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Predicting how multiple anthropogenic stressors affect natural ecosystems is a major challenge in ecology. Freshwater ecosystems are threatened worldwide by multiple co-occurring stressors, which can affect aquatic biodiversity, ecosystem functioning and human wellbeing. In stream ecosystems, aquatic fungi play a crucial role in global biogeochemical cycles and food web dynamics, therefore, assessing the functional consequences of fungal biodiversity loss under multiple stressors is crucial. Here, a microcosm approach was used to investigate the effects of multiple stressors (increased temperature and nutrients, drying, and biodiversity loss) on three ecosystem processes: organic matter decomposition, fungal reproduction, and fungal biomass accrual. Net effects of stressors were antagonistic for organic matter decomposition, but additive for fungal reproduction and biomass accrual. Net effects of biodiversity were mainly positive for all processes, even under stress, demonstrating that diversity assures the maintenance of ecosystem processes. Fungal species displayed distinct contributions to each ecosystem process. Furthermore, species with negligible contributions under control conditions changed their role under stress, either enhancing or impairing the communities' performance, emphasizing the importance of fungal species identity. Our study highlights that distinct fungal species have different sensitivities to environmental variability and have different influence on the overall performance of the community. Therefore, preserving high fungal diversity is crucial to maintain fungal species with key ecosystem functions within aquatic communities in face of environmental change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Tumor-infiltrating lymphocytes (TIL) is a predictive and prognostic biomarker for breast cancer (BC) HER2-positive and triple negative, but its presence in HER2-low tumors is unknown. We aimed to determine TIL levels in HER2-low tumors and its correlation with other clinicopathologic features., Materials and Methods: We retrospectively analyzed all the pathology reports of breast surgeries of a tertiary hospital in Sao Paulo, Brazil, from January 2021 to March 2022. Inclusion criteria were stage I to III invasive BC, and exclusion criteria were nonmalignancies and neoadjuvant therapy. We assumed HER2 categories according to ASCO/CAP guidelines. TILs were defined as absent (0), low (1%-10%), intermediate (11%40%) and high (≥ 41%). Ki-67 levels were categorized as low (up to 19%) and high (≥ 20%)., Results: From 272 patients, 198 met the inclusion criteria. Histological grade 3 was found in 10, 19 and 47% of HER2-0, low, and positive tumors (P < .001). HER2-positive tumors had 82.6% of high Ki-67 levels, while HER2-negative and HER2-low showed 25.8% and 31.4% (P = .005). TILs in HER2-0, low, and positive tumors were, respectively, absent in 16.1%, 17.6%, and 8.7%; low in 70.2%, 52.9% and 34.8%; intermediate in 11.3%, 25.5% and 47.8%; and high in 2.4%, 3.9% and 8.7%. There was a statistically significant difference in TILs between HER2-negative versus HER2-positive groups (P < .001), but not between HER2-negative versus HER2-low, or HER2-low versus HER2-positive., Conclusion: TILs in HER2-low are marginally higher than HER2-negative, but significantly lower than HER2-positive levels. HER2-low tumors do not seem to significantly differ biologically from HER2-negative tumors., Competing Interests: Disclosures Italo Fernandes, Rafael Kaliks, Marcus Corpa, Anderson Scorsato, and Eduarda Damasceno: These authors have no financial relationships to disclose. Gustavo Schvartsman, Amgen: Consulting Fees (eg, advisory boards) (Ongoing); AstraZeneca: Consulting Fees (eg, advisory boards) (Ongoing); Bristol-Myers Squibb: Consulting Fees (eg, advisory boards) (Ongoing); Merck: Consulting Fees (eg, advisory boards) (Ongoing); Sanofi: Consulting Fees (eg, advisory boards) (Ongoing)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

DEPTAL MCL® is a professional cleaning agent approved by the Portuguese Food Regulatory Authority and is used in agro-food industries, namely in fish canning industries in the north of Portugal. Its extensive use during cleaning procedures results in potential significant negative impacts on the performance of the downstream municipal wastewater treatment plant (WWTP). A lab-scale extended areation activated sludge wastewater treatment system, continuously fed by influent collected at a municipal WWTP, was used to assess the impact of a range of DEPTAL MCL® concentrations during 72 h. Despite distinct activated sludge community composition (due to its dynamic nature) and variations in real influent characteristics, a relevant impact was observed. DEPTAL MCL® effect was underscored through the use of a multivariate analysis using seventeen physicochemical operational factors and nineteen quantitative image analysis (QIA) parameters. DEPTAL MCL® exerted a severe negative impact on phosphorous (P-PO 4 ) removal, total nitrogen (TN) removal and sludge volume index (SVI). With increasing DEPTAL MCL® concentrations, both P-PO 4 and TN removal were affected and diminished proportionally. Moreover, several QIA parameters indicate defloculation when DEPTAL MCL® was present, in particular for intermediate size aggregates with significant impacts. Optical density of the effluent (Od e ), displayed an increase of effluent turbidity. Percentage of area covered by small aggregates (%Area sml ) was also significantly higher for the intermediate and higher DEPTAL MCL® concentrations tested. Principal component analysis exhibited 3 distinct ordenations: (i) control without addition of DEPTAL MCL®; (ii) addition of 0.03% and 0.06% and of (iii) 0.13 and 0.26% (v DEPTAL MCL®/v aeration tank). Canonical correspondence analysis (CCA) was used to correlate the physicochemical data, QIA and the filamentous bacteria species prevalence to DEPTAL MCL® concentration and incubation time. A time persistent DEPTAL MCL® effect was observed, underscoring the need of a pretreatment of wastewater containing this cleaning agent., Competing Interests: Declaration of competing interest All authors declare that they do not possess any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We report the case of a 44-year-old female with a prior diagnosis of Sjögren's syndrome who was treated for metastatic anal squamous cell carcinoma with second-line pembrolizumab and has achieved a sustained partial response after a follow-up of 13 months. Comprehensive genomic profiling was remarkable for PD-L1 and PD-L2 amplification and a high tumor mutational burden (19 mutations per megabase). To the best of our knowledge, we present the first report to correlate PD-L1 and PD-L2 amplification with good outcomes of immune checkpoint inhibition in metastatic anal squamous cell carcinoma., (Copyright © 2021. Published by Elsevier Inc.)

Hepatocyte growth factor (HGF)/c-Met pathway is implicated in embryogenesis and organ development and differentiation. Germline or somatic mutations, chromosomal rearrangements, gene amplification, and transcriptional upregulation in MET or alterations in autocrine or paracrine c-Met signalling have been associated with cancer cell proliferation and survival, including in renal cell carcinoma (RCC), and associated with disease progression. HGF/c-Met pathway has been shown to be particularly relevant in tumors with bone metastases (BMs). However, the efficacy of targeting c-Met in bone metastatic disease, including in RCC, has not been proven. Therefore, further investigation is required focusing the particular role of HGF/c-Met pathway in bone microenvironment (BME) and how to effectively target this pathway in the context of bone metastatic disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

The effect of five different vinegars, applied as a seasoning, on the formation of polycyclic aromatic hydrocarbons (PAH) in charcoal-grilled pork loin was investigated. PAH were assayed using acetonitrile based-extraction and high-performance liquid chromatography with fluorescence detection. Unseasoned samples presented a mean value of 31.47 ng g -1 of PAH4 (sum of benz[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene), near the maximum established by European Union (30 ng g -1 ). Significant reduction (p < .05) of PAH4 formation was observed in meat samples sprayed with vinegar. Elderberry vinegar exhibited the highest inhibition (82%), followed by white wine vinegar (79%), red wine and cider vinegars (66%), and fruit vinegar with raspberry juice (55%). The total phenolic content and antioxidant activities of vinegars had a moderate negative correlation with PAH4 formation, and 3rd degree polynomial equations had the best fitting performance to explain this relation. Spraying meat with these vinegars prior grill is an easy-to-apply strategy to limit the exposure to PAH., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020. Published by Elsevier Ltd.)

Prostate cancer (PCa) treatment remains challenging, especially in advanced stages, where the lack of sensitivity and specificity of available biomarkers makes it difficult to establish an accurate prognosis. Therefore, it is imperative to study PCa biology to identify key molecules that can improve PCa management. In this study, eight prostate tumor tissues and paired normal tissues were analyzed using two approaches-Fourier-transform infrared (FT-IR) spectroscopy for spectroscopic profiling of biomolecules and antibody microarray for signaling proteins-with the main goal of identifying metabolic and proteomic changes that enable the distinction between normal and tumor conditions. Principal component analysis of FT-IR spectra revealed different spectroscopic signals for each condition. The most relevant changes in prostate tumor tissues identified by FT-IR were dysregulation in lipid metabolism, lower polysaccharide and glycogen content, higher nucleic acid content, and increased protein phosphorylation. Using an antibody microarray, 42 proteins were identified as differentially regulated between the two conditions; 14 of those revealed changes in their phosphorylation status. These proteins include transcription factors and kinases and constitute a highly-interconnected interaction network. Altogether, our data reveal metabolic and proteomic alterations that may be of interest in future translational studies aimed at establishing PCa prognosis and treatment. SIGNIFICANCE: Prostate tumor tissues and adjacent benign tissues were analyzed using two approaches-Fourier-transform infrared (FT-IR) spectroscopy for biomolecules and an antibody microarray for signaling proteins, which allowed to identify a panel of metabolic and proteomic alterations that may be of interest in future translational studies to enable the distinction between normal and tumor conditions., Competing Interests: Declaration of Competing Interest SP and his family are the majority shareholders of Kinexus Bioinformatics Corporation. Parts of this work were presented at scientific meeting and published as extended abstracts: Felgueiras J, et al., European Journal of Cancer (2017); Patrício A, et al., The Journal of Urology (2016); Freitas MJ, et al., Medicine (2016). No more conflict of interest exists to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Kidney transplant (KT) recipients have an increased risk for urothelial carcinoma. A role for JC virus (JCV) in human cancers is not yet proved but there is an increasingly reported association between BK virus (BKV) nephropathy and renourinary neoplasms. We report a KT recipient who developed a high-grade urothelial carcinoma 5 years after a diagnosis of JCV nephropathy and 9 years after kidney transplantation. Neoplastic tissue was positive for JCV DNA by real-time polymerase chain reaction (PCR). Immunochemical staining showed strong positivity for cell cycle markers (p16, p53, and Ki67) and for early viral protein JCV large T antigen (JCV LTag; using a broad polyomavirus antibody); however, late viral protein (VP1) stained negative. In contrast, in non-neoplastic urothelium, JCV DNA and all immunochemical markers were negative. These facts suggest that malignancy was induced by JCV. To the best of our knowledge, this is the first report of urothelial high-grade carcinoma associated with JCV nephropathy in a KT recipient., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The effects of bariatric surgery can reflect in the oral cavity and can cause alterations in oral health. This high prevalence of oral alterations in the pre and post-operative periods has been highlighted in different studies., Objectives: To investigate the effect of bariatric surgery on periodontal status through a systematic review., Methods: Electronic search was conducted in PubMed, VHL, Web of Science, Science direct, Scopus, and Cochrane databases through May 2017. Manual search, gray literature, and counter-refence of included articles were also conducted. Eligibility criteria included observational studies that reported periodontal outcomes before and after bariatric surgery., Results: Search strategy resulted in 1878 articles. Following the selection process, nine studies were included in the qualitative analysis and five in the meta-analysis. Three cross-sectional studies showed risk of bias score ranging from 5 to 6 stars, and Cohort studies scored from 6 to 9 stars out of 9 possible stars on the Newcastle-Ottawa scale. The quantitative analysis showed that clinical attachment level (MD: 0.07; CI95% -0.17 to 0.31), gingival index (MD: -0.28; CI95% -1.68 to 1.11), percentage of bleeding sites (MD: -0.21; CI95% -0.77 to 0.35), and pocket probing depth (MD: 0.08 CI95% -0.14 to 0.31) were not different before and after bariatric surgery. However, the plaque index was lower after than before bariatric surgery (MD: -1.29; CI 95% -2.34 to -0.24)., Conclusions: Plaque index can be improved after bariatric surgery. The present systematic review investigated the association between bariatric surgery and periodontal status from cross-sectional and longitudinal studies. A systematic search strategy was developed until May 2017. The results of this systematic review allowed the conclusion that the plaque index can be improved after bariatric surgery., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Celiac Disease (CD) is now recognized as a worldwide epidemic. Although a gluten free diet usually induces clinical improvements within days or weeks, adhering to this routine is still troublesome. Therefore, new solutions are needed for quality-of-life improvement of CD patients. The present work intends to bring molecular and thermodynamic insights on the ability of green tea epigalhocatechin-3-gallate (EGCG) to interact and modulate the bioavailability of a major CD immunodominant peptide (32-mer). Characterization of peptide binding was assessed by means of both 1D and 2D 1 H NMR experiments, ITC and Molecular Dynamics simulations. Accordingly, EGCG not only exhibits a high reactivity towards the 32-mer peptide as its binding appears to be entropy-driven and involves two sequential binding events, each with different binding strengths. Structural rearrangements were also detected during the interaction, contributing to a greater stability of the formed complexes. In vitro transepithelial transport assays using a Caco-2 cell line model were also performed and highlighted the ability of EGCG to significantly reduce the concentration of free peptide in the basolateral compartment. Overall, this study provides important evidences regarding the structural features and molecular mechanisms by which EGCG could interact and potentially modulate the function of some bioactive CD peptides., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To better understand the impacts of multiple stressors in freshwaters, we investigated the effects of mixtures of zinc and inorganic phosphorus on microbial decomposition of leaf litter. Alder leaves were colonized in a stream and placed in microcosms with stream water supplemented or not with 3 concentrations of zinc (Zn up to 9.8 mg/l) or phosphate (P-PO(4)(3-) up to 0.5 mg/l), alone and in all possible combinations. We measured leaf mass loss, and fungal biomass, reproduction and diversity. In control microcosms, 23 species of aquatic hyphomycetes were identified on leaves, and the exposure to the highest zinc concentration reduced diversity to 14 species. Articulosporatetracladia was the dominant species followed by Flagellospora sp. and Alatosporaacuminata. The exposure to phosphate increased the contribution of A.acuminata, but this species was negatively affected by zinc. Under high zinc stress, Varicosporiumelodeae increased its contribution to the total conidial production. The exposure to high zinc concentration, alone or in mixtures with phosphate, led to shifts in fungal community structure, as indicated by cluster analysis based on sporulation data and denaturing gradient gel electrophoresis (DGGE) fingerprints of fungal DNA. These changes were accompanied by a reduction in leaf decomposition, particularly in mixtures with high Zn concentration, in which leaf mass loss was 30% lower than in the control. This suggests that the co-occurrence of zinc and phosphate may have negative effects on stream ecosystem functioning. However, we did not detect decreased leaf-associated fungal biomass and sporulation, probably because a delay in fungal colonization occurred due to the presence of stressors.

The presence of biogenic amines (BA) along the processing stages and storage period of "Painho de Portalegre" and its relationship with the NaCl concentration on their levels were evaluated. Total BA concentration of current "Painho de Portalegre" dry fermented sausage increased (P<0.001) with drying/smoking processing time, attaining 655mgkg(-1) dry matter (DM) at day 6, a level about six times higher than that obtained in seasoned raw material mixtures before casing stuffing (115mgkg(-1)DM). Between day 30 and 40 in the drying/smoking house, that amount increased 20-fold (2500mgkg(-1) DM) over the initial concentration. After one month of storage under vacuum at room temperature, the concentration decreased by almost half to 1561mgkg(-1)DM. Excluding tyramine, the other BA were already present in the minced raw materials. However the sum of cadaverine, putrescine, histamine and tyramine, was well below 5mgkg(-1) proposed as BA limit for meat of high hygienic quality. Cadaverine was the most concentrated BA at the last stage of the drying/smoking (1430-1254mgkg(-1)DM, after 30 and 40 days, respectively), almost double the concentration of putrescine (882-779mgkg(-1)DM), followed by tyramine, β-phenylethylamine and spermine (376-311, 24 and 27-23mgkg(-1)DM, respectively). Variation was detected among production batches, possibly due to poor control of the processing conditions in traditional manufactures and the effects of the prevailing weather conditions. A higher salt concentration in the final product, 6% compared to 3%, led to a significant reduction in the BA level (P<0.001). This difference was particularly relevant in the early stage of the drying/smoking phase, during which the greatest microbial development mainly occurred in relation to cadaverine, β-phenylethylamine, putrescine and tyramine levels.

A PCR assay with an internal amplification control was developed for Listeria monocytogenes. The assay has a 99% detection probability of seven cells per reaction. When tested against 38 L. monocytogenes strains and 52 nontarget strains, the PCR assay was 100% inclusive (positive signal from target) and 100% exclusive (no positive signal from nontarget). The assay was then evaluated in a collaborative trial involving 12 European laboratories, where it was tested against an additional 14 target and 14 nontarget strains. In that trial, the inclusivity was 100% and the exclusivity was 99.4%, and both the accordance (repeatability) and the concordance (reproducibility) were 99.4%. The assay was incorporated within a method for the detection of L. monocytogenes in raw milk, which involves 24 h of enrichment in half-Fraser broth followed by 16 h of enrichment in a medium that can be added directly into the PCR. The performance characteristics of the PCR-based method were evaluated in a collaborative trial involving 13 European laboratories. In that trial, a specificity value (percentage of correct identification of blank samples) of 81.8% was obtained; the accordance was 87.9%, and the concordance was 68.1%. The sensitivity (correct identification of milk samples inoculated with 20 to 200 L. monocytogenes cells per 25 ml) was 89.4%, the accordance was 81.2%, and the concordance was 80.7%. This method provides a basis for the application of routine PCR-based analysis to dairy products and other foodstuffs and should be appropriate for international standardization.

Adriamycin, a cancerostatic anthracycline antibiotic, causes considerable death of tumour cells, together with the induction of breaks in DNA single and double strands. The interaction of this compound with DNA was investigated using an electrochemical DNA-biosensor. Adriamycin intercalation in DNA disrupts the double helix and the detection of guanine and 8-oxoguanine could mimic one possible mechanism for the in vivo adriamycin drug action.

Adriamycin intercalation and in situ interaction with double helix DNA was investigated using a voltammetric DNA-biosensor. Oxidation and reduction of adriamycin molecules intercalated in double helix DNA were investigated in order to understand the in vivo mechanism of action with this anti-neoplasic drug. The results showed that the interaction of adriamycin with DNA is potential-dependent causing contact between DNA guanine and adenine bases and the electrode surface such that their oxidation is easily detected. A mechanism for adriamycin reduction and oxidation in situ when intercalated in double helix DNA immobilised onto the glassy carbon electrode surface is presented and the formation of the mutagenic 8-oxoguanine explained.

Background: Dipyridamole (Dip) was previously shown to increase renal phosphate (Pi) reabsorption in humans. However, the mechanism(s) underlying this renal tubular effect is not fully elucidated. It is known that Dip inhibits the activity of the P-glycoprotein (Pgp) multidrug resistance protein 1 (MDR1) expressed on the apical membrane of renal proximal tubular cells where the Na-Pi cotransporter (NPT2) is also expressed. We hypothesized that Dip could increase renal Pi reabsorption by inhibiting Pgp activity., Methods: To test this hypothesis, the effects of Dip, verapamil (Ver), and cyclosporine A (CsA), three unrelated Pgp inhibitors, were studied on the renal Pi reabsorption in rats., Results: All three drugs decreased the fractional excretion of Pi (FE(Pi)) in a dose-dependent manner within one hour after beginning the drug infusion, without altering the glomerular filtration rate or serum parathyroid hormone concentration. Sodium-dependent Pi uptake but not Na-glucose transport was increased in brush-border membrane vesicles (BBMVs) when comparing treated with untreated rats. Western blot analysis showed that NPT2 protein was increased in BBMVs from treated rats. Dip and Ver had no effect when applied directly to BBMVs prepared from untreated rats. Pretreatment of rats with colchicine prevented the effects of Dip on the FE(Pi) and NPT2 expression in brush-border membranes., Conclusions: Our results suggest that inhibition of Pgp in the proximal tubule increases Pi uptake and NPT2 translocation to the apical membrane.

Background: It is known that hypersulfatemia, like hyperphosphatemia, occurs in chronic renal failure (CRF). The aim of this study was to assess the effects of CRF on sulfate homeostasis and on sodium sulfate cotransport (NaSi-1) and sulfate/oxalate-bicarbonate exchanger (Sat-1) expression in the kidney. In addition, sulfate homeostasis was compared with phosphate homeostasis., Methods: Experimental studies were performed in adult male rats at three and six weeks after 80% subtotal nephrectomy (Nx) or sham-operation (S) (N = 9 per group). Transporter protein and mRNA expressions were measured by Western blot and RNase protection assay (RPA), respectively. Results were quantitated by densitometric scanning (Western) and electronic autoradiography (RPA), and were expressed in densitometric units (DUs; Western) and cpm (RPA)., Results: Creatinine clearance was lower in Nx-3 compared with S-3 rats (0.23 vs. 0.51 mL/min/100 g body weight, P < 0.001) and was further impaired in Nx-6 rats (0.15 vs. 0.48, P < 0.001). Sulfatemia was significantly higher in Nx-3 rats (1.08 vs. 0.84 mmol/L, P < 0.05) and further increased in Nx-6 rats (1.42 vs. 0.90 mmol/L, P < 0.01). Fractional sulfate excretion (FESO4) was increased by twofold in Nx-3 and Nx-6 rats compared with corresponding S rats. Phosphatemia did not differ between Nx-3 rats and controls, but was increased in Nx-6 rats (P < 0.01). Total amounts of both NaSi-1 and Sat-1 proteins were significantly decreased in both Nx-3 and Nx-6 rats when compared with controls. However, NaSi-1 protein and mRNA densities did not significantly change in Nx-3 rats, but were significantly increased in Nx-6 rats when compared with controls (4.8 vs. 3.7 DU/microg protein, P < 0.05, and 7.1 vs. 2.8 cpm/microg RNA, P < 0.01, respectively, for protein and mRNA). In contrast to NaSi-1, Sat-1 protein density was significantly decreased both in Nx-3 (2.9 vs. 3.6 DU/microg protein, P < 0.05) and Nx-6 rats (2.4 vs. 3.4 DU/microg protein, P < 0.05), and Sat-1 mRNA density significantly decreased in Nx-6 rats (10.7 vs. 14.7 cpm/microg RNA, P < 0.05). Na-PO4 cotransporter (NaPi-2) protein total abundance and density were decreased at three and six weeks in Nx rats., Conclusions: These results demonstrate that both NaSi-1 and Sat-1 total protein abundances are decreased in CRF, which may contribute to the increase in fractional sulfate excretion. Strikingly, NaSi-1 density was not decreased in CRF three weeks after Nx, and furthermore, increased six weeks after Nx, in contrast to NaPi-2 density, which was decreased at both times. The significance of this difference remains to be determined, but may explain why hypersulfatemia occurs earlier than hyperphosphatemia in CRF.