bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of the Well Intervention Index by the Implementation of Alternative Conventional Rod with Modified Pin in Artificial Lift Systems with Progressive Cavity Pumps Systems in Deviated Wells
Authors: Labrador Jimenez Laura Soraya , De Sales Bastos Paola Andrea , Arambulo Aviles Jenifer Alejandra , Antolinez Wilson Vasquez , Valderrama Arias Luisa Fernanda , George Brian , Molina Jaimes Jesus Oberto , Garcia Contreras Antonio Jose , Florez Góomez Saul Fernando
Published: November 2020

The progressive cavity pumps system (PCP) are very successful in Colombian oil fields, however, wells operated under severely deviated conditions such as abrupt changes in deviation, high dogleg severity (3-6°/100 ft), and/or inclination angles up to 60° have generated between 3 and 5 interventions per year. These high-intervention wells are considered as critical, representing high operating costs and losses of production due to well-stop periods. The wells are typically of medium depths around 3,500 feet, have fluid rates up to 800 BFPD (BS&W > 80%), are influenced by water flooding, and operate at average speeds of 200 rpm to 300 rpm. For these critical wells we have worked to identify alternatives to reduce the repetitive failures (rods and broken tubing).

As part of an integral strategy to produce these wells with high production and high failure rate, this paper describes different operational processes and design considerations. The following topics will be discussed:

Design of wells with PCP as the artificial lift system Failure analysis Lifting Cost Challenge of artificial lifting Redesign of sucker rod string configuration

This problem represents high lifting costs for a barrel of oil including the additional costs associated with well services and production losses due to closure periods.

As part of the solutions, a drive-rod test with modified pin was performed to improve the rod resistance and decrease the contact loads which allowed greater areas of flow, decreased flow restrictions, and less wear between tubing and rods. This change increased the run life by five times, allowing for the installation on a larger scale in a Colombian field. According to the previous results, the test was started in an additional field, confirming the success of the application in critical wells. This has provided ECOPETROL a significant economic benefit versus the conventional rods previously used in these wells under the same conditions. More than 30 wells have been selected to apply these different rods with successful results. All wells interventions regarding rods and tubing failures were reduced significantly (60% average) along with a decrease in production losses due to the associated downtime.
Experimental Evaluation of a Prototype Centrifugal Packer-Type Downhole Separator
Authors: Sharma Ashutosh , Iradukunda Platin , Karami Hamidreza , McCoy J. N. , Podio A. L. , Teodoriu Catalin
Published: November 2020

With the ever-increasing trend of oil production from lower pressure wells, application of artificial lift techniques is becoming inevitable. Beam pumps and electrical submersible pumps are two of the most common artificial lift methods for low and high oil production rates. But these techniques are susceptible to high gas-oil ratios, particularly at lower wellbore pressures causing gas break-out and possible gas lock. Various types of downhole separators have been recently designed upstream of the pump to resolve this issue and improve the pump efficiency. The objective of this study is to construct a state-of-art experimental facility and simulate the flow in an oil well with varying gas-oil ratios. The facility is then used to evaluate the performance of a centrifugal downhole separator.

The experimental multiphase flow setup is designed, fabricated, and constructed in an efficient and automated way to simulate a typical horizontal wellbore. The well trajectory includes a 31-ft horizontal section, inclinable to ±10o, followed by a 27-ft vertical section. The casing ID is 6-in., and a 2-in. ID tubing is placed with end-of-tubing at the bottom of vertical section. The casing and tubing streams are each led to a return column, where gas and liquid flows are metered. Automated and modulated control valves are used to monitor the pressure and production from casing and tubing streams. Five Coriolis flow meters quantify density and flow rate of different fluid streams. All of the equipment is connected to a control computer via DAQ cards.

The experiments are performed with air, supplied by a screw-type compressor, and water, supplied by a moyno pump. The experiments are conducted with different gas (Qg = 30-230 Mscfd) and liquid (QL = 17-700 bpd) flowrates to simulate the cases with both rod pump and ESP operations. The air-water ratio is increased for fixed water rates to identify the ranges of separator effectiveness. The tested downhole separator is an innovative design, applying gravity and centrifugal effects to perform the separation. The results indicate that average gas separation efficiency of the separator is 93% and average liquid separation efficiency is 96% over a wide range of operating conditions, as measured by return line flow meters for casing and tubing streams. The characteristics of multiphase flow in horizontal and vertical sections of the setup are observed and evaluated using surveillance cameras. The separator can be used widely in oil fields to improve gas-liquid separation and artificial lift performance.

The application of pumping artificial lift methods in high GOR wells can help significantly improve the production from a wide range of volatile oil and condensate wells. This illustrates the value of utilizing innovative downhole separation strategies. This paper presents one such centrifugal downhole separator and studies its performance in enhancing the production.
Magnetic Coupling in ESP Applications
Authors: Xiao J. J. , Ejim Chidi , Badr Hassan Mohamed , Abido Mohamed Ali , Khulief Yehia Abel
Published: November 2020

This paper presents a feasibility assessment of eliminating the protector of an electric submersible pump (ESP) by transferring the torque from the motor to the pump using a magnetic coupling, thereby allowing the motor to be hermetically sealed from the wellbore fluids in the operating environment. The paper also briefly discusses means of handling the motor oil expansion as well as the pump axial thrust.

The industry seeks to enhance ESP reliability by designing protectorless ESPs. This requires new techniques to handle torque transfer, motor oil volume change and pump axial thrust, critical functions that a typical protector section performs. Magnetic coupling is a potential method to handle motor/pump torque transfer. For ESP applications, a radial magnetic flux type of coupling is considered. Finite Element software is used to identify the appropriate magnet materials, estimate the coupling dimensions, and predict the coupling performance under transient loads. A sensitivity study is also included to evaluate dimensional variations for different power requirements under different pump rotational speeds.

The analysis identifies two permanent magnet (PM) materials to be appropriate for the magnetic coupling. The length of the coupling is determined for three values of the transmitted power (100, 200 and 300 HP) when operating at three different speeds (3500, 6000 and 10000 rpm). The results show that the magnetic coupling length ranges from 0.95 m to 3.7 m for the considered power range (100 to 300 HP) when operating at a speed of 3500 rpm. The length of the coupling is found to be in the range from 0.65 m to 2.55 m for the speed of 6000 rpm and from 0.4 m to 1.8 m for the speed of 10000 rpm. Mechanical integrity analysis shows that only the case of 100 HP/10000 rpm operates at a subcritical condition, where the predicted total eccentricity has a permissible value. All other operating conditions are supercritical and the whirling deflections of the shaft are likely to exceed the available space within the air-gap. To make the coupling design feasible for these operating conditions, the use of intermediate radial bearings are necessary, which can be challenging in the mechanical implementation and assembly.

This study represents the first systematic and comprehensive attempt in the ESP industry to investigate and assess the feasibility of using a magnetic coupling to replace the conventional protector section of an ESP system. It shows that under low power requirement and high operational speeds, a magnetic coupling is feasible. For other conditions, additional challenges need to be addressed to stabilize the coupling and achieve longevity with the coupling design.
Intermittent Gas Lift for Liquid Loaded Horizontal Wells in Tight Gas Shale Reservoirs
Authors: Croce Daniel David , Zerpa Luis Eduardo
Published: November 2020

The production from horizontal tight gas wells is affected negatively by the accumulation of liquids in the bottom of the well (i.e., liquid loading), to the point that additional hydrocarbon production is not possible. In this work we propose an artificial lift method for liquid-loaded horizontal wells, in tight gas shale reservoirs, based on intermittent gas lift principles. An experimental loop was built to test a prototype of the system and explore the operating envelope that determines the optimal liquid removal results. Experimental results are presented in terms of the liquid removal capacity of the device, as a function of the gas injection rate and the Eotvos (Eo) number. Liquid removal values (produced liquid volume / stagnant liquid volume) of up to 75%, and a volumetric efficiency (volume of liquid produced / volume of gas injected) of up to 78% was obtained for the lowest Eotvos number tested (12) at the lowest gas injection rate (0.25 cf/min). Both the liquid removal and the volumetric efficiency behaved inversely proportional to the Eo number and the gas injection flowrate. Reducing the ID of the line, proved to be an efficient approach to reduce the Eotvos number. Using this option resulted in better sweep, but in an increase of the frictional pressure drop. The improved liquid sweep effect of the Taylor bubble at lower Eo is related to a larger radius of the Taylor bubble and a change on the shape of its nose.
Sucker Rod Pump Downhole Valve Selection for Wells with High Sand Production: Laboratory Test Results
Authors: Del Pino Jessica , Garzon David , Nuñez Walter , Gómez Juan , Renteria Daniel , Sarmiento Dayana
Published: November 2020

Erosion and impact tests were performed on downhole valves with different materials to determine the best valve configuration for the field conditions.

Due to premature failures (less than 1 year of operation) in three wells caused by erosion of the valves, a complete investigation was conducted. First, the history of rod pumps installed in Caño Limón Field was analyzed to obtain configuration statistics of valves installed since 2005. Six different configurations were analyzed, including valves installed in failed and running wells. These configurations included six different ball metallurgies and two different seat metallurgies, combined in double valve setups installed in the pumps. The six valve setups were compared with the average run life and reservoir conditions to determine the best configuration for Caño Limón field. The statistics alone were not clear enough to determine the best configuration for the field, so a laboratory bench was designed to test the different ball and seat metallurgy configurations.

Silicon nitride balls were selected due to their resistance to abrasion, fluid cutting, and impact. The statistics showed good performance when installing silicon nitride balls with tungsten carbide seats, combined with titanium balls and tungsten carbide seats. But when installing single or double silicon nitride balls with tungsten carbide seats, the run time was less than 100 days. The laboratory tests were performed for titanium carbide, silicon nitride, and 440C balls, all of them with tungsten carbide seats. The erosion and wear tests were performed simulating the flow of a slurry around the ball. Silicon nitride balls showed less erosion than titanium carbide and 440C balls. The impact test was performed simulating the downhole pumping action, where the ball is impacted against the seat in a slurry made of water, polymer, and frac sand. Silicon nitride balls showed less wear than titanium carbide and 440C balls, but the seat working with silicon nitride ball showed higher wear than the other metallurgies. When installing single or double silicon nitride balls, the seat wear was higher than when combined when another metallurgy. It was possible to correlate the lab test results with the pump failures to determine the best configuration for the application.

When selecting the valve assembly's metallurgy, it is important to take into consideration not only the properties of the materials, but the effect of combining different metallurgies. Before standardizing an equipment change, field trials and lab tests should be performed.
Effect of Constant Pressure Boundary on Gas Lift of Horizontal Wells
Authors: Uzunoglu Harun , Fan Yilin , Pereyra Eduardo , Sarica Cem
Published: November 2020

Gas lift has been widely used for unconventional reservoirs, especially during recent years. Most of the previous experimental studies on gas lift were conducted at a constant mass flow rate boundary condition. The current study presents an experimental study that investigates gas lift performance at similar field conditions in which the production rates are driven by the formation pressure.

The experiments were conducted in a large-scale experimental facility to study gas lift operations in a toe-down gas lift well. Gas was injected at various rates through casing and tubing annulus to the end of the tubing. The formation gas was supplied by a gas tank regulated at two pressure conditions, which correspond to no production and the last stable production point, respectively. Water was used as the formation liquid phase and injected at the toe. Two liquid flowing conditions were investigated, which were a constant liquid flow rate and constant liquid permeability.

As expected for a production system with constant pressure boundaries, formation gas production rate increases first with increasing gas lift injection rate until it reaches a maximum, beyond which flow in the tubing becomes frictional-dominated, and gas production rate starts to decrease. It is found that gas lift affects the flow behavior at the upstream of the injection point. The total liquid inventory reaches a minimum at the point where the maximum gas production rate is observed. The impact of gas lift on system stability was also analyzed. Gas lift can help the well to produce when it is already dead at naturally flowing conditions. However, insufficient gas injection can kill the well faster than natural flow.
Evaluation of an Innovative Hybrid Gas Lift Technique
Authors: Khan Sikandar , Karami Hamidreza , Wang Chengbao , Joshi Mahendra , Reeves Brian , Van Dam Jeremy , Johnson Curtis
Published: November 2020

Improvements on existing wells' potential are crucial towards ensuring an economically viable project. Among various artificial lift techniques, gas lift is considered as one of the most efficient when associated gas capacity is available, and well production parameters are favorable. Also, jet pumps are specifically favorable for horizontal wells due to the relative ease in downhole installation. This paper combines these two techniques to introduce and evaluate an innovative hybrid method. It provides optimum operating windows for its design and application.

This study aims to introduce and benchmark a newly proposed hybrid lift techniques for horizontal wells. Some features of this method are: 1) The operating Gas Lift Valve (GLV) is installed at the bottom of vertical. 2) The jet pump is installed below the GLV. 3) The power fluid and gas are injected through the casing-tubing annulus. 4) The pressure of gas, provided by the compressor, is used to push the power fluid through the jet pump nozzle and into the tubing. An analytical model is applied to simulate this hybrid lift technique through nodal analysis, combining models for reservoir inflow, flow through jet pump, and two-phase flow in wellbore.

A sensitivity study is conducted to understand the effects of depth, API gravity, water cut, reservoir pressure, gas-liquid ratio (or gas injection rate), nozzle pressure, and nozzle and throat area ratio (R ratio) on the proposed hybrid lift's performance. A hybrid lift operating window is defined as the conditions that result in higher production rates than gas lift alone. The largest operating window is present for shallower wells with larger tubing diameters. The R ratio effects are variable throughout the cases and an optimal R ratio design is needed for each specific case. The required optimal GLR is observed to be always lower for the hybrid lift system compared to gas lift, making it relatively easier and cheaper to achieve. Overall, the operating window for application of hybrid lift is: 1) larger tubing size, 2) higher water cuts, 3) shallower wells, 4) lower required GLR's, 5) heavier oils, 6) higher nozzle pressures, 7) depleted reservoir pressures, 8) higher R ratios (if the well can handle the friction). Additional economic considerations are necessary to better evaluate this technique and determine its optimum operating window.

This innovative hybrid gas lift technique can be widely applied towards increasing well's performance, life, and economic viability. It shows its true merit in seemingly less promising and difficult cases with higher water cuts and lower reservoir pressures by increasing benefit throughout the life of the well.
A Non-Intrusive Condition Monitoring and Vibration Control System for Electric Submersible Pumps
Authors: Badkoubeh Amir
Published: November 2020

This paper addresses a condition monitoring and resonance mitigation method for electric submersible pumps (ESPs) based on motor intelligence. Condition monitoring has been an integral part of surface pump applications. Nonetheless, the majority of ESPs may only have a motor phase current and a process-related measurement, which do not directly indicate the operation efficiency and mechanical reliability. This gap is mainly due to the harsh operating environment for ESPs. We propose a condition monitoring method based on the motor intelligence available at the wellhead to detect the electrical, mechanical and process related issues. The proposed resonance mitigation method is based on adaptive tuning of the control parameters in the electric drives and is described in this paper. Finally, a case study is included supporting the validity of the condition monitoring method on detecting the electrical and mechanical faults on a VSD driven submersible pump.
No evidence of a synergistic effect of HIV infection and diabetes mellitus type 2 on fat distribution, plasma adiponectin or inflammatory markers.
Authors: Hove-Skovsgaard Malene , Abildgaard Julie , Gelpi Marco , Gaardbo Julie , Kolte Lilian , Ullum Henrik , Trøseid Marius , Lindegaard Birgitte , Nielsen Susanne Dam
Published: November 2020

BackgroundAltered fat distribution and chronic inflammation are found in both persons living with HIV (PLWH) and persons with diabetes mellitus type 2 (DM2) and are known risk factors for cardiovascular diseases (CVD). We aimed to investigate if a synergistic effect of HIV infection and DM2 was found on fat distribution and inflammation.MethodsA cross-sectional study was performed including PLWH with HIV RNA <200 copies/mL (18 with DM2 (HIV + DM2+), 18 without DM2 (HIV + DM2-)) and controls (19 with DM2 (controls with DM2) and 25 without DM2 (healthy controls). We measured fat distribution using dual-energy X-ray absorptiometry scan. Plasma concentrations of adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF- α) and soluble CD14 (sCD14) was measured using snap-frozen plasma.ResultsHIV+DM2+ and HIV+DM2- had comparable trunk/limb fat ratio. In contrast, HIV+DM2+ had a higher trunk/ limb fat ratio than controls with DM2 and healthy controls (p=0.013 and p<0.001, respectively). However, HIV+DM2+ and controls with DM2 had comparable amount of trunk fat mass (kg) (p=0.254). A lower concentration of plasma adiponectin and higher concentration of IL-6 was found in HIV+DM2+ than in HIV+DM2-(p=0.037 and p=0.039) and in healthy controls (p=0.001 and p=0.012). In contrast, plasma adiponectin and IL-6 concentrations were comparable in HIV+DM2+ and controls with DM2 (p=0.345 and p=0.825). Concentration of sCD14 was comparable in HIV+DM2+ and HIV+DM2–(p=0.850), but elevated in HIV+DM2+ compared to controls with DM2 (p<0.001) and healthy controls (p=0.007). No statistical interactions were found between HIV infection and DM2 for any of the depending variables.ConclusionA synergistic effect of HIV and DM2 was not found for any of the outcomes. However, HIV+DM2+ had features related to both HIV infection and DM2 with a high trunk/limb ratio, high trunk fat mass, low concentration of plasma adiponectin and elevated concentrations of IL-6 and sCD14. This could contribute to elevated risk of CVD.
Factors influencing malaria infection in Rwanda 2010: a cross-sectional survey study using generalized structural equation modeling
Authors: Bakar Muhammad Abu , Fiaz Rahma , Musenge Eustasius
Published: November 2020

Background Malaria is one of the primary public health concerns in the world and an important cause of morbidity and mortality in sub-Saharan Africa. Malaria morbidity is associated with poverty and vulnerability as it is not easy for the poor people to access preventive treatment and protective measures. In Rwanda, malaria prevention has become a major problem against the double-barreled burden of an overstretched health system and strained financial resources.Methods This work was a cross-sectional survey study design based on data from Rwanda collected in 2010 through the Malaria Indicator Survey as part of the Demographic and Health Survey. The primary outcome variable was an ordinal variable with three categories; no malaria, probable malaria, and confirmed malaria cases. The outcome variable was formulated by combining rapid malaria test and confirmatory blood smear laboratory test. Statistical analysis was done using survey ordinal logistic regression modelling adjusting for random effects for direct effects and generalised structural equation modelling (G-SEM) to obtain total (direct and indirect) effects of malaria morbidity. Results The 11,865 participants had a mean age of 22 years, and two-thirds of the participants were females (67%). Household related variables (socio-economic status, health insurance, age in years) showed a significant total effect on malaria infection. Socioeconomic status had the greatest total effect which was a sum of the direct and indirect effects influenced indirectly by education, health insurance and the number of rooms for sleeping in isolation. Conclusion Poverty is still the core issue to the morbidity patterns driving the malaria epidemic in Rwanda. Access to health facility and health insurance has a high positive impact on decreasing disease as such a special focus on some regions can be an effective intervention strategy. A better understanding of the drivers of morbidity directly and/or indirectly can better target interventions to be more efficient in those affected areas.
Mössbauer Study of Iron Gall Inks on Historical Documents
Authors: Lerf Anton E. , Wagner Friedrich E. , Dreher Monika , Espejo Teresa , Perez-Rodríguez Jose-Luis
Published: November 2020

Iron gall ink was used as a permanent writing material already in late Roman times and throughout the Middle Ages, until it became obsolete in the 20th century. There is much interest in non-destructive experimental methods to determine the state of the ink and its degradation products on historical documents. Mössbauer spectroscopy is such a method, and it has the particular advantage to be sensitive to the chemical bonding of iron, but this method has only rarely been applied to historical documents. In this paper we present Mössbauer data for two damaged documents from a Library in Granada and a handwritten German book from the 18th century. These new results are discussed in the context of previously published Mössbauer data. In one of the investigated documents Fe-(II)-oxalate, FeC2O4·2H2O, was observed. The assignment of the various Fe3+ sites in the different documents is rather difficult and often there is a superposition of various species. These species can be remains of the Fe-tannin complexes of the ink, complexes of Fe3+ with the cellulose of the paper and different iron oxide or hydroxide nanoparticles.
Short-term Impact of the COVID-19 Confinement Measures on Health Behaviours and Weight Gain Among Adults in Belgium
Authors: Drieskens Sabine , Berger Nicolas , Vandevijvere Stefanie , Gisle Lydia , Braekman Elise , Charafeddine Rana , De Ridder Karin , Demarest Stefaan
Published: November 2020

Background: In Belgium, confinement measures were introduced on the 13th of March 2020 to curb the spread of the coronavirus disease (COVID-19). However, these measures may also affect health behaviours of the population. Changes in eating habits, physical activity and alcohol consumption can lead to weight gain resulting in overweight and obesity, which increases the risk of several chronic diseases, but also of severe COVID-19. The purpose of this study is to assess the impact of confinement measures on health behaviours and their associations with weight gain.Methods: Data were derived from the second national COVID-19 health survey. Data were collected between the 16th and the 23rd of April 2020. The recruitment of participants was based on snowball sampling via Sciensano’s website, invitations via e-mail and social media. The study sample includes participants aged 18 years and over with no missing data on the variables of interest (n=28,665). The association between self-reported weight gain and health behaviour changes, adjusted for gender, age group and household composition was assessed through OR (95% CI)’s calculated with logistic regression models, using post-stratification weights.Results: Overall, 28.6% reported weight gain after 6 weeks of confinement. Higher odds of weight gain were observed among participants who increased or decreased their consumption of sugar-sweetened beverages (OR=1.39 (1.16-1.67) and 1.30 (1.05-1.61), respectively), among those who increased their consumption of sweet or salty snacks (OR=3.68 (3.30-4.10)) and food prepared out-of-home (OR=1.23 (1.03-1.48)), among those who became less physically active (OR=1.95 (1.76-2.18)), and among those who increased their alcohol consumption (1.88 (1.69-2.10)).Conclusions: The most important correlates of weight gain during confinement were an increased consumption of sweet or salty snacks and being less physically active. These findings confirm the impact of diet and exercise in short term weight gain and plead to take more action in supporting people to achieve healthier behaviours in order to tackle overweight and obesity.
Adaptation of Cucumber Seedlings to Low Temperature Stress by Reducing Nitrate to Ammonium During It’s Transportation
Authors: Liu Yumei , Bai Longqiang , Wang Jun , Sun Mintao , Li Shuzhen , Miao Li , Yan Yan , He Chaoxing , Yu Xianchang , Yansu Li
Published: November 2020

Background: Low temperature seriously depressed the uptake, translocation from root to shoot and metabolism of nitrate and ammonium in thermophilic plants such as cucumber, and the growth of plant was inhibited accordingly. However, there was no breakthrough in the effect of low temperature on nitrogen transport over the years. Results: By using the non-invasive micro-test technology the net NO3- and NH4+ fluxes rate in root hair zone and vascular bundles of main root, stem, petiole, midrib, lateral vein, and shoot tip of cucumber seedlings under normal temperature (NT) and low temperature (LT) treatment were tested, respectively. Under LT treatment, the net NO3- flux rate in root hair zone and vascular bundles of cucumber seedlings decreased, while the net NH4+ flux rate in vascular bundles of midribs, lateral veins and shoot tips increased. In accordance with this, the relative expression of CsNRT1.4a in petioles and midribs was down-regulated, while the expressions of CsAMT1.2a~1.2c in midribs were up-regulated. The results of 15N isotope tracing showed that compared with NT treatment, NO3--N and NH4+-N uptake of the seedlings under LT treatment decreased 78.1% and 58.8%, respectively, and the concentration and proportion of both NO3--N and NH4+-N distributed in the shoot decreased. Under LT treatment, the actual nitrate reductase activity (NRAact) in roots didn’t change significantly, while NRAact in stems and petioles of LT treatment increased by 113.2% and 96.2%, respectively.Conclusion: In summary, the higher net NH4+ flux rate in leaves and young tissues may be due to the higher NRact in stems and petioles, which could reduce more NO3- to NH4+ so as to reduce the energy consumption in nitrogen transportation under low temperature.
Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients
Authors: Wu Tao , Yang Ming , Xu Hanchen , Wang Lei , Wei Huafeng , Ji Guang
Published: November 2020

Background: The present study aimed to assess the ability of serum bile acid profiles to predict the development of nonalcoholic fatty liver (NAFL) in type 2 diabetes mellitus (T2DM) patients. Methods: Using targeted ultraperformance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry (TQ/MS), we compared serum bile acid levels in T2DM patients with NAFL (n=30) and age-gender matched T2DM patients without NAFL (n=36) at the first time. Second, an independent cohort study of T2DM patients with NAFL (n=17) and age-gender matched T2DM patients without NAFL (n=20) was used to validate the results. The incremental benefits of serum biomarkers, clinical variables alone or with biomarkers were then evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. Area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to evaluate the biomarker predictive abilities. Results: The serum bile acid profiles in T2DM patients with NAFL were significantly different from T2DM patients without NAFL, as characterized by the significant elevation of LCA, TLCA, TUDCA, CDCA24G and TCDCA, which may be potential biomarkers for identification of NAFL in T2DM. Based on the improvement in AUC, IDI and NRI, addition of 5 bile acids to a model with clinical variables statistically improved its predictive value. Similar results were found in the validation cohort.Conclusions: These results highlight detected biomarkers may contribute to the progression of NAFL in T2DM patients, and these biomarkers particularly in combination may help diagnosis of NAFL and allow earlier intervention in T2DM patients.
Prognostic value of atherogenic index of plasma in patients with type 2 diabetes and acute coronary syndrome
Authors: Wang Le , cong hongliang , Zhang Jingxia , Hu Yuecheng , Wei Ao , Zhang Yingyi , Yang Hua , Ren Libin , Qi Wei , Li Wenyu , Liu Chunwei
Published: November 2020

Background: Atherogenic index of plasm (AIP) has been identified as a risk factor for cardiovascular disease (CVD) and an independent predictor of mortality. However, it remains unknown whether AIP level may predict mortality in patients with diabetes and acute coronary syndrome (ACS). Methods: A total of 2531 consecutive patients with type 2 diabetes who underwent coronary angiography for ACS were enrolled in the study. Patients were divided into tertiles according to admission AIP level. The AIP was calculated as the base 10 logarithm of the ratio of the fating concentration of triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C). The primary endpoints were all-cause death and cardiovascular death. Multivariate cox hazard regression analysis were performed to calculate the hazard ratio(HR)and 95％confidence interval(CI)．C-statistics, continuous net reclassification improvement(NRI)，and integrated discrimination improvement(IDI) were calculated to evaluate the added prognostic value of AIP beyond the established mode for prediction of death．Results: During 3-year follow-up, all-cause death events occurred in 142 cases and cardiovascular death events occurred in 120 cases, respectively. The risk of all-cause death and cardiovascular death increased with AIP tertiles at a 3-year follow-up. The Kaplan-Meier curves showed that significant differences in event-free survival rates among AIP tertiles(all-cause mortality: p=0.006; cardiovascular mortality: p=0.003).Multivariate cox hazard regression analysis revealed that AIP was independently associated with all-cause death (HR: 3.859, 95% CI:1.926-7.734; p<0.001) and cardiovascular death (HR:4.723, 95% CI: 2.243-9.946; p<0.001). Addition of AIP to the established mode for mortality prediction was not associated with a significant improvement in the C-statistics value but there were significant improvements in reclassification for all-cause death (NRI: 0.198, p=0.022; IDI: 0.008, p=0.016) and cardiovascular death (NRI: 0.260, p=0.006; IDI: 0.010, p=0.021).Conclusions: Admission AIP was independently correlated with long-term mortality in patients with type 2 diabetes and ACS. These findings suggest that AIP may optimize the mortality prediction among patients with diabetes and ACS.
circFAM73A Promotes Cancer Stem Cell-like Properties of Gastric Cancer Through miR-490-3p/HMGA2 Positive Feedback and HNRNPK-mediated β-catenin Stabilization.
Authors: Xia Yiwen , Lv Jialun , Jiang Tianlu , Li Bowen , He Zhongyuan , Xuan Zhe , Sun Guangli , Wang Sen , Li Zheng , Wang Weizhi , Wang Linjun , Xu Zekuan
Published: November 2020

Background: Circular RNAs (circRNAs) have emerged as a new subclass of regulatory RNAs that exert critical roles in various cancers. Cancer stem cells (CSCs), a small subset of cancer cells, are believed to possess the capacities to initiate tumorigenesis and promote progression. Although accumulating evidences have suggested that cells with CSC-like properties are crucial for the malignance process of gastric cancer (GC), it remains inexplicit whether circRNAs are interrelated with the acquisition of CSC-like properties in GC.Methods: circFAM73A expression was analyzed by GEO datasets and verified in GC samples. The role of circFAM73A on GC cell proliferation, migration, cisplatin resistance and CSC-like properties were determined by a series of functional experiment both in vitro and in vivo. RNA pull down was used to explore the miRNAs and proteins binding to circFAM73A. Bioinformatic analysis and experimental verification confirmed the downstream of circFAM73A. The regulation of HMGA2 on circFAM73A was verified by ChIP and RIP assays.Results: Elevated circFAM73A expression was confirmed in GC tissues and higher circFAM73A predicts poor prognosis of GC patients. The upregulation of circFAM73A enhanced CSC-like properties in GC, thus, exerting the facilitating role on cell proliferation, migration and cisplatin resistance. Mechanistically, circFAM73A promoted GC malignancy by regulating miR-490-3p/HMGA2 in a positive feedback loop and recruiting HNRNPK to facilitate β-catenin stabilization. Moreover, HMGA2 further enhanced E2F1 and HNRNPL activity, which in turn promotes circFAM73A expression.Conclusions: Our work demonstrates the crucial role of circFAM73A on GC CSC-like properties and uncovers a positive feedback loop on circFAM73A regulation that leads to the progression of gastric cancer, which may provide a new insight for circRNA-based diagnostic and therapeutic strategies.
Identification of an Immune Gene-Associated Prognostic Signature and its Association with A Poor Prognosis in Gastric Cancer Patients
Authors: Guan Xiaoqing , Xu Zhi-Yuan , Chen Runzhe , Qin Jiangjiang , Cheng Xiang-Dong
Published: November 2020

Background: The immune response plays a critical role in gastric cancer (GC) initiation, progression, metastasis, and response to therapy. A better understanding of the tumor-immune system interactions in GC may provide promising diagnostic, prognostic, and therapeutic biomarkers for patients with this disease. In the present study, we aimed to identify a prognostic signature of GC through a comprehensive bioinformatics analysis on the tumor-immune interactions as well as the molecular characteristics. Methods: We employed the single sample Gene Sets Enrichment Analysis (ssGSEA) to define immune-related subtypes, used Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) to evaluate the content of tumor and stroma, and utilized Cell type Identification By Estimating Relative Subsets of RNA Transcripts (CIBERSORT) to assess the immune cell type infiltration. We also investigated the complicated biological functions and regulatory networks of these subtypes using Gene Sets Enrichment Analysis (GSEA). Next, we developed a risk model using Lasso Cox regression and verified it via the external validation set. Finally, we systematically correlated the immune signature with GC clinicopathologic features and genomic characteristics. Results: We observed two immune subgroups depending on the activity and level of immune cell in GC patients. We also identified a six-immune-gene signature as a promising independent prognostic biomarker for GC. A nomogram was constructed based on the immune signature and clinical characteristics and showed high potential for GC prognosis prediction. The receiver operating characteristic (ROC) curve analysis distinguishing patients with distinct prognosis yielded an area under the curve (AUC) of 0.779 for 5 years.Conclusions: Our work supports the clinical significance of this immune gene-associated signature for predicting the prognosis of GC patients. This study also shed light on the treatment strategies for GC patients from the perspective of immunology.
Altered Glutamine Metabolism Exposes EMT Derived Mesenchymal Cells to PI3K/Akt/mTOR Pathway Inhibition
Authors: Karvelsson Sigurdur Trausti , Sigurdsson Arnar , Seip Kotryna , Grinde Maria Tunset , Wang Qiong , Johannsson Freyr , Mælandsmo Gunhild Mari , Moestue Siver Andreas , Rolfsson Ottar , Halldorsson Skarphedinn
Published: November 2020

Background: Epithelial-to-mesenchymal transition (EMT) is a fundamental developmental process with strong implications in cancer progression. Understanding the metabolic alterations associated with EMT may open new avenues of treatment and prevention.Methods: We utilize 13C carbon analogs of glucose and glutamine to examine difference in internal flux patterns of metabolites in central carbon and lipid metabolism following EMT in breast epithelial cell lines. Furthermore, an isotopomer spectral analysis, 13C-metabolic flux analysis and weighted correlation network analysis are utilized for investigation of the alterations in metabolic functionality following EMT in breast.Results: There are inherent differences in metabolic profiles before and after EMT. We observed EMT-dependent re-routing of TCA-cycle flux characterized by increased mitochondrial IDH2 -mediated reductive carboxylation of glutamine to lipid biosynthesis with a concomitant lowering of glycolytic rates and glutamine-dependent glutathione (GSH) generation. Our network approach identified specific subtype of cancer drugs that are significantly associated with GSH abundance and we confirmed this in vitro.Conclusions: EMT-linked alterations in GSH synthesis modulate the sensitivity of breast epithelial cells to PI3K/Akt/mTOR inhibitors.
PD-1 Blockade Delays Tumor Growth by Inhibiting an Intrinsic SHP2/Ras/MAPK Signalling in Thyroid Cancer Cells
Authors: Liotti Federica , Kumar Narender , Prevete Nella , Marotta Maria , Sorriento Daniela , Ieranò Caterina , Ronchi Andrea , Marino Federica Zito , Moretti Sonia , Colella Renato , Puxeddu Efisio , Paladino Simona , Kano Yoshihito , Ohh Michael , Scala Stefania , Melillo Rosa Marina
Published: November 2020

Background: The programmed cell death-1 (PD-1) receptor and its ligands PD-L1 and PD-L2 are immune checkpoints that suppress anti-cancer immunity. Typically, cancer cells express the PD-Ls that bind PD-1 on immune cells, inhibiting their activity. Recently, PD-1 expression has also been found in cancer cells. Here, we analysed expression and functions of PD-1 in thyroid cancer (TC).Methods: PD-1 expression was evaluated by immunohistochemistry on human TC samples and by RT-PCR; western blot and FACS on TC cell lines. Proliferation and migration of TC cells in culture were assessed by BrdU incorporation and Boyden chamber assays. Biochemical studies were performed by western blot, immunoprecipitation, pull-down and phosphatase assays. TC cell tumorigenicity was assessed by xenotransplants in nude mice.Results: Human TC specimens (47%), but not normal thyroids, displayed PD-1 expression in epithelial cells, which significantly correlated with tumour stage and lymph-node metastasis. PD-1 was also constitutively expressed on TC cell lines. PD-1 overexpression/stimulation promoted TC cell proliferation and migration. Accordingly, PD-1 genetic/pharmacologic inhibition caused the opposite effects. Mechanistically, PD-1 recruited the SHP2 phosphatase to the plasma membrane and potentiated its phosphatase activity. SHP2 enhanced Ras activation by dephosphorylating its inhibitory tyrosine 32, thus triggering the MAPK cascade. SHP2, BRAF and MEK were necessary for PD-1-mediated biologic functions. PD-1 inhibition decreased, while PD-1 enforced expression facilitated, TC cell xenograft growth in mice by affecting tumour cell proliferation.Conclusions: PD-1 circuit blockade in TC, besides restoring anti-cancer immunity, could also directly impair TC cell growth by inhibiting the SHP2/Ras/MAPK signalling pathway.
Description of Surgery Technique of the Lower Trapezius Transfer with Semitendinosus and Gracilis Tendon Graft for the Treatment of Massive or Irreparable Rotator Cuff Tear
Authors: Almeida Thiago Bernardo Carvallho de , Rodrigues Luciano Miller Reis , Tamaoki Marcel Jun Sugawara , Pascarelli Luciano , Bongiovanni Roberto Rangel
Published: November 2020

Background: The current work describes a surgery technique where the autograft of hamstring tendon (semitendinosus and gracilis) was used as adjuvant in the transfer of the lower trapezius for the treatment of massive or irreparable rotator cuff tear. There is a theoretical advantage that the graft takes a greater footprint area in the greater tuberosity of the humerus corresponding to the infraspinatus, thus recreating the native anatomy more accurately.Methods: The autograft of hamstring tendon was attached to the lower trapezius through an incision of 4cm in the middle third of the scapular spine and transferred to the footprint of the infraspinatus in the greater tuberosity of the humerus, where it is attached through the second incision under the lateral acromial margin.Result: The patient was examined preoperatively and after 6 months of follow-up, and his pain, according to the Visual Analogue Scale, varied from 8 to 3, the range of motion improved in abduction from 100° to 120°, external rotation from 30° to 50° and flexion from 110° to 150°. The Shoulder Subjective Value ranged between 60 and 80% and the Disabilities of the Arm, Shoulder and Hand score went from 45 to 18.3.Conclusions: The lower trapezius transfer with autograft of hamstring tendons is a low-cost and relatively reproducible surgical technique with theoretical biomechanical and anatomic advantages that may bring about better function results.
Effect of Macrophages in Semen on Sperm Quality
Authors: Chen Gangxin , Zheng Beihong
Published: November 2020

Background: This was a cross-sectional study in China, we analyzed the levels of macrophages(Mφ) in semen. The study evaluated the influence of the levels of Mφ in semen on sperm quality.Methods: The subjects were 78 males between 25 and 35 years old. The samples were divided into a low group(Mφ<6×105/ml) and a high group (Mφ>6×105/ml). Evaluation included consideration of the influencing factors of male semen quality, macrophage concentration, sperm motility, morphology, membrane integrity DNA fragmentation index (DFI), anti-sperm antibodies (AsAb), IL-10, and IL-12 in semen.Results: There was no difference in the physical or chemical indices of the semen, sperm concentration, AsAb, IL-10, or IL-12 between the two groups (P>0.05). The percentage of sperm forward motility (PR%), the rate of normal sperm shape, and the integrity of cell membranes in the low group were higher than those in the high group (P<0.05), while the percentage of sperm inactivity (IM%), the rate of sperm head deformity, the rate of deformity in the neck and middle segment, the sperm malformation index (SDI), the abnormal sperm index (TZI), and the sperm DFI in the low group were lower than those in the high group (P<0.05). The concentration of Mφ in the semen was linearly correlated with sperm concentration, sperm PR%, IM%, sperm normal shape rate, head deformity rate, neck and middle deformity rate, SDI, TZI, sperm DFI, and sperm cell membrane integrity (P<0.05), but there was no linear correlation with IL-10 or IL-12 (P>0.05).Conclusions: The concentration of Mφ in semen had no significant correlation with semen volume or sperm concentration, but it did have a significant negative correlation with sperm motility, sperm morphology, cell membrane integrity, and DNA breakage rate. There was no significant correlation with the concentration of IL-10 or IL-12.
A Fair and EMG-validated Comparison of Recruitment Criteria, Musculotendon Models and Muscle Coordination Strategies, for the Inverse-dynamics Based Optimization of Muscle Forces During Gait
Authors: MICHAUD Florian , Lamas Mario , Lugrís Urbano , Cuadrado Javier
Published: November 2020

Experimental studies and EMG collections suggest that a specific strategy of muscle coordination is chosen by the central nervous system to perform a given motor task. A popular mathematical approach for solving the muscle recruitment problem is optimization. Optimization-based methods minimize or maximize some criterion (objective function or cost function) which reflects the mechanism used by the central nervous system to recruit muscles for the movement considered. The proper cost function is not known a priori, so the adequacy of the chosen function must be validated according to the obtained results. In addition of the many criteria proposed, several physiological representations of the musculotendon actuator dynamics along with different musculoskeletal models can be found in the literature, which hinders the selection of the best neuromusculotendon model for each application. Seeking to provide a fair base for comparison, this study measures the efficiency and accuracy of: i) four different criteria; ii) one static and three physiological representations of the musculotendon actuator dynamics; iii) a synergy-based method; all of them within the framework of inverse-dynamics based optimization. Motion/force/EMG gait analyses were performed on ten healthy subjects. A musculoskeletal model of the right leg actuated by 43 Hill-type muscles was scaled to each subject and used to calculate joint moments, musculotendon kinematics and moment arms. Muscle activations were then estimated using the different approaches, and these estimates were compared with EMG measurements. Although similar results were obtained with all the methods, it must be pointed out that a higher complexity of the method does not guarantee better results, as the best correlations with experimental values were obtained with two simplified approaches.