Successful Combination Research Articles

WAYS OF IMPLEMENTING A COMPLEX APPROACH TO INCREASE THE COMPETITIVENESS OF UKRAINE

The study focuses on examining the key factors influencing the competitive state of Ukraine’s socio-economic model at the current stage of development. An analysis of major macroeconomic parameters on the eve of Russia’s full-scale invasion revealed substantial potential for economic recovery following the losses incurred due to COVID-19 pandemic restrictions. Taking into account recent European Union reforms aimed at enhancing competitiveness based on the European Commission’s Communication to the European Parliament, the Council, the European Economic and Social Committee, and the Committee of the Regions, titled «Long-term competitiveness of the EU: looking beyond 2030,» certain related directions for implementing relevant transformations in Ukraine have been identified. As a result, the authors developed a comprehensive approach to enhance the competitiveness of Ukraine. Correspondingly, possible pathways for implementing specific components of this comprehensive approach were proposed. It has been determined that, through incentives involving public and business influence on the elite, it is necessary to ensure the development, implementation, and monitoring of the most urgent reforms, namely: security reform, institutional reform, infrastructure reconstruction, and innovation reform. The most critical steps were identified, primarily involving the deepening of cooperation with foreign partners at both business and governmental levels. The need for decisive action against corruption in all areas of life and the urgent institutional reform required was also highlighted. Using G. Hofstede’s cultural dimensions theory, a regression analysis was conducted to explore the relationship between institutional quality ratings from the “Global Competitiveness Index” and Ukraine’s cultural dimension values. Based on these calculations and the evaluation of statistical correlation density through the determination coefficient, it was found that higher individualism correlates with higher institutional quality, while higher power distance correlates with lower institutional quality. The dependency of institutions on other cultural dimensions was too weak to indicate a meaningful relationship; however, graphical analysis of long-term orientation and uncertainty avoidance suggested a shared dynamic. Three main directions for implementing institutional reform were proposed: fostering civic patriotism among the population, combating the old, corrupt, anti-national elite (oligarchs), and cultivating patriotic meritocrats as replacements. Meeting these conditions would establish a strong foundation for further development of a rule-of-law state. Regarding infrastructure reconstruction and innovation reform, plans for modernization and digitalization were proposed. Particular attention should be paid to implementing and utilizing modern tools to leverage the full spectrum of financial and stock market opportunities. The implementation of modern educational approaches at all levels is also of great importance. The successful combination and implementation of these proposed processes will lead to increased productivity and competitiveness. The driver of positive changes should be Ukrainian business and civil society: entrepreneurs understand what is needed for dynamic growth, and citizens know what is required for a decent life.

Abstract IA007: Preclinical Approaches to Discovery and Development of Novel Combination Therapies

Drug combinations provide an important tool to address the complexity of tumor biology, and the ability to drive deeper and more durable responses has led to many successful combination regimens in clinical use today. There are more possible novel combination regimens than can be feasibly explored clinically, and preclinical studies have become a common tool to identify and prioritize combinations partners for clinical investigation. Historically, these approaches have focused heavily on identification of synergy, however, a growing body of research is beginning to indicate that synergy may not be a key predictor of clinical utility. To better understand the role of synergy in combinations, we experimentally explored acquired resistance to combination therapies in preclinical models, and counterintuitively, find that combinations which derive activity through synergy rather than additivity can lead to less undesirable outcomes. Specifically, we find that the combinations which rely on synergy are more likely to develop resistance as well as demonstrate greater loss of combination activity upon acquisition of resistance than an equally active additive combination. We propose that instead of relying on synergy for combinations discovery, that a framework based on the 5Rs can be employed which emphasizes a more holistic view of combination rationale, development, and proposed clinical utility. We demonstrate the application of these principles to discovery of novel therapeutic agents in analysis of a large-scale pan-tumor screen, and how these factors can be used to identify novel rational combination partners linked to specific disease segments which drive activity in vivo. As more agents with novel mechanisms enter clinical development, preclinical studies will play an increasingly important role in designing combination regimens which can attack the tumor from multiple angles, leading to better activity, and present a more favorable therapeutic index. Citation Format: Jerome T. Mettetal Preclinical Approaches to Discovery and Development of Novel Combination Therapies. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA007

Combustion synthesis and spark plasma sintering processing of (1‐x)Ba(Zr₀.₂Ti₀.₈)O₃‐x(Ba₀.₇Ca₀.₃)TiO₃ ceramics

AbstractSolution combustion synthesis (SCS) has proven to be one of the simplest and fastest methods, using inexpensive materials and resulting in homogeneous stoichiometry with nanometric particle sizes. The spark plasma sintering (SPS) method has been used to obtain high‐density ceramic materials with excellent control of microstructure. This work reports the successful combination of these two techniques for the fabrication of the high‐density lead‐free ferroelectric system (1‐x)Ba(Zr₀.₂Ti₀.₈)O₃‐x(Ba₀.₇Ca₀.₃)TiO₃. The X‐ray diffraction of the powder indicates the majority formation of the perovskite structure and other residual reaction products, indicating a reactive powder. The SPS method resulted in highly densified samples, reaching relative density values close to 99% with a single‐phase perovskite structure. Rietveld refinement revealed the presence of at least two perovskite phases, independent of calcium concentration. Dielectric measurements showed anomalies in both the real and imaginary parts of the dielectric permittivity, which are typical of phase transitions and a low dielectric loss for all compositions. This study shows that the combined use of SCS and SPS technique can be a powerful protocol to produce dense, fine‐grained lead‐free ferroelectric ceramics at relatively low temperatures and in short time periods.

Advancements and gaps in natural language processing and machine learning applications in healthcare: a comprehensive review of electronic medical records and medical imaging

This article presents a thorough examination of the progress and limitations in the application of Natural Language Processing (NLP) and Machine Learning (ML), particularly Deep Learning (DL), in the healthcare industry. This paper examines the progress and limitations in the utilisation of Natural Language Processing (NLP) and Machine Learning (ML) in the healthcare field, specifically in relation to Electronic Medical Records (EMRs). The review also examines the incorporation of Natural Language Processing (NLP) and Machine Learning (ML) in medical imaging as a supplementary field, emphasising the transformative impact of these technologies on the analysis of healthcare data and patient care. This review attempts to analyse both fields in order to offer insights into the current state of research and suggest potential chances for future advancements. The focus is on the use of these technologies in Electronic Medical Records (EMRs) and medical imaging. The review methodically detects, chooses, and assesses literature published between 2015 and 2023, utilizing keywords pertaining to natural language processing (NLP) and healthcare in databases such as SCOPUS. After applying precise inclusion criteria, 100 papers were thoroughly examined. The paper emphasizes notable progress in utilizing NLP and ML methodologies to improve healthcare decision-making, extract information from unorganized data, and evaluate medical pictures. The key findings highlight the successful combination of natural language processing (NLP) and image processing to enhance the accuracy of diagnoses and improve patient care. The study also demonstrates the effectiveness of deep learning-based NLP pipelines in extracting valuable information from electronic medical records (EMRs). Additionally, the research suggests that NLP has the potential to optimize the allocation of medical imaging resources. The identified gaps encompass the necessity for scalable and practical implementations, improved interdisciplinary collaboration, the consideration of ethical factors, the analysis of longitudinal patient data, and the customization of approaches for specific medical situations. Subsequent investigations should focus on these deficiencies in order to fully exploit the capabilities of natural language processing (NLP) and machine learning (ML) in the healthcare sector, consequently enhancing patient outcomes and the delivery of healthcare services.

A multimodal vision transformer for interpretable fusion of functional and structural neuroimaging data.

Multimodal neuroimaging is an emerging field that leverages multiple sources of information to diagnose specific brain disorders, especially when deep learning-based AI algorithms are applied. The successful combination of different brain imaging modalities using deep learning remains a challenging yet crucial research topic. The integration of structural and functional modalities is particularly important for the diagnosis of various brain disorders, where structural information plays a crucial role in diseases such as Alzheimer's, while functional imaging is more critical for disorders such as schizophrenia. However, the combination of functional and structural imaging modalities can provide a more comprehensive diagnosis. In this work, we present MultiViT, a novel diagnostic deep learning model that utilizes vision transformers and cross-attention mechanisms to effectively fuse information from 3D gray matter maps derived from structural MRI with functional network connectivity matrices obtained from functional MRI using the ICA algorithm. MultiViT achieves an AUC of 0.833, outperforming both our unimodal and multimodal baselines, enabling more accurate classification and diagnosis of schizophrenia. In addition, using vision transformer's unique attentional maps in combination with cross-attentional mechanisms and brain function information, we identify critical brain regions in 3D gray matter space associated with the characteristics of schizophrenia. Our research not only significantly improves the accuracy of AI-based automated imaging diagnostics for schizophrenia, but also pioneers a rational and advanced data fusion approach by replacing complex, high-dimensional fMRI information with functional network connectivity, integrating it with representative structural data from 3D gray matter images, and further providing interpretative biomarker localization in a 3D structural space.

Intracorneal iontophoretic delivery of triamcinolone acetonide prodrugs: Physicochemical parameters guiding electrotransport.

Intracorneal delivery of ten amino acid (alanine, arginine, asparagine, glutamine, glycine, histidine, isoleucine, lysine, methionine and valine) ester prodrugs of triamcinolone acetonide (TA-AA) was investigated in vitro, using a corneal iontophoresis device (IONTOFOR-CXL; SOOFT Italia S.p.A.) approved for clinical use in the treatment of keratoconus. Short duration iontophoresis (1 mA for 5 min) was performed and intracorneal deposition of TA was quantified by HPLC-UV and UHPLC-MS/MS. The data evidenced the clear advantage of TA-AA prodrug iontophoresis compared to passive delivery and revealed unexpected and prodrug dependent deposition profiles. Despite their superior electrical mobility, intracorneal delivery of dications, TA-Arg and TA-Lys, did not outperform that of TA-Ala and TA-Gly. In silico investigations to relate the TA-AA prodrugs' physicochemical properties to their electrotransport confirmed that increased lipophilicity potential did not favour iontophoretic transport. For TA-Ala and TA-Gly, it was hypothesized that the greater charge distribution and decreased tendency to interact with the corneal tissue via electrostatic and H-bonds contributed to their successful iontophoretic delivery. Intracorneal biodistribution of TA confirmed that TA-Gly iontophoresis resulted in supratherapeutic concentrations in deep corneal stroma, exceeding TA IC50 by ∼ 104-fold. The results clearly demonstrated the successful combination of the SOOFT iontophoretic device and the TA-AA prodrugs for corneal iontophoresis.

Successively enhanced photoelectrochemical performance from plasmonic Au nanoparticles decorated Ta3N5-TiO2 heterostructure

Semiconductor-based photocatalysts innovation and heterojunction design incorporating novel materials have shed light on the enhancement of the photoelectrochemical performances concerning energy fields, among which the plasmonic metal/semiconductor nanostructure raised extensive research attentions due to further PEC performance enhancement. In this work, an innovatively sandwiched structure composed of Ta3N5 nanorods/ultrathin TiO2/Au nanoparticles was designed with successive PEC enhancement. The successful combination between the Ta3N5 nanorods and the dielectric TiO2 layer represented carriers’ migration, in addition with the heterojunction between TiO2 and Au NPs contributed to the synergistically suppression of the charge carriers’ recombination. Au NPs could further serve as the plasmonic absorber underlying their localized surface plasma resonance effect, expanding the light absorption over the whole visible range, and inducing hot electrons injection to the TiO2 layer effectively. The hierarchical performance improvement via surface plasmon enhanced photoelectrochemical activity in the well-designed heterostructure propose strong potential for the development of novel photocatalysts.

Next-generation combination approaches for immune checkpoint therapy.

Immune checkpoint therapy has revolutionized cancer treatment, leading to dramatic clinical outcomes for a subset of patients. However, many patients do not experience durable responses following immune checkpoint therapy owing to multiple resistance mechanisms, highlighting the need for effective combination strategies that target these resistance pathways and improve clinical responses. The development of combination strategies based on an understanding of the complex biology that regulates human antitumor immune responses has been a major challenge. In this Review, we describe the current landscape of combination therapies. We also discuss how the development of effective combination strategies will require the integration of small, tissue-rich clinical trials, to determine how therapy-driven perturbation of the human immune system affects downstream biological responses and eventual clinical outcomes, reverse translation of clinical observations to immunocompetent preclinical models, to interrogate specific biological pathways and their impact on antitumor immune responses, and novel computational methods and machine learning, to integrate multiple datasets across clinical and preclinical studies for the identification of the most relevant pathways that need to be targeted for successful combination strategies.

Successful combination of lactic acid bacteria and yeast fermentation and enzymatic treatment to re-cycle industrial bread by-products for bread making

Bread industry generates significant amounts of by-products which are discarded every day with relevant economic and environmental repercussions, despite they still contain high concentrations of potentially exploitable nutrients. Aiming to develop new sustainable solutions, this study explored the synergistic application of enzymatic treatment and sourdough fermentation to re-cycle industrial bread by-products for new sourdough bread making. Lactiplantibacillus plantarum SD69. B2 and Saccharomyces cerevisiae SD69. E3 were used as starters, while α-amylase, amyloglucosidase and protease were assessed for their ability to hydrolyze starch and proteins, providing more available carbon and nitrogen sources for the microorganisms. The bread waste-based sourdoughs made by combining protease and L. plantarum SD69. B2 alone or in combination with S. cerevisiae SD69. E3 were selected based on acidification and growth kinetics, and their biochemical, amino acid, and peptide profiles were also characterized demonstrating promising properties. Therefore, they were used, at different percentages, for bread making. Although a slightly acidic pH and a low leavening power, due to the denatured proteins and gelatinized starch in the bread by-products, the texture and sensory analyses of new breads revealed better textural attributes, smell, acidic taste, and overall acceptability compared to the control. The possible reasons behind such features were discussed. The overall results demonstrated that the approach proposed in this study was effective to valorize bread by-products, and it represents a starting point to develop strategies responding to the current perspective of circular economy in food industry.

Abstract B030: Advancing precision management in retinoblastoma via aqueous humor liquid biopsy: A case of TP53 and MDM4 alterations

Abstract Background: Precision medicine has revolutionized cancer treatment, but its application in retinoblastoma (RB) has been limited due to the risks associated with traditional tumor biopsies, which can lead to the spread of cancer outside the eye. Blood plasma has not been effective in intraocular RB management because the blood-brain barrier (BBB) prevents tumor-derived material from entering the bloodstream, and in cases of bilateral RB—occurring in over 40% of patients—each eye may harbor distinct genomic alterations, complicating the use of blood-based biomarkers. Given these challenges, the discovery of tumor-derived genomic material in the aqueous humor (AH) offers a promising and safer alternative—a liquid biopsy that provides localized and specific insights into the tumor's genetic makeup. Although AH liquid biopsies have been valuable in identifying genomic changes in RB, they have yet to guide treatment decisions. This is primarily due to the rarity of the disease, the heterogeneity of treatment modalities, and the unclear definition of in vivo RB subtype classifications. Consequently, translating these genomic insights into actionable, personalized treatment strategies has been challenging. Now, we present the first application of AH-monitored treatment in a 35-month-old male with unilateral RB, characterized by TP53 alteration and ecDNA-MDM4 amplification, highlighting a significant advancement in the precision management of RB. Methods: AH samples were obtained via clear corneal paracentesis and analyzed for copy number alterations and somatic variants using shallow whole-genome sequencing and targeted sequencing. The patient initially received systematic CEV, followed with intravitreal melphalan (IVM) monotherapy. Due to resistance, treatment was escalated to a combination of intravitreal melphalan and topotecan (IVM+IVT), monitored by the AH liquid biopsy genomic findings. Results:The patient initially showed resistance to monotherapy with intravitreal melphalan (IVM), but dual therapy with melphalan and topotecan (IVM+IVT) significantly reduced tumor fraction (TFx) from 81.61% to 26.63% and decreased tumor size. Continued dual therapy and subsequent topotecan monotherapy resulted in complete regression of vitreous seeds and stabilization of the disease, as indicated by a final AH TFx of 0%. At our institution, Children's Hospital Los Angeles (CHLA), the majority of RB cases are treated using IAC or IVM, with dual chemotherapy regimens rarely employed. Conclusions: This case underscores the importance of tailoring treatment protocols to genetic profiles identified through AH liquid biopsy in managing aggressive RB. The successful combination of genomic profiling and personalized therapy has potential to significantly improve clinical outcomes, marking a critical step toward real precision management of RB. Further clinical collaboration is essential to validate and refine protocols for TP53-altered and ecDNA-MDM4-driven RB. Citation Format: Liya Xu, Elaine Huang, Jesse Lee Berry. Advancing precision management in retinoblastoma via aqueous humor liquid biopsy: A case of TP53 and MDM4 alterations [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B030.

EXPERIENCE OF IMPLEMENTING THE DISTANCE E-COURSE “STATISTICAL METHODS IN PHARMACY” IN THE MATHEMATICAL TRAINING OF FUTURE PHARMACEUTICAL SPECIALISTS

The article is dedicated to the issue of distance and online learning in higher pharmaceutical education. In the paper, the main principles and characteristic features of the concept of distance learning are outlined, the main advantages and disadvantages of using distance and e-learning in pharmaceutical and medical higher education are discussed. Considerable attention is paid to the use of distance learning technology in the process of math training for students pursuing higher education in the field of pharmacy. In addition to technical means and the structural-methodological component of the distance course development process, special attention is given to psycho-pedagogical aspects, which includes a focus on increasing the motivation of this group of education seekers to master disciplines related to exact sciences. It is demonstrated, using the example of the developed by the authors distance course “Statistical Methods in Pharmacy”, implemented with the LMS Moodle, that a successful combination of methodological approaches and innovative teaching methods, aimed at implementing a competency-based approach in education, along with modern information technology providing online access to educational content, including tools for feedback support, practical skills development, and automated self-assessment, ensures the effectiveness of achieving educational goals by learners and the formation of professional competencies defined by the educational program. The course was tested, certified, and implemented in the fundamental training of future pharmaceutical professionals at the National University of Pharmacy. It is concluded, that the implementation of distance learning technology in the practice of Ukrainian higher pharmaceutical and medical education is necessary not only due to the current conditions that make it impossible to organize full-fledged offline education but also because of the efficiency of these technologies, primarily for organizing independent students’ work, that ensures the development of learners’ autonomy, contributes to the development of information culture, general digital competence, and a range of soft skills, including communication, interaction, collaboration in a digital environment, and the rational use of study time.

The history of the breeding of Clematis (Clematis L.) in the M. M. Gryshko National Botanical Garden, NAS of Ukraine

Purpose. Investigate the history of Clematis breeding in the M. M. Gryshko National Botanical Garden (NBG), NAS of Ukraine, determine the main directions of hybrid Clematis breeding work. Results. It was established that the result of more than 16 years of breeding Clematis in the NBG was the selection of the 61 perspective hybrid, 42 of which, the most perspective, were assigned names. Of these, large­flowered varieties are the most numerous according to the distribution of variety groups in the current Royal Horticultural Society of Great Britain classification. In particular, Late Large­flowered account for about 40% of the total and Early Large­flowered for about 29%. Small­flowered hybrids make up the smaller part, of which about 26% belong to the Viticella group and one hybrid (‘Sputnik’) to the Integrifolia. The known directions of distribution of hybrid Сlematis of the NBG breeding indicate the possibility of their successful cultivation both in continental and maritime areas with a high level of humidity in the temperate zone and in the dry Mediterranean climate of the subtropical climate zone, which reveals their significant adaptive potential. Conclusions. Obtaining varieties of hybrid Clematis of domestic breeding is important for the implementation of sustainable horticulture practices on the territory of Ukraine, since a significant part of the modern introduced assortment of Clematis raises doubts about their adaptability to the local climate, and requires additional research into their adaptive potential. A successful combination in vertical landscaping of NBG­bred Clematis belonging to different varietal groups can ensure continuous flowering from May to the end of the season. These unique characteristics of Clematis ensure the creation of not only environmentally sustainable, but also visually appealing spaces that will contribute to the overall health and beauty of the urban environment.

In Silico Design, Chemical Synthesis, Biophysical and in Vitro Evaluation for the Identification of 1-Ethyl-1H-Pyrazolo[3,4-b]Pyridine-Based BRD9 Binders.

In this work, we report the identification of novel bromodomain-containing protein 9 (BRD9) binders through a virtual screening based on our developed 3D structure-based pharmacophore model. The in silico workflow here described led to the identification of a promising initial hit (1) featuring the 1-ethyl-1H-pyrazolo[3,4-b]pyridine motif which represented an unexplored chemotype for the development of a new class of BRD9 ligands. The encouraging biophysical results achieved for compound 1 prompted us to explore further tailored structural modification around the C-4 and C-6 positions of the central core. Hence, the design and synthesis of a set of 19 derivatives (2-20) were performed to extensively investigate the chemical space of BRD9 binding site. Among them, four compounds (5, 11, 12, and 19) stood out in biophysical assays as new valuable BRD9 ligands featuring IC50 values in the low-micromolar range. Noteworthy, a promising antiproliferative activity was detected in vitro for compound 5 on HeLa and A375 cancer cell line. The successful combination and application of in silico tools, chemical synthesis, and biological assays allowed to identify novel BRD9 binders and to expand the arsenal of promising chemical entities amenable to the recognition of this important epigenetic target.

Разработка природоподобной технологии размножения низкорослых подвоев косточковых культур в закрытом грунте

Abstract. The creation of technologies in accordance with the directions for the introduction of environmentally friendly, resource-saving developments into agriculture is relevant. Accelerated reproduction of planting material of the "basic" and "proven" categories is considered equally important, which requires optimization of reproduction by green cuttings. Green cutting allows to significantly quickly increase the yield of cuttings from one mother plant, reducing the area of the mother plantations by 4-5 times. Its advantage is the genetic uniformity of own-root plants, contributing to the elimination of plant infection with diseases and pests, ensuring a shorter growing period, successful combination with other stages of recovery: microclonal reproduction, reproduction by green grafting. In the protected ground conditions, studies were carried out (2019-2023) to isolate the most effective drug for the reproduction of healthy mother rootstock bushes for small-stone crops: AI 5 B, 3-20, AI-1.10-18, 3-107 (FSBSI NCFSCHVW breeding); VSL-2 (Crimean EBS breeding). The effect of the drugs was compared: plant growth regulators: Indolyl-3-butyric acid (IMC, SP), Phytactive Extraplus, CE; microbiological fertilizers: Sporex, Zh, Ultrex, Zh; Sporion, Zh, control (water). It was found that the treatment of BCI and the phytactive Extraplus reduced the period of appearance of primary roots by 4.5 and 5 days, depending on the rootstock. The largest percentage of rooted ones was obtained using the microbiological preparation Ultrex (3-47 % more than the control variant, depending on the rootstock genotype), also in this variant, due to its positive effect on root formation of more than 2 mm, increased stress resistance, more standard planting material was obtained by 90 % relative to the control ones. Key words: basic mother plantings, green cuttings, plant growth regulators, preparations based on microorganisms and their waste products, the percentage of yield of standard rootstocks for sweet cherries and cherries.

Enhanced lithological mapping in arid crystalline regions using explainable AI and multi-spectral remote sensing data

Lithological classification is essential for understanding the spatial distribution of rocks, especially in arid crystalline areas. Artificial intelligence (AI) recent advancements with multi-spectral satellite imagery have been utilized to enhance lithological mapping in these areas. Here we employed different AI models namely, Support Vector Machine (SVM), Random Forest Classification (RFC), Logistic Regression, XGBoost, and K-nearest neighbors (KNN) for lithological mapping. This was followed by the application of explainable AI (XAI) for lithological discrimination (LD) which is still not widely explored. Based on the highest accuracy and F1 score of the previously mentioned models, RFC model outperformed all of them, and hence, it was integrated with XAI, using the SHapley Additive exPlanations (SHAP) method.This approach successfully identified critical multi-spectral features for LD in arid crystalline zones when applied on the Landsat-8, Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), and SRTM-DEM datasets covering the Hammash and the Wadi Fatimah areas in Egypt and the Kingdom of Saudi Arabia, respectively. Field validation in the Hammash area confirmed the RFC model's efficacy, achieving a satisfactory 94% overall accuracy for 18 features. SHAP was able to identify the top ten features for proper LD over the Hammash area with 90.3% accuracy despite the complex nature of the ophiolitic mélange. For validation purposes, RCF was then utilized in the Wadi Fatimah region, using only the top 10 critical features rendered from the SHAP analysis. It performed well and had 93% accuracy. Notably, XAI/SHAP results indicated that elevation data, Landsat-8's Green Band (B3), and the two ASTER SWIR bands (B5 and B6) were essential and significant for identifying island arc rocks. Moreover, the SHAP model effectively delineated complex mélange matrices, primarily using ASTER SWIR band (B8). Our findings highlight the successful combination of RFC with XAI for LD and its potential utilization in similar arid crystalline environments worldwide.

Heterogenization of Palladium Trimer and Nanoparticles Through Polymerization Boosted Catalytic Efficiencies in Recyclable Coupling and Reduction Reactions.

The development of heterogeneous palladium catalysts has shown continuous vitality in the field of catalysis and materials. In this work, we report one concise free radical polymerization approach to accomplish the aromatic palladium trimer functionalized polymers PSSy-[Pd3]+ (2) and its derived palladium nanoparticles (3). Full characterizations could confirm the successful combination of cationic [Pd3]+ or nanoparticles with poly(p-sulfonated styrene) skeleton. Compared to their monomeric tri-palladium precursor (1) and common Pd(dba)2, Pd(PPh3)4, Pd(OAc)2, heterogeneous PSSy-[Pd3]+ (2) shows much superior catalytic activities (0.15 mol %, TOF=1333.3 h-1) in the SMCC reaction. The identically ligated PdNPs (3) are formed in-suit in the presence of NaBH4 and accomplish quantitative reduction of 4-nitrophenol in just 320 s (0.50 mol %, TOF=2250 h-1). Moreover, these heterogeneous catalysts are reused for 5-6 times without significant loss of catalytic activity. Their superior catalytic ability is probably attributed to the synergistic effect of polymer entanglement and the tri-palladium fragment. This work enlightens that the immobilization of palladium clusters or nanoparticles by polymerization could offer multiple advantages in stability, efficiency and recyclability for their involved catalyses and show far-reaching future implications.

Table-top laser-based terahertz high harmonic generation spectroscopy under magnetic fields and low temperatures.

We have developed a terahertz (THz) nonlinear spectrometer at low temperatures (1.5-300K) and under high magnetic fields (up to 10T) by combining the laser-driven table-top intense THz source with a superconducting magnet. The strong-field THz pump pulse was generated from LiNbO3 crystal using the tilted-pulse-front technique and tightly focused into the center of the magnet by an off-axis parabolic mirror and a THz lens. The electric fields at the focus can achieve 500kV/cm with a monocycle waveform and 30kV/cm with a multicycle waveform at 0.5THz. The sample was mounted on a low-temperature motorized rotation stage, which enables performing the polarization dependent measurements of the third harmonic generation (THG) intensity without rotating the incident THz pulses. The magnetic field direction can be rotated using a mechanical rotator, allowing for a convenient switch between Faraday and Voigt geometry. We demonstrate the excellent performance of our instrument by conducting THG measurements in the two-band superconductor MgB2 as a function of temperature, sample azimuth angle, as well as in-plane and out-of-plane magnetic fields. The successful combination of the strong field THz source with magnetic fields enables us to study a variety of materials with magnetic-field-dependent properties of interest.

EFFECTIVE MANAGEMENT DECISIONS: METHODS AND TECHNIQUES

The article is devoted to the study of methods and techniques for making and managing effective managerial decisions. It is established that managerial decisions are multi-faceted and varied. Managerial decisions are classified depending on whether they require the development and/or modification of the methods and techniques for their implementation, based on the results of research by scholars. The conclusion is made about the necessity of conducting an in-depth analysis of management methods and techniques for companies to make effective decisions, considering diverse influencing factors on their activities under precedent conditions and circumstances, in the context of adapting to these and subsequently developing theoretical-methodological tools. Attention is focused on the fact that modern business faces constant challenges related to russia's full-scale war against Ukraine, deepening imbalances, and the continuation of negative trends as a result. It is concluded that, under such conditions, decision-making requires extensive application of modern methods and approaches at all levels of management, with appropriate modification and optimization of the decision-making process itself. The activities of LLC "Nova Poshta" are analyzed as a prominent representative of a business that successfully uses innovative approaches to management but must continuously improve and adapt methods and techniques to new challenges for successful market operation. It is determined that LLC "Nova Poshta" serves as an example of a successful combination of innovation and traditional approaches, which contributes and can have a significant impact on ensuring not only the company's viability during russia's full-scale war against Ukraine but also dynamic changes in the post-war market. The conclusion is drawn that effective managerial decision-making is the foundation of successful enterprise functioning.

UPLC-MS/MS Method Development and Validation of Tegafur, Gimeracil, and Oteracil in Rat Plasma and its Application for Pharmacokinetic Study

A successful combination of Tegafur, Gimeracil, and Oteracil is used to treat stomach cancer in adults. Once converted to 5-fluoro uracil, the active form of Tegafur inhibits the manufacture and function of DNA and RNA, hence preventing the proliferation of cancer cells. Consequently, a new, sensitive, and cost-effective bioanalytical approach for the detection of these medications performed by liquid chromatography-mass spectrometry on rat plasma is needed. Isocratic mode was employed at room temperature to achieve separation on a C18 column (150x4.6mmx3.5μm). A mobile phase composed of ACN and 0.1% formic acid was used in the 40:60 ratio with a flow rate of 1mL/min. An analysis was conducted on Tegafur, Gimeracil, and Oteracil using a 6-minute retention time and the retention times of them were found to be 2.027, 3.176, and 4.015 respectively. The R2 values were found to be 0.9999 showing the method linear. The method developed was found to be accurate and precise as per ICH guidelines.

Cutting-Edge Approach to Targeted Therapy: Repositioning of Old Drugs in Combination with Standard Clinical Chemotherapeutics Potentiates a Propitious Novel Targeted Therapy for Human Pancreatic Cancer

Metastatic pancreatic cancer leads to a fatal outcome, with a median progression-free survival of approximately six months when utilizing the most successful combination of chemotherapeutic regimens. When drug resistance develops, it facilitates an increase in primary tumor growth and new and growing metastases. Patients inevitably and quickly succumb to their disease and die. Notably, chemotherapy has an unintended impact on the development of drug resistance through the enhancement of EMT development and the enrichment of cancer stem cells (CSC). Recent report discovered that neuraminidase-1 (Neu-1) regulates EMT induction, angiogenesis, and cellular proliferation by the activation of several receptor tyrosine kinases. Here, the continual therapeutic inhibition of Neu-1 through intravenous administration of oseltamivir phosphate (OP) and aspirin (ASA) alongside GEM treatment significantly inhibits tumor progression, crucial compensatory signaling pathways, EMT program, CSC, and metastasis progression in a preclinical RAG2xCy double mutant BALB/c mouse model of human PANC-1 pancreatic cancer. The tumorigenic and metastatic potential of the xenotumors from the animals treated with the experimental protocols were significantly ablated when transferred into the mammary fat pads of NSG (NOD SCID gamma) branded mice. Keywords: pancreatic cancer; chemoresistance; drug repurposing; EMT.