Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line.

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

Understanding seasonal variations in As and Pb river fluxes and their regulatory mechanisms through monitoring data.

The Doce River Basin (DRB) suffers with the adverse impacts of mining activities, due to its high level of urbanization and numerous industrial operations. In this study, we present novel insights into contaminant flow dynamics, seasonal variations, and the primary factors driving concentration levels within the region. We conducted an extensive analysis using a database sourced from the literature, which contained data on the contamination of arsenic (As) and lead (Pb) in the Doce River. Our primary aim was to investigate the patterns of As and Pb flow throughout the entire basin, their response to seasonal fluctuations, and the key parameters influencing their concentration levels. The results showed significant seasonal fluctuations in As and Pb fluxes, peaking during the rainy season. The 2015 Fundão dam breach in the DRB led to notable changes, elevating elemental concentrations, particularly As and Pb, which were subsequently transported to the Atlantic Ocean. These increased concentrations were primarily associated with iron and manganese oxides, hydroxides, and sulfates, rather than precipitation, as evidenced by regressions with low R2 values for both As (R2 = 0.07) and Pb (R2 < 0.001), concerning precipitation. The PCA analysis further supports the connection between these elements and the oxides and hydroxides of Fe and Mn. The approach employed in this study has proven to be highly effective in comprehending biogeochemical phenomena by leveraging data from the literature and could be a model for optimizing resources by capitalizing on existing information to provide valuable insights for drainage basin management, particularly during crises.

Identification and characterization of plastic debris in the gastrointestinal tract of Guiana dolphins (Sotalia guianensis) from Espírito Santo coast, Brazil.

The Guiana dolphin (Sotalia guianensis) is categorized as vulnerable in the Brazilian list of endangered animals, and its populations suffer from several anthropological threats. In this study, we analyzed the presence of macro, meso, and microplastics (MPs) in Guiana dolphins (n = 12) in Brazil Southeastern coast by analysing their gastrointestinal tract. The MP extractions were carried out with H2O2 (35 %) to remove organic matter. Four specimens ingested meso and macroplastics, including an item of polypropylene of 19.22 cm that was produced about 943 km from the place in which the animal was found stranded. All the specimens analyzed had fragment-type microplastics in their intestines. Blue was the prevailing color, followed by black, green, and red. We highlight the contamination by microplastics in the species, still little investigated, especially the need to understand the contamination by microplastics along trophic levels.

Trace element bioaccumulation in the hepatic tissue of juvenile green turtles (Chelonia mydas) stranded along the Campos and Espírito Santo basins, southeastern Brazil.

This study analyzed the concentrations of 15 (Al, As, Ba, Cd, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se, V, Zn) toxicologically important trace elements in the livers of 110 green turtles stranded in two areas of the Brazilian coast. These areas are essential for the refuge, feeding, and reproduction of the species, and the information obtained is intended to support the development of conservation strategies. Higher concentrations were observed in the Região dos Lagos, RJ in almost all elements, except for Al, Mo, Pb, and V. This location showed statistically higher differences in the concentrations of Cd (4.66 ± 2.33 µg.g-1), Fe (846.62 ± 583.06 µg.g-1), and Zn (27.17 ± 10.90 µg.g-1). The differences in trace element concentration patterns between the two study areas are likely influenced by multiple factors, including the bioavailability of trace elements, oceanic upwelling events, anthropogenic activities, habitat characteristics, and organism-specific metabolic processes.

Geochemical soil dynamics on a bimodal post-collisional intrusive complex.

The importance of environmental quality for global social and ecological development, including soil degradation, cannot be overstated. Trace elements dispersed in the environment due to anthropogenic or geogenic activities can result in ecotoxicological impacts, negatively influencing environmental quality. The reference values for soil quality concerning trace elements are primarily based on geological, geomorphological, and pedological patterns. However, intrinsic geological factors may diverge some concentration levels from established norms. Therefore, conducting comprehensive surveys of environmental quality reference values becomes imperative, incorporating geological, geomorphological, and pedological patterns. A deeper understanding of the distribution of these elements is also required. Multivariate analysis proves crucial in compartmentalizing the most relevant factors, particularly in regions marked by bimodal magmatism arising from post-collisional distensional processes, such as the Santa Angélica intrusive suite in southeast Brazil. This study collected soil samples from pastures and natural grasslands with minimal anthropogenic intervention at two depths. These samples underwent various chemical and physical analyses. Statistical techniques such as correlation analysis, principal component analysis, hierarchical clustering, and geostatistics were utilized to interpret the data. The analysis revealed a correlation between the clay fraction and trace elements, demonstrating that clustering is an effective methodology for ascertaining landscape distribution patterns of these components. When compared to quality reference values, it was observed that most soil content levels exceeded both global and local standards. This study suggests that the presence of barium (Ba) in the soil might be due to the isomorphic replacement of feldspathic minerals in acidic and intermediate rocks, whereas molybdenum (Mo) seems to be associated with soils in the domain of porphyritic allanite granite. However, additional research is warranted to determine the concentration factor of Mo in this scenario accurately.

Seasonal variation, contribution and dynamics of trace elements in the drainage basin and estuary of the Serinhaém river, BA.

In the present study a mass balance calculation was used to quantify trace elements (Al, Ba, Cd, Cr, Cu, Fe, Mn, Pb, Ti, V and Zn) fluxes exported from the Serinhaém River estuary to the Atlantic Ocean. The studied elements exportation in the particulate fraction showed higher fluxes in the first sampling campaign and a high export rate to the Atlantic Ocean during this period. The physical-chemical parameters showed the highest values in sampling campaign 1. These variations are probably the cause of the different trace elements behavior in fluvial and estuarine areas, where removal and addition processes between particulate and dissolved phases took place, affecting distribution coefficient and fluxes to the Atlantic Ocean. EPA ecosystems present values in accordance with Brazilian legislation for pristine areas, however, monitoring programs must be carried out in the region, to avoid future environmental problems.

Microplastics in fishes in amazon riverine beaches: Influence of feeding mode and distance to urban settlements.

Microplastic (MP) pollution is a global problem and has affected several biological levels even in protected areas. In the present study, MP contamination was investigated in fish associated with sandy beaches in a permanent environmental protection area in the Amazon. In order to achieve this goal, the shape, color, abundance, richness, and chemical composition of MPs in the digestive tract of 29 fish species in 24 beaches of the Machado River, western Brazilian Amazon, were evaluated. Linear mixed models (LMMs) were adjusted to test the effects of local human modification (HMc), distance from urban settlements, distance from the closest affluent, and trophic categories of fish species on microplastic abundance and richness in their digestive tracts. From the 1082 fish analyzed, 332 (30 %) presented MPs in their digestive tracts. A total of 617 MPs was found (1.8 ± 1.6 MPs; 4.5 ± 1.9 MPs/g fish). Omnivorous and insectivorous fish presented more MPs in sandy beaches located closer to urban settlements. However, carnivorous fish presented a higher abundance of MPs in their digestive tracts compared with the other trophic guilds. This is the first study to analyze plastic contamination in fish associated with sandy beaches in the Amazon (Brazil), and it revealed contamination of the ichthyofauna mainly related to the distance from urban settlements. Our results reinforce the need for better management of landscape surrounding protected areas to mitigate MP pollution.

Mercury levels in an environmentally protected estuarine area in Northeast Brazil: partitioning in the water column and transport to the ocean.

In this study, total Hg concentrations (HgT) were determined in the suspended particulate matter (SPM) and the dissolved fraction of the water column to evaluate their behavior through a gradient of physical-chemical parameters in a continuum between rivers and the Serinhaém River estuary of the Pratigi Environmental Protection Area, a pristine environment without point sources of Hg contamination, located in Northeast Brazil. Twelve points were sampled, forming a river-estuary transect, and two samplings were carried out (April and September 2019). Significant spatial and temporal effects were detected only for particulate HgT and not for dissolved HgT. Considering both samplings, the mean HgT concentrations in SPM were 1112 ± 824 and 44 ± 33 ng·g-1 in the river and estuary, respectively. Also, HgT concentrations in the dissolved fraction (1.61 ± 0.61 ng·L-1) were below the limits established by environmental agencies (CONAMA = 2 µg∙L-1 and USEPA = 1.4 µg·L-1). Salinity and SPM concentrations were important predictors of HgT in the water column (R2 = 0.81, p < 0.0001; R2 = 0.56, p < 0.0001, respectively). Mercury transport to the ocean through SPM was 2 kg∙year-1, 4000 times greater than the dissolved fraction.

Rapid On-Site Evaluation by Endosonographer of Endoscopic Ultrasound Fine-Needle Aspiration of Solid Pancreatic Lesions: A Randomized Controlled Trial.

OBJECTIVES: Rapid on-site evaluation (ROSE) by cytopathologists during endoscopic ultrasound-fine-needle aspiration (EUS-FNA) of solid pancreatic lesions (SPLs) improves adequacy and diagnostic accuracy while reducing the number of needle passes. We evaluated the usefulness of ROSE performed by the endosonographer. METHODS: Patients with an SPL were randomly assigned to EUS-FNA with ROSE or non-ROSE. Procedure duration, number of needle passes, specimen adequacy, and adverse event rates were compared. RESULTS: Sixty-five patients were enrolled (33 in the ROSE vs 32 in the non-ROSE group). Both groups were similar in terms of age, sex, size, and location of the lesion. Specimen adequacy rates were high and similar between groups. Mean (standard deviation) procedure duration was shorter in the ROSE versus non-ROSE group (30.0 [11.3] vs 37.0 [7.2] minutes, P < 0.005), as well as the mean (standard deviation) number of needle passes (2.6 [0.8] vs 3.5 [0.8], P < 0.005). Accuracy parameters as sensitivity and accuracy of ROSE by the endosonographer for malignancy were 93% and 88%, respectively. CONCLUSIONS: After specific training, the endosonographer can accurately evaluate samples during EUS-FNA of SPL, allowing for a shorter procedure duration and a lower number of needle passes.

Letter to the editor: radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers.

A commentary on the original research article: 'Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers'. Of note, the predictor selection process, the cross-validation method, along with the lack of final testing of the developed model with a separated data set may mask overfitting, overestimating performance metrics.

Evaluation of the concentrations of elements at trace level in the Serinhaem River estuary, Bahia, Brazil, using chemometric tools.

The Serinhaém River estuary is located in the Environmental Protection Area (EPA) of Pratigi, in the State of Bahia, Brazil, which is recognized for being a relatively well-preserved environment. In this work, the levels of aluminum (Al), arsenic (As), barium (Ba), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), and zinc (Zn) were determined to evaluate the behavior of these chemical elements through geochemical parameters. Eighty-one sediment samples were collected in five sediment cores along the estuarine region. The results of the composition of the Serinhaém river basin showed high levels of Fe, Al, and Mn in the sediment samples. By using Principal Component Analysis, it was observed that 55.8% of the elements have a significant correlation with Fe, Al, and Mn, which may have the same origin or be associated with Fe and Mn oxy-hydroxides, and aluminosilicates. Although Cr, As, and V are correlated with Fe, Mn, and Al, their concentrations are above those established by NOAA, suggesting adverse effects on biota. Barium concentrations increased toward the outfall, where it meets the Camamu Bay, which is naturally enriched with this element. It was also possible to observe that along with the vertical profile, there were no variations in the concentrations of the elements, while along the estuary, it was possible to verify that the cores differ from each other. The estuary of the Serinhaém River can be considered to be influenced relatively little by human activities, and its concentrations can be considered as a base level for this coastal region.

Trace elements and stable isotopes in egg yolk of green turtles on Rocas Atoll, Brazil.

This study analyzed trace elements (As, Ba, Cd, Cu, Fe, Mn, Pb, Zn) and stable isotopes of carbon and nitrogen in egg yolk samples of female green turtles that nested in Rocas Atoll, Brazil, in 2017 and 2018. The trace elements concentration varied between years, with higher concentrations in 2017, suggesting that the nesting groups come from different foraging sites. The isotopic data indicated high overlap between years (73%), leading to an ambiguous interpretation on the turtles' foraging site. The Normalized Total Load presented a low association (0.01 < R2 < 0.41) with the stable isotopes. The Normalized Total Load that represents the trace element load in egg yolk is a holistic approach that can be applied elsewhere to predict ecotoxicology pathways in any animal species. We recommend a continuous monitoring to verify how the trace elements load behave in the nesting green turtles on Rocas Atoll.

Doce River Estuary: Geochemical Changes Following the Largest Tailing Spill in South America.

Accidents involving economic activities of great impact, such as mining, have caused massive environmental damage. In November 2015, the dam of Fundão, located in the city of Mariana, MG, broke and released 5 × 107 m3 of tailings in the nearby ecosystems, including the Doce River. The physicochemical changes that occurred in the Doce River estuary were analyzed, as well as the trace metal concentrations, both 1 day before and 1 month after the disaster. The analyses of the collected samples (water and sediment) showed changes to the physicochemistry regarding dissolved oxygen, SPM, and temperature (p = 0.008, 0.001, 0.036, respectively). It also detected metals (Fe and Al) in the dissolved fraction beyond the limits recommended by the Brazilian legislation. There was an increase in the total concentrations of Fe and Cd in the sediment after the rupture of the dam and a change in mobile metals (Al, Cd, Cr, Cu, Fe, Ni, Pb, and Zn), with higher concentrations of mobile metals being found closer to the ocean (p = 0.06356). After the rupture of the dam, there was a change in the granulometric fraction of the sediment, which became composed mainly of silt and clay. All of the results showed a change on the Doce River estuary, caused by the arrival of the tailings, which can result in future harmful effects with the release of metals present in the sediment and adsorbed to the particles. The changes to the sediment, such as changes in the granulometric fraction, can have negative consequences for the benthic community.

Geochemical evaluation of potentially toxic elements determined in surface sediment collected in an area under the influence of gold mining.

In this present paper, the distribution of toxic metals and sediment quality were evaluated in five sampling points of the Itapicuru-Mirim River located in the city of Jacobina, Bahia, Brazil. The concentration of the elements arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) were determined from sediment samples collected from the superficial layer (0-10 cm) in November 2013. After the samples' total decomposition, the total concentration of metals was determined by inductively coupled plasma optical emission spectrometry (ICP OES), except for Hg, which was measured by inductively coupled plasma atomic emission spectrometry (ICP AES). A geochemical evaluation of sediment quality was performed using enrichment factor (EF), geoaccumulation index (Igeo), and pollution load index (PLIThe results of the total concentrations in the analyzed sediment samples were compared with the threshold effect levels (TELs) and probable (PELs) effect levels (PELs) in sediment quality guidelines (SQGs). For the fraction <75 µm, the decreasing order for the metal concentrations was (ppm): Fe (10.86%) > Mn (120.8) > Cr (122) > Zn (76.5) > Pb (49.6) > Cu (32.6) > Ni (28.6) > Hg (0.31) > Cd (0.13). Igeo suggested a moderate to seriously polluted category for Hg and moderately polluted for Cu. Generally, the results indicated probable risks to the biota caused by Cr, Ni, Pb, and Hg metals. However, only Hg, Cd, and Cu were of anthropogenic origin. Although the sediments are relatively preserved from pollution by these metals, there is a progressive deterioration of this compartment downstream of the Itapicuru-Mirim River in the city of Jacobina.

Trace elements in green turtles (Chelonia mydas) from Rocas Atoll, NE Brazil: Baseline reference from a pristine nesting site.

This study presents the first report on the concentration of trace elements (Al, As, Ba, Cd, Cr, Cu, Fe, Mn, Ni, Pb, V and Zn) in the blood and egg fractions of green turtles from Rocas Atoll, a pristine nesting site in NE Brazil. The highest concentrations of all elements were in the blood or shell samples. In order, iron, Zn, Cu, Al and As presented the highest concentrations in all tissues. The nonessential trace elements were below the limit of detection for more than 50% of the yolk (Al, Cd and Pb) and albumen samples (Al, As, Ba, Cd and Pb). This study will serve as a baseline reference for future monitoring of the ecotoxicology of breeding green turtles in the southwestern Atlantic Ocean.

Near Infrared (NIR) Fluorescence is Not a Substitute for Lymphoscintigraphy and Gamma Probe for Melanoma Sentinel Node Detection: Results from a Prospective Trial.

BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard care for early detection and staging of lymph node metastasis in melanomas. Radiocolloids (RC) and blue dyes are used for SLN detection. Recently, near infrared (NIR) fluorescence tracing using indocyanine green has been developed as an alternative method for SLN detection. The relatively high tissue penetration depth of several millimeters and the ability to detect low concentrations of tracer both suggest that NIR may have significant advantages over RC and the blue dye methods. The objective of this study was to prospectively compare the performance of all three SLN detection techniques using them sequentially to evaluate the same group of patients. METHODS: One hundred twenty-one primary cutaneous melanoma patients with an indication for SLN biopsy were assigned to the procedure following NIR, blue dye, and RC detection techniques. RESULTS: No adverse event was reported. SLN was not detected in only 4.1% of cases. In 90.9%, an SLN was identified with NIR, but without any auxiliary technique in only 70.2% of cases. RC detected the SLN in 92.6% of cases. Patent blue was found in the sentinel node in 76.9%. The combination of all three techniques detected an SLN in 95.9% of cases. Metastases were present in 26.7%. The false-negative rate was 8.8%, with a negative predictive value of 91.2%. CONCLUSIONS: RC was the only technique with high SLN detection. Both the blue dye and NIR methods added sensitivity to the detection rate but should not be a substitute for RC.

Cross-talk between SUMOylation and ISGylation in response to interferon.

Interferon (IFN) plays a central role in regulating host immune response to viral pathogens through the induction of IFN-Stimulated Genes (ISGs). IFN also enhances cellular SUMOylation and ISGylation, though the functional interplay between these modifications remains unclear. Here, we used a system-level approach to profile global changes in protein abundance in SUMO3-expressing cells stimulated by IFNα. These analyses revealed the stabilization of several ISG factors including SAMHD1, MxB, GBP1, GBP5, Tetherin/BST2 and members of IFITM, IFIT and IFI families. This process was correlated with enhanced IFNα-induced anti-HIV-1 and HSV-1 activities. Also IFNα upregulated protein ISGylation through increased abundance of E2 conjugating enzyme UBE2L6, and E3 ISG15 ligases TRIM25 and HERC5. Remarkably, TRIM25 depletion blocked SUMO3-dependent protein stabilization in response to IFNα. Our data identify a new mechanism by which SUMO3 regulates ISG product stability and reinforces the relevance of the SUMO pathway in controlling both the expression and functions of the restriction factors and IFN antiviral response.

Trace metals in two commercial shrimps from southeast Brazil: Baseline records before large port activities in coastal waters.

This study presents baseline records of trace metals for two commercial shrimps from the inner continental shelf of southeast Brazil (~22°S). Organisms were sampled in 2004, 10 years before the beginning of large port activities in coastal waters. The concentrations of trace metals in muscle tissues (µg.g-1 w.w.) of Xyphopenaues kroyeri and Artemesia longinaris are as follows: Al: 141.57 and 146.71, Fe: 83.17 and 91.68, Zn: 28.69 and 29.70, Cu: 7.19 and 3.94, Mn: 1.47 and 1.72, Pb: 1.14 and 0.60, V: 0.66 and 0.56, Ni: 0.38 and 0.34, Cr: 0.42 and 0.29, and Cd: 0.15 and 0.14, respectively. Significantly higher concentrations of Cu and Pb were recorded for X. kroyeri. In general, the concentrations are below the maximum permissible limits for metals in fishery/food products, as established by the Brazilian Agency for Sanitary Vigilance (ANVISA), except for Pb and Cr. These baseline records are relevant for future monitoring.

Hg and δ15N in juvenile green turtles from southeastern Brazil (~23°S): Inferences about contamination levels and recruitment to coastal waters.

Total mercury (THg) and δ15N were analysed in liver and muscle of juvenile green turtles (Chelonia mydas) from a foraging site in southeastern Brazil (~23°S) to evaluate contamination levels and make inferences about the timescale that animals were recruited from oceanic to coastal waters. The values for THg and δ15N in liver and muscle were 432.2 and 72.8 µg kg-1 and 10.0‰ and 9.2‰, respectively. THg concentrations in tissues indirectly indicated that the main food resources for this consumer (i.e., macroalgae) had negligible levels of this element. Thus, this foraging site could be considered a pristine area in terms of Hg contamination. The THg and δ15N in liver were derived by more recent food ingestion than those in muscle. The juvenile green turtles that died because of incidental captures in fisheries practiced along this foraging site were individuals newly recruited from oceanic waters.

Characteristics of Brazilian melanomas: real-world results before and after the introduction of new therapies.

OBJECTIVE: This study is a characterization of the treatment patterns and outcomes of a Brazilian melanoma cohort collected of 1848 patients enrolled between 1996 and 2015. RESULTS: The superficial spreading subtype (35.1%) was the most prevalent, and the favoured anatomical location was the trunk (32.8%). The most common clinical stage was I (27.6%). The most frequent initial treatment was surgery (84.7%). Sentinel node biopsy was positive in 23.3% of cases. Chemotherapy was used to treat 298 patients (16.1%), immunotherapy for 67 (3.6%) and targeted therapy for 19 (1.0%). Distant recurrence was commonly observed (22.5%) and the mutation status of the BRAF gene was verified in 132 cases, with 42.4% positivity in this subset of patients. The melanoma specific actuarial 5-year survival for the cohort was 68.8%. There was a higher 5-year survival observed in metastatic melanoma patients who received immunotherapy and/or targeted therapy (34.2%) compared patients treated with just chemotherapy (20.0%). The survival analysis showed that sex, age, Breslow, clinical stage and distant recurrence were significant prognostic factors. This study provides a real-world description of how the introduction of new therapies such as immunotherapy and BRAF inhibitors is changing treatment strategies for melanoma in developing countries.