bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent advances in drug substance development – prodrug strategies for enhancing the bioavailability and potency of antiviral nucleosides
Authors: Kutner Andrzej
Published: September 2023

Bioavailability is a prerequisite for drug activity.  In vivo bioavailability (intestinal permeability), linked to drug substance solubility and drug product dissolution, became the basis of Gordon L. Amidon’s Biopharmaceutical Classification System.  One method of improving the drug substance’s bioavailability is to modify its structure chemically, leading to increased lipophilicity and the ability to penetrate the phospholipid bilayer of the cell membrane.  These modifications, known as prodrug strategies, involve derivatizing the drug substance by introducing substituents that reduce the hydrophilicity of the molecule.  The present mini-review outlines the examples of Christopher McGuigan’s prodrug strategies used to obtain antiviral nucleosides with enhanced bioavailability and activity.  These strategies primarily involve forming and optimizing the structure of esters and amino acid esters, phosphoramidates, octadecyl phosphates, and bis-pivaloxymethyl phosphates.  The review discusses the optimization of the phosphoramidate prodrug moiety of the SARS-CoV-2 antiviral nucleoside remdesivir in detail.  It presents the resulting improvement in bioavailability and antiviral activity.  Moreover, it focuses on the modern prodrug strategy as one of the major recent advances in drug substance development.  This strategy effectively optimized physicochemical properties and improved the functional activity of the existing drug substances and drug substance candidates for the first time.
Energy efficient smart manufacturing of pharmaceutical solid oral dosage forms
Authors: Dan Ashley , Ramachandran Rohit
Published: September 2023

Background: The global pharmaceuticals market is a trillion-dollar industry which grows more than 5% annually. However, in comparison to other manufacturing industries (e.g., oil refining, automotive), the pharmaceutical sector lags in manufacturing innovation and automation. In the production of pharmaceutical solid dosage forms, the use of energy utilization as a performance measure of production efficiency has neither been implemented extensively, nor been optimized to maximize efficiency. This study will focus on the development and implementation of a smart manufacturing platform to optimize energy productivity whilst maintaining tablet quality via the consideration of different manufacturing scenarios.

Methods: This study will consider three main unit operations (wet granulation, drying and milling) which are relatively more energy intensive in pharmaceutical downstream processing, used to produce solid dosage forms, such as tablets. Four case-studies will be considered, which are 1: baseline batch, 2: baseline continuous, 3: optimized batch and 4: optimized continuous. Smart manufacturing is implemented to present optimized cases 3: and 4: Improvements in the energy and performance metrics are quantified and compared to the baseline cases.   

Results and conclusions: The smart manufacturing platform used in this study, integrates advanced process model development, optimization, technoeconomic analysis and data integration. The utilization of this framework contributed to a ~70% and ~80% improvement in energy utilization in the optimized batch and continuous cases, respectively, when compared to the baseline batch case. In the optimized cases, tablet quality was maintained within targeted specifications and was comparable to the baseline batch case. This smart manufacturing framework can be generalized for drug product manufacturing and other particulate-based industries such as food, agriculture, and fine chemicals.
Recent Machine Learning and Deep Learning Theories and Methods for COVID-19 Diagnosis
Authors: Tang Wenhao
Published: September 2023

A long time has passed since COVID-19 was discovered and widely disseminated. Both machine learning and deep learning have moved towards the research of diagnosing COVID-19. Compared to deep learning, traditional machine learning-based methods can also achieve good diagnostic results if they are improved based on innovative points. And deep learning remains a more popular research object. Based on the deep neural network in the field of deep learning, the convolutional neural network, recurrent neural network, long and short-term memory network, and Transformer model have been extended. These models improve the performance and processing power of neural networks by introducing new structures and algorithms. This paper will introduce the basic concepts of machine learning and deep learning, as well as the details of using the relevant methods of both to help diagnose COVID-19.
Salt Intake- Related Knowledge, Attitudes, and Practices among Jordanian Adults
Authors: Abdel Majeed Zeina , Barham Rawhieh , Al-Jawaldeh Ayoub , Ahmad Nada , Khader Yousef
Published: September 2023

Keywords: Knowledge; Attitudes; Practices; Salt intake.
Seismic Performance of a 1:4 Scale Two-Story Rammed-Earth Model Reinforced with Steel Strips Tested on a Bi-Axial Shaking Table
Authors: Barrera Ospina Natalia , Ruiz Daniel M. , Reyes Juan C. , Alvarado Yezid A. , Carrasco-Beltrán Daniela
Published: September 2023

During the 16th and 17th centuries, Latin American cities adopted earthen construction techniques from European colonizers. As a result, rammed earth (RE) buildings now occupy an important place in Latin America's cultural heritage. However, earthquakes around the world have shown that unreinforced earthen constructions are highly vulnerable. For several years, researchers in northern South America have been proposing a technique that consists of installing confining steel plates (or wooden elements) on both sides of the RE walls forming a grid. This system has shown excellent performance in controlling seismic damage and increasing strength and ductility capacity. Although researchers have tested full-scale one- and two-story earthen walls under pseudo-static loading in the laboratory, and one- and two-story earthen walls at 1:1 and 1:2 scale on uniaxial and biaxial shaking tables, the behavior of a complete reinforced module (one- or two-story) on a shaking table has never been assessed. The present study presents the results of shaking table tests performed on two-story RE modules at 1:4 scale. The experimental data indicate that the retrofit system with confining steel strips was effective in reducing the seismic damage of earthen constructions. In addition, the comparison of the results of the 1:4 scale tests with the 1:2 and 1:1 scale tests previously conducted by the researchers, shows that the acceleration levels of the equivalent prototypes are in the same order of magnitude for the three scales.
Characteristics and Research Significance of Micro-Nanoparticles in Geothermal Fluids in the Central Area of Shandong Province
Authors: Zuo Lei , Zhang Peng , Wang Yaqin , Liu Rui , Ma Guangxi
Published: September 2023

Micro-nanoparticles' characteristics in geothermal fluids can be applied to detect of deep hidden geothermal resources. Observations using a nanoparticle tracking analyzer (NTA) indicated that the karst geothermal water collected in the central area of Shandong Province (Jinan and Zibo) contains many natural micro-nanoparticles with sizes primarily ranging between 100 nm and 5 μm. The micro-nanoparticles’ type, shape, crystal form, and chemical composition in the samples were analyzed using transmission electron microscopy (TEM). TEM images and energy dispersive spectroscopy showed that the micro-nanoparticles in geothermal water samples were mostly amorphous, irregular, or nearly spherical, with rough edges. The micro-nanoparticles were mainly carbonates, sulfates, and chlorine-containing Fe, Ca, Na, and Mg. The characteristics of the particles can reveal the properties of the deep, hot reservoirs and aquifers from where they originate. Therefore, we believe that natural micro-nanoparticles can be essential to detecting and studying deep, hidden geothermal resources, which is a novel approach to exploring deep, hidden geothermal resources.
Development of Soil Erosion Susceptibility Model Using UAV Photogrammetry in a Timber Harvesting Area, South Korea
Authors: Kim Jeongjae , Kim Ikhyun , Choi Byoungkoo
Published: September 2023

Unmanned aerial vehicle (UAV) systems are widely used in many forest-related fields owing to their cost-intensive and precise surveying technology. This study classified erosion susceptibility (ES) in a timber harvesting area using machine learning (ML) and statistical approaches. In dataset generation for the training and testing process, the digital surface model (DSM) of difference (DoD) for July–June was utilized as a dependent variable, and six terrain maps of the DSM for June were used as independent variables. The ES threshold was set at 5 cm for the binary classification of ES pixels while processing using ML (e.g., random forest and extra gradient boost [XGB]) and statistical (e.g., logistic regression) algorithms for model development. The overall accuracy (OA), receiver operating characteristics, and area under the curve (AUC) were calculated for model accuracy and validation. Although the AUC of all models did not appear acceptable (AUC > 0.7), the XGB model showed the best performance regarding time duration, OA, and AUC by 2 h, 64%, and 0.63, respectively. Despite the low AUC and accuracy of the XGB model, the wheel tracks and edges of the operation road were determined to be susceptible areas in the ES map of the XGB.
HIV-1 Controllers Exhibit an Enhanced Antiretroviral Innate State Characterized by Overexpression of p21 and MCPIP1 and Silencing of Endogenous Retroviruses
Authors: Azevedo Suwellen Sardinha Dias de , Ribeiro Alves Marcelo , Côrtes Fernanda Heloise , Delatorre Edson , Hoagland Brenda , Villela Larissa M. , Grinsztejn Beatriz , Veloso Valdiléa Gonçalves , Morgado Mariza Gonçalves , Souza Thiago Moreno , Bello Gonzalo
Published: September 2023

HIV-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWH) who naturally control HIV-1 replication. The ability of HICs to control the expression of endogenous retroviruses has not been previously addressed. In this study, we measured ERVK-6 RNA expression in PBMCs of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 restriction factors. Our study reveals that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with both ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1. In our previous study, these two cellular restriction factors were upregulated in HICs compared with control groups. Interestingly, p21 and MCPIP1 limit the activation of macrophages and T cells by downregulating the activity of NF-kB, a transcription factor that stimulates the LTR-driven transcription of HIV-1 and HERV-K proviruses. These findings support that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both HIV-1 and endogenous retroviruses.
Exploring the Impact of Turning of AISI 4340 Steel on Tool Wear, Surface Roughness, Sound Intensity, and Power Consumption under Dry, MQL, and Nano-MQL Conditions
Authors: Fedai Yusuf
Published: September 2023

Optimizing input parameters not only improves production efficiency and processing quality but also plays a crucial role in the development of green manufacturing engineering practices. The aim of the present study is to conduct a comparative evaluation at cutting performance and machinability process during the turning of AISI 4340 steel under different cooling conditions. The study analyses cutting operations during turning using dry, minimum quantity lubrication (MQL), and nano-MQL. As control parameters in the experiments, three different cooling types, cutting speed (100, 150, 200 m/min), and feed rate (0.1, 0.15, 0.20 mm/rev) levels were applied. The experiment results present that the optimal output values are found as Vb=0.15 mm, Ra=0.81µm, 88.1 dB for sound intensity, and I=4.18 A for current. Moreover, variance analysis (ANOVA) was performed to determine the effects of input parameters on response values. Under dry, MQL, and nano-MQL processing conditions, parameters affecting tool wear, surface roughness, current by the motor shaft, and sound level were examined in detail, along with the chip morphology. The responses obtained were optimized according to the Taguchi S/N method. As a result of optimization, it was concluded that the optimum values for cutting conditions (A3B1C1) were nano-MQL cooling and V=100 m/min, f=0.1 mm/rev cutting. Last but not least, it was observed that there was a 13% improvement in tool wear, 7% in current, 9% in surface roughness, and 8% in sound intensity compared to the standard conditions. In conclusion, it was determined that nano-MQL and the lowest level of cutting and feed rate values provided the optimum results.
Heuristics and Rescheduling in Prioritised Multi-Robot Path Planning: A Literature Review
Authors: Heselden James R , Das Gautham P
Published: September 2023

The benefits of multi-robot systems are substantial, bringing gains in efficiency, quality, and cost, and are useful in a wide range of environments from warehouse automation, to agriculture, and even extend in part to entertainment. In multi-robot system research, the main focus is on ensuring efficient coordination in the operation of the robots, both in task allocation and navigation. However, much of this research seldom strays from theoretical bounds; there are many reasons for this, with the most prominent and impactful being resource limitations. This is especially true for research in areas such as multi-robot path planning (MRPP) and navigation coordination. This is a large issue in practice as many approaches are not designed with meaningful real-world implications in mind and are not scalable to large multi-robot systems. This survey aims to look into the coordination and path-planning issues and challenges faced when working with multi-robot systems, especially those using a prioritised planning approach and identify key areas which are not well-explored and the scope of applying existing MRPP approaches to real-world settings.
Adipose Stromal Cell Spheroids for Cartilage Repair: A Promising Tool for Unveiling the Critical Maturation Point
Authors: Sargenti Azzurra , Pasqua Simone , Leu Marco , Dionisi Laura , Filardo Giuseppe , Grigolo Brunella , Gazzola Daniele , Santi Spartaco , Cavallo Carola
Published: September 2023

Articular cartilage lacks intrinsic regenerative capabilities, and the current treatments fail to regenerate damaged tissue and lead only to temporary pain relief. These limitations have prompted the development of tissue engineering approaches, including 3D culture systems. Thanks to their regenerative properties and capacity to recapitulate embryonic processes, spheroids obtained from mesenchymal stromal cells are increasingly studied as building blocks to obtain functional tissues. The aim of this study was to investigate the capacity of adipose stromal cells to assemble in spheroids and differentiate toward chondrogenic lineage from the perspective of cartilage repair. Spheroids were generated by two different methods (3D chips vs Ultra-Low Attachment plates), differentiated toward chondrogenic lineage, and their properties were investigated by: molecular biology analyses, biophysical measurement of mass density, weight, and size of spheroids, and confocal imaging. Overall, spheroids showed the ability to differentiate by expressing specific cartilaginous markers that correlate with their mass density, defining a critical point at which they start to mature. Considering the spheroid generation method, this pilot study suggested that spheroids obtained with chips are a promising tool for the generation of cartilage organoids that could be used for preclinical/clinical approaches, including the realization of personalized therapy.
Tocotrienol-Rich Fraction as a Protective Agent against Blue Light Induced Oxidative Stress and Melanogenesis in B16-F1 Melanocytes
Authors: Neo Juvenia Rui En , Teo Cheryl Wei Ling , Ung Yee Wei , Yap Wei Ney
Published: September 2023

Our skin is constantly exposed to blue light (BL), which is abundant in sunlight and emitted by digital devices. Prolonged exposure to BL can lead to oxidative stress-induced damages and skin hyperpigmentation. In this study, we investigated the protective effects of tocotrienol-rich fraction (TRF) on BL-induced oxidative stress and hyperpigmentation in B16-F1 melanocytes. Alpha-tocopherol (αTP) was used as a comparator. Our results showed that TRF effectively suppressed the formation of reactive oxygen species, and preserved the mitochondrial membrane potential. Additionally, TRF exhibited anti-apoptotic properties by reducing the activation of p38 mitogen-activated protein kinase molecule and downregulating the expression of cleaved caspase-3. Moreover, TRF modulated tyrosinase activity, resulting in a lowered rate of melanogenesis and reduced melanin production. In contrast, αTP did not exhibit the significant protective effects against skin damages and pigmentation in BL-induced B16-F1 cells. Therefore, this study indicates that TRF may offer superior protective effects over αTP against the effects of BL on melanocytes. These findings demonstrate the potential of TRF as a protective natural active against BL-induced skin damages and hyperpigmentation via its antioxidative and anti-melanogenic properties.
Prediction of the Flowering and Ripening Time of Strawberry (Fragaria × ananassa) Cultivars in Estonia by Using the K-Means Clustering Method
Authors: Klakotskaya Natallia , Laurson Peeter , Libek Asta Virve , Kikas Ave
Published: September 2023

Finding the ideal statistical method for grouping phenological data is always an important step for breeders to draw correct conclusions from it possibly. In this paper, K-cluster analysis is presented as a perfect tool for grouping phenological data. The present research was performed based on the phenological data of 61 strawberries (Fragaria × ananassa) cultivars of different geo-graphical origins grown in Estonian conditions. Groups of strawberry cultivars were deter-mined according to flowering and ripening time: early, middle and late, based on the sum of ef-fective temperatures above +5°C. The result of the K-cluster analysis carried out in this way makes it possible to precisely plan the ripening time of berries of different strawberry cultivars. Using such analysis data, it is possible to combine with different early, mid or late strawberry cultivars to extend the picking period. Also, this technique can be used to study the effect of cli-matic changes occurring over the years on the phenology of strawberry cultivars grown in the region.
Effect of Brewing Methods on Acrylamide Content and Antioxidant Activity Studying Eight Different Filter Coffee Preparation
Authors: Santanatoglia Agnese , Angeloni Simone , Bartolucci Davide , Fioretti Lauro , Sagratini Gianni , Vittori Sauro , Caprioli Giovanni
Published: September 2023

The aim of this study was to investigate the parameters affecting the extraction of positive molecules such as chlorogenic acids and antioxidants, as well as potentially carcinogenic substances such as acrylamide, in different coffee brewing methods. Three coffee varieties, each assigned to different roasting degree, were used to prepare coffee brews following eight diverse preparation methods. Acrylamide was quantified by HPLC-MS/MS instrument while chlorogenic acids and caffeine by HPLC-DAD system. Three spectrophotometric analyses were also performed (DPPH, TFC and TPC) to evaluate antioxidant activity as well. The results showed that the main brewing parameters, that have the greatest influence on the final content of these compounds were the volume of water used, more specifically the brewing ratio (coffee to water ratio), the extraction time and the particle size of the coffee powder.
Antimicrobial Coatings for Medical Applications—A Comprehensive Review on Active Nanoparticles Characterization
Authors: Rezić Iva , Meštrović Ernest
Published: September 2023

This comprehensive review addresses topics relevant to understanding of characterization of antimicrobial coatings used in surface modifications of yarns and materials intended for usage in medical and dental applications. These coatings are created using various physical and chemical methods to achieve efficient, homogeneous, and uniform layers on different surfaces and materials, with the goal of imparting antimicrobial and/or antiviral properties. Antimicrobial coatings must contain active compounds effective against various microorganisms, including those resistant to antibiotics. Examples of such compounds include metallic nanoparticles (such as silver, copper, and gold) and nanoparticles of metal oxides (such as zinc, titanium, and aluminum). Once materials intended for medical applications are coated, they undergo extensive testing and characterization, for which the methodologies will be presented in this chapter. Despite their wide efficiency in medical applications, concerns are raised regarding the potential toxicity of nanoparticles to living organisms. Therefore, the development of novel legal frameworks is anticipated, which will depend on proper characterization and testing procedures. This paper provides a summary of the current state-of-the-art methodologies for characterizing nanoparticles in antimicrobial coatings on materials with different roughness and structures and specifies the problems related with accumulation of antimicrobial nanoparticles in a human body.
Exploring the Effects of Rearing Densities on Epigenetic Modifications in the Zebrafish Gonads
Authors: Valdivieso Alejandro , Caballero-Huertas Marta , Moraleda-Prados Javier , Piferrer Francesc , Ribas Laia
Published: September 2023

Rearing density directly impacts fish welfare, which, in turn, affects productivity in aquaculture. Previous studies have indicated that high-density rearing during sexual development in fish can induce stress, resulting in a tendency towards male-biased sex ratios in the populations. In recent years, research has defined the relevance of the interactions between the environment and epigenetics playing a key role in the final phenotype. However, the underlying epigenetic mechanisms of individuals exposed to confinement remain elucidated. By using zebrafish (Danio rerio) the DNA methylation promotor region and the gene expression patterns of six genes: dnmt1, cyp19a1a, dmrt1, cyp11c1, hsd17b1, and hsd11b2 involved in the DNA maintenance methylation, reproduction, and stress were assessed. Zebrafish larvae were subjected to two high-density conditions (9 and 66 fish/L) during two periods of overlapping sex differentiation of this species (7 to 18 and 18 to 45 days post-fertilization, dpf). Results showed a significant masculinization in the populations of fish subjected to high densities from 18 to 45 dpf. In adulthood the dnmt1 gene was differentially hypomethylated in ovaries and its expression was significantly downregulated in the testes of fish exposed to high-density. Further, the cyp19a1a gene showed downregulation of gene expression in the ovaries of fish subjected to elevated density, as previously observed in other studies. We proposed dnmt1 as a potential testicular epimarker, and the expression of ovarian cyp19a1a as a potential biomarker for predicting stress originated from high densities during the early stages of development. These findings highlight the importance of rearing densities by long-lasting effects in adulthood conveying cautions for stocking protocols in fish hatcheries.
Identifying Spatial Pattern of White Oak (Quercus alba) Mortality and its Relationship with Soil Properties across the Eastern United States
Authors: Khadka Saaruj , He Hong S. , Bardhan Sougata , Khalyani Azad Henareh
Published: September 2023

White oak mortality is a significant concern in forest ecosystems due to its impact on biodiversity and ecosystem functions. Understanding the factors influencing white oak mortality, particularly the soil properties, is crucial for effective forest management and conservation efforts. In this study, we aimed to investigate the spatial pattern of white oak mortality and examine the influence of soil properties on mortality rates. Multicycle Forest Inventory and Analysis data were compiled to capture white oak plots across the eastern US. White oak mortality data were collected across plot systems that utilized Diameter at Breast Height between two periods. Soil variables were analyzed to assess soil properties. Spatial analysis techniques, including geostatistics and regression modeling, were used to analyze the relationship between white oak mortality and soil characteristics. Results found clustered spatial patterns of white oak mortality across a broad scale depicting the significant effects of coarser soil textures, nutrient-deficient sites, and extreme soil moisture levels. Our findings demonstrated the importance of soil properties in shaping the spatial pattern of the white oak mortality rate. This idea can inform forest management practices for the conservation of white oak populations. Future research is needed for comprehensive soil assessment including biotic and abiotic factors for forest management strategies at a broader scale aimed at mitigating white oak mortality.
The Prognostic Role of the Volumetric MRI Evaluation in the Surgical Treatment of Glioblastoma
Authors: Aiudi Denis , Iacoangeli Alessio , Dobran Mauro , Polonara Gabriele , Chiapponi Mario , Mattioli Andrea , Gladi Maurizio , Iacoangeli Maurizio
Published: September 2023

Background: Glioblastoma is the most common primary brain neoplasm in adults, with still a poor prognosis despite a constant effort to improve patients’ survival. Some neuroradiological volumetric parameters seem to play a predictive role on Overall Survival (OS) and Progression Free Survival (PFS). The aim of this study is to analyze the impact that the volumetric areas of contrast-enhancing tumor and perineoplastic edema have on survival of patients treated for glioblastoma; Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered as the end points of the study. For each patient a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology board. A manual and semi-automatic measurement were adopted to perform the radiological evaluation: contrast Enhancement Preoperative (CE-PTV) and Postoperative Tumor Volume (CE-RTV), Edema/Infiltration Preoperative (T2/FLAIR-PV) and Postoperative Volume (T2/FLAIR-RV); necrosis volume inside the tumor (NV); total tumor volume, including necrosis (TV); Results: The median OS value was 9 months and the median PFS value was 4 m; the mean values were respectively 12,3 m and 6,9 m. Multivariate analysis showed that the OS related factors were: adjuvant chemo-radiotherapy (p < 0,0001), CE-PTV < 15 cm³ (p=0,03), surgical resection > 95% (p=0,004) and the presence of a “pseudo-capsulated” radiological morphology (p=0,04); Conclusions: maximal safe resection is one of the most relevant predictive factors for patients’ survival. The semi-automatic pre-operative MRI evaluation could play a key role in prognostically categorizing these tumors.
A Deep Reinforcement Learning Approach to DropletRouting for Erroneous Digital Microfluidic Biochips
Authors: Kawakami Tomohisa , Shiro Chiharu , Nishikawa Hiroki , Kong Xiangbo , Tomiyama Hiroyuki , Yamashita Shigeru
Published: September 2023

Digital Microfluidic Biochips (DMFBs), used in various kinds of fields like DNA analysis, clinical diagnosis, and PCR testing, have made biochemical experiments more compact, efficient, and user-friendly than previous ways. However, their reliability is often compromised by their inability to adapt to all kinds of errors. All errors in biochips can be categorized into two types: known errors and unknown errors. Known errors are detectable before the start of the routing process through sensors or cameras. Unknown errors, in contrast, become apparent only during the routing process and remain undetected by sensors or cameras, which is the biggest issue to unexpectedly stop the routing process and diminishes the reliability of biochips. This paper introduces a deep reinforcement learning-based routing algorithm designed to manage not only known errors but also unknown errors. Our experiments demonstrate that our algorithm outperforms previous ones in terms of the success rate of the routing in the scenario including both known errors and unknown errors. Additionally, our algorithm contributes to detecting unknown errors during the routing process and identifying the most efficient routing path with high probability.
A Combination of Ruthenium Complexes and Photosensitizers to Treat Colorectal Cancer
Authors: Massoud Jacquie , Pinon Aline , Gallardo-Villagrán Manuel , Paulus Lucie , Ouk Catherine , Carrion Claire , Antoun Sayed , Diab-Assaf Mona , Therrien Bruno , Liagre Bertrand
Published: September 2023

Treatment regimens are regularly evolving, together with novel therapies and drugs. Such evolution is necessary to circumvent resistance mechanisms and to give patients the best possible health care. When dealing with cancer, most regimens involve multiple treatments (surgery, radiation therapy, chemotherapy, immunotherapy, etc.). The purpose of this study was to associate in a single compound metal-based drugs and photosensitizers to combine chemotherapy and photodynamic therapy. Two arene-ruthenium tetrapyridylporphyrin compounds (2H-TPyP-arene-Ru and Zn-TPyP-arene-Ru) have been synthesized and evaluated on two colorectal cancer cell lines (HCT116 and HT-29). The cytotoxicity and phototoxicity have been evaluated. In addition, the anticancer mechanism and the cell death process mediated by the two compounds were studied. The results showed that the two arene-ruthenium photosensitizer-containing complexes have a strong phototoxic effect after photoactivation. The 2H-TPyP-arene-Ru induced outstanding cytotoxicity when compared to the Zn-TPyP-arene-Ru analogue. Moreover, under light, these two arene-ruthenium photosensitizers induce an apoptotic process in human colorectal cancer cell lines.
Design, Synthesis and Bioactivity Evaluation of Heterocycle-Containing Mono- and Bisphosphonic Acid Compounds
Authors: Wu Xin , Yang Zili , Bu Mengwei , Duan Jiang , Zhang Aidong
Published: September 2023

Fosmidomycin (FOS) is a naturally occurring compound active against the enzyme DXR in the MEP pathway, and using it as a template for lead structure design is an effective strategy in developing new active compounds. In this work, by replacing the hydroxamate unit of FOS with pyrazole, isoxazole and the related heterocycles that also have the metal ion binding affinity, while retaining the monophosphonic acid in FOS or replacing it with a bisphosphonic acid group, heterocycle-containing mono- and bisphosphonic acid compounds as FOS analogs were designed. The key steps involved in the facile synthesis of these FOS analogs include the Michael addition of diethyl vinylphosphonate or tetraethyl vinylidenebisphosphonate to β-dicarbonyl compounds and the subsequent cyclic condensation with hydrazine or hydroxylamine. Two additional isoxazolinone-bearing FOS analogs were synthesized by the Michaelis-Becker reaction with diethyl phosphite as a key step. The bioactivity evaluation on model plants demonstrated that several compounds have better herbicidal activities compared to FOS, with the most active compound showing a 3.7-fold inhibitory activity on Arabidopsis thaliana, while on the root and stalk of Brassica napus L. and Echinochloa crus-galli in pre-emergence inhibitory activity test, the activities of this compound were found to be 3.2- and 14.3-, 5.4- and 9.4-fold, respectively, and in post-emergency activity test on Amaranthus retroflexus and Echinochloa crus-galli, 2.2- and 2.0-fold inhibition activities were displayed. Despite the significant herbicidal activity, this compound exhibited a DXR inhibitory activity lower than that of FOS but comparable to that of other non-hydroxamate DXR inhibitors, and the dimethylallyl pyrophosphate rescue assay gave no statistical significance, suggesting a different target might be involved in the inhibiting process. This work demonstrates that using bioisosteric replacement can be considered a valuable strategy for discovering new FOS analogs that may have high herbicidal activity.
Nutritional Laboratory Studies Prior to Total Knee Arthroplasty
Authors: Rakutt Maxwell J. , Eason Travis B. , Boyle K. Keely , Buller Leonard T. , Krueger Chad A. , Jacobs Cale A. , Duncan Stephen T. , Landy David C.
Published: September 2023

Background:

Recent emphasis has been placed on nutritional status assessment prior to total knee arthroplasty (TKA), including multiple American Academy of Orthopaedic Surgeons publications recommending specific laboratory studies; however, the frequency with which surgeons obtain these laboratory studies remains unclear. We sought to assess the incidence of ordering nutritional laboratory studies in the 90 days prior to TKA, utilizing data from a large administrative claims database.

Methods:

With use of the PearlDiver database, we identified 557,670 patients undergoing primary TKA from 2011 to 2020 with a metabolic panel or blood cell count claim within 90 days prior to TKA. We then determined the incidence of prealbumin, transferrin, vitamin D, and zinc laboratory tests claimed 90 days prior to TKA. Associations between claims and the year of surgery, patient demographics, and clinical characteristics were assessed by comparing proportions and chi-square testing.

Results:

Nutritional laboratory studies were infrequently claimed within 90 days prior to TKA, with studies for prealbumin being performed in 2.2% of patients; transferrin, 1.9%; vitamin D, 10.2%; and zinc, 0.2%. From 2011 to 2020, there was a moderate but steady increase in the proportion of patients with claims for prealbumin (change from 0.8% in 2011 to 3.4% in 2020; p < 0.001), transferrin (0.8% to 2.7%; p < 0.001), and vitamin D (7.6% to 9.4%; p < 0.001) laboratory tests but there was less of a change for zinc (0.1% to 0.2%; p < 0.001). There were weak-to-absent associations of age, gender, obesity, diabetes, and anemia with laboratory claims.

Conclusions:

Despite multiple publications and recommendations, nutritional laboratory studies are infrequently ordered prior to TKA. Although there has been a slight increase in the use of nutritional laboratory studies over the past decade, patient factors such as gender and obesity were not associated with this increase. Understanding current practice patterns may help target future areas for improvement.

Level of Evidence:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Investigation of university students’ critical thinking in debate: Justification for the “AREL” argumentation process
Authors: Dwiyoga Daniswara Landry , Bambang Yudi Cahyono
Published: September 2023

This qualitative research investigated students’ critical thinking in a debate group at a university level. It involved six students who performed a debate that used the Asian Parliamentary System. Data on students’ critical thinking were collected by using field notes and video recording. Content analysis was employed to analyze the data focusing on the use of argument traits of the AREL model. The traits consist of Assertian, Reasoning, Evidence, and Link Back (AREL). Moreover, a self-evaluation questionnaire was distributed to triangulate the students’ critical thinking levels. It was found that students’ critical thinking level was mostly below average. Four out of six students did not meet the score which is the threshold level of a high-level debater. Most of their argument traits consist of Assertion (A), Reasoning (R), and Evidence (E), leaving Link back (L) traits untouched. Interestingly, this research revealed a new finding. Many of the students used a multi-layer structure of argumentation. In practice, they occasionally used Assertions with more than one Reasoning and more than one Evidence.
Keywords: AREL, argumentation process, argument trait, critical thinking, speaking, debate
Russia's War in Ukraine: Two Decisive Factors
Authors: Merkx Gilbert W.
Published: September 2023

The various stages of the Russian invasion of Ukraine, and of Ukrainian responses, are analyzed in terms of two decisive factors: 1) force structures and 2) command and control. Both these factors are in turn conditioned by characteristics of the governing political regime and the evolution of that regime.
Experimental Measurements and Molecular Simulation of Carbon Dioxide Adsorption on Carbon Surface
Authors: Gomaa Ibrahim , Guerrero Javier , Heidari Zoya , Espinoza D. Nicolas
Published: September 2023

Geological sequestration of carbon dioxide (CO2) in depleted gas reservoirs represents a cost-effective solution to mitigate global carbon emissions. The surface chemistry of the reservoir rock, pressure, temperature, and moisture content are critical factors that determine the CO2 adsorption capacity and storage mechanisms. Shale-gas reservoirs are good candidates for this application. However, the interactions between CO2 and organic content still need further investigation. The objectives of this paper are to (i) experimentally evaluate the adsorption isotherm of CO2 on activated carbon, (ii) quantify the nanoscale interfacial interactions between CO2 and the activated carbon surface using Monte Carlo (MC) and molecular dynamic (MD) simulations, (iii) evaluate the modeling reliability using experimental measurements, and (iv) quantify the influence of temperature and geochemistry on the adsorption behavior of CO2 on the surface of activated carbon. These objectives aim at obtaining a better understanding of the behavior of CO2 injection and storage in the kerogen structure of shale-gas formations, where activated carbon is used as a proxy for thermally mature kerogen.

We performed experimental measurements, grand canonical Monte Carlo (GCMC) simulations, and MD simulations of CO2 adsorption and diffusion on activated carbon. The experimental work involved measurements of the high-pressure adsorption capacity of activated carbon using pure CO2 gas at a temperature of 300 K. The simulation work started with modeling and validating an activated carbon structure by calibrating the GCMC simulations with experimental CO2 adsorption measurements. Then, we extended the simulation work to quantify the adsorption isotherms at a temperature range of 250–500 K and various surface chemistry conditions. Moreover, CO2 self-diffusion coefficients were quantified at gas pressures of 0.5 MPa, 1 MPa, and 2 MPa using MD simulations.

The experimental results showed a typical CO2 excess adsorption trend for the nanoporous structures, with a density of the sorbed gas phase of 504.76 kg/m3. The simulation results were in agreement with experimental adsorption isotherms with a 10.6% average absolute relative difference. The self-diffusion results showed a decrease in gas diffusion with increasing pressure due to the increase in the adsorbed gas amount. Increasing the simulation temperature from 300 K to 400 K led to a decrease in the amount of adsorbed CO2 molecules by about 87% at 2 MPa pressure. Finally, the presence of charged functional groups (e.g., hydroxyl–OH and carboxyl–COOH) led to an increase in the adsorption of CO2 gas to the activated carbon surface. The outcomes of this paper provide new insights about the parameters affecting CO2 adsorption and sequestration in depleted shale-gas reservoirs. This in turn helps in screening the candidate shale-gas reservoirs for carbon capture, sequestration, and storage to maximize the CO2 storage capacity.
Experimental Study of a One-Step Multifunctional Treatment Fluid for Water-Based Mud Filter-Cake Cleanup
Authors: Hull Katherine L. , Mai Nam , Crane Brady , Saini Rajesh K. , Cairns Amy J. , Chang Fakuen F.
Published: September 2023

Filter-cake cleanup following the drilling and completion operation is important for reestablishing communication between the formation and wellbore. A dual-action cleanup system for water-based mud (WBM) was developed to dissolve the calcium carbonate (CaCO3) bridging agent and polymeric materials present in the filter cake. The novel treatment fluid contains a high concentration of nonencapsulated oxidizing salts and delayed acid generating materials and is gelled with a viscoelastic surfactant (VES)-based surfactant. The fluid provides many advantages over traditional fluids as it does not generate any residue on breaking, unlike the traditional polymeric gelling agent. The breakage or reduction in viscosity of this fluid can be accomplished by contact with the produced oil thereby disrupting the micelles. Traditional polymers on the other hand are broken by oxidizers, and if delayed breakage is desired, the breaker needs to be encapsulated. Another benefit of this system is that the VES gelation may enhance uniform filter-cake cleanup in extended reach horizontal sections of the wellbore. The novel fluid system contains a strong oxidizer, namely, sodium bromate (NaBrO3), that activates at temperatures above 160oF causing the breakdown of the polymer contained within the filter cake without affecting the VES surfactant or gelation which helps in mixing the fluid at the surface. Finally, the fluid contains an acid-generating precursor that is neutral at ambient temperature conditions. Once the fluid is heated up in the formation, acid is generated via ammonium oxidation, thereby lowering the viscosity of the gel and dissolving the CaCO3 bridging material. In summary, the fluid that can be prepared on the fly accomplishes multiple functions ranging from controlled gelation to clean break without residue or outside intervention to dissolution and degradation of inorganic and polymeric components.
A New Type Microproppant and Its Property Evaluation for Shale Gas Reservoirs
Authors: Li Jun , He Siyuan , Wu Mingyi
Published: September 2023

Modern hydraulic fracturing technologies relied on maintaining the natural fracture of the shale reservoir open and providing its long-term conductivity by injecting flow with proppant particles of various sizes. However, some natural fractures were too narrow for the conventional macro-sized proppants to enter, which greatly reduced the gas flow area and productivity and implied an increasing demand for micro-sized proppants that could be easily transported in narrow natural fractures. This study introduced innovative microproppants produced from abandoned tailings. Their basic characteristics were experimentally obtained, and the impact of various factors on microproppant placement and transportation in fractures was analyzed using a physical analog fracture model. The performed field and laboratory tests proved that this microproppant combined the merits of low activity, low cost, and easy utilization in the petroleum field. Besides, in the experiments of prefabricated fractures, the permeability of fractures filled with this type of microproppant exceeded that of fractures with no microproppant under temperature variation from 30°C to 90°C. Finally, visual examination of prefabricated fractures showed that the transport capacity of this new type of microproppant significantly outperformed that of the microproppants made of quartz sand and ceramic with the same particle size.
Prefrontal deficits in procrastinators: impaired impulse control or emotion-regulation difficulties
Authors: Feng Tingyong , Zhang Shunmin
Published: September 2023

Prefrontal aberrations are robustly associated with high tendency to procrastinate, but cognitive and neural mechanisms underlying this link remain unknown. An impulse-control hypothesis predicts insufficient prefrontal regulation over reward-processing regions, leading failure to forgo immediate pleasure. While an emotion-regulation hypothesis predicts inadequate prefrontal regulation over emotion-processing systems, resulting in deficits to endure adversity. To investigate which hypothesis is more valid, the current study presented procrastinators with conflicts between pleasant distraction (photographs watching) and difficult-but-rewarding mission (dots counting) under fMRI scanning. The results favored the emotion-regulation hypothesis relative to the impulse-control hypothesis in three regards: (1) High procrastinators performed worse in the mission because of high task difficulty but not fun distraction. (2) Inadequate prefrontal regulation over emotional insular activities underlay failure in both persisting in the mission and resisting the distraction. (3) Trait procrastination correlated with regulatory prefrontal signals during persisting in the mission but not during resisting the distraction. These results indicate procrastinators suffer from emotion-regulation prefrontal deficits, and thus recommend emotional supports rather than criticism on them.
Transformative Student-led Hybrid Mentorship Model Empowering Health Sciences Undergraduates and Young Professionals in Uganda: A MedXMentor Case Study
Authors: Tamale Elvis , Atuhairwe Irene , Ssemwogerere Arnold , Muhimbura Brian , Atimango Lorna , Malinga Paddy Derrick , Mulungi Jonathan , Ssekitto Joseph , Naigaga Josephine , Kintu Timothy Mwanje , Masood Kiran Mitha , Ohuruogu Victor , Ngonzi Joseph
Published: September 2023

Background
Students pursuing health-related courses need access to mentorship and its benefits during their formative academic and career states. Despite a few assertive health professions students knowing about mentorship, they also need help leveraging the various benefits of mentorship. The lack of a structured platform to ease access to mentorship. A student-led initiative dubbed Medxmentor was established to address these gaps. This study assessed the effectiveness of this hybrid mentorship initiative in enhancing research capacity and professional development among undergraduate health sciences students and young professionals in Uganda.
Methods
Both quantitative and qualitative methods were utilized to obtain data. The Kirkpatrick Model of Evaluation was utilized to assess mentees' emotions, learning, and behavior using Google Form questionnaires, feedback forms, and mentoring logs. Study results were summarized using descriptive statistics and thematic analysis.
Results
There were 80 mentees recruited, with 48 (60%) qualifying for one-to-one mentorship and the rest participating in group mentorship sessions. The program had 24 mentors, primarily from the medical profession. The program also had three non-Ugandan mentors. Eight online sessions were organized for group mentorship between April and September 2022, with an average attendance of 52% of mentees. Three workshops were organized; a boot camp, grant writing, and soft skills. Sixty-eight percent (68%) of the project planning webinar attendees reported an increased understanding of the basics of project management. Four themes emerged on Mentee experiences; Mentor engagement, Goal oriented study, Skills and professional development, and High yield mentor-mentee engagements.
Conclusion & Recommendations
A structured mentorship program provides a solution to access mentorship and addresses the needs of mentors and mentees. The Medxmentor program leveraging online platforms provides a broad niche of mentor resources and an efficient structure that can be easily replicated in various medical schools in low-resource settings.