bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing Deep Closed-Loop Geothermal Wells for Globally Scalable Energy Production by Leveraging Oil and Gas ERD and HPHT Well Construction Expertise
Authors: van Oort Eric , Chen Dongmei , Ashok Pradeepkumar , Fallah Amirhossein
Published: March 2021

Deep closed-loop geothermal systems (DCLGS) are introduced as an alternative to traditional enhanced geothermal systems (EGS) for green energy production that is globally scalable and dispatchable. Recent modeling work shows that DCLGS can generate an amount of power that is similar to that of EGS, while overcoming many of the downsides of EGS (such as induced seismicity, emissions to air, mineral scaling etc.). DCLGS wells can be constructed by leveraging oil and gas extended reach drilling (ERD) and high-pressure high-temperature (HPHT) drilling expertise in particular.

The objectives of this paper are two-fold. First, we demonstrate that DCLGS wells can generate significant geothermal power, i.e. on the order of 25-30 MWt per borehole initially. To this extent, we have developed a coupled hydraulic-thermal model, validated using oil and gas well cases, that can simulate various DCLGS well configurations. Secondly, we highlight the technology gaps and needs that still exist for economically drilling DCLGS wells, showing that it is possible to extend oil and gas technology, expertise and experience in ERD and HPHT drilling to construct complex DCLGS wells.

Our coupled hydraulic-thermal sensitivity analyses show that there are key well drilling and design parameters that will ultimately affect DCLGS operating efficiency, including strategic deployment of managed pressure drilling / operation (MPD/MPO) technology, the use of vacuum-insulated tubing (VIT), and the selection of the completion in the high-temperature rock formations. Results show that optimum design and execution can boost initial geothermal power generation to 25 MWt and beyond. In addition, historical ERD and HPHT well experience is reviewed to establish the current state-of-the-art in complex well construction and highlight what specific technology developments require attention and investment to make DCLGS a reality in the near-future (with a time horizon of ~10 years). A main conclusion is that DCLGS is a realistic and viable alternative to EGS, with effective mitigation of many of the (potentially show-stopping) downsides of EGS.

Oil and gas companies are currently highly interested in green, sustainable energy to meet their environmental goals. DCLGS well construction allows them to actively develop a sustainable energy field in which they already have extensive domain expertise. DCLGS offers oil and gas companies a new direction for profitable business development while meeting environmental goals, and at the same time enables workforce retention, retraining and re-deployment using the highly transferable skills of oil and gas workers.
Risk-Controlled Wellbore Stability Criterion Based on Machine Learning Assisted Finite Element Model
Authors: AlBahrani Hussain , Morita Nobuo
Published: March 2021

In many drilling scenarios that include deep wells and highly stressed environments, the mud weight required to completely prevent wellbore instability can be impractically high. In such cases, what is known as risk-controlled wellbore stability criterion is introduced. This criterion allows for a certain level of wellbore instability to take place. This means that the mud weight calculated using this criterion will only constrain wellbore instability to a certain manageable level, hence the name risk-controlled. Conventionally, the allowable level of wellbore instability in this type of models has always been based on the magnitude of the breakout angle. However, wellbore enlargements, as seen in calipers and image logs, can be highly irregular in terms of its distribution around the wellbore. This irregularity means that risk-controlling the wellbore instability through the breakout angle might not be always sufficient. Instead, the total volume of cavings is introduced as the risk control parameter for wellbore instability. Unlike the breakout angle, the total volume of cavings can be coupled with a suitable hydraulics model to determine the threshold of manageable instability.

The expected total volume of cavings is determined using a machine learning (ML) assisted 3D elasto-plastic finite element model (FEM). The FEM works to model the interval of interest, which eventually provides a description of the stress distribution around the wellbore. The ML algorithm works to learn the patterns and limits of rock failure in a supervised training manner based on the wellbore enlargement seen in calipers and image logs from nearby offset wells. Combing the FEM output with the ML algorithm leads to an accurate prediction of shear failure zones. The model is able to predict both the radial and circumferential distribution of enlargements at any mud weight and stress regime, which leads to a determination of the expected total volume of cavings.

The model implementation is first validated through experimental data. The experimental data is based on true-triaxial tests of bored core samples. Next, a full dataset from offset wells is used to populate and train the model. The trained model is then used to produce estimations of risk-controlled stability mud weights for different drilling scenarios. The model results are compared against those produced by conventional methods. Finally, both the FEM-ML model and the conventional methods results are compared against the drilling experience of the offset wells.

This methodology provides a more comprehensive and new solution to risk controlling wellbore instability. It relies on a novel process which learns rock failure from calipers and image logs.
Innovative Drilling Fluid Technology Conquered Tough Geomechanics Offshore Mexico
Authors: Reyna Ricardo , Parra Viridiana , Volbre Daniel , Ballinas Raul , Maldonado Reinaldo , Rockwood Jene
Published: March 2021

The reservoir field highlighted in this paper is located Offshore Mexico in the southeast part of Campeche Bay and hidden below a troublesome, unstable formation that must be transacted before reaching the new production zone. During the exploration phase, this section experienced severe lost circulation and unstable conditions before reaching the final depth. Based on lessons learned, the team worked to develop a best- practices approach using geomechanics analysis and a novel fluid technology which enabled the operator to safely drill through this problematic intermediate section under high-pressure, high-temperature (HPHT) conditions.

The methodology started with identifying the geomechanics challenges, implementing operational best practices, and finally, use of an innovative, low-invasion fluid technology, which creates a thin and impermeable shield at the wellbore wall, effectively sealing the fractures and preventing fracture propagation in the highly unstable formation of interspersed carbonates, shales, and sandstones. The strong mechanical properties of the thin, but firm, barrier created at the wellbore wall minimized the destabilizing effect of fluid invasion. Synergy from the geomechanical team, best practices for the operation, and innovative drilling fluid technology solved the wellbore instability drilling challenge encountered in the exploration well.

In offset wells, losses of more than 2,200 m3 of drilling fluid, stuck pipe, and major NPT were observed. By incorporating the shielding technology, wellbore instability was improved in the intermediate section. In addition, the fluid technology was easily pumped through the bottomhole assembly (BHA) to seal formation fractures between 2,000 and 3,000 μm in size. This well, utilizing the barrier technology to mitigate the wellbore instability and drill within a narrow fracture gradient operating window, was the first in the area to have zero loss of drilling fluid as compared to the typical 5 to 10-m3/hr circulation losses experienced during exploration drilling in the intermediate section characterized by interbedded layers of carbonates, shales, and sandstone under high-pressure, high-temperature (HPHT) conditions. The coordination between the teams using best practices was critical to meeting the challenge of the intermediate geomechanically weak formation.

This case history in offshore Mexico will demonstrate both the importance of teamwork and the utilization of a proven technology that improves wellbore instability, minimizes NPT, mitigates pipe tripping issues and avoids huge volumes of drilling fluid lost into the geomechanically weak formation. This barrier technology can be applied globally to troublesome formations - such as interbedded carbonates, shales, and sandstones - to improve operations and provide cost savings for the operator.
Setting a New Standard: PDC Bits Equipped with Compact Vibration Recorders Monitor Entire Run and Reveal Stick-Slip Mitigation System Dysfunction and Downhole Motor Under Performance
Authors: Pelfrene Gilles , Cuilier Bruno , Ezzeddine Dhaker , Dourfaye Alfazazi , Dimov Dimo , Gallego Gilles , Roccas Christopher , Mangeny Aurélien , Reboul Sébastien
Published: March 2021

Downhole vibration measurements are used real-time and post-run to monitor drilling dynamics. Real-time monitoring tools are applied to facilitate immediate corrective actions but their deployment adds operational constraints and costs. This paper describes a new high-capability vibration recorder embedded in the drill bit as a standard component. The analysis of two case studies in the Middle East shows how memory devices available at a reduced cost and on every run are a valuable option for many appraisal or development wells.

Developing a fleet of reliable downhole recording tools typically takes years and involves teams of experts in various fields. The paper describes the strategy followed by a drill bit manufacturer to develop and deploy a compact, high capability and cost-effective vibration recorder to provide continuous readings of accelerations, rotation speed (RPM) and temperature at 100Hz and over 250 hours. Sensors and batteries have been packaged to fit into the drill bit shank or elsewhere in the bottom hole assembly (BHA). The recording starts automatically and thus removes the need for onsite personnel. The paper also presents proprietary data analytics software used to retrieve, process and synchronize the recorded data with other available data (mud logs, Measurement/Logging While Drilling logs) and to present critical drilling events.

In the first application, the 8 ½-in. bit drilled a 20,000 ft horizontal drain. More than 250 hr of data were recorded showing intense levels of stick-slip. During the entire run, the drilling team deployed several strategies to mitigate stick-slip, including the use of two surface-based stick-slip mitigation systems. The analysis shows that these systems are sometimes unsuccessful in mitigating stick-slip and are difficult to calibrate. It is demonstrated how the vibration recorder may contribute to fine tuning these mitigation efforts through optimization of their settings. In the second application, the vibration recorder was mounted on a 12 1/4-in. bit used to drill 5,000 ft through cement and formation. The analysis shows the motor was subjected to erratic RPM cycles, leading to frequent stalls and acceleration peaks during the run. It is shown how motor performance then decreased consistently during the last hundreds of feet of the section and how this affected rate of penetration (ROP).

Deployment of a vibration recorder over the entire drill bit manufacturer's fleet allows continuous monitoring of critical drilling issues and malfunctions related to a variety of drilling equipment that enables the operator to improve drilling performance. The bit-sensor package makes high frequency data systematically available at a reduced cost for every drilling application.
Use of Fiber Optic Information to Detect and Investigate the Gas-in-Riser Phenomenon
Authors: Santos Otto L. , Williams Wesley C. , Sharma Jyotsna , Almeida Mauricio A. , Kunju Mahendra K. , Taylor Charles E.
Published: March 2021

Potential applications of optical fiber technologies in the well control area are to detect the presence of gas and to unfold the gas dynamics inside marine risers (gas-in-riser). These issues became even more relevant now when considering the application of managed pressure drilling (MPD) operations in deep and ultradeep waters that may allow for a controlled amount of gas inside the riser.

The application of these fiber optic technologies in the well control domain is currently being evaluated at Louisiana State University (LSU) as a part of a gas-in-riser research project granted by the Gulf Research Program (GRP). To accomplish that, an actual well was recompleted and instrumented with fiber optic sensors to continuously collect data along the wellbore and with four pressure and temperature downhole gauges to record those parameters at four discrete depths. A 2-7/8 in. tubing string with its lower end at a depth of 5026 ft and a chemical line to inject nitrogen at the bottom of the hole were also installed in the well.

This paper discusses the results of four out seven experimental runs that were performed in this full-scale apparatus using fresh water and nitrogen in order to calibrate the installed pieces of equipment, to train the crew of researchers to run the tests, to check experiments repeatability and to obtain experimental results under very controlled conditions since water and nitrogen have well defined and constant properties.

The paper also presents a mathematical model based on the unsteady-state flow of a two-phase mixture that was developed to help design the experimental runs. The results obtained in the seven runs were used to calibrate the model that was additionally modified to read the experimental parameters. The simulated results produced a remarkable agreement with the fiber optic and pressure and temperature sensors gathered data.

Finally, the paper shows and analyzes simulation results of gas-in-riser operations on an actual drilling floater unit after the mathematical model has been adapted to predict pressures and output flow rates during gas circulations out of the riser. The effects of circulation flow rate, backpressure applied at surface and amount of gas inside the riser on pressures and flow rates are displayed and analyzed.
Improve Installations of Liners and Lower Completions with Real-Time Downhole Data
Authors: Mathisen Kim , Sorheim Tore , Keerthivasan Vijay Kumar , Pink Stephen , Young Dustin
Published: March 2021

Well construction activities including liners and lower completions deployment have historically realized downtime and unforeseen challenges. Surface data, torque and drag simulations, and previous experience are all sources of data commonly used to plan and facilitate these installations. Field development campaigns often include longer laterals, frequent three-dimensional bends, varying pressure profiles, and other challenges that cannot be sufficiently planned for by using surface data, torque and drag simulations, and experience alone. The industry requires a better quality set of data, and quicker access to this data, to more successfully and efficiently complete wells.

Wired drill pipe is a real-time data acquisition platform that has been used on more than 146 wells, 65 of those offshore wells, since 2015. While improved drilling operations have been the primary use of the wired drill pipe platform, operators have since challenged providers to increase the scope of real-time data acquisition capabilities using the wired drill pipe platform.

In order to address the challenges of understanding downhole dynamics during liner deployment and completion operations, a dynamic logging tool with real-time data transfer capability and restriction-less internal bore was developed.

The dynamic logging tool couples the data acquisition capabilities of the memory-based dynamic logging tool with the wired drill pipe platform to provide operators with real-time access to axial loads, torque, temperature, pressures, vibrations, and RPM during the lower completion and liner deployment operations. The data provided by the inclusion of this tool can be used to facilitate the optimization and continuous improvement of liner deployment operations. This in turn allows operators to minimize non-productive time (NPT) and overcome a steep learning curve for challenging field development campaigns.

This paper discusses the real-time logging tool technology implementation and its role in development campaigns. Examples of lower completion applications and data gathering techniques are presented, along with examples of how the data can be used to improve understanding of downhole dynamics, facilitate continuous operational improvements, and ultimately achieve a robust field development strategy.
Socio-demographic correlates of public stigma about mental illness: a population study on Hong Kong’s Chinese population
Authors: Lo Lincoln Lik Hang , Suen Yi Nam , Chan Sherry Kit Wa , Sum Min Yi , Charlton Cheung , Hui Christy Lai Ming , Lee Edwin Ho Ming , Chang Wing Chung , Chen Yu Hai Eric
Published: March 2021

Background Individuals with psychiatric disorders are often unwilling to seek help or often follow treatment regimens, fearing public stigma. This study identified the sociodemographic correlates of public stigma while accounting for mental health literacy and life satisfaction. Methods This study analysed data for 1,514 individuals who participated in a population-based random telephone survey conducted in 2018. Sociodemographic characteristics included gender, age, education level, and occupation. Data on public stigma, mental health literacy and life satisfaction were also collected. A multiple linear regression was conducted to examine the effects of sociodemographic characteristics on public stigma. A moderation analysis was performed to investigate the role of age and education in the relationship between mental health literacy and public stigma. Results Sociodemographic characteristics, such as female gender, older age groups, lower education, and occupation (particularly retired and homemakers), were associated with a higher public stigma. The association between public stigma and mental health literacy was the most significant among individuals aged 50 years and above and with lower education levels. Conclusions This study showed that certain population subgroups, based on their sociodemographic profile, have higher stigma about mental illnesses. Understanding the differential effects of sociodemographic factors on public stigma is imperative to developing effective anti-stigma campaigns. Keywords public stigma, mental health literacy, sociodemographic correlates, anti-stigma campaigns
Navigating abortion dilemmas: Attitudes and practices among Ethiopian health care professionals
Authors: Ewnetu Demelash Bezabih , Thorsen Viva Combs , Solbakk Jan Helge , Magelssen Morten
Published: March 2021

Background: Ethiopia’s 2005 abortion law improved access to legal abortion. In this study we examine the experiences of abortion providers with the revised abortion law, including how they view and resolve perceived moral challenges.Methods: Thirty healthcare professionals involved in abortion provision in Addis Ababa were interviewed. Transcripts were analyzed using systematic text condensation, a qualitative analysis framework.Results: Most participants considered the 2005 abortion law a clear improvement – yet it does not solve all problems and has led to new dilemmas. As a main finding, the law appears to have opened a large space for professionals’ individual interpretation and discretion concerning whether criteria for abortion are met.Regarding abortion for fetal abnormalities, participants support the woman’s authority in deciding whether to choose abortion, and although several saw these decisions as moral dilemmas, all thought that abortion was a justified choice when a diagnosis of fetal abnormality had been made.Conclusion: To make practice more predictable and uniform, more detailed official guidance on the law and how it should be interpreted is warranted.
1H NMR Based Metabolic Profiling Distinguishes the Differential Impact of Capture Techniques on Wild Bighorn Sheep
Authors: O’Shea-Stone Galen , Lambert Rachelle , Tripet Brian , Berardinelli James , Thomson Jennifer , Copié Valérie , Garrott Robert
Published: March 2021

Environmental metabolomics has the potential to facilitate the establishment of a new suite of tools for assessing the physiological status of important wildlife species. A first step in developing such tools is to evaluate the impacts of various capture techniques on metabolic profiles as capture is necessary to obtain the biological samples required for assays. This study employed 1H nuclear magnetic resonance (NMR)-based metabolite profiling of 562 blood serum samples from wild bighorn sheep to identify characteristic molecular serum makers of three capture techniques (dart, dropnet, and helicopter-based captures) to inform future sampling protocols for metabolomics studies, and to provide insights into the physiological impacts of capture. We found that different capture techniques induce distinct changes in amino acid serum profiles, the urea cycle, and glycolysis, and attribute the differences in metabolic patterns to differences in physical activity and stress caused by the different capture methods. These results suggest that when designing experiments involving the capture of wild animals, it may be prudent to employ a single capture technique to reduce confounding factors. It also supports administration of tranquilizers as soon as animals are restrained to mitigate stress and other physiological and metabolic responses.
Tooth Problem and its Treatment-seeking Behavior among Older Adults in India
Authors: Srivast Shobhit , Kumar Pradeep , Sinha Debashree , Mishra Prem Shankar
Published: March 2021

Background: Growing untreated morbidities among the older adults on geriatric issues especially an optimal dental treatment has become an unfinished agenda and a long-neglected area for care and management in many low and middle-income countries. There is a continuous rise in the older population in India and at the same time, the rising of co-morbidities or multi-morbidities in the aging population creates catastrophic challenges at the individuals, household, community, and country levels, and therefore, it is important to address dental health problems and related issues in the aged population in India. The present study is an attempt to understand the prevalence of tooth related problems and their health-seeking behavior among the older adults in India.Methods: The present research used data from Building a Knowledge Base on Population Aging in India (BKPAI) which was a national level survey and was conducted in 2011, across seven states of India. The effective sample size of this study was 9541 older adults aged 60+ years. Descriptive statistics and bivariate analysis were used to fulfill the study objectives. Additionally, the study employed the Heckprobit selection model which is a two-equation model to understand the determinants of dental health problems.Results: Older adults in the age group of 70-79 years (36.9%) and 80+ years (51.9%) reported higher dental problems compared to 60-69 years (19.9%). Moreover, older women reported more dental problems (29.2%) and also used more dental aids (12.6%) compared to older men. Older adults in the age group 70-79 and 80+ years were 0.15 times and 0.40 times less likely to use dental aids respectively, as compared to 60-69 years older adults. Moreover, older women were 0.28 times more likely to use dental aids than older men. Education and wealth of older adults have a negative relationship with dental problems.Conclusion: This study clearly emphasized that awareness of tooth related problems should be promoted vigorously. Further, a holistic approach is needed to prevent dental diseases that occur because of other co-morbidities. For that, integration of the oral health program with programs dealing with morbidities can act as a solution to the existing problem.
MOCHIO: A Novel Multi-Objective Coronavirus Herd Immunity Optimization Algorithm for Solving Brushless Direct Current Wheel Motor Design Optimization Problem
Authors: C Kumar , D Magdalin Mary , T Gunasekar
Published: March 2021

A prominent and realistic problem in the domain of magnetics is the optimal design of a brushless direct current (BLDC) motor. A key challenge is designing a BLDC motor such that it functions efficiently with a minimum cost of materials to achieve maximum efficiency. Recently, a novel optimization technique inspired by nature, called the Coronavirus Herd Immunity Optimizer (CHIO), is proposed. The inspiration for this technique derives from the idea of herd immunity as a way of combating the coronavirus pandemic. A variant of Coronavirus Herd Immunity Optimizer called Multi-Objective Coronavirus Herd Immunity Optimizer (MOCHIO) is proposed in this paper, and it has been directly used to optimize the BLDC motor design optimization problem. The BLDC motor design problem has two main objectives, such as minimization of the motor mass and maximization of the motor efficiency with five constraints and five design variables. First, MOCHIO is tested with benchmark functions and then applied to the BLDC motor design problem. In addition, the experimental results are compared with the multi-objective whale optimization algorithm (MOWOA), multi-objective grey wolf optimizer (MOGWO), multi-objective particle swarm optimizer (MOPSO), multi-objective moth flame optimizer (MOMFO), and multi-objective bat algorithm (MOBA) are presented to confirm the viability and dominance of the proposed MOCHIO algorithm.
Quantum Chemical Investigation on D-π-A Based Phenothiazine Organic Chromophores with Spacer and Electron Acceptor Effect for DSSCs
Authors: Munusamy Anbarasan Ponnusamy , Ammasi Arunkumar , Shajahan Shanavas , Ahamad Tansir
Published: March 2021

In this work, the newly designed phenothiazine based organic dye (PT-BTBA, PT-EBTBA and PT-EBTEBA) derivatives were screened and investigated for dye-sensitized solar cells (DSSCs) application. The literature dye of SB covers the electron-donor (D) in phenothiazine and cyanoacrylic acid in electron-acceptor (A) based on D-A structure. In order to improving the π-conjugation and acceptor effects on the SB dye were investigated. The effect of D-π-A designed dyes on the optical absorption spectra and photovoltaic (PV) parameters were implemented by the density functional theory (DFT) and time‐dependent DFT (TD-DFT) calculations. Also, the hybrid functionals were initially evaluated to establish an accurate methodology for calculating the first-singlet absorption peak of SB dye. Consequently, TD-CAM-B3LYP functional and 6-311++G(d,p) theory were well match with the literature data. According to this result, phenothiazine-4-((7-ethynylbenzo[c][1,2,5]thiadiazol-4-yl)ethynyl)benzoic acid (PT-EBTEBA) dye has the strong group for more red-shifted and successfully electron inject into TiO2 surface. It is expected to provide some theoretical guidance on designing photosensitive with new metal-free organic dyes for use in DSSCs yielding highly efficient performance.
RNAi Screening in Primary Human Breast Biopsies Identifies Mitochondrial Glutamate Flux as A Metabolic Vulnerability in Locally Advanced Breast Cancer
Authors: Iorio Caterina , Bouzina Alla , Jerzak Katarzyna , Andrews David , Screaton Robert
Published: March 2021

Background: Breast cancer (BC) is a leading cause of death in women[1]. Women with Locally Advanced Breast Cancer (LABC) have high risk disease with either large primary breast tumours and/or lymph node involvement. While neoadjuvant chemotherapy eradicates breast cancer in approximately one-third of cases prior to surgery, almost 70% of patients have residual disease and many will require additional chemotherapy post-operatively. Improving pre-operative efficacy of neoadjuvant systemic treatments while reducing their iatrogenicities are critical unmet needs. Methods: Here, we develop an RNA interference (RNAi) screening approach using conditionally reprogrammed primary LABC biopsies to identify genes of the mitochondrial Solute Ligand Carrier 25 (SLC25) family that support LABC cell viability. Results: We report that silencing SLC25A12, -A15, and -A18 genes, involved in glutamate and ornithine flux, augment 5-fluorouracil (5FU) cytotoxic effectiveness in LABC cells. Conclusions: Our data suggest glutamate metabolism may be a tumour-specific metabolic vulnerability in LABC. Furthermore, we demonstrate that RNAi screening in conditionally reprogrammed primary human breast cells can identify novel targets for the development of non-genotoxic BC treatments.
Indonesian government’s public communication management during a pandemic
Authors: Herman Achmad
Published: March 2021

The COVID-19 pandemic has triggered a health emergency as a vaccine for it has not been found yet requiring the government to seriously manage it. Therefore, the government needs to effectively implement non-pharmaceutical measures. One of the measures to suppress the spread of the virus is public communication. The government’s public communication in dealing with COVID-19 has faced problems resulted in low public discipline and awareness thus far. This study used a quantitative approach with descriptive statistics analysis. The analysis does not generalize the result but it can explain the characteristics of the sample to formulate the meaning of the result. The findings show that the public communication management of the government of Indonesia has not been effective because the dissemination of public information is diverse and inconsistent. This is because the government gives freedom to various media to provide information to the public, which creates a gap in the management of COVID-19 in Indonesia and results in low public discipline and awareness (mean value 2,97). Therefore, it is difficult for the government to deal with and manage health emergencies caused by the COVID-19 pandemic. Research has shown that the government must provide the public with consistent and valid information (mean value 3,51), monitor and supervise mass and electronic media, and use social media and online media to provide valid information from the government and disseminate positive and educative information to the public (mean value 4,06).
Sterol 14α-Demethylase from Trypanosomatidae Parasites as a Promising Target for Designing New Antiparasitic Agents
Authors: da Silva Santos-Júnior Paulo Fernando , Schmitt Martine , de Araújo-Júnior João Xavier , da Silva-Júnior Edeildo Ferreira
Published: March 2021

:

Trypanosomatidae family belongs to the Kinetoplastida order, which consists of obligatory parasites that affect plants and all
classes of vertebrates, especially humans and insects. Among the heteroxenic parasites, Leishmania spp., Trypanosoma cruzi, and
T. brucei are protozoa of most significant interest for medicinal chemistry, being etiological agents of Leishmaniasis, Chagas, and
Sleep Sickness diseases, respectively. Currently, inefficient pharmacotherapy, especially in chronic phases and low selectivity towards
parasite/host cells, justifies the need to discover new drugs to treat them effectively. Among other targets, the sterol 14α-demethylase
(CYP51), an enzyme responsible for ergosterol's biosynthesis in Trypanosomatidae parasites, has received more attention in the development
of new bioactive compounds. In this context, antifungal ravuconazole proved to be the most promising drug among this class against
T. cruzi, being used in combined therapy with Bnz in clinic trials. Non-antifungal inhibitors, such as VFV and VNF, have shown promising
results against T. cruzi and T.brucei, respectively, being tested in Bnz-combined therapies. Among the experimental studies involving
azoles, compound (15) was found to be the most promising derivative, displaying an IC50 value of 0.002 µM against amastigotes from
T. cruzi, in addition to being non-toxic and highly selective towards TcCYP51 (< 25 nM). Interestingly, imidazole analog (16) was
active against infectious forms of these three parasites, demonstrating Ki values of 0.17, 0.02, and 0.36 nM for CYP51 from T. cruzi,
T. brucei, and L. infantum. Finally, this review will address promising inhibitors targeting sterol 14α-demethylase (CYP51)
from Trypanosomatidae parasites, highlighting SAR studies, interactions with this target, and recent contributions and advances in the
field, as well.
Development and Validation of a UPLC-MS/MS Method for the Simultaneous
Determination of Verapamil and Trandolapril in Rat Plasma: Application
to a Pharmacokinetic Study
Authors: Vejendla Anuradha , Talari Subrahmanyam , Shetty Ratna Kumari
Published: March 2021

Background:

Verapamil is an excellent drug used for the medication of hypertension
and trandolapril. It is an angiotensin-converting-enzyme inhibitor. Hence, it is an interesting
method to develop a novel and reliable MS/UPLC strategy for the simultaneous development of
verapamil and trandolapril.

Objective:

This research study aims to develop a new, rapid, and sensitive UPLC-MS/MS method
for the simultaneous estimation of verapamil and trandolapril in rat plasma using D6-
verapamil and D6-trandolapril.

Method:

Separation was carried on column Symmetry C18 column (150x4.6 mm, 3.5 μm) using
isocratic elution with a buffer containing 1mL of formic acid in 1L of water and the mixture of
two components like Buffer and Acetonitrile in the ratio of 80:20 as mobile phase with
1mL/min flow rate at ambient temperature.

Results:

Analysis was performed within 5 minutes over a good linear concentration range from
2.4 ng/mL to 48 ng/mL (r2 = 0.9993 ± 0.018) for verapamil and 10pg/mL to 200pg/mL (r2
=0.9993± 0.006) for trandolapril .The extraction recoveries and matrix effect of verapamil and
trandolapril were 98.45, 99.95, 98.12, 99.66% and 98.27, 99.89, 97.78, 99.23% respectively, at different
QC concentration levels. Precision and recovery study results were determined within the
acceptable limit. An electrospray ionization source was used to study verapamil and Trandolapril at
m/z 454.72→182.16, 430.25→201.48, and IS for m/z 460.18→ 324.39, 436.28 → 340.52, which
were ion pairs of mass analysis. This method has successfully been applied to explore verapamil
(1.2mg/kg) with its internal standard (D6-Verapamil), trandolapril (0.005 mg/kg) with its internal
standard (D6-Trandolapril) extracted from rat plasma using liquid-liquid extraction.

Conclusion:

This manuscript focuses on the consistent evaluation of the key bioanalytical validation
parameters, and the following are discussed: accuracy, precision, sensitivity, selectivity,
standard curve, limits of quantification, range, recovery, and stability. These validation parameters
are described, together with illustrations of validation methodology applied in the case of
chromatographic methods used in bioanalysis.
Antifungal Activity of Green and Red Brazilian Propolis Extracts
Authors: de Freitas Márcia Christina Dornelas , de Sá Nívea Pereira , Carvalho Blenda Fernandes , Messias Anny Caroline , Lopes Gabriela Fonseca , de Moura Almeida Bruno , Almeida Jane José , Abreu José Alexandre , Binda Nancy S. , Caligiorne Rachel Basques , Vieira-Filho Sidney Augusto , Johann Susana , de Figueiredo Sônia Maria
Published: March 2021

Background:

Diseases associated to Candida spp. are recurrent and can be difficult to
treat, mainly due to the new strains resistant to the limited number of available antifungals.

Objective:

The objective of this study is to evaluate the in vitro and in vivo activity of Brazilian
green propolis (GrProp) and red propolis (RdProp) ethanolic extracts against standard strains of
Candida albicans, C. tropicalis, C. krusei, C. glabrata, C. parapsilosis and 10 clinical isolates of
C. albicans.

Methods:

Antifungal activity in vitro was tested using the M-27-A3/CLSI protocol. The in vivo antifungal
activity was evaluated using Tenebrio molitor model and, the effect of extracts on adhesion
of C. albicans in human buccal epithelial cells (BECs) was also studied.

Results:

GrProp and RdProp exhibited antifungal activity against at least one of the Candida
strains tested. The adhesion inhibition of C. albicans in BECs was 45% (GrProp28), 60% (Gr-
Prop50) and 82% (RdProp), in comparison to amphotericin B (82%). All propolis extracts showed
synergistic activity with fluconazole and amphotericin B. GrProp50 (10 mg/kg) showed better protection
of T. molitor, blocking the progression of C. albicans infection, increasing survival and delayed
the larvae death.

Conclusion:

Brazilian GrProp and RdProp extracts inhibit the in vitro C. albicans growth and protect
T. molitor against infection by this yeast. The physiochemical parameters found for the analyzed
samples were in accordance to the standards established by the Brazilian Legislation for
propolis and derivatives. GrProp and RdProp have potential to be used against Candida spp. infections,
mainly in association with fluconazole or amphotericin B.
Simultaneous Photocatalytic Abatement of NO and SO2: Influence of the TiO2 Nature and Mechanistic Insights
Authors: Hernández-Alonso María D. , Suárez Silvia , Fresno Fernando , Coronado Juan M. , Sánchez Benigno
Published: March 2021

Background:

TiO2 is currently being incorporated into several construction materials, such
as cement and asphalt because this photocatalyst can act as a passive system to reduce the concentration
of typical urban pollutants like NOx and SO2 under solar illumination.

Objective:

In order to get further insights on the possible influence of the interaction between common
pollutants, the present work investigates the mechanism of NOx photo-oxidation in the presence of
SO2 traces over TiO2 samples of different textural and morphological characteristics.

Methods:

The performance for the photo-oxidation of NOx and SO2 in a dry air stream over TiO2
samples, both commercial and lab-prepared by hydrothermal and thermal methods, was evaluated by
means of FTIR analyses of the gas phase. These materials were characterized by XRD, N2 adsorption
isotherms, and DR UV-vis spectroscopy. Mechanistic studies were performed by in situ DRIFT under
UV irradiation.

Results:

Photocatalytic tests showed a very efficient removal of the two selected pollutants using most
of the TiO2 samples. In the case of SO2, elimination of these molecules is due not only to photocatalytic
oxidation but also to a significant extent, to adsorption. Although in shorter periods, no byproducts
are generated, following irradiation for several hours, the production of NO2 progressively
increases and reaches 100 % selectivity over some photocatalyst. In situ DRIFTS analyses show the
evolution of the surface composition and reveal the formation of the different types of surface nitrates
with different symmetry. Under these operating conditions, a minor amount of sulfates are also
formed.

Conclusions:

The presence of a low concentration of SO2 does not appear to be detrimental for NO
removal. NO2 formation is delayed on the TiO2 samples with high specific surface area, which also
tend to be more active. The spectroscopic results confirm the involvement of surface hydroxyls in the
formation of adsorbed nitrate species.
PENGEMBANGAN BAHAN AJAR MENULIS RESENSI CERPEN BERBASIS LITERASI KRITIS BAGI SISWA SMA KELAS XI
Authors: Mubasiroh Siti Latifah , Priyatni Endah Tri , Susanto Gatut
Published: March 2021

Literasi kritis dalam pembelajaran menulis resensi diperlukan untuk menumbuhkan kesadaran kritis bagi siswa untuk menemukan praktik sosial yang termuat dalam teks. Fenomena di lapangan menunjukkan bahwa pembelajaran menulis resensi belum mencapai level kritis. Oleh sebab itu, perlu dikembangkan bahan ajar yang dapat membantu siswa untuk menghasilkan resensi kritis dengan panduan yang jelas dan sesuai dengan level berpikir siswa. Penelitian ini bertujuan untuk menghasilkan bahan ajar menulis resensi cerpen berbasis literasi kritis yang memenuhi kelayakan isi, penyajian materi, keterbacaan, kegrafikaan, daya terap dan serap, kebermanfaatan, serta efektivitas bahan ajar dalam pembelajaran bagi siswa SMA kelas XI. Penelitian ini merupakan jenis penelitian pengembangan. Data diperoleh dari hasil validasi produk dan komentar validator serta responden. Hasil validasi dosen ahli, guru, dan respon siswa menunjukkan bahwa produk yang dikembangkan termasuk dalam kategori layak diimplementasikan dalam pembelajaran menulis resensi kritis cerpen. Kata kunci: Bahan ajar, menulis resensi, literasi kritis
Hybrid SPECT/CT Somatostatin Receptor Imaging of Neuroendocrine Tumours
Authors: Maršić Matej , Grbac-Ivanković Svjetlana , Bogović Crnčić Tatjana , Pribanić Ivan , Girotto Neva , Klarica Gembić Tihana
Published: March 2021

Cilj: Cilj rada bio je procijeniti doprinos jednofotonske emisijske tomografije / kompjutorizirane tomografije somatostatinskih receptora (SR SPECT/CT) s 99mTc-EDDA/HYNIC-Tyr3-oktreotidom (99mTc-Tektrotyd) u dijagnostici i procjeni proširenosti bolesti kod pacijenata oboljelih od neuroendokrinih tumora (NET-ova). Ispitanici i metode: Retrospektivno je analizirano 120 SR SPECT/CT snimanja pacijenata s patohistološki dokazanim NET-om s obzirom na vizualizaciju primarnih lezija i metastaza. U 45 pacijenata učinjena je i pozitronska emisijska tomografija 18F-fluorodeoksiglukozom (18F-FDG PET/CT) te su nalazi uspoređeni s nalazima SR SPECT/CT-a i vrijednostima kromogranina A. Rezultati: Od 120 pacijenata 47 (39 %) je na SR SPECT/CT upućeno nakon odstranjenja primarne lezije. Od preostala 73 pacijenta (61 %), u 56 (77 %) primarni je tumor bio vidljiv SR SPECT/CT-om, a u 9 (12 %) poznata lezija nije akumulirala radiofarmak. U 8 (11 %) pacijenata s NET-om nepoznatog primarnog sijela nalaz je bio negativan. Od 68 (57 %) pacijenta s dokazanim metastazama, u njih 57 (84 %) bile su vidljive SR SPECT/CT-om, a u 11 (16 %) nisu akumulirale radiofarmak. Od 45 (38 %) pacijenata kojima je učinjen i 18F-FDG PET/CT, u 27 (60 %) detekcija primarnih lezija i metastaza bila je sukladna nalazu SR SPECT/CT-a. Osjetljivost SR SPECT/CT-a bila je 77 % za primarne lezije i 84 % za metastaze, a 18F-FDG PET/CT-a 75 % za primarne lezije i 76 % za metastaze. Vrijednosti kromogranina A nisu pokazale statistički signifikantnu korelaciju s nalazima slikovne dijagnostike. Zaključci: SR SPECT/CT ima visoku osjetljivost za detekciju NET-ova. Osim toga, potvrđena je komplementarnost s 18F-FDG PET/CT-om te kod pacijenata s negativnim nalazom SR SPECT/CT-a treba učiniti 18F-FDG PET/CT i obrnuto.
Different expression of lumican glycoforms in non-metastatic and metastatic laryngeal squamous cell carcinoma
Authors: Car Iris , Visentin Sarah , Đanić Davorin , Klobučar Marko
Published: March 2021

Objective: Association of altered growth factor receptors-mediated intracellular pathways and biological processes associated with extracellular matrix composition and structure in laryngeal squamous cell carcinoma (LSCC) were described previously. In particular, the expression and glycosylation of important extracellular matrix molecules (ECM) such as small leucine rich proteoglycan lumican, may be generally associated with disrupted extracellular matrix integrity and inflammation processes which have a role in tumour invasiveness. In this study, the relative expression of different lumican glycoforms were evaluated in primary tumour and tumour-unaffected tissue samples of ten patients with metastatic and ten non-metastatic LSCC by Western blot and 2D immunoblot analysis. Materials and methods: Tissue samples from the primary tumours and paired adjacent non-tumour tissues were surgically resected from ten untreated LSCC patients with non-metastatic disease and ten LSCC patients with lymph nodes metastases. The relative expression of different lumican glycoforms in primary tumours and paired adjacent non-tumour tissues were evaluated by Western blot and 2D immunoblot analysis. Results: Results of Western blot analysis have revealed elevated expression of the moderately glycosylated lumican form in metastatic (p<0,05) and non-metastatic primary tumour tissues in comparison with tumour unaffected tissues. In addition, moderately glycosylated form of lumican with negatively charged oligosaccharide residues in the N-glycan molecule part was exclusively determined in metastatic primary tumour tissues by 2D immunoblot analysis. Conclusion: We demonstrated elevated expression of the moderately glycosylated lumican form with negatively charged oligosaccharide residues in the N-glycan portion exclusively in primary laryngeal squamous cell carcinoma from patients with metastatic disease.
Point-of-Care Quantification of Serum Alpha-Fetoprotein for Screening Birth Defects in Resource-Limited Settings: Proof-of-Concept Study (Preprint)
Authors: Srinivasan Balaji , Finkelstein Julia L , Erickson David , Mehta Saurabh
Published: March 2021

BACKGROUND

Maternal serum alpha-fetoprotein (MSAFP) concentration typically increases during pregnancy and is routinely measured during the second trimester as a part of screening for fetal neural tube defects and Down syndrome. However, most pregnancy screening tests are not available in the settings they are needed the most. A mobile device–enabled technology based on MSAFP for screening birth defects could enable the rapid screening and triage of high-risk pregnancies, especially where maternal serum screening and fetal ultrasound scan facilities are not easily accessible. Shifting the approach from clinic- and laboratory-dependent care to a mobile platform based on our point-of-care approach will enable translation to resource-limited settings and the global health care market.

OBJECTIVE

The objective of this study is to develop and perform proof-of-concept testing of a lateral flow immunoassay on a mobile platform for rapid, point-of-care quantification of serum alpha-fetoprotein (AFP) levels, from a drop of human serum, within a few minutes.

METHODS

The development of the immunoassay involved the selection of commercially available antibodies and optimization of their concentrations by an iterative method to achieve the required detection limits. We compared the performance of our method with that of commercially obtained human serum samples, with known AFP concentrations quantified by the Abbott ARCHITECT chemiluminescent magnetic microparticle immunoassay (CMIA).

RESULTS

We tested commercially obtained serum samples (N=20) with concentrations ranging from 2.2 to 446 ng/mL to compare the results of our point-of-care assay with results from the Abbott ARCHITECT CMIA. A correlation of 0.98 (P<.001) was observed on preliminary testing and comparison with the CMIA. The detection range of our point-of-care assay covers the range of maternal serum AFP levels observed during pregnancy.

CONCLUSIONS

The preliminary test results from the AFP test on the mobile platform performed in this study represent a proof of concept that will pave the way for our future work focused on developing a mobile device–enabled quad-screen point-of-care testing with the potential to enable the screening of high-risk pregnancies in various settings. The AFP test on the mobile platform can be applied to enable screening for high-risk pregnancies, within a few minutes, at the point of care even in remote areas where maternal serum tests and fetal ultrasound scans are not easily accessible; assessment of whether clinical follow-up and diagnostic testing may be needed after a positive initial screening evaluation; and development of surveillance tools for birth defects.