Search Results (70)

Background/Objectives: RAF pathway aberrations are one of the hallmarks of lung cancer. Sorafenib is a multi-kinase inhibitor targeting the RAF pathway and is FDA-approved for several cancers, yet its efficacy in lung cancer is controversial. Previous clinical research showed that a ARAF p.S214C mutation exhibited exceptional responsiveness to sorafenib in lung adenocarcinoma. Methods: Considering this promising clinical potential, the oncogenic potential and sorafenib response of the ARAF p.S214C mutation were investigated using lung cancer models. ARAF p.S214C mutant, ARAF wild-type (WT), and EGFP control genes were ectopically expressed in lung adenocarcinoma cell lines retroviral transduction. In vitro and in vivo sorafenib sensitivity studies were performed, followed by transcriptomics and proteomics analyses. Results: Compared to the ARAF-WT and EGFP-engineered cells, the ARAF p.S214C-engineered cells activated Raf-MEK-ERK signaling and exhibited enhanced oncogenic potential in terms of in vitro cell proliferation, colony and spheroid formation, migration, and invasion abilities, as well as in vivo tumorigenicity. The ARAF p.S214C-engineered cells also displayed heightened sensitivity to sorafenib in vitro and in vivo. RNA sequencing and reverse-phase protein array analyses demonstrated elevated expression of genes and proteins associated with tumor aggressiveness in the ARAF p.S214C mutants, and its sorafenib sensitivity was likely moderated through inhibition of the cell cycle and DNA replication. The ERK and PI3K signaling pathways were also significantly deregulated in the ARAF p.S214C mutants regardless of sorafenib treatment. Conclusions: This study demonstrates the oncogenicity and sorafenib sensitivity of the ARAF p.S214C mutation in lung cancer cells, which may serve as a biomarker for predicting the sorafenib response in lung cancer patients. Importantly, investigating the gene–drug sensitivity pairs in clinically exceptional responders may guide and accelerate personalized cancer therapies based on specific tumor mutations. Full article

This survey study aims to understand how college students use and perceive artificial intelligence (AI) tools in the United Arab Emirates (UAE). It reports students’ use, perceived motivations, and ethical concerns and how these variables are interrelated. Responses (n = 822) were collected from seven universities in five UAE emirates. The findings show widespread use of AI tools (79.6%), with various factors affecting students’ perceptions about AI tools. Students also raised concerns about the lack of guidance on using AI tools. Furthermore, mediation analyses revealed the underlining psychological mechanisms pertaining to AI tool adoption: perceived benefits fully mediated the relationship between AI knowledge and usefulness perceptions, peer pressure mediated the relationship between academic stress and AI adoption intent, and ethical concerns fully mediated the relationship between ethical perceptions and support for institutional AI regulations. The findings of this study provide implications for the opportunities and challenges posed by AI tools in higher education. This study is one of the first to provide empirical insights into UAE college students’ use of AI tools, examining mediation models to explore the complexity of their motivations, ethical concerns, and institutional guidance. Ultimately, this study offers empirical data to higher education institutions and policymakers on student perspectives of AI tools in the UAE. Full article

Per- and polyfluoroalkyl substances (PFASs) are found everywhere, including food, cosmetics, and pharmaceuticals. This review introduces PFASs comprehensively, discussing their nature and identifying their interconnection with microplastics and their impacts on public health and the environment. The human cost of decades of delay, cover-ups, and mismanagement of PFASs and plastic waste is outlined and briefly explained. Following that, PFASs and long-term health effects are critically assessed. Risk assessment is then critically reviewed, mentioning different tools and models. Scientific research and health impacts in the United States of America are critically analyzed, taking into consideration the Center for Disease Control (CDC)’s PFAS Medical Studies and Guidelines. PFAS impact and activities studies around the world have focused on PFAS levels in food products and dietary intake in different countries such as China, European countries, USA and Australia. Moreover, PFASs in drinking water and food are outlined with regard to risks, mitigation, and regulatory needs, taking into account chemical contaminants in food and their impact on health and safety. Finally, PFAS impact and activities briefings specific to regions around the world are discussed, referring to Australia, Vietnam, Canada, Europe, the United States of America (USA), South America, and Africa. The PFAS crisis is a multifaceted issue, exacerbated by mismanagement, and it is discussed in the context of applying the following problem-solving analytical tools: the Domino Effect Model of accident causation, the Swiss Cheese Theory Model, and the Ishikawa Fish Bone Root Cause Analysis. Last but not least, PFASs’ impacts on the Sustainable Development Goals (SDGs) of 2030 are rigorously discussed. Full article

Tick bites and tick-related diseases are on the rise. Diagnostic tests that identify well-characterised tick-borne pathogens (TBPs) possess limited capacity to address the causation of symptoms associated with poorly characterised tick-related illnesses, such as debilitating symptom complexes attributed to ticks (DSCATT) in Australia. Identification of local signals in tick-bitten skin that can be detected systemically in blood would have both clinical (diagnostic or prognostic) and research (mechanistic insight) utility, as a blood sample is more readily obtainable than tissue biopsies. We hypothesised that blood samples may reveal signals which reflect relevant local (tissue) events and that the time course of these signals may align with local pathophysiology. As a first step towards testing this hypothesis, we compared molecular signatures in skin biopsies taken from the tick-bite location of human participants, as published in our previous study, together with peripheral blood signatures obtained concurrently. This approach captures differentially expressed molecules across multiple omics datasets derived from peripheral blood (including cellular and cell-free transcriptomics, proteomics, metabolomics, and DNA methylation), and skin biopsies (spatial transcriptomics). Our original data revealed that extracellular matrix organisation and platelet degranulation pathways were upregulated in the skin within 72 h of a tick bite. The same signals appeared in blood, where they then remained elevated for three months, displaying longitudinally consistent alterations of biological functions. Despite the limited sample size, these data represent proof-of-concept that molecular events in the skin following a tick bite can be detectable systemically. This underscores the potential value of blood samples, akin to a liquid biopsy, to capture biomarkers reflecting local tissue processes. Full article

This research demonstrates how confirmation and disconfirmation biases manifest based on individuals’ political affiliations when processing a self-disclosure message in the context of a political crisis. An experiment presented a crisis message in which a politician voluntarily revealed his campaign finance violations. The results revealed that confirmation bias and disconfirmation bias significantly influenced the information processing of participants based on their political affiliations. Democrat participants were significantly more open to and forgiving of the crisis message when it featured a Democrat politician. In contrast, Republican participants showed a strong tendency to be more critical and less forgiving under the same conditions. However, this pattern reversed when a Republican politician was shown in the crisis message. The research also tested moderated mediation hypotheses: the interaction effects between study participants’ political affiliations and politicians’ parties were mediated by perceived attitude toward the politician and crisis responsibility, leading to ethical perceptions about the politician. The study contributes to our understanding of the mechanisms underlying political polarization and the ways in which the biases of confirmation and disconfirmation influence individuals’ processing of political messages. Full article

Mining activities, particularly in large excavations like the Bingham Canyon Copper Mine in Utah, have been increasingly linked to respiratory conditions due to heavy-metal-enriched waste and dust. Operating continuously since 1906, the Bingham Canyon Copper Mine contributes 4.4% of the Salt Lake Valley PM2.5 pollution. However, the extent of its contributions to larger-sized particulate matter (PM10) dust, soil and water contamination, and human health impacts is largely unknown. Aerosol optical depth data from Sentinel-2 imagery revealed discernible dust clouds downwind of the mine and smelter on non-prevailing-wind days, suggesting potential heavy metal dispersion from this fugitive dust and subsequent deposition to nearby surface soils. Our analysis of topsoils from across the western Salt Lake Valley found mean arsenic, copper, lead, and zinc concentrations to be well above global background concentrations. Also, the minimum values for arsenic and maximum values for lead were well above the US EPA regional screening levels for residential soils. Thus, arsenic is the metal of greatest concern for impacts on human health. Elevated concentrations of all metals were most notable near the mine, smelter, and tailings pond. Our study linked these elevated heavy metal levels to regional asthma outcomes through cluster analysis and distance-related comparison tests. Significant clusters of high asthma rates were observed in regions with elevated topsoil heavy metal concentrations, impacting both low- and high-income neighborhoods. The findings of this preliminary study suggest that the mine, smelter, and recent construction activities, especially on lands reclaimed from former tailings ponds, could be contributing to atmospheric dust containing high levels of heavy metals and exacerbating asthma outcomes for residents. However, the methods used in the study with aggregated health outcome data cannot determine causal links between the heavy metal contents of soil and health outcomes; they can only point to potential links and a need for further investigation. Such further investigation should involve individual-level data and control for potential confounding factors, such as socioeconomic status, access to healthcare, and lifestyle factors, to isolate the effect of metal exposures on asthma outcomes. This study focused on atmospheric deposition as a source of heavy metal enrichment of topsoil. However, future research is also essential to assess levels of heavy metals in subsoil parent materials and local surface and groundwaters to be able to assess the links between the sources or methods of soil contamination and health outcomes. Full article

Therapeutic antibodies such as monoclonal antibodies (mAbs), bispecific and multispecific antibodies are pivotal in therapeutic protein development and have transformed disease treatments across various therapeutic areas. The integrity of therapeutic antibodies, however, is compromised by sequence liabilities, notably deamidation, where asparagine (N) and glutamine (Q) residues undergo chemical degradations. Deamidation negatively impacts the efficacy, stability, and safety of diverse classes of antibodies, thus necessitating the critical need for the early and accurate identification of vulnerable sites. In this article, a comprehensive antibody deamidation-specific dataset (n = 2285) of varied modalities was created by using high-throughput automated peptide mapping followed by supervised machine learning to predict the deamidation propensities, as well as the extents, throughout the entire antibody sequences. We propose a novel chimeric deep learning model, integrating protein language model (pLM)-derived embeddings with local sequence information for enhanced deamidation predictions. Remarkably, this model requires only sequence inputs, eliminating the need for laborious feature engineering. Our approach demonstrates state-of-the-art performance, offering a streamlined workflow for high-throughput automated peptide mapping and deamidation prediction, with the potential of broader applicability to other antibody sequence liabilities. Full article

Women’s experiences of military service and transition occur within a highly dominant masculinized culture. The vast majority of research on military veterans reflects men’s experiences and needs. Women veterans’ experiences, and therefore their transition support needs, are largely invisible. This study sought to understand the role and impact of gender in the context of the dominant masculinized culture on women veterans’ experiences of military service and transition to civilian life. In-depth qualitative interviews with 22 Australian women veterans elicited four themes: (1) Fitting in a managing identity with the military; (2) Gender-based challenges in conforming to a masculinized culture—proving worthiness, assimilation, and survival strategies within that culture; (3) Women are valued less than men—consequences for women veterans, including misogyny, sexual harassment and assault, and system failures to recognize women’s specific health needs and role as mothers; and (4) Separation and transition: being invisible as a woman veteran in the civilian world. Gendered military experiences can have long-term negative impacts on women veterans’ mental and physical health, relationships, and identity due to a pervasive masculinized culture in which they remain largely invisible. This can create significant gender-based barriers to services and support for women veterans during their service, and it can also impede their transition support needs. Full article

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing—a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes. Full article

Reduced heart rate variability (HRV) is an autonomic nervous system (ANS) response that may indicate dysfunction in the human body. Consistent evidence shows cancer patients elicit lower HRV; however, only select cancer locations were previously evaluated. Thus, the aim of the current study was to explore HRV patterns in patients diagnosed with and in varying stages of the most prevalent cancers. At a single tertiary academic medical center, 798 patients were recruited. HRV was measured via an armband monitor (Warfighter Monitor^TM, Tiger Tech Solutions, Inc., Miami, FL, USA) equipped with electrocardiographic capabilities and was recorded for 5 to 7 min with patients seated in an upright position. Three time-domain metrics were calculated: SDNN (standard deviation of the NN interval), rMSSD (the root mean square of successive differences of NN intervals), and the percentage of time in which the change in successive NN intervals exceeds 50ms within a measurement (pNN50). Of the 798 patients, 399 were diagnosed with cancer. Cancer diagnoses were obtained via medical records one week following the measurement. Analysis of variance models were performed comparing the HRV patterns between different cancers, cancer stages (I–IV), and demographic strata. A total of 85% of the cancer patients had breast, gastrointestinal, genitourinary, or respiratory cancer. The cancer patients were compared to a control non-cancer patient population with similar patient size and distributions for sex, age, body mass index, and co-morbidities. For all HRV metrics, non-cancer patients exhibited significantly higher rMSSDs (11.1 to 13.9 ms, p < 0.0001), SDNNs (22.8 to 27.7 ms, p < 0.0001), and pNN50s (6.2 to 8.1%, p < 0.0001) compared to stage I or II cancer patients. This significant trend was consistently observed across each cancer location. Similarly, compared to patients with stage III or IV cancer, non-cancer patients possessed lower HRs (−11.8 to −14.0 bpm, p < 0.0001) and higher rMSSDs (+31.7 to +32.8 ms, p < 0.0001), SDNNs (+45.2 to +45.8 ms), p < 0.0001, and pNN50s (19.2 to 21.6%, p < 0.0001). The HR and HRV patterns observed did not significantly differ between cancer locations (p = 0.96 to 1.00). The depressed HRVs observed uniformly across the most prevalent cancer locations and stages appeared to occur independent of patients’ co-morbidities. This finding highlights the potentially effective use of HRV as a non-invasive tool for determining common cancer locations and their respective stages. More studies are needed to delineate the HRV patterns across different ages, between sexes and race/ethnic groups. Full article

Climate change is predicted to impact corn yields. Previous studies analyzing these impacts differ in data and modeling approaches and, consequently, corn yield projections. We analyze the impacts of climate change on corn yields using two statistical models with different approaches for dealing with county-level effects. The first model, which is novel to modeling corn yields, uses a computationally efficient spatial basis function approach. We use a Bayesian framework to incorporate both parametric and climate model structural uncertainty. We find that the statistical models have similar predictive abilities, but the spatial basis function model is faster and hence potentially a useful tool for crop yield projections. We also explore how different gridded temperature datasets affect the statistical model fit and performance. Compared to the dataset with only weather station data, we find that the dataset composed of satellite and weather station data results in a model with a magnified relationship between temperature and corn yields. For all statistical models, we observe a relationship between temperature and corn yields that is broadly similar to previous studies. We use downscaled and bias-corrected CMIP5 climate model projections to obtain detrended corn yield projections for 2020–2049 and 2069–2098. In both periods, we project a decrease in the mean corn yield production, reinforcing the findings of other studies. However, the magnitude of the decrease and the associated uncertainties we obtain differ from previous studies. Full article

Research into gender dynamics in the Public Relations (PR) industry has suggested that the gendered perceptions of PR roles, gender bias, and cultural norms may contribute to gender-related issues in the field. The current study, framed as an exploratory investigation, examines how PR professionals in the United Arab Emirates (UAE) perceive gender equality issues within their industry. Drawing on survey responses from 152 PR practitioners in the UAE, this research investigates the extent to which these professionals perceive gender equality issues in the PR sector. The survey results reveal positive perceptions of gender equality issues, although some specific gender-related concerns emerge. One key finding is that there are minimal gender differences in perceiving gender equality issues between male and female professionals. Respondents also expressed confidence that their organizations are implementing practices in support of gender equality and recognizing the impact of such practices on employee performance. Given the lack of data on gender equality in the UAE, this exploratory study contributes to a better understanding of gender equality among professionals and provides insights into the strategies for advancing gender equality in the sector. Full article

This study investigates the association between sustainable living knowledge and the intention to live sustainably among university students in the UAE. Using a survey method, the research examines students’ perceptions, attitudes, and intentions. The results indicate a positive correlation between sustainable living knowledge and the intention to live sustainably. Specifically, higher levels of sustainable living knowledge are correlated with a strong inclination towards engaging in sustainable behaviors. Additionally, the data analysis supports a proposed serial mediation model, suggesting that sustainable living knowledge influences the intention to live sustainably through perceived benefits and attitudes. These findings emphasize the significance of providing education on sustainable living practices to university students, as it can foster environmentally conscious behaviors and contribute to community development. This research enhances our understanding of the factors influencing individuals’ inclination towards adopting sustainable behaviors, offering valuable insights for designing interventions and educational programs targeted at promoting sustainable living among UAE students. Full article

E’Jiao is a traditional Chinese medicine derived from donkey skin. E’Jiao is reported to suppress elevated bone remodelling in ovariectomised rats but its mechanism of action is not known. To bridge this research gap, the current study aims to investigate the effects of E’Jiao on skeletal mineralisation, osteocyte and WNT signalling inhibitors in ovariectomised rats. Female Sprague–Dawley rats (3 months old) were ovariectomised and supplemented with E’Jiao at 0.26 g/kg, 0.53 g/kg and 1.06 g/kg, or 1% calcium carbonate (w/v) in drinking water. The rats were euthanised after two months of supplementation and their bones were collected for Fourier-transform infrared spectroscopy, histomorphometry and protein analysis. Neither ovariectomy nor treatment affected the skeletal mineral/matrix ratio, osteocyte number, empty lacunar number, and Dickkopf-1 and sclerostin protein levels (p > 0.05). Rats treated with calcium carbonate had a higher Dickkopf-1 level than baseline (p = 0.002) and E’Jiao at 0.53 g/kg (p = 0.002). In conclusion, E’Jiao has no significant effect on skeletal mineralisation, osteocyte and WNT signalling inhibitors in ovariectomised rats. The skeletal effect of E’Jiao might not be mediated through osteocytes. Full article

Comprehensive genomic profiling (CGP) allows for the detection of driver alterations at high resolution, but the limited number of approved targeted therapies and their high costs have contributed to its limited clinical utilization. We retrospectively compared data of 946 women with ovarian cancer (11.4% were referred to CGP, and 88.6% served as control) to examine whether CGP provides a prognosis benefit. Patient baseline parameters were similar between the groups. Cox regression analysis adjusted for age, disease stage at diagnosis, and recurrence status showed statistically significantly longer median overall survival (mOS) in the CGP group versus the control (73.4 versus 54.5 months, p < 0.001). Fifty-four patients (52.9%) had actionable mutations with potential treatments; twenty-six (48.2%) were treated with matched targeted therapy, showing a trend for longer mOS than the eighty-six women in the CGP group who were not given a suggested treatment (105.5 versus 63.6 months, p = 0.066). None of the genomic alterations predicted metastasis location. CCNE1 amplification and KRAS mutations were associated with shorter mOS. Patients with tumor mutation burden ≥4 mutations/megabase had longer mOS. High loss of heterozygosity was associated with longer mOS (99.0 versus 48.2 months, p = 0.004). CGP testing may provide both prognostic and predictive insights for treatment of patients with ovarian cancer. Prospective studies of larger cohorts are warranted. Full article