent studies have revealed that many long non-coding RNAs (lncRNAs) regulate the Wnt/β-catenin signaling pathway in several types of cancer. Hyperactivation of the Wnt/β-catenin pathway has been extensively presented in breast cancer and is involved in breast cancer progression. However, the underlying molecular mechanism remains elusive. In the current study, we found lncRNA RBM5-AS1 was remarkably upregulated in breast cancer cells and tissues. Overexpression of RBM5-AS1 facilitated proliferation, migration, invasion, EMT, and stemness maintenance of breast cancer cells in vitro and in vivo. Mechanism studies suggested that RBM5-AS1 could be transcriptionally activated by hypoxia-induced RUNX2. Upregulated RBM5-AS1 further activated the Wnt/β-catenin signaling by preventing β-catenin degradation and by helping organize β-catenin-TCF4 transcriptional complex. These findings suggested that RBM5-AS1, a regulator of Wnt/β-catenin signaling, plays a vital role in breast cancer initiation and progression, implicating its potential as a new target for breast cancer treatment.
Itaconate inhibits ferroptosis of macrophage via Nrf2 pathways against sepsis-induced acute lung injury
Authors: He Ruyuan , Liu Bohao , Xiong Rui , Geng Boxin , Meng Heng , Lin Weichen , Hao Bo , Zhang Lin , Wang Wei , Jiang Wenyang , Li Ning , Geng Qing
Published: February 2022

Itaconate, a metabolite produced during inflammatory macrophage activation, has been extensively described to be involved in immunoregulation, oxidative stress, and lipid peroxidation. As a form of iron and lipid hydroperoxide-dependent regulated cell death, ferroptosis plays a critical role in sepsis-induced acute lung injury (ALI). However, the relationship between itaconate and ferroptosis remains unclear. This study aims to explore the regulatory role of itaconate on ferroptosis in sepsis-induced ALI. In in vivo experiments, mice were injected with LPS (10 mg/kg) for 12 h to generate experimental sepsis models. Differential gene expression analysis indicated that genes associated with ferroptosis existed significant differences after itaconate pretreatment. 4-octyl itaconate (4-OI), a cell-permeable derivative of endogenous itaconate, can significantly alleviate lung injury, increase LPS-induced levels of glutathione peroxidase 4 (GPX4) and reduce prostaglandin-endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA), and lipid ROS. In vitro experiments showed that both 4-OI and ferrostatin-1 inhibited LPS-induced lipid peroxidation and injury of THP-1 macrophage. Mechanistically, we identified that 4-OI inhibited the GPX4-dependent lipid peroxidation through increased accumulation and activation of Nrf2. The silence of Nrf2 abolished the inhibition of ferroptosis from 4-OI in THP-1 cells. Additionally, the protection of 4-OI for ALI was abolished in Nrf2-knockout mice. We concluded that ferroptosis was one of the critical mechanisms contributing to sepsis-induced ALI. Itaconate is promising as a therapeutic candidate against ALI through inhibiting ferroptosis.
OTUB2 regulates KRT80 stability via deubiquitination and promotes tumour proliferation in gastric cancer
Authors: Ouyang Siwen , Zeng Ziyang , Liu Zhen , Zhang Zimu , Sun Juan , Wang Xianze , Ma Mingwei , Ye Xin , Yu Jianchun , Kang Weiming
Published: February 2022

OTUB2 is a deubiquitinating enzyme that contributes to tumor progression. However, the expression of OTUB2 and its prognostic importance in gastric cancer remain unclear. The expression of OTUB2 and KRT80 in GC tissues was investigated using western blotting, qRT-PCR, multiple immunofluorescence staining, and immunohistochemistry. For survival studies, Kaplan–Meier analysis with the log-rank test was used. The role of OTUB2 during GC proliferation was investigated using in vivo and in vitro assays. OTUB2 was found to be overexpressed in GC tissues and to act as an oncogene, which was linked to patients’ poor prognosis. Knockdown of OTUB2 inhibited the proliferative capacity of GC cells in vitro and in vivo, although the proliferative capacity was restored upon re-supplementation with KRT80. OTUB2 mechanically stabilized KRT80 by deubiquitinating and shielding it from proteasome-mediated degradation through Lys-48 and Lys-63. Furthermore, by activating the Akt signaling pathway, OTUB2 and KRT80 facilitated GC proliferation. In summary, OTUB2 regulates KRT80 stability via deubiquitination promoting proliferation in GC via activation of the Akt signaling pathway, implying that OTUB2 could be a novel prognostic marker.
Salmonella pSLT-encoded effector SpvB promotes RIPK3-dependent necroptosis in intestinal epithelial cells
Authors: Dong Kedi , Zhu Yuan , Deng Qifeng , Sun Lanqing , Yang Sidi , Huang Kai , Cao Yu , Li Yuanyuan , Wu Shuyan , Huang Rui
Published: February 2022

Salmonella is one of the most important worldwide zoonotic pathogens. After invading a host orally, the bacteria break through the intestinal epithelial barrier for further invasion. Intestinal epithelial cells (IECs) play a crucial role in maintaining the integrity of the intestinal epithelial barrier. Necroptosis is considered one of the virulence strategies utilized by invasive Salmonella. Our previous work has shown that SpvB, an effector encoded by S. Typhimurium virulence plasmid (pSLT), promotes bacterial translocation via the paracellular route. However, it is still unknown whether SpvB could promote bacterial invasion through disrupting the integrity of IECs. Here, we demonstrated that SpvB promoted necroptosis of IECs and contributed to the destruction of the intestinal barrier during Salmonella infection. We found that SpvB enhanced the protein level of receptor-interacting protein kinase 3 (RIPK3) through inhibiting K48-linked poly-ubiquitylation of RIPK3 and the degradation of the protein in an autophagy-dependent manner. The abundant accumulation of RIPK3 upregulated the phosphorylation of MLKL, which contributed to necroptosis. The damage to IECs ultimately led to the disruption of the intestinal barrier and aggravated infection. In vivo, SpvB promoted the pathogenesis of Salmonella, favoring intestinal injury and colonic necroptosis. Our findings reveal a novel function of Salmonella effector SpvB, which could facilitate salmonellosis by promoting necroptosis, and broaden our understanding of the molecular mechanisms of bacterial invasion.
BACE2 variant identified from HSCR patient causes AD-like phenotypes in hPSC-derived brain organoids
Authors: Luo Juan , Zou Hailin , Guo Yibo , Huang Ke , Ngan Elly Sau-Wai , Li Peng
Published: February 2022

β-site APP-cleaving enzyme 2 (BACE2) is a homolog of BACE1, which is considered as the most promising therapeutic target for Alzheimer’s disease (AD). However, the expression and functional role of BACE2 in central nervous system (CNS) remain obscured. Previously, we identified several BACE2 rare variants in Hirschsprung disease (HSCR) patients and proved that BACE2-mediated APP cleavage might represent a novel HSCR pathogenesis mechanism in enteric nervous system. Here, we validated that these HSCR-associated BACE2 variants were loss-of-function mutations. Using the human pluripotent stem cell (hPSC)-derived brain organoids (BOs), we further demonstrated that BACE2 was mainly expressed in the ventricular zone and cortical plate of BOs, and its expression level was gradually increased along with the BO maturation. Functionally, we found that the BOs carrying the BACE2 loss-of-function mutation (BACE2G446R) showed greater apoptosis and increased levels of Aβ oligomers compared to the control BOs, resembling with the AD-associated phenotypes. All these phenotypes could be rescued via the removal of APP protein in BACE2G446R BOs. Furthermore, rather than BACE2G446R, BACE2WT overexpression in BOs carrying the APP Swedish/Indiana mutations attenuated the AD-associated phenotypes, including Aβ accumulation and neuronal cell death. Taken together, our results unravel that BACE2 can protect the neuronal cell from apoptosis caused by Aβ accumulation, and the deficiency of BACE2-mediated APP cleavage may represent a common pathological mechanism for both HSCR and AD.
Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy
Authors: Nguyen Hung X. , Wu Tianyu , Needs Daniel , Zhang Hengtao , Perelli Robin M. , DeLuca Sophia , Yang Rachel , Pan Michael , Landstrom Andrew P. , Henriquez Craig , Bursac Nenad
Published: February 2022

Therapies for cardiac arrhythmias could greatly benefit from approaches to enhance electrical excitability and action potential conduction in the heart by stably overexpressing mammalian voltage-gated sodium channels. However, the large size of these channels precludes their incorporation into therapeutic viral vectors. Here, we report a platform utilizing small-size, codon-optimized engineered prokaryotic sodium channels (BacNav) driven by muscle-specific promoters that significantly enhance excitability and conduction in rat and human cardiomyocytes in vitro and adult cardiac tissues from multiple species in silico. We also show that the expression of BacNav significantly reduces occurrence of conduction block and reentrant arrhythmias in fibrotic cardiac cultures. Moreover, functional BacNav channels are stably expressed in healthy mouse hearts six weeks following intravenous injection of self-complementary adeno-associated virus (scAAV) without causing any adverse effects on cardiac electrophysiology. The large diversity of prokaryotic sodium channels and experimental-computational platform reported in this study should facilitate the development and evaluation of BacNav-based gene therapies for cardiac conduction disorders.
Fast plasmoid-mediated reconnection in a solar flare
Authors: Yan Xiaoli , Xue Zhike , Jiang Chaowei , Priest E. R. , Kliem Bernhard , Yang Liheng , Wang Jincheng , Kong Defang , Song Yongliang , Feng Xueshang , Liu Zhong
Published: February 2022

Magnetic reconnection is a multi-faceted process of energy conversion in astrophysical, space and laboratory plasmas that operates at microscopic scales but has macroscopic drivers and consequences. Solar flares present a key laboratory for its study, leaving imprints of the microscopic physics in radiation spectra and allowing the macroscopic evolution to be imaged, yet a full observational characterization remains elusive. Here we combine high resolution imaging and spectral observations of a confined solar flare at multiple wavelengths with data-constrained magnetohydrodynamic modeling to study the dynamics of the flare plasma from the current sheet to the plasmoid scale. The analysis suggests that the flare resulted from the interaction of a twisted magnetic flux rope surrounding a filament with nearby magnetic loops whose feet are anchored in chromospheric fibrils. Bright cusp-shaped structures represent the region around a reconnecting separator or quasi-separator (hyperbolic flux tube). The fast reconnection, which is relevant for other astrophysical environments, revealed plasmoids in the current sheet and separatrices and associated unresolved turbulent motions.
Phase classification of multi-principal element alloys via interpretable machine learning
Authors: Lee Kyungtae , Ayyasamy Mukil V. , Delsa Paige , Hartnett Timothy Q. , Balachandran Prasanna V.
Published: February 2022

There is intense interest in uncovering design rules that govern the formation of various structural phases as a function of chemical composition in multi-principal element alloys (MPEAs). In this paper, we develop a machine learning (ML) approach built on the foundations of ensemble learning, post hoc model interpretability of black-box models, and clustering analysis to establish a quantitative relationship between the chemical composition and experimentally observed phases of MPEAs. The originality of our work stems from performing instance-level (or local) variable attribution analysis of ML predictions based on the breakdown method, and then identifying similar instances based on k-means clustering analysis of the breakdown results. We also complement the breakdown analysis with Ceteris Paribus profiles that showcase how the model response changes as a function of a single variable, when the values of all other variables are fixed. Results from local model interpretability analysis uncover key insights into variables that govern the formation of each phase. Our developed approach is generic, model-agnostic, and valuable to explain the insights learned by the black-box models. An interactive web application is developed to facilitate model sharing and accelerate the design of MPEAs with targeted properties.
Fragile topological band in the checkerboard antiferromagnetic monolayer FeSe
Authors: Luo Aiyun , Song Zhida , Xu Gang
Published: February 2022

By means of the first-principles calculations and magnetic topological quantum chemistry, we demonstrate that the low-energy physics in the checkerboard antiferromagnetic (AFM) monolayer FeSe, very close to an AFM topological insulator that hosts robust edge states, can be well captured by a double-degenerate nearly flat band with fragile topology just below the Fermi level. The Wilson loop calculations identify that such fragile topology is protected by the S4z symmetry, which gives rise to a 2D second-order topological insulator that supports the bound state with fractional charge e/2 at the sample corner. This work provides a platform to study the intriguing properties of magnetic fragile topological electronic states. Previous observations of the edge states and bound states in checkerboard AFM monolayer FeSe can also be well understood in our work.
CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells
Authors: Junghof Julia , Kogure Yuta , Yu Tian , Verdugo-Sivianes Eva María , Narita Megumi , Lucena-Cacace Antonio , Yoshida Yoshinori
Published: February 2022

The epicardium is a mesothelial layer covering the myocardium serving as a progenitor source during cardiac development. The epicardium reactivates upon cardiac injury supporting cardiac repair and regeneration. Fine-tuned balanced signaling regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) via epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a biomarker defining lineage specification in human active epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results highlight the importance of tracing CDH18 expression in hiPSC-derived epicardial cells, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine.
Neoantigen cancer vaccine augments anti-CTLA-4 efficacy
Authors: Salvatori Erika , Lione Lucia , Compagnone Mirco , Pinto Eleonora , Conforti Antonella , Ciliberto Gennaro , Aurisicchio Luigi , Palombo Fabio
Published: February 2022

Immune checkpoint inhibitors (ICI) based on anti-CTLA-4 (αCTLA-4) and anti-PD1 (αPD1) are being tested in combination with different therapeutic approaches including other immunotherapies such as neoantigen cancer vaccines (NCV). Here we explored, in two cancer murine models, different therapeutic combinations of ICI with personalized DNA vaccines expressing neoantigens and delivered by electroporation (EP). Anti-cancer efficacy was evaluated using vaccines with or without CD4 epitopes. Therapeutic DNA vaccines showed synergistic effects in different therapeutic protocols including established large tumors. Flow cytometry (FC) was utilized to measure CD8, CD4, Treg, and switched B cells as well as neoantigen-specific immune responses, which were also measured by IFN-γ ELIspot. Immune responses were augmented in combination with αCTLA4 but not with αPD1 in the MC38 tumor-bearing mice, significantly impacting tumor growth. Similarly, neoantigen-specific T cell immune responses were enhanced in combined treatment with αCTLA-4 in the CT26 tumor model where large tumors regressed in all mice, while monotherapy with αCTLA-4 was less efficacious. In line with previous evidence, we observed an increased switched B cells in the spleen of mice treated with αCTLA-4 alone or in combination with NCV. These results support the use of NCV delivered by DNA-EP with αCTLA-4 and suggest a new combined therapy for clinical testing.
A reusable neural network pipeline for unidirectional fiber segmentation
Authors: Fioravante de Siqueira Alexandre , Ushizima Daniela M. , van der Walt Stéfan J.
Published: February 2022

Fiber-reinforced ceramic-matrix composites are advanced, temperature resistant materials with applications in aerospace engineering. Their analysis involves the detection and separation of fibers, embedded in a fiber bed, from an imaged sample. Currently, this is mostly done using semi-supervised techniques. Here, we present an open, automated computational pipeline to detect fibers from a tomographically reconstructed X-ray volume. We apply our pipeline to a non-trivial dataset by Larson et al. To separate the fibers in these samples, we tested four different architectures of convolutional neural networks. When comparing our neural network approach to a semi-supervised one, we obtained Dice and Matthews coefficients reaching up to 98%, showing that these automated approaches can match human-supervised methods, in some cases separating fibers that human-curated algorithms could not find. The software written for this project is open source, released under a permissive license, and can be freely adapted and re-used in other domains.
An Australian rental housing conditions research infrastructure
Authors: Baker Emma , Daniel Lyrian , Beer Andrew , Bentley Rebecca , Rowley Steven , Baddeley Michelle , London Kerry , Stone Wendy , Nygaard Christian , Hulse Kath , Lockwood Anthony
Published: February 2022

Each year the proportion of Australians who rent their home increases and, for the first time in generations, there are now as many renters as outright homeowners. Researchers and policy makers, however, know very little about housing conditions within Australia’s rental housing sector due to a lack of systematic, reliable data. In 2020, a collaboration of Australian universities commissioned a survey of tenant households to build a data infrastructure on the household and demographic characteristics, housing quality and conditions in the Australian rental sector. This data infrastructure was designed to be national (representative across all Australian States and Territories), and balanced across key population characteristics. The resultant Australian Rental Housing Conditions Dataset (ARHCD) is a publicly available data infrastructure for researchers and policy makers, providing a basis for national and international research.
Comparison between headless cannulated screws and partially threaded screws in femoral neck fracture treatment: a retrospective cohort study
Authors: Wang Yilin , Han Na , Zhang Dianying , Zhang Peixun , Jiang Baoguo
Published: February 2022

The choices of the treatments for femoral neck fractures (FNF) remain controversial. The purpose of this study is to evaluate the prognoses of the variable pitch fully threaded headless cannulated screws (HCS) in the fixation of femoral neck fractures and to compare them with those of partially threaded cannulated screws (PCS). Between 1st January 2012 and 31st December 2016, there were 89 patients with the main diagnose of FNF who accepted the treatment of closed reduction cannulated screw fixation in Peking University People’s Hospital. 34 cases of PCS and 23 cases of HCS met the criterion. The characteristics, prognoses and the imaging changes of all cases were described and the differences between the two groups were compared. Statistical analyses were performed using SPSS version 23.0 (SPSS Inc., USA). Mann–Whitney U test, Analysis of Variance and Chi-square test were used. Statistical significance was defined as P value (two sided) less than 0.05. There was no significant difference in the general characteristics, fracture classifications and reduction quality between the two groups. HCS group had a significant lower angle decrease rate (30.4% vs. 58.8%, P = 0.035), femoral neck shortening rate (26.1% vs. 52.9%, P = 0.044) and screw back-sliding rate (21.7% vs. 50.0%, P = 0.032), but a higher screw cut-out rate (21.7% vs. 0.0%, P = 0.008). In non-displacement fracture subgroup, HCS had significant higher Harris Score (92 vs. 90, P = 0.048). Compared with PCS, HCS had a lower screw back-sliding rate, femoral shortening rate, angle decrease rate and similar function score, but would result in more screw cut-outs in displaced FNF. As a conclusion, HCS should not be used in displaced FNF due to its higher screw cut-out rate, and its potential advantage in non-displaced FNF needs to be further proved. Further qualified investigations with a larger scale of patients and longer follow-up are needed in the future.
Electroporation and cell killing by milli- to nanosecond pulses and avoiding neuromuscular stimulation in cancer ablation
Authors: Gudvangen Emily , Kim Vitalii , Novickij Vitalij , Battista Federico , Pakhomov Andrei G.
Published: February 2022

Ablation therapies aim at eradication of tumors with minimal impact on surrounding healthy tissues. Conventional pulsed electric field (PEF) treatments cause pain and muscle contractions far beyond the ablation area. The ongoing quest is to identify PEF parameters efficient at ablation but not at stimulation. We measured electroporation and cell killing thresholds for 150 ns–1 ms PEF, uni- and bipolar, delivered in 10- to 300-pulse trains at up to 1 MHz rates. Monolayers of murine colon carcinoma cells exposed to PEF were stained with YO-PRO-1 dye to detect electroporation. In 2–4 h, dead cells were labeled with propidium. Electroporation and cell death thresholds determined by matching the stained areas to the electric field intensity were compared to nerve excitation thresholds (Kim et al. in Int J Mol Sci 22(13):7051, 2021). The minimum fourfold ratio of cell killing and stimulation thresholds was achieved with bipolar nanosecond PEF (nsPEF), a sheer benefit over a 500-fold ratio for conventional 100-µs PEF. Increasing the bipolar nsPEF frequency up to 100 kHz within 10-pulse bursts increased ablation thresholds by < 20%. Restricting such bursts to the refractory period after nerve excitation will minimize the number of neuromuscular reactions while maintaining the ablation efficiency and avoiding heating.
Construction and validation of safe Clostridium botulinum Group II surrogate strain producing inactive botulinum neurotoxin type E toxoid
Authors: Nowakowska Maria B. , Selby Katja , Przykopanski Adina , Krüger Maren , Krez Nadja , Dorner Brigitte G. , Dorner Martin B. , Jin Rongsheng , Minton Nigel P. , Rummel Andreas , Lindström Miia
Published: February 2022

Botulinum neurotoxins (BoNTs), produced by the spore-forming bacterium Clostridium botulinum, cause botulism, a rare but fatal illness affecting humans and animals. Despite causing a life-threatening disease, BoNT is a multipurpose therapeutic. Nevertheless, as the most potent natural toxin, BoNT is classified as a Select Agent in the US, placing C. botulinum research under stringent governmental regulations. The extreme toxicity of BoNT, its impact on public safety, and its diverse therapeutic applications urge to devise safe solutions to expand C. botulinum research. Accordingly, we exploited CRISPR/Cas9-mediated genome editing to introduce inactivating point mutations into chromosomal bont/e gene of C. botulinum Beluga E. The resulting Beluga Ei strain displays unchanged physiology and produces inactive BoNT (BoNT/Ei) recognized in serological assays, but lacking biological activity detectable ex- and in vivo. Neither native single-chain, nor trypsinized di-chain form of BoNT/Ei show in vivo toxicity, even if isolated from Beluga Ei sub-cultured for 25 generations. Beluga Ei strain constitutes a safe alternative for the BoNT research necessary for public health risk management, the development of food preservation strategies, understanding toxinogenesis, and for structural BoNT studies. The example of Beluga Ei generation serves as template for future development of C. botulinum producing different inactive BoNT serotypes.
A scoring system for predicting hepatocellular carcinoma risk in alcoholic cirrhosis
Authors: Lee Kyunghan , Choi Gwang Hyeon , Jang Eun Sun , Jeong Sook-Hyang , Kim Jin-Wook
Published: February 2022

The role of hepatocellular carcinoma (HCC) surveillance is being questioned in alcoholic cirrhosis because of the relative low HCC risk. This study aimed to assess the risk and predictors of HCC in Korean patients with alcoholic cirrhosis by using competing risk analysis. A total of 745 patients with alcoholic cirrhosis were recruited at a university-affiliated hospital in Korea and randomly assigned to either the derivation (n = 507) and validation (n = 238) cohort. Subdistribution hazards model of Fine and Gray was used with deaths and liver transplantation treated as competing risks. Death records were confirmed from Korean government databases. A nomogram was developed to calculate the Alcohol-associated Liver Cancer Estimation (ALICE) score. The cumulative incidence of HCC was 15.3 and 13.3% at 10 years for derivation and validation cohort, respectively. Age, alpha-fetoprotein level, and albumin level were identified as independent predictors of HCC and incorporated in the ALICE score, which discriminated low, intermediate, and high risk for HCC in alcoholic cirrhosis at the cut-off of 60 and 100. The risk of HCC can be stratified by using a combination of readily available clinical parameters (age, AFP level, and albumin level) in patients with alcoholic cirrhosis.
Neuropeptidergic regulation of compulsive ethanol seeking in C. elegans
Authors: Salim Chinnu , Kan Ann Ke , Batsaikhan Enkhzul , Patterson E. Clare , Jee Changhoon
Published: February 2022

Despite the catastrophic consequences of alcohol abuse, alcohol use disorders (AUD) and comorbidities continue to strain the healthcare system, largely due to the effects of alcohol-seeking behavior. An improved understanding of the molecular basis of alcohol seeking will lead to enriched treatments for these disorders. Compulsive alcohol seeking is characterized by an imbalance between the superior drive to consume alcohol and the disruption or erosion in control of alcohol use. To model the development of compulsive engagement in alcohol seeking, we simultaneously exploited two distinct and conflictingCaenorhabditis elegansbehavioral programs, ethanol preference and avoidance of aversive stimulus. We demonstrate that theC. elegansmodel recapitulated the pivotal features of compulsive alcohol seeking in mammals, specifically repeated attempts, endurance, and finally aversion-resistant alcohol seeking. We found that neuropeptide signaling via SEB-3, a CRF receptor-like GPCR, facilitates the development of ethanol preference and compels animals to seek ethanol compulsively. Furthermore, our functional genomic approach and behavioral elucidation suggest that the SEB-3 regulates another neuropeptidergic signaling, the neurokinin receptor orthologue TKR-1, to facilitate compulsive ethanol-seeking behavior.
Quantification metrics for telangiectasia using optical coherence tomography
Authors: Cardinell Jillian L. , Ramjist Joel M. , Chen Chaoliang , Shi Weisong , Nguyen Nhu Q. , Yeretsian Tiffany , Choi Matthew , Chen David , Clark Dewi S. , Curtis Anne , Kim Helen , Faughnan Marie E. , Yang Victor X. D. ,   the Brain Vascular Malformation Consortium HHT Investigator Group, Chakinala Murali , Clancy Marianne S. , Faughnan Marie , Gossage James R. , Henderson Katharine , Iyer Vivek , Kasthuri Raj S. , Kim Helen , Krings Timo , Lawton Michael T. , Lin Doris , Mager Johannes Jurgen , Marchuk Douglas A. , McWilliams Justin P. , McDonald Jamie , Pawlikowska Ludmila , Pollak Jeffrey , Ratjen Felix , Swanson Karen , Vethanayagam Dilini , White Andrew J. , Wilcox Pearce
Published: February 2022

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing bleeding and anemia. A recent increase in potential HHT treatments have created a demand for quantitative metrics that can objectively measure the efficacy of new and developing treatments. We employ optical coherence tomography (OCT)—a high resolution, non-invasive imaging modality in a novel pipeline to image and quantitatively characterize dermal HHT lesion behavior over time or throughout the course of treatment. This study is aimed at detecting detailed morphological changes of dermal HHT lesions to understand the underlying dynamic processes of the disease. We present refined metrics tailored for HHT, developed from a pilot study using 3 HHT patients and 6 lesions over the course of multiple imaging dates, totalling to 26 lesion images. Preliminary results from these lesions are presented in this paper alongside representative OCT images. This study provides a new objective method to analyse and understand HHT lesions using a minimally invasive, accessible, cost-effective, and efficient imaging modality with quantitative metrics describing morphology and blood flow.
Assessing assemblage-wide mammal responses to different types of habitat modification in Amazonian forests
Authors: Almeida-Maués Paula C. R. , Bueno Anderson S. , Palmeirim Ana Filipa , Peres Carlos A. , Mendes-Oliveira Ana Cristina
Published: February 2022

Tropical forests are being heavily modified by varying intensities of land use ranging from structural degradation to complete conversion. While ecological responses of vertebrate assemblages to habitat modification are variable, such understanding is critical to appropriate conservation planning of anthropogenic landscapes. We assessed the responses of medium/large-bodied mammal assemblages to the ecological impacts of reduced impact logging, secondary regrowth, and eucalyptus and oil palm plantations in Eastern Brazilian Amazonia. We used within-landscape paired baseline-treatment comparisons to examine the impact of different types of habitat modification in relation to adjacent primary forest. We examined assemblage-wide metrics including the total number of species, number of primary forest species retained in modified habitats, abundance, species composition, and community integrity. We ranked all types of habitat modification along a gradient of assemblage-wide impact intensity, with oil palm and eucalyptus plantations exerting the greatest impact, followed by secondary regrowth, and selectively logging. Selectively-logged and secondary forests did not experience discernible biodiversity loss, except for the total number of primary forest species retained. Secondary forests further experienced pronounced species turnover, with loss of community integrity. Considering the biodiversity retention capacity of anthropogenic habitats, this study reinforces the landscape-scale importance of setting aside large preserved areas.
Behavioural traits of rainbow trout and brown trout may help explain their differing invasion success and impacts
Authors: McGlade Ciara L. O. , Dickey James W. E. , Kennedy Richard , Donnelly Shannon , Nelson Clare-Ann , Dick Jaimie T. A. , Arnott Gareth
Published: February 2022

Animal behaviour is increasingly recognised as critical to the prediction of non-native species success and impacts. Rainbow trout and brown trout have been introduced globally, but there appear to be differences in their patterns of invasiveness and ecological impact. Here, we investigated whether diploid rainbow trout and diploid and triploid brown trout differ among several key behavioural measures linked to invasiveness and impact. We assessed activity, boldness, aggression, and feeding, using open field, novel object, shelter, mirror, feeding, and functional response experiments. We also tested within each fish type for behavioural syndromes comprising correlations among activity, boldness and aggression. Rainbow trout were more active and aggressive but less bold than diploid and triploid brown trout. In small groups, however, rainbow trout were bolder than both types of brown trout. Diploid brown trout were more active and bolder than triploids when tested individually, and had a higher functional response than both rainbow trout and triploid brown trout. In terms of behavioural syndromes, there was no association between activity and boldness in rainbow trout, however, there was in both brown trout types. The increased activity and aggression of rainbow trout may reflect an increased stress response to novel situations, with this response reduced in a group. These results suggest that rainbow trout do not manage their energy budgets effectively, and may explain why they have limited survival as invaders. In addition, the lower functional response of rainbow trout may explain why they are implicated in fewer ecological impacts, and the triploidy treatment also appears to lower the potential impact of brown trout. Comparative analyses of multiple behaviours of invasive species and genetic variants may thus be key to understanding and predicting invader success and ecological impacts.
Entropy generation from convective–radiative moving exponential porous fins with variable thermal conductivity and internal heat generations
Authors: Din Zia Ud , Ali Amir , De la Sen Manuel , Zaman Gul
Published: February 2022

The performance and thermal properties of convective–radiative rectangular and moving exponential porous fins with variable thermal conductivity together with internal heat generation are investigated. The second law of thermodynamics is used to investigate entropy generation in the proposed fins. The model is numerically solved using shooting technique. It is observed that the entropy generation depends on porosity parameter, temperature ratio, temperature distribution, thermal conductivity and fins structure. It is noted that entropy generation for a decay exponential fin is higher than that of a rectangular fin which is greater than that of a growing exponential fin. Moreover, entropy generation decreases as thermal conductivity increases. The results also reveal that entropy generation is maximum at the fin’s base and the average entropy production depends on porosity parameters and temperature ratio. It is further reveal that the temperature ratio has a smaller amount of influence on entropy as compared to porosity parameter. It is concluded that when the temperature ratio is increases from 1.1 to 1.9, the entropy generation number is also increase by $$30\%$$

30
%

approximately. However, increasing porosity from 1 to 80 gives 14-fold increase in average entropy generation.
Real-time factory smoke detection based on two-stage relation-guided algorithm
Authors: Wang Zhenyu , Yin Duokun , Ji Senrong
Published: February 2022

Recently, air quality analysis based on image sensing devices has attracted much attention. Since most smoke images in real scenes have challenging variances, which is difficult for existing object detection methods. To keep real-time factory smoke under efficient and universal social supervision, this paper proposes a mobile-platform-running efficient smoke detection algorithm based on image analysis techniques. We introduce the two-stage smoke detection (TSSD) algorithm based on the lightweight detection framework, in which the prior knowledge and contextual information are modeled into the relation-guided module to reduce the smoke search space, which can therefore significantly improve the performance of the single-stage method. Experimental results show that the proposed TSSD algorithm can robustly improve the detection accuracy of the single-stage method and the model has good compatibility for image resolution inputs. Compared with various state-of-the-art detection methods, the accuracy $$AP_{mean}$$

A

P

mean

of our proposed TSSD model reaches 59.24$$\%$$
%
, even surpassing the current detection model Faster RCNN. In addition, the detection speed of our proposed model can reach 50 ms (20 FPS), meeting the real-time requirements. This knowledge-based system has the advantages of high stability, high accuracy, fast detection speed. It can be widely used in some scenes with smoke detection requirements, such as on the mobile terminal carrier, providing great potential for practical environmental applications.