bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Neutrophil Superoxide Production by Uremic Concentrations of Guanidino Compounds
Authors: HIRAYAMA AKI , NORONHA-DUTRA ALBERTO A. , GORDGE MICHAEL P. , NEILD GUY H. , HOTHERSALL JOHN S. 
Published: April 2021

Abstract.
In uremia, diminished reactive oxygen intermediate production is an important consequence of impaired neutrophil function. The effects of guanidino compounds, which are known uremic toxins, on neutrophil reactive oxygen intermediate production in vitro were studied. Neutrophils from healthy volunteers were exposed for 3 h to individual guanidino compounds or mixed guanidino compounds (GCmix), at concentrations observed in uremic plasma. After removal of the guanidino compounds, the neutrophils were activated by adhesion, N-formylmethionylleucylphenylalanine, phorbol myristate acetate, or opsonized zymosan, and superoxide production was measured by monitoring lucigenin chemiluminescence. The direct effects of guanidino compounds on superoxide production in activated neutrophils were also measured. The energy status (ATP and creatine phosphate), antioxidant status (total glutathione), and glycolytic flux (lactate production) were measured. GCmix pretreatment decreased superoxide production in activated neutrophils (activated by N-formylmethionylleucylphenylalanine or zymosan) by 50% (P < 0.01), decreased ATP concentrations by 60% (P < 0.05), and inhibited glycolytic flux (lactate production) by 45% (P < 0.01) but did not alter glutathione concentrations. Simultaneous GCmix exposure and activation did not inhibit NADPH oxidase activity in cell lysates but inhibited superoxide formation in zymosan-activated intact neutrophils; this inhibition was reversed after removal of the guanidino compounds. Guanidinosuccinic acid, guanidinopropionic acid, and guanidinobutyric acid, when tested individually, were each as potent as GCmix. The inhibition of neutrophil superoxide generation by guanidino compounds results from decreased energy status. Micromolar concentrations of guanidino compounds significantly inhibit neutrophil metabolism, with serious implications for the functions of neutrophils in host defenses.
Vascular Proliferation and Enhanced Expression of Endothelial Nitric Oxide Synthase in Human Peritoneum Exposed to Long-Term Peritoneal Dialysis
Authors: COMBET SOPHIE , MIYATA TOSHIO , MOULIN PIERRE , POUTHIER DOMINIQUE , GOFFIN ERIC , DEVUYST OLIVIER 
Published: April 2021

Abstract.
Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and loss of ultrafiltration. These changes originate from increased peritoneal surface area, but the morphologic and molecular mechanisms involved remain unknown. The hypothesis that modifications of activity and/or expression of nitric oxide synthase (NOS) isozymes might play a role in these modifications, via enhanced local production of nitric oxide, was tested in this study. NOS activities were measured by the L-citrulline assay in peritoneal biopsies from seven control subjects, eight uremic patients immediately before the onset of PD, and 13 uremic patients on short-term (<18 mo, n = 6) or long-term (>18 mo, n = 7) PD. Peritoneal NOS activity is increased fivefold in long-term PD patients compared with control subjects. In uremic patients, NOS activity is positively correlated with the duration of PD. Increased NOS activity is mediated solely by Ca2+-dependent NOS and, as shown by immunoblotting, an upregulation of endothelial NOS. The biologic relevance of increased NOS in long-term PD was demonstrated by enhanced nitrotyrosine immunoreactivity and a significant increase in vascular density and endothelial area in the peritoneum. Immunoblotting and immunostaining studies demonstrated an upregulation of vascular endothelial growth factor (VEGF) mostly along the endothelium lining peritoneal blood vessels in long-term PD patients. In the latter, VEGF colocalized with the advanced glycation end product pentosidine deposits. These data provide a morphologic (angiogenesis and increased endothelial area) and molecular (enhanced NOS activity and endothelial NOS upregulation) basis for explaining the permeability changes observed in long-term PD. They also support the implication of local advanced glycation end product deposits and liberation of VEGF in that process.
Effect of Glucose Degradation Products on Human Peritoneal Mesothelial Cell Function
Authors: WITOWSKI JANUSZ , KORYBALSKA KATARZYNA , WISNIEWSKA JUSTYNA , BREBOROWICZ ANDRZEJ , GAHL GERHARD M. , FREI ULRICH , PASSLICK-DEETJEN JUTTA , JÖRRES ACHIM 
Published: April 2021

Abstract.
Bioincompatibility of conventional glucose-based peritoneal dialysis fluids (PDF) has been partially attributed to the presence of glucose degradation products (GDP) generated during heat sterilization of PDF. Most previous studies on GDP toxicity were performed on animal and/or transformed cell lines, and the impact of GDP on peritoneal cells remains obscure. The short-term effects of six identified GDP on human peritoneal mesothelial cell (HPMC) functions were examined in comparison to murine L929 fibroblasts. Exposure of HPMC to acetaldehyde, formaldehyde, glyoxal, methylglyoxal, furaldehyde, but not to 5-hydroxymethyl-furfural, resulted in dose-dependent inhibition of cell growth, viability, and interleukin-1 β (IL-1 β)-stimulated IL-6 release; for several GDP, this suppression was significantly greater compared with L929 cells. Although the addition of GDP to culture medium at concentrations found in PDF had no major impact on HPMC function, the exposure of HPMC to filter-sterilized PDF led to a significantly smaller suppression of HPMC proliferation compared to that induced by heat-sterilized PDF. The growth inhibition mediated by filter-sterilized PDF could be increased after the addition of clinically relevant doses of GDP. These effects were equally evident in L929 cells. In conclusion, GDP reveal a significant cytotoxic potential toward HPMC that may be underestimated in test systems using L929 cells. GDP-related toxicity appears to be particularly evident in experimental systems using proliferating cells and the milieu of dialysis fluids. Thus, these observations may bear biologic relevance in vivo where HPMC are repeatedly exposed to GDP-containing PDF for extended periods of time.
Cigarette Smoking in Renal Transplant Recipients
Authors: KASISKE BERTRAM L. , KLINGER DAGMAR 
Published: April 2021

Abstract.
Cigarette smoking increases the risk for cancer and cardiovascular disease in the general population, but the effects of smoking in renal transplant recipients are unknown. The effects of smoking were investigated among patients transplanted at Hennepin County Medical Center between 1963 and 1997. Information on smoking was available in 1334 patients. The 24.7% prevalence of smoking at the time of transplantation was similar to that in the general population. After adjusting for multiple predictors of graft failure, smoking more than 25 pack-years at transplantation (compared to smoking less than 25 pack-years or never having smoked) was associated with a 30% higher risk of graft failure (relative risk 1.30; 95% confidence interval [CI], 1.04 to 1.63; P = 0.021). Having quit smoking more than 5 yr before transplantation reduced the relative risk of graft failure by 34% (relative risk 0.66; 95% CI, 0.52 to 0.85; P < 0.001). The increase in graft failure was due to an increase in deaths (adjusted relative risk 1.42; 95% CI, 1.08 to 1.87; P = 0.012). The relative risk for major cardiovascular disease events with smoking 11 to 25 pack-years at transplant was 1.56 (95% CI, 1.06 to 2.31; P = 0.024), whereas that of smoking more than 25 pack-years was 2.14 (95% CI, 1.49 to 3.08; P < 0.001). The relative risk of invasive malignancies was 1.91 (95% CI, 1.05 to 3.48; P = 0.032). Smoking had no discernible effect on the rate of return to dialysis or on serum creatinine during the first year after transplantation. Thus, cigarette smoking is associated with an increased risk of death after renal transplantation. The effects of smoking appear to dissipate 5 yr after quitting. These results indirectly suggest that greater efforts to encourage patients to quit smoking before transplantation may decrease morbidity and mortality.
Proximal Tubular Cysts in Fetal Human Autosomal Recessive Polycystic Kidney Disease
Authors: NAKANISHI KOICHI , SWEENEY WILLIAM E. , ZERRES KLAUS , GUAY-WOODFORD LISA M. , AVNER ELLIS D. 
Published: April 2021

Abstract.
Standard texts describe human autosomal recessive polycystic kidney disease (ARPKD) as a cystic kidney disease in which lesions are localized to collecting tubules. Murine models of ARPKD consistently demonstrate an early phase of proximal tubular (PT) cystic involvement, which disappears shortly after birth. This is followed by a phase of collecting tubular (CT) cyst formation and progressive enlargement leading to compromise of renal function and death. Because the description of cystic lesions in human ARPKD has been largely based on postnatal specimens, PT cyst formation was hypothesized to be a characteristic feature of fetal human, as well as murine, ARPKD. This study examines nephron segment-specific cyst localization histochemically by lectin binding in 11 human ARPKD specimens obtained at different fetal and postnatal ages. PT cysts were found in human fetal specimens from gestational age 14 wk to 26 wk. The percentage of cysts involving PT segments ranged from 2 to 41%. The cystic index of PT cysts ranged from 2 to 5. In all specimens in which PT cysts were found, both the percentage of CT cysts and their cystic index were equal to or greater than the percentage of PT cysts and the associated PT cystic index. PT cysts were absent in all kidney specimens older than 34 wk gestational age. It is concluded that human ARPKD, like murine ARPKD, has a transient phase of PT cyst formation during early fetal development.
Borders, Kinship Disruption, and Collapsed Immobility: A Pendula of All My Relations
Authors: Cheechoo Keri , Cheechoo Patrick 
Published: April 2021

Words are like arrows…
Through poetic inquiry and art, this co-authored submission will include an inter/textual representation of Indigenous Métissage which will ask readers to ‘explore’ the lived experiences of colonialist displacement that has (re)framed kinship disruption through a lens that includes collapsed immobility. By engaging both ethical relationality and collapsed immobility (a response to a threat or strategies), the authors will navigate ‘the self’ through a lens that will speak to the (de)lineation and/or (non)existence of governmentally enforced borders present on ancestral territories. Leaning into ancestral aptitude, the authors will make space for All Our Relations to simultaneously step forward by reaching back to “come home” (McLeod, 2007, p. 67).
Epithermal Fluorite Deposits in Transbaikalia (Geochemical Features, Sources of Matter and Fluids, and Genesis)
Authors: Lastochkin E.I. , Ripp G.S. , Tsydenova D.S. , Posokhov V.F. , Murzintseva A.E. 
Published: April 2021

Abstract
—We consider the isotope-geochemical features of epithermal fluorite deposits in Transbaikalia, including the REE compositions, Sr isotope ratios, Sm–Nd systems, and isotope compositions of oxygen, carbon, hydrogen, and sulfur. The 87Sr/86Sr ratios in fluorites are within 0.706–0.708, and the εNd values are negative. Oxygen in quartz, the main mineral of the deposits, has a light isotope composition (δ18O = –3.4 to +2.6‰), and the calculated isotope composition of oxygen in the fluid in equilibrium with quartz (δ18O = –9 to –16‰) indicates the presence of meteoric water. The latter is confirmed by analysis of the isotope compositions of oxygen and hydrogen in gas–liquid inclusions in fluorites from three deposits. These isotope compositions are due to recycling caused by the impact of shallow basic plutons. The isotope composition of sulfur indicates its deep source. During ascent, sulfur became enriched in its light isotope (δ34S = –1.8 to –7.7‰). We assess the association of fluorite ores with basaltoids widespread in the study area. The isotope and geochemical parameters suggest their spatial proximity. Probably, the basaltoids were responsible for the recycling of meteoric water. It is shown that the epithermal fluorite deposits formed by the same mechanism as fissure–vein thermal waters in western Transbaikalia.
Multistage Thrust and Nappe Tectonics in the Southeastern Part of East Sayan and Its Role in the Formation of Large Gold Deposits
Authors: Gordienko I.V. , Dobretsov N.L. , Zhmodik S.M. , Roshchektaev P.A. 
Published: April 2021

Abstract
––Comprehensive studies of structural geology and metallogeny, taking into account the authors’ previous works started as early as the last century, have shown that the southeastern part of East Sayan formed mainly in the Neoproterozoic–early Paleozoic in the settings of multistage thrust and nappe tectonics and tectonomagmatic restructuring of autochthonous and overthrust allochthonous oceanic (ophiolitic), island arc, and ocean-marginal terranes as well as amalgamation of accretion–collision and postcollisional igneous complexes that formed during the opening and subsequent closure of the Paleoasian Ocean marginal structures. In the middle and late Paleozoic, active intraplate volcanic and plutonic processes continued in the thrust/overthrust fault setting, which led to the formation of new dome-shaped nappe structures and the redistribution of ore matter (gold etc.) in large mineral deposits. The final structure of the East Sayan region formed during the late Cenozoic as a result of mountain uplifting and volcanic eruptions, including those in the valley of the Zhombolok River.
Simultaneous Hydraulic Fracturing Improves Completion Efficiency and Lowers Costs Per Foot
Authors: Russell David , Stark Price , Owens Sean , Navaiz Awais , Lockman Russell 
Published: April 2021

Abstract
Reducing well costs in unconventional development while maintaining or improving production continues to be important to the success of operators. Generally, the primary drivers for oil and gas production are treatment fluid volume, proppant mass, and the number of stages or intervals along the well. Increasing these variables typically results in increased costs, causing additional time and complexity to complete these larger designs. Simultaneously completing two wells using the same volumes, rates, and number of stages as for any previous single well, allows for more lateral length or volume completed per day.
This paper presents the necessary developments and outcomes of a completion technique utilizing a single hydraulic fracturing spread to simultaneously stimulate two or more horizontal wells. The goal of this technique is to increase operational efficiency, lower completion cost, and reduce the time from permitting a well to production of that well—without negatively impacting the primary drivers of well performance. To date this technique has been successfully performed in both the Bakken and Permian basins in more than 200 wells, proving its success can translate to other unconventional fields and operations.
Ultimately, over 200 wells were successfully completed simultaneously, resulting in a 45% increase in completion speed and significant decrease in completion costs, while still maintaining equivalent well performance. This type of simultaneous completion scenario continues to be implemented and improved upon to improve asset returns.
An Operators Investigation of Performance Drivers Using Diagnostics and Data Analytics
Authors: Klaassen Trevor , Haffener Jackson , Borell Jarret , Senters Chad 
Published: April 2021

Abstract
In multi-stage plug-and-perf horizontal well completions, there are a multitude of moving parts and variables to consider when evaluating performance drivers. Properly identifying performance drivers allows an operator to focus their efforts to maximize the rate of return of resource development. Typically, well-to-well comparisons are made to help identify performance drivers, but in many cases the differences are not clear. Identifying these drivers may require a better understanding of performance variability along a single lateral. Data analytics can help to identify performance drivers using existing data from development activities. In the case study below, multiple diagnostics are utilized to identify performance drivers.
A combination of completion diagnostics including oil and water tracers, stimulation data, reservoir data, 3D seismic, and borehole image logs were collected on a set of wells in the early appraisal phase of a field. Using oil tracers as the best indication of stage level performance along the laterals, data analytics is applied to uncover the relationships between the tracers and the numerous diagnostics.
After smoothing was applied to the dataset, trends between oil tracer recovery, several independent variables and features seen in image logs and 3D seismic were identified. All the analyses pointed to decreasing tracer recovery, and likely decreased oil production, near faulted areas along each lateral. A random forest model showed a moderate prediction power, where the model's predicted tracer recovery on blind stages was able to explain 54% of the variance seen in the tracer response (r2=0.54). This analysis suggests the identification of certain faulted areas along the wellbore could lead to ways of improving individual well economics by adjusting completion design in these areas.
Well Spacing and Stimulation Design Optimization in the Vaca Muerta Shale: Hydraulic Fracture Simulations on the Cloud
Authors: Malhotra Sahil , Lerza Alejandro , Cuervo Sergio 
Published: April 2021

Abstract
Well spacing and stimulation design are amongst the highest impact design variables which can dictate the economics of an unconventional development. The objective of this paper is to showcase a numerical simulation workflow, with emphasis on the hydraulic fracture simulation methodology, which optimizes well spacing and completion design simultaneously. The workflow is deployed using Cloud Computing functionality, a step-change over past simulation methods.
Workflow showcased in this paper covers the whole cycle of 1) petrophysical and geomechanical modeling, 2) hydraulic fracture simulations and 3) reservoir simulation modeling, followed by 4) design optimization using advanced non-linear methods. The focus of this paper is to discuss the hydraulic fracture simulation methods which are an integral part of this workflow. The workflow is deployed on a dataset from a multi-well pad completed in late 2018 targeting two landing zones in the Vaca Muerta shale play. On calibrated petrophysical and geomechanical model, hydraulic fracture simulations are conducted to map the stimulated rock around the wellbores. Finely gridded base model is utilized to capture the property variation between layers to estimate fracture height. The 3d discrete fracture network (DFN) built for the acreage is utilized to pick the natural fracture characteristics of the layers intersected by the wellbores. The methodology highlights advances over the past modeling approaches by including the variation of discrete fracture network between layers. The hydraulic fracture model in conjunction with reservoir flow simulation is used for history matching the production data.
On the history matched model, a design of experiments (DOE) simulation study is conducted to quantify the impact of a wide range of well spacing and stimulation design variables. These simulations are facilitated by the recent deployments of cloud computing. Cloud computing allows parallel running of hundreds of hydraulic fracturing and reservoir simulations, thereby allowing testing of many combinations of stimulation deigns and well spacing and reducing the effective run time from 3 months on a local machine to 1 week on the cloud. Output from the parallel simulations are fitted with a proxy model to finally select the well spacing and stimulation design variables that offer the minimum unit development cost i.e. capital cost-$ per EUR-bbl. The workflow illustrates that stimulation design and well spacing are interlinked to each other and need to be optimized simultaneously to maximize the economics of an unconventional asset. Using the workflow, the team identified development designs which increase EUR of a development area by 50-100% and reduce the unit development cost ($/bbl-EUR) by 10-30%.
Employing a Suite of Machine Learning Algorithms in a Holistic Approach to Trouble Stage Recognition and Failure Diagnostics
Authors: Iriarte Jessica , McConnell Matthew , Hoda Sam , Siegel Emily , Wolfbrandt Carly 
Published: April 2021

Abstract
This paper explores a holistic approach to characterize trouble stages by applying automated event recognition of abnormal pressure increases and associating those events to formation and operational causes. This analysis of pressure increases provides insight into the potential causes of operational difficulties, and the related diagnostics can suggest improvements to future pump schedules. Improving how stages are pumped is profitable both in the short-term (reducing wasted fluid and chemicals, and other remediation measures) and in the long-term (increased well productivity). Quantifying how design decisions ultimately affect operations can help decrease the frequency of operational problems and help realize these gains.
In this study, the identification of problematic frac stages was initially performed manually (stage-by-stage) using a cloud-based hydraulic fracture data application. During this process, the team recognized that the problem stages had their own characteristic pressure signature - a sudden unexplained pressure increase in the absence of rate changes. A machine learning algorithm was then developed to automatically identify this type of signature. Additionally, previously published machine learning algorithms were used to recognize other operational events of interest, e.g., when proppant reaches the perforations. Then by combining the various events and creating short search windows around each abnormal pressure increase, it is possible to find concurrent operations that may be associated with the observed pressure behavior.
A subsequent statistical analysis revealed that abnormal pressure increases often coincided with changes in proppant concentration in problem stages (stages with abnormal treating pressure behavior). This behavior may be due to near-wellbore effects caused by the changing fluid flow dynamics. Furthermore, it was observed that treating pressures that behaved contrary to hydrostatic pressure effects may be useful in identifying when injectivity is lost and provide an early signal for screen outs.
Through this holistic approach, we were able to identify trouble stages and discern some diagnostics for automated detection of abnormal treating pressure increases. The team was able to identify areas within the stages that were inefficiently pumped, resulting in cost-savings through optimization of proppant and friction reducer (FR) loadings while maintaining a level of caution to prevent screen outs. Finally, the automated detection of pressure anomalies offers a pathway to the real-time prediction and avoidance of operational difficulties such as pressure outs and screen outs.