bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Antibiotic Activity of Chitosan-Based Comb-Like Co-Polypeptides
Authors: Enright Timothy P. , Garcia Dominic L. , Storti Gia , Heindl Jason E. , Sidorenko Alexander
Published: March 2023

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.
Biochemical Characteristics of Laccases and their Practical Application in the Removal of Xenobiotics from Waters
Authors: Gałązka Agnieszka , Jankiewicz Urszula , Szczepkowski Andrzej
Published: March 2023

Industrialization, intensive farming, rapid population growth and urbanization are the source of a large number of pollutants entering the environment. The current concentration of xenobiotics released into the environment exceeds its natural ability to decompose them. Enzymatic degradation of pollutants seems to be an environmentally friendly process. Due to the wide spectrum of substrate specificity, from inorganic compounds to high molecular weight organic compounds such as PAH or dyes, as well as favorable biochemical properties, laccase has been used in the biological removal of xenobiotics from the environment. It is important to understand the degradation mechanisms of pollutants and to evaluate the final products in terms of their toxicity. The laccase oxidizes the substrates with the simultaneous reduction of molecular oxygen to water, which is the purest reaction co-substrate. That is why it is called a green biocatalyst. The trend is an increase in the production of enzymes related to the intensive development of industry, bioremediation or synthetic chemistry. This leads to the search for laccases with greater activity and stability under extreme conditions. The potential of laccases to degrade xenobiotics can be promoted by improving enzymatic catalytic characterization using protein engineering and other genetic engineering methods.
Penalized Cox Regression Analysis from Parkinson Disease to Freezing of Gait Using Multiple Kernels
Authors: Kim Da-Woon , Lee Jooyoung
Published: March 2023

Objectives: The objective of this study was to investigate complex non-linear associations of multiple genetic and brain imaging factors and the interactions of the two factors with the risk of gait freezing for patients with Parkinson’s disease (PD).Methods: We employed a penalized kernel machine Cox proportional hazard regression model. Multiple kernels were created to account for multiple genetic factors and their interactions with brain imaging factors, and we identified significant elements using the group lasso penalty. We applied the proposed method to Parkinson’s Progression Markers Initiative (PPMI) data.Results: We identified LRRK2 genes and the volume of six regions of interest in brain interacting with COMT, GBA, LRRK2, and SNCA genes that are associated with the occurrence of freezing of gait for PD patients.Conclusions: It was found that there is evidence of gene-brain interactions in freezing of gait. The proposed penalized Cox model using the kernel machine method enables us to identify the nonlinear relationship between genetic and neuroimaging factors and the occurrence of neurodegenerative diseases.
Royal Sites as Core Element of Early Modern Monarchies: Social Integration in Seventeenth-Century Castile
Authors: Hortal Muñoz José Eloy
Published: March 2023

A great deal of research has been published on royal sites, although up until now studies have focused primarily on their artistic heritage. This article brings a more holistic approach to the study of these sites in order to reconsider their role in the construction of European identities in the early modern period, drawing mainly from the field of court studies. This article examines the social role played by royal sites in terms of integrating the population of the Castilian kingdom from the reign of Philip IV (1621-1665) onwards. During his rule the bonds between the royal possessions and the central court were tightened more than ever before, and, as a result, the material resources of these royal sites were used to provide those servants with retirement deals, creating a system of social welfare for those directly or indirectly related to the royal households and royal sites, especially at the middle and lower levels of society.
The 2022 Royal Studies Journal and The University of Winchester Biennial Book Prize Report
Authors: Rohr Dr. Zita Eva
Published: March 2023

The 2022 Royal Studies Journal and The University of Winchester Biennial Book Prize Report.
Safe and rapid development of advanced materials : a research case study for safe development of nanoenabled environmental sensors
Authors: Ballentine Mark , Kennedy Alan , May Lauren , Shih Wu-Sheng , Patel Rishi , Kavastha Vijaya , Price Cynthia , Chappell Mark , Gust Kurt , Rycroft Taylor , Laird Jennifer
Published: March 2023

The enhanced understanding of nanomaterials properties and processing has led to increased use of nanotechnologies, which has also led to greater scrutiny on the commercialization and acquisition of emerging nanoenabled technologies. Caused by knowledge gaps on the unique behaviors, risks, and liabilities of novel engineered nanomaterials, this caution, when not evidence based, slows production and stifles innovation. Reducing the uncertainty surrounding the environmental risks and benefits of nanoenabled technologies, including their resilience in harsh environments, will speed the development and transition of advanced material technologies. In this work, a multifaceted research program generated data and processes to reduce that environmental uncertainty. Specifically, this case study examined printed, nanoenabled environmental sensors and their components to develop toxicological data and parameterize a life-cycle assessment. The study tested the sensors’ resilience in environmental weathering studies that considered both the potential release of the ingredient nanomaterials and the performance of the sensors after exposure to several harsh environmental climates and then created life-cycle inventories to determine environmental impact and reduce cost of research and development. Finally, this case study developed software tools to mitigate the cost of research and provide a framework for presenting toxicology data.
Optimizing Reservoir Pressure Management with Relief Wells During CO2 Storage in Finite Aquifers
Authors: Al Zayer Hassan A. , Saeed Muhammad S.
Published: March 2023

Storing CO2 in deep saline aquifers is a viable technology to manage carbon emissions. However, in finite aquifers, reservoir pressure builds up quickly which can reduce injectivity and limit the ultimate storable quantities of CO2. Therefore, the purpose of this work is to investigate the optimum design for reservoir pressure-management wells during carbon dioxide (CO2) storage in finite aquifers using a numerical simulation method.

In this paper, a synthetic aquifer model was used to investigate the optimal well placement and geometry, and well spacing to maximize CO2 storable quantities with a less total number of wells. Furthermore, the main target is to maximize the pore volume utilization and target injection rate per well without exceeding the reservoir fracture limit. A fit-for-purpose 3D reservoir simulation model used in this study was built to allow robust and accurate large-scale numerical simulation studies related to CO2 sequestration and storage using synthetic data.

Multiple CO2 gas injectors were placed at the crest of the structure to utilize most of the available pore volume and maximize the injection rate. Various pressure management schemes were modeled and compared to find out the optimal design which can provide maximum injection rate and ultimate storage capacity. The results showed that well placement depth and the number of active relief wells both are playing a major role in maximizing the ultimate storage efficiency. Since reservoir heterogeneity and anisotropy can significantly affect the relief wells’ design, streamlines tracing can be very helpful to optimize the well spacing and orientation. After 80 years of injection, the simulation sensitivity study showed a significant difference (10-20% of CO2 storage efficiency) between the different pressure management schemes. In conclusion, relief wells are often needed to manage reservoir pressure build-up during CO2 storage in finite aquifers and their design is vital in maximizing the ultimate CO2 storage capacity.

The outcome of this study is providing a useful guideline to optimize the field development plans and maximize the CO2 storage capacity in finite aquifers.
Data-Driven Decision Making Through Digital Field Data Visualization Dashboard and Automated Process
Authors: Al-Aradi Huda , Rajab Sayed Yaseen , Al-Mototeh Nasser , Al-Anjawi Ali , Winuksa Mahindra , Achmad Pajar , Ladraa Ahcene , Baamara Abdelouahab
Published: March 2023

The daily field reports of The Kuwait Oil Company (KOC) West Kuwait asset (WK) were captured through Excel spreadsheets. Consolidation of these reports into a single report presentation for The WK Deputy Chief Executive Office (DCEO) had been inefficient and time-consuming. Exploration and Production (E&P) Information Management (IM) team delivered a solution to replace the current work practices with an automated process to capture, consolidate, and centralize these reports into E&P Corporate Data Management System and present them in a comprehensive and user-friendly visualization dashboard for KOC top-level management and business analysts of WK asset providing a complete picture of key performance indicators (KPIs) of their production assets enabling data-driven decision that support business objectives.
Study on Horizontal Well Indirect Fracturing Technology in the Gangue of Broken Soft Coal Seams for CBM Development
Authors: Li Xuejiao , Zhao Haifeng , Wang Chaowei , Wang Dongchenhao , Yao Wenjie , Zhen Huaibin , Wang Zongfei
Published: March 2023

Crushed soft coal seams have the features of low mechanical strength and broken coal structure. Fracturing directly in broken soft coal seams, short and coarse fractures are formed and a large amount of coal powder is produced. In this study, horizontal well indirect fracturing technology in the gangue of crushed soft coal seams was proposed to improve the coalbed methane (CBM) development effect.

Based on the No. 5 coal seam in the Daning-Jixian block of the Ordos Basin in China, the fracability of the gangue and coal seam were evaluated by logging interpretation, rock mechanical tests and immersion experiments. The technological process of horizontal well staged fracturing in the gangue of crushed soft coal seams was constructed by field test. A corresponding hydraulic fracturing physical simulation experiment was performed, and fracture propagation behaviors were investigated.

The results show that compared with crushed soft coal seams, gangue has better brittleness and fracability. Horizontal well indirect fracturing in gangue can well stimulate upper and lower coal seams, significantly decrease the fracturing pressure and fracture extension pressure, and reduce the production of coal power. The desirable crack extension and considerably enhanced production effect demonstrated the remarkable engineering feasibility of this technology. The suitable thickness is 0.5~1 m for mudstone gangue, whereas a thickness of 2~3 m is appropriate for interbedded sandstone and mudstone gangue. The stage spacing should be larger than 80 m, and the cluster spacing should be greater than 24 m to avoid the stress shadow effect. Hydraulic fractures initiated from the gangue of coal seams, first spread vertically in the gangue layer and extend rapidly along the interfaces between the coal seams and gangue, then penetrated the lithologic interface and expanded into the coal seams. The upper and lower coal seams were torn open, and 3D complex fractures were formed in the coal seams, creating flow channels for CBM into the horizontal wellbore.

This research presents a novel technical idea for the CBM extraction of crushed soft coal seams. The findings can offer guidance for the optimal design of horizontal well indirect fracturing in the gangue of crushed soft coal seams.
Artificial Intelligence (AI) Based - Under Suspended Load Detection - Case Study in Rokan Drilling & Completion Operation
Authors: Rizki Freddy Frinly , Santoso Ade Anggi Naluriawan , Negara Ari Sukma , Janasri Bayu Raka , Fikri Bima Surya Khoirul
Published: March 2023

Automatic under suspended load detection system is a term for an image processing method which is used to identify compliance and safety aspect of crane or lifting & rigging operations in drilling & completion activities especially under suspended load for line of fire prevention which possibly leads to a serious incident and fatality. According to company data statistics, approximately 30% of safety findings are contributed by lifting & rigging operations. As a state-owned company that operates one of the largest fields in Indonesia with an extensive drilling and well intervention programs, Pertamina Hulu Rokan (PHR) commits to protect the safety of their people by reducing lifting & rigging operations safety findings and improving its monitoring process. The company has taken the initiative to explore any digital alternatives that can be applied such as utilization of computer vision and artificial intelligence in online Closed-Circuit Television (CCTV) units to enable prevention of under suspended load case in drilling & completion operations by using deep learning algorithm such as Yolov4 and/or Faster R-CNN.

During development process, the team has several technical challenges to be addressed such as the diversity of lifting and rigging scenarios such as lifting direction, lifting equipment type, and load variety to capture and detect under suspended load zone in 2-dimensional image using straightforward logic. The first step towards building this system is collecting lifting and rigging operations image datasets from various rig areas and with different lifting scenarios and equipment. Deep learning algorithm such as Yolov4, Faster R-CNN are being used to train the model using the dataset which has been labelled on specific objects related to the lifting operation such as crane boom, crane hook, crane loads, crane tires, crane cabin, and crane box to construct under suspended load zone on the given scenarios. The Preliminary results indicate that the method has been useful to identify under suspended load zone and deliver real time automatic notification during lifting and rigging on a drilling or well intervention operations and prevent the safety risk exposure of our personnel.
A Mathematical Modelling of the Plunger Lift Considering Effects of Fluid Friction and Plunger Travel Velocity
Authors: Rajvanshi Saurabh , Nischal Rajiv , Prasad Bulusu V. R. V , Yadav Mahendra Prasad , Kumar Avinav , Gaur Devendra Pratap , Sethi Divyansh , Sharma Aman
Published: March 2023

Plunger lift technique is a well-known, widely accepted and economical artificial lift alternative, especially in deliquification of gas wells and to increase the efficiency of intermittently flowing oil wells. This study includes impact of fluid friction losses and variable plunger travel velocity in mathematical modelling of plunger lift design.

The design of plunger lift system, in most models, is simulated by a fix value of fluid friction losses based on plunger velocity, which does not consider the variable effects of the friction factor calculation based on Colebrook equation or complex multiphase flow. To consider these effects, other equations must be solved simultaneously with the well-known Foss and Gaul equations. Solution of the plunger lift design equation becomes even more complicated if the fluid friction properties are not uniform.

Foss and Gaul suggested an approximation for gas and liquid friction are constant for a given tubing size and a plunger velocity of 1,000 ft/min. Plunger travel velocity is the important parameter in design. The velocity at which the plunger travels up the tubing also affects the plunger efficiency. Very low velocity of plunger increases gas slippage and subsequently lead to inefficient operation. Whereas, high plunger velocities tend to push the plunger through the liquids. A steady state mathematical modelling and sensitivity analysis considering broad estimates, has been done using Python language. This approach can simulate any combination of associated parameters for plunger lift design in a relatively simple and effective manner.

The numerical results are compared to the actual available data. Analysis of the numerical results shows that the effects of fluid friction losses and plunger travel velocity are important for accurate modelling and design of the plunger lift system.
Insights from the Development of Fractured Carbonate Reservoirs in Structurally Complex Geological Settings
Authors: Funk Erich , Olmeda Mariana Alejandra
Published: March 2023

The wide range in geological complexity encountered in fractured carbonate reservoirs requires the combination of several elements to optimize their development: a favorable structural position for drilling needs to be paired with the understanding of the fluid connectivity pathways affecting its location. In addition, the well placement criteria will vary depending on the stage of maturity of the field. This work aims to summarize key observations acquired by the authors during over a decade of field development experience in faulted and fractured carbonate oil reservoirs in the Zagros Fold and Thrust Belt in the Kurdistan Region of Iraq.

The methodology of this work includes the analysis of different fracture types and their context of occurrence with respect to well behaviors during drilling, production and surveillance stages. These correlations are based on the authors’ observations from a number of producing oil fields where vertical and horizontal wells in deformed sections provided insights to the wide spectrum of geological features and their hierarchical range in flow potential. Commonalities observed from these fields are presented in this paper in a generic fashion covering multi-scale data sets.

The work summarizes the understanding of the diverse fracture networks and their dynamic behavior along with key remarks on optimizing well placement criteria and completion strategies according to the maturity of the field and, ultimately, to improve the field development strategy. Outcrop examples are used to introduce the array of fracture categories encountered in subsurface and to guide the discussion on the dimension of scale and their spatial relationship relative to each other as contributors to reservoir plumbing systems and observed reservoir dynamics. As a result of this analysis, the challenges related to fractured and faulted carbonate fields such as water breakthrough scenarios, cumulative rise in water production and underperforming reservoir sections are addressed.

This paper therefore intends to contribute to the discussion on development strategies, definition, and selection of drilling targets and well design applied in fractured and faulted carbonate reservoirs by utilizing observations from different reservoir types in the Kurdistan Region of Iraq.
Smart Knowledge Submission System Based on Natural Language Processing (NLP) Leveraging on Language Modelling Approach
Authors: Idris Muhammad Azmi , Alsultan Hussah
Published: March 2023

Having a reliable classification of knowledge assets in a corporate knowledge base system in an oil and gas company is challenging. This is due to the tremendous amount and variety of knowledge assets generated by complex business and engineering processes. Submission of the knowledge assets is one of the main challenges as users may choose the wrong knowledge type or classification. A lengthy manual review process is required to evaluate the submission and some need to be rejected and returned to users. Incorrect classification of knowledge assets may cause issues in knowledge search engines as users cannot find correct articles due to the misclassification of the knowledge assets. In another challenge, some assets knowledge submission is duplicated as other users have submitted the same assets.

Our research evaluates the potential of Natural Language Processing (NLP) applications in the form of neural language modeling transformers. The models will generate the following functions: Knowledge categorization: Automatically categorizes the knowledge items based on the given abstract. This will reduce the possibility of the wrong classification that can prevent the knowledge from being published, simplify knowledge submission and expedite the knowledge review process.Text Summarization: Automatically generating a summary of knowledge assets that can be used as short descriptions or abstracts during knowledge submission.Document Semantic Similarity: Identifies similar documents in terms of the context that can help for document search or deletion of duplicate documents
Improving the Productivity of Highly Damaged Intervals in Low Draw-Down Oil Wells Using Dynamic Under-Balance Gun Type: Case Study in Gulf of Suez Offshore Field, Egypt
Authors: El Shiekh Mahmoud Ibrahim , Koriesh Mahmoud Mohamed , Vazquez Maria Leticia , Mousa Ali ELbasyouni , Ibrahim Mostafa Mamdouh
Published: March 2023

Through tubing perforating guns that are deployed by means of electric line has been the most economic perforation technique to provide connectivity between the pay zone and the wellbore in cased hole wells. Conventional E-line guns was the most common type of guns used, however during the last two decades various types of guns has been raised to improve the perforation efficiency.

In offshore operating companies including Gulf of Suez Petroleum Company "GUPCO" rig-less perforation has been proved to be the cheapest stimulation method, in case of re-perforating an existing interval, when compared to coiled tubing jobs that requires rig-assist or even acid bull-heading which will need at least a fully prepared vessel for chemical tank storage in addition to the highly cost acid itself. Moreover, it is much cheaper than tubing conveyed type that is always accompanied with rig work-over. So using dynamic under-balance gun has become a smart solution that will recover all debris in perforation tunnels in order to achieve the maximum oil recovery.

When using conventional guns for re-perforating existing intervals there is a large contrast in the degree of success, and it was obvious that in law draw-down wells re-perforating the low productivity intervals has minor improvement and in most cases it was useless this was latterly explained to be resulted from the insufficient underbalance.

In this work, implementation of a specific type of guns (Dynamic under-balance perforating guns) will be presented. The mentioned type generates in-situ underbalance creating an instantaneous and controlled surge of formation fluids into the well, which cleans the perforation tunnels up to 97% and enhances the well's productivity. The dynamic under-balance perforation technique has been tried in four wells that seemed from production logs are contributing with little share or sometimes not sharing at all which has been attributed to skin effect. After re-perforation, the results were outstanding with an increase of 20–40% in the total liquid rate and incremental increase in the oil rate with more than 2000 BOPD in the mentioned wells. The stated results revealed that the oil-bearing intervals are now competing with the high productivity high water cut intervals which considered a valuable gain with considerable very low job cost.

The new guns type has proved its success especially when compared its results with the previous re-perforation jobs using conventional guns in the same wells where the incremental oil gain was much less. It can be used as a cheap alternative for near well-bore stimulation jobs especially for offshore platform wells.
Modified Testing Protocol to Determine the Precise Thickening Time of Cement Slurry: A Field-centered Approach to Prevent the Premature Setting of Cement Slurry while Placement and Maximizing the Operational Efficiency
Authors: Ali Wajid , Al-Turki Faisal Abdullah , Lopez Fabian , Bouaraki Mouloud
Published: March 2023

This paper addresses some challenges concerning cement slurry designs, focused on thickening time, requiring careful engineering practices, and proper cementing operational considerations. It presents a series of thickening time test studies compared to "conventional testing practice" versus "field simulated testing" to illustrate the differences between results.

Many aspects of oilfield cementing are sufficiently important to warrant study. One area that requires attention is the procedures used to design the cement slurry in the well. The batch-mix and static conditions influence the physical attributes of oilfield cement, including thickening time. Conventional laboratory testing invariably follows the API procedure for thickening time. Although this might be adequate in most cases, it may only precisely predict field behavior (at actual conditions) in some cases.

Conventional thickening time tests may not necessarily indicate the true responsiveness of cement slurry. Traditional thickening time waiting periods do not relate directly to how long a slurry can remain static and still be moveable after an inadvertent or intentional shutdown during placement. Mixing, pumping, and displacing the cement (including any shutdown) affect the hydration and thickening behavior. Therefore, it is imperative to understand the relative contributions from each part of the process toward the thickening time to help prevent failures. These contributions might not significantly impact slurry properties but should be quantified and understood. The reliable prediction of cement thickening time can be vital to the success of oilfield cementing operations. Because cement placement techniques have become complex, delivering slurry with accurate thickening time can be crucial to the job's success.

This paper presents a modified testing protocol to evaluate the effects of batch-mixing and static-period on cement slurry's thickening time to minimize the incidents related to the premature setting of cement slurry.
Sufficient conditions for the optimal control problems with interval-valued objective function in admissible orders
Authors: Li Lifeng , Zhang Jianke
Published: March 2023

This paper addresses the optimal control problems with interval-valued objective function. We consider a kind of total order relationships ≤adm between two intervals. For each total order relationship, Kuhn-Tucker sufficient conditions for the optimal control problems with interval-valued objective function are obtained. And numerical example has been considered and solved. Kuhn-Tucker sufficient conditions given under total order relationship ≤adm are sufficient conditions under partial order relationship ≼LU for interval-valued optimal control problems. The results of this paper can be used to construct evolutionary algorithms for solving interval-valued optimal control problems.
Advertisement by medical facilities as an opportunity of APOE genetic testing in Japan: a website analysis
Authors: Sato Kenichiro , Niimi Yoshiki , Ihara Ryoko , Iwata Atsushi , Ikeuchi Takeshi , Iwatsubo Takeshi
Published: March 2023

Background: The APOE-ε4 allele[s] is a strong risk factor for Alzheimer’s disease (AD). Its significant opportunity route includes out-of-insurance APOE testing services provided in medical facilities in Japan via their website advertisements. Therefore, there is a concern that adequate self-determination of whether to undergo APOE testing may be spared depending on the content of website advertisement descriptions.
Methods: In this study, we searched medical facility websites in Japan advertising APOEgenetic testing as one of their services. The defining features of the advertisements were manually assessed based on deemed-preferable features that we prespecified in the aspects of legal regulations or other applicable guidelines published by related societies.
Results: We identified 220 medical facilities that had created advertisements for the provision of APOE genetic testing on their websites. Of these, 85% were small clinics, and the remaining 15% were outpatient departments of large hospitals. The median cost of APOE testing (when clarified) was US$ 123.1 (in 143 JP¥/US$). Contact information, details, and costs of testing were described on most of the websites. Meanwhile, features’ explaining APOE as a risk gene,’ ‘notes on interpreting APOEresults,’ or ‘explaining examination methods (e.g., blood sampling) were described to a variable degree depending on individual facilities. ‘Notes on genetic testing’ or ‘genetic counseling’ were hardly referred to, and ‘specialists with appropriate expertise’ were considered to participate in clinical practice in approximately one-third of these facilities providing APOEtesting services.
Conclusions: These results suggest that self-determination on taking out-of-insurance APOE testing at some medical facilities in Japan may possibly be influenced in an inappropriate manner. Further discussion might be warranted on how and to what extent information on APOE testing should be provided to patients on the website of medical facilities advertising the test in order to support the well-informed self-determination of patients.
The fungal quorum-sensing molecule, farnesol, regulates the immune response of vaginal epithelial cells against Candida albicans
Authors: Li Ting , Liu Zhao-Hui , Fan Lin-Yuan , Zhang Zhan , Bai Hui-Hui , Wang Feng-Juan , Shang Chen-Guang , Zong Xiao-Nan , Liu Yong
Published: March 2023

Background
Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections—candidiasises, especially vulvovaginal candidiasis (VVC).
Methods
The effect of farnesol on cellular morphology and viability and evaluated the production of Th1 (IL-2), Th2 (IL-4), proinflammatory (IL-6), chemotactic (IL-8), and Th17 (IL-17) cytokines in the culture supernatants of vaginal epithelial cell line (VK2) were evaluated. Moreover, we tested the inhibitory effect of farnesol on C. albicans adhesion. Scanning electron microscopy was conducted to observe any VK2 cell ultrastructural changes.
Results
Only low concentrations (≤ 50 µM) of farnesol did not affect the morphology and viability of the VK2 cells (P > 0.05). Farnesol reduced the adhesion of C. albicans to the VK2 cells. When treated with farnesol, statistical elevated levels of both IL-4 and IL-17 secreted by the infected VK2 cells were present in the culture supernatants (P < 0.05). Farnesol acts as a stimulator to up-regulate the Th17-type innate immune response, as well as Th2-type humoral immunity following C. albicans infection. Further research is required to select the optimal therapeutic dose to develop efficacious and safe mucosal immune adjuvant for treating VVCs.
Protocol of a prospective multicenter randomized controlled trial of robot-assisted stereotatic lesioning in the treatment of focal drug-resistant epilepsy
Authors: Mingkun Gong , Xu Ke , Shan Yongzhi , Wang YiHe , Zhang Chao , Wang Xiongfei , Zhou Jian , Guan Yuguang , Li Tianfu , Luan Guoming
Published: March 2023

Background
This protocol describes the design of a multicenter randomized controlled trial of robot-assisted stereotactic lesioning versus epileptogenic foci resection. Typical causes of focal epilepsy include hippocampal sclerosis and focal cortical dysplasia. These patients usually present with drug resistance and require surgical treatment. Although epileptogenic foci resection is still the most commonly used treatment for such focal epilepsy, there is increasing evidence that epileptogenic focus resection may lead to neurological impairment. The treatment of epilepsy with robot- assisted stereotactic lesioning mainly includes two new minimally invasive surgical methods: radiofrequency thermocoagulation (RF-TC) and laser interstitial thermal therapy (LITT). Seizure-free is less likely to be achieved by these two procedures, but neurologic preservation is better. In this study, we aimed to compare the safety and efficacy of RF-TC, LITT, and epileptogenic foci resection for focal drug-resistant epilepsy.
Methods
This is a multicenter, three-arm, randomized controlled clinical trial. The study will include patients older than 3 years of age with epilepsy who have had medically refractory seizures for at least 2 years and are eligible for surgical treatment with an epileptogenic focus as determined by multidisciplinary evaluation prior to randomization. The primary outcome measure is seizure outcome (quantified by seizure remission rate) at 3-month, 6-month, and 1-year follow-up after treatment. Postoperative neurologic impairment, spectrum distribution change of video electroencephalogram, quality of life, and medical costs are also assessed as secondary outcomes.
Trial registration
URL: https://chictr.org.cn. ChiCTR2200060974. Registered on June 14, 2022. The status of the trial is recruiting and the estimated study completion date is December 31, 2024.
Association of a Healthy Lifestyle with Mortality in Older People
Authors: Robb Catherine , Carr Prudence , Ball Jocasta , Owen Alice , Beilin Lawrence J. , Newman Anne B. , Nelson Mark R. , Reid Christopher M , Orchard Suzanne G. , Neumann Johannes T , Tonkin Andrew M. , Wolfe Rory , McNeil John J.
Published: March 2023

Background
Unhealthy lifestyle behaviours such as smoking, high alcohol consumption, poor diet or low physical activity are associated with morbidity and premature mortality. Public health guidelines provide recommendations for adherence to these four factors, however, their impact on the health of older people is less certain.
Methods
The study involved 11,340 Australian participants (median age 7.39 [Interquartile Range (IQR) 71.7, 77.3]) from the ASPirin in Reducing Events in the Elderly study, followed for a median of 6.8 years (IQR: 5.7, 7.9). We investigated whether a point-based lifestyle score based on adherence to guidelines for a healthy diet, physical activity, non-smoking and moderate alcohol consumption was associated with all-cause and cause-specific mortality.
Results
In multivariable adjusted models, compared to those in the unfavourable lifestyle group, individuals in the moderate lifestyle group (Hazard Ratio (HR) 0.73 [95% CI 0.61, 0.88]) and favourable lifestyle group (HR 0.68 [95% CI 0.56, 0.83]) had lower risk of all-cause mortality. A similar pattern was observed for cardiovascular related mortality and non-cancer/non-cardiovascular related mortality. There was no association of lifestyle with cancer-related mortality. Stratified analysis indicated larger effect sizes among males, those ≤ 73 years old and among those in the aspirin treatment group.
Conclusions
In a large cohort of initially healthy older people, reported adherence to a healthy lifestyle is associated with reduced risk of all-cause and cause-specific mortality.
Homocysteine levels in first-episode, drug-naïve patients with psychiatric disorders
Authors: Fan Ning , Zhao Wenxuan , Yun Yajun , Bai Luyuan , An Huimei , Zhang Qi , Yan Jiangling , Fan Fengmei , Han Xiaole , Yang Fude
Published: March 2023

A high homocysteine (Hcy) level is reportedly a risk factor for schizophrenia, depression, bipolar disorder, and other psychiatric disorders. The purpose of this study was to examine Hcy levels in first-episode, drug-naïve inpatients with psychotic symptoms and a diversity of psychiatric diseases to further investigate the association between Hcy levels and psychiatric disorders. In this study, we enrolled 247 psychiatric patients, aged 18–40year. Seventy-five were diagnosed with schizophrenia, 48 with acute and transient psychotic disorders, 36 with manic episodes with psychosis, 32 with major depressive episodes with psychosis, and 56 healthy controls. Serum Hcy levels were measured by enzyme cycle method. Concentration of Hcy levels > 15 µmol/L was defined as hyperhomocysteinemia. Hcy levels were significantly higher in first-episode and drug-naïve psychotic patients compared to healthy controls (F = 12.778, P < 0.001). In the psychiatric disorder groups, Hcy levels were significantly higher in males and females (P < 0.05) in schizophrenia, acute and transient psychotic disorder, and major depressive disorder, but not in mania (P > 0.05). However, serum Hcy levels were not significantly different among the psychiatric disorder groups (F = 1.549, P = 0.227). The prevalence of hyperhomocysteinemia was 37.3% for schizophrenia, 45.8% for acute and transient psychotic disorders, 66.7% for manic episodes with psychosis, and 37.5% for major depressive episodes with psychosis. Hyperhomocysteinemia was more frequent in manic episodes with psychosis than in the other groups (χ2 = 10.026, P = 0.018). Moreover, binary logistic regression showed that male sex was an independent risk factor for hyperhomocysteinemia (OR = 6,577, 95% CI = 3.398–12.731, P < 0.001). These results suggest that first-episode, drug-naïve patients with the psychiatric disorders studied here have higher Hcy levels than does the general population, and those at greatest risk are men. However, we observed no differences in Hcy levels across different psychotic disorders. It has been suggested that elevated Hcy level contributes to the pathogenesis of psychiatric disorders, and our results clarify that it is likely an unspecific risk factor for psychiatric disorders generally.
Combinatorial interactions among natural structural variants of Brassica SOC1 promoters and SVP depict conservation of binding affinity despite molecular diversity
Authors: Kaur Simran , Sisodia Rinki , Gupta Bharat , Madhurantakam Chaithanya , Singh Anandita
Published: March 2023

Genes constituting floral regulatory network can be targeted to generate climate resilient, early flowering crops. SOC1, a central integrator of flowering, is downregulated by SVP. In highly duplicated, amphidiploid genome of Brassica juncea, flowering is plausibly mediated by combinatorial interactions among natural variants of multiple SOC1 promoters and SVP. Although fluctuating temperatures can influence energetics of molecular interactions, a mechanistic view on how these impact phenotypes remains unexplored. Analysis of binding patterns of biomolecules thus underpin new paradigms for precision trait engineering. Herein, we characterize 9 natural variants (homeologs and isoforms) of B. juncea SVP differing in MIKC domains. Generation and characterization of refined models of 15 SVP proteins (natural and hypothetical) and 3 SOC1 promoter fragments revealed extensive structural diversity. Despite this, binding affinity of 48 docked complexes were comparable except in cases where truncated proteins were involved. Investigation of 27 docked complexes for distribution and type of molecular contacts (π-π stacking, hydrophobic interactions, Van-der-Waals forces, Hydrogen bonds); shared or unique interacting patterns, revealed substantial variation suggesting involvement of compensatory mutations for preserving binding. Yeast one-hybrid assays validated binding potential predicted in docked complexes. Conserved amino-acid residues and nucleotides involved in non-covalent interactions were identified. Computational alanine substitution, established the cruciality of amino-acid hotspots conferring stability to docked complexes. Our study is relevant from an application standpoint. Identification of conserved amino-acid hotspots is essential for rational protein design since targeted mutagenesis of these can modify natural binding spectrum of regulatory proteins, and is a way forward for trait engineering.
Determination of pesticide residues in fruits: a systematic review and meta-analyses
Authors: Rahimi Alireza , Khazaei Salman , Ahmadi Sarina , Mehri Fereshteh
Published: March 2023

The present study assessed different pesticide residues (insecticide, fungicide, herbicide, acaricide, ovacide, nematicide, miticide, and veterinary substance) in various fruits based on the type of fruits and the mainland. The studies conducted on concentrations of pesticides in various fruits were collected from reliable databases such as Web of Science, PubMed, and Scopus from November 17, 1995, to October 26, 2021. Based on the findings, the average level of pesticides in various fruits was 0.44 mg/kg and 95% CI (0.39-0.49 mg/kg). The ranking of pesticides in different fruits was in the order of fungicide> nematicide > insecticide > herbicide > acaricide > ovacide > veterinary substance. The highest and the lowest mean and 95% CI of pesticides were related to raspberries 6.03 mg/kg (1.4, 8.5 mg/kg) and nectarine 0.015mg/kg (0.012, 0.019 mg/kg). Furthermore, according to the mainland the pesticide concentration in different fruits was in the order of fungicide> veterinary substance > nematicide > insecticide > herbicide > acaricide > ovacide > miticide. The highest concentration of pesticides in Europe and North America was related to veterinary substance and herbicide while fungicide was reported in Africa, Asia, and South America. The value of this meta-analysis lies in risk models and that it can be used by health strategists and monitoring programs aiming to lower the concentration of different pesticide residues in various fruits.
A novel defined basement membrane-related genes signature for predicting the prognosis of Hepatocellular carcinoma
Authors: Luo Yijiang , Zhang Xueyong , Yang Hao
Published: March 2023

Background.Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with poor prognosis, making the prediction of the prognosis much challenges. Basement membrane-related genes (BMRGs) play an important role in the progression of cancer. Thus, they are often used as targets to inhibit tumor progression. However, the value of BMRGs in predicting prognosis of HCC still remains to be further elucidated. This study aimed to find the relationship between BMRGs and HCC and the value of BMRGs in predicting the prognosis of HCC.Methods.We acquired transcriptome and clinical data of HCC from The Cancer Genome Atlas (TCGA) and randomly divided the data into training and test sets in order to develop a reliable prognostic signature of BMRGs for HCC. The BMRGs model was built using multivariate Cox regression, least absolute shrinkage and selection operator (LASSO), and univariate Cox regression. The risk signature was further validated and assessed using the principal component analysis (PCA), Kaplan-Meier analysis, and time-dependent receiver operating characteristics (ROC). To forecast the overall survival, a nomogram and calibration curves were created (OS). Functional enrichment analysis was used to evaluate the potential biological pathways. We also conducted immunological research and a pharmacological comparison between the high- and low-risk groups in this study.Results.We identified 16 differentially expressed genes and constructed a risk model of four BMRGs, including COL2A1, CTSA, LAMB1,P3H1. The PCA analysis showed that the signature could distinguish the high- and low-risk groups well. Patients in the low-risk group showed significantly better outcome compared with patients in the high-risk group. Receiver operating characteristic (ROC) curve analysis show predictive capacity. Moreover, the nomogram showed good predictability. Univariate and multivariate Cox regression analysis validated that the model results supported the hypothesis that BMRGs were independent risk factors for HCC. Furthermore, analysis of clinical characteristics and tumor microenvironment (TME) between risk groups showed significant difference. Functional analysis revealed different immune-related pathways were enriched, and immune status were different between two risk groups. Mediation analysis with IC50 revealed that the two risk group were significantly different, which could be a guidance of systemic treatment. Finally, we further verified in clinical samples that the mRNA and protein expression levels of the four genes in this model are significantly higher in liver cancer tissues than in adjacent tissues.Conclusion.A novel BMRGs signature can be used for prognostic prediction in HCC. This provide us with a potential progression trajectory as well as predictions of therapeutic response.
Cyclic Betaines act as feeding deterrents in Nereis diversicolor
Authors: Fletcher Nichola , Ohnstad Hannah , Hardege Joerg D.
Published: March 2023

Nereis diversicolor is a widely distributed bioturbating ragworm that inhabits the coastal and estuarine regions of Northwestern Europe and is prey to numerous fish and crustacean species. In order for survival, this like many other invertebrate species, needs to develop strategies to detect and/or escape the numerous predators. The worms utilise chemical cues within the environment to aid predator detection and avoidance. Trigonelline and Homarine are cyclic betaines both present in a variety of animals within the marine environment including crustaceans and fish that are established predators of the worms and have been shown to inhibit feeding behaviours in other prey species (Poulin et al, 2018). We explored potential impacts that these chemicals have on the foraging behaviour of Nereis diversicolor populations from the Humber Estuary, UK. In lab experiments both Trigonelline and Homarine at specific concentrations (10− 3 M and 10− 4 M) significantly reduce foraging behaviour confirming that predator associated odour compounds can impact prey feeding behaviours.