bluuebunny/crossref_metadata_2025 huggingface dataset:
Coiled Tubing Dewaxing Operations: Case Studies in Reduced Production Wells of Northeast India
Authors: Singh Ishaan , Pathak Akash Ramesh , Kaushik Juhi , Bandyopadhyay Bholanath , Wijoseno Danny Aryo , Dehingia Madhurjya , Khound Debanuj , Medhi Ajit Kumar , Sharma Pritam
Published: June 2021

Executing interventions in wells encrusted with wax is challenging because experience with global coiled tubing (CT) dewaxing operations is limited, and equipment failure and stuck pipe risks are high. With few jobs performed worldwide, CT dewaxing (hot oil circulation with CT) operations are largely unexplored. The deviated wells in a field in northeast India pose several challenges including completely seized wellbore due to paraffin/asphaltene deposition, previous failed well cleanout attempts, very slow and low bottomhole assembly (BHA) penetration, pumping corrosive and flammable low wax crude (LWC) through CT, high chances of CT getting stuck, and pumping heated 69°C LWC through the CT. This case study delivers insights about design, safety, and operational considerations for 1.5-in. CT dewaxing and nitrogen lift operations in a subhydrostatic well in the field. The objective of this CT dewaxing and nitrogen kickoff operation was to clear the well of paraffin/asphaltene/wax to 1600 m and activate it with nitrogen, and this paper describes solutions for cleaning out and nitrogen-lifting wells with declining production due to paraffin and asphaltene deposition. One well is described in this case study, but this approach can be used perform CT intervention in similar wells.

For this case, simulations were sensitized to identify the best combination of pumping rates, CT speeds, and fluid temperature to remove deposits hindering BHA penetration. This study proposes prevention measures using appropriate grounding and procedures, which determine if the crude oil can be pumped through CT. By use of this methodology, 581 dewaxing runs have been performed in 78 wells. Extensive on-job experience and lessons learnt by performing this operation over the last 3 years bring excellent results and prevent misruns. In many cases, production has been restored from nil; several examples feature a fivefold improvement of productivity thanks to this intervention method. Optimized operational parameters such as CT speed, pumping rates, and the use of smaller outer diameter BHAs doubled operational efficiency during those operations. In addition, strict application of the recommendations prevented the occurrence of operational problems such as stuck CT, crude oil flashing, sand bridging, and equipment failure.
Advances in the Quantitative Geological Evaluation of Development Wells in Challenging Geological Targets
Authors: Austin Simon , Wang Xuandong , Ndokwu Chidi , Ajisafe Isaac , Inenemo Abdulwahab , Olare Jemine
Published: June 2021

Reservoir navigation is a common and integrated part of the drilling process to steer wells very precisely. It is a requirement for many of today's complex deviated and horizontal development wells steered through challenging and small geological targets that can be as small as two metres in size. The capability is a key enabler for the oil industry and has contributed significantly to the prolongation of the economic well being of most oil producing provinces around the world.

In order to be successful, reservoir navigation must combine advanced downhole logging while drilling (LWD) tools, telemetry of LWD data to surface in real-time, the ability to steer while drilling, fit-for purpose software applications and perhaps most important of all, skilled personnel. That said, it is currently common practice for reservoir navigation to be performed with a dataset that is restricted to a vertical ‘curtain’ section derived from the development well. This is an unnecessary restriction that is often self imposed because of the limitations of the software applications being employed. With improving computer power, it can and should be superceded in favour of a more holistic approach.

The new reservoir navigation analytical processes are all designed to be performed at speed and in real-time while drilling the reservoir, on demand, at any stage, within minutes. These enhancements quantitatively illuminate the critical financial consequences of a well's geological drilling results. These are usually greater than the economic benefits of more efficient well operations. It means well owners can now operate in an information rich environment leading to better multi-disciplined team work and improved operational decision making. The benefit is better wells that produce more hydrocarbons at lower cost.

A real data set comparing a pre-well 3D model with realistic real-time geological updates and visualisations in three dimensions demonstrates the validity of the method. The pre-well and real-time 3D models can also be utilized to generate quantitative volumetrics calculations while drilling. The workflows provide an information rich environment for operational decision making leading to better wells.
Extending Temperature Limit of HMX: A Case Study for Perforation in the Gulf of Thailand
Authors: Sirirattanachatchawan Thum , Chaiwan Phuvit , Ut-ang Pradondate , Pattarachupong Wiwat , Puttisounthorn Toon , Chotipunyo Therdpong
Published: June 2021

The current explosive limit chart using in the oil and gas industry published with unclear condition of safety factor and consequence of overexposing temperature and time, resulting in many published papers disclose the possibility of expanding the safe-operating envelope of HMX. HMX is preferable because it typically provides deeper penetration than HNS but less stability at high temperature. Therefore, this study aims to maximize use of HMX for hollow gun perforation in typical environment in the GOT.

The explosive temperature limit depends on two parameters, exposure time and temperature. The maximize use of HMX could achieve by, either ways, reducing the exposure time or extending the temperature limit line. Firstly, the operating time optimization is doable by using statistic record of the depth perforated by HNS and practical running speed together with a 20% safety margin. Secondly, expanding the temperature limit of HMX is a precise task because the HMX once exceeding the stability temperature, the perforating performance losses and explosion hazard arises due to thermal decomposition. However, this could be creditable by integrating the published explosive testing results over the current operating-envelope and applying a safety margin.

The represented operating time, counting from running in hole to tool on surface, for perforation with E-line unit in the high-temperature environment could reduce by an hour. This operating time allows the temperature limit of HMX increasing by only 7 F, which considering as insignificant. The integrating result of three published paper indicated no explosive deflagration happens if the temperature is below the "Fiasco line" – introduced by a company, however, the operating time longer than 200 hours is not incorporated. By applying safety margin, the new operating envelope of HMX in the hollow carrier proposes between the typical and the Fiasco line. Combing time optimization and the new line, the HMX temperature limit extends from 375 F to 394 F for 2.2 operating hours. This new criterion has been applied successfully since 2018; 325 m of HMX achieved perforation condition without an indication of misfire or catastrophic self-detonation, resulting in reduce 50% of HNS consumption. In conclusion, the new temperature cutoff is valid for maximizing the use of HMX with a reasonable safety margin.
Innovative Approach Lead to Best in Class Development Campaign Drilling and Sand Control Completion, Myanmar Offshore
Authors: Follett Meth , Pensook Teerapat , Piyakunkiat Nuttapon , Benjaboonyazit Veerawit , Nopsiri Noppanan
Published: June 2021

The operator relentlessly thrives for the minimum well construction cost. Continuous improvement and Innovative approach are the major drives for developing the marginal gas field, Myanmar offshore. Whereas, routine and consistent operations may mask up the operator and leave out many rooms for improvement from operation excellence during the development phase of the project life cycle.

PTTEPI successfully started up the second development campaign, Myanmar offshore in early 2016. Since then the team has brought up many ideas to continuously improve the operation and achieve milestones for both safety and performance. This paper will share the best in class for well construction of Myanmar offshore on well design, drilling engineering, rig selection, offline utilization, drilling and sand control practices and fit for purpose procedures. The performance is significantly improved on both drilling and sand control operation which results in total days per well reduction over 50% and 80% for drilling operation and sand control operation respectively.

Total days per well for drilling performance on the last platform in 2019 is reduced to 4 days per well compared to 9 days per well when the first development platform was drilled in 2013. Sand Control performance is improved further. Total days per well for Sand Control performance on the last platform in 2019 is reduced to 3.5 days per well (dual-zone completion) compared to 18 days per well when the first development platform was completed in 2013.

Recommended practices and well designs are shared as a case study of drilling and sand control operation for Myanmar offshore development. This can be a guideline for another operator to develop oil and gas field offshore Myanmar.
Towards Sustainable Economic Growth: Use of Brick Waste Powder in Oil Well Cement Applications
Authors: Chawla Tamanjot Singh , Hazra Abhinav , Raigar R. K , Lal Kishori
Published: June 2021

The construction waste generated annually in India is around 165-175 million tonnes, as per 2019 India's insights. This paper investigates the use of brick waste (B/W) as an aggregate in Oil Well cement and studies it's viability. Bricks are made from calcination of alumino-silicate clay hence they are expected to have artificial pozzolanic material. The addition of B/W significantly influences particle volume fraction, which is further elaborated in this paper.

The construction industry in India is booming. Already at 10 percent of the GDP, it has been growing at an annual rate of 10 percent over the last 10 years against the world's average of 5.5 percent per annum and the built-up area is expected to grow 5 times by 2030. This will lead to a subsequent increase in construction waste, including brick waste. As per TIFAC (Technology Information, Forecasting and Assessment Council), a Government of India agency, a new construction generates 40-60 kg of brick waste per sq. meter.
An Integrated Approach for the Modelling of Silicon Carbide Components Laser Milling Process
Authors: Leone Claudio , Genna Silvio , Tagliaferri Vincenzo
Published: June 2021

The paper deals with characterisation and modelling of laser milling process on Silicon Carbide hard ceramic. To this end, a Yb:YAG pulsed fiber laser was adopted to mill Silicon Carbide bars. Square pockets, 5x5 mm2 in plane dimension, were machined at the maximum nominal average power (30W), under different laser process parameters: pulse frequency, scan speed, hatching distance, repetitions and scanning strategy. After machining, the achieved depth and the roughness parameters were measured by way of digital microscopy and 3D surface profiling, respectively. In addition, the material removal rate was calculated as the ratio between the removed volume/process time. ANalysis Of VAriance (ANOVA) was adopted to assess the effect of the process parameters on the achieved depth, the material removal rate (MRR) and roughness parameters, while Response Surface Methodology (RSM) and Artificial Neuronal Networks (ANNs) were adopted to model the process behaviours. Results show that both RSM and ANNs fault in MRR and RSm roughness parameters modelling. Thus, an integrated approach was developed to overcome the issue; the approach is based on the use of the RSM model to obtain a hybrid Training dataset for the ANNs. The results show that the approach can allow improvement in model accuracy.
Correlation of metabolic factors with endometrial atypical hyperplasia and endometrial cancer: development and assessment of a new predictive nomogram
Authors: Zhang He , Kong Weimin , Han Chao , Liu Tingting , Li Jing , Song Dan
Published: June 2021

Purpose: This study aimed to investigate the association of metabolic factors with endometrial atypical hyperplasia and endometrial cancer, and to develop a Nomogram model to predict the risk of developing endometrial cancer.Patients and methods: A total of 205 patients with 102 cases of endometrial atypical hyperplasia and 103 cases of endometrial carcinoma treated by the Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 1, 2010, to December 31, 2015 were collected as the study group. And 205 patients with simple endometrial hyperplasia or polyp hyperplasia in the same period were selected as the control group using age-matched method. Laboratory results of metabolic factors such as blood pressure (BP), glucose (GLU), triglycerides (TC), and high-density lipoprotein (HDL) were retrieved from the clinical data of two groups of patients. Multivariable logistic regression analysis was used to determine the risk factors associated with endometrial malignant hyperplasia and to develop a nomogram prediction model of risk factors associated with endometrial malignant hyperplasia. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using the bootstrapping validation.Results: Predictors included in the Nomogram prediction model included hypertension, diabetes, BMI, uric acid, hyperlipidemia and CA199. The model had a C-index of 0.782 (95% confidence interval 0.738-0.826) with good discrimination and good calibration. A high C-index value of 0.771 could still be reached in the interval validation. Decision curve analysis showed that it is meaningful to use this Nomogram for patient interventions when the threshold probability is within 22-86%.Conclusion: The development of endometrial malignant hyperplasia is significantly associated with metabolic factors. BMI>25, hyperuricemia, and hyperlipidemia are the main risk factors for the development of endometrial malignant hyperplasia. Hypertension, hyperglycemia and elevated CA199 were also associated with the development of endometrial malignant hyperplasia in our study. The Nomogram prediction model based on physical examination and laboratory testing developed in this study can be used as a rapid method for predicting the risk of endometrial malignancy development and screening for risk factors in a population of women with metabolism-related high-risk factors.
Evaluation of timber floor in-plane retrofitting interventions on the seismic response of masonry structures by DEM analysis: a case study
Authors: Gubana Alessandra , Melotto Massimo
Published: June 2021

The seismic response of existing masonry structures is strongly influenced by floor and roof in-plane properties. An in-plane strengthening intervention is often needed on traditional timber floors to overcome their low in-plane stiffness and to preserve historical buildings. In this study, the effect of un-stiffened and stiffened timber floors on the seismic behaviour of an existing listed masonry building is investigated with dynamic non-linear analyses by means of the Discrete Element Method (DEM). With this approach, the failure processes and collapse sequences of masonry structures can be followed in detail. A previously developed model of the floor cyclic behaviour, based on experimental data, is here applied in the DEM models of the masonry building. Different seismic ground accelerations, different floor types and different wall-to-diaphragm connections are considered. The results highlight the effectiveness of the analysed floor strengthening solution in reducing the out-of-plane displacements of masonry walls. With adequate connections, the reinforced floor is able to transfer the seismic forces to the shear resistant walls up to the shear-sliding collapse of the side walls of the structure. A comparison with the ideal rigid diaphragm case confirms the good performance of the strengthened floors. The small observed out-of-plane displacements are compatible with the masonry wall capacity, and the reinforced floor hysteretic cycles contribute to dissipating part of the input energy. Moreover, different designs of the connections can also cap the transferred seismic forces to an acceptable level for seismic resistant walls.
What is the Effect of Splenic Involvement Sites in Advanced Ovarian, Tubal and Peritoneal Epithelial Cancer on Overall Survival?
Authors: Ayhan Ali , Kucukyildiz Irem , Akilli Huseyin , Gunakan Emre , Serbetcioglu Gonca Coban , Haberal Nihan
Published: June 2021

Purpose: In this study, we evaluated the significance of parenchymal, hilar, and capsular involvement of the spleen with regard to the overall survival of patients who required a splenectomy during cytoreduction procedures for primary or recurrent cancer. Methods: This study includes data from 287 patients who underwent a splenectomy during optimal cytoreduction in epithelial ovarian, tubal, and peritoneal cancers. Spleen involvement regions were divided into four main groups, and the groups were classified as capsule, hilus, capsule + hilus, and other region involvement (paranchyma ± other(s) involvement site). The overall survivals of these four groups were compared.Results: The mean age of the study group was 57.9 years, and the mean follow-up period of the patients was 43.2 months. The splenic involvement site was most frequently observed as hilus + capsule (42.2% n:121). Splenic parenchymal involvement was present in 27.9% (n: 80) of the patients. The overall survival for patients was 42 months. In the subgroup analysis, the worst overall survival was found in the group with capsule involvement at 33 months.Conclusion: While parenchymal involvement of the spleen was considered to be stage IV according to FIGO staging, we could not detect low overall survival in patients with parenchymal involvement in our study. Our study, which has the largest number in the literature examining the relationship between splenic involvement and overall survival, can provide a remarkable perspective on the relationship between parenchymal involvement of the spleen and prognosis.
Biometric-Based Remote Mutual Authentication Scheme for Mobile Device
Authors: Chen Sheng-Kai , Leu Jenq-Shiou , Wen-Bin Hsieh , Wang Jui-Tang , Song Tian
Published: June 2021

Remote user authentication schemes provide a system to verify the legitimacy of remote users’ authentication request over insecure communication channel. In last years, many authentication schemes using password and smart card have been proposed. However, password might be revealed or forgotten and smart card might be shared, lost or stolen. In contrast, the biometrics, such as face, ﬁngerprint or iris, have no such weakness. With the trend of mobile payment, more and more applications of mobile payment use biometrics to replace password and smart card. In this paper, we propose a biometric-based remote authentication scheme substituting biometric and mobile device bounded by user for password and smart card. This scheme is more convenient, suitable and securer than the schemes using smart cards on mobile payment environment.
Sensitization of the UPR by Loss of PPP1R15A Promotes Fibrosis and Senescence in IPF
Authors: Monkley Susan , Overed-Sayer Catherine , Parfrey Helen , Rassl Doris , Crowther Damian , Escudero-Ibarz Leire , Davis Nicola , Carruthers Alan , Berks Richard , Coetzee Marisa , Kolosionek Ewa , Karlsson Maria , Clausen Maryam , Belfield Graham , Hogaboam Cory , Murray Lynne
Published: June 2021

The unfolded protein response (UPR) is a direct consequence of cellular endoplasmic reticulum (ER) stress and a key disease driving mechanism in IPF. The resolution of the UPR is directed by PPP1R15A (GADD34) and leads to the restoration of normal ribosomal activity. While the role of PPP1R15A has been explored in lung epithelial cells, the role of this UPR resolving factor has yet to be explored in lung mesenchymal cells. The objective of the current study was to determine the expression and role of PPP1R15A in IPF fibroblasts and in a bleomycin-induced lung fibrosis model. A survey of IPF lung tissue revealed that PPP1R15A expression was markedly reduced. Targeting PPP1R15A in primary fibroblasts modulated TGF-b-induced fibroblast to myofibroblast differentiation and exacerbated pulmonary fibrosis in bleomycin-challenged mice. Interestingly, the loss of PPP1R15A appeared to promote lung fibroblast senescence. Taken together, our findings demonstrate the major role of PPP1R15A in the regulation of lung mesenchymal cells, and regulation of PPP1R15A may represent a novel therapeutic strategy in IPF.
Course of Lactate, pH and Base Excess for Prediction of Mortality in Medical Intensive Care Patients
Authors: Schork Anja , Moll Kathrin , Haap Michael , Riessen Reimer , Wagner Robert
Published: June 2021

Introduction: As base excess (BE) had shown superiority over lactate as a prognostic parameter in intensive care unit (ICU) surgical patients we aimed to evaluate course of lactate, base excess and pH for prediction of mortality of medical ICU patients. Materials and Methods: For lactate, pH and base excess, values at the admission to ICU, at 24 ± 4 hours, maximum / minimum in the first 24 hours and in 24 – 48 hours after admission were collected from all patients admitted to the Medical ICU of the University Hospital Tübingen between January 2016 until December 2018 and investigated for prediction of in-hospital-mortality. Results: Mortality in the cohort of 4067 patients was 22 % and significantly correlated with all evaluated parameters. Strongest predictors of mortality determined by ROC were maximum lactate in 24 h (AUROC 0.74, cut off 2.7 mmol/L, hazard ratio of risk group with value > cut off 3.20) and minimum pH in 24 h (AUROC 0.71, cut off 7.31, hazard ratio for risk group 2.94). Kaplan Meier Curves stratified across these cut offs showed early and clear separation. Hazard ratios per standard deviation increase were highest for maximum lactate in 24 h (HR 1.65), minimum base excess in 24 h (HR 1.56) and minimum pH in 24 h (HR 0.75). In multiple logistic regression analysis, age, minimum pH in 24 h, pH at 24 h after admission, maximum lactate in 24 h, maximum lactate in 24 – 48 h, minimum base excess in 24 h and minimum base excess in 24 – 48 h were independent predictors of mortality. Discussion: Lactate, pH and base excess were all suitable predictors of mortality in internal ICU patients, with maximum / minimum values in 24 and 24-48 h after admission altogether stronger predictors than values at admission. Base excess and pH were not superior to lactate for prediction of mortality.
Conserved Aquaporins in Gossypium and Silencing of Ghpip2;7 and Ghtip2;1 Decreased Salt and Osmotic Stress Tolerances in Upland Cotton
Authors: Guo Anhui , Hao Jianfeng , Su Ying , Li Bin , Zhu Meng , Ma Xingkun , Huang Yi , Tian Baoming , Shi Gongyao , Hua Jinping
Published: June 2021

Aquaporins (aquaporin), membrane channel proteins, facilitate the transport of water and small molecules across intrinsic membranes and play a critical role in abiotic stresses. Here, 111, 54, and 56 candidate AQP genes were identified in Gossypium hirsutum (AD1), G. arboreum (A2), and G. raimondii (D5), and classified into five subfamilies including PIP, TIP, NIP, SIP, and XIP, respectively. Some GhPIPs and GhTIPs exhibited high expression levels in drought and salt stress verified by transcriptome analysis and Quantitative Real-time PCR (qRT-PCR). The chlorophyll content, SOD activity, and POD activity were decreased in GhPIP2;7 gene-silenced plants versus the control (using blank vector) under 400 mM NaCl treatment, which indicated a negative role of GhPIP2;7 in cotton salt tolerance. Comparing with mock plants, GhTIP2;1 silenced cotton plant was more sensitive to osmotic stress. Overexpressed GhTIP2;1 plants exhibited less accumulation of H2O2 and MDA with higher proline contents detected under osmotic stress. Taken together these results, provide in-depth knowledge into plant response to abiotic stress and gene resource.
Physical and Mechanical Properties of Clay After Heating in Different Oxygen Levels and Cooling With Different Methods
Authors: Dong Zhihao , Sun Qiang , Zhang Weiqiang
Published: June 2021

Clay is a vital industrial raw material, and its physical and mechanical properties undergo significant changes when heated at high temperatures. A good understanding of those properties can provide details on the best use of clay, and may eventually facilitate new application areas. In this paper, the physical and mechanical properties of clay after exposure to high temperatures at two different oxygen levels and cooled in two different ways are studied. In the experiment, the clay samples are heated at high temperatures in anoxic conditions and air. The anoxic conditions are facilitated by a closed crucible. After the sample reaches the target temperature (400°C, 500°C, 600°C, 700°C, 800°C and 900°C), it is cooled to room temperature slowly in the furnace. The samples that are heated in air are either cooled in the furnace or quenched in water. Finally, the appearance of the clay samples in terms of their surface color and development of cracks, as well as their shrinkage, mass loss, hardness, strength and deformation, and the color of the core are examined and measured. The results show that the color of the surface of the clay samples heated in anoxic conditions and air significantly differs, and the color of the core is grayish black at temperatures that are below 800°C, which is possibly related to the oxidation and reduction of iron ions. Cracks in the clay samples partially offset shrinkage. The clay samples quenched in water show larger cracks and lower compressive strength. The mass of the samples does not change at temperatures that exceed 800°C. The hardness also does not change at temperatures that are higher than 700°C. In summary, temperatures between 700°C and 800°C have the most impact on clay because many of the physical properties (including their surface color and color of the core, shrinkage, mass, hardness, and strength) vary greatly at this temperature range.
Effect of Tensile Strain on Performance Parameters of Different Structures of MoS2 Monolayer
Authors: kaushal Priya , Chaudhary Tarun , Khanna Gargi
Published: June 2021

The present work is based on the computational study of MoS2 monolayer and effect of tensile strain on its atomic level structure. The bandgap for MoS2 monolayer, defected MoS2 monolayer and Silicon-doped monolayer are 1.82 eV (direct bandgap), 0.04 (indirect bandgap) and 1.25eV (indirect bandgap), respectively. The impact of tensile strain (0-0.7%) on the bandgap and effective mass of charge carriers of these three MoS2 structure has been investigated. The bandgap decrease of 5.76%, 31.86% and 6.03% has been observed in the three structures for biaxial strain while the impact of uniaxial strain is quite low. The impact of higher temperature on the bandgap under biaxial tensile strain has been also analyzed in this paper. These observations are extremely important for 2D material-based research for electronic applications.
Machine Learning for Warpage Prediction of Fused Deposition Modelling Processed Parts
Authors: Nardi Davide
Published: June 2021

This paper provides a methodology for the application of a machine learning-based framework for fused deposition modelling manufacturing. The approach was developed to take into account the influence of the material, the part geometry, the process parameters on the maximum part warpage defined by the user. The results showed the effectiveness of machine learning for both classification and regression purposes so that the printability of the part is firstly provided, based on the selected warpage threshold, and secondly, the part warpage can be predicted within the problem design space variables, i.e. part material, part height, part length, and layer thickness. The limitations of the use of the analytic equation as a data-points generator are widely discussed, along with the future research based on the obtained preliminary results. In conclusion, the described methodology represents a concrete step towards a first-time-right strategy in the field of manufacturing processes.
Hypoxic Tumor-Derived Exosomes Induce M2 Macrophage Polarization via AMPK/p38 To Promote Lung Cancer Progression
Authors: Zhou Shiyu , Lan Yu , Li Yuqun , Li Zhenxing , Pu Jinding , Wei Liping
Published: June 2021

Background

Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined.
Methods

Exos isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer.
Results

Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK/p38 pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells.
Conclusions

Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK/p38 pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.
Intraorbital Mercury Removal by DSA Positioning and Route Marking: A 4-year Follow-up
Authors: Cai Yuting , Wei Xin , Zhu Hui , Chen Baihua , Li Yun
Published: June 2021

Background: Mercury is a widely used heavy metal. Traumatic mercury residue often leads to contact dermatitis, granuloma, even chronic poisoning. Due to its unique physical and chemical properties, mercury beads can be difficult to retrieve, especially in the eyes. Most previous studies have focused only on the rigid orbital foreign bodies rather than the injuries related to liquid heavy metal and their extraction method.Methods: We reported a case of thermometer-related orbital injuries in a 4-year-old boy. To better locate, visualize and remove the mercury beads without complications, a Digital Subtraction Angiography (DSA)-guided, methylene blue marked access was taken, followed by further removal of scattered tiny mercury droplets with an adapted aspirator. Result: At least 0.7411g mercury was taken out during the surgery. After a four-year follow-up, the boy had no residual symptoms, with his urine mercury decreased gradually.Conclusion: Assessing the risk-return coefficient and making an appropriate therapeutic plan is an integral part of the pursuit of therapeutic progress. With the guidance of DSA and methylene blue, the suction of the reformative aspirator, we finally locate the mercury beads, maximize the removal of beads, reduce the length and depth of incisions, and keep the essential structures intact. Hence, we found it a valuable surgical skill on such occasions, worth sharing for future references.
ortho-Ethynyl group assisted regioselective and diastereoselective [2+2] cross-photocycloaddition of alkenes
Authors: Xie Xiaofei , Pan Hong , Zhou Tai-Ping , Han Man-Yi , Li Pinhua , Geng Xiao , Ma Yongmin , Liao Rong-Zhen , Wang Zhi-Ming , Yang Jianguo , Wang Lei
Published: June 2021

A highly regioselective and diastereoselective [2+2] cross-photocycloaddition between the electron-poor and electron-rich/electron-neutral alkenes under visible-light irradiation was developed. In the absence of an external photocatalyst, the substrates 1 and 4 reacted with rigid cyclic alkoxyethenes to generate (cis,cis)-anti-head-to-head heterocoupled [2+2] products in high yields with regiospecificity and good diastereoselectivity. Meanwhile, the reactions of 1 and 4 with (Z)- and (E)-1,2-diphenylethenes yielded the desired products in good yields with a high ratio of d.r. It is important to note that no geometric isomerization of olefins was observed during the reaction. Mechanistic studies and DFT calculations suggested that 1 and 4 having ortho-ethynyl and cyano groups as a self-photocatalyst play a very important role in the reaction and a five-membered ring diradical intermediate (Int1) was formed via an intramolecular radical addition. The obtained regioselectivity and diastereoselectivity were confirmed by X-ray structural analysis of the representative products.
A CTL/M2 Macrophage-Related Four-Gene Signature Predicting Metastasis-Free Survival in Triple-Negative Breast Cancer Treated with Adjuvant Radiotherapy
Authors: Ye Yunfei , Ma Jungang , Zhang Qin , Xiong Kai , Zhang Zhimin , Chen Chuan , Xiao He , Wang Dong
Published: June 2021

Purpose This study aimed to develop and validate a prognostic model for metastasis-free survival (MFS) based on genes that may functionally interact with cytotoxic T lymphocytes (CTLs) and M2 macrophages in patients with triple-negative breast cancer (TNBC) who underwent adjuvant radiotherapy.Methods The transcriptional profiles and phenotypical files of TNBC and other subtypes of breast cancer were downloaded from the Gene Expression Omnibus (GEO). The abundance of infiltrated immune cells was evaluated through CIBERSORTx or MCP-counter. A weighted linear model, the score for MFS (SMFS), was developed by using least absolute shrinkage and selection operator (LASSO) in GSE58812 and validated in GSE2034 and GSE12276. The biological implication of SMFS was explored by evaluating its associations with TNBC molecular subtypes and other radiosensitivity- or immune-related signatures. Results A model consisting of the gene expression ratios of PCDH12/ELP3, PCDH12/MSRA and FAM160B2/MSRA with nonzero coefficients finally selected by LASSO was developed in GSE58812. In GSE2034 (treatment with adjuvant radiotherapy), SMFS was significantly associated with MFS in TNBC patients (HR=8.767, 95% CI: 1.856-41.408, P=0.006) and, to a lesser extent, in non-TNBC patients (HR=2.888, 95% CI: 1.076-7.750, P=0.035). However, the interaction of subtype (TNBC vs non-TNBC) and SMFS tended to be significant (Pinteraction=0.081). In contrast, SMFS was not significantly associated with MFS in either TNBC patients (P=0.499) or non-TNBC patients (P=0.536) in GSE12276 (treatment without radiotherapy). Among the four TNBC molecular subtypes, the c1 and c4 subtypes exhibited higher CTL infiltration and lower SMFS values than the c2 and c3 subtypes. In addition, SMFS was positively correlated with the abundance of endothelial cells (r=0.413, P<0.001).Conclusions The proposed model has the potential to predict MFS in TNBC patients after adjuvant radiotherapy. SMFS may represent a measurement of tumor immune suppression.
Integrative and Complementary Practices to Control Nausea and Vomiting in Pregnant Women: A Systematic Review Protocol
Authors: Nassif Melissa Santos , Costa Isabelle Cristinne Pinto , Moura Caroline de Castro , Ribeiro Patrícia Mônica
Published: June 2021

BackgroundThe stages of pregnancy are accompanied by several biopsychosocial changes, among them are nausea and vomiting, which are often associated with negative feelings, in addition to generating physical impacts and impacts on the maternal quality of life. In this scenario, the Integrative and Complementary Practices (ICPs) are inserted as a potential treatment to control nausea and vomiting in this public. This review aims to synthesize the available evidence in the literature on the effects of integrative and complementary practices in the treatment of nausea and vomiting in pregnant women. MethodThe review will include only randomized controlled trials (RCTs) that examine the effects of ICPs versus placebo, routine treatment, or pharmacological intervention for the control of nausea and vomiting in healthy pregnant women. The outcomes of interest are those related to nausea and vomiting and possible adverse effects of the intervention. A search for studies will be carried out in the following databases: MEDLINE via PubMed, EMBASE, CINAHL, CENTRAL, ICTRP, LILACS, CUMED, IBECS, Web of Science, Scopus, CNKI, the World Health Organization’s International Clinical Trials Registry Platform (ICTRP) and ReBEC until July 31, 2021. There will be no restrictions on the publication year or language of the manuscripts. The texts will be evaluated in their entirety, after which they will be selected, the data of interest will be extracted, and the risk of bias and quality of evidence will be evaluated. The entire selection process will be carried out by two independent reviewers and a third reviewer will be available in case of disagreement. In the event that a meta-analysis can be conducted, it will evaluate interventions for the absolute difference between averages and potential heterogeneity. If the data are deemed inadequate for a meta-analysis, a systematic narrative synthesis will be carried out. This protocol was proposed based on the preferred reporting item guidelines for systematic review and meta-analysis protocols (PRISMA-P). DiscussionThe results of this systematic review will robustly fill this knowledge gap and possibly assist in evidence-based practices provided for pregnant women experiencing nausea and vomiting.Systematic review registration: PROSPERO CRD42020221570
Fasudil-Triggered Phagocytosis of Myelin Debris Promoted Meylin Regeneration via the Activation of TREM2/DAP12 Signaling Pathway in Cuprizone-Induced Mice
Authors: Ding Zhi-Bin , Han Qing-Xian , Song Li-Juan , Wang Qing , Han Guang-Yuan , Chu Guo-Guo , Li Yan-Qing , Chai Zhi , Yu Jie-Zhong , Xiao Bao-Guo , Ma Cun-Gen
Published: June 2021

The inflammation and demyelination of the central nervous system (CNS) are mainly involved in multiple sclerosis (MS), in which the disorder of myelin regeneration leads to continual neurologic impairment. Fasudil, one of the ROCK inhibitors, has been shown protective functions in some models of demyelinating diseases. In this study, Fasudil treatment ameliorated the behavioral performance and myelin loss in CPZ-fed mice. Here, we demonstrated a new role of Fasudil, which triggered microglia to uptake myelin debris in both cell and animal experiments. This increased phagocytosis was associated with the polarization of M2 microglia. Furthermore, we found that Fasudil enhanced the expression of triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12), which regulated microglial phagocytosis and M2 polarization. The silence of TREM2 effectively blocked Fasudil-triggered phagocytic capacity, suggesting that Fasudil-triggered phagocytosis depends on TREM2 signaling pathway. Based on these evidences that TREM2 regulates microglial M2 polarization and phagocytosis, future studies targeted Fasudil as a therapy for demyelinating and neurodegenerative diseases are warranted.
Current global Status and the Epidemiology of Entamoeba gingivalis in humans: a systematic review and meta-analysis
Authors: Badri Milad , Eslahi Aida Vafae , Olfatifar Meysam
Published: June 2021

Purpose Entamoeba gingivalis (E. gingivalis) is one of the members of the wide range of oral resident pathogens in humans, particularly found in dental plaques, surfaces of gingiva or teeth, interdental spaces and carious lesions. The purpose of the current review and meta-analysis was to determine the global prevalence of E. gingivalis infection and its association with oral diseases based on published literatures. Methods Multiple English databases (PubMed, Scopus, Science Direct, Web of Science and Google Scholar) were explored for papers published until August 2020. A total of 52 studies (including 7596 participants) met the inclusion criteria. Results The overall prevalence of E. gingivalis was estimated to be 37% (95% CI: 29% - 46%). With regard to different countries, the highest and lowest pooled prevalence of E. gingivalis infection were related to Jordan with 87% (95% CI: 81% - 92%) and Portugal with 3% (95% CI: 0% - 10%), respectively. Based on WHO regions, the highest prevalence was related to the region of the Americas with 56% (95% CI: 31%-79%). The infection was most prevalent in 46-55 mean age groups [61% (95% CI: 21% - 94%)]. Among different diagnostic methods, the highest rate of the pooled prevalence was related to the molecular [53% (95% CI: 24% - 81%)] and the direct methods [36% (95% CI: 25% - 47%)], respectively. Our analyses revealed that E. gingivalis infection was associated with 4.34-fold increased risk of oral diseases (P < 0.05).Conclusion Our findings revealed a high prevalence rate of the infection among periodontal disease patients with 37% (95% CI: 20% - 57%). To conclude, it must be considered that E. gingivalis can be a risk factor associated with oral diseases and a wide range of research is needed to specify its role in the pathogenesis of these disorders.
Effects of Attraction of Vacuum Extractors of Different Materials and Pressures on the Fetal Head During Delivery
Authors: Chen Yu-Hsuan , Su Kuo-Min , Tsai Ming-Tzu , Lin Chi-Kung , Chang Cheng-Chang , Su Kuo-Chih
Published: June 2021

PurposeIn some cases where operative deliveries are required with vacuum extractor, and obstetricians could choose the vacuum extractor to facilitate the process smoother and safer. However, there is no related biomechanical literature about the influences of vacuum extractors fabricated from different materials and pressures of vacuum on the fetal head. Hence, we utilized the finite element method to investigate the influences of vacuum extractors manufactured from different materials on the fetal head under various extractive pressures.MethodsFirst, the finite element analysis models of vacuum extractor and fetal head were established. The vacuum extractor model was designed as a hemispherical shape and we compared silicone rubber and stainless steel for the materials of vacuum extractor. Subsequently, four different vacuum pressures were applied as the factors for investigation—500-cm H2O, 600-cm H2O, 700-cm H2O, and 800-cm H2O. Finally, we observed and analyzed the reactive force on the fetal head, von Mises stress of vacuum extractor, and von Mises stress on the skull of fetal head to evaluate the influences of vacuum extractors of different materials under different pressures. ResultsThe results demonstrated that different vacuum pressures had only a slight difference of influences on the fetal head. The use of stainless-steel vacuum extractors caused a relatively larger reactive force (358.04–361.37 N) and stress (13.547–13.675 MPa) on the fetal head. ConclusionsNon-metallic or relatively softer materials could be selected when using a vacuum extractor for operative delivery to avoid complications such as scalp scratch, and even cephalohematoma and intracerebral hemorrhage.
Multiple-Centre Clinical Evaluation of Rapid Recombinase-Aided Amplification Assays for Five Pathogens
Authors: Shen Xin-xin , Nie Dan-wen , Zhang Hong , Zhan Zhi-fei , Gao Yuan , Xiang Xing-yu , Rong Xiu-ge , Liu Xin-ying , Bai Xue-ding , Zhong Li-li , Zhu Ru-nan , Xiao Fei , Zhang Rui-qing , Wang Jin-rong , Li Xin-na , Chen Zi-wei , Li Hao , Zhao Lin-qing , Ma Xue-jun
Published: June 2021

Background: Recombinase-aided amplification(RAA) is a new, simple, and ultrafast isothermal molecular diagnostic technique performed within 30min at 39°C–42°C.In this study, we evaluated the clinical performance of four duplex RAA kits for hepatitis B virus(HBV), human adenovirus 3(HAdV3), human adenovirus 7(HAdV7), and Bordetella pertussis and one duplex reverse-transcription RAA (RT-RAA) kit for respiratory syncytial virus (RSV).Methods: A total of 392 sera and 374 respiratory tract samples were collected from five institutions in four China regions. Each RAA kit’s sensitivity and specificity were compared with those of real-time quantitative polymerase chain reaction(qPCR),real-time quantitative reverse-transcription polymerase chain reaction(qRT-PCR), or sequencing. Results: Compared with qPCR or qRT-PCR, the sensitivities of HBV RAA,RSV RT-RAA, and B.pertussis RAA were 97.55%,96.67%, and 100%,respectively,and all of the specificities were 100%.The total coincidence rates were 97.78%(383/392,95%CI:95.63%–98.85%),97.70%(212/217, 95%CI:94.57%–99.16%), and 100%(60/60,95%CI:92.80%–100%),respectively.The Kappa values were 0.977,0.947, and 1,respectively(P<0.05).Regarding the sequencing, the sensitivities of HAdV3 RAA and HAdV7 RAA were 100% and 97.37%, respectively,and all specificities were 100%.The total coincidence rates were 100%(97/97,95%CI:91.58%–100%) and 98.97%(96/97,95%CI:94.39%–99.82%),and the Kappa values were 1 and 0.978 (P<0.05),respectively.Conclusions: With comparable clinical performance, these RAA kits are suitable assays for rapidly detecting pathogens in resource-limited laboratories.
The ring of truth: Irrelevant insights make worldviews seem true
Authors: Laukkonen Ruben , Kaveladze Benjamin , Protzko John , Tangen Jason , von Hippel William , Schooler Jonathan
Published: June 2021

The authors have requested that this preprint be removed from Research Square.
Adrenergic Receptor Beta 2and 3 Polymorphism Modulate Gastro Intestinal Motility in Ttype 2 Diabetes Mellitus Patients
Authors: Malik Aastha , Saha Sarama , Morya Rajesh Kumar , Bhadada Sanjay Kumar , Rana Satya Vati
Published: June 2021

BackgroundIndividuals with type 2diabetes mellitus (T2DM) commonly present with gastro intestinal symptoms. Exact pathophysiology behind these symptoms is not elucidated. Previous studies reported the role of adrenoceptors on gut motility. However, no study has been conducted to observe whether adrenergic beta receptor (ADRB) 2 and 3 gene polymorphism could influence the gut motility in T2DM. Materials and Methods:Three hundred T2DM patients and 200 age and sex matched healthy controls were enrolled for this study. Participants were subjected to lactulose hydrogen breath test for estimation of orocecal transit time (OCTT). To carry out polymorphism study, buffy coat of EDTA blood was used for DNA isolation followed by polymerase chain reaction and restriction fragment length polymorphism. Results:In this study, the frequency of C allele as well as CC genotype of ADRB3 gene polymorphism and A allele as well as AA genotype of ADRB2 gene polymorphism were significantly higher in patients than controls and was associated with increased risk for T2DM. On comparison of gut motility, OCTT was found to be significantly prolonged (p<0.01) in individuals with CC genotype compared to TT or CT genotype in ADRB3 polymorphism and AA genotype, compared to AG and GG genotype in case of ADRB2 polymorphism. Combined effect of both adrenoceptors on gut motility revealed that individuals having AG or AA genotype in combination with other genotypes had significantly prolonged OCTT. Conclusion:It could be concluded that beta adrenoceptor gene polymorphism has significant role on regulation of gut motility in T2DM.