Innovative Research Development Research Articles

METHOD TO DEVELOP HYBRID MANAGEMENT MODELS FOR R&D PROJECTS BY USING A MORPHOLOGICAL ANALYSIS MATRIX

Management professionals are increasingly adopting hybrid implementation models for applicative R&D projects, specific to dynamic environments, for rapidly adapting to various challenges. In this paper, being aware of the inadequacy of traditional management models in today's volatile and innovative socio-economic landscape, we made somehow a literature review and we adapted a method that, based on the use of a morphological analysis matrix, allowed us to prepare, by implementing in the first phase a focus-group pilot, the elaboration of personalized hybrid models, targeting mainly, as an original approach, research – development - innovation (RDI) projects. In the future, we intend to validate the method, through a case study evaluation, aiming to provide professionals with appropriate managerial solutions by developing a guide for selecting the best practices and adopting high-performing hybrid management models.

METHOD TO DEVELOP HYBRID MANAGEMENT MODELS FOR R&D PROJECTS BY USING A MORPHOLOGICAL ANALYSIS MATRIX

Management professionals are increasingly adopting hybrid implementation models for applicative R&D projects, specific to dynamic environments, for rapidly adapting to various challenges. In this paper, being aware of the inadequacy of traditional management models in today's volatile and innovative socio-economic landscape, we made somehow a literature review and we adapted a method that, based on the use of a morphological analysis matrix, allowed us to prepare, by implementing in the first phase a focus-group pilot, the elaboration of personalized hybrid models, targeting mainly, as an original approach, research – development - innovation (RDI) projects. In the future, we intend to validate the method, through a case study evaluation, aiming to provide professionals with appropriate managerial solutions by developing a guide for selecting the best practices and adopting high-performing hybrid management models.

A review of the medicinal uses and biological activity of Piliostigma thonningii (Schum). Milne-Redh.

Abstract Objective Piliostigma thonningii is a medicinal plant commonly found in Eastern and Western Africa with a potential traditional usage to treat various diseases. Several studies have revealed interesting pharmacological activity of the plant and different phytochemicals were identified. This study critically reviewed the medicinal uses, phytochemistry, and bioactivity of P. thonningii. Methods Relevant databases including ISI Web of Knowledge, Science Direct, Scopus, PubMed, and Google Scholar as well as databases for these were searched for information using the keyword P. thonningii and its synonym. Key findings P. thonningii is majorly prepared in Africa as a decoction, infusion, maceration, and ointment and administered orally or topically to treat several diseases such as malaria, cancer, hepatitis, diabetes, and others. Pharmacological studies have demonstrated activity including antimalarial, antiviral, antimicrobial, anti-proliferative, and other medicinal properties. Compounds including piliostigmin, C-methyl flavonols, quercetin, and others were among the active components. Conclusions The general use of P. thonnigii in various medicinal forms in Africa presents a great opportunity for the development of innovative research toward the production of natural products and nutraceuticals. Nevertheless, additional studies especially in vivo are necessary to further elucidate the mechanism mediating the bioactivities, especially in relation to the medicinal and nutritional uses.

Applications of Flow Chemistry in Total Synthesis of Natural Products

Abstract: A vital driving force for chemists to discover novel synthetic protocols is the improvement of more effective synthetic technologies and sustainable methodologies. This is associated with the development of innovative research that stimulates the creative reevaluating of known conceptions. Currently, these robust methodologies, as well as green synthetic procedures, have been designed for the total synthesis of secondary metabolites. Flow chemistry and flow photochemistry have emerged as powerful tools to promote valuable transformations in the total synthesis of natural products as key step(s). Flow chemistry development offers many merits over a traditional batch format, namely a round-bottom flask. The advantages of this green tool comprise waste minimization, simple scale-up, reduction of reaction time, safety betterment as, well as energy and cost efficiency. Flow chemistry comprises a fascinating prospect for the synthesis of promising organic molecules and bioactive complex natural products as it represents a suitable modern synthetic technology for the improvement of sustainable chemistry. Continuous flow chemistry is an assembly of chemical processes carried out in continuous flowing streams. Compared to conventional organic synthesis, it is a process that strengthens technology and is superior in enhancing and scaling up synthesis, accurately controlling reaction rate, and providing the desired products with maximum yields. In the past and likely in the future natural products and their analogue will continue to deliver the stimulation for drug discovery and development programs. Total synthesis of natural products is very useful to synthesize natural products in the laboratory as many secondary metabolites are available in low quantities from their sources of origin. So, this review wishes to cover the brilliant applications of flow chemistry in the total synthesis of natural products in the field of novel technological advances.

Building the Research Infrastructure module in the Ukrainian Research Information System (URIS)

In recent years, Ukraine has made significant progress in developing open science practices to ensure open access to research infrastructure. In 2019, in accordance with the program "On Approval of the Concept of the State Targeted Program for the Development of Research Infrastructures in Ukraine for the Period up to 2026" [1], the effectiveness of the program implementation is ensured by attracting targeted investments to increase the competitiveness of research infrastructures, coordinating their operation, collecting and analyzing data on such infrastructures, implementing the provisions of international legislation in the relevant field into national legislation to ensure the implementation of the Agreement on the Association of Research Infrastructures. In 2020, the Ministry of Education and Science of Ukraine published the National Research Infrastructure Roadmap, which outlines the strategic priorities for the development of research infrastructure in the country. The Roadmap included plans to create new research facilities, modernize existing infrastructure, and develop human capital in research. In 2021, the Government of Ukraine approved the Concept of the State Targeted Program for the Development of Research Infrastructures in Ukraine for the period of 2022-2026 [1]. The program aims to modernize the research infrastructure in Ukraine and support the development of innovative research [1]. The program is a significant step forward for the research infrastructure in Ukraine and has the potential to improve research capacity and stimulate innovation in the country. In 2022, the Government of Ukraine adopted the National Plan for Open Science, covering the period from 2023 to 2030. The aim of the plan was to bring Ukraine's research practices in line with the EU's open science policy [2]. The development of research infrastructure in Ukraine has been a priority for the government in recent years, as the country seeks to modernize its scientific potential and support innovation.

CARE program: NCI and FDA interagency collaborations to support oncology small business entrepreneurs.

The National Cancer Institute's Small Business Innovation Research Development Center (NCI SBIR) supports the commercialization of novel cancer-related technologies by providing resources to 300-400 small businesses each year. Whereas Federal funding is crucial for the translation of technologies to the clinic, the majority of these technologies will need to undergo regulatory review to reach clinical testing. Many small businesses find navigating their regulatory pathway challenging, largely due to lack of regulatory expertise on small startup teams with limited revenue. In collaboration with the US Food and Drug Administration (FDA), NCI SBIR launched a new regulatory assistance program called Connecting Awardees with Regulatory Experts (CARE). The goal of the CARE program is to connect NCI-funded small businesses with the FDA to receive feedback on their regulatory questions during early-stage product development. The program has a multipronged support approach and also educates companies about the FDA process and existing resources. To date, 141 companies have participated in the interagency program. Follow-up surveys indicate that the program guided the companies in planning the next regulatory steps for their technology development (89%) and provided critical information that changed their future NCI small business grant project aims (81%). Overall, companies reported they would recommend the program to other companies (90%). This paper will discuss the CARE program outcomes as well as other NCI and FDA collaborations that support early-stage small businesses, including the joint development of funding opportunities and online resources that focus on the oncology startup community.

Abstract IA009: National Cancer Institute Small Business Innovation Research Development Center NCI SBIR & STTR resources for commercializing innovative cancer prevention

Abstract The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs at the National Institutes of Health (NIH) serve as one of the largest sources of early-stage capital for technology commercialization in the United States (US). In FY2021, the National Cancer Institute (NCI) SBIR and STTR Programs provided approximately $182M in non-dilutive funding to US small businesses and managed over 400 different projects. By supporting startups and other small businesses in the cancer space, the NCI SBIR and STTR Programs act as catalysts of innovation for novel technologies and products to achieve NCI’s mission to prevent, diagnose, and treat cancer. Staffed by a dedicated team of scientists with wide-ranging technology and industry experience, the NCI SBIR Development Center provides both funding and non-funding resources to US small businesses all aimed at translating technologies to the clinic to help cancer patients and providers. During the past 5 years, NCI has provided SBIR/STTR funding to approximately 25 companies who are developing novel cancer prevention agents. Companies focused on prevention of several indications such as colorectal cancer, oral squamous cell carcinomas, and human papillomavirus-related cancers. Award sizes ranged from $200k-$2M and included support for companies with technologies in the preclinical and clinical stages of development. NCI provided opportunities for non-funding support as well, including entrepreneurial training programs such as I-Corps™ at NIH and programs to facilitate connections between innovators and potential investors. Whether a technology is in the preclinical or clinical stage of development, NCI can help small businesses translate their innovative research to the marketplace so they become available to healthcare providers and their patients. Citation Format: Jonathan Franca-Koh. National Cancer Institute Small Business Innovation Research Development Center NCI SBIR & STTR resources for commercializing innovative cancer prevention [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA009.

Synthesis of bioactive natural products and their analogs at room temperature – an update

Abstract Sustainability is a concept that is employed to distinguish methods and procedures that can ensure the long-term productivity of the environment as it includes environmental, social, and economic dimensions. New generations can live on this planet with less hazardous substances and minimum requirement of energy for chemical transformations as green chemistry is related to creativity and the development of innovative research. Among the 12 principles of this clean chemistry, the sixth principle is devoted to the “design of energy efficiency” which discloses that less or the minimum amount of energy is required to conduct a specific reaction with optimum productivity. The most successful way to save energy is to construct strategies/methodologies that are capable enough to carry out the chemical transformations at ambient temperature and standard pressure. Hence, the present review wishes to cover the synthesis of bioactive natural products and their derivatives at room temperature. Bioactive secondary metabolites play a crucial role in the drug discovery together with drug development process; chiefly anticancer along with antibiotic molecules is noticeably enriched with molecules of natural origin. Natural sources, structures, and biological activities of natural products are highlighted in this review and it is also aimed to offer an overview of the design and synthesis of bioactive natural products and their analogs at room temperature for the first time efficiently.

A look at the focus shift in innovation literature due to Covid-19 pandemic

This study explores the problems related to the development of innovation research in the field of business and economics and the change in their characteristics following the coronavirus disease 2019 (COVID-19) pandemic. We compile a comprehensive bibliometric analysis of 17,277 pre-epidemic publications and 4,240 post-epidemic publications from the Web of Science. Using bibliometric methods and visualization tools, we present the changes in these publications following the COVID-19 pandemic, and identify the influential countries and regions, sources, and references, and obtain features of keywords over time. The results show that innovation research is rich in content, and involves a wide range; it has been focusing on emerging topics, such as those concerning low-carbon, innovation forms, and epidemic environments, following the COVID-19 pandemic. This study contributes to the body of knowledge on innovation, and helps to understand the features and structures of innovation research in business and economics.

Investor initiatives program: Public-private partnerships to expedite commercialization for NCI-funded small business entrepreneurs.

The National Cancer Institute’s Small Business Innovation Research Development Center (NCI SBIR) provides federal research and development funding and commercialization resources to more than 400 small businesses each year developing novel technologies to prevent, diagnose, and treat cancer. Although federal funding is vital for life science startups at the early stage of development, it is often insufficient to translate the technology from discovery to commercial product. Early‐stage startups must connect to follow‐on capital and resources to bring NCI‐funded technologies to patients. Most startups face challenges in securing additional funding due to lack of access to investors and strategic partners and the ability to effectively pitch their technology. In 2015, the NCI SBIR started the Investor Initiatives program to connect funded small businesses with targeted investors and strategic partners to address the aforementioned obstacles. This program leverages an extensive network of investors and partners to conduct business‐focused reviews and provide pitch coaching. The program incentivizes earlier collaborations between NCI‐funded companies and private investors through various channels. The program has supported 117 companies from years 2016–2019 to attend 27 investor showcase events. Follow‐up surveys show that the program and the assistance offered by NCI SBIR have contributed to a total of 32 completed deals as of April 29, 2020. This paper will discuss the Investor Initiatives program and its outcomes from 2016 to 2019 and demonstrate the effectiveness of a federal program that leverages public‐private partnerships to assist portfolio companies with raising follow‐on funding to accelerate the translation of research into clinical practice.

Use of contrast enhanced ultrasound in testicular diseases: A comprehensive review.

BackgroundContrast‐enhanced ultrasound (CEUS) is a sonographic technique that increases the diagnostic accuracy of ultrasound and color Doppler ultrasound (CDUS) when studying testicular abnormalities. However, its role in clinical practice is still debatable because there are no accepted standards regarding how and when this technique should be used for patients with testicular disease.ObjectivesTo perform a nonsystematic review of the current literature to highlight the strength and flaws of performing CEUS and to provide a critical overview of current research evidence on this topic.Materials and methodsA thorough search of published peer‐reviewed studies in PubMed was performed using proper keywords.ResultsStrong enhancement of neoplastic lesions (both benign and malignant) during CEUS aids in differential diagnosis with non‐neoplastic lesions, which usually appears either nonenhanced or enhanced in a manner similar to that of the surrounding parenchyma. CEUS enhancement has a high predictive value in the identification of neoplastic lesions, whereas a similar or complete absence of enhancement may be interpreted as strong evidence of benignity, although there are exceptions. Literature on quantitative analysis is still scarce, though promising, particularly in distinguishing benign from malignant neoplasms. Furthermore, CEUS may be useful in many emergency situations, such as acute scrotum, blunt scrotal trauma, and focal infarction of the testis. Finally, CEUS can help increase the probability of sperm recovery in azoospermic males.Discussion and conclusionCEUS is a safe, easy‐to‐perform, and cost‐effective diagnostic tool that can provide a more accurate diagnosis in testicular lesions and acute scrotal disease. However, further studies with larger cohorts are required to refine the differential diagnosis between benign and malignant neoplasms. Finally, these preliminary results can instigate the development of innovative research on pre‐testicular sperm extraction to increase the chances of sperm recovery.

Development of racks for maximization of biological harvesting of N and P from sea and marine through aquatic birds producing resource guano

Huge increase of global population was creating stress on terrestrial ecosystems which worry food policy thinkers and planners. Biological nitrogen (N) and phosphorus (P) harvesting was an innovative research development using well accepted and circulated data about seven decades before, which was accepted as innovative way of linking hydro, fishery, aquatic birds, agriculture and environment. This linkage made easy way of opening vast ocean and marine resources harnesssible for extracting organic macro nutrients for agriculture and industrial products. Objective of this study was to develop racks for enabling harvest of the guano. Study facilitated birds social and stochastic and heuristic on inspire design for racks for sitting of aquatic birds and collection of bird droppings in daily routines. The architecture of racks and materials of construction were developed. It was suggested to launch operational research project on harvesting of guano for intended use. Thus new world was created to harness sea resources for innovative product to benefit agriculture, industry and environment by effective use of vast ocean and other existing aquatic systems. This research created new dimension of linking ocean, fish, birds, agriculture, environment and human life easy and reducing stress on terrestrial ecosystems.

Experimental realization of Lieb-Mattis plateau in a quantum spin chain

Topological properties in material science have recently received tremendous attention, as exemplified by topological insulators. As for quantum spin systems, the Haldane chain with integer spins is the best known example1. The realization of a topological quantum phase in the Haldane chain is an innovative research development related to the 2016 Nobel Prize in Physics. For mixed spin chains composed of two different spins, the appearance of a topologically quantized magnetization plateau is predicted by the Lieb-Mattis theorem2 in combination with the Oshikawa-Yamanaka-Affleck criterion3. However, the actual magnetization plateau in the mixed spin chain has not yet been observed. Here, we present a model compound forming a mixed spin-(1/2, 5/2) chain. We observe a clear Lieb-Mattis plateau and well explain it quantitatively. The present results demonstrate a quantum many-body effect based on quantum topology and provide a new stage in the search for topological properties in condensed matter physics.

Radiation Biomarkers: Can Small Businesses Drive Accurate Radiation Precision Medicine?

Radiation therapy is an essential component of cancer treatment. Currently, tumor control and normal tissue complication probabilities derived from a general patient population guide radiation treatment. Its outcome could be improved if radiation biomarkers could be incorporated into approaches to treatment. A substantial number of cancer patients suffer from side effects of radiation therapy. These side effects can result in treatment interruption. Such unplanned treatment interruptions not only jeopardize anticancer treatment efficacy but also result in poor post-treatment quality-of-life. To develop and translate radiation biomarkers for clinical use, NCI's Radiation Research Program, in collaboration with the Small Business Innovation Research Development Center, funded four small businesses through the request for proposals after peer review during 2015-2019. Here, we summarize publicly available information on intellectual property rights, the status of development, ongoing clinical trials, success in obtaining financing and regulatory approval. An analysis of publicly available information indicates all four companies have completed phase I of SBIR funding and advanced to further development, validation and clinical trials with phase II SBIR funding. These biomarkers are: 1. A panel of genomic biomarkers of radiation response to predict toxicity and radioimmune response (MiraDx Inc., Los Angeles, CA); 2. A multiplex assay for single nucleotide polymorphism (SNP) biomarkers of radiation sensitivity to identify a subset of prostate cancer patients for which radiotherapy is contraindicated (L2 Diagnostics, New Haven, CT); 3. A cell-free DNA assay in blood to measure tissue damage shortly after radiation exposure (DiaCarta Inc., Richmond, CA); and 4. A metabolomic/lipidomic assay to predict late effects that adversely affect quality-of-life among patients treated with radiation for prostate cancer (Shuttle Pharmaceuticals, Rockville, MD). This work also provides a bird's eye view of the process of developing radiation biomarkers for use in radiation oncology clinics, some of the challenges and future directions.

Improvement of the National Research, Development and Innovation Strategy 2014-2020 in Comparison with the National Research, Development and Innovation Strategy 2007-2013

Abstract The European Union regularly develops research, development, innovation (RDI) strategies for seven years for member countries. Romania benefited from the first RDI strategy during the period 2000-2007, during which our country was trying to meet the conditions of EU accession. Romania is a member of the EU since 1st January 2007 and started, based on the EU’s RDI strategy, to develop its own strategy. The present paper aims to analyze the achievement of the general and specific objectives established by National Strategy for Research, Development and Innovation (NSRDI) 2007-2013, the evolution of the results 2014-2017 and what could be the measures and programs taken by Romania in 2019-2020 to bring our country closer to achieving the established objectives through NSRDI for the period 2014-2020.

USE OF INTERNATIONAL SCIENTIFIC DATA BASES WEB OF SCIENCE AND SCOPUS FOR SCIENTIFIC RESEARCH AT AGRICULTURAL HIGHER EDUCATION INSTITUTIONS

USE OF INTERNATIONAL SCIENTIFIC DATA BASES WEB OF SCIENCE AND SCOPUS FOR SCIENTIFIC RESEARCH AT AGRICULTURAL HIGHER EDUCATION INSTITUTIONS

Application of artificial intelligence in the field of geotechnics and engineering education

The work is devoted to the theoretical and legal study of the features of the application of artificial intelligence in geotechnics and engineering education. The conceptual approaches to the definition of the concept of artificial intelligence, the problems of its use, and the features of legal regulation are considered. In this paper, for the first time, artificial intelligence in the geological industry was studied through the prism of engineering education, a logical correlation of the provisions on artificial intelligence in the field of engineering education, the practice of using artificial intelligence in geotechnics was traced. It is concluded that a strategically important task can be realized only through the formation of an institutional environment based on the principles of partnership of educational institutions and engineering business for the development of innovative research and educational programs focused on employer requests to increase the level of specialized education in the application of artificial intelligence in the field of geotechnics.

<i>CYP2D6</i> Genotype-Guided Tamoxifen Dosing in Hormone Receptor-Positive Metastatic Breast Cancer (TARGET-1): A Randomized, Open-Label, Phase 2 Study

Background: In patients taking tamoxifen, the CYP2D6 genotype causes different exposure of active metabolite endoxifen. There is a high frequency of CYP2D6 decreased-function variant in Asian populations. Therefore, we prospectively evaluated whetherCYP2D6 genotype-guided tamoxifen dosing in patients with hormone receptor-positive metastatic breast cancer could have an impact in the clinical outcome. Methods: In this randomized, open-label, multicenter, phase 2 study, patients who needed first-line tamoxifen therapy were enrolled in Japan. Based on individual CYP2D6 genotype, patients heterozygous (wt/V) or homozygous (V/V) for variant alleles of decreased or no-function were randomly assigned (1:1) to tamoxifen at increased dose (40 mg daily, ID arm) or regular dose (20 mg daily, RD arm), and patients homozygous for wild-type alleles (wt/wt) received tamoxifen at 20 mg daily. The primary endpoint was progression-free survival (PFS) rate at 6-month. The secondary endpoints included PFS and correlation of (Z)-endoxifen concentration with clinical outcomes. Findings: Between December 2012 and July 2016, 186 patients were enrolled. Of 184 evaluable patients, 136 carried wt/V or V/V (ID arm, 70; RD arm, 66), and 48 carried wt/wt. PFS rates at 6-month were not significantly different between ID and RD arms (67·6% vs. 66·7%). The serum trough concentrations of (Z)-endoxifen in the ID arm were significantly higher than those in the RD arm (median, 89·2 nM vs. 51·1 nM; P < 0.0001) and were also higher compared with wt/wt patients (72·0 nM; P = 0·0452). No significant difference in (Z)-endoxifen concentrations was observed between patients with and without progression at 6-month (p = 0·43). Interpretation: In patients with CYP2D6 variant alleles, increasing tamoxifen dosing did not achieve higher PFS rate at 6-month. The CYP2D6 genotype solely cannot explain individual variability in the efficacy of tamoxifen. Clinical Trial Number: This study is registered with UMIN Clinical Trials Registry, number UMI09155. Funding Statement: This study was supported by grants from the Project for Development of Innovative Research on Cancer Therapeutics and from the Tailor-made Medical Treatment Program (BioBank Japan Project) funded by the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the AMED under Grant Number 17ck0106191h0003). Declaration of Interests: YF reports grants from the Japan Agency for Medical Research and Development (AMED). MK reports grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT). KT reports grants from AstraZeneca and Daiichi-Sankyo outside the submitted work. CKI, MT, and YT report personal fees from AstraZeneca outside the submitted work. TT and JT report grants and personal fees from Daiichi-Sankyo outside the submitted work. SS reports grants and personal fees from AstraZeneca, and personal fees from Daiichi-Sankyo outside the submitted work. TY and YF report personal fees from AstraZeneca and Daiichi-Sankyo outside the submitted work. NTU reports grants from Daiichi-Sankyo outside the submitted work. YT reports personal fees from Meiji Seika Pharma outside the submitted work. All other authors declare no competing interests. Ethics Approval Statement: We obtained written informed consent from each patient before participation. The trial followed the ethical principles of the Declaration of Helsinki and Japanese Ethical Guidelines and Clinical Research. This study protocol and any amendments thereof were approved by an independent Ethics Committee or Institutional Review Board at each institution.

Retracted: The Moroccan university and the programs of training in entrepreneurship: state of play, issues and critical look

The new reform of the Moroccan Higher Education (Law 01/00) has positioned the university as a leading actor in the socioeconomic development. Indeed, the university contributes to the entrepreneurship awareness and preparation of students to be able to pass to entrepreneurial action. A contribution can be through entrepreneurship training and the development of innovation and scientific research. Through this study, we will try to present in the first place, the main training programs for students in Moroccan universities, based on the analysis of the objectives and teaching approaches of each program. Then we will pay, secondly, a critical look at these programs.

Sensor technologies for the energy-water nexus – A review

In this paper, a comprehensive review of the sensing technologies, capabilities and requirements in the energy-water nexus is presented considering the interdependence of variables in the interconnected energy and water sectors. Conventional sensor technologies that are used in the energy and water sectors of today are critiqued from the perspectives of accuracy, weight, volume, power consumption, commercial availability, data storage capabilities, ability to communicate with established electronic interfaces and portability of operation for remote sensing. The impacts of having multiple parameters, indefinite variables and/or unresolved dependencies in sensing energy usage for water applications and in sensing water usage for energy applications have been investigated. The paper also reviews innovative research developments on sensor technologies in the energy-water nexus that are based on bio-technology, nano-technology and wireless networks and that could possibly resolve sensing challenges such as the interdependencies of variables in the energy-water nexus. In addition, a network of sensor technologies that are most appropriate to each sector in the nexus is presented to improve the operational efficiency of the energy-water nexus.