bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Casing Perforate Wash and Cement for Annular Isolation
Authors: Teo Choon Hoong , Bakri Faiz , Koh Qianhui , Mat Jusoh Muhammad Faizol , Bin Alias Saiful Hisham , Othman Azmi , Idris Syahiran , Thien Ronny
Published: November 2020

Following the successful proof of concept of the closed system dual casing perforate, wash and cement for environmental plug application in 2018 (SPE-193989-MS), the same system was optimized for 2 subsea wells to isolate a gas sand behind 2 casings (9-5/8" × 13-3/8" × 16" open hole).

Learning from recent operations, it was discovered that there is significant improvement achievable with specialized gun system, and refined washing and cementing parameters. Such improvement was critical to the success of the annular remediation and thus, the long-term isolation of the gas sand.

The first successful closed system dual casing perforate, wash and cement for annular isolation is discussed and evaluated in this paper.
Improving Cement Bond and Zonal Isolation in Deviated Production Casing Through the Application of a New Generation Environmentally Friendly Enhanced Spacer System
Authors: Al-Ajmi Abdullah , Al-Rushoud Abdulaziz , Al-Naqa Faisal , Chouhan Manoj , Al-Mekhlef Alanoud , Alasoosy Fawaz , Albohamad Dalal , Alshab Mustafa , Ismail Maizura
Published: November 2020

A successful cement job is a crucial element of obtaining and maintaining well integrity and ensuring safe and efficient hydrocarbon production. The success of cementation starts with a full understanding of good parameters such as formation characteristics and depends on a properly designed slurry and spacer system.

The most challenging part of cementing a wellbore is cementing one with a low fracture gradient. There's a high risk of formation breakdowns and hole instability if maximum allowable equivalent circulation densities (ECDs) are exceeded. In addition to severe losses and formation damage, the outcome includes inefficient placement of the cement that warrants time-consuming and costly operations to assure zonal isolation.

In Kuwait, first trial of a new generation of an environmentally friendly enhanced aqueous spacer system was used successfully in a highly deviated well for cementing the production casing covering shale formations. This paper discusses the design of the enhanced aqueous system and its technical features and benefits, which helped improve the cement bond and achieve zonal isolation.
Bytes to Barrels: Analogue for Real Time Drilling Assistant
Authors: Sharma Ayush Sharma , Raj Kriti Raj , Patidar Atul Kumar
Published: November 2020

Interpretation of subsurface lithology has been an integral part of bottom-hole investigation while drilling a well for hydrocarbon exploration. Conventional methods such as mud logging and open-hole logging have proven to be effective in this aspect. But there arises a need of the real time interpretation of subsurface drilling lithologies to have a better control over desired well path and economics, which is very limited through available conventional methods. This paper aims to provide a classifier that can deliver a justified chance of success in lithology estimation based on input matrix provided to the classifier. The dataset is taken from open source platform (Equinor), which provided the drilling history of 15_9_F_15_D well of North Sea Basin along with the interpreted lithology. This dataset is used to prepare the input matrix and the corresponding output used for the classifier. It incorporates seven drilling parameters, i.e. rate of penetration (ROP), weight on bit (WOB), bit rotation per minute, total bit rotations, corrected drilling exponent, mud flow & mud weight and the corresponding recorded subsurface lithology for each foot. It is made sure that the chosen drilling parameters have a direct impact on the rate of penetration with changing physical characteristics of the formations being penetrated. The formations are calibrated with the integer values from 1 to 5 for easier numerical computations. The prepared dataset is divided into two components i.e. training Set (80%), and test Set (20%) with feature scaling implemented. The most intuitive classification model among all the tested classification algorithms i.e. multiple classification algorithm, artificial neural network, and KNN search method is stated based on their individual F (1) score on the test set. It is observed that the cost function for the multiple classification model stopped reducing after the first few iterations irrespective of learning rate value alterations, which induced a limit on the accuracy provided by the chosen algorithm. It is observed that the performance of ANN is quite good for the lithology present in majority, such as claystone. However, the performance degrades exponentially for the lithologies occurring in minorities such as sandstone, dolomite, marl and limestone. The results obtained from KNN classification model not only provides an accuracy of 95% in claystone, 92% in sandstone and 89% in marl which makes this model the most appropriate classifier to be used among the three.

The preliminary results, through the comparison among the three classifiers not only provides the most intuitive model for subsurface lithology prediction using real-time drilling data, but also gives an idea about the most appropriate classifier to be used in the future reference, be it any basin, given that the same set of drilling parameters are used as the input matrix for training the classifier.
Enabling Subsea Well P&A with Modern Vessels
Authors: Lim Tze King , Tellier Elizabeth , Campbell Mike
Published: November 2020

An increasingly common problem faced by subsea well operators is plugging and abandonment (P&A) of wells using modern drilling vessels. This challenge is due to older wellhead and conductor designs which are not fatigue resistant and which have less bending load capacity. Combined with the current trend of using larger and heavier BOP stacks provided by 5th and 6th generation drilling vessels, this results in large motions and loads transferred to the wellhead, and hence higher risk of fatigue failure or component capacities being exceeded during P&A. This paper discusses the methodology for assessing the feasibility of performing P&A on wells with modern vessels and evaluates mitigation options available.

Firstly, analysis is performed to determine historical fatigue accumulation in the wellhead and conductor system from drilling and completion operations. Historical fatigue accumulation can be refined by incorporating details from the operational history including vessel heading, metocean conditions, and riser configuration. Fatigue accumulation from planned P&A operations with modern day drilling rigs is then assessed to determine if there is sufficient remaining fatigue margin for the planned P&A operations. If required, mitigation measures such as optimizing riser tension and vessel heading, reducing BOP stack size, calibrating analysis models using monitoring data and using a BOP tether system are evaluated. Strength assessment for P&A operations is also performed to determine vessel station keeping requirements. Examples from a number of case studies of recent subsea well P&A in Australia are presented.

The effectiveness of different fatigue mitigation measures are compared. Findings presented in the paper allow operators to efficiently evaluate and plan safe P&A operations on older wells with modern drilling vessels.
Matrix Water Injection – A Novel Technique
Authors: Eshtewi Abdullah , White Richard , Campbell Stewart
Published: November 2020

The Greater Enfield Project (GEP) is a challenging offshore oil development, designed to produce from the Laverda Canyon, Cimatti and Norton over Laverda oil fields. Six water injection wells are required to provide pressure support and sweep oil to three production wells in the Laverda Canyon and Cimatti oil accumulations to improve oil recovery. The GEP injection wells are a critical aspect of water flood design in a complex field, new to Woodside and with limited global benchmarks.

A specific drilling and completion fluid system (Reservoir drilling fluid, completion fluid and chemical filter cake breaker) combined with a unique clean up and displacement technique have been adopted to provide high and sustainable matrix injection performance. While filter cake breakers have been previously used in the industry, they are typically combined with a flowback for filter cake removals. Filter cake clean up by means of flowback was discounted for GEP due to cost and the inability of some wells to naturally flow during early life.

All GEP injection wells were completed in 2018-2019, one of which is globally the longest horizontal water injection well completed to date based on the Rushmore data base. Fieldwide injection commenced in July 2019 with favorable results. This paper summarises the key design aspects adopted to deliver successful matrix injection performance, presents the improvements implemented during offshore execution and provides an insight into the early life injection performance.
Using Data-Mining CRISP-DM Methodology to Predict Drilling Troubles in Real-Time
Authors: Al Gharbi Salem , Al-Majed Abdulaziz , Abdulraheem Abdulazeez , Patil Shirish , Elkatatny Salaheldin
Published: November 2020

Drilling is considered one of the most challenging and costly operations in the oil and gas industry. Several initiatives were applied to reduce the cost and increase the effectiveness of drilling operations. One of the frequent difficulties that faces these operations is unexpected drilling troubles that take place and stops the operation, resulting in losing a lot of time and money, and could lead to safety issues culminating in a fatality situation. For that, the industry is in continues efforts to prevent drilling troubles. Part of these efforts is utilizing the artificial intelligence (AI) technologies to identify troubles in advance and prevent them before maturing to a serious situation. Multiple approaches were tried; however, errors and significant deviation were observed when comparing the prediction results to the actual drilling data. This could be due to the improper design of the artificial intelligent technology or inappropriate data processing. Therefore, searching for dynamic and adequate artificial intelligent technology and encapsulated data processing model is very essential.

This paper presents an effective data-mining methodology to determine the most efficient artificial intelligent technology and the applicable data processing techniques, to identify the early symptoms of drilling troubles in real-time. This methodology is CRISP-DM that stands for Cross Industry Standard Process for Data Mining. This methodology consists of the following phases: Business Understanding, Data Understanding, Data Preparation, Modeling, Evaluation and Deployment. During these phases, multiple data-quality techniques were applied to improve the reliability of the real-time data.

The developed model presented a significant improvement in identifying the drilling troubles in advance, compared to the current practice. Parameters such as hook-load and bit-depth, were studied. Actual data from several oil fields were used to develop and validate this smart model. This model provided the drilling engineers and operation crew with bigger window to mitigate the situation and resolve it, prevent the occurrence of several drilling troubles, result in big time and cost savings. In addition to the time and cost savings, CRISP-DM provided the artificial intelligent experts and the drilling domain experts with a framework to exchange knowledge and sharply increase the synergy between the two domains, which lead to a common and clear understanding, and long-term successful drilling and AI teams collaboration.

The novelty of this paper is the introduction of data-mining CRIPS methodology for the first time in the prediction of drilling troubles. It enabled the development of a successful artificial intelligence model that outperformed other drilling troubles prediction practices.
Efficient Optimization and Uncertainty Analysis of Field Development Strategies by Incorporating Economic Decisions in Reservoir Simulation Models
Authors: Browning James , Gorell Sheldon , Andrews Justin
Published: November 2020

Design, evaluation and approval of a field development plan is generally very iterative, requiring meetings, design and execution of simulation models, then financial reviews, back to updating and running the models, then financial evaluations again, and on and on. This paper presents a system (tools and processes) designed to significantly reduce the iterations of simulation runs and financial reviews. This is accomplished through implementing financial logic directly inside the model. This novel ability assesses and controls individual well operations every time step, eliminating the need to modify (and rerun) a model after every run due to financial review indicating a well is losing money and needs to be shut in or modified. Even with the simple model presented, with 23 wells, at least one new iteration would be required every time post run financial analysis indicates a well's operation needs modification due to its financial performance. This would require a minimum of 23 additional runs because changing a well will also impact the performance of other nearby wells.

The system presented also provides the flexibility to configure multiple parameters into the model, enabling the automatic execution of multiple combinations of operational and financial scenarios. Such a capability enables the rapid analysis and review of parameter impacts resulting in the confidant selection of the best operating for the organization.

The impact of financial realities is demonstrated through the simulation of operating five different field scenarios, each with its own combination of producers and injectors. A variety of operational and financial parameters were included. The results indicate that including financial parameters and decisions inside the simulation run significantly improves the usefulness of the production forecast and provides considerable efficiencies in the modeling and analysis processes.
Using Digital Twins for Condition Monitoring of Subsea Mechanical Equipment
Authors: Holberg Geir Ivar , Grennberg Viktor , Martens Joakim
Published: November 2020

The focus on digitalization and how to reap the benefits from it, is increasing in the oil and gas industry. To make this happen subsea by using machine learning and neural networks on mechanical products, we need to understand how we can digitize them.

In this paper we will show how we can generate a true digital twin that could enable the step change in how we monitor and understand the mechanical products placed out of reach for normal preventive maintenance.

We look at the industry’s current information philosophy regarding mechanical products; from idea to development and testing to installation and operation. Where the products are currently designed to end up with a nominal 3D model, test components and the verification that they are fit for purpose is made through a test scope simulating certain scenarios defined by the industry. The products are then installed, and their condition is assumed to be fine until evidence of the opposite is apparent, and the time window to perform mitigative intervention is gone.

Creating true digital twins of mechanical products will require more data. In recent tests we have focused on generating data points to understand the response/behaviour of the products in multiple scenarios and utilized this data to describe the behaviour accurately and numerically; from this we can generate a digital representation of what state the products are in.

The results are based on recent work in developing a digital twin for mechanical products. In this work we have proven through documented testing and quantitative analysis that we can generate a validated numerical model for mechanical products. This will form the basis for understanding the state of the products and predict when intervention/maintenance is imminent for the operator. Using this model and method, condition monitoring of the mechanical products can now be enabled with relative few datapoints extracted in time intervals, and through the use of its numerical representation, establish an actual condition history of the product itself.

Further this model would enable a deeper understanding of the actual operational effects, to which the product is exposed during its lifetime, leading to more precise and cost-efficient industry requirements and system knowledge.
Carnarvon Basin: Mungaroo Formation, The Challenges in Estimating Permeability
Authors: Pillai Paul , Shams Asghar
Published: November 2020

There was always the challenge to match Permeability estimated from logs to Permeability derived from well tests. The main reason for this is the difference in scale, both vertically in the borehole (net contributing sands) as well as radially out into the formation. The well test that takes into consideration many hours of fluid flow into the borehole was always deemed more representative than permeability derived from logs that measures a smaller area and volume. However, this perception should not relegate log-derived permeability to an insignificant parameter within dynamic models. When wells are stimulated prior to well test (e.g. under-balanced perforation or chemical stimulation for clean-up), it is expected that the permeability from the well test be enhanced as seen in Iago-2 and Gorgon-3 wells.

This paper takes core data from wells in the Carnarvon Basin, create log relationships to predict permeability that match these core data, and compare these to wireline formation tester mobility and to well tests. The results are very promising, and the workflow proposed can be applied to any well in the basin. One of the objectives of this paper is to create a workflow that can be replicated easily and to use raw logs that are available across all wells, in order to reduce the uncertainty in the predicted permeability.

The reservoir sands of the Mungaroo formation are easily recognised by the cross over in the neutron-density logs, in both gas zones and water zones. This is the criteria used by operators to obtain formation pressure tests (MDT/RFT) and this is the same criteria used in this paper to define reservoir sands. Only those core data acquired in reservoir sands are used as the "Learning" dataset to predict permeability. Several learning datasets were created, and these were blind tested on other wells that were not part of the learning dataset. The results of these predicted permeabilities were cross plotted against core permeability that have been over-burden corrected and depth shifted to wireline logs. Where the match is not satisfactory, new learning datasets are derived and this step of the workflow is repeated. At the end, there are four groups of learning datasets that are used as the final results.

These four groups of datasets are associated with four sets of equations and these provides a very good match between the predicted log-derived permeabilities and core plug permeabilities. When compared to mobilities from formation pressure testers, the predicted permeabilities are a very good match. These were then compared to well test permeabilities showing an overall good match. This gives confidence that the predicted permeabilities from the four sets of equations are good and can be applied to any new well targeting the Mungaroo Formation in the Carnarvon Basin.
Approaching the Necessity of Pediatric Palliative Care in Colombia: A challenge for the Health System. A Retrospective Cross Sectional Study.
Authors: Villegas Susana Orrego , España Karine Maria Posada , Flores Silvia Librada , Solano Juliana Lopera
Published: November 2020

Background: Pediatric Palliative Care (PPC) focuses on achieving quality of life and control the symptoms for children during the sickness process, also provide support to the family in order to relief suffering and give response to needs assessment. In Colombia, this subspecialty does not exist, as a result of not having clinic practice guides and information about the population who benefit under 18 years of age. This study is to approach the necessity of PPC in our country, defining a methodology to characterize and estimate prevalence of pediatric population who may need special care in order to develop an attention model. Methods: A retrospective descriptive study was conducted among 80,926 members between 0 and 18 years of age who has a private health insurance in Colombia between January 1, 2016 and December 31, 2018. Data was obtained from the insurance transactional database. Patients were grouped based on the Association for children with life threatening conditions and their families (ACT) of the Royal College of Pediatrics four classifications plus perinatal group. Results were processed and analyzed using descriptive statistical functions in Microsoft Excel. Results: 1,694 patients (2,09%) were eligible to enter a PPC program according to their IDC-10 diagnoses based on ACT plus Perinatal Group classification. Approximately 54% were male, 57.97% were considered early childhood, 26.56% childhood and 15,47% adolescence. With regards to ACT classification and Perinatal Group; 55.55% of patients had diagnosis from Perinatal Group (55.55%) followed by group 4 (23.2%) and group 1 non-cancer (9.68%). Conclusion: Being able to identify patients in need of PPC programs early may increase it being utilize at the time of diagnosis and not wait till the end of life. This might also help alleviate misconception of PPC only being offered during the end of life period. This study should help with the development of public and private politics aimed to promote the creation of PPC programs in developing countries.
Immunomagnetic separation is a suitable method for electrophysiology and ion channel pharmacology studies on T cells
Authors: Tajti Gabor , Szanto Tibor Gabor , Csoti Agota , Racz Greta , Evaristo César , Hajdu Peter , Panyi Gyorgy
Published: November 2020

Background:Ion channels play emerging role in the physiological and pathological function in many cell types, including the non-excitable immune cells. As immune cells represent a heterogeneous population with considerable functional diversity, subtype-specific functional studies, such as single-cell electrophysiology of ion channels (patch-clamp), require proper subset identification and separation. Magnetic-activated cell sorting (MACS) techniques provide an alternative to fluorescence-activated cell sorting (FACS), however, the potential impact of MACS on patch-clamp experiments were not studied yet. Among others, the presence of MACS-related beads on the cell surface may alter the biophysical and pharmacological parameters of the ion channels expressed in the membrane. This motivated our experiments to describe the feasibility of MACS for electrophysiology studies on immune cells. We examined the biophysical and pharmacological parameters of the voltage gated Kv1.3 K+ channel in activated CD4+ T-cells as well as the membrane capacitance following immunomagnetic positive separation, using the REAlease® kit. This kit allows three experimental configurations: bead-bound configuration, bead-free configuration following the removal of magnetic beads and the label-free configuration following removal of the REAlease® complex congaing the antibody fragment that recognizes CD4. As controls we used FACS separation as well as immunomagnetic negative selection.Results:We found similar purity and cell viability using FACS or MACS-based positive (REAlease®) and negative selection approaches. The membrane capacitance and of the biophysical parameters of Kv1.3 gating, voltage-dependence of steady-state activation and inactivation kinetics of the current were oblivious to the presence of the beads or any components of the REAlease® kit on the cell surface. We found subtle differences in the activation kinetics of the Kv1.3 current in cells obtained using various cell isolation configurations that could not be explained by the presence of MACS-related compounds on the cells. Neither the equilibrium block of Kv1.3 by TEA or charybdotoxin (ChTx) nor the kinetics of ChTx block are affected by the presence of the magnetics beads on the cell surface. Conclusions:Taken together our results support, that MACS is a suitable method for studying ion channel in non-excitable cells, such as T-lymphocytes with the benefit of easy application and relatively low instrumentation costs.
Real Time Viral Sub-Strains Discovery in Emerging Infectious Disease Situation – The African Perspective
Authors: Ekpenyong Moses Effiong , Uzoka Faith-Michael , Edoho Mercy , Inyang Udoinyang G. , Udo Ifiok J , Uto Nseobong P. , Ekaidem Itemobong S. , Moses Anietie E. , Anwana Enoabasi D. , Tatfeng Youchou M. , Joseph Geoffery , Dan Emmanuel A. , Ndunagu Juliana
Published: November 2020

Background: The increased number of accessible genomes has prompted large-scale comparative studies for discerning evolutionary knowledge of infectious diseases, but challenges such as non-availability of close reference sequence(s), incompletely assembled or large number of genomes, preclude real time multiple sequence alignment and sub-strain(s) discovery. This paper introduces a cooperatively inspired open-source framework, for intelligent mining of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes. We situate this study within the African context, to drive advancement on state-of-the-art, towards intelligent infectious disease characterization and prediction. The outcome is an enriched Knowledge Base, sufficient to provide deep understanding of the viral sub-strains’ identification problem. We also open investigation by gender, which to the best of our knowledge has been ignored in related research. Data for the study came from the Global Initiative on Sharing All Influenza Data database (https://gisaid.org) and processed for precise discovery of viral sub-strains transmission between and within African countries. To localize the transmission route(s) of each isolate excavated and provide appropriate links to similar isolate strain(s), a cognitive solution was imposed on the genome expression patterns discovered by unsupervised self-organizing map (SOM) component planes visualization. The Freidman-Nemenyi’s test was finally performed to validate our claim. Results: Evidence of inter- and intra-genome diversity was noticed. While some isolates (or genomes) clustered differently, implying different evolutionary source (or high-diversity), others clustered closely together, indicating similar evolutionary source (or less-diversity). SOM component planes analysis revealed multiple sub-strains patterns, strongly suggesting local- or intra-community and country to country transmissions. Cognitive maps of both male and female isolates revealed multiple transmission routes. Freidman’s test results showed highly significant difference (p<0.01) among the various isolate groups. Nemenyi’s test revealed groups that differed in their isolates.Conclusion: The proposed framework offers explanations to SARS-CoV-2 diversity and provides real time identification to disease transmission routes, as well as rapid decision support for facilitating inter- and intra-country contact tracing of infected case(s). Intermediate data produced in this paper are helpful to enrich the genome datasets for intelligent characterization and prediction of COVID-19 and related pandemics, as well as the construction of intelligent device for accurate infectious disease monitoring.
Treatment of Non-small cell lung cancer with AiDi injection based on network pharmacology
Authors: Qiu Suishan , Xue Lianfang , Liu Hui , Zhong Huiting , Li Leping
Published: November 2020

Background: This study aimed to determine the bioactive compounds, core genes, and pharmacological mechanisms underlying the effects of Aidi injection (ADI) in non‐small cell lung cancer (NSCLC), and to provide a further research directions. Material and Methods: The bioactive compounds of ADI were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and the Traditional Chinese Medicines Integrated Database, while targets related to these bioactive compounds and NSCLC were obtained from the GEO database. Cytoscape software was used to construct ingredients–protein-targets–pathway networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses and network analysis were performed to investigate potential mechanisms underlying the effects of ADI on NSCLC.Results: This study screened 45 bioactive compounds and 38 major proteins of ADI as potential agents that can act against NSCLC. The results revealed the following potential therapeutic targets of ADI in the treatment of NSCLC: FOS, VEGFA, EGFR, JUN, MMP9, IL2, STAT1, CASP1, NFKBA, and CDK2. The potential mechanisms via which ADI acts against NSCLC are closely related to the inhibition of apoptosis and the activation of signaling pathways. Conclusion: This study has revealed the multicompound, multitarget, and multichannel characteristics of ADI. This provides novel insight into further research investigations of the mechanism of ADI in NSCLC treatment.
Successful Treatment of Severe Myocardial Injury Complicated With Refractory Cardiogenic Shock Caused by AOPP Using Extracorporeal Membrane Oxygenation
Authors: Li Yang , Cao ChunShui , Luo XiaoLong , Huang Liang
Published: November 2020

Acute organophosphorus pesticide poisoning (AOPP) is a common critical illness observed in clinical practice, and severe AOPP can cause serious cardiac toxicity. We report a case of severe myocardial injury caused by AOPP complicated with refractory cardiogenic shock that was successfully rescued with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy. We suggest that for patients with severe myocardial injury complicated with cardiogenic shock following AOPP, the use of VA-ECMO therapy can improve the prognosis.
A Novel Amorphous Curcumin Preparation Improved Oral Absorption Efficiency in Healthy Volunteers: A Single-Dose, Double-Blind, Two-Way Crossover Study
Authors: Sunagawa Yoichi , Miyazaki Yusuke , Funamoto Masafumi , Shimizu Kana , Shimizu Satoshi , Nurmila Sari , Katanasaka Yasufumi , Ito Masashi , Ogawa Tatsuya , Ozawa-Umeta Hitomi , Hasegawa Koji , Morimoto Tatsuya
Published: November 2020

Background: Curcumin has diverse biological activities such as anti-cancer, antioxidant, and anti-inflammatory properties and is assumed to exhibit beneficial effects in the prevention and treatment of various diseases. Although curcumin is known to be safe in humans, its therapeutic efficacy is limited owing to its poor bioavailability. To overcome this problem, we prepared a novel curcumin preparation curcuRougeTM using the amorphous solid dispersion method. In this study, we aimed to investigate the oral absorption efficiency of curcuRougeTM and compare its efficiency with that of Theracurmin®, a highly absorptive curcumin preparation dispersed with colloidal submicron-particles exhibiting improved bioavailability, in rats and healthy volunteers. Methods: In the animal experiment, male Sprague–Dawley rats were orally administered curcuRougeTM or Theracurmin® (10 mg/kg of curcumin). The plasma curcumin levels were measured at 0.25, 0.5, 1, 2, 4, and 6 h after administration. In addition, we performed a single-dose, double-blind, two-way crossover study to compare plasma curcumin levels after the administration of curcuRougeTM or Theracurmin® in humans. Twelve healthy volunteers were administered curcuRougeTM or Theracurmin® containing 30 mg curcumin. The plasma curcumin concentrations at 0.5, 1, 2, 4, and 8 h after ingestion were determined. Results: The area under plasma concentration–time curve (AUC0-6 h) and maximum plasma concentration (Cmax) of curcuRougeTM in rats were 3.7- and 9.6-fold higher than those of Theracurmin®, respectively. Twelve healthy volunteers were orally administered 90 mg of curcuRougeTM or Theracurmin® in a randomized double-blind crossover study. In these volunteers, the AUC0-8 h and Cmax of curcuRougeTM were 3.4-fold and 5.4-fold higher than those of Theracurmin®, respectively. Conclusion: These findings indicate that curcuRougeTM shows better bioavailability than other highly absorptive curcumin preparations, such as Theracurmin®. Hence, curcuRougeTM is assumed to exhibit clinical efficacy for managing various diseases at a low dose.Trial registration: The trial was registered with the UMIN Clinical Trials Registry (January 8, 2020, UMIN000039083, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000044573).
Inflammatory Arthritis Complicating Galactosialidosis: A Case Report
Authors: Verkuil F. , Bosch A.M. , Struijs P.A.A. , Hemke R. , Berg J.M. van den
Published: November 2020

Background Galactosialidosis (GS) is a rare inherited lysosomal storage disorder (LSD) which is characterized by a defect in the lysosomal glycoprotein catabolism. We report, for the first time, the case of a child affected by GS presenting with recurrent episodes of extensive joint inflammation in both knee joints. The aim of this case-report is to describe the clinical presentation as well as the laboratory, radiologic and microscopic features of this unique presentation of GS. Furthermore, we explore inflammatory mechanisms potentially responsible for the origination of the arthritic joint pathology observed in our patient.Case presentationWe describe the rare case of a 12-year-old boy diagnosed with GS (late infantile form) who presented with multiple episodes of inflammatory arthritis involving both knees; no other joints were suspected for joint inflammation. Laboratory results did not indicate an autoimmune disorder. Synovial fluid tested negative for any bacterial infection and ruled out a malignancy and crystal induced arthritis. Microscopic examination of the synovial tissue revealed numerous foamy macrophages with extensive vacuolization, consistent with the previous diagnosis of GS. Treatment consisted of aspiration of excessive joint fluid and subsequent intra-articular injection of triamcinolonhexacetonide with excellent but transient result. Given the evidence of storage products within macrophages of the inflamed synovial tissue and the absence of other etiological clues, GS itself was considered as the primary cause for the relapsing inflammatory joint pathology. According to the restricted data on articular manifestations in GS, to date, GS cannot be linked directly to joint inflammation. Nevertheless, in several other LSDs, the accumulation of storage material has been associated with numerous osteoimmunological changes that might play a role in the pathophysiology of arthritic processes. Conclusions We hypothesize that the articular build-up of GS storage products triggered systemic as well as local inflammatory processes, resulting in the extensive inflammatory joint pathology as observed in our patient. Future identification of other patients with GS is required to corroborate the existence of an arthritic clinical phenotype of GS and to assess the underlying pathophysiology.
Platelets Count During Circulatory Assistance: Involvement in the Changes of Oxygenation Membrane
Authors: Azhari Alaa , Sawadogo Adama , D'ostrevy Nicolas , Lambert celine , Pereira Bruno , Azarnoush Kazra , CAMILLERI Lionel
Published: November 2020

BackgroundTo study the evolution of platelet count during patient treatment with Extra-Corporeal Membrane Oxygenation (ECMO) and the causes of Membrane Oxygenation (MO) exchange. Assessment of the morbidity and mortality rate was our secondary objective. MethodsA single center retrospective study was conducted from January 2014 to December 2015. One-hundred and thirty-nine MO exchanges were studied over 73 patients who received 66 MO exchange. Alterations in biological parameters were compared before and after each MO exchange, to study the device-related platelet count evolution. ResultsMean patient age was 56.8 ± 13.4 years. The mean duration of the MO was 5.9 ± 3.1 days, exchanged 26 times (68%) after clot formation. The median Survival After Veno-arterial ECMO score (SAVE score) was -3.5 [-4; -1] interquartile range [IQR]. The median Respiratory Extra-corporeal membrane Oxygenation Survival Prediction score (RESP score) was -1 [-3; 0] [IQR]. A significant decrease (p<0.001) in platelet count between the first and second MO exchange was observed in comparison with the baseline. Yet a steady decline was noted after the third MO exchange, afterwards, normalization was observed after ECMO weaning. During ECMO, a decrease in platelet count from the baseline was found after the first MO on day 2 (p<0.001), the delta was 58.000 ± 19.000 /µL, followed by an additional significant decrease on day 3 (p=0.001). The average platelet transfusion was 0.6 ± 1.4 units. Interestingly, the more MO was exchanged, the lesser blood products transfusion was done. The overall mortality rate was 39 %; in Veno-Arterial ECMO (VA-ECMO) it was 34.48% and 41.38 % in Veno-Venous ECMO (VV-ECMO). Conclusion﻿Clot formation is the leading cause of MO exchange during ECMO. Therefore, there is a significant decrease in platelets count starting from day 2 that indicates platelets transfusions in order to prevent complications of hemostasis.
Estimation of 18F-FDG PET Image Texture Features for Metastasis Prediction in Non-Small Cell Lung Cancer Using Epithelial Mesenchymal Transition-Related Genes
Authors: Kim Byung-Chul , Lim Ilhan , Byun Byung Hyun , Kim Jingyu , Woo Sang-Keun
Published: November 2020

Purpose: The aim of this study was to estimate a metastasis prediction image factor in non-small cell lung cancer by correlation next generation sequence gene expression level and fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography image features.Methods: RNA-sequencing data and 18F-FDG PET images of 63 patients with NSCLC (29 metastasis and 34 non-metastasis) from The Cancer Imaging Archive and The Cancer Genome Atlas Program databases were used in a combined analysis. Weighted correlation network analysis was performed to identify gene groups were related metastasis. Module was selected with high module significance. Genes selection was performed by gene function related metastasis and high AUC (AUC > 0.6). A total of 47 image features were extracted from PET images as radiomics. The relationship of Gene expression and image features were calculated by using a hypergeometric distribution test with the Pearson correlation method. Metastasis prediction model was validated by random forest algorithm using image texture features related gene expression.Results: 36 modules were identified by gene expression pattern with WGCNA assay. The modules had highest module significance was selected assay. 7 genes from selected module were identified to involve in the epithelial mesenchymal transition pathway that have important role in the cancer metastasis and had high AUC. Also, expression of these genes was related to quantitative of image feature (GLCM_contrast, -log10 P-value: 2.45~3.89). The AUC value (accuracy: 0.856 ± 0.06, AUC: 0.868 ± 0.05) was shown from the EMT-related gene and GLCM_contrast model and AUC value (accuracy: 0.842 ± 0.06, AUC: 0.838 ± 0.09) was shown from GLCM_contrast image texture model. Conclusion: GLCM_contrast image texture feature shows relationship with EMT related gene expression. We developed a model for predicting metastasis of non-small cell lung cancer using 18F-FDG PET image feature and evaluated its accuracy.
Far Infrared Light Irradiation Enhances Microglial Aβ Clearance and Ameliorates Cognitive Deficit in Alzheimer’s Disease-Like Mice
Authors: Li Qingyong , Wu Wensi , Lu Yanan , Wen Jing , Ren Jiaoyan , Zhao Huiying , WANG Zhi
Published: November 2020

BackgroundExposure to sunlight may decrease the risk of developing Alzheimer’s disease (AD). However, the wavelength of the light with this therapeutic effect and the related mechanism remain elusive. MethodWe evaluated the behaviors of AD-like mice treated by light of different wavelengths and showed that far infrared (FIR) light (λ = 3 - 25 μm) had a great potential in ameliorating cognition dysfunction. ResultsFIR light treatment promoted the recruitment of microglia to Aβ plaques, enhanced the phagocytosis of Aβ and decreased neuroinflammatory responses. Thus, FIR light treatment had a broad spectrum of beneficial effects on the brain, including alleviating the Aβ burden and neuroinflammation. Conclusions﻿As a result, FIR light treatment ameliorates the learning and memory impairment in AD-like mice. Our findings uncovered a previously unappreciated function of FIR light, suggesting that FIR light treatment may be a potential therapeutic strategy for AD.
Genetic Profiling in Heterogeneous High-Grade Adenoid Cystic Carcinoma Identifies NOTCH1 Inhibition as a Therapeutic Strategy
Authors: Wang Yu , Sun Bao , Zhang Chunye , Xia Ronghui , Wang Lizhen , Sun Jingjing , Gu Ting , Tian Zhen , Li Jiang
Published: November 2020

Background

High-grade adenoid cystic carcinomas (ACCs), consisting mostly of the solid type along with the occasional high-grade transformation (ACC-HGT) type, are highly aggressive and heterogeneous tumors. Because of the rarity of the tumors, therapeutic strategy guided by genetic profiles based on next generation sequencing (NGS) has been not published on these tumors.
Results

Forty-four tissues microdissected from 36 high-grade ACC cases (31 solid type ACCs and 5 ACC-HGTs) were included in our study. The solid components from the 31 solid ACCs, were enriched for mutations of genes in the NOTCH (NOTCH1, 68%; SPEN 23%) and the chromatin-remodeling pathway and were absent of the myoepithelial cell differentiation. The cases with NOTCH1 mutation exhibited strong NCID expression, which was associated with poor distant metastasis-free survival. BRCA2 mutation was observed in 23% of solid ACCs, conferring sensitivity to PARP inhibitors. From 5 of the solid ACCs, the intratumor heterogeneity was delineated between the cribriform/tubular and the solid components. NOTCH1 and FGFR2 mutations as well as NOTCH2 amplification were restricted to the solid component indicating the clonal selection within the same tumor. From 2 aggressive solid ACCs the subclones evolved in progression for local relapse and distant metastasis, although they manifested close genomic resemblance to primary tumors. Five tumors of ACC-HGTs were characterized by a loss of biphasic ductal-myoepithelial differentiation in HGT area and enriched for alterations in the NOTCH, P53 and PI3K pathways. Guided by the genetic profiles, the preclinical efficiency of a gamma-secretase inhibitor BMS-906024 was evaluated in the ACC patient-derived xenografts (PDXs) models with activating NOTCH1 mutation and it demonstrated robust antitumor effects.
Conclusion

This is the first report to describe the intratumor heterogeneity within a solid ACC as well as the intertumor evolution of clones among the primary/recurrent/metastatic tumors. Different from conventional ACCs, high-grade ACCs should be approached with a distinct therapeutic strategy particularly targeting NOTCH1 by gamma-secretase inhibitors. Microdissecting the highest grade component guided by histology is a highly recommended tumor sampling strategy and facilitates the detection of key molecular targets.
PACAP-derived peptide MPAPO impacts Adipose-derived stem cells adipogenic differentiation
Authors: Xian Wang Zi , Qian Liu , Min Liu Jian , Qiong Zheng Zi , Jia Feng , Yan Ji Chun , Xin Dai Jia , Qing Zhou Hai , Yi Ma
Published: November 2020

BackgroundRegenerative medicine and tissue engineering have brought new therapeutic prospects to the treatment of soft tissue defects, but the selection of seed cells is the key to treatment. Adipose-derived stem cells (ASCs) have always been a popular candidate for seed cells because of their rich sources, easy access, high plasticity, and strong value-added capabilities. The purpose of the current study is to explore the role of PACAP -derived peptide MPAPO on the adipogenic differentiation of ASCs and its molecular mechanism.MethodsThe effect of MPAPO on the proliferation of adipose-derived stem cells were detected by CCK-8 assay and PI single-staining-flow. To reveal the direct effect of MPAPO on the adipogenic differentiation of ASCs, a model of adipogenic differentiation of adipose stem cells was established. In addition, adipogenic differentiation capacity was assessed using Oil-Red-O Staining, Triglyceride (TG) assay and quantification of gene expression. Finally, the relationship between ASCs adipogenic differentiation and the ERK signaling pathway was explored by Western blot.ResultsMPAPO treatment can significantly promote the proliferation of ASCs. In addition, PACAP treatment improves the adipogenic differentiation efficiency of ASCs, including promoting the accumulation of lipid droplets and triglycerides, and the expression of adipogenic-related transcription factors PPARγ and C/EBPα. The mechanism studies showed that MPAPO selectively binds to the PAC1 receptor to promote the adipogenic differentiation of ASCs via activating the ERK signaling pathway.ConclusionsThe present study shows that MPAPO could promote the adipogenic differentiation of ASCs by activating the ERK signaling pathway, and provide relevant experimental evidence for the filling of clinical tissue defects.
Sex-dependent Gut Microbiota-brain-cognition Associations: A Multimodal MRI Study
Authors: Zhang Shujun , Cai Huanhuan , Wang Chunli , Zhang Cun , Zhao Wenming , Zhang Tingting , Zhang Biao , Chen Jingyao , Liu Siyu , Zhu Jiajia , Yu Yongqiang
Published: November 2020

Background: There is bidirectional communication between the gut microbiota and the brain. Empirical evidence has demonstrated sex differences in both the gut microbiome and the brain. However, the effects of sex on the gut microbiota-brain associations have yet to be determined. Methods: 157 healthy young adults underwent brain structural, perfusion, functional and diffusion MRIs to measure gray matter volume (GMV), cerebral blood flow (CBF), functional connectivity strength (FCS) and white matter integrity, respectively. Fecal samples were collected and 16S rRNA gene amplicon sequencing was utilized to assess gut microbial diversity. Correlation analyses were conducted to test for sex-dependent associations between microbial diversity and brain imaging parameters, and mediation analysis was performed to further characterize the gut microbiota-brain-cognition relationship. Results: We found that higher gut microbial diversity was associated with higher GMV in the right cerebellum Ⅵ, higher CBF in the bilateral calcarine sulcus yet lower CBF in the left superior frontal gyrus, higher FCS in the bilateral paracentral lobule, and lower diffusivity in widespread white matter regions in males. However, these associations were absent in females. Of more importance, these neuroimaging biomarkers significantly mediated the association between gut microbial diversity and behavioral inhibition in males. Conclusions: These findings highlight sex as a potential influential factor underlying the gut microbiota-brain-cognition relationship, and expose the gut microbiota as a biomarker-driven and sex-sensitive intervention target for mental disorders with abnormal behavioral inhibition.