bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of Missing Segments in Well Data History Using Data Analytics
Authors: Li Yuanjun , Horne Roland , Al Shmakhy Ahmed , Felix Menchaca Tania
Published: December 2021

The problem of missing data is a frequent occurrence in well production history records. Due to network outage, facility maintenance or equipment failure, the time series production data measured from surface and downhole gauges can be intermittent. The fragmentary data are an obstacle for reservoir management. The incomplete dataset is commonly simplified by omitting all observations with missing values, which will lead to significant information loss. Thus, to fill the missing data gaps, in this study, we developed and tested several missing data imputation approaches using machine learning and deep learning methods.

Traditional data imputation methods such as interpolation and counting most frequent values can introduce bias to the data as the correlations between features are not considered. Thus, in this study, we investigated several multivariate imputation algorithms that use the entire set of available data streams to estimate the missing values. The methods use a full suite of well measurements, including wellhead and downhole pressures, oil, water and gas flow rates, surface and downhole temperatures, choke settings, etc. Any parameter that has gaps in its recorded history can be imputed from the other available data streams.

The models were tested on both synthetic and real datasets from operating Norwegian and Abu Dhabi reservoirs. Based on the characteristics of the field data, we introduced different types of continuous missing distributions, which are the combinations of single-multiple missing sections in a long-short time span, to the complete dataset. We observed that as the missing time span expands, the stability of the more successful methods can be kept to a threshold of 30% of the entire dataset. In addition, for a single missing section over a shorter period, which could represent a weather perturbation, most methods we tried were able to achieve high imputation accuracy. In the case of multiple missing sections over a longer time span, which is typical of gauge failures, other methods were better candidates to capture the overall correlation in the multivariate dataset.

Most missing data problems addressed in our industry focus on single feature imputation. In this study, we developed an efficient procedure that enables fast reconstruction of the entire production dataset with multiple missing sections in different variables. Ultimately, the complete information can support the reservoir history matching process, production allocation, and develop models for reservoir performance prediction.
Core-to-Field-Scale Simulations of Polymer Viscoelastic Effect on Oil Recovery Using the Extended Viscoelastic Model
Authors: Zeynalli Mursal , Al-Shalabi Emad W. , AlAmeri Waleed
Published: December 2021

Being one of the most commonly used chemical EOR methods, polymer flooding can substantially improve both macroscopic and microscopic recovery efficiencies by sweeping bypassed oil and mobilizing residual oil, respectively. However, a proper estimation of incremental oil to polymer flooding requires an accurate prediction of the complex rheological response of polymers. In this paper, a novel viscoelastic model that comprehensively analyzes the polymer rheology in porous media is used in a reservoir simulator to predict the recovery efficiency to polymer flooding at both core- and field-scales. The extended viscoelastic model can capture polymer Newtonian and non-Newtonian behavior, as well as mechanical degradation that may take place at ultimate shear rates. The rheological model was implemented in an open- source reservoir simulator. In addition, the effect of polymer viscoelasticity on displacement efficiency was also captured through trapping number. The calculation of trapping number and corresponding residual-phase saturation was verified against a commercial simulator.

Core-scale tertiary polymer flooding predictions revealed the positive effect of injection rate and polymer concentration on oil displacement efficiency. It was found that high polymer concentration (>2000 ppm) is needed to displace residual oil at reservoir rate as opposed to near injector well rate. On the other hand, field-scale predictions of polymer flooding were performed in a quarter 5-spot well pattern, using rock and fluid properties representing the Middle East carbonate reservoirs. The field-simulation studies showed that tertiary polymer flooding might improve both volumetric sweep efficiency and displacement efficiency. For this case study, incremental oil recovery by polymer flooding is estimated at around 11 %OOIP, which includes about 4 %OOIP residual oil mobilized by viscoelastic polymers. Furthermore, the effect of different parameters on the polymer flooding efficiency was investigated through sensitivity analysis. This study provides more insight into the robustness of the extended viscoelastic model as well as its effect on polymer injectivity and related oil recovery at both core- and field-scales. The proposed polymer viscoelastic model can be easily implemented into any commercial reservoir simulator for representative field-scale predictions of polymer flooding.
Age Doesn't Matter: Digitizing the as-is Condition of Brownfield Assets is Part of a Leaner & Greener Future
Authors: Tedstone Lee
Published: December 2021

The energy sector is facing more challenges than ever before – from the impacts of the pandemic on already low margins, to Environmental, Social and Governance pressures mounting to gain investment and attract skilled workers in a competitive market. Over past year, the oil and gas sector has accelerated a critical path to digital transformation, paving its way to a more agile, greener future.

Data-sharing and collaboration enabled through the Digital Twin helps companies drive efficiency, which in turn creates opportunities to improve sustainability performance, even on legacy assets. This presentation will demonstrate how moving to Digital Twin technology is a viable brownfield solution to many of the industries pressing challenges today. It will also make the business case for how digitalization and digital twin connectivity are not only possible on a brownfield asset but also, why it is critical to meet the needs of the plant of the future.
Underwater Inspection Using ROV
Authors: Elshahawy Mahmoud Ahmed , Younes Helmy Abdel Wahab , Al Hamlawi Imad
Published: December 2021

ADNOC Drilling operates a growing fleet of 22 jack up units. These units require various inspections and tests to ensure that their integrity is maintained while conducting the drilling operations. One of these inspections is the underwater inspection which is required to be carried out twice every 5 years. Traditionally, this inspection is carried out by divers at the shipyard where it is safe for divers to carry out cleaning, visual inspections and NDT of structural welds.

Moving the rig to a drydock or a shipyard is a costly and involves a lot of activities related to safety in addition to the out of service time. Loss of revenue is experienced while the rig is out of service, as well as costs associated to the survey, shipyard costs, vessel costs etc. all combining to create an expensive inspection process.

ADNOC Drilling Marine and Group Technology adapted a new method for performing the full scope of the underwater inspection offshore using small remotely operated vehicles (ROV), most of the scope is carried out while the rig remains in full operation (while drilling).
Promotive Selectivity to C2-C3 Polyols From Alkaline Cellulose Hydrogenated by Ionic Liquid-stablized Ru Nanoparticles
Authors: Liu Mingrui , Wang Hua
Published: December 2021

Alkaline cellulose hydrogenolysis on metal catalyst was an effective way to get C2~C3 polyols. The alkaline cellulose was obtained by treating cellulose with 4 wt% NaOH solution. Ionic liquid-stablized Ru nanoparticles were prepared by reducing metal salt in ionic liquid. The SEM results indicate that the amorphous part of alkaline cellulose is helpful for getting the catalyst into the cavities to have a further hydrogenation reaction. When hydrogenolysis of alkaline cellulose over Ru/[Bmim]BF4 nanoparticles was conducted at 433 K, 63.78% of the substrate was converted with glycerol, 1,2-propanediol and ethylene glycol as main products of which selectivity was up to 58.91 %, whereas the conversion rate over Ru/C catalyst of alkaline cellulose was 59.23 % and only 26.11 % C2~C3 polyols were detected. Moreover, if the ionic liquid-stablized Ru nanoparticles were doped with 53.7 % Ni, the selectivity of C2~C3 polyols was promoted to 65.07 %. These results suggested the advantages of the ionic liquid-stablized Ru nanoparticles, especially doping with Ni, have potentials for promotive selectivity to C2~C3 alcohols. Put forward the plausible mechanism finally.
Heavy Metal Contamination of Urban Mangrove Sediments and Their Environmental Significance in the Zhanjiang Bay
Authors: Zhou Xun , Wang Yao-Ping , Gao Yuan , Xia Jia , Wang Sibo , Song Zhiguang
Published: December 2021

Urban mangroves can be used to measure the impact of human activities on the urban ecological environment because mangroves are sensitive to human activities. However, studies on the evaluation of heavy metal elements in urban mangroves are still limited. Consequently, this study selected the urban mangroves in a central commercial area of Zhanjiang Bay as a case study to investigate the content and distribution of the heavy metal elements in mangrove sediments. Combined with the results of elemental analysis, grain size analysis, risk level, influencing factors, and sources of heavy metal pollution in the surficial sediments of the mangroves in the study area were evaluated based on mathematical models and multivariate statistical analysis. The results show that (1) concentration of heavy metals: V> Pb> Cu> Ni> As> Co> Cd> Hg; (2) the content of the eight heavy metal elements has a significant positive correlation with total organic carbon (TOC) and total nitrogen (TN) values, likely as a result of adsorption, complexation, or precipitation of heavy metals by organic matter in the sediments; (3) the mangrove sediments in the study area are affected by heavy metal pollution, among which Cd pollution is the heaviest, followed by Hg pollution; (4) comprehensive analyses of multiple heavy metals using Potential Ecological Risk Index shows that the risk level of the study area is slight to very strong ecological risk; (5) the heavy metals in the study area are mainly derived from human activities such as urban domestic sewage, transportation, and ship pollution.
The Persistence of Natural SARS-CoV-2 Antibodies 12 Months Post COVID-19, a Prospective Cohort Study.
Authors: Jurgens F. , Hogema B. , Siegerink S. , Samwel L. , Gils R. van , Albers S. , Pettai F. , Laar T. van , Molier M. , Thiesbrummel H. , Bresser P. , Brinkman K.
Published: December 2021

Background: It is unknown how long SARS-CoV-2 antibodies persist after COVID-19. The natural course of anti-SARS-CoV-2 antibodies was analyzed in a large post-COVID-19 cohort, until 12 months post-infection. Methods: The total antibodies SARS-CoV-2 (IgM and IgG) were tested in a cohort of patients with different COVID-19 disease severity sampled at 4 timepoints up to 12 months post COVID-19. In 23 randomly selected patients, the antibody isotypes: anti-spike IgM, IgA and IgG and anti-nucleocapsid IgG were analysed. Results: In total 152/153 patients (99%) tested positive for total anti-SARS-CoV-2 after 12 months of COVID-19; 3 patients tested positive at 8 to 10 months post infection just before vaccination. The SARS-CoV-2 antibody subclasses anti-nucleocapsid IgG, anti-spike IgG and IgA were all still detectable after 12 months. Anti-spike IgM waned after 12 months in the majority of patients.Conclusion: IgG and IgA antibodies against SARS-CoV-2 persisted 12 months post-COVID-19.
A Comparison of mRNA Sequencing (RNA-Seq) Library Preparation Methods for Transcriptome Analysis
Authors: Ura Hiroki , Togi Sumihito , Niida Yo
Published: December 2021

Background
mRNA sequencing is a powerful technique, which is used to investigate the transcriptome status of a gene of interest, such as its transcription level and splicing variants. Presently, several RNA sequencing (RNA-Seq) methods have been developed; however, the relative advantage of each method has remained unknown. Here we used three commercially available RNA-Seq library preparation kits; the traditional method (TruSeq), in addition to full-length double-stranded cDNA methods (SMARTer and TeloPrime) to investigate the advantages and disadvantages of these three approaches in transcriptome analysis.
Results
We observed that the number of expressed genes detected from the TeloPrime sequencing method was fewer than that obtained using the TruSeq and SMARTer. We also observed that the expression patterns between TruSeq and SMARTer correlated strongly. Alternatively, SMARTer and TeloPrime methods underestimated the expression of relatively long transcripts. Moreover, genes having low expression levels were undetected stochastically regardless of any three methods used. Furthermore, although TeloPrime detected a significantly higher proportion at the transcription start site (TSS), its coverage of the gene body was not uniform. SMARTer is proposed to be yielded for nonspecific genomic DNA amplification. In contrast, the detected splicing event number was highest in the TruSeq. The percent spliced in index (PSI) of the three methods was highly correlated.
Conclusions
TruSeq detected transcripts and splicing events better than the other methods and measured expression levels of genes, in addition to splicing events accurately. However, although detected transcripts and splicing events in TeloPrime were fewer, the coverage at TSS was highest. Additionally, SMARTer was better than TeloPrime among the understudied full-length double-stranded cDNA methods. In conclusion, for short-read sequencing, TruSeq has relative advantages for use in transcriptome analysis.
Generation of Dystrophin Short Product-Specific Tag-Insertion Mouse: Distinct Dp71 Glycoprotein Complexes at Inhibitory Postsynapse and Glia Limitans
Authors: Fujimoto Takahiro , Yaoi Takeshi , Nakano Kenta , Arai Tetsuya , Okamura Tadashi , Itoh Kyoko
Published: December 2021

Duchenne muscular dystrophy (DMD), the most severe form of dystrophinopathies, is a fatal X-linked recessive neuromuscular disorder characterized by progressive muscle degeneration and various extents of intellectual disabilities. Physiological and pathological roles of the responsible gene, dystrophin, in the brain remain elusive due to the presence of multiple dystrophin products, mainly full-length dystrophin, Dp427, and the short product, Dp71. In this study, we generated a Dp71-specific hemagglutinin (HA) peptide tag-insertion mice to enable specific detection of intrinsic Dp71 expression by anti-HA tag antibodies. Immunohistochemical detections in the transgenic mice demonstrated Dp71 expression not only at the blood-brain barrier, where astrocytic endfeet surround the microvessels, but also at the inhibitory postsynapse of hippocampal dentate granule neurons. Interestingly, hippocampal cornu ammonis (CA)1 pyramidal neurons were negative for Dp71 although Dp427 detected by anti-dystrophin antibody was clearly present at the inhibitory postsynapse, suggesting cell-type dependent dystrophin expressions. Precise examination using the primary hippocampal culture validated exclusive localization of Dp71 at the inhibitory postsynaptic compartment but not at the excitatory synapse in neurons. We further performed interactome analysis and found that Dp71 formed distinct molecular complexes, i.e. synapse-associated Dp71 interacted with dystroglycan (Dg) and dystrobrevinb (Dtnb) whereas glia-associated Dp71 did with Dg and dystrobrevina (Dtna). Thus, our data indicates that Dp71 and its binding partners are relevant to the inhibitory postsynaptic function of hippocampal granule neurons and the novel Dp71-transgenic mouse provides a valuable tool to understand precise physiological expressions and functions of Dp71 and its interaction proteins in vivo and in vitro.
Systematic Evaluation of the Safety and Therapeutic Effects of Para-aortic Lymphadenectomy for Advanced Gastric Cancer: a Systematic Review and Meta-analysis
Authors: Ge Jie , Liao Xiaofeng , Tang Mimi , Yang Zhiyun , Zhao Tingyu , Liu Heli
Published: December 2021

Background: At present, there is still no definite conclusion on whether advanced gastric cancer requires additional para-aortic nodes dissection (PAND). The purpose of this study is an attempt to provide significant data to guide clinical decision-making. Methods: The literature was searched using the terms of gastric cancer, para-aortic lymphadenectomy and D2+ lymphadenectomy and D3 lymphadenectomy. The databases searched included PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Database for Chinese Technical Periodicals, and China Biology Medicine disc. RevMan 5.3 software was used for the meta-analysis.Results: In total, 20 studies were included, consisting of 6 randomized controlled trials (RCT) and 14 non-randomized controlled trials (nRCT). These studies involved 5643 patients. The meta-analysis showed the following results: (1) compared with group D2 (D2 lymphadenectomy), the operating time in group D2+ (D2+ lymphadenectomy) was longer [mean difference (MD)=99.45 min, 95% confidence interval (CI) (48.93, 149.97), P<0.001], with more intra-operative blood loss [MD=262.14 mL, 95%CI (165.21, 359.07), P<0.001]; (2) there were no significant differences in five-year overall survival [HR=1.09, 95%CI (0.95, 1.25), P=0.22] and post-operative mortality [RR=0.96, 95%CI (0.59, 1.57), P=0.88] between the two groups; (3) the rate of post-operative complication in group D2+ was higher than that in group D2 [RR=1.42, 95%CI (1.11, 1.81), P<0.001]. Conclusions: It is noteworthy that the combination of perioperative chemotherapy and D2+ surgery, particularly D2+ PAND, shows some survival advantages for specific patients. Although prophylactic D2+ surgery is not recommended as it increases postoperative complications and does not improve long-term survival in patients with advanced gastric cancer.
Research on Security Risk Assessment Mechanism of Important Event Based on Multi-Source Data
Authors: Wang Qilei
Published: December 2021

In order to effectively assess all types of security risks in the important event, the important decision-making basis for security risk warning and emergency management of important event is provided by analyzing the coupling relationship and evolution mechanism between various risks. The criminal causes, management defects, security and emergency system construction are analyzed from the possibility of accidents and risks. The multi-source data risk assessment system based on five subsystems and its index set of human factors, management factors, site factors, event factors and audit factors are proposed. The weight of each index in the assessment system is determined by the method of information entropy, and then the risk grade of important event is determined according to the weight calculation function and the improved fuzzy matter element model. The verification with an example shows that: the risk assessment model is optimized by combining entropy weight with fuzzy matter-element model，the influence of weight data extreme value was weakened，the qualitative description and quantitative analysis of multi-source data could be combined，and the subjective error was reduced. The risk grade of important event is reasonably evaluated, and the assessment effect is basically consistent with the expert inspection analysis, which shows that the method had certain application value.
Integrated Omics Approach to Unveil Antifungal Bacterial Polyynes as acetyl-CoA Acetyltransferase Inhibitors
Authors: Lin Ching-Chih , Hoo Sin Yong , Ma Li-Ting , Lin Chih , Huang Kai-Fa , Ho Ying-Ning , Sun Chi-Hui , Lee Han-Jung , Chen Pi-Yu , Shu Lin-Jie , Wang Bo-Wei , Hsu Wei-Chen , Ko Tzu-Ping , Yang Yu-Liang
Published: December 2021

Bacterial polyynes are highly active natural products with a broad spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. By integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), in the biosynthesis gene cluster of antifungal polyynes (massilin A 1, massilin B 2, collimonin C 3, and collimonin D 4) of Massilia sp. YMA4. Crystallographic analysis indicated that bacterial polyynes serve as covalent inhibitors of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited cell viability of Candida albicans by targeting ERG10, the homolog of MasL. Thus, this study demonstrated that acetyl-CoA acetyltransferase is a potential target for the development of antifungal agents.
Phylogenetic Analysis of Canonical/non-canonical Dicers and RNase III Containing Proteins in Fungal Kingdom
Authors: Wu Jiayao , Choi Jaeyoung , Asiegbu Fred O. , Lee Yong-Hwan
Published: December 2021

Background: Dicers were member of RNase III containing proteins family with important RNAi function in eukaryotes. In this study, we tried to address the potential distribution of all RNase III containing proteins among the fungal kingdom, as well as their possible evolution paths including canonical Dicers, non-canonical Dicers and non-canonical Dicer-like proteins.Result: RNase III containing proteins were collected from 83 species, and discussed the features and possible evolution pathways of RNase III containing protein family. In general, RNase III containing protein family could be characterized into three different groups as canonical Dicer, non-canonical Dicers and Dicer-like proteins based on their domain structures and functional annotation. Most eukaryotes obtained multiple RNase III protein of different types at the same time, including canonical Dicers and Dicer-like proteins. Phylogenetic analysis showed that the RNase III domains were different between canonical Dicers and Dicer-like proteins, for the first and second RNase III domains had different insertions in different regions with certain extent of conservation. Regardless of the types, RNA-binging domains in RNase III protein family were very similar to each other. Furthermore, short insertions were found in different positions from the first and second RNase III domains in canonical Dicers separately. RNA-binging domains from all types were quite similar to each other.Conclusion: RNase III containing proteins in general widely exist in eukaryotes with minor divergent among different types and groups. Suggested by the RNase III and RDB domains, the canonical/non-canonical Dicers Dicer-like proteins might share the same ancestor and have evolved from separate mild-types through different directions.
Comparative Transcriptome Analysis of Rice Cultivars Resistant and Susceptible to Rhizoctonia Solani AG1-IA
Authors: Wang Yan , Luo Hang , Wang Haining , Xiang Zongjing , Wei Songhong , Zheng Wenjing
Published: December 2021

Background: Rice sheath blight, which is caused by Rhizoctonia solani, is the most destructive disease affecting rice production, but the resistance mechanism to this pathogen has not been fully elucidated. Results: In this study, we selected two rice cultivars based on their resistance to the pathogen and analyzed and compared the transcriptomic profiles of two cultivars, the moderately resistant variety Gangyuan8 and the highly susceptible variety Yanfeng47, at different time points after inoculation. The comparative transcriptome profiling showed that the expression of related genes gradually increased after pathogen inoculation. The number of differentially expressed genes (DEGs) in Yanfeng47 was higher than that in Gangyuan8, and this result revealed that Yanfeng47 was more susceptible to fungal attack. At the early stage (24 and 48 h), the accumulation of resistance genes and a resistance metabolism occurred earlier in Ganguan8 than in Yanfeng47, and the resistance enrichment entries were more abundant in Ganguan8 than in Yanfeng47. Conclusions: Based on the GO and KEGG enrichment analyses at five infection stages, we concluded that phenylalanine metabolism and the jasmonic acid pathway play a crucial role in the resistance of rice to sheath blight. Through a comparative transcriptome analysis, we preliminarily analyzed the molecular mechanism responsible for resistance to sheath blight in rice, and the results lay the foundation for the development of gene mining and functional research on rice resistance to sheath blight.
Subglacial sedimentary basins focus key vulnerabilities of the Antarctic ice-sheet
Authors: Li Lu , Aitken Alan , Lindsay Mark , Kulessa Bernd
Published: December 2021

Antarctica preserves Earth’s largest ice sheet which, in response to climate warming, may lose ice mass and raise sea level by several metres. The ice-sheet bed exerts critical controls on dynamic mass loss through feedbacks between water and heat fluxes, topographic forcing and basal sliding. Here we show that through hydrogeological processes, sedimentary basins amplify critical feedbacks that are known to impact ice-sheet retreat dynamics. We create a high-resolution subglacial bedrock classification for Antarctica by applying a supervised machine learning method to geophysical data, revealing the distribution of sedimentary basins. Sedimentary basins are found in the upper reaches of Antarctica’s most rapidly changing ice streams, including Thwaites and Pine Island Glaciers. Hydro-mechanical numerical modelling reveals that where sedimentary basins exist, water discharge rate scales with the rate of ice unloading and the resulting hydrological instabilities are likely to amplify further retreat and unloading. These results indicate that the presence of a sedimentary bed in the catchment focuses instabilities that increase the vulnerability of the ice streams to rapid retreat and enhanced dynamic mass loss.
Real Life Comparison of Afatinib and Erlotinib in Non-small Cell Lung Cancer With Rare EGFR Exon 18 and Exon 20 Mutations: a Turkish Oncology Group (TOG) Study.
Authors: Gürsoy Pınar , Tatlı Ali Murat , Erdem Dilek , Goker Erdem , Çelik Emir , Demirci Nebi Serkan , Sakin Abdullah , Atçı Muhammed Mustafa , Bayram Ertuğrul , Telli Tuğba Akın , Bilgin Burak , Bilici Ahmet , Akagündüz Baran , Ballı Sevinç , Demirkazık Ahmet , Selcukbiricik Fatıh , Menekşe Serkan , Cavdar Eyyup , Öztürk Akın , Bekmez Esma Türkmen , Turhal Serdal , Kılıçkap Saadettin , Yıldırım Hasan Çağrı , Oyan Başak , Aksoy Asude , TURKOZ Fatma Paksoy , Kut Engin , Katgı Nuran , Sakalar Teoman , Akyol Murat , Ellez Halil İbrahim , Topcu Atakan , Erdoğan Atike Pınar , Pilancı Kezban Nur , Hedem Engin , Arak Hacı , Akdeniz Nadiye , Alan Özkan , Yapar Burcu , Nart Deniz , Yumuk Perran Fulden
Published: December 2021

Objectives To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC).Materials and Methods We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study.Results EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p=0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p=0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p=0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p=0.323).Conclusion In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options.
Uterine Factors Modify the Association Between Embryo Transfer Depth and Clinical Pregnancy: A Retrospective Study in 7849 Fresh Transfer In Vitro Fertilization Cycles
Authors: Sun Xiaohua , Cai Jiali , Liu Lanlan , Chen Haixiao , Jiang Xiaoming , Ren Jianzhi
Published: December 2021

The embryo position is supposed to affect implantation following embryo transfer. However, embryo dislodging caused by uterine contraction may occurred after transfer. The retrospective study was to investigated whether the factors associated with uterine contractility, such as endometrial thickness and progesterone elevation, affect the association between embryo position and implantation. A total of 7849 fresh transfer cycles on conventional stimulation in a single IVF centre during the period 2013–2015 was reviewed. Patients were categorized according to quartiles of embryo-fundus distance (≤9, 9.1-11, 11.1-14, ≥1.4 mm, respectively). Adjusted for confounding factors, the odds ratio (OR) (95%CI) for clinical pregnancy was 0.90 (0.79-1.02), 0.86 (0.74-0.99) and 0.70 (0.60-0.82) respectively in quartiles 2 through 4, comparing with quartile 1. However, ORs were significantly increased when endometrial thickness was < 8 mm. The ORs comparing quartiles 2 through 4 with quartile 1 increased 1.96 (95%: 1.33-2.90), 1.20 (95%: 0.78-1.87) and 1.98 (95%: 1.20-3.26) fold respectively in cycles with an endometrial thickness < 8 mm than in cycles with a normal endometrial thickness (8-11 mm). Elevated progesterone on the day of hCG and blastocyst stage transfer reduced the ORs. Our data suggested an interaction between patient characteristics and embryo transfer techniques.
Short-term, Low-Dose Etoposide in Refractory Adult-Onset Still’s Disease-Associated Macrophage Activation Syndrome, a Case Series Study
Authors: Wang Ran , Li Ting , Ye Shuang , Lv Liangjin , Chen Sheng , Wang Xiaodong , Bao Chun-de , Fu Qiong
Published: December 2021

Objectives:In this study, we modified the classical regimen of the hemophagocytic lymphohistiocytosis-04 protocol and evaluated the efficacy and safety of short-term, low-dose etoposide in patients with refractory macrophage activation syndrome (MAS) associated with adult-onset Still’s disease (AOSD).Methods:A total of 17 patients with refractory AOSD-associated MAS were enrolled and received short-term, low-dose etoposide (100 mg twice a week for four times). Another 11 patients, who were not treated with etoposide, were included as historical controls. Patient information, such as clinical manifestations, laboratory results, treatments, and short-term prognosis, were recorded and analyzed.Results:In this case series, 88.24% of the patients with MAS who were treated with short-term, low-dose etoposide had a favorable response in 3 weeks, which was significantly higher (p = 0.017) than that in the patients with MAS who were treated without etoposide (45.45%). The 90-day survival rate after the onset of MAS was significantly higher (p = 0.0029) among the patients in the short-term etoposide group (16/17, 94.12%) than in the control group (5/11, 45.45%). Conclusion:The regimen of short-term (2-week), low-dose etoposide was highly effective in the treatment for patients with refractory AOSD associated MAS with an acceptable safety profile.
Ropivacaine Inhibits Wound Healing by Suppressing the Proliferation and Migration of Keratinocytes via the PI3K/Akt/mTOR Pathway
Authors: Wu Xiaoyang , Sun Quanyu , He Simeng , Wu Ya , Du Shihan , Gong Lirong , Yu Jianbo , Guo Haifeng
Published: December 2021

Background
After surgery, millions of people suffer from delayed healing or wound dehiscence with subsequent severe complications, even death. Previous studies have reported that ropivacaine exhibits anti-proliferative and anti-migratory activities on numerous cells. Whether ropivacaine is able to influence the proliferation and migration of keratinocytes is still unclear. This study aimed to investigate the effect of ropivacaine and migration on keratinocytes and its underlying molecular mechanism.
Methods
Adult male Sprague-Dawley rats were allocated to establish wound healing models with or without 0.75% ropivacaine treatment and assessed the epidermal thickness by HE staining. HaCaT cells were cultured to evaluate the effect of ropivacaine on wound healing. The cell proliferation, apoptosis status and migration were detected in vitro. Moreover, western blotting was used to examine expression related with PI3K/AKT/mTOR signaling pathways for molecular studies and the changes in inflammatory factors (IL-6, IL-10, TNF-α) were detected by ELISA.
Results
In the present study, we found that ropivacaine delayed wound closure in vivo. In vitro experiments, it was demonstrated that ropivacaine significantly inhibited the proliferation and migration of HaCaT cells via the suppression of PI3K/Akt/mTOR signaling pathway. Activation of PI3K/Akt/mTOR signaling pathway reversed the effects of ropivacaine on the proliferation and migration of HaCaT cells. Furthermore, ropivacaine contributed to the release of pro-inflammatory cytokines (IL-6 and TNF-α) and inhibited the secretion of anti-inflammatory cytokines of keratinocytes (IL-10).
Conclusions
Our research demonstrated that ropivacaine treatment showed a more decreased wound closure rate. Mechanistically, we found that ropivacaine suppressed the proliferation and migration of keratinocytes and altered the expression of cytokines by inhibiting PI3K/AKT/mTOR pathway.
Robust Probabilistic Discriminative Model Prediction Tracker via Improved Model Update Strategy
Authors: Chen Shaolong , Qiu Changzhen , Huang Yurong , Zhang Zhiyong
Published: December 2021

In the visual object tracking, the tracking algorithm based on discriminative model prediction have shown favorable performance in recent years. Probabilistic discriminative model prediction (PrDiMP) is a typical tracker based on discriminative model prediction. The PrDiMP evaluates tracking results through output of the tracker to guide online update of the model. However, the tracker output is not always reliable, especially in the case of fast motion, occlusion or background clutter. Simply using the output of the tracker to guide the model update can easily lead to drift. In this paper, we present a robust model update strategy which can effectively integrate maximum response, multi-peaks and detector cues to guide model update of PrDiMP. Furthermore, we have analyzed the impact of different model update strategies on the performance of PrDiMP. Extensive experiments and comparisons with state-of-the-art trackers on the four benchmarks of VOT2018, VOT2019, NFS and OTB100 have proved the effectiveness and advancement of our algorithm.
Improving the Plasmid Stability by a Hok/Sok System for L-Homoserine Production in Escherichia Coli
Authors: Sun Bing-Yao , Tao Xin-Yi , Sui Hua-Lu , Wang Feng-Qing , Liu Qing-Hai , Gao Bei , Zhao Jian , Ma Yu-Shu , Liu Min , Wei Dong-Zhi
Published: December 2021

Background: The production of bioactive compounds using microbial hosts is considered a safe, cost competitive and scalable approach. However, the efficient engineering of cell factories with well stability, such as for the production of L-aspartate family amino acids and derivatives, remains an outstanding challenge.Results: In the work, the toxin/antitoxin system and genome modification strategy were used to construct a stable Escherichia coli strain for L-homoserine production. The metabolic engineering strategies were focused on the enhancement of precursors for L-homoserine synthesis, reinforcement of the NADPH generation and efflux transporters using CRISPR-Cas9 system at the genome level. To improve the plasmid stability, two strategies were explored, including construction of the aspartate-auxotrophic and hok/sok systems. Constructing the auxotrophic complementation system to maintain plasmid stability was failed herein. The plasmid stability was improved by introducing the hok/sok system, resulting in 6.1 g/L (shake flask) and 44.4 g/L (5 L fermenter) L-homoserine production of the final engineered strain SHL19 without antibiotics addition. Moreover, the hok/sok system was also used to improve the plasmid stability for ectoine production, resulting in 36.7% and 46.5% higher titer of ectoine at shake flask and 5L fermenter without antibiotics addition, respectively. Conclusion: This work provides valuable strategies to improve plasmid stability for producing L-aspartate family amino acids and derivatives and eliminate environmental concerns associated with the application of antibiotics.
Measuring adulterants in street drugs: Implementation of drug residue testing using portable mass spectrometry in a Northeastern U.S. harm reduction program, 2019-2020
Authors: Boulad Mathieu , Matsumoto Atsushi , Santelices Claudia , Stopka Thomas J.
Published: December 2021

Background: Fatal opioid overdose deaths involving illicitly manufactured fentanyl continue to escalate in the U.S. Drug checking services, as a harm reduction intervention for people who use drugs, has gained support as an effective strategy to reduce fatal overdoses. We examined implementation of drug checking services using portable devices in a syringe services program in the Northeastern U.S. Methods: Trained staff collected trace drug specimens from used paraphernalia provided by participants who requested drug checking services. All the specimens were tested using a portable mass spectrometer and sub-samples were tested for the detection of fentanyl using fentanyl testing strips. We assessed characteristics of participants who used drug checking services, self-reported types of trace specimens of substances that participants reported providing for testing, the actual mass spectrometer test results of these specimens, and agreement of the mass spectrometer and fentanyl testing strips results in detection of fentanyl and fentanyl analogues. Results: Of 155 unique participants who provided demographic information, 59% identified as male and 74.1% as White, with a mean age of 37.7 years. Based on analysis of 396 specimens tested with the portable mass spectrometer, the most common single substance detected was fentanyl (37.7%), without a trace of heroin or other adulterants, followed by methamphetamine (18.2%), and cocaine (13.6%). Fentanyl and fentanyl analogues were detected in specimens provided by participants that were reported as heroin (60.8%), cocaine (11.1%), and methamphetamine (6.7%). We found modest agreement of testing results between the mass spectrometer and fentanyl testing strips. Conclusions: Use of drug checking services within syringe services programs is in its initial test stages. Knowledge about the contents of substances purchased, and conversations between syringe services program participants and staff, have the potential to facilitate informed decisions to decrease overdose risks through engagement in harm reduction strategies. Through analysis of newly implemented drug checking services, we noted participant characteristics and dissonance between participants’ reports of the trace drug specimens submitted for testing and the actual drugs and adulterants detected by mass spectrometer results, which has implications for overdose risk, highlighting opportunities for harm reduction responses.
Low dose dexamethasone in combination with Remdesivir does not cause immune dysregulation
Authors: Kannan Kalyan Reddy , Damerla Kshiraja , Mitnala Sasikala , Vemula Venkata Krishna , P Naveen Reddy , Vishnubhotla Ravikanth , Duvvur Nageshwar Reddy
Published: December 2021

BackgroundThe administration of Remdesivir/Dexamethasone combination on T and B cell responses in patients with COVID-19 is sparse. To compare cell mediated immune response in patients treated with only Remdesivir and Remdesivir/dexamethasone combinationStudy DesignProspective, cohort studyMethodsRT-PCR positive SARS-CoV-2 patients (n=49) were enrolled. Patients not requiring O2-supplementation were on remdesivir and those requiring were on remdesivir/dexamethasone. Baseline parameters (complete blood picture, inflammatory markers), T and B cells (flow cytometry: day 5 and 30) and neutralizing antibodies (chemiluminescence: day 30) were estimated. Students “t’’ test was used to evaluate the differences.ResultsOf the 49 patients, 26 (Mean age-44.68±13.45) were treated with remdesivir and 23 (Mean age-48.33±14.76) with remdesivir/dexamethasone combination. While blood counts and immune cells increased, inflammatory markers decreased post treatment in both the groups. A significant increase in WBC (6357±981Vs10700±1363; p=0.01), absolute neutrophil counts (4578±711Vs8256±1323; p=0.01) with decrease in levels of CRP (31±7.1Vs10±4.2; p=0.01), D-Dimer (172.3±8Vs118.1±12; p=0.0005), IL6 (17.6±3.8Vs1.72±0.2; p=0.0001), CD4 cells (2681±86Vs1256±369; p=0.0003), CD8 cells (1749±88 Vs 1256±221; p=0.01) and neutralizing antibodies were seen post treatment in the combination group. Correction of hypoxia and maintenance of oxygen >95% was also noted. ConclusionRemdesivir/dexamethasone combination given to patients requiring oxygen supplementation is safe at 4-6mg/day and showed a marked decrease in inflammation and no immune dysregulation.
Parents’ and teachers’ perceptions of emotional and behavioural problems of school-going adolescents
Authors: Harikrishnan U. , Sailo Grace Lalhlupuii
Published: December 2021

Self-reported studies alone cannot be used to deduce the significance of adolescent problems. Therefore, the current study focuses on parents’ and class teachers’ perspectives of school-going adolescents’ emotional and behavioural problems. The objectives are to apprehend the prevalence of adolescent problems, comparisons on gender, school-area; and its association with socio-demographic details. A cross-sectional questionnaire-based study was conducted among 19 schools from government-private and rural-urban schools across Kollam District, Kerala. Malayalam/English version of the Strength and Difficulties Questionnaire (SDQ) was administered among a sample of 600 parents and 60 class teachers of school-going adolescents. Gender correlation with parents’ report found emotional problems (P<0.01), conduct problems (P<0.01), hyperactivity (P<0.001), peer problems (P<0.001) whereas in teachers’ report found relationship with emotional problems (P<0.05) and hyperactivity (P<0.001). Multivariate test results reveal that there is a statistically significant difference in emotional and behavioural problems of school-going adolescents based on school area (government-urban, government-rural, private-urban and private-rural). Multiple linear regression analysis on parents reports is significantly predicted with gender (P<0.01), urban-rural settings (P<0.001) and socioeconomic status (P<0.01). Teachers’ report has significantly been predicted with urban-rural settings (P<0.01) and socioeconomic status (P<0.001). Parents’ reports revealed a less overall prevalence of emotional and behavioural problems than teachers’ reports. Female adolescents tend to have more emotional problems and males were found to be more hyperactive. A significant difference was found with the school-area settings and significant association with socio-demographic details of adolescents. More attention is needed for the protection of adolescents’ mental health and fills mental health gaps in services.
Within-subjects Effects of Standardized Prosthetic Socket Modifications on Physical Function and Patient-Reported Outcomes
Authors: Anderst William , Fiedler Goeran , Onishi Kentaro , McKernan Gina , Gale Tom , Paulus Paige
Published: December 2021

• Background: Among the challenges of living with lower limb loss is the increased risk of long-term health problems that can be either attributed directly to the amputation surgery and/or prosthetic rehabilitation or indirectly to a disability-induced sedentary lifestyle. These problems are exacerbated by poorly fit prosthetic sockets. There is a knowledge gap regarding how the socket design affects in-socket mechanics, and how in-socket mechanics affect patient-reported comfort and function. The objectives of this study are: 1) to gain a better understanding of how in-socket mechanics of the residual limb in transfemoral amputees are related to patient-reported comfort and function, 2) to identify clinical tests that can streamline the socket design process, and 3) to evaluate the efficacy and cost of a novel, quantitatively informed socket optimization process.• Methods: Users of transfemoral prostheses will be asked to walk on a treadmill wearing their current socket plus 8 different check sockets with designed changes in different structural measurements that are likely to induce changes in residual limb motion, skin strain, and pressure distribution within the socket. Dynamic biplane radiography and pressure sensors will be used to measure in-socket residual limb mechanics. Patient-reported outcomes will also be collected after wearing each socket. The effects of in-socket mechanics on both physical function and patient-reported outcomes (aim 1) will be assessed using a generalized linear model. Partial correlation analysis will be used to examine the association between research grade measurements and readily available clinical measurements (aim 2). In order to compare the new quantitative design method to the Standard of Care, patient reported outcomes and cost will be compared between the two methods, utilizing the Wilcoxon Mann-Whitney non-parametric test (aim 3).• Discussion: Knowledge on how prosthetic socket modifications affect residual bone and skin biomechanics itself can be applied to devise future socket designs, and the methodology can be used to investigate and improve such designs, past and present. Apart from saving time and costs, this may result in better prosthetic socket fit for a large patient population, thus increasing their mobility, participation, and overall health-related quality of life. • Trial registration: clinicaltrials.gov: NCT05041998
Salt-Induced Damage Alleviation in Tanacetum Balsamita L. by Foliar Application of Dobogen Biofertilizer, Glucose and KNO3
Authors: Hassanpouraghdam Mohammad Bagher , Mehrabani Lamia Vojodi , Kheiri Mehdi , Chrysargyris Antonios , Tzortzakis Nikolaos
Published: December 2021

The effects of NaCl salinity stress and foliar application of KNO3, glucose and Dobogen were tested on Tanacetum balsamita. The results showed the significant interaction effects of salinity and foliar sprays on chlorophyll a, K+, Na+, Mg2+, Fe2+, Zn2+, Mn2+ and Si content, K/Na ratio and total phenolic and flavonoid contents. The highest phenolic content was acquired with 100 mM salinity and foliar spray of Dobogen and glucose, 50 mM NaCl × KNO3 application and 50 mM salinity× nonfoliar application. The highest K/Na ratio was observed in control plants and controls × KNO3 and/or Dobogen application. The greatest Si content was recorded with controls × Dobogen and KNO3 applications and no saline × no foliar control plants. Malondialdehyde, flavonoid and proline contents as well as catalase activity were influenced by the independent effects of treatments. Chlorophyll b and superoxide dismutase were affected by salinity. Total soluble solids and Ca2+ were influenced by foliar applications. Malondialdehyde and proline were the highest at 150 mM salinity. Salinity adversely affected the physiological responses of costmary. However, foliar treatments partially ameliorated the salinity effect, and the results would be advisable to the extension section and pioneer farmers.