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Incivility, a growing challenge in higher education institutions, interferes with and disrupts the learning process. This study examined faculty members' experiences of students' incivilities in institutions of higher education in Afghanistan. A survey questionnaire was used to collect data from 289 faculty members who were teaching in various higher education institutions across Afghanistan. Descriptive and inferential statistics and thematic analysis were used to analyze the data. The findings showed that faculty members experienced varying degrees of a wide range of incivilities in and outside the classroom, including conversing loudly in the class, interruption, and harassment. They also experienced a variety of incivilities related to assessment and grading. A small number of them experienced more serious forms of incivilities including beating, stabbing, and death threats. The findings also revealed that there were not significant differences between participants' experiences of student incivility by their gender, but there were significant differences between faculty members' experience by their level of education and years of teaching experience. The study recommends faculty members and higher education institutions take practical measures to address incivilities inside and outside the classroom in order to create a safe learning environment for faculty members and students.

In the short history of smart contracts, substantial losses have occurred due to unaccounted vulnerabilities in the smart contracts loaded onto the blockchain. Vulnerabilities in smart contracts threaten the viability and confidence of blockchain technology. Machine and deep learning architectures have been increasingly proposed to assist with writing smart contracts and detecting vulnerabilities to minimize the risks of successful attacks. This paper presents the findings of deep learning vulnerability detection in smart contracts collated from selected research papers and provides an overview of the vulnerability detection architecture. This paper assessed each component of the overall architecture, individually and in combinations, to infer potential relationships in increasing detection rates in smart contract vulnerability detection tools. This study found that the area of detecting smart contract vulnerabilities is gravitating towards deep learning models, with a particular focus on combining neural networks in serial or parallel to achieve high detection results. Feature extraction of syntax and semantic information greatly determines the detection results of a model, which suggests a strong relationship between the use of source code and neural networks. Despite this relationship, given the inaccessibility and unavailability of smart contract source code, future work should focus on efficiently extracting features and context from opcodes, which are more readily available on the blockchain. Based on these findings, the study offers an in-depth discussion of the matters arising, open issues, and key aspects such as bytecode and opcode in smart contracts, failure of attention mechanisms, the rationale of hybrid models, dataset challenges, computational complexity in a large-scale blockchain environment, optimization strategies, Expunge and interdisciplinary approaches to smart contract vulnerability detection. These discussions enhance the practical relevance of the paper, highlighting the opportunities for scaling deep learning models for real-world blockchain applications.

Background: Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19). Methods: This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021. Adults hospitalized with severe COVID-19 (diagnosed ≤2 weeks before screening) were randomized 1:1 to receive oral placebo or SIR1-365 100 mg three times daily for ≤14 consecutive days, with standard-of-care. The primary objective was to evaluate SIR1-365 safety and tolerability. Secondary objectives included an assessment of SIR1-365 efficacy. Descriptive statistics were used to summarize safety. The study was not powered for efficacy testing. Relevant inferential statistical tests were used to aid interpretation of differences in clinical efficacy. Results: Forty-five patients were randomized, 42 were treated. Eighteen patients experienced treatment-emergent adverse events (TEAEs) and 7 patients were ≥ grade 3. Fewer SIR1-365-treated vs. placebo-treated patients experienced TEAEs (30.4% vs. 57.9%) and serious TEAEs (13.0% vs. 26.3%) within 28 days of the first dose. There were no serious treatment-related TEAEs or deaths. Compare to placebo, SIR1-365 significantly increased arterial oxygenation from baseline to day 7 (least-squares mean change [standard error]: 109.4 [26.4] vs. -24.2 [23.6]; P=0.0095), significantly reduced hospitalization duration after treatment (mean±standard deviation: [4.7±3.7] days vs. [8.6±5.6] days; P=0.0145) and respiratory failure incidence (8.3% vs. 38.1%; two-sided P=0.0291) during the study, and numerically shortened the time to clinical improvement in World Health Organization ordinal scale (median: 5.0 days vs. 9.0 days, P=0.0766). Conclusions: SIR1-365 was well tolerated and demonstrated a trend toward quicker recovery than placebo in hospitalized patients with severe COVID-19.Trial Registration ClinicalTrials.gov number: NCT04622332

Abstract The land use transition plays an important role for terrestrial environmental services, which had a mixed impact of positive and negative on the groundwater and terrestrial water resource. The health of ecological systems and groundwater depends on the mapping and management of land use. The Ganga basin is one of the most densely populated and agriculture-intensive river systems in the South Asia and the world. The multi-temporal spatial database includes land use (ESA-CCI), satellite-based gravity anomaly (GRACE/GRACE-FO), and well log (CGWB) adopted in this study for assessment of the impact of land use transition on groundwater depth, groundwater drought, and terrestrial water storage. The methodology includes the computation of land use transition, trend magnitude by Sen’s slope, Innovative Trend Analysis (ITA) for graphical visualization, clustering techniques employ to identify pattern & structure, and finally space-time transformation was assessed based on multi-dimensional scaling using Alternating Least Squares Scaling (ALSCAL). The land use transition over two decades shows an increase in forest (2.23%), wetland (2.2%), settlement (208.4%), bare area (3.18%), water (5.18%), and a decrease in agriculture (-1.16%), grassland (-4.5%), & vegetation (-2.8%). The non-parametric climatological trend of groundwater depth, drought, and terrestrial water loss was maximally observed during the post-monsoon season in the Ganga basin. The seasonal climatological trend statistics shows that, the upper Ganga and northern (left) of the Ganga basin shows an alarming rate of groundwater depletion, with increased in the severity of groundwater drought in near future with the loss in terrestrial water storage. The ITA shows the monotonic decreasing trend depicting loss of groundwater and terrestrial water resources. Bi-dimensional regression, ALSCAL shows that the model is efficient based on the input data having stress value and RSQ (proportion of variance) of 0.09 and 0.97 with excellent linear fit. The impact assessment of land use transition was obtained in low dimensional space showing that the conversion from sparse vegetation, agriculture, grassland, wetland and forest to settlement has the maximum impact on groundwater and TWSA loss, although the persistent settlement area is also responsible. The results are extremely useful for the policymakers, scientists, concern Govt. section, and local communities must work together to manage groundwater sustainably. Water resource management can also help to lessen the effects of climate change on groundwater and terrestrial water loss by focusing on the environmental, economic, social, and institutional dimensions of UN-SDG.

Background and objectives: Of the ever-increasing non-communicable diseases (NCDs), cardiometabolic morbidity and mortality constitute the major health burden world-wide. Several cross-sectional studies revealed the increasing prevalence of NCDs irrespective of cast, culture, ethnicity, socio-economic growth and geopolitical environment. Recent cross-sectional studies revealed South Asians are the most susceptible to cardiovascular diseases (CVD). Few cohort studies addressed cardiometabolic morbidity and related risks, particularly in the rural population.This study was carried out to find out the prevalence of metabolic syndrome (MetSyn) and its changes overtime in a rural cohort of Bangladesh. Methods: The study used baseline data of a study conducted in 2011- 2013 on prevalence of coronary artery disease among a cohort living in 16 villages. During 2021-2023, the baseline data collected in 2011-2013 were retrieved and the participants were searched and categorized into a) physically present, b) died and c) missing. Those who were present were requested to volunteer for re-investigations. Briefly the investigations included interviewing on social, family, personal and clinical history, anthropometry, blood pressure measurement, blood biochemistry and electrocardiography (ECG). Results: A total of 3928 people participated in baseline study of 2011- 2013. Of them, 1075 could be tracked by village and household. Of them, 953 were found alive. Of the 953 available participants, 651 (254 men and 397 women) volunteered to participate in 2021-2023 study. Compared to 2011-2013 baseline, the prevalence of MetSyn and type 2 diabetes mellitus (T2DM) increased to 31.6% and 5.2% from 7.5% and 0.8% respectively in 2021-2023. Similarly, compared to baseline, the prevalence of obesity and hypertension also showed significant increase overtime. Estimated incidence of MetSyn was 260.8 per 1000 population, which was more profound in women than men (W: M= 300.3:200.8). Conclusions: The study revealed a significant increase of obesity, hypertension, diabetes and metabolic syndrome within a decade indicating an emerging health burden among the rural people of Bangladesh. January 2025; Vol. 19(1):003. DOI:https://doi.org/10.55010/imcjms.19.003 *Correspondence: MA Sayeed, Department of Community Medicine, Ibrahim Medical College, 1/A Ibrahim Sarani, Segunbagicha, Dhaka 1000, Bangladesh. Email: sayeed950@gmail.com; © 2025 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License(CC BY 4.0).

The main objective of the present study was to investigate undergraduate students' perception of smartphone addiction and its impact on themselves and their academic performance in Takhar province. 1321 participants from Takhar University and 4 private universities responded to an online survey questionnaire. The researchers used SPSS Version 26.0 to analyze the data. The findings revealed that undergraduate students were highly addicted to smartphones, and the excessive use of smartphones had an adverse effect on the academic performance of students. The results showed that there were statistically significant differences in smartphone addiction by the respondents' gender, access to social media and daily hours of smartphone usage. Moreover, a strong negative correlation was found between smartphone addiction and its impact on students' academic performance. The findings of the study are crucial to higher education leaders because they may help them develop policies to reduce the excessive and inappropriate use of smartphones in classrooms.

The healthcare supply chain encounters difficulties with transparency, efficiency, and security, which have an impact on patient safety and the quality of treatment concerning the items involved. The use of blockchain technology, which has intrinsic characteristics such as confidentiality, transparency, and traceability, offers a possible resolution to tackle these problems. This paper aims to comprehensively review the adoption of blockchain technology in healthcare supply chain management, particularly in response to the challenges posed by the COVID-19 pandemic. It investigates the significance of efficient and transparent healthcare supply chains, focusing on blockchain's application in vaccine distribution, Personal Protective Equipment (PPE), drugs, medical devices and blood products. The analysis critically evaluates research papers proposing innovative blockchain-powered solutions, discussing their benefits, challenges, and the need for further research. Findings highlight blockchain's potential in enhancing vaccine traceability, preventing counterfeit vaccines, and ensuring equitable access to immunization. It also outlines blockchain's role in real-time tracking of PPE shipments, secure distribution of medical devices, managing blood products, and combating counterfeit drugs. The paper also emphasizes the prevalence of consortium-based and public blockchain implementations and the importance of smart contracts while advocating for addressing scalability and technological challenges. This review offers a critical assessment of blockchain's potential in fortifying healthcare supply chains during crises, underscoring the need for ongoing research and development to overcome implementation limitations. Doi: 10.28991/HIJ-2024-05-04-019 Full Text: PDF

This study critically examines the concept of eco-spirituality, exploring its intersection with spirituality and environmental concerns and its profound implications for contemporary society. The objective of this study is to systematically analyze the expanding literature on eco-spirituality and environmental behavior, highlighting key influencers, seminal works, and emerging trends to provide a comprehensive overview and suggest future research directions. Drawing from a synthesis of 138 studies, the research sheds light on the transformative role of eco-spirituality in facilitating the transition towards environmental sustainability. A comprehensive analysis of scholarly publications reveals notable trends in eco-spirituality research. Despite emerging in the early 1990s, scholarly attention remained limited until the 21st century, witnessing a significant surge post-2019, indicating growing recognition within academia. Publications predominantly originated from the United States, the United Kingdom, Canada, India, and Switzerland, reflecting global interest and engagement across diverse cultural landscapes. Key journals, including Religions, emerged as prominent platforms, underscoring the interdisciplinary nature of eco-spirituality research. The study underscores the interdisciplinary nature of eco-spirituality, transcending disciplinary boundaries to incorporate insights from environmental studies, theology, psychology, sociology, anthropology, and philosophy. The synthesis of 138 studies reveals eco-spirituality's pivotal role in promoting environmental sustainability, with notable trends in scholarly interest and global distribution of publications. Scholarly attention to eco-spirituality surged post-2019, resulting in 74 published articles, with 2021 marking the peak at 15 articles and the United States contributing 38 publications. This study underscores the interdisciplinary nature of eco-spirituality research and its potential to bridge theoretical insights with practical applications, urging inclusive approaches and further exploration beyond academia. This study contributes to meaningful societal change through environmental education, community engagement, and policy development. While acknowledging limitations such as database constraints and language bias, the study offers a nuanced understanding of the multifaceted impacts of eco-spirituality on individuals and communities. It prompts further inquiry into the dynamic relationship between spirituality, environmental ethics, and sustainable development. The study also underscores the significance of eco-spirituality as a catalyst for environmental consciousness and sustainable action. The innovation of the study is that it has revealed eco-spirituality's transformative role in promoting environmental sustainability and bridging interdisciplinary insights with practical applications. By synthesizing existing evidence and highlighting avenues for future research, it contributes to ongoing discussions on the role of spirituality in shaping human interactions with the natural world, ultimately empowering individuals and communities to enact meaningful change and promote a more harmonious relationship with the planet.

Abstract Background Left ventricular assist device (LVAD) recipients report symptom improvement but find adjusting to life with the LVAD challenging. These challenges are unique, and existing patient‐reported outcome measures (PROMs) do not reflect their experiences. This study aimed to develop a culturally relevant quality of life PROM for use with LVAD recipients in future research, design evolutions and clinical practice. Methods A three‐stage mixed‐methods approach was used to develop a PROM: stage 1 included group concept mapping (GCM); stage 2 semi‐structured qualitative interviews were conducted with 11 LVAD recipients and 10 clinicians, and a questionnaire was developed using a conceptual framework; and stage 3 used exploratory psychometric analysis of the PROM data using Rasch measurement theory. This paper presents stages 2 and 3. Results The conceptual framework consisted of four key concepts, including general health, life with the LVAD, equipment and clothing and emotional impact. Statements from interviews and GCM were used to create items for the LVAD quality of life (LVAD‐QoL). Cognitive interviews tested face validity and participant comprehension. Forty‐nine participants were recruited from three UK transplant centres. PROM data were collected and analysed using Rasch analysis. Four items displayed misfit; dependency between item sets was the biggest issue (57/485 pairwise differences). After restructuring and dealing with item misfit, the LVAD‐QoL conformed to the Rasch model, supporting the psychometric properties and quality of the LVAD‐QoL. Conclusions Using a mixed‐methods approach ensured the development of a robust and psychometrically sound tool for research, design evolution and clinical practice with LVAD recipients.

Background: India is home to 14 million survivors of human trafficking, with most being trafficked for sexual exploitation. Trafficking constitutes crimes that violate the rights of survivors, and despite its psychological consequences, there is little evidence-based guidance to meet the needs of these individuals. Aim: The current study aimed to examine the outcome of narrative exposure therapy (KIDNET) among adolescent survivors of sex trafficking in improving trauma-related symptoms, along with psychological distress, dissociation, depression, and anxiety. Methods: A pre-post study design was used with 20 adolescent female survivors of trafficking aged 13 to 17 years, with ten participants in the KIDNET group and ten participants in a waitlist control group. Trafficking Victim Identification Tool and Standard Progressive Matrices were administered as screening measures. The Clinician-Administered PTSD Scale for Children and Adolescents, Kessler’s Psychological Distress Scale, Shutdown Dissociation Scale, Patient Health Questionnaire, and Beck Anxiety Inventory were administered as outcome measures. Fourteen sessions of KIDNET were conducted for the clinical group, while sessions were conducted for the control group post delivery of intervention for the clinical group. Results: Findings suggest an overall improvement in the severity of trauma-related symptoms in the KIDNET group, with significant improvement in psychological distress, depression, and anxiety. Conclusion: Results indicate that KIDNET may be a promising and acceptable treatment for adolescent survivors of sex trafficking, and this intervention module may be safely delivered in further randomised controlled trials to ensure that the holistic needs of this vulnerable group are appropriately addressed.

The functional and structural features of microbial load in soil are influenced by the presence of insecticides. This study examined the impact of two organophosphorus insecticides, dimethoate and parathion on the microbial load of soil. The colony count of fungi, actinomycetes, bacteria, and nitrogen fixing bacteria was reduced after insecticides application at 7 and 14 days, but at 28 days the colony count began to increase. The growth of two white rot fungi including Pleurotus sajor-caju and Phanerochaete chrysosporium was affected by parathion, which was reflected by a decrease in colony radius to 1.85±0.05 and 0.75±0.06 cm, respectively, and by dimethoate, reflected by a decrease in colony radius to 3.33±0.12 and 1.85±0.05 cm, respectively at 40 mg/L compared to colony radius at control 7.90±0.12 and 7.50±0.06 cm, respectively. The applied low concentration (10 mg/L) encouraged P. sajor-caju and P. chrysosporium to remove up to 87.7% and 81.8% of dimethoate, respectively, and 69.20 and 68.30% of parathion, respectively compared with the decomposition at high dose (40 mg/L) at 28 days. The presence of insecticides induced the production of ligninolytic enzymes lignin peroxidase, laccase, and manganase peroxidase.

Issues such as inequality, collapsed state capacity, and spatial exclusion, particularly in South Africa, affect economic development negatively. This study aims to assess the relationship between inclusive growth and economic development and employs the autoregressive distributed lag (ARDL) approach in annual time series data ranging from 1990-2022. Data were obtained from the South African Reserve Bank and the World Bank. The findings of this study reveal that, in the long run, a percentage change in gross fixed capital formation will positively affect economic development by 44%. Similarly, in the short term, a percentage change in gross fixed capital formation will affect economic development by 33%. Lastly, trade openness has an insignificant impact in the short run and long run. In addition, the error correction term coefficient is negative and significant. The implication is that the economic development model has a speed of adjustment of about 11% to reach equilibrium. This study improves the understanding of the link between economic development and inclusive growth, contributing to academia and policymaking for more equitable and sustainable economic development. This study explores the impact of inclusive growth on South Africa's economic development, offering recommendations for policy formulation to promote equitable benefit distribution across various social segments

Sustainable construction technologies have recently acquired more attention in the construction industry. However, their adoption has faced different barriers. This study aimed to identify and rank the impediments to sustainable construction technologies in developing countries. A systematic literature review (SLR) method was employed. After screening using inclusion/exclusion criteria, 22 publications were selected for further analysis. Afterwards, ten major impediments were explored with a thematic analysis method. Therefore, the finding of this study reveals that developing countries could enhance the implementation of sustainable technologies and alleviate environmental consequences, boost economic growth, and promote inclusive development by designing and implementing corresponding strategies that could tackle the identified impediments.

Lignocellulosic biomass is contemplated to be an inexpensive and copious feedstock that can be used for numerous industrial applications. However, lignin forms the lignin sheath and provides a physical barrier to enzymatic hydrolysis. In addition, lignin physically blocks cellulase, preventing it from being combined with the substrate in a process known as non-productive binding. Therefore, the depletion of lignin is a crucial method for obtaining fermentable sugars from the lignocellulosic biomass. Different white-rot fungi secrete different sets of lignin-mineralizing enzymes and each fungus secretes one or more of the three enzymes essential for lignin degradation. Among efficient redox enzymes, versatile peroxidase is extensively studied for its ability to degrade aromatics without the need for a mediator or polyvalent catalytic site. However, the presence of versatile peroxidase in F. spp. has not been studied. This study was planned with the objective of screening and comparing the production of versatile peroxidase enzymes from F. spp. and a standard culture of Pleurotus ostreatus MTCC-142. These fungal strains were first screened on solid media containing tannic acid, malachite green, or bromocresol green. The potency index for the tannic acid, malachite green, and bromocresol green on the 16th day of incubation was reported to be 1.28, 1.07, 1.09, and 1.10, respectively. Versatile peroxidase production patterns were investigated under solid state fermentation conditions for a period of 25 days at different temperatures ranging from 10 to 35 °C. The highest versatile peroxidase activity (592 UL−1) in F. sp. was observed at 30 °C after the 7th day of incubation. The molecular confirmation showed the presence of the vp gene in F. sp. along with Pleurotus ostreatus MTCC-142. The results determined that F. sp. possesses a versatile peroxidase enzyme and is able to degrade lignin efficiently, and thus it could be utilized as an alternative to other ligninolytic enzyme-producing fungi.

The study examined faculty's research productivity, their perceptions of influence of factors and policy directives on their research productivity. It also examined the correlation between faculty's gender, level of education, years of teaching experience and their research productivity. A questionnaire was used to collect data from 162 faculty members at four public higher education institutions (HEIs). Descriptive and multiple regression analysis were used to analyze the data. The results showed that faculty's research productivity was significantly low. For instance, 76% of the participants reported publishing 468 articles in national journals while 71% of them reported publishing 253 works in international journals since they started working as faculty. Around 82% of the participants did not publish any articles in international journals indexed in Web of Science, Scopus, or PubMed. Furthermore, 54% of the participants did not publish any articles in international journals over the one-year period (2022). The participants believed that various factors influenced their publications in international journals including lack of access to funding, journal articles and data analysis tools. Furthermore, Faculty perceived policy mandates to have varying degrees of influence on their decisions to publish their works on different venues including international and high-impact journals. The study revealed a significant correlation between participants' characteristics, particularly their years of teaching experience and their research productivity, which highlights the significance of tailoring policies and interventions to diverse needs of various faculty groups to enhance their research productivity.

This study explored the relationship between principals' transformational leadership and teachers' emotional intelligence. The authors collected data from 395 teachers at Takhar high schools and statistically analyzed them using SPSS. The study found that there was a statistically significant positive correlation between principals' transformational leadership and teachers' emotional intelligence. It also revealed that there were statistically significant differences in teachers' level of emotional intelligence by their demographic factors: gender, education, work experience, and school location. The finding of the study will lead to the improvement of policies to advance principals' transformational leadership and teachers' emotional intelligence.

The growing significance of social media in research demands new ethical standards and practices. Although a substantial body of literature on social media ethics exists, studies on the ethics of conducting research using social media are scarce. The emergence of new evidence sources, like social media, requires innovative methods and renewed consideration of research ethics. Therefore, we pose the following question: What are the defining characteristics of ethics papers on social media research? Following a modified version of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, we analyzed 34 publications based on ten variables: author gender, publication year, region, academic discipline, type, design, methodology, social media platform in focus, positionality statement, and ethical issues. Our findings suggest contemporary social media research ethics primarily reflects the ethical ideals of the Global North, with limited representation from the Global South. Women authors have published more papers than men authors. Previous studies have prioritized ethical concerns such as privacy, informed consent, and anonymity while overlooking researchers' risks and the ethics of social media sites. We particularly emphasized the lack of researchers' positionality statements in research. Our findings will pave the way to understanding social media ethics better, especially with the rapid growth of social media research in global scholarship.

Background: Over the past few decades, the gonadotropin-releasing hormone agonist goserelin has been evaluated in ovarian function suppression (OFS) with adjuvant endocrine therapy and ovarian function preservation (OFP) during chemotherapy. Objective: The goal of this systematic literature review was to assess the efficacy of goserelin in OFS and OFP in combination with endocrine therapies and chemotherapy, respectively, in pre- and perimenopausal women with early-stage breast cancer. Design: This study is a systematic review. Data sources and methods: The literature search was conducted using PubMed. Prospective clinical studies evaluating the efficacy of goserelin in OFS or OFP in pre- or perimenopausal breast cancer were identified by four reviewers working in teams of two. Results: Twenty-nine studies were included in this systematic review. The addition of goserelin as OFS to adjuvant endocrine therapy generally resulted in significant benefits in disease-free survival. Studies have shown better OFP results among women 40 years or younger compared with older patients. Chemotherapy in association with goserelin for OFP resulted in a higher recovery rate of menses within 6–24 months, a shorter time for menstrual recovery, and significantly higher pregnancy rates when compared with cytotoxic therapy without goserelin. Hormonal recovery with higher anti-Müllerian hormone and estradiol levels, and lower follicle-stimulating hormone and luteinizing hormone levels occurred more frequently among women who received goserelin during chemotherapy as compared with those receiving cytotoxic therapy alone. The benefits of goserelin in OFP were more substantial among women 40 years or younger than in older patients. Conclusion: The findings of this systematic review highlight the benefits of adding goserelin to endocrine therapies for OFS and chemotherapy for OFP in early-stage breast cancer. Additionally, scientific data supporting OFS (including goserelin) in combination with newer agents such as cyclin-dependent kinase 4 and 6 inhibitors and bone-modifying agents are emerging.