Research Challenges Research Articles

Academic education in environmental chemistry in Europe-addressing future challenges in research and regulation.

Following the tradition of the 16th International Conference on Chemistry and the Environment (ICCE) in Oslo, Norway (2017), and the subsequent 17th ICCE in Thessaloniki, Greece (2019), a follow-up session on higher education in environmental science was organized at the 18th ICCE in Venice, Italy (June 2023). The aim of the session was to stimulate the exchange of experiences and knowledge on graduate and post-graduate level educational programmes, including their development, prioritization, and implementation. The session discussed the integration of practical training activities, which included the integration of environmental chemistry in various bachelor's and master's programmes. The aim was to demonstrate the versatility of environmental chemistry as an interdisciplinary scientific discipline that allows the development of essential green skills for developing sustainable strategies for the environmental experts of tomorrow. Furthermore, during the session, a survey was conducted among the conference participants to collect attitudes and reflections from the audience on the education of environmental chemistry (and related fields).

Ion-Ion Selectivity of Synthetic Membranes with Confined Nanostructures.

Synthetic membranes featuring confined nanostructures have emerged as a prominent category of leading materials that can selectively separate target ions from complex water matrices. Further advancements in these membranes will pressingly rely on the ability to elucidate the inherent connection between transmembrane ion permeation behaviors and the ion-selective nanostructures. In this review, we first abstract state-of-the-art nanostructures with a diversity of spatial confinements in current synthetic membranes. Next, the underlying mechanisms that govern ion permeation under the spatial nanoconfinement are analyzed. We then proceed to assess ion-selective membrane materials with a focus on their structural merits that allow ultrahigh selectivity for a wide range of monovalent and divalent ions. We also highlight recent advancements in experimental methodologies for measuring ionic permeability, hydration numbers, and energy barriers to transport. We conclude by putting forth the future research prospects and challenges in the realm of high-performance ion-selective membranes.

New systemic treatment options for advanced cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors (ICIs) have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high (MSI-H) population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.

Unveiling emerging interdisciplinary research challenges in the highly threatened sclerophyllous forests of central Chile

BackgroundThe potential ecosystem collapse of forests in Mediterranean-type ecosystems (MTEs) by unprecedented droughts is worrisome due to the impacts on its exceptional biodiversity and human well-being. However, research integrating the impacts of global change drivers, forest resilience and the challenges facing human-nature relationships is still scarce.Methods and resultsUsing the central Chile megadrought and recently massive forest browning event as a model scenario, we identified, through a scientific literature review and an interdisciplinary scientific workshop, the research priorities and questions to address for MTEs in a context of global change. Our results highlighted knowledge gaps that need to be covered, particularly in social and environmental sciences, with an emphasis on soil science. Research priorities must focus on (1) the understanding of interactive effects of global and local anthropogenic drivers on MTEs and (2) the evaluation of the potential impacts of MTEs collapse on human well-being and ecosystem functioning.ConclusionsWe highlight the need for a collaborative approach involving scientists, landowners, managers/administrators, and policymakers to apply adaptive forest management against the current socio-environmental challenges under a global change context.

The Ethnographic Interview: An Interdisciplinary Guide for Developing an Ethnographic Disposition in Health Research.

Interviews are central to the health ethnographers' toolkit. In this article, we offer a critical engagement with methodological literature coupled with reflective examples from our own research, in order to articulate the value of the ethnographic interview in health research. We contribute to literature on ethnographic interviews in two ways: by decoupling ethnographic interviews from the necessity of accompanying participant observation, and by outlining an ethnographic disposition towards interviewing. We define the seven key epistemic dispositions underpinning the ethnographic interview. These are humility, a readiness to revise core assumptions about a research topic, attentiveness to context, relationality, openness to complexity, an attention to ethnographic writing, and a consideration of the politics and history of the method. The strength of an epistemic understanding of the ethnographic interview is that it offers flexibility for developing a diverse array of interview techniques responsive to the needs of different research contexts and challenges. Ethnographic interviews, we show, contribute to the study of health through a richly explorative, responsive, contextualised, and reflexive approach.

Role of Curcuma longae Rhizoma in medical applications: research challenges and opportunities

Curcuma longae Rhizoma, commonly known as turmeric, is extensively utilized not only in Traditional Chinese Medicine (TCM) but also across various traditional medicine systems worldwide. It is renowned for its effectiveness in removing blood stasis, promoting blood circulation, and relieving pain. The primary bioactive metabolites of Curcuma longae Rhizoma—curcumin, β-elemene, curcumol, and curdione—have been extensively studied for their pharmacological benefits. These include anti-tumor properties, cardiovascular and cerebrovascular protection, immune regulation, liver protection, and their roles as analgesics, anti-inflammatories, antivirals, antibacterials, hypoglycemics, and antioxidants. This review critically examines the extensive body of research regarding the mechanisms of action of Curcuma longae Rhizoma, which engages multiple molecular targets and signaling pathways such as NF-κB, MAPKs, and PI3K/AKT. The core objective of this review is to assess how the main active metabolites of turmeric interact with these molecular systems to achieve therapeutic outcomes in various clinical settings. Furthermore, we discuss the challenges related to the bioavailability of these metabolites and explore potential methods to enhance their therapeutic effects. By doing so, this review aims to provide fresh insights into the optimization of Curcuma longae Rhizoma for broader clinical applications.

Artificial Neural Network Application in Construction and the Built Environment: A Bibliometric Analysis

Over the past decade, there has been a dramatic increase in the use of various technologies in the Architecture, Engineering, and Construction sector. Artificial intelligence has played a significant role throughout the different phases of the design and construction process. A growing body of literature recognizes the importance of artificial neural network applications in numerous areas of the construction industry and the built environment, presenting a need to explore the main research themes, attributes, benefits, and challenges. A three-step extensive research method was utilized by conducting a bibliometric search of English language articles and conducting quantitative and qualitative analyses. The bibliometric analysis aimed to identify the current research directions and gaps forming future research areas. The scientometric analysis of keywords revealed diverse areas within the construction industry linked to ANNs. The qualitative analysis of the selected literature revealed that energy management in buildings and construction cost predictions were the leading research topics in the study area. These findings recommend directions for further research in the field, for example, broadening the application ranges of ANNs in the current Construction 4.0 technologies, such as robotics, 3D printing, digital twins, and VR applications.

Optimizing the Influence of Fly Ash as an Anti-Sagging Additive in Highly Deviated Geothermal Well Drilling Fluids Using Surface Response Method

Weighting materials such as barite and ilmenite are crucial for controlling fluid density during deep or ultra-deep drilling operations. However, sagging poses significant challenges, especially in highly deviated high-pressure and high-temperature (HP/HT) wells. This leads to inadequate well control, wellbore instability, and variations in hydrostatic pressure in extended-reach wells. Given the challenges of experimental research, reliable prediction models are imperative for evaluating the interaction between the ratio of anti-sagging additives, temperature, and wellbore inclination on sag factor (SF). This research presents statistical-based empirical models for predicting the SF at various wellbore inclinations (0°, 30°, 45°, 60°, 70°, 80°, and 90°) and assessing the influence of fly ash on the SF. The regression equations, developed using the Response Surface Methodology in Minitab 18 software, show high reliability, with R2 values approaching unity. Contour and surface response plots provide a clear understanding of the variable interactions. The analysis reveals that sagging is most severe at 60° to 65° inclination. At 400 °F and 60° inclination, adding 4 lb/bbl of fly ash reduces sagging in barite and ilmenite-densified fluid by 63.9% and 63.1%, respectively. Model validation shows high accuracy, with percentage errors below 3%. This study offers valuable insights for optimizing drilling fluid formulations in HP/HT well environments.

Advances in Research on the Impact of Diet on Human Gut Microbiota Composition and Metabolites

As research into gut microbiota deepens, the impact of diet on the composition of human gut microbiota and their metabolites has gradually become a focal point. This paper reviews recent advancements in understanding how diet influences gut microbiota composition and their metabolic products. Firstly, it introduces the basic concepts of gut microbiota and their role in maintaining health. Next, it explores the effects of different types of diets (such as high-fiber, high-fat, high-protein, and refined sugar diets) on the composition of gut microbiota and analyzes their impact on microbiota diversity. Then, it discusses the influence of diet on gut microbiota metabolites, including short-chain fatty acids, amino acid metabolites, and gases. Further, it examines the practical applications of dietary interventions on health, especially their potential impact on chronic diseases. Finally, the paper summarizes the limitations of current research and suggests future research directions and challenges. Overall, the influence of diet on gut microbiota and their metabolites holds profound health significance and provides important evidence for formulating scientific dietary recommendations.

Multimodal multiobjective differential evolution algorithm based on enhanced decision space search

Multimodal multiobjective optimization problems (MMOPs) have attracted extensive research interest. These problems are characterized by the presence of multiple equivalent optimal solutions in the decision space, all corresponding to the same optimal values in the objective space. However, effectively finding a high-quality and evenly distributed Pareto sets (PSs) remains a challenge for researchers. This paper introduces a multimodal multiobjective differential evolution algorithm based on enhanced decision space search (MMODE_EDSS). By adopting two types of strategies to enhance the decision space search capability, the algorithm generates multiple high-quality non-dominated solutions. In the early stages of evolution, neighborhood information is used to enhance search capabilities, while in the later stages, data interpolation methods following clustering are employed for searching. Moreover, to improve the overall population distribution, an environmental selection mechanism based on dual-space crowding distance is adopted. The effectiveness of the proposed algorithm, MMODE_EDSS, is evaluated by comparing it with eight state-of-the-art multimodal multiobjective evolutionary algorithms (MMOEAs). Experimental results confirm the significant advantages of MMODE_EDSS.

The role of social determinants of health in mental health: An examination of the moderating effects of race, ethnicity, and gender on depression through the all of us research program dataset

We investigate how select identity characteristics moderate the role of several SDoH domains on major depressive disorder (MDD). Our study considers an analytical sample of 86,954 participants from the NIH-funded All of Us (AoU) Research Program in the USA. Our independent variables and moderators come from survey responses and our outcome is an EHR diagnostic code. We include race/ethnicity and gender/sexual identity to moderate the role of food insecurity, discrimination, neighborhood social cohesion, and loneliness in assessing risk for MDD diagnosis. We examine those moderating effects based on connections seen in the literature. Our findings illustrate the complexity of where and how people live their lives can have significant differential impact on MDD. Women (AOR = 1.60, 95% CI = [1.53, 1.68]) and LGBTQIA2+ individuals (AOR = 1.71, 95% CI = [1.60, 1.84]) exhibit a significantly higher likelihood of MDD diagnosis compared to cisgender heterosexual males. Our study also reveals a lower likelihood of MDD diagnosis among Asian/Asian American individuals (AOR = 0.41, 95% CI = [0.35, 0.49]) compared to White individuals. Our results align with previous research indicating that higher levels of food insecurity (AOR = 1.30, 95% CI = [1.17, 1.44]) and loneliness (AOR = 6.89, 95% CI = [6.04, 7.87]) are strongly associated with an increased likelihood of MDD. However, we also find that social cohesion (AOR = 0.92, 95% CI = [0.81, 1.05]) does not emerge as a significant predictor, contradicting some literature emphasizing the protective role of neighborhood cohesion. Similarly, our finding that transience (AOR = 0.95, 95% CI = [0.92, 0.98]) reduces the likelihood of MDD diagnosis contradicts conventional wisdom and warrants further exploration. Our study provides a reminder of the substantial challenges for research focused on marginalized community segments and that deliberate sampling plans are needed to examine those most marginalized and underserved.

A telo‐centric approach to rethink grand challenges: Digital wellbeing as an example

AbstractHow can grand challenge‐related issues be studied while comprehensively addressing contemporary needs? The literature on grand challenges has been growing, with an abundance of phenomena on which research is undertaken in a piecemeal fashion, without sufficiently offering integrated insights. In this debate essay, we challenge the proposal offered in Seelos, C., Mair, J. & Traeger, C. (2023) The future of grand challenges research: retiring a hopeful concept and endorsing research principles, International Journal of Management Reviews, 25(2), 251–269 on retiring the grand challenge concept. Instead, we advocate for revitalizing, not retiring, so that grand challenges research can be adapted with the ultimate human purpose of achieving wellbeing. We propose that the solution lies in taking a telo‐centric approach to navigate the intersections between various grand challenge issues, offering a novel lens to delve into the ultimate end of human endeavours and to ensure the continued relevance of the grant challenge concept. We exemplify the application of this telo‐centric approach through the prism of digital wellbeing, demonstrating how it can pave the way for innovative theoretical frameworks, rigorous empirical investigations and practical developments. We conclude by forwarding future directions for research, practice and policy.

Substance Delivery across the Blood-Brain Barrier or the Blood-Retinal Barrier Using Organic Cation Transporter Novel Type 2 (OCTN2)

The membrane impermeability of a drug poses a significant challenge in drug research and development, preventing effective drug delivery to the target site. Specifically, the blood-brain barrier (BBB) presents a formidable obstacle to the delivery of drugs targeting the central nervous system (CNS) into the brain, whereas the blood-retinal barrier (BRB) presents a tremendous obstacle to the delivery of drugs targeting the ocular diseases into the eyes. The development of drugs for Alzheimer’s or Parkinson’s disease targeting the CNS and for diabetic retinopathy and age-related macular degeneration targeting the eyes remains an unmet medical need for patients. Transporters play a crucial physiological role in maintaining homeostasis in metabolic organs. Various types of solute carrier (SLC) transporters are expressed in the capillary endothelial cells of the BBB, facilitating the delivery of nutrients from the blood flow to the brain. Therefore, carrier-mediated transport across the BBB can be achieved using SLC transporters present in capillary endothelial cells. It is well-known that CNS drugs typically incorporate N-containing groups, indicating that cation transporters facilitate their transport into the brain. In fact, carrier-mediated transport across the BBB can be accomplished using glucose transporter type 1 (Glut1) as a glucose transporter, L-type amino acid transporter 1 (LAT1) as a large neutral amino acid transporter, and H+/cation antiporter as a cation transporter. Surprisingly, although organic cation transporter novel type 2 (OCTN2) is expressed in the capillary endothelial cells, there has been limited investigation into OCTN2-mediated substance delivery into the brain across the BBB. Furthermore, it is suggested that OCTN2 is expressed at the BRB. In this prospective review, I present the advantages and possibilities of substance delivery into the brain across the BBB or into the eyes across the BRB, mediated by OCTN2 via carrier-mediated transport or receptor-mediated transcytosis.

Progress in Additive Manufacturing of Magnesium Alloys: A Review

Magnesium alloys, renowned for their lightweight yet high-strength characteristics, with exceptional mechanical properties, are highly coveted for numerous applications. The emergence of magnesium alloy additive manufacturing (Mg AM) has further propelled their popularity, offering advantages such as unparalleled precision, swift production rates, enhanced design freedom, and optimized material utilization. This technology holds immense potential in fabricating intricate geometries, complex internal structures, and performance-tailored microstructures, enabling groundbreaking applications. In this paper, we delve into the core processes and pivotal influencing factors of the current techniques employed in Mg AM, including selective laser melting (SLM), electron beam melting (EBM), wire arc additive manufacturing (WAAM), binder jetting (BJ), friction stir additive manufacturing (FSAM), and indirect additive manufacturing (I-AM). Laser powder bed fusion (LPBF) excels in precision but is limited by a low deposition rate and chamber size; WAAM offers cost-effectiveness, high efficiency, and scalability for large components; BJ enables precise material deposition for customized parts with environmental benefits; FSAM achieves fine grain sizes, low defect rates, and potential for precision products; and I-AM boasts a high build rate and industrial adaptability but is less studied recently. This paper attempts to explore the possibilities and challenges for future research in AM. Among them, two issues are how to mix different AM applications and how to use the integration of Internet technologies, machine learning, and process modeling with AM, which are innovative breakthroughs in AM.

Restoring Mental Balance through Mantras as a Transcendental Communication: a Systematic Review of Insights from the Atharva Veda

In the pursuit of mental balance and psychological well-being, the ancient practice of mantra recitation, as detailed in the Atharva Veda, offers a compelling intersection of traditional wisdom and modern science. This systematic literature review synthesizes insights from 30 rigorously selected journals and reports, revealing the profound impact of mantra-based practices on mental health. By examining the vibrational and cognitive effects of mantras, this study bridges historical perspectives with contemporary empirical findings, highlighting their potential in addressing mental imbalances such as anxiety, depression, and stress. Our review delineates key research areas, including the neurophysiological mechanisms through which mantras influence brainwave patterns and emotional states. It explores the practical applications of mantra practices across diverse settings—from clinical environments to daily life—and assesses their effectiveness in enhancing mental clarity, resilience, and emotional stability. The review also identifies novel research opportunities and challenges, such as the need for more robust scientific validation and the exploration of mantra practices in diverse cultural contexts. This paper not only provides a comprehensive overview of current knowledge but also proposes a practical framework for integrating mantra recitation into mental health interventions. By combining ancient spiritual practices with modern scientific methodologies, this study aims to pave the way for innovative therapeutic approaches and enrich our understanding of holistic mental health solutions.

Network Security Challenges and Countermeasures for Software-Defined Smart Grids: A Survey

The rise of grid modernization has been prompted by the escalating demand for power, the deteriorating state of infrastructure, and the growing concern regarding the reliability of electric utilities. The smart grid encompasses recent advancements in electronics, technology, telecommunications, and computer capabilities. Smart grid telecommunication frameworks provide bidirectional communication to facilitate grid operations. Software-defined networking (SDN) is a proposed approach for monitoring and regulating telecommunication networks, which allows for enhanced visibility, control, and security in smart grid systems. Nevertheless, the integration of telecommunications infrastructure exposes smart grid networks to potential cyberattacks. Unauthorized individuals may exploit unauthorized access to intercept communications, introduce fabricated data into system measurements, overwhelm communication channels with false data packets, or attack centralized controllers to disable network control. An ongoing, thorough examination of cyber attacks and protection strategies for smart grid networks is essential due to the ever-changing nature of these threats. Previous surveys on smart grid security lack modern methodologies and, to the best of our knowledge, most, if not all, focus on only one sort of attack or protection. This survey examines the most recent security techniques, simultaneous multi-pronged cyber attacks, and defense utilities in order to address the challenges of future SDN smart grid research. The objective is to identify future research requirements, describe the existing security challenges, and highlight emerging threats and their potential impact on the deployment of software-defined smart grid (SD-SG).

Recent Progress in Synthesis of Alkyl Fluorinated Compounds with Multiple Contiguous Stereogenic Centers

Organic fluorides are widely used in pharmaceuticals, agrochemicals, material sciences, and other fields due to the special physical and chemical properties of fluorine atoms. The synthesis of alkyl fluorinated compounds bearing multiple contiguous stereogenic centers is the most challenging research area in synthetic chemistry and has received extensive attention from chemists. This review summarized the important research progress in the field over the past decade, including asymmetric electrophilic fluorination and the asymmetric elaboration of fluorinated substrates (such as allylic alkylation reactions, hydrofunctionalization reactions, Mannich addition reactions, Michael addition reactions, aldol addition reactions, and miscellaneous reactions), with an emphasis on synthetic methodologies, substrate scopes, and reaction mechanisms.

Biomimetic design and integrated biofabrication of an in-vitro three-dimensional multi-scale multilayer cortical model

The lack of accurate and reliable in vitro brain models hinders the development of brain science and research on brain diseases. Owing to the complex structure of the brain tissue and its highly nonlinear characteristics, the construction of brain-like in vitro tissue models remains one of the most challenging research fields in the construction of living tissues. This study proposes a multi-scale design of a brain-like model with a biomimetic cortical structure, which includes the macroscopic structural features of six layers of different cellular components, as well as micrometer-scale continuous fiber structures running through all layers vertically. To achieve integrated biomanufacturing of such a complex multi-scale brain-like model, a multi-material composite printing/culturing integrated bioprinting platform was developed in-house by integrating cell-laden hydrogel ink direct writing printing and electrohydrodynamic fiber 3D printing technologies. Through integrated bioprinting, multi-scale models with different cellular components and fiber structural parameters were prepared to study the effects of macroscopic and microscopic structural features on the directionality of neural cells, as well as the interaction between glial cells and neurons within the tissue model in a three-dimensional manner. The results revealed that the manufactured in vitro biomimetic cortical model achieved morphological connections between the layers of neurons, reflecting the structure and cellular morphology of the natural cortex. Micrometer-scale (10 μm) cross-layer fibers effectively guided and controlled the extension length and direction of the neurites of surrounding neural cells but had no significant effect on the migration of neurons. In contrast, glial cells significantly promoted the migration of surrounding PC12 cells towards the glial layer but did not contribute to the extension of neurites. This study provides a basis for the design and manufacture of accurate brain-like models for the functionalization of neuronal tissues.

Applying SPH-DEM theory to the motion of particulate solid-liquid flow on continuous screening

Challenges in current research on fine mesh wet screening (≥50 mesh) include representing fine wire boundaries, contentious porous media handling, and low computational efficiency. To address these challenges, this study employs an averaged SPH-DEM method for modeling solid-liquid flow on screen. It integrates the Symplectic scheme and quaternion method to enhance computational accuracy and scalability. The fine wire boundaries are discretized into spheres to facilitate hertz contact of DEM particles, and a novel screen aperture-fluid resistance model is introduced to calculate the resistance exerted on SPH particles by screen surface. The simulation results of dam break and periodic screening exhibit robust consistency with experimental data and other models, effectively validating the feasibility and accuracy of this methodology. Moreover, simulations of continuous screening using a 0.2 mm wire demonstrate that liquid enhances particle passage, further substantiating the practical viability of employing this model for simulating fine mesh wet screening.

Comparative analysis of FDA approvals by top 20 pharma companies (2014–2023)

This article addresses the research and development (R&D) productivity challenge of the pharmaceutical industry, focusing on United States Food and Drug Administration (FDA)-related new drug approvals of the top 20 pharmaceutical companies (2014-2023). We evaluated the degree of innovation in new drugs to determine the innovativeness of these leading companies. A key finding of our analysis is the decline in the number of new drugs approved by the FDA for these leading companies over the investigated time period. This trend suggests that some of the leading companies are losing ground in R&D innovation, raising concerns about their ability to sustain competitive advantage, ensure long-term market success, and maintain viable business models.