Unresolved Issues Research Articles

Explaining Public-Private Partnership Through the Prism of Political Economy

Unresolved issues and lack of models of national public private partnership (PPP) practices implementation predetermine limited use of the potential of various partnership forms between the state and private business, as well as lack of a generally accepted understanding of their role in shaping the future systemic integrity in the economy and society at the national level. We offer an interpretation from the perspective of the political economy of the phenomenon of partnership between the state and private companies in the organization of business, as well as factors that determine the diversity of organizational structures of partnership between the public and private sectors of the economy.

Nanostructure Engineering of Alloy-Based Anode Materials with Different Dimensions for Sodium/Potassium Storage

Sodium/potassium-ion batteries have drawn intensive investigation interest from researchers owing to their abundant element resources and significant cost advantages. Anode materials based on alloy reaction mechanisms have the prominent merits of a suitable reaction potential and high theoretical specific capacity and energy density. However, very large volumetric stresses and volume changes during the charge/discharge process and the resulting electrode structural cracking, deactivation and capacity fading seriously hinder their development. To date, a series of modification strategies have been proposed to tackle these challenges and achieve good electrochemical performance. Herein, we review the recent advances in the structural engineering of alloy-type anodes for sodium/potassium storage, mainly including phosphorus, tin, antimony, bismuth and related alloy materials, from the perspective of dimensional structure. Furthermore, some future research directions and unresolved issues are presented for the investigation of alloy-based anode materials. It is hoped that this review can serve as a guide for the future development and practical application of sodium/potassium-ion batteries.

Causal effects of gut microbiota on appendicitis: a two-sample Mendelian randomization study.

Previous research has posited a potential correlation between the gut microbiota and the onset of appendicitis; however, the precise causal connection between appendicitis and the gut microbiota remains an unresolved and contentious issue. In this investigation, we performed a Mendelian randomization (MR) analysis employing publicly accessible summary data extracted from genome-wide association studies (GWAS) to elucidate the potential causal nexus between the gut microbiota and the development of appendicitis. We initially identified instrumental variables (IVs) through a comprehensive array of screening methodologies, subsequently executing MR analyses using the Inverse Variance Weighted (IVW) technique as our primary approach, supplemented by several alternative methods such as MR Egger, weighted median, simple mode, and weighted mode. Additionally, we implemented a series of sensitivity analysis procedures, encompassing Cochran's Q test, MR-Egger intercept test, Mendelian Randomized Polymorphism Residual and Outlier (MR-PRESSO) test, and a leave-one-out test, to affirm the robustness and validity of our findings. Our investigation indicates that an elevated prevalence of Deltaproteobacteria, Christensenellaceae, Desulfovibrionaceae, Eubacterium ruminantium group, Lachnospiraceae NK4A136 group, Methanobrevibacter, Desulfovibrionales, and Euryarchaeota is inversely associated with the risk of appendicitis. Conversely, we observed a positive correlation between an increased abundance of Family XIII, Howardella, and Veillonella and the susceptibility to appendicitis. Sensitivity analyses have corroborated the robustness of these findings, and Mendelian randomization analyses provided no indications of reverse causality. Our Mendelian randomization (MR) analysis has unveiled potential advantageous or detrimental causal associations between the gut microbiota and the occurrence of appendicitis. This study offers novel theoretical and empirical insights into the understanding of appendicitis pathogenesis, along with its implications for preventive and therapeutic strategies.

Exploring the quality and safety issues in the coconut oil processing industry in Sri Lanka: A Review

Coconut oil is a significant dietary component in Sri Lanka and serves as the primary source of fat for Sri Lankans, primarily used for culinary purposes. This review focuses on the quality and safety concerns within the coconut oil processing industry of Sri Lanka. The study collected data through interviews with industry personnel, conducted field visits to both small-scale and large-scale operations, and analyzed existing research. Several factors impact the quality and safety of coconut oil products. Key issues include the increase in free fatty acid content, the production of aflatoxin in copra, phthalate contamination from packaging, and the contamination of coconut oil with polyaromatic hydrocarbons (PAH). These quality and safety concerns result from cross-contamination with metals and other chemicals during equipment use, a shortage of trained personnel, insufficient laboratory testing of oil quality parameters before market distribution, and inadequate surveillance of small and medium-sized oil mills by regulatory bodies. Additionally, the local market faces high levels of adulteration, where coconut oil is mixed with lower-quality oils, stored improperly, or is of overall poor quality. Issues related to coconut cultivation include a decline in yields due to inefficient land usage, reduced productivity, climate change impacts, pest infestations, diseases, and increased production costs. The adulteration problem arises from the supply-demand gap for coconut oil in Sri Lanka and the high cost of producing one litre of good-quality coconut oil. The Sri Lankan government and the Sri Lanka Standards Institution have introduced a product standard for coconut oil production, outlining key parameters for the final product. Nevertheless, the absence of a comprehensive process standard affects quality control throughout production. Small and medium-scale producers lack awareness of SLSI standards, leading to non-compliance, along with an absence of regular quality and safety checks. Consequently, stringent enforcement is necessary to address these challenges. While improvements have been made, unresolved issues remain; therefore, a quality assurance system for the coconut oil processing industry is an urgent requirement, especially for small and medium-scale oil production facilities, which are key suppliers to the local market.

The «Situational Nationalism»: A New Age of Nation and State Building in Montenegro?

For a long time, the political development of Montenegro has been determined by the peculiarities of historical development and the legacy of the former Yugoslavia. The divisions between groups of citizens identifying themselves as Serbs or Montenegrins, as well as contradictions between the state and the church, have determined the configuration of political forces. The fear of national minorities of Serbian national policy and the skillful maneuvering of M. Djukanovic contributed to their support for his regime. However, the problems of economic development, Djukanovic’s miscalculations regarding the Orthodox Church, as well as the lack of serious progress on the way to the EU, led to an increase in opposition sentiment and the defeat of Djukanovic in 2023 presidential elections, and the DPS in the parliamentary ones. Representatives of the younger generation of politicians came to power in Montenegro, relying to a lesser extent on traditional ethno-confessional divisions for Montenegro and aimed at solving economic problems and accelerating the process of the country’s accession to the EU. The article concludes that the end of a long period of dominance of one political force does not mean the end of the process of democratization. The unresolved issues of national and state building, the influence of external centers, the lack of effective institutions for the achievement of compromise and the protection of the interests of minorities make political life unstable and complicate the adoption of effective political decisions. Despite the victory of a new generation of politicians in the last national elections, the country’s traditional divisions still determine the choice of many voters and may again become relevant under the influence of market circumstances.

Comparison of the diagnostic accuracy of resting-state fMRI driven machine learning algorithms in the detection of mild cognitive impairment

Mild cognitive impairment (MCI) is a potential therapeutic window in the prevention of dementia; however, automated detection of early cognitive deterioration is an unresolved issue. The aim of our study was to compare various classification approaches to differentiate MCI patients from healthy controls, based on rs-fMRI data, using machine learning (ML) algorithms. Own dataset (from two centers) and ADNI database were used during the analysis. Three fMRI parameters were applied in five feature selection algorithms: local correlation, intrinsic connectivity, and fractional amplitude of low frequency fluctuations. Support vector machine (SVM) and random forest (RF) methods were applied for classification. We achieved a relatively wide range of 78–87% accuracy for the various feature selection methods with SVM combining the three rs-fMRI parameters. In the ADNI datasets case we can also see even 90% accuracy scores. RF provided a more harmonized result among the feature selection algorithms in both datasets with 80–84% accuracy for our local and 74–82% for the ADNI database. Despite some lower performance metrics of some algorithms, most of the results were positive and could be seen in two unrelated datasets which increase the validity of our methods. Our results highlight the potential of ML-based fMRI applications for automated diagnostic techniques to recognize MCI patients.

Machine learning models in trusted research environments - understanding operational risks.

Trusted research environments (TREs) provide secure access to very sensitive data for research. All TREs operate manual checks on outputs to ensure there is no residual disclosure risk. Machine learning (ML) models require very large amount of data; if this data is personal, the TRE is a well-established data management solution. However, ML models present novel disclosure risks, in both type and scale. As part of a series on ML disclosure risk in TREs, this article is intended to introduce TRE managers to the conceptual problems and work being done to address them. We demonstrate how ML models present a qualitatively different type of disclosure risk, compared to traditional statistical outputs. These arise from both the nature and the scale of ML modelling. We show that there are a large number of unresolved issues, although there is progress in many areas. We show where areas of uncertainty remain, as well as remedial responses available to TREs. At this stage, disclosure checking of ML models is very much a specialist activity. However, TRE managers need a basic awareness of the potential risk in ML models to enable them to make sensible decisions on using TREs for ML model development.

HERITAGE DECAY VISIBLE IN HBIM MODELS

Abstract. The research purpose aims to develop and analyse a workflow centred around decay representation within a selected BIM modelling environment. It involves conducting a comparative analysis based on accuracy criteria, process complexity, estimation of processing time, and the advantages and disadvantages of different methodologies explored. The objective of this research is to enhance the modelling process for building description by incorporating the representation of decay verified within the 3D model. The workflow proposed starts from a digital survey of a cultural heritage architecture and subsequent BIM modelling that generates significant interest within the scientific community not only from the advantages offered by the BIM process but also from the challenges encountered. One challenge relates to the complexity of modelling and unresolved interoperability issues between different NURBS and BIM modelers. Another challenge involves the time wasted in striving for a high degree of accuracy in existing models. Additionally, difficulties arise in uploading data encompassing historical information about the monument, previous renovations, material conditions, and overall state of the structure. Among these challenges, representing the decay state of an artifact within a model remains largely experimental and the paper will demonstrate the efficacy of its representation into a BIM model.

MENTORING AS A MODERN METHOD OF BUILDING THE PEDAGOGICAL PROCESS

The article is devoted to the study and analysis of mentoring as a modern method of constructing the pedagogical process. It includes the disclosure of the main content aspects inherent in the defi nition of this concept, reveals current trends, as well as shows its historical base. The article outlines the main theoretical aspects of the concept of mentoring and raises very topical issues of our time. In foreign and domestic literature, many teachers have considered the concept in their research. But priority and special attention have earned it in our time. Vari-ous mentoring models are created, the peculiarities of the process are revealed from diff erent sides and modern concepts of building productive activities are modeled. Thanks to mentoring, as a modern method of building the pedagogical process, we will be able to organize activities at a high level. All this will help the participants of the pedagogical process in their further professional development, as well as in the development of personal qualities that are necessary for every person. Despite the understanding of the signifi cance of this process, there are a lot of unresolved issues: how to build the concept of building work with the help of mentoring, what are the ways and methods of productive interaction with teenagers and much more.

Exploring the involvement of tax audit experts in the early stages of tax audits

Tax compliance and evasion pose significant challenges to tax authorities in South Africa and other countries. In recent times, corporate governance issues have increasingly involved tax compliance. This study focuses on unresolved audit issues with the South African Revenue Service (SARS), expensive litigation, and lengthy arbitration with the tax Ombudsman. These issues are complicated by legal elucidations, legislative components, and regulatory frameworks. The paper aims to clarify the purpose of a tax legal audit expert at SARS in the initial phases of an audit procedure. To answer this research question, a thorough mapping review using methodical, technique-based literature evaluation was conducted. The study found that the lack of skilled tax legal audit experts hampers the effectiveness and efficiency of tax audits. Therefore, tax authorities must invest in the skills of tax legal audit experts to improve audit outcomes.

Cancer cells possess different isotopic enrichment: Isotopic induced functionalizations of normal DNA mutations leading to cancer

Although the dynamics of telomeres during the life expectancy of normal cells has been extensively studied, there are still some unresolved issues regarding this research field. For example, the conditions required for telomere shortening leading to malignant transformations are not fully understood. In this work, we mass analyzed DNA of normal and cancer cells for comparing telomere isotopic compositions of white blood cells and cancer cells. We have found that the 1327 Da and 1672 Da characteristic telomere mass to charges cause differential mass distributions of about 1 Da among normal cells relative to cancer cells. These isotopic differences are consistent with a prior theory according to which replacing primordial, common isotopes of 1H, 12C, 14N, 16O, 24Mg, 31P and/or 32S by nonprimordial, uncommon isotopes of 2D, 13C, 15N, 17O, 25Mg and/or 33S leads to altered enzymatic dynamics. This replacement may subsequently modulate DNA and telomere codons resulting in transformation of normal cells to cancer cells (in 15 N depletion in telomeres dependent manner). The prior theory and the current data are consistent also with a recently observed non-uniform methylation pattern of the DNA of cancer cells relative to a more uniform methylation in the DNA of normal cells. We observe further evidence of nonprimordial isotopic accelerations of acetylations, methylations, hydroxylations and aminations of nucleosides with alterations of phosphorylations of nucleotides; which may explain the induction of mutations at the DNA, RNA and proteins leading to cancer and more general alterations of DNA, which are associated with aging. This difference in mass spectra between normal and cancer DNA may stem from different functionalizations and isotopic enrichments affecting the motion derived from nuclear magnetic moments (NMMs). We suggest that this phenomenon may lead to malignant transformation.

Understanding Cell Differentiation Through Single-Cell Approaches: Conceptual Challenges of the Systemic Approach.

The cells of a multicellular organism are derived from a single zygote and genetically almost identical. Yet, they are phenotypically very different. This difference is the result of a process commonly called cell differentiation. How the phenotypic diversity emerges during ontogenesis or regeneration is a central and intensely studied but still unresolved issue in biology. Cell biology is facing conceptual challenges that are frequently confused with methodological difficulties. How to define a cell type? What stability or change means in the context of cell differentiation and how to deal with the ubiquitous molecular variations seen in the living cells? What are the driving forces of the change? We propose to reframe the problem of cell differentiation in a systemic way by incorporating different theoretical approaches. The new conceptual framework is able to capture the insights made at different levels of cellular organization and considered previously as contradictory. It also provides a formal strategy for further experimental studies.

Oxidative Stress and the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Pathway in Multiple Sclerosis: Focus on Certain Exogenous and Endogenous Nrf2 Activators and Therapeutic Plasma Exchange Modulation.

The pathogenesis of multiple sclerosis (MS) suggests that, in genetically susceptible subjects, T lymphocytes undergo activation in the peripheral compartment, pass through the BBB, and cause damage in the CNS. They produce pro-inflammatory cytokines; induce cytotoxic activities in microglia and astrocytes with the accumulation of reactive oxygen species, reactive nitrogen species, and other highly reactive radicals; activate B cells and macrophages and stimulate the complement system. Inflammation and neurodegeneration are involved from the very beginning of the disease. They can both be affected by oxidative stress (OS) with different emphases depending on the time course of MS. Thus, OS initiates and supports inflammatory processes in the active phase, while in the chronic phase it supports neurodegenerative processes. A still unresolved issue in overcoming OS-induced lesions in MS is the insufficient endogenous activation of the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) pathway, which under normal conditions plays an essential role in mitochondria protection, OS, neuroinflammation, and degeneration. Thus, the search for approaches aiming to elevate endogenous Nrf2 activation is capable of protecting the brain against oxidative damage. However, exogenous Nrf2 activators themselves are not without drawbacks, necessitating the search for new non-pharmacological therapeutic approaches to modulate OS. The purpose of the present review is to provide some relevant preclinical and clinical examples, focusing on certain exogenous and endogenous Nrf2 activators and the modulation of therapeutic plasma exchange (TPE). The increased plasma levels of nerve growth factor (NGF) in response to TPE treatment of MS patients suggest their antioxidant potential for endogenous Nrf2 enhancement via NGF/TrkA/PI3K/Akt and NGF/p75NTR/ceramide-PKCζ/CK2 signaling pathways.

Best practice for improving children's and adolescents’ sport skills with motor imagery

ABSTRACTOver the past 50 years, a large number of studies have been carried out on the use of motor imagery practice (also called mental practice) to train motor functions. Because of its proven effectiveness for motor learning in adults, many researchers have investigated whether this technique can also improve the motor (especially sport) performances of children and adolescents. Although there is evidence that mental practice positively affects motor learning in young athletes, questions remain about the best way of implementing this type of training when participants’ motor imagery and cognitive functions are not yet fully developed. We reviewed the literature on mental practice in typically developing children and adolescents. Based on our findings, we then drew up a list of recommendations and guidelines for practitioners and coaches to develop effective motor imagery interventions for young athletes. Unresolved issues, methodological limitations of empirical studies, and research perspectives in the field of motor imagery training are discussed.

Immunophenotypic profile defines cytogenetic stability and unveils distinct prognoses in patients with newly-diagnosed multiple myeloma (NDMM).

Prognostic significance of multiple immune antigens in multiple myeloma has been well established. However, a level of uncertainty remains regarding the intrinsic relationship between immunophenotypes and cytogenetic stability and precise risk stratification. To address these unresolved issues, we conducted a study involving 1389 patients enrolled in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Our results revealed that the correlation between antigen expression and cytogenetics is more prominent than cytopenia or organ dysfunction. Most immune antigens, apart from CD38, CD138, and CD81, exhibit significant associations with the incidence of at least one cytogenetic abnormality. In turn, we identified CD138-low/CD27-neg as specific adverse immunophenotypic profile, which remaining independent impact on progression-free survival (HR, 1.49; P = 0.007) and overall survival (HR, 1.77; P < 0.001) even in the context of cytogenetics. Importantly, CD138-low/CD27-neg profile was also associated with inferior survival after first relapse (P < 0.001). Moreover, the antigen expression profiles were not strictly similar when comparing diagnosis and relapse; in particular, the CD138-low/CD27-neg pattern was notably increased after disease progression (19.1 to 29.1%; P = 0.005). Overall, our study demonstrates that diverse immune profiles are strongly associated with cytogenetic stability, and a specific immunophenotype (CD138-low/CD27-neg) could effectively predict prognoses across different disease stages.

Advances in understanding RSV glycoproteins: Insights into viral entry and implications for vaccines and therapeutic development

Respiratory syncytial virus (RSV) causes a significant number of deaths in newborns annually due to respiratory infections. Since its first isolation in 1955, great progress has been made in the development of related vaccines and monoclonal antibodies. Currently, two RSV vaccines and two monoclonal antibodies have been approved for marketing. Understanding the structure, function, and mechanism of RSV glycoproteins interaction with their receptors involved in its entry is of great significance for the development of vaccines and therapeutic drugs. In this review, we will introduce the substantial progress made in the understanding of the structure of RSV glycoproteins, the receptors they bind with, and the process of RSV entry. Progress made in developing vaccines and neutralizing antibodies which benefit from these studies will also be briefly discussed. Finally, we will outline the unresolved issues and controversies in RSV glycoprotein and entry mechanism research, propose some possible approaches to address these issues, and provide insights into future drug and vaccine development.

Impact of a cuff-based device calibration method on the agreement between invasive and noninvasive aortic and brachial pressure.

Brachial cuff-based methods are increasingly used to estimate aortic systolic blood pressure (aoSBP). However, there are several unresolved issues. to determine to what extent the scheme used to calibrate brachial records (1) can affect noninvasive obtained aoSBP levels, and consequently, the level of agreement with the aoSBP recorded invasively, and (2) how different ways of calibrating ultimately impact the relationship between aoSBP and cardiac properties. brachial and aortic blood pressure (BP) was simultaneously obtained by invasive (catheterisation) and noninvasive (brachial oscillometric-device) methods (89 subjects). aoSBP was noninvasive obtained using three calibration schemes: 'SD': diastolic and systolic brachial BP, 'C': diastolic and calculated brachial mean BP (bMBP), 'Osc': diastolic and oscillometry-derived bMBP. Agreement between invasive and noninvasive aoSBP, and associations between BP and echocardiographic-derived parameters were analysed. 'C' and 'SD' schemes generated aoSBP levels lower than those recorded invasively (mean errors: 6.9 and 10.1 mmHg); the opposite was found when considering 'Osc'(mean error: -11.4 mmHg). As individuals had higher invasive aoSBP, the three calibration schemes increasingly underestimated aoSBP levels; and viceversa. The 'range' of invasive aoSBP in which the calibration schemes reach the lowest error level (-5-5 mmHg) is different: 'C': 103-131 mmHg; 'Osc': 159-201 mmHg; 'SD':101-124 mmHg. The calibration methods allowed reaching levels of association between aoSBP and cardiac characteristics, somewhat lower, but very similar to those obtained when considering invasive aoSBP. There is no evidence of a clear superiority of one calibration method over another when considering the association between aoSBP and cardiac characteristics.

Assessing PROSPECT performance on aquatic plant leaves

PROSPECT is the most widely used optical leaf model for a wide range of remote sensing applications on vegetation and has been developed and parameterised based on empirical data measured almost exclusively on terrestrial plant leaves. As aquatic plants differ substantially from terrestrial plants in leaf morphology and physiology, the validity of the relationships underlying PROSPECT in aquatic plants needs to be verified empirically. To this end, we compiled a comprehensive dataset of leaf spectra and biochemical-structural parameters sampled along a water affinity gradient, including floating and emergent hydrophytes, helophytes and riparian species, and terrestrial plants. In parallel, we designed a multidimensional experiment to explore the performance of PROSPECT across different groups and to characterise sources of modelling error, focusing on aquatic plants. Our results showed that estimates of most leaf parameters from PROSPECT inversions diverged increasingly from measured traits when moving from terrestrial to aquatic species. The suboptimal performance of PROSPECT on aquatic plants appears to be driven by three main factors: difficulties in disentangling leaf dry matter components (particularly proteins), unresolved issues related to the overlap of primary and secondary pigment mixtures and absorption, and the peculiarities of internal leaf structure (i.e. the presence of ‘aerenchyma’). These findings highlight the need for careful preliminary evaluation of the applicability and limitations of PROSPECT when applied to vegetation types that differ significantly from the typical terrestrial trees and grasses used for model calibration, including aquatic plants. Such evaluation should be preferably based on empirical data covering natural heterogeneity, so that future applications of remote sensing for mapping aquatic and wetland vegetation characteristics can be improved in terms of robustness and transferability.

AT-PINN: Advanced time-marching physics-informed neural network for structural vibration analysis

Solving partial differential equations through deep learning has recently received wide attention, with physics-informed neural networks (PINNs) being successfully used and showing great potential. This study focuses on the development of an efficient PINN approach for structural vibration analysis in “long-duration” simulation that is still a technical but unresolved issue of PINN. The accuracies of the standard PINN (STD-PINN) and conventional time-marching PINN (CT-PINN) methods in solving vibration equations, especially free-vibration equations, are shown to decrease to varying degrees with the simulation time. To resolve this problem, an advanced time-marching PINN (AT-PINN) approach is proposed. This method is used to solve structural vibration problems over successive time segments by adopting four key techniques: normalization of the spatiotemporal domain in each time segment, a reactivating optimization algorithm, transfer learning and the sine activation function. To illustrate the advantages of the AT-PINN approach, numerical simulations for the forced and free vibration analysis of strings, beams and plates are performed. In addition, the vibration analysis of plates under multi-physics loads is also studied. The results show that the AT-PINN approach can provide accurate solutions with lower computational cost even in long-duration simulation. The techniques adopted are verified to effectively avoid the offset of the spatiotemporal domain, reduce the accumulative error and enhance the training efficiency. The present one overcomes the drawback of the existing PINN methods and is expected to become an effective method for solving time-dependent partial differential equations in long-duration simulation.

Circulating Tumor DNA Is a Variant of Liquid Biopsy with Predictive and Prognostic Clinical Value in Breast Cancer Patients

This paper introduces the reader to the field of liquid biopsies and cell-free nucleic acids, focusing on circulating tumor DNA (ctDNA) in breast cancer (BC). BC is the most common type of cancer in women, and progress with regard to treatment has been made in recent years. Despite this, there remain a number of unresolved issues in the treatment of BC; in particular, early detection and diagnosis, reliable markers of response to treatment and for the prediction of recurrence and metastasis, especially for unfavorable subtypes, are needed. It is also important to identify biomarkers for the assessment of drug resistance and for disease monitoring. Our work is devoted to ctDNA, which may be such a marker. Here, we describe its main characteristics and potential applications in clinical oncology. This review considers the results of studies devoted to the analysis of the prognostic and predictive roles of various methods for the determination of ctDNA in BC patients. Currently known epigenetic changes in ctDNA with clinical significance are reviewed. The possibility of using ctDNA as a predictive and prognostic marker for monitoring BC and predicting the recurrence and metastasis of cancer is also discussed, which may become an important part of a precision approach to the treatment of BC.