bluuebunny/crossref_metadata_2025 huggingface dataset:
Waterflood Analysis with Pulse-Code Pressure Interference Testing in Eastern Siberia Carbonate Reservoirs
Authors: Kim Vasiliy , Aslanyan Artur , Gulyaev Danila , Farakhova Rushana
Published: June 2020

The waterflood performance depends on two major components: the sweep efficiency and displacement efficiency.

The sweep efficiency depends on proper understanding of the vertical and lateral distribution of reservoir properties.

One of the methods to check and calibrate this understanding is to perform pressure interference test (PIT) in few cross-well intervals.

Unfortunately, a proper implementation of traditional step-response PIT with objective for quantitative interpretation requires shutting-down the wells, preferably the whole area around receiving well resulting in punishing production deferment.

This was a bottle-neck for wide spread of quantitative PIT for many decades.

This paper describes the experience with a specific implementation of PIT – Pressure Pulse Code Test (PCT) – which allows data acquisition under scheduled production.

The trade-offs are usually acceptable: longer field operations, high resolution downhole gauges, more complex and longer data processing, advanced software tools and as result – a more expensive service, which anyway comes much cheaper than production deferment.

The paper shows how PCT can be qualified using the synthetic field tests and real field tests and shows a typical application of PCT findings in one of the Eastern Siberian carbonate reservoirs.
Assessment on Gas Re-Injection Performance After 19 Years: A Brownfield Case Study
Authors: Abdul Razak Muhammad Firdaus , Ariffin Mohd Hafizi , Ratwant Singh Gurveen Singh , Khalid Aizuddin
Published: June 2020

Field D is located in an average water depth of about 115ft in the Balingian province, about 35 km northwest offshore of Bintulu, Sarawak. The field was discovered in 1983 by drilling D-1 exploration well, and subsequently delineated by seven (7) appraisal wells. The field recovery mechanism is predominantly solution gas drive with limited aquifer support in the North and North-east of the Cycle II Sheet reservoir. Within three years of production, oil rate has rapidly declined to around 10,000 stb/d with gas oil ratio (GOR) increasing from 800 scf/stb to around 3,000 scf/stb. Gas re-injection scheme was introduced in 2000 with Gi/Gp performance was the main control measure to optimize the injection efficiency. This paper presents the performance of two major reservoirs in D Field with gas re-injection schemes.

The first part of this paper discusses the performance of Reservoir C3-3A. Wells performance during pre-injection period was studied. Basic performance plots such as Qo vs Time and GOR vs Time were utilized to understand the well behavior and decline curve analysis (DCA) was used to calculate the NFA reserves for this reservoir. The performance of this reservoir after the gas re- injection was then further analyzed. Similar performance plots are utilized (Qo vs t, GOR vs t, DCA) with the addition of injection wells performance plot. The oil producers performance were plotted to compare their reaction toward different injection rates. The Gi/Gp control measure was applied as part of the reservoir management target. In order to quantify the incremental reserves from the gas re-injection, oil DCA plots were established. Similar approach was applied for the second reservoir, C3-4A.

In overall, the gas re-injection in D Field has successfully arrested the annual field decline rate from 45% to 20% and increased the ultimate recovery factor to 35% after 19 years of re-injection. However, further scrutiny towards each well showed that some inefficiencies did occur in the re- injection schemes. Due to poor location of injector wells, some oil producers produced excessive GOR due to gas recycling if the gas injection rate was maintained as per Gi/Gp target. This resulted in lower oil recovery and lower revenue from gas export. Furthermore, some injectors were also not injecting as per target due to poor reservoir quality and mechanical issues. Lessons captured from 19 years of re-injection history will be the reference to set the operating strategy of existing and future injection wells at field D.

The information and lessons learnt from this paper will be applicable for future field development involving gas re-injection by setting an example on how to design optimum gas injection strategy.
Acid Fracture Design Optimization in Naturally Fractured Carbonate Reservoirs
Authors: Alsulaiman Monther Mohammed , Aljawad Murtada Saleh , Palharini Schwalbert Mateus , Alafnan Saad , Abdlwahab Mohammed
Published: June 2020

Carbonate formations, which are candidates for acid fracturing, are usually naturally fractured. The existence of fracture networks has important impacts on fracture design outcomes. Previous studies have investigated the interaction between induced and natural fractures. However, these studies have seldom considered the impact of reactive fluid systems. In this work, a model was developed to explain acid distribution in hydraulic and intersecting natural fractures. This model was then used to optimize acid fracture design parameters based on the goal of maximizing productivity.

A fracture propagation model coupled with acid transport, reaction, and heat transfer was employed to determine the acid etched-width distribution and stimulated reservoir area. The outcome of the coupled model was the acid dissolution and conductivity distribution of a natural fracture network intersecting a hydraulic fracture. Then, a productivity model was utilized to evaluate the performance of the acid fractured well.

A parametric study was also conducted to understand the impact of natural fractures on the optimum design conditions. Different natural fracture intensities (i.e., spacing) were investigated at different reservoir permeability. It was observed that the existence of natural fractures significantly altered acid placement in the reservoir. The result was well productivity quite different from what was seen in cases with no natural fractures. Also, the optimum design conditions (e.g., injection rate) differed based on the natural fractures' characteristics and reservoir properties. It was found that the existence of natural fractures significantly reduced the productivity of fractured wells.

The model developed here was used to explain the complex interactions of acid fractures in naturally fractured carbonate formations. The effects of natural fractures on acid placement and optimum design conditions can now be estimated. Such information, which has rarely been considered, is imperative for better stimulation design in this type of formation.
LNG Market - Passing Trend or Effective Solution During Energy Transition - Global Market Forecast for 2020-2030
Authors: Kiebzak Piotr Wojciech , Czerniawski Filip Krzysztof
Published: June 2020

LNG shipments are nothing new in the face of technology. The first tanker shipment of LNG took place from Lake Charles, LA bound for Canvey Island in the UK in 1958 aboard the experimental vessel, the Methane Pioneer. So, why do people focus on this subject so much since mid 2000's? One of the key factors is technology, that reduced costs of LNG trades. More and more countries see that as a chance to diversify their imports. In 2023 Poland wants to cover over 35% of annual consumption with 7,5 bln cubic meters in LNG shipments. With this strategy there is a big chance for Poland to stop being dependent to Russia in 2023. Main forces that drive the interest for LNG shipments are:

The growing concern for traditional supplies in the face of growing consumption, The effects of technology on cost reduction making previously uneconomic trades attractive, Environmental concerns, in some countries gas will replace coal in energy mix, Increasing liquidity in the global gas market,

LNG trade gives new opportunities for both seller and buyer. It enables importing markets to shift trading directions thus gain energy independence as well as avoid supply shortages.

Liberalization of market - influencing changes in contracts align with spot transactions drain the prices, making LNG even more attractive. On the other hand, the sellers experience completely new trading opportunities. Companies are able to engage in markets that were previously unavailable and escape adverse stockpile abundance.

Aim of the research is to identify major trends in LNG industry. Forecast main course and future role of LNG and natural gas in the energy mix. Model global supply and demand 2020 - 2030. Analysis also covers incoming investments and check their potential. Research based on the available resources from GLE investment database and similar resources from other regions. Data broaden by other documents from energy companies and local statistic ministries. Model with trusted available data adjusted by current news and energy trends in Europe and in global gas industry.

LNG market is expected to grow at around 1.3% annually. Global demand could increase from its current level of about 406 million tons per annum to 430 MTPA in 2025. For now natural gas is supported by policies to reduce air pollution and greenhouse gas emission and it will partly replace coal in energy mix in European countries. Today's challenge is to create liberal gas market and LNG is the answer on how to connect american, arab and european gas markets.
Development of the Prototype Concise Safe Systems Checklist Tool for General Practice
Authors: Litchfield Ian J , Spencer Rachel , Bell Brian , Avery Anthony , Perryman Katherine , Marsden Kate , Greenfield Sheila , Campbell Stephen
Published: June 2020

Background In the course of producing a patient safety toolkit for primary care, we identified the need for a concise safe-systems checklist designed to address areas of patient safety which are under-represented in mandatory requirements and existing tools. This paper describes the development of a prototype checklist designed to be used in busy general practice environments to provide an overview of key patient safety related processes and prompt practice wide-discussion. Methods An extensive narrative review and a survey of world-wide general practice organisations were used to identify existing primary care patient safety issues and tools. A RAND panel of international experts rated the results, summarising the findings for importance and relevance. The checklist was created to include areas that are not part of established patient safety tools or mandatory and legal requirements. Four main themes were identified: information flow, practice safety information, prescribing, and use of IT systems from which a 13 item checklist was trialled in 16 practices resulting in a nine item prototype checklist, which was tested in eight practices. Qualitative data on the utility and usability of the prototype was collected through a series of semi-structured interviews.Results In testing the prototype four of nine items on the checklist were achieved by all eight practices. Three items were achieved by seven of eight practices and two items by six of eight practices. Participants welcomed the brevity and ease of use of the prototype, that it might be used within time scales at their discretion and its ability to engage a range of practice staff in relevant discussions on the safety of existing processes. The items relating to prescribing safety were considered particularly useful. Conclusions As a result of this work the concise patient safety checklist tool, specifically designed for general practice, has now been made available as part of an online Patient Safety Toolkit hosted by the Royal College of General Practitioners. Senior practice staff such as practice managers and GP partners should find it a useful tool to understand the safety of less explored yet important safety processes within the practice.
Identifying essential proteins in dynamic protein networks based on an improved h-index algorithm
Authors: Dai Caiyan , Ju HE , Kongfa HU , Youwei DING
Published: June 2020

Background: The essential proteins in protein networks play an important role in complex cellular functions and in protein evolution. Therefore, the identification of essential proteins in a network can help to explain the structure, function, and dynamics of basic cellular networks. The existing dynamic protein networks regard the protein components as the same at all time points; however, the role of proteins can vary over time. Methods: To improve the accuracy of identifying essential proteins, an improved h-index algorithm based on the attenuation coefficient method is proposed in this paper. This method incorporates previously neglected node information to improve the accuracy of the essential protein search. Based on choosing the appropriate attenuation coefficient, the values, such as monotonicity, SN, SP, PPV and NPV of different essential protein search algorithms are tested.Results: The experimental results show that, the algorithm proposed in this paper can ensure the accuracy of the found proteins while identifying more essential proteins.Conclusions: The described experiments show that this method is more effective than other similar methods in identifying essential proteins in dynamic protein networks. This study can better explain the mechanism of life activities and provide theoretical basis for the research and development of targeted drugs.
Stigma and discrimination: barriers to the utilisation of a nutritional program in HIV care services in the Tigray region, Ethiopia.
Authors: Tesfay Fisaha , Javanparast Sara , Mwanri Lillian , Ziersch Anna
Published: June 2020

Background: In Ethiopia, stigmatising attitudes towards people living with HIV have reduced over time. This is mainly due to improved HIV knowledge and the expansion of access to HIV care and support services. However, HIV stigma and discrimination remain a key challenge and have negative impacts on access to and utilisation of HIV services including nutritional programs in the HIV care setting. A small number of studies have examined the experience of stigma related to nutritional programs, but this is limited. This study explored HIV status disclosure and experience of stigma related to a nutritional program in HIV care settings in Ethiopia and impacts on nutritional program utilisation. Methods: As part of a larger study, qualitative in-depth interviews were conducted with 20 adults living with HIV, 15 caregivers of children living with HIV and 13 program staff working in the nutritional program in three hospitals in the Tigray region of Northern Ethiopia. Framework thematic analysis was employed to analyse the data and NVivo 11 was used to analyse the qualitative interview data. This study is presented based on the consolidated criteria for reporting of qualitative research (COREQ). Results: The study found varying levels of positive HIV status disclosure, depending on who the target of disclosure was. Disclosing to family members was reported to be less problematic by most participants. Despite reported benefits of the nutritional program in terms of improving weight and overall health status, adults and caregivers of children living with HIV revealed experiences of stigma and discrimination that were amplified by enrolment to the nutritional program and concerns about unwanted disclosure of positive HIV status. This was due to: a) transporting, consuming and disposing of the nutritional support (Plumpynut/sup) itself, which is associated with HIV in the broader community; b) required increased frequency of visits to HIV services for those enrolled in the nutritional program and associated greater likelihood of being seen there. Conclusion: There was evidence of concerns about HIV-related stigma and discrimination among individuals enrolled in this program and their family members, which in turn negatively affected the utilisation of the nutritional program and the HIV service more broadly. Stigma and discrimination are a source of health inequity and undermine access to the nutritional program and other HIV services. Nutritional programs in HIV care should include strategies to take these concerns into account by mainstreaming stigma prevention and mitigation activities. Further research should be done to identify innovative ways of facilitating social inclusion to mitigate stigma and improve utilisation.
Meeting Psychosocial Needs to Improve Health: A Prospective Cohort Study
Authors: Snowden Austyn , Young Jenny , Savinc Jan
Published: June 2020

Background:Cancer impacts on patients and their families across a range of different domains. For that reason, optimal cancer care has moved away from a disease-centric focus to a more holistic approach in order to proactively support people with their individual needs and concerns. While international policy clearly advocates this agenda, implementation into routine care is limited. Therefore, relevant interventions that measurably improve patient outcomes are essential to understand if this ideal is to become routine multidisciplinary practice. The aim of this study was to analyse the impact of a proactive, holistic, community-based intervention on health-related quality of life in a cohort of people diagnosed with cancer. Secondary aim was to explore the relationship between changes in health status and: cancer type, cancer stage, number of concerns expressed and change in severity of concerns pre and post intervention.Method:Prospective observational cohort study. A convenience sample of 437 individuals were referred to the service ‘Improving the Cancer Journey (ICJ) in the UK. Each completed the Euroqol EQ-5D-3L and visual analogue scale (VAS) and a Holistic Needs Assessment (HNA) during initial visit to the service and again at follow-up review, median 84 days later. Change between scores was tested with paired t-tests and relationships between variables with multiple regression models with heteroscedasticity-consistent standard errors.Results:Participants were White British with median age between 50-64 years. Cancer type and stage were varied. EQ-5D utility scores improved at follow-up by 0.121 [0.0891-0.153], p<.001, and VAS scores improved by 7.81 [5.88-9.74], p<.001. The strongest predictor of change was a decrease in severity of concerns. Cancer stage ‘palliative care’ contributed to a reduction in health status.Conclusion:This study is the first to show that a holistic community intervention dedicated to supporting the individual concerns of participants had both a statistically significant and clinically meaningful impact on participants’ health-related quality of life. The mean change in EQ-5D scores was more than the ‘minimally important clinical difference’ described in the literature. This is important because while quality of life has multiple determinants, this study has shown for the first time that it is possible to capture a clinically meaningful improvement as a function of reducing someone’s personally identified concerns.
Designing and evaluating an interprofessional education conference approach to antimicrobial education
Authors: Guilding Clare , Hardisty Jessica , Randles Elsa , Statham Louise , Green Alan , Bhudia Roshni , Thandi Charan Singh , Teodorczuk Andrew , Scott Lesley , Matthan Joanna
Published: June 2020

Background Arguably, Medical School curricula are deficient in learning opportunities related to the safe and effective use of medicines, in particular antimicrobials. Infection management is complex and multidisciplinary, and learning opportunities should reflect these principles. Aligned to the complexity of the subject matter, simulation and interprofessional based teaching are methods that can foster the collaborative skills required of future healthcare professionals. There have been calls to develop these methods in the teaching of safe prescribing and the management of infections; however, reports of such studies are limited. Methods We developed an interprofessional education (IPE) conference for second year undergraduate medical and pharmacy students based in the North East of England. We considered contact theory in the design of three small group interprofessional workshops, on the broad themes of antimicrobial stewardship, infection management and patient safety. A mixed methods approach assessed students’ attitudes towards IPE, barriers and facilitators of learning, and perceived learning gains. Qualitative data from workshop evaluation forms were analysed thematically, while quantitative data were analysed descriptively and differences between medical and pharmacy cohorts analysed using unpaired two-tailed t-tests.Results 226/352 students returned the workshop evaluation forms (66% of pharmacy students, 62% of medical students). 281/352 students responded to a series of Likert scale questions on the value of interprofessional education (88% of pharmacy students, 70% of medical students). Students reported acquisition of knowledge and skills, including concepts and procedures related to infection management and antimicrobial prescribing, and the development of problem-solving and critical evaluation skills. Students reflected on their attitude towards interprofessional collaboration. They reported a greater understanding of the roles of other healthcare professionals, reflected on the importance of effective communication in ensuring patient safety, and were more confident to work in interprofessional teams after the conference. Conclusions A robust IPE event, theoretically underpinned by contact theory and developed collaboratively, achieved interprofessional learning at scale and helped develop healthcare professionals willing to collaborate across disciplines. The resources, and evaluation insights based on the 3P (presage, process, and product) model of learning and teaching, will be of value to other educators who seek to develop theoretically-sound IPE interventions.
Determining a Critical Threshold for G6PD Activity below which RBC Response to Oxidative Stress is Poor
Authors: Swastika Maria , Harahap Alida R , Panggalo Lydia V , Jusman Sri Widia A , Satyagraha Ari W
Published: June 2020

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder in the world. Its main function is to generate NADPH that is required for anti-oxidative pathway in the cells especially in red blood cells (RBC). G6PD deficiency is X-linked and thus subject to random X-chromosome inactivation in women giving them mosaic expression of G6PD activities in their individual cells. This phenomenon makes it difficult for diagnosis with the currently available G6PD qualitative diagnostic tests. With the rolling out of newly marketed anti-malarial drug tafenoquine, which has a long half-life, screening for G6PD deficiency becomes a necessity where those with <70% G6PD activity cannot receive this drug. Thus, evidence for a quantitative cut-off for G6PD activity is needed to ensure safe drug administration.Methods RBC models were developed to analyse the effect of oxidant on RBC oxidative markers namely total glutathione (GSH)and malondialdehyde (MDA). G6PD activity was measured using quantitative assay from Trinity Biotech and was correlated with cytofluorometric assay. RBC from twoG6PD heterozygous women with different G6PD activities were also analysed for comparison.Results There was a negative correlation between G6PD activity and CuCl concentration and a strong association between G6PD activities and proportion of G6PD normal RBC in CuCl-treated models and in ex vivo RBC. However, in terms of oxidative stress markers analyses, unlike the hypothesis where the lower G6PD activity, the higher MDA and the lower GSH level, the CuCl RBC model showed that in low G6PD activities (10-30%) cells, the MDA level is lower compared to the rest of the models (p<0.05). The ex vivo models however were in line with the hypothesis, although the result was not significant (p=0.5). There was a significant difference between RBC with <60% and those with >80% G6PD activities in CuCl RBC model, but not in ex vivo RBC (p=0.5). Genotyping heterozygous subjects showed G6PDViangchan variant with 2.97U/gHb (33% activity) and 6.58 U/gHb (74% activity). Conclusions The GSH analysis has pointed to the 60% G6PD activity cut-off and this data is supportive of the old World Health Organization threshold for intermediate upper limit of 60% G6PD activity. However, there are significant limitations in using MDA assay with CuCl RBC model because the RBC was already stressed due to the copper treatment and thus present a different result when compared to the ex-vivo model.
Motivations and expectations driving community participation in entomological research projects: Target Malaria as a case study in Bana, Western Burkina Faso
Authors: Barry Nourou , Toé Patrice , Pare/Toe Lea , Lezaun Javier , Drabo Mouhamed , Dabiré Roch , Diabate Abdoulaye
Published: June 2020

Background Most field entomology research projects require active participation by local community members. Since 2012, Target Malaria, a not-for-profit research consortium, has been working with residents in the village of Bana, in Western Burkina Faso, in various studies involving mosquito collections, releases and recaptures. The long-term goal of this work is to develop innovative solutions to combat malaria in Africa with the help of mosquito modification technologies. Since the start of the project, Bana residents have played an important role in research activities, yet the motivations and expectations that drive their participation remain under-investigated. This study examines the factors that motivate some members of the local community to contribute to the implementation of Target Malaria’s activities, and, more broadly, explores the reasons that animate citizen participation in entomological research work in malaria-endemic regions. Methods A qualitative approach was used to survey the factors motivating members of the local community to assist in the implementation of Target Malaria’s entomological research activities in Bana. Eighty-five individual in-depth and semi-structured interviews were conducted, followed by three focus groups, one with youths who had participated in mosquito collections, and two with adult men and women from the village. All data collected were fully transcribed, processed, and subjected to thematic content analysis. Results Data showed that the willingness of local community members to participate in entomological research activities was informed by a wide range of motivational factors. Although interviewees expressed their motivations under different semantic registers, the data showed a degree of consistency around five categories of motivation: (a) enhance domestic protection from mosquitoes and malaria, (b) contribute to a future world free of the disease, (c) acquire knowledge and skills, (d) earn financial compensation, and (e) gain social prestige for the village.Conclusion These varying motivations reflect a set of differing personal and collective perceptions about the participation process, combining short and long-term, individual and collective motivations. Beyond the specific circumstances of this case, the study highlights the complex reasons that drive collective participation in entomological research and vector control activities. Detailed knowledge of community expectations should underpin any effort to mobilize local participation in field research activities.
Clinical features, treatment, and survival outcome of primary pulmonary NUT midline carcinoma
Authors: Xie Xiaohong , Wang Liqiang , Qin Yinyin , Lin Xinqing , Xie Zhanhong , Liu Ming , Zhang Jiexia , Ouyang Ming , Liu Jun , Gu Yingying , Li Shiyue , Zhou Chengzhi
Published: June 2020

Objective: NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinical features and report the treatments, especially with immune checkpoint inhibitors (ICIs), and outcomes of patients with primary pulmonary NMC. Methods: A retrospective review of patients with primary pulmonary NMC was performed in the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2018. Clinical manifestations as well as radiographic and pathological findings were recorded. Whole-exome sequencing (WES), a predictor for ICI response, was used to determine the tumour mutational burden (TMB). Treatments, especially by immune checkpoint blockade, and patient survival were analysed.Results: Seven patients with primary pulmonary mass (four men and three women) with a mean age of 42 years (range, 23–74) who were diagnosed with NMC according to NUT immunohistochemistry staining were included for analysis. One patient had a rare fusion of CHRM5-NUTM1 by tumour sequencing. A wide range of TMB (1.75–73.81 mutations/Mbp) was observed. The initial treatments included chemotherapy (5/7, 71.4%), surgery (1/7, 14.3%), and radiotherapy (1/7, 14.3%). Five patients (5/7, 71.4%) received ICIs (programmed cell death protein 1 [PD1]/programmed cell death ligand 1 [PDL1] monoclonal antibody) as second- or higher-line treatments. The median overall survival (OS) was 4.1 months (range, 1.5–26.7 months). Conclusions: Patients with primary pulmonary NMC have a poor prognosis and chemotherapy is often preferred. Checkpoint immunotherapy is a good option as the second- or higher-line treatment. TMB seems to be not associated with OS.
Association of MC4R (rs17782313) with diabetes and cardiovascular disease in Korean men and women
Authors: Sull Jae Woong , Kim Gitae , Jee Sun Ha
Published: June 2020

Background: Diabetes is mostly assessed by the fasting glucose level. Several studies reported that serum fasting glucose levels and cardiovascular disease are associated with MC4R. Methods: A total of 4,294 subjects participated in this study. There were 1810 subjects with cardiovascular disease among the 4294 subjects. We used multivariate linear regression models and multiple logistic regression analysis. Results: Individuals with the TC/CC genotype had a 1.29-fold higher risk of diabetes than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.29; 95% CI, 1.04-1.60). For healthy subjects, the association was significant in women (OR, 1.99; 95% CI, 1.01-3.93). Men with the TC/CC genotype had a 1.21-fold higher risk of cardiovascular disease than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.21; 95% CI, 1.04-1.41). The relationship between MC4R and cardiovascular disease was stronger in lean men (OR, 1.40; 95% CI, 1.12–1.74, p = 0.0028) than in overweight men.Conclusions: This study suggests that the rs17782313 SNP in MC4R is related to diabetes and the SNP is also associated with cardiovascular disease in lean men.
Innovative use of data sources: A Cross-sectional study of Data Linkage and Artificial Intelligence Practices across European Countries
Authors: Haneef Romana , Delnord Marie , Vernay Michel , Bauchet Emmanuelle , Gaidelyte Rita , Oyen Herman Van , Or Zeynep , Pérez-Gómez Beatriz , Palmieri Luigi , Achterberg Peter , Tijhuis Mariken , Zaletel Metka , Mathis-Edenhofer Stefan , Májek Ondřej , Haaheim Håkon , Tolonen Hanna , Gallay Anne
Published: June 2020

Background: The availability of data generated from different sources is increasing with the possibility to link these data sources with each other. However, linked administrative data can be complex to use and may require advanced expertise and skills in statistical analysis. The main objectives of this study were to describe the current use of data linkage at the individual level and artificial intelligence (AI) in routine public health activities, to identify the related estimated health indicators (i.e., outcome and intervention indicators) and health determinants of non-communicable diseases and the obstacles to linking different data sources. Method: We performed a survey across European countries to explore the current practices applied by national institutes of public health, health information and statistics for innovative use of data sources (i.e., the use of data linkage and/or AI). Results: The use of data linkage and AI at national institutes of public health, health information and statistics in Europe varies. The majority of European countries use data linkage in routine by applying a deterministic method or a combination of two types of linkages (i.e., deterministic & probabilistic) for public health surveillance and research purposes. The use of AI to estimate health indicators is not frequent at national institutes of public health, health information and statistics. Using linked data, 46 health outcome indicators, 34 health determinants and 23 health intervention indicators were estimated in routine. The complex data regulation laws, lack of human resources, skills and problems with data governance, were reported by European countries as obstacles to routine data linkage for public health surveillance and research. Conclusions: Our results highlight that the majority of European countries have integrated data linkage in their routine public health activities but only a few use AI. A sustainable national health information system and a robust data governance framework allowing to link different data sources are essential to support evidence-informed health policy development. Building analytical capacity and raising awareness of the added value of data linkage in national institutes is necessary for improving the use of linked data in order to improve the quality of public health surveillance and monitoring activities.
Molecular identification of severe fever with thrombocytopenia syndrome viruses from tick and bitten patient in Southeast China
Authors: Tong Yongxi , wang qiujing , Fu Yongfeng , Li Shibo , Zhang Zhao , Zhang Zheen , Yu Xuewen
Published: June 2020

Background Severe fever and thrombocytopenia bunyavirus (SFTSV) infection causes severe fever and thrombocytopenia syndrome with high mortality. It is extremely rare that a transmitting tick can be directly captured in bite wounds, and that SFTSV can be isolated from both the captured tick and patient’s serum to establish a solid pathogen diagnosis.Case presentation We report a case infected with severe fever and thrombocytopenia bunyavirus. The 69-year-old male patient presented with fever and tenderness on two lymph nodes in the right groin. A visible tick bite mark appeared on right upper quadrant of the patient’s abdomen, and a live tick was captured in the bite wound upon physical examination. The virus was detected in both the blood of the patient and in the tick that stayed in the bite wound for seven days. The phylogenetic analysis indicated that the SFTSV isolated from the tick and the patient’s serum sample belonged to type B, in which the L/S segment of these two isolates shared 100% homology, while the M segment had 99.9% homology. The bitten patient was given various supportive care, but eventually died of multiple organ failure. Conclusion The present case provides a strong evidence of SFTSV transmission from H. longicornis to humans, and suggests that direct cross-species transmission can occur without additional intermediate hosts.
Intra-articular Delivery of Celastrol by Hollow Mesoporous Silica Nanoparticles for pH-sensitive Anti-inflammatory Therapy against Knee Osteoarthritis
Authors: Jin Tian , Wu Di , Liu Xiao-Ming , Xu Jiang-Tao , Ma Bing-Jie , Ji Yun , Jin Yu-Ying , Wu Si-Yin , Wu Tao , Ke Ma
Published: June 2020

Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine(CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment. Methods: The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs.Results: CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment(pH=7.7) but revealed good solubility and therapeutic effect in acidic environment(pH=6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration(200 μg/mL) and the cell viability of chondrocytes stimulated by IL-1β was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1β, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group.Conclusion: Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.
Viewing an alpine environment positively affects emotional analytics in patients with stress-related psychiatric disorders and healthy controls
Authors: Hüfner Katharina , Ower Cornelia , Kemmler Georg , Vill Theresa , Martini Caroline , Schmitt Andrea , Sperner-Unterweger Barbara
Published: June 2020

Background: Patients with stress-related psychiatric (psychosomatic) disorders often don´t respond well to medical treatment and experience many side effects. It is thus of clinical relevance to identify alternative, scientifically based, treatments. Our approach is based on the recent evidence that urbanicity has been shown to be associated with an increased risk for mental disorders. Conversely green and blue environments show a dose-dependent beneficial impact on mental health. Methods: Here we evaluate the effect of viewing stimuli of individuals in an alpine environment on emotional analytics in 183 patients with stress-related psychiatric disorders and 315 healthy controls (HC). Emotional analytics (valence: unhappy vs happy, arousal: calm vs excited, dominance: controlled vs in control) were assessed using the Self-Assessment Manikin. Further parameters related to mental health and physical activity were recorded. Results: Emotional analytics of patients indicated that they feel less happy, less in control and had higher levels of arousal than HC when viewing neutral stimuli. The comparison alpine>neutral stimuli showed a significant a positive effect of alpine stimuli on emotional analytics in both groups. Patients and HC both felt attracted to the scenes displayed in the alpine stimuli. Emotional analytics correlated positively with resilience and inversely with perceived stress. Conclusions: Preventive and therapeutic programs for patients with stress-related psychiatric disorders should consider taking the benefits of outdoor natural environments into account. Organizational barriers which are preventing the implementation of such programs in clinical practice need to be identified and addressed.
Longitudinal changes in EEG power, sleep cycles and behaviour in a tau model of neurodegeneration.
Authors: Holton Christopher , Hanley Nicola , Shanks Elaine , Oxley Penny , McCarthy Andrew , Eastwood Brian J. , Murray Tracey K. , Nickerson Aidan , Wafford Keith A.
Published: June 2020

BACKGROUND: Disturbed sleep is associated with cognitive decline in neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The progressive sequence of how neurodegeneration affects aspects of sleep architecture in conjunction with behavioural changes is not well understood. METHODS: We investigated changes in sleep architecture, spectral power and circadian rhythmicity in the tet-off rTg4510 mouse overexpressing human P301L tau within the same subjects over time. Doxycycline-induced transgene-suppressed rTg4510 mice, tTa carriers and wild-type mice were used as comparators. Spectral power and sleep stages were measured from within the home cage environment using EEG electrodes. In addition, locomotor activity and performance during a T-maze task were measured. RESULTS: Spectral power in the delta and theta band showed a time-dependent decrease in rTg4510 mice compared to all other groups. After the initial changes in spectral power, wake during the dark period increased whereas NREM and number of REM sleep bouts decreased in rTg4510 compared to wild-type mice. Home cage locomotor activity in the dark phase significantly increased in rTg4510 compared to wild-type mice by 40 weeks of age. Peak-to-peak circadian rhythm amplitude and performance in the T-maze was impaired throughout the experiment independent of time. At 46 weeks rTG4510 mice had significant degeneration in the hippocampus and cortex whereas doxycycline treated rTG4510 mice were protected. Pathology significantly correlated with sleep and EEG outcomes, in addition to locomotor and cognitive measures. CONCLUSIONS: We show that reduced EEG spectral power precedes reductions in sleep and home-cage locomotor activity in a mouse model of tauopathy. The data shows increasing mutant tau changes sleep architecture, EEG properties, behaviour and cognition; which suggest tau related effects on sleep architecture in patients with neurodegenerative diseases.
Unmet supportive care needs and its relation to quality of life among adult acute leukaemia patients in China: a cross-sectional study
Authors: Yan Jie , Wang Ying , Chen Jingyi , Wang Chunfeng , Lin Yingchun , Hu Rong , Wu Yong
Published: June 2020

Background Patients with acute leukaemia (AL) usually require prolonged periods of hospitalisation. The treatment and clinical symptoms may lead to patients’ supportive care needs (SCNs) not being met and impairs their quality of life (QoL). Studies on QoL and SCNs among AL patients are limited. This study aimed to identify the unmet SCNs and its relation to QoL of adult AL patients in China. Methods This multicentre cross-sectional study recruited 346 participants to complete a self-developed questionnaire, detailing demographic information and disease-related variables. A 34-item Supportive Care Needs Survey (SCNS-SF34) was used to identify unmet SCNs, and the Functional Assessment of Cancer Therapy-Leukaemia (FACT-Leu) questionnaire measured patients’ QoL. Results Unmet SCN rates for the 34 items ranged from17.6% to 81.7%. Patients’ needs were high for health systems and information, but low in the sexual domain. The results reveal nine factors associated with the unmet SCNs of adult AL patients, including marital status, original residence, age, education, occupation, other diseases, chemotherapy course, disease course, and treatment stage ( p <0.05). The total score of the FACT-Leu negatively correlated with the SCNS-SF34 in the physical/daily living (r = - 0.527, p <0.01), psychological (r = - 0.688, p <0.01), sexual (r = - 0.170, p <0.01), patient care and support (r = - 0.352, p <0.01), and health systems and information (r = - 0.220, p <0.01) domains. Conclusions Adult AL patients exhibit a high demand for unmet SCNs, especially in the domain of health systems and information. There was a significant association between patients’ unmet SCNs and QoL. Future research should develop tailored interventions to address the unmet SCNs of adult AL patients, to further improve their QoL.
Defective migration and dysmorphology of neutrophil granulocytes in atypical chronic myeloid leukemia treated with ruxolitinib
Authors: Bornemann Lea , Schuster Marc , Schmitz Saskia , Sobczak Charlyn , Bessen Clara , Merz Simon F. , Jöckel Karl-Heinz , Haverkamp Thomas , Gunzer Matthias , Göthert Joachim R.
Published: June 2020

Background: The identification of pathologically altered neutrophil granulocyte migration patterns bears strong potential for surveillance and prognostic scoring of diseases. We recently identified a strong correlation between impaired neutrophil motility and the disease stage of myelodysplastic syndrome (MDS). Here, we apply this assay to study quantitively increased neutrophils of a patient suffering from a rare leukemia subtype, atypical chronic myeloid leukemia (aCML).Methods: A 69-year-old male was analyzed in this study. Besides routine analyses, we purified the patient’s neutrophils from peripheral whole blood and studied their migration behavior using time-lapse video microscopy in a standardized assay. These live cell migration analyses also allowed for the quantification of cell morphology. Furthermore, the cells were stained for the markers CD15, CD16, fMLPR, CXCR1 and CXCR2. Results: Despite cytoreductive therapy with hydroxyurea, the patient’s WBC and ANC were poorly controlled and severe dysgranulopoiesis with hypogranularity was observed. Neutrophils displayed strongly impaired migration when compared to healthy controls and migrating cells exhibited a more flattened-out morphology than control neutrophils. Because of a detected CSF3R (p.T618I) mutation and constitutional symptoms treatment with ruxolitinib was initiated. Within one week of ruxolitinib treatment, the cell shape normalized and remained indistinguishable from healthy control neutrophils. However, neutrophil migration did not improve over the course of ruxolitinib therapy but was strikingly altered shortly before a sinusitis with fever and bleeding from a gastric ulcer. Molecular work-up revealed that under ruxolitinib treatment, the CSF3R clone was depleted, yet the expansion of a NRAS mutated subclone was promoted. Conclusion: These results demonstrate the usefulness of neutrophil migration analyses to uncover corresponding alterations of neutrophil migration in rare myeloid neoplasms. Furthermore, in addition to monitoring migration the determination of morphological features of live neutrophils might represent a useful tool to monitor the effectiveness of therapeutic approaches.