Specific Vulnerability Research Articles

An ESR1-Related Gene Signature Identifies Head and Neck Squamous Cell Carcinoma with Imputed Susceptibility to Endocrine Therapy.

Head and neck squamous cell carcinoma (HNSCC) is associated with high morbidity and mortality. New personalized treatment strategies represent an unmet medical need to improve the overall survival and the quality of life of patients, which are often limited by the toxicity of established multimodal treatment protocols. Several studies have reported an increased expression of the estrogen receptor 1 (ESR1) in HNSCC, but its potential role in the disease outcome of these tumors remains elusive. Using an integrative analysis of multiomics and clinical data from The Cancer Genome Atlas (TCGA)-HNSC, we established a prognostic risk model based on an ESR1-related 25-gene set. The prognostic value was confirmed in an independent cohort of HNSCC and other solid tumors from TCGA. Finally, we performed in silico drug sensitivity modeling to explore potential vulnerabilities for both risk groups. This approach predicted a higher sensitivity for HNSCC, with prominent ESR1 pathway activity under treatment with specific estrogen receptor modulators. In conclusion, our data confirm the involvement of ESR1-related pathway activity in the progression of a defined subset of HNSCC, provide compelling evidence that these tumors share a specific vulnerability to endocrine therapy, and pave the way for preclinical studies and clinical trials to demonstrate the efficacy of this new therapeutic option.

Early childhood malnutrition impairs adult resting brain function using near-infrared spectroscopy.

Early childhood malnutrition affects 200+ million children under 5 years of age worldwide and is associated with persistent cognitive, behavioral and psychiatric impairments in adulthood. However, very few studies have investigated the long-term effects of childhood protein-energy malnutrition (PEM) on brain function using a functional hemodynamic brain imaging technique. This study aims to investigate functional brain network alterations using near infrared spectroscopy (NIRS) in adults, aged 45-51 years, from the Barbados Nutrition Study (BNS) who suffered from a single episode of malnutrition restricted to their first year of life (n = 26) and controls (n = 29). A total of 55 individuals from the BNS cohort underwent NIRS recording at rest. Using functional connectivity and permutation analysis, we found patterns of increased Pearson's correlation with a specific vulnerability of the frontal cortex in the PEM group (ps < 0.05). Using a graph theoretical approach, mixed ANCOVAs showed increased segregation (ps = 0.0303 and 0.0441) and decreased integration (p = 0.0498) in previously malnourished participants compared to healthy controls. These results can be interpreted as a compensatory mechanism to preserve cognitive functions, that could also be related to premature or pathological brain aging. To our knowledge, this study is the first NIRS neuroimaging study revealing brain function alterations in middle adulthood following early childhood malnutrition limited to the first year of life.

Abstract B019: BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response

Abstract Alternative Lengthening of Telomeres (ALT) is a homology-directed repair (HDR) mediated telomere maintenance mechanism that is prevalent in cancers of mesenchymal origin. ALT cells exhibit more endogenous replication stress and DNA damage at the telomere compared to ALT-negative cells. The Bloom Syndrome helicase (BLM) is critical for ALT and promotes replication stress and DNA damage specifically at telomeres in ALT cells. Here, we determine that BLM helicase acts on lagging strand telomere intermediates that occur specifically in ALT-positive cells to assemble a replication stress-associated DNA damage response. Loss of ATRX was permissive for BLM localization to ALT telomeres in S and G2 commensurate with the appearance of telomere C-strand specific single-stranded DNA. Moreover, DNA2 nuclease deficiency increased 5’-flap formation in a BLM-dependent manner, and BLM promoted ALT in response to telomere C-strand, but not G-strand, nicks. These findings define the seminal events in the ALT DNA damage response, linking aberrant lagging strand DNA replication with a BLM-directed HDR mechanism that sustains telomere length in a subset of human cancers (Jiang et al. submitted). These findings will be discussed and how BLM activity is a key determinant of the specific vulnerability of ALT cells to FANCM inhibition, which is currently being developed to target ALT-dependent cancers. Citation Format: Haoyang Jiang, Tianpeng Zhang, Hardeep Kaur, Tao Shi, Aravind Krishnan, Youngho Kwon, Patrick Sung, Roger Greenberg. BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B019.

An evolutionary game-theoretic analysis of the "multi-agent co-governance" system of unfair competition on internet platforms.

The increasingly prominent issue of unfair competition on Internet platforms (IPUC) severely restricts the healthy and sustainable development of the platform economy. Based on the IPUC "multi-agent co-governance" scenario, this paper introduces stochastic disturbances and continuous strategy set to improve the classical binary deterministic evolutionary game system. The results show that after considering stochastic disturbances, the positive state corresponding to the equilibrium point (1,1) is no longer stable, and the required parameter conditions are more stringent. The IPUC "multi-agent co-governance" system under stochastic disturbances exhibits specific vulnerability. In the continuous strategy set evolutionary game system, government departments and Internet platforms can flexibly make optimal decisions based on maximizing expected returns, and strategy selection has better elasticity. Regardless of the evolutionary game scenario, maintaining the participation level of NGOs and the public above a certain threshold while increasing the penalty intensity is conducive to the evolution of the game system toward the positive state. The analysis process and conclusions provide insights and guidance for the governments to design the IPUC regulatory system and frameworks.

No compassion, together in action!

Start a caring neighborhood from the direction of people with a specific vulnerability (autism) with the support of very diverse actors, it is possible!&#x0D; De Vijver (organization that supports people with disabilities) went in search of interesting places in the neighborhood with people with autism and connects them to a short walk. Around those places we went together with schools in the neighborhood, the art academy, service centers for the elderly, to make texts, images, works of art and videos. These were canned and put behind a QR code. Anyone who takes the walk in the area can discover the many stories via the QR code at each spot. To launch the walking route, a work of art was made with neighbours at the starting point of the route for 4 weeks.&#x0D; The objective of this approach was, on the one hand, to see vulnerable people not always as people seeking for help, but as a very valuable actor in a neighbourhood. On the other hand, we also wanted to create the first basic condition for strengthening living together and caring for each other in a neighbourhood, namely getting to know each other organically by building something for the neighborhood together.&#x0D; In this workshop we will show you how we succeeded.&#x0D; We also zoom in on the difficulties we encountered and the keys to success. We let you enjoy live images of how everything came about.&#x0D; Then we want to confront our approach with your experiences.&#x0D; We end with some take home messages.

Particulate Matter in Human Elderly: Higher Susceptibility to Cognitive Decline and Age-Related Diseases.

This review highlights the significant impact of air quality, specifically particulate matter (PM), on cognitive decline and age-related diseases in the elderly. Despite established links to other pathologies, such as respiratory and cardiovascular illnesses, there is a pressing need for increased attention to the association between air pollution and cognitive aging, given the rising prevalence of neurocognitive disorders. PM sources are from diverse origins, including industrial activities and combustion engines, categorized into PM10, PM2.5, and ultrafine PM (UFPM), and emphasized health risks from both outdoor and indoor exposure. Long-term PM exposure, notably PM2.5, has correlated with declines in cognitive function, with a specific vulnerability observed in women. Recently, extracellular vesicles (EVs) have been explored due to the interplay between them, PM exposure, and human aging, highlighting the crucial role of EVs, especially exosomes, in mediating the complex relationship between PM exposure and chronic diseases, particularly neurological disorders. To sum up, we have compiled the pieces of evidence that show the potential contribution of PM exposure to cognitive aging and the role of EVs in mediating PM-induced cognitive impairment, which presents a promising avenue for future research and development of therapeutic strategies. Finally, this review emphasizes the need for policy changes and increased public awareness to mitigate air pollution, especially among vulnerable populations such as the elderly.

Assessment of aquifer specific vulnerability to total nitrate contamination using ensemble learning and geochemical evidence

Henan Province's plain area is the granary of China, yet its regional aquifer is being polluted by industrial wastewater, agricultural pesticide, fertilizer and domestic wastewater. In order to safeguard the security of food and drinking water, and in response to the problem of low prediction accuracy caused by the lack of samples and unevenly distributed groundwater monitoring data, we propose a new way to predict the aquifer vulnerability in large areas by rich small-scale data, so as to identify the pollution risks and to address the issue of sample shortage. In small regions with abundant nitrate data, we employed a Random Forest model to screen key impact indicators, using them as features and nitrate-N concentration as the target variable. Consequently, we established six machine learning prediction models, and then selected the best bagging model (R2 = 0.86) to predict the vulnerability of aquifers in larger regions lacking nitrate data. The predicted results showed that highly vulnerable areas accounted for 20 %, which were mainly affected by aquifer thickness (65.91 %). High nitrate-N concentration implies serious aquifer contamination. Therefore, a long series of groundwater nitrate-N concentration monitoring data in a large scale, the trend and slope of nitrate-N concentration showed a significant correlation with the model prediction results (Spearman's correlation coefficients are 0.75 and 0.58). This study can help identify the risk of aquifer contamination, solve the problem of sample shortage in large areas, thus contributing to the security of food and drinking water.

Elemental composition of salt and vulnerability assessment of saline groundwater sources selected based on ethnoarchaeological evidence in Romania

The study aimed to evaluate the elemental composition of salt extracted from shallow to saline groundwater sources selected based on ethnoarchaeological evidence in the Eastern Carpathians and Sub-Carpathians area of Romania and to assess their specific vulnerability using groundwater pollution potential (DRASTIC and DRASTIC-LU methodology). 198 saline water samples were collected from different site types, including natural saline springs, catchment saline springs, brine wells, salted lakes and ponds, during the period between 2007 and 2019. Scanning electron microscopy with energy-dispersive X-ray spectroscopy was employed to characterize the elemental composition of salt after dry-evaporating a predetermined volume of each collected sample. The results indicated that the salt concentration in the brines ranged from 0.1% to 41.3%, with the highest concentration found in wells and natural saline springs. The dominant component was sodium chloride, but several sites had high concentrations of potassium chloride, which is essential for human health. Over 95% of the analyzed samples also contained other minerals like calcium and magnesium, further highlighting the health benefits of these brine sources. However, two sites were slightly contaminated with heavy metals, posing potential health risks if consumed. The DRASTIC index, a standardized system for evaluating groundwater pollution potential, gave scores between 99 and 208, indicating moderate to very high intrinsic pollution potential. Similarly, the DRASTIC-LU index, which takes into account and the land use aspects, showed scores ranging from 114 to 258, suggesting low to very high vulnerability to contamination. These findings provide valuable information on the elemental composition of salt and the vulnerability of these brine sources, which are still used by rural communities for traditional practices like meat and fish preservation, milk curdling, and pickling. The study has important implications for sustainable management from both ethnoarchaeological and economic perspectives.

Multidimensional Linear Cryptanalysis of Feistel Ciphers

This paper presents new generic attacks on Feistel ciphers that incorporate the key addition at the input of the non-invertible round function only. This feature leads to a specific vulnerability that can be exploited using multidimensional linear cryptanalysis. More specifically, our approach involves using key-independent linear trails so that the distribution of a combination of the plaintext and ciphertext can be computed. This makes it possible to use the likelihood-ratio test as opposed to the χ2 test. We provide theoretical estimates of the cost of our generic attacks and verify these experimentally by applying the attacks to CAST-128 and LOKI91. The theoretical and experimental findings demonstrate that the proposed attacks lead to significant reductions in data-complexity in several interesting cases.

Echoes of ancestral trauma: Russo-Ukrainian War salience and psychological distress among subsequent generations in Holocaust survivor families.

The Russo-Ukrainian War intensified when Russian troops invaded Ukraine in February 2022. The current study examined whether children (second generation; G2) and grandchildren (third generation; G3) of Holocaust survivors are more preoccupied with the war relative to comparisons. Moreover, whether there was more exacerbation in psychological distress in Holocaust survivor families relative to comparisons since the escalation of the war. A random sample from a web-based survey company included 1,071 Jewish Israeli adults (297 Holocaust G2, 224 comparison G2, 379 Holocaust G3, and 171 comparison G3). The average age of the participants was 62.95 ± 10.25, 61.79 ± 10.13, 34.02 ± 8.65, and 33.55 ± 8.26, respectively. Participants answered questionnaires on background characteristics, Russo-Ukrainian War exposure, Russo-Ukrainian War salience, and general psychological distress before and since the escalation of the war. Findings showed that Holocaust G2 and G3, relative to comparisons, reported more Russo-Ukrainian War salience. Moreover, more psychological distress symptom exacerbation was found in Holocaust survivor families relative to comparisons since the escalation of the war. Finally, Holocaust G2 and G3 with more Holocaust survivors in the family showed higher anxious preoccupation with the war and Holocaust G3 with more survivor grandparents showed more exacerbation in psychological distress. Findings suggest a specific vulnerability due to intergenerational transmission of trauma in Holocaust survivor families, including increased preoccupation with and perceptiveness to potential threats of human-induced trauma. Strengthening previous recommendations, mental health practitioners should focus on reducing the preoccupation with threat and the increased psychological distress of Holocaust survivor families when faced with current adversity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Software Tools for Digitalizing the Basic Processes and Services in the Higher Schools of the Republic of Bulgaria

The article examines the issues of the application of modern software tools and technologies for digitization of the main processes and services in the higher education institutions of the Republic of Bulgaria. The topic is complex and debatable, both from the point of view of the applied methods and technologies, and in terms of reporting the effectiveness of these services. The acceleration of the digitization processes necessitates and requires the taking of specific measures to ensure the level of cyber security of the organization. One of the measures in this direction is for the developed web applications to be based on the latest technologies, as well as to carry out specific vulnerability tests before launching the services. As a result of the analyzed theoretical statements, as well as on the basis of the specific software implementation, some of the positive moments in expanding students’ access to modern digital services have been outlined.

Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia

Pharmacologic targeting of chromatin-associated protein complexes has shown significant responses in KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) but resistance frequently develops to single agents. This points to a need for therapeutic combinations that target multiple mechanisms. To enhance our understanding of functional dependencies in KMT2A-r AML, we have used a proteomic approach to identify the catalytic immunoproteasome subunit PSMB8 as a specific vulnerability. Genetic and pharmacologic inactivation of PSMB8 results in impaired proliferation of murine and human leukemic cells while normal hematopoietic cells remain unaffected. Disruption of immunoproteasome function drives an increase in transcription factor BASP1 which in turn represses KMT2A-fusion protein target genes. Pharmacologic targeting of PSMB8 improves efficacy of Menin-inhibitors, synergistically reduces leukemia in human xenografts and shows preserved activity against Menin-inhibitor resistance mutations. This identifies and validates a cell-intrinsic mechanism whereby selective disruption of proteostasis results in altered transcription factor abundance and repression of oncogene-specific transcriptional networks. These data demonstrate that the immunoproteasome is a relevant therapeutic target in AML and that targeting the immunoproteasome in combination with Menin-inhibition could be a novel approach for treatment of KMT2A-r AML.

Toxic UDPGA Accumulation Is a Metabolic Vulnerability of Cancer Cells.

UXS1-mediated clearance of the sugar nucleotide UDPGA is a specific vulnerability of cancer cells.

TP53 Aberrant B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Are Uniquely Sensitive to a Combination of Pyrimidine De Novo Synthesis Blockade and Replication Checkpoint Inhibition

Background Unlike most solid tumors, the incidence of TP53 aberrations in ALL is only 3% at diagnosis. However, in relapsed ALL this number increases to 12%. More importantly, at relapse, loss of p53 function is associated with therapy failure, with an overall survival of only 20%. Hence, there is a clear clinical need for more effective strategies to treat TP53 aberrant relapsed ALL. Owing to their high proliferative state, leukemic blasts show a high dependency on pyrimidines for DNA synthesis. A lack of pyrimidines leads to replication stress, causing activation of p53 and the DNA damage response pathway. Results We used CRISPR/Cas9 to generate TP53 deficient variants of the TP53 proficient BCP-ALL cell lines Nalm6 and RCH-ACV. We used these cell lines in a CRISPR screens and high throughput drug screen, and identified a strong synergy between the targeting of pyrimidine synthesis and DNA checkpoint kinase ATR and its downstream effectors Chk1 and Wee1 in TP53 deficient ALL. To validate these results, we tested the efficacy of a checkpoint inhibition together with Orludodstat (BAY-2402234), an inhibitor of Dihydroorotate Dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis. This clinical grade inhibitor was evaluated in either wild type or TP53 deficient BCP-ALL and T-ALL cell line models and patient derived xenografts (PDX). A strong apoptotic response was observed when Orludodstat was combined with the ATR inhibitor Berzosertib, most notably in TP53 deficient ALL. This p53 dependency was confirmed using ex vivo cultures of patient derived xenografts (PDX) of diagnosis and relapse pairs, where each diagnostic sample was wild type for TP53, and the relapse carried a TP53 aberration. While little or no synergy was observed in the diagnostic samples, a strong efficacy of the combination was observed in the matched TP53 deficient relapsed samples (Figure 1 A). Preliminary results from i n vivo experiments using p53 deficient patient derived xenografts indicate that the combination of Orludodstat and Berzosertib is well tolerated, while significantly delaying leukemic growth (Figure 1 B). Conclusion Together, our findings suggest that the combined targeting of de novo pyrimidine synthesis and ATR signaling may present a specific and non-genotoxic vulnerability for TP53 aberrant ALL.

The Nonclinical Assessment of Trans-1,3,3,3-tetrafluoropropene (HFO-1234ze (E)), a Near Zero Global Warming Potential Propellant for Use in Metered Dose Inhalation Products.

HFO-1234ze (E) is proposed as a near zero global warming propellant for use in metered dose inhaled (MDI) products. This paper describes the non-clinical safety assessment in mice, rats, and dogs and supplements previously reported data (genetic toxicology, short-term toxicology, and reproductive toxicology). In all species, HFO-1234ze (E) was only detectable in blood for a short period after dosing with no evidence of accumulation. HFO-1234ze (E) was without any toxicological effects at very high doses in subchronic (13-week mouse) and chronic (39-week dog) studies. Chronic (26-week) administration to rats at very high doses was associated with an exacerbation of rodent progressive cardiomyopathy, a well-documented background finding in rodents. In a 2-generation study, extremely high doses were associated with the early euthanasia of some lactating female rats. This finding was considered to be significantly influenced by a state of negative energy balance, reflecting the specific vulnerability of rats during lactation. These findings are considered to not pose a risk to humans with typical MDI use given they occurred at doses which far exceed those expected in patients. Overall, the nonclinical safety data for HFO-1234ze (E) support its further development as an MDI propellant.

VRK3 depletion induces cell cycle arrest and metabolic reprogramming of pontine diffuse midline glioma - H3K27 altered cells.

We previously identified VRK3 as a specific vulnerability in DMG-H3K27M cells in a synthetic lethality screen targeting the whole kinome. The aim of the present study was to elucidate the mechanisms by which VRK3 depletion impact DMG-H3K27M cell fitness. Gene expression studies after VRK3 knockdown emphasized the inhibition of genes involved in G1/S transition of the cell cycle resulting in growth arrest in G1. Additionally, a massive modulation of genes involved in chromosome segregation was observed, concomitantly with a reduction in the level of phosphorylation of serine 10 and serine 28 of histone H3 supporting the regulation of chromatin condensation during cell division. This last effect could be partly due to a concomitant decrease of the chromatin kinase VRK1 in DMG following VRK3 knockdown. Furthermore, a metabolic switch specific to VRK3 function was observed towards increased oxidative phosphorylation without change in mitochondria content, that we hypothesized would represent a cell rescue mechanism. This study further explored the vulnerability of DMG-H3K27M cells to VRK3 depletion suggesting potential therapeutic combinations, e.g. with the mitochondrial ClpP protease activator ONC201.

Differences in perceived online communication and disclosing e-motions among adolescents and young adults: The role of specific social media features and social anxiety.

Social media are widely used by adolescents and young adults as a mean to maintain interpersonal relationships. Recent studies have found that young individuals with high levels of social anxiety feel more confident in communicating online. However, little is known about the role of perceived social media characteristics that could minimize the distress they experienced in face-to-face interactions. In this study, we rely on the tenets of the Transformation Framework, according to which social media, with its own features, may transform social relationships, including disclosing emotions and communicating with others online, in ways that may differ across individuals with or without specific vulnerability (e.g., social anxiety). Therefore, this cross-sectional study aims at examining the contribution of three specific social media features (i.e., asynchronicity, cue absence, and visualness) in explaining perceived breadth and depth of online communication, both directly and via e-motional processes (i.e., expression and facilitating use of e-motions), across groups of individuals with high versus low levels of social anxiety. Participants were 1046 Italian adolescents and young adults (61.4% females; Mage = 17.9, SD = 3.23) who completed an anonymous self-report questionnaire between 2021 and 2022. Participants with very high scores on social anxiety (above the 90th percentile; socially anxious), were distinguished from all others (socially nonanxious) and a multigroup analysis (MGA) was run to compare the pattern of associations across the two different groups. Results from the MGA showed significant differences between the two groups, partially confirming our hypotheses. Specifically, among socially anxious individuals, perceived cue absence was found to benefit perceived breadth and depth of online communication, and asynchronicity to enhance online emotional processes; conversely, these associations were negative in the group of socially nonanxious. Thus, these findings underly the contribution of social media in explaining youngsters' online experiences and support the potential beneficial role of some social media features for those more socially vulnerable.

Neurocognitive skills and vulnerability for psychosis in depression and across the psychotic spectrum: findings from the PRONIA Consortium.

Neurocognitive deficits are a core feature of psychosis and depression. Despite commonalities in cognitive alterations, it remains unclear if and how the cognitive deficits in patients at clinical high risk for psychosis (CHR) and those with recent-onset psychosis (ROP) are distinct from those seen in recent-onset depression (ROD). This study was carried out within the European project 'Personalized Prognostic Tools for Early Psychosis Management', and aimed to characterise the cognitive profiles of patients with psychosis or depression. We examined cognitive profiles for patients with ROP (n = 105), patients with ROD (n = 123), patients at CHR (n = 116) and healthy controls (n = 372) across seven sites in five European countries. Confirmatory factor analysis identified four cognitive factors independent of gender, education and site: speed of processing, attention and working memory, verbal learning and spatial learning. Patients with ROP performed worse than healthy controls in all four domains (P < 0.001), whereas performance of patients with ROD was not affected (P > 0.05). Patients at CHR performed worse than healthy controls in speed of processing (P = 0.001) and spatial learning (P = 0.003), but better than patients with ROP across all cognitive domains (all P ≤ 0.01). CHR and ROD groups did not significantly differ in any cognitive domain. These findings were independent of comorbid depressive symptoms, substance consumption and illness duration. These results show that neurocognitive abilities are affected in CHR and ROP, whereas ROD seems spared. Although our findings may support the notion that those at CHR have a specific vulnerability to psychosis, future studies investigating broader transdiagnostic risk cohorts in longitudinal designs are needed.

Adopting a child perspective for exposome research on mental health and cognitive development - Conceptualisation and opportunities.

Mental disorders among children and adolescents pose a significant global challenge. The exposome framework covering the totality of internal, social and physical exposures over a lifetime provides opportunities to better understand the causes of and processes related to mental health, and cognitive functioning. The paper presents a conceptual framework on exposome, mental health, and cognitive development in children and adolescents, with potential mediating pathways, providing a possibility for interventions along the life course. The paper underscores the significance of adopting a child perspective to the exposome, acknowledging children's specific vulnerability, including differential exposures, susceptibility of effects and capacity to respond; their susceptibility during development and growth, highlighting neurodevelopmental processes from conception to young adulthood that are highly sensitive to external exposures. Further, critical periods when exposures may have significant effects on a child's development and future health are addressed. The paper stresses that children's behaviour, physiology, activity pattern and place for activities make them differently vulnerable to environmental pollutants, and calls for child-specific assessment methods, currently lacking within today's health frameworks. The importance of understanding the interplay between structure and agency is emphasized, where agency is guided by social structures and practices and vice-versa. An intersectional approach that acknowledges the interplay of social and physical exposures as well as a global and rural perspective on exposome is further pointed out. To advance the exposome field, interdisciplinary efforts that involve multiple scientific disciplines are crucial. By adopting a child perspective and incorporating an exposome approach, we can gain a comprehensive understanding of how exposures impact children's mental health and cognitive development leading to better outcomes.

Evaluation of Smart Contract Vulnerability Analysis Tools: A Domain-Specific Perspective

With the widespread adoption of blockchain platforms across various decentralized applications, the smart contract’s vulnerabilities are continuously growing and evolving. Consequently, a failure to optimize conventional vulnerability analysis methods results in unforeseen effects caused by overlooked classes of vulnerabilities. Current methods have difficulty dealing with multifaceted intrusions, which calls for more robust approaches. Therefore, overdependence on environment-defined parameters in the contract execution logic binds the contract to the manipulation of such parameters and is perceived as a security vulnerability. Several vulnerability analysis tools have been identified as insufficient to effectively identify certain types of vulnerability. In this paper, we perform a domain-specific evaluation of state-of-the-art vulnerability detection tools on smart contracts. A domain can be defined as a particular area of knowledge, expertise, or industry. We use a perspective specific to the area of energy contracts to draw logical and language-dependent features to advance the structural and procedural comprehension of these contracts. The goal is to reach a greater degree of abstraction and navigate the complexities of decentralized applications by determining their domains. In particular, we analyze code embedding of energy smart contracts and characterize their vulnerabilities in transactive energy systems. We conclude that energy contracts can be affected by a relatively large number of defects. It also appears that the detection accuracy of the tools varies depending on the domain. This suggests that security flaws may be domain-specific. As a result, in some domains, many vulnerabilities can be overlooked by existing analytical tools. Additionally, the overall impact of a specific vulnerability can differ significantly between domains, making its mitigation a priority subject to business logic. As a result, more effort should be directed towards the reliable and accurate detection of existing and new types of vulnerability from a domain-specific point of view.