Research Agency Research Articles

Evaluating the combined and individual cytotoxic effect of beauvericin, enniatin B and ochratoxin a on breast cancer cells, leukemia cells, and fresh peripheral blood mononuclear cells

Beauvericin (BEA), Enniatin B (ENN B), and Ochratoxin A (OTA) are mycotoxins produced by fungi species. Their main effect on several organs and systems is associated with chronic exposure going from immunotoxicity, estrogenic disorders, and renal failure to cancer (in animals and humans). OTA belongs to Group 1 according to the International Agency for Research in Cancer (IARC) and it has legislated limited values; not happening for BEA nor ENN B. Exposure to mixtures of mycotoxins occurs through food intake in daily consumption. The aim of this study was to evaluate the implication of BEA, ENN B, and OTA individually and combined in producing cytotoxicity in cells for immunological studies and cancer cell lines (human leukemia cells (HL-60), fresh human peripheral blood mononuclear cells (PBMCs), and human breast cancer (MDA-MB-231) cells). Cells were treated for 4 h and 24 h at different concentrations of BEA, ENN B, and OTA, respectively. Viability assays were carried out by flow cytometry using DAPI (4′,6-diamindino-2-phenylindole, dihydrochloride) as a viability dye and the potential effects of synergism, addition, and antagonism were assessed through the Chou and Talalay method. Individual OTA treatment exerted the greatest cytotoxicity for PBMC cells (IC50 0.5 μM) while ENN B for HL-60 (IC50 0.25 μM) and MDA-MB-231 (IC50 0.15 μM). In binary combination [ENN B + OTA] resulted in exerting the greatest cytotoxicity for HL-60 and MDA-MB-231 cells; while [BEA + OTA] in PBMC cells. The triple combination resulted in being highly cytotoxic for PBMC cells compared to HL-60 and MDA-MB-231 cells. In summary, PBMC cells were the most sensible cells for all three mycotoxins and the presence of OTA in any of the combinations had the greatest toxicity causing synergism as the most common cytotoxic effect.

Cancer incidence in a cohort of Danish firefighters: An extended long-term follow-up 1968-2021.

To update and extend the examination of cancer incidence in a cohort of Danish firefighters, now adding 7 years of follow-up and 2766 additional firefighters. The primary focus was directed toward cancer sites that recently contributed to the hazard evaluation conducted by the International Agency for Research on Cancer (IARC). The updated cohort consisted of 11,827 male Danish firefighters who were followed up for cancer from 1968 to 2021. Cohort cancer morbidity was compared with a working population reference group, and standardized incidence ratios (SIR) were used for estimation of relative risks, along with 95% confidence intervals (95% CI). Among full-time firefighters, SIR of skin melanoma was 1.30 (95% CI: 1.02-1.66), and SIR = 1.37 (95% CI: 1.02-1.85) for over 5 years of employment. Slightly positive associations were also observed for cancer of the urinary bladder (SIR = 1.16; 95% CI: 0.93-1.45), prostate (SIR = 1.11; 95% CI: 0.97-1.28), and testis (SIR = 1.11; 95% CI: 0.75-1.63). This updated study provides evidence indicating an elevated risk of skin melanoma in firefighters. Consistent with IARC's evaluation, we also identified positive associations for urinary bladder, prostate, and testis cancer. In contrast, our findings did not suggest an increased risk of colon cancer, non-Hodgkin lymphoma, and mesothelioma. The latter may be due to small numbers in our still relatively young cohort. Continuous follow-up for cancer in firefighters is warranted, including assessment of influence from surveillance bias.

Application of Photoactive Compounds in Cancer Theranostics: Review on Recent Trends from Photoactive Chemistry to Artificial Intelligence

According to the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC), the number of cancer cases and deaths worldwide is predicted to nearly double by 2030, reaching 21.7 million cases and 13 million fatalities. The increase in cancer mortality is due to limitations in the diagnosis and treatment options that are currently available. The close relationship between diagnostics and medicine has made it possible for cancer patients to receive precise diagnoses and individualized care. This article discusses newly developed compounds with potential for photodynamic therapy and diagnostic applications, as well as those already in use. In addition, it discusses the use of artificial intelligence in the analysis of diagnostic images obtained using, among other things, theranostic agents.

The impact of urban configuration types on urban heat islands, air pollution, CO2 emissions, and mortality in Europe: a data science approach

The world is becoming increasingly urbanised. As cities around the world continue to grow, it is important for urban planners and policy makers to understand how different urban configuration patterns affect the environment and human health. However, previous studies have provided mixed findings. We aimed to identify European urban configuration types, on the basis of the local climate zones categories and street design variables from Open Street Map, and evaluate their association with motorised traffic flows, surface urban heat island (SUHI) intensities, tropospheric NO2, CO2 per person emissions, and age-standardised mortality. We considered 946 European cities from 31 countries for the analysis defined in the 2018 Urban Audit database, of which 919 European cities were analysed. Data were collected at a 250 m × 250 m grid cell resolution. We divided all cities into five concentric rings based on the Burgess concentric urban planning model and calculated the mean values of all variables for each ring. First, to identify distinct urban configuration types, we applied the Uniform Manifold Approximation and Projection for Dimension Reduction method, followed by the k-means clustering algorithm. Next, statistical differences in exposures (including SUHI) and mortality between the resulting urban configuration types were evaluated using a Kruskal-Wallis test followed by a post-hoc Dunn's test. We identified four distinct urban configuration types characterising European cities: compact high density (n=246), open low-rise medium density (n=245), open low-rise low density (n=261), and green low density (n=167). Compact high density cities were a small size, had high population densities, and a low availability of natural areas. In contrast, green low density cities were a large size, had low population densities, and a high availability of natural areas and cycleways. The open low-rise medium and low density cities were a small to medium size with medium to low population densities and low to moderate availability of green areas. Motorised traffic flows and NO2 exposure were significantly higher in compact high density and open low-rise medium density cities when compared with green low density and open low-rise low density cities. Additionally, green low density cities had a significantly lower SUHI effect compared with all other urban configuration types. Per person CO2 emissions were significantly lower in compact high density cities compared with green low density cities. Lastly, green low density cities had significantly lower mortality rates when compared with all other urban configuration types. Our findings indicate that, although the compact city model is more sustainable, European compact cities still face challenges related to poor environmental quality and health. Our results have notable implications for urban and transport planning policies in Europe and contribute to the ongoing discussion on which city models can bring the greatest benefits for the environment, climate, and health. Spanish Ministry of Science and Innovation, State Research Agency, Generalitat de Catalunya, Centro de Investigación Biomédica en red Epidemiología y Salud Pública, and Urban Burden of Disease Estimation for Policy Making as a Horizon Europe project.

A Sampling Strategy for High-Dimensional, Simulation-Based Transportation Optimization Problems

When tackling high-dimensional, continuous simulation-based optimization (SO) problems, it is important to balance exploration and exploitation. Most past SO research focuses on the enhancement of exploitation techniques. The exploration technique of an SO algorithm is often defined as a general-purpose sampling distribution, such as the uniform distribution, which is inefficient at searching high-dimensional spaces. This work is motivated by the formulation of exploration techniques that are suitable for large-scale transportation network problems and high-dimensional optimization problems. We formulate a sampling mechanism that combines inverse cumulative distribution function sampling with problem-specific structural information of the underlying transportation problem. The proposed sampling distribution assigns greater sampling probability to points with better expected performance as defined by an analytical network model. Validation experiments on a toy network illustrate that the proposed sampling distribution has important commonalities with the underlying and typically unknown true sampling distribution of the simulator. We study a high-dimensional traffic signal control case study of Midtown Manhattan in New York City. The results show that the use of the proposed sampling mechanism as part of an SO framework can help to efficiently identify solutions with good performance. Using the analytical information for exploration, regardless of whether it is used for exploitation, outperforms benchmarks that do not use it, including standard Bayesian optimization. Using the analytical information for exploration only yields solutions with similar performance than when the information is used for exploitation only, reducing the total compute times by 65%. This paper sheds light on the importance of developing suitable exploration techniques to enhance both the scalability and the compute efficiency of general-purpose SO algorithms. Funding: T. Tay thanks the Agency for Science, Technology and Research (A*STAR) Singapore for funding his work. Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2023.0110 .

Disparities in incidence and mortality of hematologic cancers in Southeast Asia: A 2020 analysis.

e23291 Background: Hematologic cancers (HCs) in Southeast Asia (SEA), a diverse population of over 680 million, are still understudied. Data from the 2020 Global Cancer Observatory (GCO) was used to estimate the incidence and mortality of HCs in the region to provide direction for effective disease control and improve population outcomes. Methods: The International Agency for Research on Cancer’s publicly available GCO data aggregates global cancer incidence and mortality. We report cumulative incidence rate (CIR) and cumulative mortality rate (CMR) defined per 100,000 people, and weighted average age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) in 2020. Data for Hodgkin Lymphoma (HL), Non-Hodgkin's Lymphoma (NHL), Leukemia, and Multiple Myeloma (MM) in the world, in SEA, and in the 11 individual SEA countries are presented. Results: The table presents CIR, ASIR, CMR, and ASMR of hematologic cancers in SEA compared to overall global data. CIR, ASIR, CMR, and ASMR were higher for males than females in SEA. For NHL, CIR was highest in Singapore (18.8), Thailand (10.2), and Brunei (9.6) and lowest in Myanmar & Cambodia (3.6), and Timor-Leste (2.7). ASIR trends were parallel albeit differences were smaller. CMR was highest in Singapore (6.2) and Thailand (5.9) and lowest in Timor-Leste (1.5). ASMR was highest in Brunei (4.5) and lowest in Timor-Leste (2.0). For leukemia, CIR was highest in Singapore (11.1) and lowest in Myanmar (3.1) and Timor-Leste (2.6); ASIR was highest in Singapore (8.9) and lowest in Myanmar (3.2) and Timor-Leste (2.9). CMR was highest in Singapore (5.2) and lowest in Myanmar (2.6) and Timor-Leste (2.3). ASMR was highest in Lao PDR (4.7) and Vietnam (4.5), and lowest in Singapore (3.1) and Timor-Leste (2.9). For MM, CIR was highest in Singapore (4.1), ASIR was highest in Brunei (2.4) and both are lowest in Myanmar (0.4). CMR was highest in Singapore & Thailand (1.8) and lowest in Myanmar (0.35); ASMR rates were similar. For HL, CIR was highest in Brunei Darussalam (1.8) and Singapore (1.4) and lowest in Myanmar (0.2). ASIR trends were similar. CMR was highest in Vietnam (0.26) and lowest in Singapore (0.1) and Myanmar (0.08). ASMR trends were similar. Conclusions: Despite lower regional average incidence and mortality, significant intra-regional variations exist reflecting disparities in the management of HCs. In addition, while data suggests lower disease burden in SEA, mortality rates are still comparable and in some cases worse than the global average. More work is needed to investigate HC epidemiology in SEA to inform cancer control in the region and improve its blood cancer outcomes. [Table: see text]

Cancer survival in sub-Saharan Africa (SURVCAN-3): a population-based study

The Cancer Survival in Africa, Asia, and South America project (SURVCAN-3) of the International Agency for Research on Cancer aims to fill gaps in the availability of population-level cancer survival estimates from countries in these regions. Here, we analysed survival for 18 cancers using data from member registries of the African Cancer Registry Network across 11 countries in sub-Saharan Africa. We included data on patients diagnosed with 18 cancer types between Jan 1, 2005, and Dec 31, 2014, from 13 population-based cancer registries in Cotonou (Benin), Abidjan (CÔte d'Ivoire), Addis Ababa (Ethiopia), Eldoret and Nairobi (Kenya), Bamako (Mali), Mauritius, Namibia, Seychelles, Eastern Cape (South Africa), Kampala (Uganda), and Bulawayo and Harare (Zimbabwe). Patients were followed up until Dec 31, 2018. Patient-level data including cancer topography and morphology, age and date at diagnosis, vital status, and date of death (if applicable) were collected. The follow-up (survival) time was measured from the date of incidence until the date of last contact, the date of death, or until the end of the study, whichever occurred first. We estimated the 1-year, 3-year, and 5-year survival (observed, net, and age-standardised net survival) by sex, cancer type, registry, country, and human development index (HDI). 1-year and 3-year survival data were available for all registries and all cancer sites, whereas availability of 5-year survival data was slightly more variable; thus to provide medium-term survival prospects, we have focused on 3-year survival in the Results section. 10 500 individuals from 13 population-based cancer registries in 11 countries were included in the survival analyses. 9177 (87·4%) of 10 500 cases were morphologically verified. Survival from cancers with a high burden and amenable to prevention was poor: the 3-year age-standardised net survival was 52·3% (95% CI 49·4-55·0) for cervical cancer, 18·1% (11·5-25·9) for liver cancer, and 32·4% (27·5-37·3) for lung cancer. Less than half of the included patients were alive 3 years after a cancer diagnosis for eight cancer types (oral cavity, oesophagus, stomach, larynx, lung, liver, non-Hodgkin lymphoma, and leukaemia). There were differences in survival for some cancers by sex: survival was longer for females with stomach or lung cancer than males with stomach or lung cancer, and longer for males with non-Hodgkin lymphomas than females with non-Hodgkin lymphomas. Survival did not differ by country-level HDI for cancers of the oral cavity, oesophagus, liver, thyroid, and for Hodgkin lymphoma. For cancers for which population-level prevention strategies exist, and with relatively poor prognosis, these estimates highlight the urgent need to upscale population-level prevention activities in sub-Saharan Africa. These data are vital for providing the knowledge base for advocacy to improve access to prevention, diagnosis, and care for patients with cancers in sub-Saharan Africa. Vital Strategies, the Martin-Luther-University Halle-Wittenberg, and the International Agency for Research on Cancer. For the French and Portuguese translations of the abstract see Supplementary Materials section.

Public awareness of the association between the risk of breast cancer (BC) development and alcohol consumption (AC) among women aged 18–75 years.

e22547 Background: Worldwide, 4·4% of all new cases of female BC are attributable to alcohol use. Alcohol is recognized as a group 1 carcinogen, as classified by the International Agency for Research on Cancer. However, public awareness of the association remains low. We aim to look at the awareness of the association between AC and the risk of BC development among female employees of a community hospital in the United States. Methods: We sent an 8-item survey to 100 randomly selected adult females working in a community hospital via an online link. The survey was voluntary, with no incentives. We captured the following measures: age, alcohol use, awareness of AC as a BC risk factor, education level, screening for BC, and personal or family history(FH) of BC. Analyses examined correlates of associations between awareness and conceptual predictors. Results: Sixty females (60% response rate) responded to the survey. The age groups were: 28%(17): 18-39 years, 25%(15): 40-49 years, and 47%(28): 50-75 years. 22%(13) had a graduate(Gr), 56%(34) had an undergraduate(UG), and 22% (13) had a high school level of education. 33% (20/60) consumed alcohol. 61% (37/60) did not consider AC as a risk factor(RF) for BC development. 54% with Gr, 62% with UG, and 71% with a high school level of education did not consider AC to be a RF for BC. 41% among 18-39, 67% among 40-49, and 72% among 50-75 year-olds did not consider AC an RF for BC. 92% (55/60) never received education about the association of BC with alcohol intake. 23% with Gr, 5% with UG, and 0% with high school received education about the association of Alcohol and BC. 86% of 40-49 years and 75% of 50-75 years had undergone screening mammograms in the last three years. Mammogram rates were 75% in women with positive FH, compared to 45% without positive FH. Conclusions: The results revealed a low level of awareness of the risk of alcohol use with BC, with just 40% of females considering it as a risk factor. Younger age and higher academic levels were the variables that had the strongest association with better awareness. A further lower level of education was reported, with more than 90% never having received education about the association. We must orchestrate awareness of this association with attention to individuals with lower educational levels.

Characterizing TP53 mutations in bone and soft tissue sarcoma.

e23521 Background: Tumor protein P53 (TP53) is the most frequently mutated gene in cancer and most mutations inactivate wild type TP53 activity through heterogenous mechanisms. Whether different variants of mutant TP53 have different biologic potencies or clinical outcomes remain unclear. This ongoing study aims to characterize the spectrum of TP53 mutations in patients with bone and soft tissue sarcoma. Methods: We retrospectively identified and analyzed patients with bone and soft tissue sarcoma who underwent MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel and had at least one mutation in the TP53 gene at Memorial Sloan Kettering Cancer Center. Mutations in the TP53 gene were categorized into the following sub-types: fusion, missense, splice site, or protein-truncating. Hotspots were defined as variants with frequency of 10 or greater. We queried the missense variants for the 800 most frequent variants recorded in the International Agency for Research on Cancer R20 (IARC), which were structurally characterized based on their impact on TP53 protein and rescue potencies with arsenic trioxide (ATO) in vitro (Song et al. Sci Transl Med. 2023). Results: We identified a total of 1257 patients with bone and soft tissue sarcoma who had at least one mutation in TP53. 92.5% of patients had only 1 mutation in TP53. In total, 1363 mutations were detected with 541 variants identified across all sarcoma subtypes. Most TP53 mutations were identified in soft tissue leiomyosarcoma (18.05%), uterine leiomyosarcoma (12.84%), sarcoma not otherwise specified (15.62%), undifferentiated pleomorphic sarcoma (12.11%), and osteosarcoma (7.78%). Of the 541 variants identified, the most frequent alterations were intragenic fusion (6.23%), R175H missense (2.93%), R248Q missense (2.27%), R273H missense (2.13%), and R213* protein-truncating (2.05%) mutations. Of the 800 most frequent missense variants in IARC R20 database, 233 missense variants were detected representing 52% of all mutations detected. Structural or likely structural mutations represented most of the identified missense mutations (77.46%). These mutations were clustered in the following hotspots: R175H, Y220C, R282W, H179Y, and C135Y. DNA-contact mutations were clustered in the following hotspots: R248Q, R273H, R273C, and R248W. Conclusions: This analysis highlights the heterogenous landscape of TP53 mutations in bone and soft tissue sarcomas. Structural variants are prevalent in sarcoma and occur at hotspots that may represent novel drug targets in the future.

Cancer in Southeast Asia: A comparative analysis of 2022 incidence and mortality data.

10564 Background: Southeast Asia (SEA), home to over 680 million people representing almost 9% of the global population, is amongst the most diverse and fastest-growing regions in the world. This study evaluates cancer incidence and mortality in Association of Southeast Asian Nations (ASEAN) countries with the goal of informing future research, health services, and cancer policy in the region. Methods: The number of new cases of and deaths from the leading cancers in the ASEAN region, colorectum including anus (ICD-10 C18-C21), liver including intrahepatic bile ducts (C22), lung including trachea and bronchus (C33-34), female breast (C50), cervix uteri (C53) and prostate (C61), were extracted from the International Agency for Research on Cancer GLOBOCAN 2022 database for the 10 ASEAN countries by sex and age groups. Age-standardized incidence and mortality rates (ASIR and ASMR) per 100,000 person-years are presented. Results: In 2022, breast cancer was the most common cancer among women in all ten ASEAN countries (ASIR: Singapore 72.6, Philippines 60.3, Brunei 50.2, Malaysia 46.1, Indonesia 41.8, Vietnam 38.0, Thailand 37.4, Laos 31.6, Cambodia 25.1, Myanmar 23.4). Breast cancer was also the most common cause of cancer mortality among women in five ASEAN countries (ASMR: Philippines 21.5, Malaysia 19.3, Singapore 17.8, Vietnam 14.7, Indonesia 14.4). In Thailand for which time trends are available, ASIR has risen from 19 per 100,000 in 2000 to 37.4 per 100,000 in 2022. Lung cancer was the most common cancer among men in the Philippines (ASIR 37.7), Malaysia (ASIR 23.3), Myanmar (ASIR 21.6), and Indonesia (ASIR 21.3). Lung cancer is also the leading cause of cancer death among men in the Philippines (ASMR 33.6), Singapore (ASMR 31.9), Brunei Darussalam (ASMR 23.8), Malaysia (ASMR 20.4), Myanmar (ASMR 19.9), and Indonesia (ASMR 19.0). Lung cancer is also the leading cause of cancer death among women in Brunei Darussalam (ASMR 18.4). Liver cancer contributes the greatest incidence and mortality among men in Cambodia (ASIR 39.4, ASMR 37.2), Laos (ASIR 36.5, ASMR 36.4), Vietnam (ASIR 34.9, ASMR 33.3), and Thailand (ASIR 34.4, ASMR 33.4). Liver cancer was also the leading cause of cancer death among women in Laos (ASMR 13.5), Cambodia (ASMR 13.3), and Thailand (ASMR 12.1). Cervical cancer is the leading cause of cancer death amongst women in Myanmar (ASMR 13.4). Colorectum cancer is the most common cancer in men in Singapore (ASIR 39.4) and Brunei Darussalam (ASIR 37.7). Conclusions: In 2022, cancer incidence and mortality in SEA were driven primarily by breast cancer among women and lung cancer among men. Liver cancer drives incidence and mortality in Cambodia, Laos, Thailand, and Vietnam. Cervical cancer and colorectal cancer are also significant contributors to incidence and mortality in SEA. Regional and global collaboration is needed to improve cancer prevention, access to diagnosis and care, and research in Southeast Asia.

Comprehensive investigation of the mutagenic potential of six pesticides classified by IARC as probably carcinogenic to humans

Pesticides are significant environmental pollutants, and many of them possess mutagenic potential, which is closely linked to carcinogenesis. Here we tested the mutagenicity of all six pesticides classified probably carcinogenic (Group 2A) by the International Agency of Research on Cancer: 4,4’-DDT, captafol, dieldrin, diazinon, glyphosate and malathion. Whole genome sequencing of TK6 human lymphoblastoid cell clones following 30-day exposure at subtoxic concentrations revealed a clear mutagenic effect of treatment with captafol or malathion when added at 200 nM or 100 μM initial concentrations, respectively. Each pesticide induced a specific base substitution mutational signature: captafol increased C to A mutations primarily, while malathion induced mostly C to T mutations. 4,4’-DDT, dieldrin, diazinon and glyphosate were not mutagenic. Whereas captafol induced chromosomal instability, H2A.X phosphorylation and cell cycle arrest in G2/M phase, all indicating DNA damage, malathion did not induce DNA damage markers or cell cycle alterations despite its mutagenic effect. Hypersensitivity of REV1 and XPA mutant DT40 chicken cell lines suggests that captafol induces DNA adducts that are bypassed by translesion DNA synthesis and are targets for nucleotide excision repair. The experimentally identified mutational signatures of captafol and malathion could shed light on the mechanism of action of these compounds. The signatures are potentially suitable for detecting past exposure in tumour samples, but the reanalysis of large cancer genome databases did not reveal any evidence of captafol or malathion exposure.

Evaluation of an E6/E7 PCR-capillary electrophoresis fragment analysis in the genotyping of human papillomavirus in archival FFPE samples of oropharyngeal cancer.

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.

Prospective iterative data visualization (DV) study to enhance health literacy in prostate cancer (PC).

11061 Background: Methods used to visualize and present comparative effectiveness research (CER) impact patient (pt) and caregiver (CG) understanding and ultimately treatment decisions. Evidence-based approaches to optimize DV and comprehension in PC are lacking. We studied the presentation and DV of CER with key stakeholders aiming to overcome health disparity/inequity barriers related to understanding of CER DV. Methods: A panel representing pt and advocate, industry, and health care provider viewpoints provided qualitative feedback on multiple CER DV methods and generated a survey for US PC pts and CGs. Respondents were identified by a market research agency (buzzback, n=192) or a pt advocacy group (ZERO Prostate Cancer, n=58). Respondents first reported on comfort with and understanding of scientific data on PC using a Likert scale, then evaluated a randomly assigned graphic (1 of 2 versions each depicting the same information) for each of 4 topics. For efficacy and prostate-specific antigen (PSA) data, figures showed superiority of treatment over placebo; for safety, figures positively or negatively represented outcomes. For quality of life (QoL), overall QoL and specific QoL domains were illustrated. For each graphic, respondents first suggested their own key takeaway, then selected the best from 4 options, and reason for selection. Graphics were then assessed side by side with better key takeaway selected to create an overall story. Results: Respondents (pts, n=199; CGs, n=51) enrolled between Aug and Sep 2023; 54% were non-White; 52% had an annual income <$75,000/yr; 45% had no college degree. Some respondents reported being uncomfortable/neutral toward PC scientific data (26%) or found data difficult to understand (35%) or overwhelming (29%). >70% identified correct takeaways for Efficacy and PSA. Figures with numerical data showing a difference between treatment groups (Efficacy, PSA) more effectively communicated key takeaways than those without (Safety, QoL). Figures representing pts without toxicity (positive reporting) versus pts with toxicity (negative reporting) were better understood (62% vs 37%) and communicated (67% vs 33%). Respondents (~55-60%) chose the correct key takeaway for QoL figures, not containing quantitative data, and were divided as to which version best communicated the key takeaway. There were no consistent, robust patterns of differences in accuracy of interpretation based on respondent characteristics, especially for top performing Efficacy and PSA graphics. Conclusions: This is one of the first prospective multistakeholder studies in PC to explore comprehension and preferences from a diverse group of pts and CGs. Figures showing a difference between treatments were more accurately interpreted than those conveying parity. We provide a benchmark for best practices for CER DV for pts and CGs to assist in their education and optimize shared decision-making.

Soluble guanylate cyclase stimulator as an emerging therapeutic option in the management of arrhythmias in heart failure rat model

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This research was supported by VEGA grant no. 2/0002/20 and 2/0006/23, the Slovak Research and Development Agency under contract no. 21-0410, European Regional Development Fund: ITMS2014+: 313011AVG3. This research was also partially supported by the Ministry of Health of the Czech Republic within the project for the development of the research organization [grant number 00023001 (IKEM)—institutional support] and also supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU Heart failure (HF) is a complex clinical syndrome characterized by a decrease in the efficiency of the heart pump, leading to a decline in hemodynamic status and cardiac remodelling, that can contribute to the formation of a substrate for arrhythmias. Antiarrhythmic drug therapy is still suboptimal and current therapies are not efficacious enough. The purpose of the current study was therefore to examine the efficiency of nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) stimulator. We used as an experimental model male hypertensive Ren-2 transgenic rats (TGR, n = 16), normotensive Hannover Sprague–Dawley rats (HSD, n = 17), and a rat model of HF surgically induced by aortocaval fistula (ACF) in rats of both strains (n = 27). After ACF induction were rats treated by sGC stimulator BAY41-8543 (3 mg/kg/day for 30 weeks) alone or combined with angiotensin-converting enzyme inhibitor (ACEi) Trandolapril (0.25 mg/kg/day for 30 weeks). Age of the animals at the end of the experiment was 40 weeks. Left ventricle tissue and plasma samples were used for further analyses. Treatment by sGC stimulator significantly decreased rats' mortality, and systolic blood pressure, and significantly increased levels of antioxidant enzyme superoxide dismutase 1, matrix metalloproteinase 2, total and phosphorylated connexin 43 as well as protein kinase C epsilon, implicated in remodelling of extracellular matrix and intercellular communication, in the left ventricle of TGR rats. Application of sGC stimulator slightly normalized elevated collagen deposition and hydroxyproline content in the left ventricular tissue of TGR rats. Unfortunately, we did not observe any effect of the sGC stimulator in the TGR ACF group. These results support the hypothesis that sGC stimulators might represent a class of drugs suitable for combating heart failure with partially anti-arrhythmic potential, but further studies are needed.

Cardioprotective effects of Empagliflozin in cardiac volume overload-induced by aortocaval fistula in rats

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Slovak Research and Development Agency under the contract no. 21-0410 VEGA grants no. 2/0006/23 Heart failure is characterized by reduction in cardiac output and the occurrence of malignant arrhythmias, thereby contributing significantly to high morbidity and mortality worldwide. Myocardial structural remodelling is a key factor contributing to the development of these life-threatening events and belongs to unsolved clinical issues challenging to investigate in animal models. The aim of our study was to explore the impact of cardiac volume overload (VO) on structural remodelling and electrical coupling protein, connexin43 (Cx43) in the left and right heart ventricles as well as the efficacy of treatment with SGLT2i, Empagliflozin. Aortocaval fistula (ACF) was surgically induced in 6-month-old Wistar rats, to develop VO during 4 weeks, followed by oral administration of Empagliflozin 10 mg/kg/b.w. daily for 5 weeks. At the end of the experiment, biometric parameters were registered and left and right heart tissue samples were snap-frozen and kept at -80°C for western blot analysis and microscopic examination. Findings revealed an increase of heart, left and right ventricular mass due to ACF-VO versus sham controls, which was associated, with eccentric myocardial hypertrophy. Noteworthy, Empagliflozin reduced heart, left and right ventricular mass. Levels of myocardial protein Cx43, that determine electrical coupling among cardiomyocytes, were reduced by ACF-VO, while normalized by treatment with Empagliflozin. Moreover, treatment attenuated ACF-VO-induced increase of interstitial collagen visualized by van Gieson staining. It was in line with the protein expression of MMP-2, which is involved in structural remodeling. The protein levels of PKCε, concerned/associated with modulation of Cx43 and extracellular matrix, were decreased due to ACV-VO but normalized after treatment with Empagliflozin. On the other hand, protein levels of PKCδ, involved in proapoptotic and prohypertrophic pathways, were increased and normalized by Empagliflozin. The changes were more pronounced in the right ventricle compared to the left heart ventricle. In summary, our pilot results point out the benefit of Empagliflozin due to the suppression of myocardial structural remodelling and preservation of Cx43 in the rat ACF-VO model. Furthermore, this Empagliflozin-induced cardioprotection was associated with the normalization of Cx43, MMP-2, and PKC levels independent of glucose control. However, further analyses are needed to reveal the molecular mechanisms of the cardioprotective effects of Empagliflozin.

Indirect Effects of PM2.5 Exposure on COVID-19 Mortality in Greater Jakarta, Indonesia: An Ecological Study.

Air pollution, including PM2.5, was suggested as one of the primary contributors to COVID-19 fatalities worldwide. Jakarta, the capital city of Indonesia, was recognized as one of the ten most polluted cities globally. Additionally, the incidence of COVID-19 in Jakarta surpasses that of all other provinces in Indonesia. However, no study has investigated the correlation between PM2.5 concentration and COVID-19 fatality in Jakarta. To investigate the correlation between short-term and long-term exposure to PM2.5 and COVID-19 mortality in Greater Jakarta area. An ecological time-trend study was implemented. The data of PM2.5 ambient concentration obtained from Nafas Indonesia and the National Institute for Aeronautics and Space (LAPAN)/National Research and Innovation Agency (BRIN). The daily COVID-19 death data obtained from the City's Health Office. Our study unveiled an intriguing pattern: while short-term exposure to PM2.5 showed a negative correlation with COVID-19 mortality, suggesting it might not be the sole factor in causing fatalities, long-term exposure demonstrated a positive correlation. This suggests that COVID-19 mortality is more strongly influenced by prolonged PM2.5 exposure rather than short-term exposure alone. Specifically, our regression analysis estimate that a 50 µg/m3 increase in long-term average PM2.5 could lead to an 11.9% rise in the COVID-19 mortality rate. Our research, conducted in one of the most polluted areas worldwide, offers compelling evidence regarding the influence of PM2.5 exposure on COVID-19 mortality rates. It emphasizes the importance of recognizing air pollution as a critical risk factor for the severity of viral respiratory infections.

Tools and methods to study and replicate experiments addressing human social cognition in interactive scenarios.

In the last decade, scientists investigating human social cognition have started bringing traditional laboratory paradigms more "into the wild" to examine how socio-cognitive mechanisms of the human brain work in real-life settings. As this implies transferring 2D observational paradigms to 3D interactive environments, there is a risk of compromising experimental control. In this context, we propose a methodological approach which uses humanoid robots as proxies of social interaction partners and embeds them in experimental protocols that adapt classical paradigms of cognitive psychology to interactive scenarios. This allows for a relatively high degree of "naturalness" of interaction and excellent experimental control at the same time. Here, we present two case studies where our methods and tools were applied and replicated across two different laboratories, namely the Italian Institute of Technology in Genova (Italy) and the Agency for Science, Technology and Research in Singapore. In the first case study, we present a replication of an interactive version of a gaze-cueing paradigm reported in Kompatsiari et al. (J Exp Psychol Gen 151(1):121-136, 2022). The second case study presents a replication of a "shared experience" paradigm reported in Marchesi et al. (Technol Mind Behav 3(3):11, 2022). As both studies replicate results across labs and different cultures, we argue that our methods allow for reliable and replicable setups, even though the protocols are complex and involve social interaction. We conclude that our approach can be of benefit to the research field of social cognition and grant higher replicability, for example, in cross-cultural comparisons of social cognition mechanisms.

Carcinogenicity of dietary MelQx in the prostate, breast, colon, and liver cancers, and the inhibitory effects of some compounds on MelQx: a mini review

Heterocyclic amines (HCAs) are among the most common toxic compounds formed in food, particularly protein-rich foods when prepared at high temperatures for an extended period. To date, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is considered one of the most abundant HCAs. However, only a few studies have been conducted on MeIQx, particularly on its carcinogenic potential, despite being labelled as Group 2B Carcinogens by the International Agency for Research on Cancer. MeIQx has been shown to contribute to various types of cancer such as prostate, breast, colon and liver cancers. In most cancers, the genotoxic metabolites of MeIQx induce cancer primarily through the formation of DNA-carcinogen adducts, although some studies show their association with oxidative damage. Nonetheless, the involvement of various enzymes such as Nacetyltransferase, sulfotransferases, and glutathione S-transferases equally plays a crucial role in determining whether this carcinogen undergoes bio-activation or detoxification. This review sought to highlight the most recent research on the carcinogenic effects of MeIQx in prostate, colon, breast, and liver cancers, and provide a list of some potential compounds that can inhibit MeIQx formation. Epidemiological studies exploring the association between MeIQx exposure and prostate, breast and colon cancers produced mixed results. However, most of the experimental studies demonstrated the carcinogenic role of MeIQX in prostate, breast, colon, and liver cancers in both in vitro and in vivo models. Further investigation on the effects of its consumption on human health is needed which may help in understanding and reducing its potential to cause cancer. The inhibitory properties of other natural compounds on this carcinogen should also be explored

Application of ChatGPT in soil science research and the perceptions of soil scientists in Indonesia

Since its arrival in late November 2022, ChatGPT-3.5 has rapidly gained popularity and significantly impacted how research is planned, conducted, and published using a generative artificial intelligence approach. ChatGPT-4 was released four months later and became more popular in November 2023. However, there is little study about the perception of scientists of these chatbots, especially in soil science. This article presents the new findings of a brief research investigating soil scientists' responses and perceptions towards chatbots in Indonesia. This artificial intelligence application facilitates conversation-based interactions in text format. The study evaluated ten ChatGPT answers to fundamental questions in soil science, which has developed into a normal science with a mutually agreed-upon paradigm. The evaluation was carried out by seven soil scientists recognized for their expertise in Indonesia, using a scale of 1–100. In addition, a questionnaire was distributed to soil scientists at the National Research and Innovation Agency of the Republic of Indonesia (BRIN), universities, and Indonesian Soil Science Society (HITI) members to gauge their perception of ChatGPT's presence in the research field. The study results indicate that the scores of ChatGPT answers range from 82.99 to 92.24. ChatGPT-4 is better than both the paid and free versions of ChatGPT-3.5. There is no significant difference between the English and Indonesian versions of ChatGPT-4.0. However, the perception of general soil scientists about the level of trust is only 55%. Furthermore, 80% of soil scientists believe that chatbots can only be used as digital tools to assist in soil science research and cannot be used without the involvement of soil scientists.

Food safety knowledge, hygiene practices among food handlers, and microbiological quality of animal side dishes in contract catering

Food poisoning is a major concern in catering services in Indonesia, with multiple outbreaks being reported in factories and offices. This study aimed to assess the level of food safety knowledge, personal hygiene practices, and microbiological quality of chicken and egg dishes at three catering companies in the Yogyakarta Special Region of Indonesia, which provide mass catering for workers. From March to July 2019, a cross-sectional study was conducted using validated questionnaires, observation checklists, and microbiological tests to measure the parameters of Escherichia coli and Staphylococcus aureus. Pearson and Rank-Spearman correlation tests, as well as independent sample t-tests, were used for statistical analysis. The study revealed that 75% of the subjects had limited knowledge of food safety, with only 5% having a good understanding. Furthermore, 95% of the subjects had not received any food safety training, resulting in poor hygiene practices among the food handlers. Although there was no significant correlation between food safety knowledge and hygiene practices (p>0.05), certain practices, such as appearance and hand washing, were significantly correlated with age. Employment duration was negatively correlated with food safety knowledge (p=0.027; r=-0.494). While chicken samples were free from E. coli and S. aureus, one egg sample was found to be contaminated with E. coli. The research emphasizes the significance of providing frequent food safety training to food handlers, ideally every year. Additionally, it recommends conducting larger sample studies and collaborating with government agencies for future research.