bluuebunny/crossref_metadata_2025 huggingface dataset:
Technology Focus: Extended-Reach and Complex Wells (May 2022)
Authors: Qiu Kaibin
Published: June 2022

In the past several decades, technology continuously pushed the technical limit of extended-reach and complex wells, bringing records for lateral length, depth, and number of laterals. In the past few years, however, the design and operations of extended-reach and complex wells started to evolve under the volatile oil market pricing conditions and the stride of digital transformation. The technology front is shifting from marching toward longer and more-complex wells to smarter wells with better return on investment (ROI).

Artificial intelligence (AI) and machine learning, which can effectively mine deep insight from a large amount of drilling operational data and synthetic forward modeling data, are starting to shape the design and operations of extended-reach and complex wells. AI and machine learning have been demonstrating their ability to provide early warning of stuck pipe, reveal root causes of drilling accidents, improve drilling design, optimize completion design, and find new ways to improve production performance.

Rather than competing on going even farther, U-shape (or “horseshoe”) wells have been drilled to tap shale gas through leveraging state-of-the-art extended-reach drilling technology and stimulation technology to improve the economics of the development of unconventional reservoirs.

Looking to the future, the march toward longer extended-reach wells and more-complex multilateral wells to access formidable reservoirs will continue. The great potential, however, lies in the application of state-of-the-art extended-reach and complex well technology to versatile oil and gas fields (both conventional and unconventional) for the purpose of further improving ROI of the project, and AI and machine learning will play a vital role in enabling a step change in design and operations.

Recommended additional reading at OnePetro: www.onepetro.org.

SPE 202046 Automated Geosteering While Drilling Using Machine Learning—Case Studies by Ivan Denisenko Denisenko, Rogii, et al.
Data-Driven Approach Detects, Classifies Screenout in Horizontal Wells
Authors: Carpenter Chris
Published: June 2022

This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 199707, “A Data-Driven Approach to Screenout Detection for Horizontal Wells,” by Xiaodan Yu, Whitney Trainor-Guitton, and Jennifer Miskimins, SPE, Colorado School of Mines. The paper has not been peer reviewed.

Multistage hydraulic fracturing has gained global popularity as more tight geologic formations are developed economically for hydrocarbon resources. However, screenout is a major issue caused by the blockage of proppant inside the fractures. The complete paper presents a screenout-classification system based on Gaussian hidden Markov models (GHMMs) trained on simulated data that predicts screenouts and provides early warning by learning prescreenout patterns in surface-pressure signals. The methodology is a useful tool for early screenout detection and shows the promise of other fracturing time-series data analysis.

Materials and Methods

In the complete paper, fracturing treatment data are generated using a hydraulic fracturing simulation software. A well-logging profile acquired from a vertical well located in the Denver-Julesburg (DJ) Basin is used to generate the reservoir rock properties in the fracturing simulations.
Ultrasonic Measurements Evaluate and Qualify Annular Creep Barriers
Authors: Carpenter Chris
Published: June 2022

This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 208782, “Annular Creep Barrier Evaluation and Qualification Using Ultrasonic Measurements,” by Eric van Oort, SPE, The University of Texas at Austin, and Akshay Thombare, SPE, and Munir Aldin, SPE, Metarock Laboratories, et al. The paper has not been peer reviewed.

Creep barriers can simplify well abandonments, particularly in high-cost offshore environments. Evaluation and qualification of creep barriers in the field, however, have proven challenging and labor-intensive when casing is perforated and annular rock material is pressure-tested to verify its sealing ability. This work seeks to eliminate the need for pressure testing by allowing the barrier to be qualified using only cased-hole log measurements.

Creep Barrier Formation and Stimulation

Plastically deforming shale and salt or evaporite formations under certain conditions can move into uncemented or poorly cemented annular spaces, filling them and contacting the casing to form an effective pressure-tight barrier. Supporting evidence overwhelmingly points toward creep as the fundamental rock-mechanical mechanism behind this type of barrier formation. Creep barriers have, in fact, become commonplace considerations in the plugging and abandonment of offshore wells in the UK and the Norwegian sectors of the North Sea, leading to simplified and more-cost-effective rigless offshore well-plugging operations. The latter is accomplished by eliminating the need for casing cutting and pulling or casing milling followed by setting openhole abandonment plugs. Materials that present alternatives to ordinary Portland cement (OPC) for well plugging-and-abandonment barrier construction include the use of shale or salt as a barrier (SAAB).

Comparison of category scores for SAAB with other materials reveals that SAAB offers a well-rounded performance envelope with no weaknesses in any categories, whereas the other materials, including cement, show weaknesses in one or more categories. A main advantage of SAAB is that it offers the ability to “replace” the caprock, the desired goal in most well abandonments. Moreover, for many materials including OPC, long-term (i.e., hundreds or thousands of years and beyond) sealing performance is unknown for well abandonment. The only category in which SAAB technology appears to lag is in its technology readiness level score. This, then, provides motivation for further research.
USP25-PKM2-Glycolysis axis participates in ischemia reperfusion-induced acute kidney injury by promoting M1 macrophage polarization and proinflammatory response
Authors: Yang Yi , Zhan Xiao-Na , Zhang Cailin , Shi Jia , Wu Jianliang , Deng Xuan , Xing Xue , Cheng An-Ying , Hong Yu , Wang Ya-Nan , Li Jie , Wang Yuyao , Li Qing , Ge Shuwang , Xu Gang , He Fan
Published: June 2022

M1 macrophage, characterized by the production of proinflammatory cytokines, has been reported to exert a critical role in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). Recently, increasing evidence suggests that aerobic glycolysis plays an important role in the M1 polarization of macrophages. However, the M1 polarization area still needs continuous studies although it has been developed a lot. Here, we found that the upregulation of ubiquitin-specific protease 25 (USP25), a deubiquitinase, was correlated with renal function in patients with acute kidney tubular injury. In the model of murine I/R-induced AKI, the expression of USP25 was increased in the kidney, and USP25 knockout lowered murine I/R-induced AKI and reduced the infiltration of M1 macrophages in the kidney. In vitro, USP25 was highly expressed in LPS-induced M1 macrophages. Silencing of USP25 expression efficiently suppressed the levels of M1 polarization and proinflammatory response. This suppression was restored by plasmid-mediated overexpression of wild-type USP25, but not by an enzyme-inactivated mutant USP25 (C178S). By performing rapid immunoprecipitation mass spectrometry of endogenous proteins, we screened out M2 isoform of pyruvate kinase, muscle (PKM2) as a target substrate of USP25. By USP25 knockout and overexpression, we showed that USP25 cleaved the K48-linked ubiquitin chain from PKM2. We furthermore confirmed that USP25 affected the aerobic glycolysis during M1 polarization using extracellular acidification rate and determination of lactate production. By PKM2 inhibition and supplement of USP25−/− BMDMs with PKM2, we derived that the USP25-PKM2-aerobic glycolysis axis positively regulated M1 polarization and proinflammatory response, and exacerbated murine I/R induced AKI. Our data suggest that the USP25-PKM2-aerobic glycolysis axis was expected to be a therapeutic target for AKI.
Creation of new germplasm resources, development of SSR molecular markers and screen of monoterpene synthase in thyme
Authors: Sun Meiyu , Zhu Li , Zhang Yanan , Liu Ningning , Zhang Jinzheng , Li Hui , Bai Hongtong , Shi Lei
Published: June 2022

Background
Thymus-derived essential oil (EO) and their compositions have numerous applications in medicine, food and cosmetics, while also displaying antibacterial, antifungal, and antiviral properties. In order to obtain EOs different terpene compositions of thyme, we want to use hybridization to create new germplasm resources of thyme.
Results
The phenotypic of three Chinese wild thymes and seven European thymes, including EO yield (extraction rate), glandular trichomes density, EO compositions content, plant type and fertility had been evaluated and analysed. Two F1 populations were constructed with EOs terpene compositions content and yield as the main breeding goal, and refer to other traits to select suitable parental design hybrid combinations. At the same time, simple sequence repeat (SSR) primers were developed based on T. quinquecostatus whole-genome sequencing (date unpublished) to authenticate of F1 hybrid progenies. The primers of 300 pairs were selected from the designed primers, and polymerase chain reaction (PCR) amplification was carried out in the parents of the two populations of in T. longicaulis (Tl) × T. vulgaris 'Fragrantissimus' (Tvf) and T. vulgaris 'Elsbeth' (Tve) × T. quinquecostatus (Tq). Based on the chemotype of the parents and F1 progenies, we screened two γ-terpinene synthase, one α-terpineol synthase, and one geraniol synthase, and performed real-time quantitative PCR (qRT-PCR) of them in the parents and some F1 progenies.
Conclusions
We use hybridization to create new germplasm resources of thyme, develop SSR molecular markers from T. quinquecostatus, and screen of monoterpene synthase in thyme. The above results laid the foundation for the creation of new germplasm resources, construction of genetic linkage map, location of quantitative trait locus (QTL) and insight into the mechanism of monoterpenoids biosynthesis in thymes.
External Debt and Human Development Index: MENA Region Case
Authors: Mezni Mohamed , Djebali Nesrine
Published: June 2022

In this paper, we have tried to examine the effect of loans granted by the international monetary fund on the human development index (measured by 3 components). To do this, we used a sample of 12 countries in the MENA region. Our sample is composed of two groups of countries namely; A group of 6 countries from the North Africa region (Algeria, Djibouti, Egypt, Mauritania Morocco and Tunisia) and a group of 6 countries from the Middle East region (Iran, Jordan, Kuwait, Lebanon, Syria, and Yemen) during the period (1990-2019). The econometric approach used in this study is based on the analysis of panel data. Our main results have shown that the flows granted by the (IMF) which have been used in the financing of living sectors have a positive influence on the human development index. Similarly, trade openness and foreign direct investment are positively and significantly correlated with the HDI. The variables, gross fixed capital formation, and domestic private sector credits negatively affect the human development index of MENA countries.
In-situ generation of hydroxyl radicals by B-doped TiO2 for efficient photocatalytic degradation of acetaminophen in wastewater
Authors: Xiao Caofan , Chen Xueqi , Tao Xiumei , Liu Xian , Wang Xun , Zhu Lei
Published: June 2022

Acetaminophen (AP) is a widely used antipyretic analgesic belonging to the class of PPCPs, which is difficult to be effectively degraded by traditional water treatment processes. However, photocatalytic technology may be an effective approach. Herein, B-doped TiO2 photocatalytic materials were synthesized by sol-gel method, calcinated at 600℃ for 2 h, investigated by XRD, TEM, XPS and other characterization methods. The photocatalytic efficiency and factors affecting the photocatalytic activity were assessed by degradation of AP under 365 nm UV light. Compared with naked TiO2, 4%B-TiO2 nanopowder had smaller grain size, higher porosity and lower bandgap energy of 3.11 eV. Scavenging experiments and ESR results showed that •OH was the principal active species. Hence, the degradation efficiency of AP was as high as 98.8% in 30 min when adopting 10 mg/L AP initial concentration and 1 g/L 4%B-TiO2 loading, owing to efficient •OH generated by B-TiO2.
SIRT2 promotes invasion and metastasis of osteosarcoma cells via inhibiting the degradation of Snail
Authors: tian yonghao , liu ruijuan , gao zhixiao , hou xiaoyan , liu xinyu , zhang weifang
Published: June 2022

Osteosarcomas (OS) are highly metastatic and usually lead to poor outcome. Epithelial-mesenchymal transition (EMT) is reported as a critical event in metastasis. SIRT2 exerts dual functions in many different tumors. However, the underlying molecular mechanisms of SIRT2 in osteosarcoma cell metastasis and EMT have not been fully explored. In this study, we confirmed that SIRT2 was highly-expressed in human osteosarcoma MG63 and Saos-2 cell lines. Knockdown of SIRT2 inhibited and overexpression of SIRT2 enhanced migration and invasion of osteosarcoma cells. Moreover, SIRT2 positively regulated EMT and increased the protein levels of mesenchymal markers N-cadherin, Vimentin and MMP2, MMP9. A xenograft mouse model showed that SIRT2 knockdown in osteosarcomas cells led to reduced tumor growth and impaired lung and liver metastasis in vivo. Furthermore, we showed that SIRT2 interacted with and up-regulated the protein level of EMT-associated transcription factor Snail. SIRT2 inhibited the degradation of Snail via its deacetylase activity. In conclusion, SIRT2 plays a crucial role in osteosarcomas metastasis by inhibiting Snail degradation and may serve as a novel therapeutic target to manage osteosarcomas.
CBL-interacting protein kinases (CIPKs) in Chickpea: Genome- wide identification, structure and expression analysis under abiotic stresses and development
Authors: Poddar Nikita , Deepika Deepika , Singh Amarjeet , Kumar Shailesh
Published: June 2022

Calcineurin B-like proteins (CBL)-interacting protein kinases (CIPKs) regulate the developmental processes, hormone signal transduction and stress responses in plants. Although the genome sequence of chickpea is available, information related to the CIPK gene family is missing in this important crop plant. Here, a total of 22 CIPK genes were identified and characterized in chickpea. We found a high degree of structural and evolutionary conservation in the chickpea CIPK family. Our analysis showed that chickpea CIPKs have evolved with dicots from common ancestors, and extensive gene duplication events have played an important role in the evolution and expansion of the CIPK gene family in chickpea. The three-dimensional structure of chickpea CIPKs was described by protein homology modelling. Most CIPK proteins are localized in the cytoplasm and nucleus, as predicted by in-silico subcellular localization. Promoter analysis revealed various cis-regulatory elements related to plant development, hormone signaling, and abiotic stresses. RNA-seq expression analysis indicated that CIPKs are significantly expressed through a spectrum of developmental stages, tissue/organs that hinted at their important role in plant development. The qRT-PCR analysis revealed that several CaCIPK genes had specific and overlapping expressions in different abiotic stresses like drought, salt, and ABA, suggesting the important role of this gene family in abiotic stress signaling in chickpea. Thus, this study provides an avenue for detailed functional characterization of the CIPK gene family in chickpea and other legume crops.
Key traits influencing wind resistance of Eucalyptus camaldulensis
Authors: Xiu-hua Shang , Pei-jian Zhang , Guo Liu , Zhi-hua Wu
Published: June 2022

Background
Wind is an important driving factor influencing forest structure, ecology, and the carbon cycle in temperate and tropical regions. Damage from typhoons poses a significant threat to eucalyptus production in coastal regions of southeast China. However, few strategies have been used and account for key traits impact on wind damage/resistance of eucalyptus. To identify key factors affecting eucalyptus wind resistance, 20 Eucalyptus camaldulensis genotypes were selected, and wind damage indices and traits were measured and evaluated using correlation analysis and principal component analysis.
Results
We identified a correlation between tree traits, wind damage indices, and the traits related to H, V, FP BT, FL, and FW. Five PCs from the above-mentioned traits were obtained and could represent the standing tree traits explained by PCA. PCs and tree-pulling variables were further used for typical correlation and path analyses. Canonical correlation analysis showed the top two canonical correlation coefficients were 0.9547 and 0.9012, respectively, while PC2 reflected that the growth traits were the main trait affecting pull tree variables. The PA-OV model and its modifications with PC functions and tree-pulling variables were introduced and developed for wind resistance estimation. The fitting effect of the two models and the observed data was good, with a P-value of 1.000, RMSEA of 0.000, and other goodness of fit indices over 0.9. Based on effects from model 2, PC4 had the greatest impact on tree-pulling variables. Therefore, our results implied that PC4, composed of holocellulose content, lignin, and fibre width, was the most important factor affecting standing tree stability under windy conditions.
Conclusion
This study provides insights into forest management and planning in coastal typhoon prone areas. Determining the effect of wind on trees can expand our understanding of the factors that contribute to wind damage, thereby improving management practices.
Groundwater storage change estimation using GRACE satellite data in the Helmand River Basin of Afghanistan
Authors: Nazari Aref , Zaryab Abdulhalim , Ahmadi Abdullah
Published: June 2022

Understanding dynamic changes of groundwater storage and quantifying the trends of groundwater fluctuations in the Helmand River Basin (HRB) aquifers, where the groundwater is the main source for drinking and irrigation applications is significantly important for effective management of groundwater resources. This case study quantifies the changes in groundwater storage over 18 years (i.e., from 2003 to 2021) in the HRB by employing the Gravity Recovery and Climate Experiment (GRACE) observations and Global Land Data Assimilation System (GLDAS) data due to sparse groundwater monitoring networks and lack of ground-based information. The data of observation wells was used to validate the results of the GRACE and GLDAS outputs. The results indicate that changes in groundwater storage on average from 2003 to 2021 are equal to (-112.4 ± 237.14 mm or -2.048 ± 4.32 km3/year). In average, during 2003 to 2021 groundwater table decline was -6.10 m in the HRB. The study indicated relatively strong correlation (0.75) between the GRACE derived data and direct in situ measurements. This study highlights the effectiveness of the GRACE-derived data for the reliable estimation of groundwater storage changes in the HRB and may contribute to sustainable groundwater resources management in the region.
Climate Change and Its Impact on Agricultural GDP Growth in Ethiopia: a Time Series Analysis
Authors: Mammo Behailu Tamiru
Published: June 2022

Climate change is now a global phenomenon with growth, poverty, food security, and stability implications, and is one of the greatest challenges the world is facing today. The economic impact of climate change mainly depends on the sectoral composition of the economy. That is certain sectors like agriculture are more sensitive to climate change and the associated variability. The main objective of this paper is to investigate the impact of climate change on agricultural gross domestic product growth in Ethiopia. This study uses time-series annual data from 1992/93to 2017/18 and, an effort is made to identify the long run and short-run impact of climate change in Ethiopia using an autoregressive distributed lag (ARDL) and error correction methods. The results of the study provide evidence that climate change and variability affect real agricultural gross domestic product growth negatively in the long run. The coefficient of the error term that captures the speed of adjustment toward the long-run equilibrium is found with the correct sign and magnitude. The overall findings of the study underlined the importance of building resilience to climate change and minimizing the adverse impacts of climate change to promote agricultural output and hence economic growth in Ethiopia.
Pregnancy and Childbirth Outcomes of Gestational Diabetes Mellitus: A Retrospective Cohort Study
Authors: Shirzadfardjahromi Malihe , Shekari Mitra , Ranjbar Amene , Mehrnoush Vahid , Darsareh Fatemeh , Roozbeh Nasibeh
Published: June 2022

Background: Understanding the various outcomes of gestational diabetes mellitus (GDM) is essential for initiating a cascade of preparatory steps to address them. Therefore, we aimed to evaluate the pregnancy and childbirth outcomes of GDM.Methods: We retrospectively assessed singleton pregnant mothers diagnosed with GDM who gave birth at Khaleej-e-Fars Hospital (a tertiary hospital) in Bandar Abbas, Iran, between January 1st, 2020, and January 1st, 2022. Records of women with pre-existing diabetes mellitus, chronic hypertension, cardiovascular disease, thyroid dysfunction, preeclampsia, abnormal placentation (previa or acreta), severe anemia (hemoglobin≤7), infertility, and COVID-19 at the time of admission were excluded. Pregnancy and childbirth outcomes included the incidence of the need for induction of labor, placenta abruption, preterm birth, intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), meconium fluid, fetal distress, methods of delivery, perineal lacerations, postpartum hemorrhage, childbirth injury, shoulder dystocia, macrosomia, low birth weight, congenital malformation, neonatal asphyxia, need for cardiac, respiratory resuscitation, transfer to neonatal intensive care unit (NICU), and newborn death.Results: The records of 7748 eligible mothers were included in the analysis. GDM was diagnosed in 1087 (14%) of mothers. Age was the only sociodemographic factor that differed significantly between GDM and non-GDM mothers. The Chi-square test result revealed that macrosomia, labor induction, instrumental deliveries, NICU admissions, and IUFD were more common in GDM mothers, while the incidence of CS, meconium fluid, and IUGR were less common in GDM mothers. The impact of GDM on adverse events of pregnancy and childbirth was evaluated using logistic regression analysis. GDM mothers had a significantly higher risk of macrosomia (aOR: 2.94, 95%CI: 1.71–4.61), labor induction (aOR: 3.14, 95%CI: 1.72–6.95), instrumental delivery (aOR: 3.16, 95%CI: 1.51–3.87), IUFD (aOR: 1.95, 95%CI: 1.17–3.06), and NICU admission (aOR: 2.19, 95%CI: 0.99–3.82). Other common complications, such as CS, postpartum hemorrhage, shoulder dystocia, childbirth trauma, and extensive perineal lacerations, were not significantly different between GDM and non-GDM mothers.Conclusions: Despite the higher incidence of labor induction and instrumental delivery, we found no significant association between GDM and adverse maternal outcomes. Regarding neonatal outcomes, GDM was linked to macrosomia, IUFD, and NICU admission.
Brown adipose tissue–associated postprandial thermogenesis in humans: Different effects of isocaloric meals rich in carbohydrate, fat, and protein
Authors: Aita Sayuri , Matsushita Mami , Yoneshiro Takeshi , Hatano Takuya , Kameya Toshimitsu , Ohkubo Iwao , Saito Masayuki
Published: June 2022

The increase of whole-body energy expenditure seen after a single meal ingestion, referred to as diet-induced thermogenesis (DIT), substantially varies depending on the meal’s macronutrient composition. Brown adipose tissue (BAT), a site of nonshivering thermogenesis, may be involved in DIT. To examine the effects of meal composition on BAT-associated DIT in humans, healthy male participants underwent [18F]fluorodeoxyglucose–positron emission tomography to assess BAT activity, and respiratory gas analysis for 2 hours after ingestion of a carbohydrate-, protein-, or fat-rich meal (C-meal, P-meal, and F-meal, respectively). The calculated DIT at 2 hours was 6.44 ± 2.01%, 3.49 ± 2.00%, and 2.32 ± 0.90% of the ingested energy after the P-meal, C-meal, and F-meal, respectively. The DIT after C-meal ingestion correlated positively with BAT activity (P = 0.011), and was approximately twice greater in the group with high-BAT activity than in the group with low-BAT activity (4.35 ± 1.74% vs. 2.12 ± 1.76%, P < 0.035). Conversely, the DIT after F-meal or P-meal ingestion did not correlate with BAT activity, with no difference between the two groups. Thus, BAT has a significant role in facultative DIT after ingestion of a carbohydrate-rich meal, but hardly after ingestion either protein- or fat-rich meal.
Network structure indexes to forecast epidemic spreading in real-world complex networks
Authors: Bellingeri Michele , Bevacqua Daniele , Turchetto Massimiliano , Scotognella Francesco , Alfieri Roberto , Nguyen Ngoc-Kim-Khanh , Le Thi Trang , Nguyen Quang , Cassi Davide
Published: June 2022

Complex networks are the preferential framework to model spreading dynamics in several real-world complex systems. Complex networks can describe the contacts between infectious individuals, responsible for disease spreading in real-world systems. Understanding how the network structure affects an epidemic outbreak is therefore of great importance to evaluate the vulnerability of a network and optimize the disease control. Here we argue that the best network structure indexes (NSIs) to predict the disease spreading extent in real-world networks are based on the notion of network node distance rather than on network connectivity as commonly believed. We numerically simulated, via a type-SIR model, epidemic outbreaks spreading on 50 real-world networks. We then tested which NSIs, among 40, could a priori better predict the disease fate. We found that the “average normalized node closeness” and the “average node distance” are the best predictors of the initial spreading pace, whereas indexes of “topological complexity” of the network, are the best predictors of both the value of the epidemic peak and the final extent of the spreading. Furthermore, most of the commonly used NSIs are not reliable predictors of the disease spreading extent in real-world networks.
Distribution patterns of astrocyte populations in the human cortex
Authors: Forrest Shelley L. , Kim Jordan Hanxi , Crockford Daniel R. , Huynh Katharine , Cheong Rosie , Knott Samantha , Kane Madison A. , Ittner Lars M. , Halliday Glenda M. , Kril Jillian J.
Published: June 2022

Astrocytes are a major class of glial cell in the central nervous system that have a diverse range of types and functions thought to be based on their anatomical location, morphology and cellular properties. Recent studies highlight that astrocyte dysfunction contributes to the pathogenesis of neurological conditions. However, few studies have described the pattern, distribution and density of astrocytes in the adult human cortex. This study mapped the distribution and density of astrocytes immunolabelled with a range of cytoskeletal and membrane markers in the human frontal cortex. Distinct and overlapping astrocyte populations were determined. The frontal cortex from ten normal control cases (75±9 years) was immunostained with glial fibrillary acidic protein (GFAP), aldehyde dehydrogenase-1 L1 (ALDH1L1), connexin-43 (Cx43), aquaporin-4 (AQP4), and glutamate transporter 1 (GLT-1). All markers labelled populations of astrocytes in the grey and white matter, separate cortical layers, subpial and perivascular regions. All markers were informative for labelling different cellular properties and cellular compartments of astrocytes. ALDH1L1 labelled the largest population of astrocytes, and Cx43-immunopositive astrocytes were found in all cortical layers. AQP4 and GLT-1 labelled distal astrocytic process and end-feet in the same population of astrocytes (98% of GLT-1-immunopositive astrocytes contained AQP4). This study highlights the diversity of astrocytes in the human cortex, providing a reference map of the distribution of distinct and overlapping astrocyte populations which can be used for comparative purposes in various disease, inflammatory and injury states involving astrocytes.
Multivariate outlier filtering for A-NFVLearn: an Advanced Deep VNF Resource Usage Forecasting Technique
Authors: St-Onge Cédric , Kara Nadjia , Edstrom Claes
Published: June 2022

Virtual Network Function Resource Adaptation (VNF-RA) aims at adequately adapting Network Function Virtualization Infrastructure (NFVI) resources according to the geographical fluctuation of user demand by maximizing the quality of service (QoS) of the offered services and the energy consumption of the NFVI while limiting the risks of Service Level Agreement (SLA) breaches, the CAPEX and OPEX of the cloud operators and their customers. Virtual Network Function (VNF) resource usage forecasting leads therefore a key role in enabling proactive resource adaptation in dynamic Network Function Virtualization (NFV) environments whose resource demand constantly changes. In parallel, Long Short-Term Memory (LSTM)-based prediction has garnered huge interest in the research community and several research teams have therefore proposed different VNF resource usage prediction algorithms based on this machine learning technique. However, current LSTM-based VNF resource usage forecasting techniques lack the flexibility to take several resource attributes of different scales, over many time steps, in order to predict several other resource attributes over many time steps from a Service Function Chain (SFC). In this paper, we push the state of the art forward by presenting A-NFVLearn, a flexible multivariate, LSTM-based model with an attention mechanism which uses different attributes of resource load history (CPU, memory, I/O bandwidth) from various VNFs of an SFC to forecast future load of multiple resources of a VNF. Next, we propose a multivariate outlier filtering scheme at pre-processing based on Adjusted Outlyingness (AO), which improves training time performance of LSTM-based models without impacting prediction accuracy.
Predictive Potential of ACE phenotyping in Extrapulmonary Sarcoidosis
Authors: Danilov Sergei M. , Kurilova Olga V. , Sinitsyn Valentin E. , Kamalov Armais A. , Garcia Joe GN , Dudek Steven M.
Published: June 2022

Background.Elevated ACE expression in tissues (reflected by blood ACE levels) is associated with increased risk of cardiovascular diseases and is a marker for granulomatous diseases. We developed a new approach for characterization of ACE status in the blood - ACE phenotyping - and established normal values of ACE levels as 50–150% of control pooled plasma.Methods.ACE phenotyping was performed in citrated plasma of 120 patients with known interstitial lung diseases and included 1) simultaneous determination of ACE activity with 2 substrates (ZPHL and HHL); 2) calculation of the ratio of hydrolysis of two substrates (ZPHL/HHL ratio); 3) determination of the levels of ACE immunoreactive protein and ACE conformation with a set of monoclonal antibodies (mAbs) to ACE.Results.In the 1st set of 100 patients, 22 patients had ACE levels > 150%; ACE phenotyping also objectively identified the presence of ACE inhibitors in the plasma of 15 patients. After excluding these patients and one other patient with ACE mutation that increases ACE shedding, 17 patients were identified as a suspicious for systemic sarcoidosis based on elevation of blood ACE (> 150% of mean). Our newly established parameter–ACE immunoreactivity (with mAb 9B9)—allowed us to detect 22 patients with decreased values (< 80%) of this parameter, which may indicate the presence of ACE in the blood that originates from macrophages/dendritic cells of granulomas. In the remaining 20 patients, this new parameter (mAbs binding/activity ratio) was calculated using 3 mAbs (9B9, 3A5 and i1A8 - having overlapping epitopes), and 8 patients were identified as having decreased levels, thus increasing dramatically the sensitivity for detection of patients with systemic sarcoidosis. Whole body PET scan confirmed extrapulmonary granulomas in some patients with lower immunoreactivity towards anti-ACE mAbs.Conclusions.These results demonstrate that ACE phenotyping has novel potential to noninvasively detect patients with systemic sarcoidosis.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in an Australian institution: Lessons from 20 years experience
Authors: Farrell Rhonda , Liauw Winston , Morris David
Published: June 2022

Objectives: We report the 20-year experience of the largest Australian unit performing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer and reflect on learning opportunities. Methods: A retrospective review of all cases of CRS for ovarian cancer at St George Peritonectomy Unit from Jan 1998- Jan 2018 was performed. Prospectively collected data include age, stage, histology, disease extent (PCI), completeness of cytoreduction (CC score), HIPEC regime, 30-day surgical morbidity, disease recurrence, and death. Survival was computed using Kaplan-Meier method and analysed using log-rank tests and Cox-proportional hazards models. Results: Forty-one women with advanced ovarian cancer (11 primary stage III/IV, 30 recurrent) underwent CRS, 29 (71%) with HIPEC. Most (68%) had high-volume disease (PCI >15). In 98%, CC0/CC1 (residual <2.5mm) was achieved. Fourteen (34%) had grade 3/4 complications, 1 patient (2%) died within 30 days and 2 patients (5%) died within 90 days. Progression-free and median overall survival was 30.0 and 67.0 months for primary cancer, and 6.7 and 18.1 months for recurrent cancer. Survival was associated with platinum-sensitivity, PCI£15, and CC score 0, but not HIPEC. Conclusion: This study reports outcomes for patients with advanced ovarian cancer patients treated in an Australian centre offering CRS and HIPEC. Whilst survival and morbidity outcomes were good for primary disease, they were poorer than predicted from the literature for cases of recurrent disease. The incorporation of evidence-based predictors of survival and multidisciplinary input are essential to achieve the best survival outcomes.
Circ_001422 aggravates osteosarcoma progression through targeting miR-497-5p/E2F3 axis
Authors: Li Xinyu , Zhao Xin , Li Jin , Zhang Xiaozhan
Published: June 2022

Circ_001422 has been confirmed to be involved in regulating osteosarcoma progression, but its specific mechanism has not been clearly studied. This work aimed to analyze circ_001422’s role in osteosarcoma (OS) cell biological behaviors and the possible molecular mechanisms. This work carried out RT-qPCR for detecting circ_001422, E2F3 and miR-497-5p levels, whereas CCK-8 together with Transwell assays for measuring cell growth, migration as well as invasion abilities. Relation of miR-497-5p with E2F3, as well as circ_001422 with miR-497-5p was analyzed through dual-luciferase reporter gene assay. Protein level was identified by westernblot. According to our results, circ_001422 expression within osteosarcoma tissue significantly increased compared with corresponding healthy samples. Inhibition of circ_001422 significantly decreased OS cell growth, invasion and migration. From mechanism research, miR-497-5p was proved as circ_001422’s target, and E2F3 was miR-497-5p’s target. Besides, miR-497-5p down-regulation or E2F3 overexpression abolished circ_001422 inhibition-mediated inhibition on OS cell proliferation, invasion and migration. Collectively, this study has first suggested circ_001422’s role in enhancing OS proliferation, migration as well as invasion via miR-497-5p/E2F3 axis. Our results will offer new ideas and new anti-OS targets.
Disrupted tenogenesis in masseter as a potential cause of micrognathia
Authors: LIU CHAO , Zhou Nan , Li Nan , Xu Tian , Chen Xiaoyan , Zhou Hailing , Xie Ailun , Liu Han , Zhu Lei , Wang Songlin , Xiao Jing
Published: June 2022

Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for the masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.
Does Social Rigidity predict Cognitive Rigidity? Profiles of Socio-Cognitive Polarization
Authors: Salvi Carola , Iannello Paola , Cancer Alice , Cooper Samuel E. , McClay Mason , Antonietti Alessandro , Dunsmoor Joseph E.
Published: June 2022

Recent research has investigated the relationship between rigid political ideologies and underlying cognitive functions, highlighting discrepancies on how different ‘cognitive styles’ are defined and measured in relation with different shapes of social rigidity. Cognitive rigidity is often operationalized using problem solving which translates into the ability to generate novel and original ideas by exploring unusual reasoning paths and challenging rigid perspectives around us. Thus, we hypothesized a relation between forms of social rigidity, including (socio-cognitive polarization, a factor capturing conservative political ideology, absolutism/intolerance of ambiguity, and xenophobia), believing in bullshit (i.e., overestimating pseudo-profound statements), overclaiming (tendency to self-enhance) and cognitive rigidity (problem solving). Our results showed four latent profiles of social rigidity performance on problem solving tasks. Specifically, those low in socio-cognitive polarization, bullshit, and overclaiming (i.e., less rigid) performed the best on problem solving. Thus, we conclude that social and cognitive rigidity may share an underlying socio-cognitive construct, wherein those who are more socially rigid are also more likely to be also cognitively rigid when processing non-political information.
Independent Assessment of Global Temperature Rise Based Upon Approved Algorithms
Authors: GERSCHULTZ James
Published: June 2022

This is not for a pre-submission inquiry but is provided at your request. This Article describes the total derivation process used for the determination of estimated global temperature increases based upon three prescribed emission reduction pathways. Those pathways were selected to meet the 1.5 C to 2.0 C goals of the Paris Climate Agreement. The derivation includes the methods published in two papers on the estimation of carbon sink values, and the calculation of radiative forcing based upon the atmospheric concentrations of CO2, CH4 and N2O. A new climate sensitivity factor is also derived based upon anomalies in the past temperature profile. Lastly, the reasons for the large differences between this Article and the various Reports from the IPCC, UNEP and CAT are fully explained.
This new assessment shows that the 1.5 C goal can be met by pursuing a linear reduction pathway of 0.6 GtCO2 per year from 40 Gt in 2020 to 12.4 Gt in 2066. Similarly, a 1.7 C goal can be met in 2094 by following a reduction pathway of 0.4 Gt per year to 10.0 Gt at net zero.
Prognostic value of lymph node density on Cancer Staging System for non-metastatic gastric cancer: a population-based analysis of SEER database
Authors: Liu Yuhua , Cui Hao , Xu Xinxin , Liang Wenquan
Published: June 2022

Background
Accurate tumor staging is the cornerstone of tumor treatment. Current tumor staging system for gastric cancer (GC) is based on regional positive lymph nodes while ignoring the total number of examined lymph nodes. We aim to assess the prognostic value of lymph node density (LND), the ratio of positive nodes to the total number examined nodes, in non-metastatic GC.
Methods
Clinical information of patients with histologically confirmed GC and without distal metastasis was identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-Tile software was used to identify the ideal prognosis-related cutoff point for LND. The prognostic value of LND on cancer-specific survival (CSS) and overall survival (OS) was assessed in Cox regression models. Subgroup analysis stratified by LND was performed on current lymph node staging system to further explore the interaction between LND and current lymph node staging system.
Results
A total of 4281 participants were identified from the SEER database for the final analysis. The optimal prognosis-related cutoff values of LND were calculated as 0.1 and 0.4, and LND was divided into three levels. The higher level of LND was associated with worse CSS and OS in GC patients. Compared to patients with the lower level of LND, those with the middle and higher level of LND had 2.43 (HR = 2.43, 95% CI 2.09–2.84, P < 0.001) and 4.69 (HR = 4.69, 95% CI 4.02–5.48, P < 0.001) folds increase in mortality in CSS, respectively. Similar results were found in the evaluation of OS in GC patients. Subgroup analysis stratified by LND also found that patients in the same current lymph node stage still had different prognosis due to the different LND levels after adjustment for other prognosis-related covariates (all P values < 0.001).
Conclusion
LND is an independent prognostic factor for non-metastatic GC. In the current lymph node staging system, LND has potential value in further accurately classifying non-metastatic GC patients.
Radiomic features derived from [18F]FET or [18F]GE-180 PET images of gliomas – does feature harmonization facilitate data pooling?
Authors: Zounek Adrian Jun , Albert Nathalie Lisa , Holzgreve Adrien , Unterrainer Marcus , Brosch-Lenz Julia , Lindner Simon , Bollenbacher Andreas , Boening Guido , Rupprecht Rainer , Brendel Matthias , von Baumgarten Louisa , Tonn Joerg-Christian , Bartenstein Peter , Ziegler Sibylle , Kaiser Lena
Published: June 2022

Purpose

Large datasets are required to ensure reliable non-invasive glioma assessment with radiomics-based machine learning methods. This can often only be achieved by pooling images from different centers. Moreover, trained models should perform with high accuracy when applied to data from different centers. In this study, the impact of reconstruction settings and segmentation methods on radiomic features derived from amino acid and TSPO PET images of glioma patients was examined. Additionally, the ability to model and thus reduce feature differences was investigated.

Methods

[ 18 F]FET and [ 18 F]GE-180 PET data were acquired from 19 glioma patients. For each acquisition, 10 reconstruction settings and 9 segmentation methods were included to emulate multicentric data. Statistical robustness measures were calculated before and after ComBat harmonization. Differences between features due to setting variations were assessed using Friedman test, coefficient of variation (CV) and inter-rater reliability measures, including intraclass and Spearman’s rank correlation coefficients and Fleiss’ Kappa.

Results

According to Friedman analyses, most features (> 60%) showed significant differences. Yet, CV and inter-rater reliability measures indicated higher robustness. ComBat resulted in almost complete harmonization (> 87%) according to Friedman test and little to no improvement according to CV and inter-rater reliability measures. [ 18 F]GE-180 features displayed higher sensitivity to reconstruction settings than [ 18 F]FET features.

Conclusions

According to Friedman test, feature distributions could be successfully aligned using ComBat. However, depending on settings, changes in patient ranks were observed for some features and could not be eliminated by harmonization. Thus, for clinical utilization it is recommended to exclude affected features.
A Multi-Rail Structure in the Cell Envelope for the Bacteroidetes Gliding Machinery
Authors: Shibata Satoshi , Tahara Yuhei O. , Katayama Eisaku , Kawamoto Akihiro , Kato Takayuki , Zhu Yongtao , Nakane Daisuke , Namba Keiichi , Miyata Makoto , McBride Mark J. , Nakayama Koji
Published: June 2022

Many bacteria belonging to the phylum Bacteroidetes move on solid surfaces, which is called gliding motility. In our previous study with the Bacteroidetes gliding bacterium Flavobacterium johnsoniae, we proposed a helical loop track model, where adhesive SprB filaments are propelled along a left-handed closed helical loop on the cell surface. Attachment of SprB to the substratum results in cell movement. In this study, we observed the gliding cell rotating counterclockwise about its axis when viewed from the rear to the advancing direction of the cell, which was consistent with the helical loop track model. Total internal reflection fluorescence microscopy of SprB on a gliding cell revealed that one labeled SprB focus sometimes overtook and passed another SprB focus that was moving in the same direction, suggesting the presence of multiple lanes in the helical loop track. Several electron microscopic analyses revealed the presence of a multi-rail structure underneath the outer membrane, which was associated with SprB filaments and contained GldJ protein. A similar structure was observed in the distantly related marine gliding Bacteroidetes Saprospira grandis. These results provide new insights into the mechanism of Bacteroidetes gliding motility, in which the SprB filaments are propelled along the multi-rails underneath the outer membrane.
Analysis of the Change of Productive Matrix of Fossil Fuels by Biofuel in Ecuador
Authors: Nevárez Eddie Zambrano , Murillo Sandra Peña , Correa William
Published: June 2022

The search for energy for humanity’s various activities led to the discovery of fossil fuels such as coal, oil, and natural gas. Today, fossil fuels provide 85% of the energy used worldwide. The use of fossil fuels causes environmental damage that has become more noticeable in recent decades. For this purpose, information is compiled through a bibliographic review of reliable sources such as Springer, Scielo, and other documentary sources, highlighting the advantages and disadvantages of a change in the productive matrix from fossil fuels to biofuels in Latin America. It is concluded that a significant investment must be made to make a difference in the abundant matrix; however, there is a great variety of raw materials in the Latin American area to obtain biofuels, and the necessary technology to process them is not available.