Research Efforts Research Articles

Exploring the Roles, Functions, and Work Experiences of Nurse Scientists in the Veterans Health Administration.

The aim of this project was to describe nurse scientists' roles, functions, and work experiences in the Veterans Health Administration (VHA). Nurse scientists play a critical role in shaping the culture of clinical inquiry and closing the gap between knowledge and practice. A cross-sectional survey was used to collect information on sociodemographics, workload, research, clinical practice, education, and time/effort. Data were examined using descriptive statistics and χ2 analyses. One hundred forty-four nurse scientists completed the survey. These nurse scientists serve dynamic and critical roles in conducting research, implementing evidence-based practice, and reforming policy. Research effort was limited due to workload and infrastructure constraints. Better research infrastructure was associated with higher research productivity and funding. This survey highlights the needs and challenges nurse scientists experience in conducting research and advancing VHA's mission. Given the national shortage of PhD-prepared nurses, long-term strategies are needed to attract, hire, and retain nurse scientists in healthcare systems.

Financial medicine: A multi-dimensional concept moving towards contextually specific working definitions for use in the South African prehospital setting

IntroductionThe phenomenon that has been described as Financial Medicine has been occurring within the South African Healthcare sector for at least the last decade. Despite the ongoing effect of this phenomenon, there is no organised body of knowledge or formulated working definitions to guide knowledge sharing and theorisation within this research focus area. The practice of Financial Medicine exerts a deleterious effect on the South African prehospital healthcare system, and represents an area in dire need of focused research efforts. Establishing appropriate working definitions and associated taxonomy is an important first step in supporting further research efforts into this aspect of South African prehospital healthcare systems. MethodsA qualitative research methodology following a constructivist grounded theory design was used. Participants voluntarily consented to be enrolled into one-on-one in-depth interviews, and were selected using purposive and theoretical sampling techniques. Data was subjected to validated coding procedures and analysed using the constant comparative analysis approach, analytical diagramming, and supported by researcher theoretical sensitivity. ResultsA working definition for Financial Medicine is provided. Six new terms are introduced, with associated working definitions, namely Financial Medicine Practices, Treatment-based profiteering, Cost-of-care-aversion, Personal-gain-at-patient-expense, Money-racketeering-in-healthcare, and Impoverishing-healthcare-earning. ConclusionThe working definitions and suggested taxonomy presented in this article are the first step in formally conceptualising and theorising the phenomenon of Financial Medicine, in order to support further research and collaboration in this space.

A Comprehensive Review of the Benzimidazole Scaffold as a Potential Nucleus for Anti-Ulcer Activity

Abstract: The benzimidazole scaffold is a promising nucleus for developing novel therapeutic agents for ulcer treatment. Its unique chemical structure provides desirable pharmacological properties, such as excellent bioavailability, metabolic stability, and low toxicity, making it an attractive candidate for ulcer treatment. Several benzimidazole derivatives have shown significant anti-ulcer activity in preclinical and clinical studies, acting through multiple pathways, including inhibition of gastric acid secretion, suppression of gastric inflammation, and promotion of mucosal protection. Some benzimidazole derivatives have also demonstrated anti-Helicobacter pylori activity, suggesting their potential for eradicating bacteria associated with ulcer formation. However, challenges such as poor solubility and limited selectivity remain. Various approaches, such as prodrug design and formulation optimization, have been explored to overcome these issues and improve the therapeutic profile of benzimidazole derivatives. Overall, the benzimidazole scaffold holds great promise as a nucleus for developing novel anti-ulcer agents. Further research and optimization efforts are needed to harness its full potential and translate it into effective treatments for ulcers. With continued advancements in medicinal chemistry and drug design, benzimidazole-based compounds may offer new therapeutic options for patients suffering from ulcers and related gastrointestinal disorders. Hence, this review highlights the knowledge about benzimidazole scaffold, the mechanism of ulcer formation, and various benzimidazole derivatives with anti-ulcer activity, which can be further studied in pre-clinical and clinical trials.

Harnessing the power of blockchain technology to support decision-making in e-commerce processes

Technology, such as blockchain, has emerged as a promising solution for addressing the challenges of e-commerce decision-making. In this study, we explore the potential benefits of integrating blockchain technology into e-commerce and its role in supporting decision-making in e-commerce. We also examine blockchain’s benefits in terms of enhanced security, transparency, and efficiency for e-commerce platforms. Furthermore, the study discusses the challenges of implementing blockchain for e-commerce, including scalability, integration, regulatory frameworks, user experience, privacy, interoperability, and sustainability. By analyzing these challenges, the study provides valuable insights for future research and development efforts to facilitate a seamless adoption of blockchain technology in e-commerce decisions. Blockchain technology holds the potential to transform an e-commerce ecosystem by overcoming these challenges and unlocking its transformative potential.

Meeting Report for the 2023 International Scientific Conference on Complex Lymphatic Anomalies

Objectives: Complex lymphatic anomalies (CLAs) are rare diseases with variable clinical manifestations caused by the abnormal development of lymphatic vessels. The Lymphatic Malformation Institute (LMI), Lymphangiomatosis & Gorham’s Disease Alliance (LGDA), and LGD Alliance Europe sponsored an international conference on CLAs so leaders in the field could discuss recent advances in research on CLAs. Methods: The conference occurred in Dallas, Texas, between September 29th and September 30th, 2023. The event had 22 distinguished speakers and 38 attendees. Additional researchers, clinicians, and patients attended the conference virtually. Results: In this article, we summarize the key takeaways from the meeting. The conference emphasized the crucial role of the patient voice in guiding research, and attendees heard stories from patients and parents of children with CLAs. The conference covered topics such as the genetic causes of CLAs, preclinical models, clinical advances, new technologies for CLA research, lymphatic imaging, and patient-centered research. Videos of all the presentations can be found on the LGDA website. Conclusions: The meeting revealed that while progress has been made, many challenges still exist surrounding the diagnosis and treatment of CLAs. Sustained research efforts are necessary to fill the gaps in knowledge and improve the care and quality of life of CLA patients.

Moving Immunotherapy Into the Treatment of Resectable Non-Small Cell Lung Cancer.

Clinical investigation of immune checkpoint inhibitors (ICIs) has expanded from indications in metastatic non-small cell lung cancer (NSCLC) to add to the treatment of early-stage or resectable NSCLC. Although completed randomized trials supported the approvals of some ICIs as perioperative therapies (ie, adjuvant, neoadjuvant, or neoadjuvant followed by adjuvant), ongoing trials are evaluating other anti-PD-(L)1 antibodies for similar indications, or in combination with stereotactic body radiotherapy (SBRT). The incorporation of immunotherapy brings potential to improve outcomes of patients with resectable NSCLC, but these advances have also increased the complexity of the treatment landscape and created important knowledge gaps. This article reviews the current standards for local therapies in NSCLC, describes the clinical trials exploring the combination of ICIs to SBRT, and explains the recent approvals of ICIs as perioperative therapies. A discussion follows to highlight three important areas of uncertainty: (1) the contribution of ICIs given in each treatment phase (neoadjuvant and adjuvant) to the overall effect of neoadjuvant chemoimmunotherapy followed by adjuvant ICIs; (2) the selection of regimens to serve as comparators in future randomized trials of perioperative therapies; and (3) the role of pathologic complete response as an intermediate end point and aid for selection of patients for adjuvant therapy. Moving forward, stakeholders will need to engage in concerted research efforts to address the relevant clinical questions regarding the optimal management of resectable NSCLC.

Innovations in science education: A bibliometric exploration of trends and future directions

This article carries out a bibliometric research review to present the evolving landscape of innovations in science education. The study acknowledges the dynamism of the contemporary educational practices and uses the bibliometric analyses for identification of trends, assessment of impacts of scholarly outputs, and mapping the future directions in the field of science education innovation. Starting with a review of the standard bibliometric indicators, e.g., citation analysis and co-authorship, the review lays down the theoretical basis for the understanding of the scientific impact of the innovations in science education. The analysis, moreover, consists of identifying thematic foci and emerging topics through keyword mapping, which together present a holistic picture of the intellectual map of the field. The review points to seminal works and trends, demonstrating the nature of interdisciplinarity in research in science education innovation. By the analysis of collaborative networks and research hotspots the research not only demonstrates the present status of the field, but also predicts its future directions, which could help researchers and educators at the same time. Also, as a retrospective tool, the article explores the general relevance of bibliometric insights for educators, administrators, and other researchers. It highlights the application of bibliometrics in evidence-based decision-making, curricula design and international collaboration, because it is common knowledge that it can trigger the great revolution in innovative science education. This bibliometric review generates useful outcomes, which are beneficial to academic discussions and provide guidelines for future research efforts as a key reference for researchers who would like to have a deep, general overview of the innovations in science education.

Feature selection techniques for microarray dataset: a review

For many researchers working on feature selection techniques, finding an appropriate feature from the microarray dataset has turned into a bottleneck. Researchers often create feature selection approaches and algorithms with the goal of improving accuracy in microarray datasets. The main goal of this study is to present a variety of contemporary feature selection techniques, such as Filter, Wrapper, and Embedded methods proposed for microarray datasets to work on multi-class classification problems and different approaches to enhance the performance of learning algorithms, to address the imbalance issue in the data set, and to support research efforts on microarray dataset. This study is based on Critical Review Questions (CRQ) constructed using feature election methods described in the review methodology and applied to a microarray dataset. We discussed the analysed findings and future prospects of feature selection strategies for multi-class classification issues using microarray datasets, as well as prospective ways to speed up computing environment

Analysis of Manifold and its Application

Manifold learning is a field of study in machine learning and statistics that is closely associated with dimensionality reduction algorithmic techniques is gaining popularity these days. There are two types of manifold learning approaches: linear and nonlinear. Principal component analysis (PCA) and multidimensional scaling (MDS) are two examples of linear techniques that have long been staples in the statistician's arsenal for evaluating multivariate data. Nonlinear manifold learning, which encompasses diffusion maps, Laplacian Eigenmaps, Hessian Eigenmaps, Isomap, and local linear embedding, has seen a surge in research effort recently. A few of these methods are nonlinear extensions of linear approaches. A nearest search, the definition of distances or affinities between points (a crucial component of these methods' effectiveness), and an Eigen problem for embedding high-dimensional points into a lower dimensional space make up the algorithmic process of the majority of these techniques. The strengths and weaknesses of the new method are briefly reviewed in this article. In the field of computer graphics, we utilize a particular manifold learning method was first presented in statistics and machine learning to create a global, Spectral-based shape descriptor.

Exploring the Capacity of Agricultural Residue as a Sustainable Energy Resource to Enhance Madagascar's Energy Security

Biomass represents a significant and emerging energy source. This study assessed and compared the potentiality of agricultural waste to be converted into renewable energy sources in Madagascar. A model for estimating biomass energy potential was exploited, and relevant data about crop and animal populations was extracted from the Food and Agriculture Organization's statistics database (FAOSTAT). Five types of crop residue were considered, including rice, sugarcane, corn, beans, and cassava, and four animal species like cattle, pigs, chickens, and sheep. Diverse conversion actors; the Ratio Product (RPR), Surplus Availability Factor (SAF), and Low Heating Value (LHV), were obtained from various literature sources and were used to assess the potential energy from agricultural residue. Subsequently, all collected data were meticulously compiled utilizing Microsoft Excel and subjected to comprehensive descriptive analysis facilitated by the OriginLab software, enabling advanced data manipulation and visualization. Our findings reveal that Madagascar generates approximately 27.78 million tons of agricultural residue annually, with the potential to produce 181.91 petajoules (PJ) of energy, primarily derived from crop residue, estimated at 128.75 PJ annually, which constitutes 70.8% of the total energy potential. With appropriate technology, the estimated energy potential could fulfill 48.7% of total energy consumption in Madagascar. Consequently, future investigations should prioritize research efforts to identify and implement optimal conversion technologies.

Recent advances and challenges of the green ZnO-based composites biosynthesized using plant extracts for water treatment.

Recently, there has been a notable rise in the prevalence of persistent pollutants in the environment, posing a significant hazard due to their toxicity and enduring nature. Conventional wastewater treatment methods employed in treatment plants rarely address these persistent pollutants adequately. Meanwhile, the concept of green synthesis has garnered considerable attention, owing to its environmentally friendly approach that utilizes fewer toxic chemicals and solvents. The utilization of materials derived from sustainable sources presents a promising avenue for solving pressing environmental concerns. Among the various sources of biological agents, plants stand out for their accessibility, eco-friendliness, and rich reserves of phytochemicals suitable for material synthesis. The plant extract-mediated synthesis of zinc oxide nanoparticles (ZnONPs) has emerged as a promising solution for applications in wastewater treatment. Thorough investigations into the factors influencing the properties of these green ZnONPs are essential to establish a detailed and reliable synthesis process. Major weaknesses inherent in ZnONPs can be addressed by changing the optical, magnetic, and interface properties through doping with various semiconductor materials. Consequently, research efforts to mitigate water pollution are being driven by both the future prospects and limitations of ZnO-based composites. This review underscores the recent advancements of plant extract-mediated ZnONP composites for water treatment.

A framework and process for community-engaged, mixed-methods cancer needs assessments.

Community health needs assessments are required for most state and local public health agencies and non-profit hospitals. Typically based on community health improvement planning models, these assessments encompass overall community health and multiple diseases to inform program planning. National Cancer Institute (NCI)-designated Cancer Centers and community-based cancer-focused programs share the goal of reducing cancer burden in the catchment areas they serve. However, to date, no published models exist to guide cancer-specific needs assessments for a determined geographic area that can inform both public health and research initiatives. The purpose of this article is to outline a cancer needs assessment (CNA) framework and community-engaged, mixed-methods process, along with a case study of how we applied it in Kentucky. We convened a steering committee of key organizational partners to provide input throughout the process. We developed a conceptual framework of multi-level determinants affecting cancer-related outcomes. We incorporated both quantitative and qualitative data gathered through a variety of means, including a novel application of group concept mapping to guide definition of priorities. The resulting CNA has helped guide strategic planning and priorities for Kentucky's Cancer Action Plan, Markey Cancer Center, state agencies, and community-based organizations. This framework and process can be used collaboratively by cancer center Community Outreach and Engagement offices, public health agencies, oncology programs, and community partners to plan impactful cancer control programs and research in their catchment areas. Universities can also use them to inform the planning of community engagement and health equity research efforts.

Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies

Triple-negative breast cancer (TNBC) poses significant challenges in oncology due to its aggressive nature, limited treatment options, and poorer prognosis compared to other breast cancer subtypes. This comprehensive review examines the therapeutic and diagnostic landscape of TNBC, highlighting current strategies, emerging therapies, and future directions. Targeted therapies, including PARP inhibitors, immune checkpoint inhibitors, and EGFR inhibitors, hold promise for personalized treatment approaches. Challenges in identifying novel targets, exploring combination therapies, and developing predictive biomarkers must be addressed to optimize targeted therapy in TNBC. Immunotherapy represents a transformative approach in TNBC treatment, yet challenges in biomarker identification, combination strategies, and overcoming resistance persist. Precision medicine approaches offer opportunities for tailored treatment based on tumor biology, but integration of multi-omics data and clinical implementation present challenges requiring innovative solutions. Despite these challenges, ongoing research efforts and collaborative initiatives offer hope for improving outcomes and advancing treatment strategies in TNBC. By addressing the complexities of TNBC biology and developing effective therapeutic approaches, personalized treatments can be realized, ultimately enhancing the lives of TNBC patients. Continued research, clinical trials, and interdisciplinary collaborations are essential for realizing this vision and making meaningful progress in TNBC management.

Charting a new course: ungraying the fleet and comprehensively supporting fishing livelihoods and communities

This article provides perspectives on the graying of the fleet and research efforts to understand it in Alaska fisheries, discusses recent abrupt multifaceted challenges faced by Alaskan fishermen, and compares divergent public perceptions and support programs for farmers and fishermen in the United States. Equity concerns have seen a resurgence in academic and policy realms and the graying of the fleet is now a common example of distributional inequity, yet despite in-depth research attention on the issue, few substantive programmatic modifications have been made to address it in Alaska. Aging trends in United States fisheries have typically been framed as one of changing aspirational preferences. Research suggests coastal youth do desire and highly value fishing careers, but structural and financial barriers limit opportunities for new generations. The precarity of the fishing industry was highlighted in 2023 with sudden global seafood market instability, rising interest rates and operating costs, destabilized geopolitical tensions, and hastening climate change impacts. This recent industry turmoil disproportionately impacts those on the margins and adds an additional layer of complexity to addressing graying of the fleet trends. Unlike in fisheries, there are numerous federal programs to support young farmers and the agricultural industry. This paper calls for proactive and comprehensive measures to stabilize and support fishing communities and the viability of next generation pathways amidst recent fishing industry market turmoil and longer term inequities in fishery governance.

Beyond Survival: A Scoping Review on the Sexual Health of Sexual and Gender Minority Women Following Curative Cancer Treatment.

To explore the existing research on sexual health experiences of sexual and gender minority women (SGMW) post-curative cancer treatment. This scoping review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Four articles that focused on sexual health experiences of SGMW post-curative cancer treatment were included. Four themes were identified: (a) sexual function; (b) sexual orientation and gender identity, including disclosure and health care provider reactions; (c) relationship dynamics, such as relationship status and the quality of romantic relationships; and (d) body image. The findings underscore substantial challenges faced by SGMW cancer survivors in achieving optimal sexual well-being, impacting their access to post-treatment care. This study advocates for more expansive research efforts involving diverse participant cohorts, extending beyond breast cancer, to gain deeper insights into these critical issues.

Recent Advances in Carbon Nitride Supported Single‐Atom Catalysts: Synthesis, Characterization, and Applications for CO2 Photoreduction

AbstractPhotoreduction of CO2 into value‐added chemicals and fuels is a promising green technology for solar‐to‐chemical conversion. Owing to the atomic utilization, unique metal‐support interaction, and unsaturated coordination active sites, single‐atom catalysts (SACs) have been attracting great attention in achieving high activity and selectivity of CO2 photoreduction reactions. On the other hand, carbon nitride (C3N4) with abundant periodically unsaturated coordination of nitrogen atoms can serve as an excellent support for anchoring metal single atoms. In this context, extensive research efforts have been paid in C3N4‐based SACs for CO2 photoreduction in recent years. In this review, we report the recent advances in C3N4 supported SACs for CO2 photoreduction. We start from the introduction of synthetic strategies of various C3N4 supported metal SACs. Secondly, the main advanced characterization techniques and calculation methods for identifying the single‐atoms and their coordination environments of C3N4‐based SACs are summarized. Thirdly, some state‐of‐the‐art works on the rational design of C3N4‐based SACs and their applications in CO2 photoreduction are introduced. Lastly, we briefly summarize the main challenges and propose important perspectives of C3N4‐based SACs in CO2 photoreduction. This review is expected to provide some useful guidelines for the development of efficient and stable C3N4‐based SACs for CO2 photoreduction.

Severe Avian Influenza A H5N1 Clade 2.3.4.4b Virus Infection in a Human with Continuation of SARS-CoV-2 Viral RNAs

Background. Since 2020, global attention has heightened towards epidemics caused by avian influenza A H5N1 virus of clade 2.3.4.4b in birds and mammals. This study presents the epidemiological history, clinical manifestations, and prognosis of a unique case infected with avian influenza A H5N1 clade 2.3.4.4b, along with the continuation of SARS-CoV-2 viral RNAs, in Eastern China. Methods. We collected and analysed the patient’s clinical, epidemiological, and virological data. Both sputum and bronchoalveolar lavage fluid (BALF) samples were subjected to real-time RT-PCR to test for respiratory pathogens of interests, including SARS-CoV-2 and influenza virus. Influenza virus isolation and propagation were performed on embryonated eggs. Serological tests were used to determine the presence of SARS-CoV-2 antibodies. Phylogenetic analysis was constructed to explore viral evolution and origin of A/H5N1 virus. Results. A 53-year-old female farmer with chronic bronchiectasis was hospitalized with severe pneumonia. Real-time RT-PCR revealed the presence of avian influenza A H5N1 and SARS-CoV-2 in BALF and sputum samples. Sequence analyses classified the human isolate as clade 2.3.4.4b of avian influenza A H5N1. The amino acid motif GlnSerGly at residues 226–228 of the haemagglutinin protein indicated avian-like receptor binding preference. Epidemiological investigation established that the patient had exposure to sick or dead poultry 3 days before illness onset, while no cases of human-to-human H5N1 virus transmission were identified in 31 close contacts. Conclusion. We presented that the clade 2.3.4.4b H5N1 avian influenza virus has the potential to cross-infect humans with serious symptoms, especially in individuals already affected by COVID-19. It is indeed crucial to closely monitor the virus’s evolution in both avian populations and humans. Continued research and surveillance efforts are vital to monitor any potential changes in the virus, as well as to inform public health policies and interventions.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

A Comprehensive Review of Life Cycle Cost Assessment of Recycled Materials in Asphalt Pavements Rehabilitation

This paper provides a comprehensive review of the use of life cycle cost assessment (LCCA) and life cycle assessment (LCA) methods for evaluating the sustainability and costs of using recycled materials in asphalt pavement rehabilitation projects. The review begins with an introduction to pavement rehabilitation strategies and the importance of choosing techniques based on thorough engineering and economic analyses. It then explores the different types of recycled materials that can be utilized, including reclaimed asphalt pavement, recycled concrete aggregate, and recycled asphalt shingles, discussing the key characteristics and properties of these materials based on previous laboratory studies. The review also examines the various rehabilitation methods that employ recycled content, such as cold in-place recycling, hot in-place recycling, and full-depth reclamation, providing a detailed breakdown of the construction, maintenance, and rehabilitation costs considered in LCCA and analyzing the environmental benefits of recycled material usage through a review of LCA techniques and criteria like carbon footprint reduction, impacts on air and water quality, and considerations of technological factors. Software tools for conducting LCA are compared and challenges to advancing the adoption of recycled materials are reviewed along with directions for future research efforts. The unique contribution of this work is its holistic assessment of LCCA and LCA methodologies to inform the sustainable and cost-effective deployment of recycled materials in asphalt pavement rehabilitation, a topic of growing importance for transportation infrastructure management. In summary, this current work provides a valuable review of how LCCA and LCA methodologies can assess the sustainability and costs of employing recycled content in asphalt pavement rehabilitation projects.

Studying the Pathogenic Effect of New Nucleotide Changes in the Promoter Region of the TERT Gene in Patients with Glioblastoma Brain Tumor

Introduction: Brain tumors are considered to be one of the most dangerous types of cancer, despite decades of research and treatment efforts. The activation of the telomerase enzyme is a critical factor in the immortality of these cells. Mutations in the promoter region of the TERT gene, particularly in the promoter hot spots, can influence the binding of activating transcription factors and inhibit the binding of negative regulatory factors of the TERT gene, ultimately regulating the gene's expression. This study aimed to identify and investigate the mutations of the TERT gene promoter region in glioblastoma, a malignant brain tumor, using bioinformatics. Methods: A study was conducted using the case-control method where 35 patients with glioblastoma multiform brain tumor were examined along with 40 people who were examined as control samples. In this research, the Touchdown PCR technique and direct DNA sequencing were used to detect mutations in the promoter region of the TERT gene in patients with glioblastoma. Furthermore, bioinformatic analyses were conducted to investigate the pathogenic effect of nucleotide changes in this gene region. Results: In the core region of the TERT gene promoter, three-point mutations were identified (c.*146C>T، c.*144C>G and c.*143G>C). Two of these mutations were novel and have been observed for the first time in glioblastoma multiform. The remaining mutation was located in the promoter core's hot spot of the gene. This mutation was known as c.*146C>T. Conclusion: In this research, the harmful impact of TERT promoter region mutations as a biomarker for glioblastoma was examined. These findings suggest that mutations in regulatory regions, as well as coding sequences, could be significant contributory factors in the process of carcinogenesis.