bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Production Forecasting in a Mature Onshore Oilfield Brownfield in Southern Trinidad by Making Use of Software Modeling
Authors: Paul Simon , Dukhoo Gerard , Phillip Murchison , Persadsingh Jediael
Published: June 2021

In Trinidad's mature onshore oilfields, operators have traditionally forecasted the initial production rates back calculated from decline models. These rates, then reduced annually by a predetermined decline model has been used to evaluate financial feasibility. This method does not make use of the reservoir pressure. This paper demonstrates how software modelling, utilizing the reservoir pressure can reasonably forecast the performance of low rate oil producers and alert the operator of the need for artificial lift from the inception of the production cycle.

The objectives of the project were to determine remaining recoverable reserves, evaluate the potential for redevelopment (workovers and infill drilling) and to demonstrate that software modeling can be used to forecast production for an oil reservoir in a mature onshore oilfield in Southern Trinidad. Petroleum Experts Integrated Production Modeling (IPM) software suite was used for building all models. A comparison of the production forecasted by software modelling and the traditional method of forecasting initial production rates by back calculating from decline models was also undertaken.

Using the available data and net oilsand maps, the fault block bulk volumes, oil in place and the remaining reserves were determined. These results were then used to identify fault blocks with potential workover well candidates and infill well locations. Research of well files and well logs were used in evaluating zones for potential recompletions, reperforation or perforation of additional footage for production. Forecasting and comparison of the initial production rates and ultimate cumulative production for the proposed infill wells and recompletions using the traditional IP/Decline model method and computer modeling was then performed.

Form the data available, it was determined there were four blocks with remaining reserves that could be successfully recovered. The recovery methods proposed included the workover of two existing wells and drilling of two infill wells. Initial production rates and ultimate production volumes obtained by modeling of workover and new well performance had reasonably close agreement with those obtained by the traditional IP/Decline models. The results of the modeling, however indicated that all the wells required the use of pumping mechanisms (sucker rod/beam pumps) to sustain production over a ten-year period. The need for this important production mechanism would not have been realized from the IP/Decline method. An important distinction is that the modelling makes direct use of the reservoir pressure, whereas the IP/Decline model does not.
New Technology Allows for Hands-Off Intervention During Cementing Operations Increasing Safety and Operational Efficiency
Authors: Ramon Michael , Wooley Tony , Martens Kyle , Farrar Amy , Fadaol Seth
Published: June 2021

The culture of safety within the oil and gas industry has undergone an evolution since the advent of significant E&P operations in the late 1800s. The initial focus on safety was to protect property, not people. This mentality has shifted over time to include a greater focus on the safety of personnel, in parallel with technology developments that have pushed the limits of operators’ and service providers’ abilities to drill and complete more complicated wells. The safety efforts introduced to date have yielded results in every major HS&E category; however, falls and dropped objects continue to be areas in need of improvement.

During cementing rig up and operations there are still many manual activities that require working at heights in the derrick. New technological advances have allowed the industry to reduce the number of hands-on activities on the rig and operators have moved to eliminate these activities by automating operations. Man lifting operations are recognized as a high-risk activity and, as such, many rigs require special permitting. During cementing operations, not only are personnel lifted into hazardous positions, but they are usually equipped with potential dropped objects. Some of these objects, if dropped, reach an impact force that could seriously injure or, in worst cases, result in a fatality. During these operations, personnel are also hoisted along with a heavy cement line in very close proximity. This introduces other dangers such as tangling, pinch points, and blunt force trauma. These risks are heavily increased when working in adverse conditions, such as high winds or rough seas. By utilizing a wireless cement line make up device, along with wireless features on a cement head to release the darts/plugs/balls and operate the isolation valves, an operator can eliminate the need for hands-on intervention.

This paper will discuss current cement head technologies available to the operator that allow them to improve safety and efficiencies in operational rig time. Three field studies will be presented that detail running cement jobs with all functions related to the wireless attributes of the cement head. The field studies will present the operational efficiencies achieved by utilizing the wireless features compared to the standard manual method.

Before the recent introduction of a wireless cementing line make-up device, a wireless cement head still required hands-on intervention to rig up the tools, putting people in high-risk situations.
An Assessment of and Proposed Updates to the National Oil Spill Contingency Plan of Trinidad and Tobago Based on the Readiness Evaluation Tool for Oil Spills
Authors: Rudder Marc , Barzey Derval , Ramlal Amy , Gopie Shaleni , Alfred Ronald
Published: June 2021

The Ministry of Energy and Energy Industries assessed the National Oil Spill Contingency Plan of Trinidad and Tobago (NOSCP, 2013) for its effectiveness as a preparedness and response mechanism. Using the Readiness Evaluation Tool for Oil Spills (RETOS™), the NOSCP attained a score of 42% in the Level A Assessment. Gaps were identified in areas including National Legislation, Risk Management, Logistics, Training and Exercises, and Operational Response. Further, lessons learned from past spills were examined to highlight deficiencies in oil spill response (OSR) planning and readiness. Proposed updates to the NOSCP include: designation of appropriate Lead Agency depending on the nature of the spill scenario, mandating Oil Spill Risk Assessments, and the use of SIMA as a decision-making tool for oil spill response; development of comprehensive guidelines for Dispersant Use, Oiled Wildlife Response and Oil Spill Waste Management. The NOSCP is being re-designed to facilitate a national response management system that meets best management practice for oil spill contingency planning. This will enable the efficient and effective deployment of the appropriate resources (equipment, expertise and oversight) to mitigate impacts to human health and the environment, and minimize production down time and socio-economic costs.
Development Features of Cold Production with Horizontal Wells in a Foamy Extra-Heavy Oil Reservoir
Authors: Yang Zhaopeng , Li Xingmin , Xu Xinxia , Shen Yang , Shi Xiaoxing
Published: June 2021

The block M as a foamy extra-heavy oil field in the Carabobo Area, the eastern Orinoco Belt, has been exploited by foamy oil cold production utilizing horizontal wells. The early producing area of block M has been put into production more than 10 years. And the development features of cold production in foamy extra-heavy oil reservoirs are different from the conventional oil field. It is necessary to investigate the development features of this kind reservoir and analyze its influence factors.

Combining the production data with the reservoir geological characteristics of the research area, the cold production features of foamy extra-heavy oil using horizontal wells are analyzed. Then numerical simulations were adopted to study the influence factors of cold production performance.

In the early stage of cold production, the oil production rate is high and the producing GOR is low. With the process of cold production, the reservoir pressure decreases gradually, the producing GOR increases gradually, and the oil production rate decreases gradually. When the bottom hole flowing pressure drops to below the bubble point pressure, the flow of extra-heavy oil in the reservoir can be divided into two zones: far well zone and near well area. In the far well zone, the pressure is higher than the bubble point pressure. The flow of oil is a single-phase flow, and the displacement mode is elastic driving. In the near well area, the pressure is lower than the bubble point pressure, and the oil flow is foamy oil flow, and the displacement mode is the dissolving gas drive driven by foamy oil. There exists many factors that influence the cold production performance of foamy extra-heavy oil, including reservoir depth, reservoir thickness, reservoir physical property and heterogeneity. The oil recovery factor per unit pressure drop can evaluate the cold production performance of foamy extra-heavy oil reservoirs. The effectiveness of cold production is closely related to reservoir parameters. Larger reservoir thickness, deeper reservoir depth and greater reservoir permeability will enhance the performance of cold production. Closer, larger and more interlayers above the horizontal well will hinder the performance of cold production.

This research provides certain guidance and reference for further development adjustment and new project evaluation for foamy extra-heavy oil reservoirs in the Eastern Orinoco Belt.
Using Machine Learning Methods to Identify Reservoir Compartmentalization in Mature Oilfields from Legacy Production Data
Authors: Ramcharitar Kamlesh , Ramdhanie Arti Kandice
Published: June 2021

Despite long production histories, operators of mature oilfields sometimes struggle to account for reservoir compartmentalization. Geological-led workflows do not adequately honor legacy production data since inherent bias is introduced into the process of allocating production by interpreted flow units. This paper details the application of machine learning methods to identify possible reservoir compartments based on legacy production data recorded from individual well completions. We propose an experimental data-driven workflow to rapidly generate multiple scenarios of connected volumes in the subsurface. The workflow is premised upon the logic that well completions draining the same connected reservoir space can exhibit similar production characteristics (rate declines, GOR trends and pressures). We show how the specific challenges of digitized legacy data are solved using outlier detection for error checking and Kalman smoothing imputation for missing data in the structural time series model. Finally, we compare the subsurface grouping of completions obtained by applying unsupervised pattern recognition with Hierarchal clustering. Application of this workflow results in multiple possible scenarios for defining reservoir compartments based on production data trends only. The method is powerful in that, it provides interpretations that are independent of subsurface scenarios generated by more traditional workflows. We demonstrate the potential to integrate interpretations generated from more conventional workflows to increase the robustness of the overall subsurface model. We have leveraged the power of machine learning methods to classify more than forty (40) well completions into discrete reservoir compartments using production characteristics only. This effort would be extremely difficult, or otherwise unreliable given the inherent limitations of human spatial, temporal, and cognitive abilities.
Experiments and Simulation on Integrated Approach of CO2 EOR and Storage in Mature Reservoirs
Authors: Wang Rui , Lv Chengyuan , Liu Xuan , Tang Yongqiang , Cui Maolei , Yang Zhaopeng
Published: June 2021

CO2 storage mechanisms in an EOR process in mature reservoirs are measured to determine three types of storage factors, which are introduced into compositional numerical simulation. The hybrid objective function coupli ng the oil recovery factor and the CO2 storage ratio is proposed to optimize the injection and production parameters in CO2 flooding. Three storage factors of the oil and water partition coefficient, the permeability change coefficient and the CO2 retention factor are measured in a laboratory, which is utilized to modify the grid properties of oil, brine, rock in compositional numerical simulation. The restart procedure is automatically adopted to consider these storage mechanisms in CO2 EOR. The bi-objective function of the oil recovery factor and the CO2 storage ratio is used to optimize the injection and production parameters for CO2 EOR, which concludes the design principles on CO2 EOR and storage. The oil and water partition coefficient defined as the ratio of the CO2 solubility in the oil phase and the brine phase is a constant for a specific reservoir condition. The permeability change coefficient caused by the mineral dissolution effect of carbonate water decreases slightly in the early stage and increases gradually with the long term injection. The CO2 retention factor that is induced by the relative permeability hysteresis decreases with the pressure and the permeability. These equivalent treated methods that modify fluids and rock in the real-time are inserted into the procedure of compositional numerical simulation to take into account the storage mechanisms in CO2 EOR. The results show that the effect of the storage mechanisms on EOR is evident. Furthermore, the bi - objective optimization indicates that the injection rate should be reduced largely in the medium and the later stages to control gas channeling as the EOR scenario is focused. And the bottom wellhole pressure of producers should be decreased to the lower level to maximize oil recovery. As the storage scenario is concentrated, the injection rate is required to be slightly controlled. As the producers are shut off, the injection rate must be increased significantly to maximize CO2 storage. The storage mechanisms in the CO2 EOR process have not been understood thoroughly. The methodology of numerical simulation coupling CO2 EOR and storage is not mature, which is still not taken into account in commercial software. The results above provide a way to optimize CO2 EOR and storage simultaneously, which is significant for the large scale storage after CO2 EOR in mature oilfield.
Short-Term Outcomes of Laparoscopic Versus Open Liver Resection for Hepatocellular Carcinoma in Elderly Patients: A Propensity Score Matching Analysis
Authors: Monden Kazuteru , Sadamori Hiroshi , Hioki Masayoshi , Ohno Satoshi , Takakura Norihisa
Published: June 2021

BackgroundThe number of elderly patients with hepatocellular carcinoma (HCC) requiring surgical treatment has been continuously increasing. This study aimed to examine the safety and feasibility of laparoscopic liver resection (LLR) versus open liver resection (OLR) for HCC in elderly patients at our institution in Japan.MethodsBetween 2010 and 2018, LLR and OLR were performed in 80 and 138 elderly patients (aged > 70 years) who were diagnosed with HCC, respectively. Propensity score matching (PSM) analysis with covariates of baseline characteristics was applied. Intra- and postoperative data were evaluated in both groups.ResultsAfter PSM, 56 patients who underwent LLR and OLR, respectively, were compared. No significant differences in demographic, clinical data, and operative times were observed. Blood loss (OLR: 327 mL, LLR: 50 mL [P < 0.001]), length of postoperative hospital stay (OLR: 12 days, LLR: 7 days [P < 0.001]), and time to start oral intake (OLR: 2 days, LLR: 1 day [P < 0.001]) were significantly lower and shorter in the LLR group than in the OLR group. The incidence of complications over Clavien-Dindo class IIIa was similar between both groups.ConclusionsOur results suggest that advanced age alone is not a contraindication, and LLR can be a treatment option for elderly patients with HCC.Trial registration: retrospectively registered
The application of the strength reduction shortest path method to the stability analysis of shallow buried tunnel
Authors: Wang Wei , Zhang Jiaqi , Liu Ao
Published: June 2021

In order to improve the theoretical analysis of surrounding rock stability of shallow buried tunnel. The strength reduction shortest path theory is applied to the stability analysis of shallow buried tunnel surrounding rock, combined with the ultimate equilibrium strength reduction theory. We discussed the influence of the depth and span ratio of tunnel, cohesion, and internal friction angle on the shortest path of the strength reduction, and studied the effects of various factors on shallow buried tunnel safety relationship by using strength reduction factor of safety and the shortest path of the shallow buried tunnel surrounding rock and the grey relational analysis theory. The results show that: In the analysis of shallow buried tunnel in strength reduction, the approximate distribution obeys parabolic between reduction path length and the reduction ratio. When the strength reduction of cohesion is the shortest path the reduction rate is greater than the internal friction angle. The internal friction angle and cohesive force have a great influence on the stability of shallow tunnel under the method of shortest path of strength reduction. Finally, the comprehensive safety factor of shallow buried tunnel calculated by the finite element strength reduction shortest path method is greater than that calculated by the limit equilibrium method.
A Liquid Chromatographic Method for Determination of Acetamiprid and Buprofezin Residues and Their Dissipation Kinetics in Paddy Matrices and Soil
Authors: Majumder Sujan , Mandal Somnath , Majumder Biswajit , Paul Anindita , Paul Tarun , Sahana Nandita , MONDAL PRITHUSAYAK
Published: June 2021

The present study was conducted to investigate the residue status of two insecticides (acetamiprid and buprofezin) and their dissipation kinetics in three matrices viz. paddy grain, straw and soil. The extraction protocol for residues of these two insecticides was executed using acetonitrile solvent. The analytical method was validated, which showed good linearity with the limit of quantification (LOQ) value of 0.01 and 0.02 mg kg− 1 for acetamiprid and buprofezin respectively. The recovery range was 79.67–98.33 % concerning all the matrices in both the insecticides. Acetamiprid (20% SP) and Buprofezin (25% SC) were applied separately in the paddy field in two doses: single dose (recommended dose) and double dose along with untreated control throughout the experiment. Residue analysis of these two insecticides in paddy (grain and straw) and soil was accomplished employing high-pressure liquid chromatography (HPLC) with a UV detector. The dissipation data showed that acetamiprid exhibited higher dissipation in comparison with buprofezin. However, their persistence was found slightly higher in soil. The dissipation dynamics in the rice and soil were discussed with biological half-lives of both the insecticides. Consumer risk assessment study was also made considering its fate to the consumers.
Safety and Efficacy of Intermittent Presumptive Treatment with Sulfadoxine-Pyrimethamine Using Rapid Diagnostic Test Screening and Treatment with Dihydroartemisinin-Piperaquine at the First Antenatal Care Visit (IPTp-SP+): Study Protocol for a Randomized Controlled Trial
Authors: Kabuya Jean-Bertin Bukasa , Ippolito Matthew M. , Sikalima Jay , Tende Clifford , Champo Davies , Mwakazanga David , Young Anna Marie P. , Mulenga Modest , Chongwe Gershom , Manyando Christine
Published: June 2021

Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization for the prevention of malaria in pregnancy (MIP)-associated adverse outcomes in high burden areas. However, the efficacy of IPTp-SP has decreased in step with increasing parasite drug resistance. Suitable alternative strategies are needed. Methods: This is a protocol for a phase IIIb open-label, two-armed randomized controlled superiority trial to assess the safety and efficacy of a hybrid approach to IPTp combining screening and treatment with dihydroartemisinin-piperaquine (DP) to the current IPTp-SP regimen at the first antenatal care clinic visit. Pregnant women without HIV infection and without signs or symptoms of malaria will be randomized to either standard IPTp-SP or hybrid IPTp-SP plus screening and treatment (IPTp-SP+). In the IPTp-SP+ arm, participants who screen positive by rapid diagnostic test for P. falciparum will be treated with DP at the first antenatal visit while those who screen negative will receive SP per current guidelines. All participants will be administered SP on days 35 and 63 and will be actively followed biweekly up to day 63 and then monthly until delivery. Infants will be followed until 1 year after delivery. The primary endpoint is incident PCR-confirmed MIP at day 42. Secondary endpoints include incident MIP at other time points, placental malaria, congenital malaria, hemoglobin trends, birth outcomes, and incidence of adverse events in infants up to the first birthday.Discussion: A hybrid approach to IPTp that combines screening and treatment with an artemisinin-based combination therapy at the first visit with standard IPTp-SP is hypothesized to confer added benefit over IPTp-SP alone in a high malaria transmission area with prevalent SP resistant parasites. Trial Registration {2a and 2b}.Pan African Clinical Trials Registry, ID: PACTR201905721140808. Registered on May 20, 2019 – Retrospectively, http://www.pactr.org
Bibliometric study of ‘overviews of systematic reviews’ of health interventions: evaluation of prevalence, citation and impact factor
Authors: Lunny Carole , Neelakant Trish , Chen Alyssa , Shinger Gavindeep , Stevens Adrienne , Tasnim Sara , Sadeghipouya Shadi , Adams Stephen , Zheng Yi Wen , Lin Lester , Yang Pei Hsuan , Dosanjh Manpreet , Ngsee Peter , Ellis Ursula , Shea Beverley J. , Reid Emma K. , Wright James M.
Published: June 2021

Background: Overviews synthesising the results of multiple systematic reviews help inform evidence-based clinical practice. In this first of two companion papers, we evaluate the bibliometrics of overviews, including their prevalence and factors affecting citation rates and journal impact factor.Methods: We searched MEDLINE, Epistemonikos and Cochrane databases. We included overviews that: (a) synthesised reviews, (b) conducted a systematic search, (c) had a methods section, and (d) examined a healthcare intervention. Multivariate regression was conducted to determine the association between citation density, impact factor and 6 predictor variables. Results: We found 1218 overviews published from 2000 to 2020; the majority (73%) were published in the most recent 5-year period. We extracted a selection of these overviews (n=541; 44%) dated from 2000 to 2018. The 541 overviews were published in 307 journals; Cochrane Database (8%), PLOS ONE (3%) and Sao Paulo Medical Journal (2%) were the most prevalent. The majority (70%) were published in journals with impact factors between 0.05 and 3.97. We found a mean citation count of 10 overviews per year, published in journals with a mean impact factor of 4.4. In multivariate analysis, overviews with a high number of citations and impact factors had more authors, larger sample sizes, were open access and reported the funding source. Conclusions: An 8-fold increase in the number of overviews was found between 2009 and 2020. We identified 332 overviews published in 2020, which is equivalent to 1 overview published per day. Overviews perform above average for the journals in which they publish.
Vibration Therapy as an Intervention for Enhancing Trochanteric Hip Fracture Healing in Elderly Patients: A Randomized Double-Blinded, Placebo-Controlled Clinical Trial
Authors: WONG Ronald Man Yeung , CHOW Simon Kwoon Ho , TANG Ning , CHUNG Yik Lok , GRIFFITH James , LIU Wing Hong , NG Raymond Wai Kit , TSO Chi Yin , Cheung Wing-Hoi
Published: June 2021

BackgroundThere are more than 300,000 hip fractures yearly in the US with mortality rates of 20% within 1 year. The treatment of osteoporotic fractures is a major challenge as bone quality is poor, and healing is expected to delay due to the impaired healing properties with respect to bone formation, angiogenesis and mineralization. Enhancement of osteoporotic fracture healing and function is therefore critical as a major goal in modern fracture management. Previous pre-clinical studies have shown that low-magnitude high-frequency vibration (LMHFV) accelerates osteoporotic fracture healing. The objective of this study is to investigate the effect of LMHFV on accelerating trochanteric hip fracture healing and functional recovery.MethodsThis is a randomized, double-blinded, placebo-controlled clinical trial to evaluate the effect of LMHFV in accelerating trochanteric hip fracture healing. All fractures undergo cephalomedullary nail fixation. The primary outcome of this study is time to fracture healing by X-ray. Computed tomography (CT) and Dual-energy X-ray absorptiometry (DXA) will also be performed. Blood circulation at the fracture site will be assessed by dynamic perfusion magnetic resonance (MR). Clinical results include functional recovery by muscle strength, timed up and go test (TUG), quality of life questionnaire (SF-36), balancing, falls, and mortality. DiscussionPrevious animal studies have demonstrated LMHFV to improve both normal and osteoporotic fracture healing by accelerating callus formation and mineralization. The mechanical stimulation stimulates angiogenesis by significantly enhancing vascular volume and blood flow velocity. This is the first study to translate LMHFV to enhancing hip fracture healing clinically. Positive results would provide a huge impact in the recovery of hip fracture patients and save healthcare costs. Trial registrationClinicaltrials.gov, NCT04063891. Registered on August 21, 2019
Effect of Omega-3 Fatty Acids on TH1/TH2 Polarization in Individuals with High Exposure To Particulate Matter ≤ 2.5 μm (PM2.5): A Randomized, Double-Blind, Placebo-Controlled Clinical Study
Authors: Wang Zhenxing , Wang Xiaomin , Li Shuiqin , Wu Yongcan , Huang Demei , Pei Caixia , Wang Yilan , Shi Shihua , Wang Fei
Published: June 2021

Background: Long-term exposure to high concentrations of PM2.5 may cause immune system dysfunction and damage to the respiratory and cardiovascular systems. PM2.5 may cause CD4 + T helper cells to polarize toward TH1 or TH2 cell types, which may be associated with the onset and progression of many human diseases. Recent studies have shown that omega-3 fatty acids can regulate human immune function and reduce physiological damage caused by air pollution; however, only limited research has examined the therapeutic effects of omega-3 fatty acids on subjects with high exposure to PM2.5 in mass transit systems such as subways.Methods: This study was designed as a prospective, randomized, double-blinded (to participants and researchers), placebo-controlled trial. The research plan is to recruit 120 qualified volunteers in the Chengdu Metro Station. All participants will receive omega-3 fatty acids or placebo for 8 weeks. The primary outcomes will be changes in the TH1/TH2 cell polarization index and changes in serum cytokine concentrations. Secondary outcomes will be changes in early indicators of atherosclerosis, pulmonary function, COOP/WONCA charts, and scores on the Short Form 36 Health Survey for quality of life. Results will be analyzed to evaluate differences in clinical efficacy between the two groups. A six-month follow-up period will be used to assess the long-term value of omega-3 fatty acids for respiratory and cardiovascular disease end-points.Disscussion: We will explore the characteristics of TH1/TH2 cell polarization index in a population with high exposure to PM2.5. Omega-3 fatty acids and placebo will be compared in many ways to test the effect on people exposed to PM2.5 subway stations. This study is expected to provide reliable evidence to support the promotion of omega-3 fatty acids in clinical practice to protect individuals who are highly exposed to PM2.5.Trial registration: Chinese Clinical Trial Registry (ChiCTR2000038065). Registered on September 9, 2020.
Diet or Additional Supplement to Increase Potassium Intake: Protocol For An Adaptive Clinical Trial
Authors: Hiremath Swapnil , Fergusson Dean , Knoll Greg , Ramsay Tim , Kong Jennifer , Ruzicka Marcel
Published: June 2021

Background
High blood pressure is the leading cause of cardiovascular disease worldwide. The prevalence of high blood pressure is steadily rising, with the growing and ageing population. Many medicines are available to decrease blood pressures successfully, as well as many non-medical options, such as dietary changes and exercise. There is a marked preference amongst patients, reiterated in a Hypertension Canada report, for more research into methods for controlling blood pressure without medicines or to reduce the burden of taking many pills to control high blood pressure. Indeed, effective options do exist, especially with diet, specifically decreasing sodium and increasing potassium in diet. Current public health outreach mostly focusses on sodium intake, even as the potassium intake in diet remains low especially in the Western world. Excellent data exist in the published research reporting that increasing potassium intake, either as diet or even as supplements, reduces blood pressure and reduces risk of cardiovascular outcomes such as stroke. However, the advice most often provided is to ‘eat more fruits and vegetables’ which does not get translated into concrete change.
Methods
We propose to do a clinical trial in two stages, with an adaptive trial design. In the first stage, participants with high blood pressure and proven low potassium intake (measured on the basis of a 24 hour urine collection) will get individually tailored dietary advice, reinforced by weekly supportive phone/email support. If at 4 weeks, there has not been a desired increase in potassium intake, they will be prescribed an additional potassium supplement. Testing will be conducted again at 4 weeks post initiating the potassium supplement, to confirm the efficacy of the potassium supplement. Final measurements will be planned at 52 weeks to observe and measure the persistence of the effect of diet or additional supplement. Concurrent measurements of sodium intake, blood pressure, participant satisfaction, and safety measures will also be done.
Discussion
The results of the study would help determine the most effective method of increasing potassium intake, thus reducing blood pressure, need for blood pressure lowering medicines, at the same time potentially increasing participant satisfaction. The current guidelines recommend changes in diet, not supplement, to increase potassium intake, hence the two stage design will only add supplements if the most rigorous dietary advice does not work.
Trial registration:
This study has been registered on ClinicalTrials.gov identifier NCT03809884, registered on January 18, 2019. URL: https://clinicaltrials.gov/ct2/show/NCT03809884
LncRNA ASAP1-IT1 Enhances Cancer Cell Stemness via Regulating miR-509-3p/YAP1 Axis in NSCLC
Authors: Liu Yantao , Yang Yuping , Zhang Lingli , Lin Jiaqiang , Li Bin , Yang Min , Li Honghui , Chen Kangwu , Zhao Wei
Published: June 2021

Background: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is mainly responsible for the poor clinical outcome of NSCLC. Although previous reports indicated long noncoding RNAs (lncRNAs) play important roles in cancer stemness maintain, the underlying causes mechanisms remain is still mysterious. Our study aims to investigate the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods: qRT-PCR analysis the expression of ASAP1-IT1 and microRNA-509-3p (miR-509-3p) in NSCLC tissues, cancer cells and spheres of cancer cells-derived cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection. Sphere formation and colony formation detects NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays analyzed the interaction between lncRNA and miRNA, qRT-PCR and Western blot detect ASAP1-IT1/miR-509-3p axis's regulation on the expression of regulated genes. NSCLC xenograft mice model validates ASAP1-IT1 role in NSCLC stemness and tumor growth in vivo. Results: ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulated ASAP1-IT1 or miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked miR-509-3p mediated regulation of stem cell-like properties, cell growth, and cell apoptosis of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p.Conclusions: YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness，and targeting related signaling is a promising therapeutic strategy to overcome NSCLC stemness.
Efficacy and Safety of Xiaoyao Pills for Mild to Moderate Depression With Syndrome of Liver Stagnation and Spleen Deficiency: Study Protocol for a Randomized Controlled Trial
Authors: Xue Zhe , Huang Zhen , Cheng Shu-li , Wang Xi-hong , Zhou Xuan , Ma Qing-yu , Chen Jia-xu
Published: June 2021

Background: Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients with syndrome of liver stagnation and spleen deficiency.Methods: This study is a multi-center, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants will be assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline(before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks.Discussion: The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency.Trial registration: International Standard Randomized Controlled Trial Number Register: ISRCTN12746343. Registered on September 25, 2020.
Fuzheng Xiaoliu granules reduce the 2-year recurrence rate of early-stage hepatitis B virus-related hepatocellular carcinoma after comprehensive minimally invasive surgery: a study protocol for a prospective, multicenter, central randomized, double-blind, placebo-controlled clinical trial
Authors: Chen Xinju , Ma Suping , Chen Xiaoqi , Hao Yaokun , Zhao Qing , Zhang Chuanlei , Wang Xinting , Zhao Qiang , Wang Lei , Zhao Wenxia , Ji Aiying
Published: June 2021

Background: Hepatitis B virus (HBV) infection is one of the most common risk factors for hepatocellular carcinoma (HCC). With the continuous improvement of minimally invasive treatment techniques such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), comprehensive minimally invasive treatment (TACE & RFA) has been widely used in the treatment of early-stage (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A) HCC and has good safety and clinical efficacy. However, recurrence and metastasis after comprehensive minimally invasive treatment are still key factors affecting the survival rate of patients. In recent years, Chinese medicine has highlighted its unique advantages in the adjuvant treatment of liver cancer surgery and minimally invasive treatment. Thus, this study aimed to evaluate the efficacy and safety of Fuzheng Xiaoliu granules (FZXLG) for treating early-stage HBV-related HCC after comprehensive minimally invasive treatment and to explore whether FZXLG can delay the progression of HBV-related HCC. Methods: This is a prospective, multicenter, central randomized, double-blind, placebo-controlled clinical trial. A total of 312 patients with early HBV-related HCC who underwent comprehensive minimally invasive treatment within 2 months were randomized in a 1:1 ratio into two groups: the experimental group and the control group. The experimental group will receive basic FZXLG plus Western medicine treatment, and the control group will receive basic FZXLG simulator plus Western medicine treatment. Each group will be treated for 1 year and followed-up for 1 year. The primary outcome measure is the 2-year recurrence rate of patients with early-stage HBV-related HCC after minimally invasive treatment. The secondary outcomes include (1) measurable active lesions, (2) alpha-fetoprotein (AFP), (3) immunological indicators, such as comparison of CD3+, CD4+, CD8+ absolute values, CD4+/CD8+ before and after the test, (4) hepatitis B virus quantity, and (5) Karnofsky functional status score. Discussion: These results will provide research data on the efficacy and safety of FZXLG for the treatment of early-stage HBV-related HCC after comprehensive minimally invasive treatment. These findings will also be based on laboratory indicators and adverse events for safety assessment to determine whether FZXLG can reduce the 2-year recurrence rate of HCC after minimally invasive surgery, which will provide reliable evidence for the clinical treatment of HCC.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900022999. Registered on 5 May 2019.
Linking Industrial Point Sources to PFAS Contamination in Wells: Michigan Case Study
Authors: Schulz Katarina , Filbin Ryan , Silva Marcia R. , Klaper Rebecca , Boyer Tracy
Published: June 2021

In recent years, concern has grown over widespread environmental contamination of per- and polyfluoroalkyl substances (PFAS) in the environment and especially in drinking water. These manmade chemicals were first synthesized in the mid-20th century and contain thousands of individual species, some of which are still used today. A wide variety of industries use or have historically used PFAS in their products and processes. PFAS chemicals are recalcitrant by design and thus do not break down in the environment. Federal and state agencies have begun testing of drinking water and other media for PFAS in order to understand the extent of contamination and determine any necessary regulatory actions. Testing is expensive, however, and it would be beneficial to be able to prioritize wells for testing based on their likely vulnerability. This study presents a methodology for identifying locations of industrial sites likely to use PFAS, and uses Michigan’s robust well testing data alongside industry and environmental factors to identify any spatial relationships that can be used to help prioritize testing of wells.
Understanding And Restoring Dopaminergic Function In Fibromyalgia Patients Using A Mindfulness-Based Psychological Intervention: A [18F]-DOPA PET StudyStudy Protocol For The FIBRODOPA Study- A Randomized Controlled Trial
Authors: Ledermann Katharina , von Känel Roland , Berna-Renella Chantal , Sprott Haiko , Jenewein Josef , Garland Eric , Martin-Sölch Chantal
Published: June 2021

Background: (FM). Fibromyalgia (FM) is a very prevalent and debilitating chronic pain disorder that is difficult to treat. Mindfulness-based techniques are regarded as a very promising approach for the treatment of chronic pain and in particular FM. The Mindfulness-Oriented Recovery Enhancement (MORE) intervention, a mindfulness-based group intervention, has shown beneficial effects in opioid-treated chronic pain patients, including reduced pain severity, functional interference, and opioid dosing, by restoring neurophysiological and behavioral responses to reward. First evidence for a hypodopaminergic state and impaired reward processing in FM have been reported. However, little is known about its impact on dopamine (DA) function and in particular with regard to DA responses to monetary reward in FM. The aim of the present study protocol is to evaluate if MORE is able to restore the DA function in FM patients, in particular with regard to the DA responses to reward, and to reduce pain and mood complaints in FM.Methods/design: The present study is a multi-center RCT with 3 time points: before the intervention, after completion of the intervention and 3-months after completion of the intervention. Eighty FM patients will be randomly assigned to either the MORE intervention (N=40) or to a wait-list control group (N=40). Additionally a comparison group of healthy women (N=20) will be enrolled. The MORE intervention consists of eight 2-hour long group sessions administered weekly over a period of 8 weeks. Before and after the intervention, FM participants will undergo [18F] DOPA Positron Emission Tomography (PET) and functional MR imaging while performing a monetary reward task. The primary outcome will be endogeneous DA changes measured with [18F] DOPA PET at baseline, after the intervention (after 8 weeks for control group), and at 3 months’ follow-up. Secondary outcomes will be (1) clinical pain measures and FM symptoms using standardized clinical scales 2) functional brain changes 3) measures of negative and positive affect, stress and reward experience in daily life using the Experience Sampling method (ESM) 4) biological measures of stress including cortisol and alpha-amylase.Design: If the findings of this study confirm the effectiveness of MORE in restoring DA function, reducing pain and improving mood symptoms, MORE can be judged to be a promising means to improve quality of life in FM patients. The findings of this trial may inform health care providers about the potential use of the MORE intervention as a possible non-pharmacological intervention for FM.Trial registration: ClinicalTrials.gov NCT 04451564. Registered on 3 July 2020. The trial was prospectively registered.
Delineating the Elusive BaMMV Resistance Gene rym15 in Barley by Medium-Resolution Mapping
Authors: Wang Yaping , Habekuss Antje , Snowdon Rod J , Ordon Frank , Perovic Dragan
Published: June 2021

Barley mild mosaic virus (BaMMV), transmitted by the soil-borne protist Polymyxa graminis, has a serious impact on winter barley production. Previously, the BaMMV resistance gene rym15 was mapped on chromosome 6HS, but the order of flanking markers was non-collinear between different maps. To resolve the position of the flanking markers and to enable map-based cloning of rym15, two medium-resolution mapping populations Igri (susceptible) × Chikurin Ibaraki 1 (resistant) (I×C) and Chikurin Ibaraki 1 × Uschi (susceptible) (C×U), consisting of 342 and 180 F2 plants, respectively, were developed. Efficiency of the mechanical inoculation at susceptible standards varied from 87.5–100% and in F2 populations from 90.56–93.23%. Phenotyping of F2 plants and corresponding F3 families revealed segregation ratios of 250s:92r (I×C, χ2 = 0.659) and 140s:40r (C×U, χ2 = 0.741), suggesting the presence of a single recessive resistance gene. Eight KASP assays, developed after screening the parents with the 50K Infinium chip and anchoring corresponding SNPs to the barley reference genome, were used to remap the gene. Newly constructed maps revealed a collinear order of markers, thereby allowing the identification of high throughput flanking markers. This study demonstrates how construction of medium-resolution mapping populations in combination with robust phenotyping can efficiently resolve conflicting marker ordering and reduce the size of the target interval. In an era of reference genomes and high throughput marker platforms, medium-resolution mapping will help accelerate candidate gene identification for traits where phenotyping is difficult.
Effect of Traditional Chinese Medicine Collaborative Model (TCMCM) combined Adjuvant Chemotherapy in IIIb and IIIc Gastric Cancer: Protocol for a Randomized Controlled Trial
Authors: li zhaoyan , Li Jia , Cao Nida , Zhu Xiaohong , Xu Yan , Han Chen , Qin Mengmeng , Liu Feng , Zhang Guangtao , Wang Rui , Xia Xiang , Zhao Gang , Huan Xiangkun , Fan Jin , Zhao Aiguang
Published: June 2021

BackgroundMetastasis and/or recurrence are the primary cause in decreasing the survival time of gastric cancer patients who experienced radical operation. Among whom, patients with stage IIIb and IIIc are especially in high risk of metastasis and recurrence, result in a significant poor survival time than patients with earlier stages. Herbal medicines are natural substances that have been used for centuries in China, auricular acupressure and acupoints has shown promise in reducing side effects of chemotherapy，this traditional Chinese medicine collaborative model（TCMCM）has been studied in cancer, however, the specific effects have not been systematically evaluated. This study was designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence rate and metastasis in stage IIIb and IIIc gastric cancer. Method/designThis prospective，multicenter, randomized, open-label trail will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery with D2 lymphadenectomy. Randomization to usual adjuvant chemotherapy or the intervention (TCMCM) with a 1:1 ratio will be used. Patients in the intervention group received an oral traditional Chinese formula, auricular acupressure and acupoints, all participants will be continuing to receive usual adjuvant chemotherapy. The primary outcome is 3-year disease free survival rate. Secondary outcomes include quality of life，side effects caused by chemotherapy and safety outcome measures. Assessments will be performed at Screening period and 4，8 cycles after adjuvant chemotherapy，9, 12, 18, 24,30 and 36 months after randomization, and adverse events will be recorded.In addition,biological samples will be collected for mechanism exploration studies. DiscussionThis will be the first clinical trial to evaluate the disease-free survival (DFS) and improvements in quality of life in patients of stage IIIb and IIIc gastric cancer receiving TCMCM, which may be used to formulate a standardized TCMCM plan. We are also performing this trial to assess the feasibility of a larger-scale clinical trial in the future. Trail registrationClinicalTrials.gov，NCT03607656. Registered on 1 July 2018.The final protocol version was V1.1.