bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging the Gap Between Reservoir and Sample; Reducing Asset Development Risk by using Down-Hole Mercury Trapping and Non-Reactive Sampler for Trace Component Sampling
Authors: Dybdahl Bjorn , Lie Siv , Langford Michael , Thowsen Oddfinn
Published: November 2020

Accurate mercury and hydrogen sulphide measurements are essential for facilities design. Existing sampling methods are flawed in that they are not guaranteed to preserve the full quantity of reactive trace components present in a hydrocarbon sample. Subsequent incomplete measurements can have significant cost and HSE impact.

A novel down-hole sample capture and preservation of reactive components system is presented, enabling quicker, definitive identification of risks to plant integrity, worker and environmental exposures and sales value.

A selection of materials and coatings were tested for their inertness in relation to both mercury and hydrogen sulphide, in a variety of fluids (gas, oil, water and multiphase). All materials also had to be suitable for use in anticipated down-hole conditions.

The available literature was reviewed, and a mercury capturing system was designed and tested in a variety of fluids.

Once materials and designs had been selected, prototypes were tested using both certified calibration materials and samples spiked with known amounts of mercury.

The selected material and coating combination, when constructed in a chamber free from lubricants, O-rings and pistons, was shown to result in minimal sulphur component loss over an extended period, and to sufficiently delay the loss of mercury to allow it to be captured at reservoir concentrations.

Hydrogen sulphide concentrations were maintained in the tools for an extended period of time, allowing for the retrieval to surface of bottom-hole samplers, resulting in surface concentrations representative of those down-hole.

Mercury was successfully captured at down-hole conditions, preventing the impact of temperature and pressure changes at surface. Once at surface the mercury can be quantified without any losses associated with traditional sample handling.

Earlier identification of the presence of these species, along with accurate quantification, will aid facility design, such as whether removal facilities are required to meet sales specifications, and prevent harm to workers and the environment through unconsidered emissions of toxic components during production.

This paper presents a data collection process enhancing the quality of information essential for field development and maintenance planning and introduces a novel sampling approach that is capable of capturing representative down-hole samples for trace analysis of mercury and sulphur species, without losses experienced using existing techniques. The tool can be used within traditional sampling systems.
Optimising the Placement of Acid Treatments for Damage Removal and Well Stimulation
Authors: Mokogwu Ike , Wilson Sam , Stalker Robert , Graham Gordon
Published: November 2020

The requirement for appropriate placement in matrix acidizing to achieve efficient, effective stimulation or removal of formation damage has long been recognized. Despite this, assessing the effectiveness of an acid treatment in terms of placement and treatment efficiency prior to field deployment remains a challenge.

This paper presents a scenario where carefully designed core flood tests have been deployed alongside the use of a near-wellbore simulator to model and predict acid stimulation using viscosified fluids for treatments in a range of scenarios. Dual linear core flood tests were conducted to assess placement and clean-up efficacy of a viscosified acid treatment.

The efficiency of the treatment was then modelled using a state-of-the-art computer simulator. The computer simulator used is one which has been used extensively to model and optimize scale-inhibitor squeeze treatments in long-reach/complex wells. Its capability was extended to evaluate effects of fluid viscosification (staged or otherwise) on stimulation treatments.

Cases where partial/localised clean-up of a damaged zone was achieved, resulting in uneven stimulation were also examined. Results obtained from the model were validated with dual-linear core flood tests using simulated damaged and non-damaged zones. Resulting laboratory injection/diversion was compared to model predictions.

Core flood tests highlighted the importance of laboratory simulation of viscosified treatments. These tests showed how improved placement can be achieved by careful fluid design using viscosity alterations. The model was used to demonstrate the benefit (or otherwise) of different degrees of viscosification on evenness of treatment placement for systems with permeability contrasts, pressure differentials, presence of a water-producing zone, and various degrees and depths of skin per zone (including consideration of the effects on placement of acid reactivity on this damage).

Results showed that often even modest viscosification of the treatment fluid (~20 cP) improved placement. The greater the fraction that was viscosified (for staged treatments), the more even the placement. Viscosification invariably improved placement where a difference in native permeability existed (as opposed to a difference due to damage) and in most cases reduced the fraction of treatment fluid entering a water-producing zone.
What Does a Carbon Price do to Your Reserves and Development Plans?
Authors: Wong Daniel Lorng , Solomon Phillip , Jenvey Nigel
Published: November 2020

The paper presents a risk management tool that assesses the impact that potential future carbon taxes will have on a company's hydrocarbon Reserves base and associated cashflows. Based on a number of case studies, this paper will present a practical application of the open-source engineering-based model called Oil Production Greenhouse Gas Emissions Estimator (OPGEE), developed by Stanford University. The paper will demonstrate the application of the OPGEE model in the assessment of a range of carbon taxes, how they may vary the economic limit of a field's Reserves, and how this may influence a company's future field development decisions. This tool becomes useful in the risk management of the portfolio planning and capital allocation process where carbon tax risk can be objectively assessed and tested. If utilised correctly, the model can help to future-proof a company's hydrocarbon assets in an increasingly carbon constrained world. Asset owners or potential asset acquirers can assess the materiality of potential carbon tax impositions on assets and can prepare and adjust portfolios accordingly on an informed basis.
Application of Machine Learning for Fatigue Prediction of Flexible Risers - Digital Twin Approach
Authors: Repalle Nitin , Thethi Ricky , Viana Pedro , Tellier Elizabeth
Published: November 2020

Flexible pipes have a range of potential failure modes, however fatigue damage of the tensile, and eventually, the pressure armour, is one of the most common problems affecting the longevity of service life and the OPEX due to the common need for flexible riser replacement. With increasing utilisation of flexible pipe for current and future field developments, compounded by the recurrent need for field life extension, it is essential to monitor the riser fatigue regularly to maintain integrity, maximise asset life and to allow for informed appraisal before extending its operational life.

This paper presents a novel method of using the refined finite element analysis (FEA) in combination with Artificial Neural Network (ANN) to develop a riser digital twin that can be utilised as an operational decision-making tool for integrity management and life extension. A digital twin model is trained on a subset of available metocean and vessel motion data utilising advanced neural networks which can then be utilised to predict fatigue under the full spectrum of metocean and internal pressure conditions. This approach allows for a significant reduction in the estimation time of the fatigue damage compared to conventional FEA as well as improved accuracy of prediction.

The methodology presented in the paper has been primarily developed with the view of deepwater riser applications but is easily adaptable to shallow water application in combination with various floating vessels. A case study is presented to demonstrate how this technology is being deployed offshore. A comparison of FEA and digital twin approach is also presented to highlight the speed and efficiency of digital twin model whereby real-time insights on fatigue life can be evaluated for informed operational decisions.
Novel MYO15A Variants are Associated with Hearing Loss in the Two Iranian Pedigrees
Authors: Khatami Somayeh , Askari Masomeh , Bahreini Fatemeh , Chaleshtori Morteza Hashemzadeh , Hematian Saeed , Asgharzade Samira
Published: November 2020

Background: Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods.Methods: This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families.Results: The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects.Conclusion: In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.
Benefit of dosimetry distribution for patients with multiple brain metastases from non-small cell lung cancer by Cyberknife Stereotactic radiosurgery (SRS) system
Authors: YU Xuyao , Wang Yuwen , Yuan Zhiyong , Yu Hui , Song Yongchun , Zhao Lujun , Wang Ping
Published: November 2020

Background: In order to obtain a high dose conformal index of tumor and steep dose fall-off in healthy tissues for brain metastasis stereotactic radiosurgery (SRS), the aim of this study was to investigate SRS planning optimization by comparing one multiple-lesions plan (MLP) with multiple single-lesion plans (SLPs) for patients with multiple brain metastases using the Cyberknife (CK) system.Methods: Fifty non-small cell lung cancer (NSCLC) patients (28 males and 22 females) with 2-4 brain metastases, inter-tumour distances less than 3 cm, were retrospectively replanned with the original prescription dose (12-32 Gy) in the original fractions (1-3). Two different clinical CK SRS plans (SLPs and MLP) were generated for the same patients with the same collimator and prescription isodose line (62-68%) by the CK Multiplan System. Both SLPs and MLP were able to achieve >95% PTV volume covered prescription dose and met the Timmerman 2011 organs at risk (brainstem, optic nerve and pituitary) constraints.Results: Compared with those in the SLPs, the maximum dose (Dmax) and mean dose (Dmean) of brainstem in the MLP were reduced 0.22-3.13% (2.62%) and 2.71-12.56% (5.57%), respectively, all P<0.05. Meanwhile, the volumes of the whole brain minus the tumors that received a single dose equivalent of 8-16 Gy (V8Gy-V16Gy) were effectively reduced in the MLP. The treatment time parameters, the total number of beams and monitor units, of the MLP were reduced by 3.31% and 1.47% (P<0.05), respectively. Although there were a few differences in the conformity index (CI) and homogeneity index (HI) between the two treatment plans, the differences were not statistically significant (P = 2.94 and 1.08>0.05).Conclusion: One multiple-lesions plan for brain metastases could achieve higher precision in the target and lower doses in healthy tissue while shortening the treatment time and improving the treatment efficiency over multiple single-lesion plans.
Socializing One Health: An Innovative Strategy to Investigate Social and Behavioral Risks of Emerging Viral Threats
Authors: Saylors Karen , Wolking David J. , Hagan Emily , Martinez Stephanie , Francisco Leilani , Euren Jason , Olson Sarah H. , Miller Maureen , Daszak Peter , Kreuder-Johnson Christine , Mazet Jonna A.K.
Published: November 2020

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT program funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security.
Isolation of axenic cyanobacterium and the promoting effect of associated bacterium on axenic cyanobacterium
Authors: Gao Suqin , Kong Yun , Yu Jing , Miao Lihong , Ji Lipeng , Song Lirong , Zeng Chi
Published: November 2020

Background: Harmful cyanobacterial blooms have attracted wide attention all over the world as they cause water quality deterioration and ecosystem health issues. Microcystis aeruginosa associated with a large number of bacteria is one of the most common and widespread bloom-forming cyanobacteria that secret toxins. These associated bacteria are considered to benefit from organic substrates released by the cyanobacterium. In order to avoid the influence of associated heterotrophic bacteria on the target cyanobacteria for physiological and molecular studies, it is urgent to obtain an axenic M. aeruginosa culture and further investigate the speciﬁc interaction between the heterotroph and the cyanobacterium.Results: A traditional and reliable method based on solid-liquid alternate cultivation is carried out to purify the xenic cyanobacterium M. aeruginosa FACHB-905. On the basis of 16S rDNA gene sequences, two associated bacteria named strain B905-1 and strain B905-2, are identified as Pannonibacter sp. and Chryseobacterium sp. with a 99% and 97% similarity value, respectively. The axenic M. aeruginosa FACHB-905A (Microcystis 905A) is not able to form colonies on BG11 agar medium without the addition of strain B905-1, while it grows well in BG11 liquid medium. Although the presence of B905-1 is not indispensable for the growth of Microcystis 905A, B905-1 has a positive effect on promoting the growth of Microcystis 905A. Conclusions: The associated bacteria are eliminated by solid-liquid alternate cultivation method and the axenic Microcystis 905A is successfully purified. The associated bacterium B905-1 has the potential to promote the growth of Microcystis 905A. Moreover, the purification technique for cyanobacteria described in this study is potentially applicable to a wider range of unicellular cyanobacteria.
Association of childhood undernutrition with water supply, sanitation and hygiene interventions in Kersa and Omo Nada districts of Jimma Zone, Ethiopia: A case-control study
Authors: Soboksa Negasa Eshete , Gari Sirak Robele , Hailu Abebe Beyene , Alemu Bezatu Mengistie
Published: November 2020

Objective: This study aimed to describe the association of childhood undernutrition with water supply, sanitation, and hygiene interventions in Kersa and Omo Nada districts of the Jimma Zone, Ethiopia.Design: A case-control study design was undertaken from December 2018 to January 2019.Setting: Kersa and Omo Nada districts of the Jimma Zone, Ethiopia.Subjects: 128 cases and 256 controls were randomly selected from malnourished and well-nourished children, respectively.Outcome measures: Bodyweight, length/height, mid-upper arm circumference and presence of edema of the children were measured according to the WHO references. Then, the nutritional status of children was identified as case or control using cutoff points recommended by the WHO based on the Z-score, edema, and MUAC values recorded.Results: A total of 378 children were included in this study, with a response rate of 98.44%. Undernutrition was significantly increased among children who delayed breastfeeding initiation (AOR=2.60; 95% CI: 1.02-6.65), diarrhea (AOR=9.50; 95% CI: 5.19-17.36), living with households indexed as the poorest (AOR=2.57; 95% CI: 1.09-6.07) and defecated in a pit latrine without slab/open pit (AOR=2.49; 95% CI: 1.17-5.30), and sometimes practiced hand washing at the critical times (AOR=2.52; 95% CI: 1.10-5.75) compared with their counterparts. However, lactating during the survey (AOR=0.35; 95% CI: 0.18-0.71) and collection and disposal of under-five children feces elsewhere (AOR = 0.08; 95% CI: 0.01-0.75) significantly reduced the likelihood of undernutrition.Conclusions: Early initiation of exclusive breastfeeding, diarrhea prevention, the use of improved latrine, and always handwashing practices at critical times could be important variables to improve the nutritional status of children.
Modifying ways to perform ICU tracheostomies in COVID-19 patients: Approach to a safe and secure method
Authors: Bhavana Kranti , Srinivaa Arun , Ouseph Sheelia , Suneha Swati , Prakash Rudra , Bharti Bhartendu
Published: November 2020

Background- This study outlines the unique modifications to surgical tracheostomy procedure to combat the extraordinary situation the world has found itself in due to COVID 19 pandemic. We explain the modifications employed to the operative setup, anesthetic considerations and surgical procedure to enable us to provide timely and safe tracheostomy to the COVID ICU patients requiring it, while simultaneously maximally protecting our surgical personnel from the deadly exposure.Methods- We conducted 55 surgical tracheostomies in severely sick ICU patients with the modifications deemed fit to achieve safe procedure for both the patient and the operating team. We analyzed the hospital record data of these patients and the surgical teams COVID 19 status to assesss the efficacy of our procedural modifications.Discussion- The COVID 19 pandemic has thrown the entire medical fraternity into a dilemma as to how to provide the best possible care to the patients while protecting ourselves from its grip. Severely sick COVID patients often require tracheostomy for improved prognosis. We performed bedside open surgical tracheostomy and induced transient apnoea periprocedur along with carinal intubation. By making these simple and cost effective modifications to the procedure, we have ensured that patients get tracheostomised as and when required but not at the cost of the health and lives of our health care workers.
Effect of Empagliflozin on Liver Function in type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Roostaei Davoud
Published: November 2020

Background Many reports are indicating the blood sugar-lowering potential of Empagliflozin in type 2 diabetes mellitus and its anti-lipogenesis effects in the liver, as studied in mice models; while few clinical trials have evaluated its effect on liver fat content and liver function. Objectives This study aimed to evaluate the effect of Empagliflozin on the treatment of non‐alcoholic fatty liver disease in type 2 diabetes mellitus patients.Search methods Scopus, Cochran Library, PubMed, and Web of Science databases were searched from 1990 to 2020 together with reference checking and citation searching to identify additional studies. Selection criteria Inclusion criteria for studies were the evaluation of patients with non‐alcoholic fatty liver disease and type 2 diabetes being treated with Empagliflozin for 24 weeks. Our interest outcomes were Liver fat, ALT, and AST. Data analysis Random effect size model was used for pooling data to calculate mean differences in RevMan Version 5.3. I2 was used to evaluate heterogeneity. Results Three clinical trial studies were included with 2344 patients. In pooled ALT ‎mean difference evaluation within 24 weeks of studies, there was a significant ‎difference between subjects receiving Empagliflozin versus controls (MD=-6.6 ‎CI95%(-10.27 to -3.73; P=0.06; I2=99%). ‎ In case of AST (MD=-9.06 CI95% (-20.45 to 2.34; P=0.12; I2=98%) and Liver fat (MD=-4.46 CI95% (-10.06 to 0.77; P=0.09; I2=98%), ‎there was not any significant difference between subjects receiving Empagliflozin ‎versus controls. Conclusion While Empagliflozin seems to be effective in lowering ALT levels; further studies are needed to confirm its efficacy in lowering liver fat.
WITHDRAWN: Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic
Authors: Elgazzar Ahmed , Hany Basma , Youssef Shaimaa Abo , Hany Basma , Hafez Mohy , Moussa Hany
Published: November 2020

Background: Up-to-date, there is no recognized effective treatment or vaccine for the treatment of COVID-19 that emphasize urgency around distinctive effective therapies. This study aims to evaluate the anti-parasitic medication efficacy "Ivermectin" plus standard care (azithromycin, vitamin C, Zinc, Lactoferrin & Acetylcystein & prophylactic or therapeutic anticoagulation if D-dimer > 1000) in the treatment of mild/moderate and severely ill cases with COVID 19 infection, as well as prophylaxis of health care and/ or household contacts in comparison to the Hydroxychloroquine plus standard treatment.

Subject and methods: 600 subjects; 400 symptomatic confirmed COVID-19 patients and 200 health care and household contacts distributed over 6 groups; Group I: 100 patients with Mild/Moderate COVID-19 infection received a 4-days course of Ivermectin plus standard of care; Group II: 100 patients with mild/moderate COVID-19 infection received hydroxyxholorquine plus standard of care; Group III: 100 patients with severe COVID-19 infection received Ivermectin plus standard of care; Group IV: 100 patients with Severe COVID-19 infection received hydroxyxholorquine plus standard of care. Routine laboratory investigations and RT-PCR were reported before and after initiation of treatment. Group V stick to personal protective equipment (PPE) plus Ivermectin 400mcg / kg to be repeated after one week, and Group VI stick to PPE only and both groups V&VI were followed for two weeks.

Results: Patients received ivermectin reported substantial recovery of laboratory investigations; and significant reduction in RT-PCR conversion days. A substantial improvement and reduction in mortality rate in Ivermectin treated groups; group I (mild/moderate cases), (99%, and 0.0%, respectively) and group III (severe cases), (94%, and 2.0%, respectively) versus hydroxychloroquine plus standard care treated groups; group II (mild/moderate cases), (74% and 4%, respectively) and group IV (severe cases) (50% and 20%, respectively). Ivermectin had significantly reduced the incidence of infection in health care and household contacts up to 2% compared to 10% in non ivermectin group

Conclusion: Addition of Ivermectin to standard care is very effective drug for treatment of COVID-19 patients with significant reduction in mortality compared to Hydroxychloroquine plus standard treatment only. Early use of Ivermectin is very useful for controlling COVID 19 infections, prophylaxis and improving cytokines storm
Statistical Analyses of the Strengths of Particulate Reinforced Metal Matrix Composites (PRMMCs) Subjected to Multiple Tensile and Shear Stresses
Authors: Chen Geng , Xin Shengzhen , Zhang Lele , Broeckmann Christoph
Published: November 2020

Predicting the material strengths of particulate reinforced metal matrix composites (PRMMCs) and understanding how these properties are related to the constituents and microstructural features are essential for material designers and application engineers. To this end, a computational approach consists of the direct methods, homogenization, and statistical analyses is introduced in our previous studies [1,2]. Since in various engineering applications failure of PRMMC materials are caused by time-varied combinations of tensile and shear stresses, to take into account of such situations the established approach is extended in the present work. In this paper, ultimate strengths and endurance limits of an exemplary PRMMC material, WC-Co, are predicted under three independently varied tensile and shear stresses. In order to cover the entire load space with least amount of weight factors, a new method for generating optimally distributed weight factors in an n dimensional space is formulated. Employing weight factors determined by this algorithm, direct method calculations were performed on many statistically equivalent representative volume elements (SERVE) samples, and through analyzing statistical characteristics associated with results the study suggests a simplified approach to estimate the material strength under superposed stresses without solving the difficult high dimensional shakedown problem.
Computational Design of Stable, Soluble and Highly Active Alcohol Dehydrogenase for NADPH Regeneration
Authors: Xu jinling , Zhou Haisheng , Deng Tong , Yu Haoran , Wang Ziyuan , Zhang Hongyu , Wu Jianping , Xu Gang , Yang Lirong
Published: November 2020

Nicotinamide adenine dinucleotide phosphate (NADPH), as a well-known cofactor, is widely used in the most of enzymatic redox reactions, playing an important role in industrial catalysis. However, the absence of a comparable method for efficient NADP + to NADPH cofactor regeneration radically impairs efficient green chemical synthesis. Alcohol dehydrogenase (ADH) enzymes, allowing the in situ regeneration of the redox cofactor NADPH with high specific activity and easy by-product separation process, are provided with great industrial application potential and research attention. Accordingly, herein a NADP + specific ADH from Clostridium beijerinckii was selected to be engineered for cofactor recycle, using an automated algorithm named Protein Repair One-stop Shop (PROSS). The mutant CbADH-6M exhibited a favorable soluble and highly active expression with an activity of 46.3 U/mL, which was 16 times higher than the wild type (2.9 U/mL), and a more stable protein conformation with an enhanced thermal stability: Δ = +3.6°C (temperature of 50% inactivation after incubation for 60 min). Furthermore, the activity of CbADH-6M was up-graded to 2401.8 U/mL by high cell density fermentation strategy, demonstrating its industrial potential. Finally, the superb efficiency for NADPH regeneration of the mutant enzyme was testified in the synthesis of some fine chiral aromatic alcohols coupling with anther ADH from Lactobacillus kefir (LkADH). Nicotinamide adenine dinucleotide phosphate (NADPH), as a well-known cofactor, is widely used in the most of enzymatic redox reactions, playing an important role in industrial catalysis. However, the absence of a comparable method for efficient NADP + to NADPH cofactor regeneration radically impairs efficient green chemical synthesis. Alcohol dehydrogenase (ADH) enzymes, allowing the in situ regeneration of the redox cofactor NADPH with high specific activity and easy by-product separation process, are provided with great industrial application potential and research attention. Accordingly, herein a NADP + specific ADH from Clostridium beijerinckii was selected to be engineered for cofactor recycle, using an automated algorithm named Protein Repair One-stop Shop (PROSS). The mutant CbADH-6M exhibited a favorable soluble and highly active expression with an activity of 46.3 U/mL, which was 16 times higher than the wild type (2.9 U/mL), and a more stable protein conformation with an enhanced thermal stability: ΔT60 min 1/2 = +3.6°C (temperature of 50% inactivation after incubation for 60 min). Furthermore, the activity of CbADH-6M was up-graded to 2401.8 U/mL by high cell density fermentation strategy, demonstrating its industrial potential. Finally, the superb efficiency for NADPH regeneration of the mutant enzyme was testified in the synthesis of some fine chiral aromatic alcohols coupling with anther ADH from Lactobacillus kefir (LkADH).
Laparoscopic Petersen’s Hernia Reduction Was Associated With A Better Clinical Course Than Open Reduction After Gastrectomy: A Multicenter Observational Cohort Study
Authors: Min Jae-Seok , Seo Kyung Won , Jeong Sangho , Kim Ki Hyun , Park Ji-ho , Yoon Ki Young , Kim Tae-Han , Jung Eun-Jung , Ju Young-tae , Jeong Chi-Young , Kim Ju-Yeon , Lee Young-Joon
Published: November 2020

Background The aim of this multicenter cohort study was to compare the clinical courses between open and laparoscopic Petersen’s hernia (PH) reduction.Materials and method We retrospectively collected the clinical data of patients who underwent PH repair surgery after gastrectomy for gastric cancer from 2015-2018. Forty patients underwent PH reduction operations that were performed by six expert surgeons at four hospitals. Among the 40 patients, 15 underwent laparoscopic PH reduction (LPH), and 25 underwent open PH reduction (OPH), including 4 patients who underwent LPH but required conversion to OPH.Results We compared the clinical factors between the LPH and OPH groups. In the clinical course, we found no differences in operation times or intraoperative bowel injury, morbidity, or mortality rates between the two groups (p>0.05). However, the number of days on a soft fluid diet (OPH vs. LPH; 5.8 vs. 3.7 days, p=0.03) and length of hospital stay (12.6 vs. 8.2 days, p=0.04) were significantly less in the LPH group than the OPH group. Regarding postoperative complications, the OPH group had a case of pneumonia and sepsis with multi-organ failure, which resulted in mortality. In the LPH group, one patient experienced recurrence and required reoperation for PH.Conclusion Laparoscopic PH reduction was associated with a faster postoperative recovery period than open PH reduction, with a similar incidence of complications. The laparoscopic approach should be considered an appropriate strategy for PH reduction.
Gonadal Development and Associated Changes in Estradiol, Thyroid Hormones, and Sex-Related Genes During Different Growth Stages in Cultured Female Rainbow Trout (Oncorhynchus Mykiss) in Yunnan
Authors: Kong Lingfu , Bi Baoliang , Su Yanhua , Rong Hua , Hu Qing
Published: November 2020

Background: Rainbow trout (Oncorhynchus mykiss) is an important fishing resource in Yunnan. However, the oocyte quality and fecundity are particularly affected by environmental factors when fish are undergoing sexual maturation, which hinders the development of the O. mykiss industry.Results: Estradiol (E2), thyroid hormones (THs), and sex-related genes transcription associated with gonadal development were analyzed in different growth stages of O. mykiss cultured in Yunnan. Females were classified into four growth stages: growth stage Ⅰ, growth stage Ⅱ, growth stage Ⅲ, and growth stage Ⅳ. Histological analysis found a correlated relationship between body growth and ovary development. Serum levels of E2 and THs increased during ovarian development and reached the highest level at growth stage Ⅳ indicated that E2 and THs play important roles in the development and maturation of oocytes in O. mykiss. Furthermore, real-time PCR analysis showed that the vitellogenin mRNA (vtg) transcription level increased significantly both in ovaries and liver during ovarian development, then reaching its peak at the post-vitellogenetic (growth stage Ⅳ) period. The same transcription trend was detected in the levels of ovarian estrogen receptors (ers). Conclusions: These results indicated that the high level of E2 promotes the transcription of the vtg mediated by different types of ers, and then accelerates the maturation of oocytes, and THs also participate in the regulation of maturation of oocytes in cultured O. mykiss during the individual development in Yunnan.
Seasonally evolving hydraulic transmissivity beneath Greenland supraglacial lakes
Authors: Lai Ching-Yao , Stevens Laura , Chase Danielle , Creyts Timothy , Behn Mark , Das Sarah , Stone Howard
Published: November 2020

Surface meltwater reaching the base of the Greenland Ice Sheet transits through drainage networks, modulating the flow of the ice sheet. Dye-tracing studies indicate that drainage efficiency evolves seasonally along the drainage pathway. However, the local evolution of drainage systems further inland, where ice thicknesses exceed 1000 m, remains largely unknown. Here, we develop a novel method to infer transmissivity of the drainage system based on surface uplift relaxation following rapid lake drainage events. Combining field observations of five lake drainage events with a mathematical model and laboratory experiments, we show that the surface uplift decreases exponentially with time, as the water in the blister formed beneath the drained lake permeates through the subglacial drainage system. This deflation obeys a universal relaxation law with a timescale that reveals hydraulic transmissivity and indicates a two-order-of-magnitude increase in subglacial transmissivity as the melt season progresses, suggesting significant changes in basal hydrology beneath the lakes.
Protective Effects of Aquaporin-4 Deficiency on Longer-Term Neurological Outcomes in a Mouse Model of Traumatic Brain Injury
Authors: Liu Xiaosong , Xie Yingxin , Wan Xiangdong , Wu Jianliang , Fan Zhenzeng , Yang Lijun
Published: November 2020

Background: Traumatic brain injury (TBI) has been a crucial health problem, with more than 50 million patients worldwide each year. Glymphatic system is a fluid exchange system that relies on the polarized water channel aquaporin-4 (AQP4) at the astrocytes, accounting for the clearance of abnormal proteins and metabolites from brain tissues. However, the dysfunction of glymphatic system and alteration of AQP4 polarization during the progression of TBI remain unclear.Methods: AQP4−/− and Wild Type (WT) mice were used to establish the TBI mouse model respectively. Morris water maze (MWM) was used to establish the cognitive functions of AQP4−/− and WT mice post TBI. Western-blot and qRT-PCR assays were performed to demonstrate protective effects of AQP4 deficiency to blood-brain barrier (BBB) integrity and amyloid-β clearance. The inflammation of cerebral tissues post TBI was estimated by ELISA assay.Results: AQP4 deficiency alleviated the brain edema and neurological deficit in TBI mice. AQP4-knockout led to improved cognitive outcomes in mice post TBI. The BBB integrity and cerebral amyloid-β clearance were protected by AQP4 deficiency in TBI mice. AQP4 deficiency ameliorated the TBI-induced inflammation.Conclusion: AQP4 deficiency improved longer-term neurological outcomes in a mouse model of TBI.
Coronin 1A Expression in Human Astroglia, its Function in Physiology and Astrogliosis in HIV-1 Neuropathogenesis
Authors: Pandey Hriday Shanker , Kapoor Rishabh , Bindu  , Seth Pankaj
Published: November 2020

BackgroundIn most neurodegenerative disorders, including neuroAIDS, reactive astroglia are detrimental to the neuronal population. Calcium and its downstream regulators play a central role in mediating glial activation. Coronin 1A, an acting binding protein, majorly reported in cells of hematopoietic origin, regulates cell activity in a calcium-dependent manner, but its role in astroglial physiology and astrogliosis is largely unknown. We explored the roles of Coronin 1A in astroglia physiology and the mechanisms by which it facilitates reactive astrogliosis. MethodsCoronin 1A expression was assessed in different cell types including astroglia using western blotting and immunocytochemistry. Loss of function assays were performed after siRNA-mediated knockdown of coronin 1A. Live-cell calcium imaging was performed on ATP-stimulated astroglia using confocal microscopy. To induce astrogliosis, HIV-1 Tat B expression vector was used after which gene and protein expressions were assessed using qPCR and western blotting, cytokine release was measured using flow cytometry, glutamate release was assessed using enzyme-kinetics based kit. TUNEL assay was performed to assess the glia-mediated neuronal death on neurons treated with the astrocyte-conditioned media. Small RNA-sequencing and qPCR assays were performed to get miRNAs differentially regulated a result of HIV-1 Tat transfection. Transfection with mimic and inhibitor against selected miRNA, and luciferase assay were performed to confirm the miRNA regulation.ResultsIn this study, we report for the first time, that human primary astroglia express Coronin 1A, and it plays activity-dependent roles in events such as PLCγ1 phosphorylation followed by Calcium mobilization from the intracellular stores. HIV-1 Tat, a potent neurotoxicant that induces astrogliosis, enhances the expression of Coronin 1A, apart from affecting GFAP and pro-inflammatory molecules. Downregulation of Coronin 1A ameliorated the HIV-1 Tat-induced deleterious effects of reactive astroglia, measured as enhanced GFAP expression and release of IL-6, and Glutamate and thus reduced glia-mediated neurodegeneration. Our findings also suggest that out of a pool of dysregulated miRNAs studied by us, hsa-miR-92b-5p regulates Coronin 1A expression which further facilitates reactive astrogliosis under the effect of HIV-1 Tat. ConclusionThese findings highlight the novel roles of Coronin 1A in regulating the astroglial physiology and astrogliosis observed in HIV-1 neuropathogenesis.
The Let's Talk toolkit: developing a theory-informed complex intervention to improve nurse-patient therapeutic engagement on an acute mental health ward by employing Experience-based Co-design and the Behaviour Change Wheel
Authors: McAllister Sarah , Simpson Alan , Tsianakas Vicki , Canham Nick , Meo Vittoria De , Stone Cady , Robert Glenn
Published: November 2020

Background

Lack of high-quality nurse-patient therapeutic engagement is a longstanding problem on acute mental health wards, with a dearth of interventions to address this. A collaborative, theory-driven approach to developing and implementing complex interventions is more likely to be effective and sustainable. This paper describes an integrated co-design-behaviour change approach which developed the Let’s Talk intervention toolkit for improving the quality of therapeutic engagement on acute mental health wards.
Methods

We describe a theory-driven approach to co-designing an intervention by adapting and integrating Experience-based Co-design (EBCD) with the Behaviour Change Wheel (BCW). Fieldwork was informed by the results of a systematic integrative review and was guided by our co-design-behaviour change approach. It was conducted over 12-months at an acute mental health organisation in England. We undertook semi-structured interviews with 14 service users (seven of which were filmed), two carers and 12 clinicians, 80 hours of non-participant observations and a facilitated intervention co-design process that involved two feedback workshops, one joint co-design workshop and seven small co-design team meetings. Data analysis comprised the identification of touchpoints and use of the BCW and behaviour change technique taxonomy to inform intervention development.
Results

The co-designed Let’s Talk toolkit addressed four joint priorities for change: 1) improve communication with withdrawn people; 2) nurses to help service users help themselves; 3) nurses to feel confident when engaging with service users; 4) improving team relations and ward culture. Intervention functions included training, education, enablement, coercion and persuasion; 14 behaviour change techniques supported these functions. We detail how we implemented our integrated co-design-behaviour change approach with service users, carers and clinicians to co-design the toolkit to improve nurse-patient therapeutic engagement.
Conclusions

Our theory-driven approach enhances both EBCD and the BCW. It introduces a robust theoretical approach to guide intervention development within the co-design process and sets out how to meaningfully involve service users and other stakeholders when designing and implementing complex interventions.
The Role of Participatory Action Research on Clinicians’ Attitudes toward Medication Management
Authors: Bakhshi Fatemeh , Mitchell Rebecca , Nasrabadi Alireza Nikbakht , Javadi Mostafa , Varaei Shokoh
Published: November 2020

Background: Medication management is a cyclic and multidisciplinary approach to enhance safe medication therapy. This paper explores clinician attitude toward medication management which is both open to influence and strongly linked to successful changes in mediation behavior.Purpose: To investigate effects of engaging in participatory action research to improve emergency medicine clinicians’ attitudes toward implementing effective medication management.Methodology: Data are drawn from two-cycle participatory action research. Within the study, a total of 85 clinicians including nurses and physicians from emergency department of one university affiliated hospital participated as participants. Eight managers and clinicians participated as representatives. Initially, a situation analysis on the current medication management and clinician views regarding medication management was conducted using three focus groups. Evaluation and reflection data were obtained through qualitative interviews. All qualitative data were analyzed using content analysis. Results: Clinicians initially expressed negative attitudes toward existing and new plans for medication management, in that they were critical of current medication-related policy and procedures, as well as wary of the potential relevance and utility of potential changes to medication management. Through the action research, improvement actions were implemented including interprofessional courses, pharmacist-led interventions, and the development of new guidelines regarding medication management. Participants and their representatives were engaged in all participatory action research stages. Extracted results from evaluation and reflection stages revealed that by engaging in the action research and practice new interventions, clinicians’ attitude toward medication management was improved. Conclusion: The results support the impact of participatory action research on enhanced clinicians’ positive attitudes through involvement in planning and implementing medication management actions.
The Prognostic Influence of Venous Thromboembolism in Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review
Authors: Bai Yu , Ma Xu , Han Sen , Fang Jian
Published: November 2020

Background: Patients with non-small cell lung cancer (NSCLC) have a significantly higher risk of developing venous thromboembolism (VTE), a condition that significantly influences the prognosis of these patients. However, the impact of VTE on the survival of NSCLC patients remains unclear. We aim to evaluate the impact of VTE on the mortality of patients with NSCLC. Methods: We systematically reviewed all indexed studies examining the prognosis of NSCLC patients with VTE. Web of Science, EMBASE, PubMed, and the Cochrane Library were searched through December 31, 2019 to identify relevant studies. Fixed- or random-effects models were chosen based on heterogeneity. Results: Twelve articles with 6480 patients were included in this analysis. The heterogeneity of these studies was significant (I2=81%, P<0.01). The overall survival (OS) of NSCLC patients with VTE was shorter compared to patients without VTE (HR=1.71, 95% CI [1.39–2.10], P<0.01). Two small groups of SCLC patients were excluded and the remaining patients were divided into the Asian and non-Asian groups. The Asian group showed low heterogeneity (I2=35%, P=0.20), in which NSCLC patients with VTE also had shorter OS (HR=1.49, 95% CI [1.19–1.88], P<0.01). Conclusions: VTE is significantly associated with a shorter OS of NSCLC patients, especially in Asian patients. Proper prevention and management of VTE is the key to improving the survival of patients with NSCLC.
Validation of the pediatric refractory septic shock definition: Posthoc analysis of a controlled trial
Authors: MORIN Luc , RAMASWAMY Karthik Natayanan , JAYASHREE Muralidharan , Bansal Arun , NALLASAMY Karthi , Tissieres Pierre , SINGHI Sunit
Published: November 2020

BackgroundThe European Society of Pediatric and Neonatal Intensive Care (ESPNIC) developed and validated a definition of pediatric refractory septic shock (RSS), based on two septic shock scores (SSS). Both bSSS and cSSS were found to be strongly associated with mortality. We aimed at assessing the accuracy of the RSS definition on a prospective cohort from India. Methods Post-hoc analysis of a cohort issued from a double-blind randomized trial that compared first-line vasoactive drugs in children with septic shock. Sequential bSSS and cSSS from 60 children (single center study, 53% mortality) were analyzed. The prognostic value of the ESPNIC RSS definition was tested for 28-day all-cause mortality. ResultsIn this septic shock cohort, RSS was diagnosed in 35 patients (58.3%) during the first 24 hours. Death occurred in 30 RSS patients (85.7% mortality) and in 2 non-RSS patients (8% mortality), OR=60.9 [95% CI: 10.5-676.2], p<0.001 with a median delay from sepsis onset of 3 days [1.0-6.7]. Among patients diagnosed with RSS, the mortality was not significantly different according to vasopressors randomization. Diagnosis of RSS with bSSS and cSSS had a high discrimination for death with an area under the receiver operating curve of 0.916 [95% CI: 0.843-0.990] and 0.925 [95% CI: 0.845-1.000], respectively. During the first day of septic shock, the best interval for prognostication was after the 12th hour following septic shock as compared to 0-6 hours or 6-12 hours (AUC 0.973 [95% CI: 0.925-1.000] versus 0.876 [95% CI: 0.780-0.972] and 0.955 [95% CI: 0.899-1.000] respectively), p=0.011. ConclusionsThe ESPNIC SSS accurately identifies children in refractory septic shock with a best interval between 12 and 24 hour of septic shock. Both bSSS and cSSS had high discrimination for 28-day mortality.