Tag: nevin manimala

Hum Pathol. 2024 Apr 7:S0046-8177(24)00053-4. doi: 10.1016/j.humpath.2024.04.001. Online ahead of print.

ABSTRACT

Upper tract urothelial carcinoma (UTUC) presents diagnostic challenges due to small biopsy specimen size, poor orientation, and technical obstacles that can yield equivocal diagnoses. This uncertainty often mandates repeated biopsies to evaluate the necessity of nephroureterectomy. Prior studies have suggested cytokeratin 17 (CK17) immunostain as an adjunctive tool for diagnosing bladder urothelial neoplasia in both urine cytology and tissue biopsy specimens. We evaluated the utility of CK17 in differentiating UTUC from benign urothelium and its ability to stratify low-grade from high-grade neoplasia. Our study involved a cohort of previously diagnosed cytology (n = 29) and tissue specimens from biopsies and resections (n = 85). We evaluated CK17 staining percentage in cytology and tissue samples and localization patterns in biopsy/resection samples. Our findings showed a statistically significant distinction (p < 0.05) between UTUC and benign tissue specimens based on full thickness localization pattern (odds ratio 8.8 [95% CI 1.53-67.4]). The percentage of CK17 staining failed to significantly differentiate neoplastic from non-neoplastic cases in cytology or tissue samples. Additionally, based on prior research showing the efficacy of CK20/CD44/p53 triple panel in bladder urothelial neoplasia, we utilized tissue microarrays to evaluate if these markers could distinguish UTUC from benign urothelium. We found that CK20/CD44/p53, individually or in combination, could not distinguish urothelial neoplasia from non-neoplasia. Full thickness CK17 urothelial localization by immunohistochemistry was highly reproducible with excellent interobserver agreement and may play a supplementary role in distinguishing upper tract urothelial neoplasia from benign urothelium.

PMID:38593961 | DOI:10.1016/j.humpath.2024.04.001

Chemosphere. 2024 Apr 7:141868. doi: 10.1016/j.chemosphere.2024.141868. Online ahead of print.

ABSTRACT

Antibiotics, as a class of environmental pollutants, pose a significant challenge due to their persistent nature and resistance to easy degradation. This study delves into modeling and optimizing conventional Fenton degradation of antibiotic sulfamethoxazole (SMX) and total organic carbon (TOC) under varying levels of H₂O₂, Fe²⁺ concentration, pH, and temperature removal using both statistical and artificial intelligence techniques including Multiple Regression Analysis (MRA), Support Vector Regression (SVR) and Artificial Neural Network (ANN). In statistical analysis, ANN model showcased an elevated predictive accuracy compared to its counterparts due to having lowest RMSE values of 0.986 and 1.173 for both SMX and TOC, respectively. Sensitivity showcased H₂O₂/Fe²⁺ ratio, time and pH as pivotal for SMX degradation, while in simultaneous SMX and TOC reduction, fine tuning the time, pH, and temperature was essential. Leveraging a Hybrid Genetic Algorithm-Desirability Optimization approach, the trained ANN model revealed an optimal desirability of 0.941 out of 1000 solutions which yielded a 91.18% SMX degradation and 87.90% TOC removal under following specific conditions: treatment time of 48.5 min, Fe²⁺: 7.05 mg L^-1, H₂O₂: 128.82 mg L^-1, pH: 5.1, initial SMX: 97.6 mg L^-1, and a temperature: 29.8 °C. LC/MS analysis reveals multiple intermediates with higher m/z (242, 270 and 288) and lower m/z (98, 108, 156 and 173) values identified, however no aliphatic hydrocarbon was isolated, because of the low mineralization performance of Fenton process. Furthermore, some inorganic fragments like NH₄⁺ and NO₃^– were also determined in solution. This comprehensive research enriches AI modeling for intricate Fenton-based contaminant degradation, advancing sustainable antibiotic removal strategies.

PMID:38593957 | DOI:10.1016/j.chemosphere.2024.141868

Environ Pollut. 2024 Apr 7:123925. doi: 10.1016/j.envpol.2024.123925. Online ahead of print.

ABSTRACT

Legacy and emerging per- and polyfluoroalkyl substances (PFASs) were measured in livers of finless porpoises (Neophocaena asiaeorientalis; n = 167) collected in Korean waters from 2002 to 2015 to investigate their occurrence, bioaccumulation feature, temporal trends, and ecotoxicological implications. Perfulorooctane sulfonate (PFOS), perfluoroundecanoate (PFUnDA), and perfluorotridecanoate (PFTrDA) were the predominant PFASs found in the porpoises. The concentration of 6:2 chlorinated polyfluoroalkyl ether sulfonate (F-53B), an alternative to PFOS, was comparable to that of PFTrDA. Perfluorooctane sulfonamide (FOSA), a precursor of PFOS, was also detected in all the porpoises examined. All PFASs, including F-53B, accumulated to higher concentrations in immature porpoises compared with mature specimens, implying substantial maternal transfer and limited metabolizing capacity for PFASs. A significant correlation was observed between PFOS and F-53B concentrations, indicating similar bioaccumulation processes. Based on prenatal exposure and toxicity, F-53B is an emerging contaminant in marine ecosystems. Significantly increasing trends were observed in the concentrations of sulfonates, carboxylates, and F-53B between 2002/2003 and 2010, whereas the FOSA concentration significantly decreased. During 2010-2015, decreasing trends were observed in the concentrations of FOSA and sulfonates, whereas concentrations of carboxylate and F-53B increased without statistical significance, likely due to a gap for the implementation of regulatory actions between sulfonates and carboxylates. Although PFOS and PFOA were found to pose little health risk to porpoises, the combined toxicological effects of other contaminants should be considered to protect populations and to mitigate PFAS contamination in marine ecosystems.

PMID:38593937 | DOI:10.1016/j.envpol.2024.123925

Homeopathy. 2024 Apr 9. doi: 10.1055/s-0044-1779337. Online ahead of print.

ABSTRACT

BACKGROUND: The Academy of Homeopathy Education is a US-based accredited teaching institution offering homeopathy education services to professional and medically licensed homeopathy students. This study reports on clinical outcomes from the teaching clinic from 2020 to 2021.

METHODS: Data collected using the patient-generated outcome measure, the Measure Yourself Concerns and Wellbeing (MYCaW), were anonymized. Mean MYCaW values for initial and subsequent consultations were analyzed for the degree of change across the intervention period in 38 clients. Each client listed up to two complaints. MYCaW scores between initial and subsequent consultations were analyzed for the degree of change (delta) across the intervention period.

RESULTS: A total of 95 body system-related symptoms were analyzed for change in intensity following the homeopathic intervention. Statistically significant improvements in the intensity of main symptoms were observed between initial and subsequent follow-ups. The main symptom scores showed a mean change in intensity (delta MYCaW) of -0.79 points (95% confidence interval (CI), -1.29 to -0.29; p = 0.003) at first follow-up, a mean change of -1.67 points (95% CI, -2.34 to -0.99; p = 0.001) at second follow-up compared with the initial visit, and a mean change of -1.93 points (95% CI, -3.0 to -0.86; p = 0.008) at third follow-up compared with the initial visit. For clients with four or more follow-ups, the mean delta MYCaW was -1.57 points (95% CI, -2.86 to -0.28; p = 0.039).

CONCLUSION: Statistically significant improvements as well as some clinically meaningful changes in symptom intensity were found across a diverse group of individuals with a variety of long-term chronic conditions. The improvement was evident across different body systems and different levels of chronicity. There are limitations to the generalizability of the study due to the research design. Further research and investigation are warranted given the promising results of this work.

PMID:38593861 | DOI:10.1055/s-0044-1779337

Proc Biol Sci. 2024 Apr 10;291(2020):20240295. doi: 10.1098/rspb.2024.0295. Epub 2024 Apr 10.

ABSTRACT

Interdependence occurs when individuals have a stake in the success or failure of others, such that the outcomes experienced by one individual also generate costs or benefits for others. Discussion on this topic has typically focused on positive interdependence (where gains for one individual result in gains for another) and on the consequences for cooperation. However, interdependence can also be negative (where gains for one individual result in losses for another), which can spark conflict. In this article, we explain when negative interdependence is likely to arise and, crucially, the role played by (mis)perception in shaping an individual’s understanding of their interdependent relationships. We argue that, owing to the difficulty in accurately perceiving interdependence with others, individuals might often be mistaken about the stake they hold in each other’s outcomes, which can spark needless, resolvable forms of conflict. We then discuss when and how reducing misperceptions can help to resolve such conflicts. We argue that a key mechanism for resolving interdependent conflict, along with better sources of exogenous information, is to reduce reliance on heuristics such as stereotypes when assessing the nature of our interdependent relationships.

PMID:38593846 | DOI:10.1098/rspb.2024.0295

Am J Vet Res. 2024 Apr 13:1-10. doi: 10.2460/ajvr.23.12.0285. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate associations between hepatic fat accumulation, fibrosis, and plasma values of primary metabolites, biochemical measurands, insulin, and lipoproteins in bearded dragons.

ANIMALS: 48 adult central bearded dragons (Pogona vitticeps).

METHODS: Dragons were sedated with alfaxalone, and a blood sample was collected. Plasma was submitted for untargeted primary metabolomics using gas chromatography time-of-flight mass spectrometry, a biochemistry panel, and a lipoprotein panel determined by PAGE. Hepatic lipid content was quantified by liver attenuation measurements from CT images and digital image analysis of standardized histologic sections of the liver. Fibrosis was quantified by digital image analysis on Masson’s trichrome-stained histologic sections. Severity was determined from pathologic review of liver sections according to a standardized grading system. Statistical associations were investigated using serial linear models adjusted for false discovery rate and multivariate statistics.

RESULTS: Both hepatic fat and fibrosis had a significant effect on CT liver attenuation values. Several oligosaccharides (maltotriose, maltose, ribose, trehalose) and alkaline phosphatase were significantly and linearly increased with hepatic lipid content (all q < .05). On partial least square-discriminant analysis, β-hydroxybutyric acid was the most important discriminatory variable between fatty liver severity grades on histology. No significant associations were found with insulin, lipoproteins, and succinic acid.

CLINICAL RELEVANCE: Bearded dragons with hepatic lipid accumulation experienced multiple metabolic pathway disruptions, some being compatible with mitochondrial dysfunction. No evidence of insulin resistance or dyslipidemia was found. Hepatic biopsy and histopathology remain recommended for reliably diagnosing and staging fatty liver disease in bearded dragons.

PMID:38593838 | DOI:10.2460/ajvr.23.12.0285

Cell Chem Biol. 2024 Apr 5:S2451-9456(24)00091-6. doi: 10.1016/j.chembiol.2024.03.002. Online ahead of print.

ABSTRACT

Identification of new druggable protein targets remains the key challenge in the current antimalarial development efforts. Here we used mass-spectrometry-based cellular thermal shift assay (MS-CETSA) to identify potential targets of several antimalarials and drug candidates. We found that falcilysin (FLN) is a common binding partner for several drug candidates such as MK-4815, MMV000848, and MMV665806 but also interacts with quinoline drugs such as chloroquine and mefloquine. Enzymatic assays showed that these compounds can inhibit FLN proteolytic activity. Their interaction with FLN was explored systematically by isothermal titration calorimetry and X-ray crystallography, revealing a shared hydrophobic pocket in the catalytic chamber of the enzyme. Characterization of transgenic cell lines with lowered FLN expression demonstrated statistically significant increases in susceptibility toward MK-4815, MMV000848, and several quinolines. Importantly, the hydrophobic pocket of FLN appears amenable to inhibition and the structures reported here can guide the development of novel drugs against malaria.

PMID:38593807 | DOI:10.1016/j.chembiol.2024.03.002

Cell Stem Cell. 2024 Apr 2:S1934-5909(24)00090-0. doi: 10.1016/j.stem.2024.03.008. Online ahead of print.

ABSTRACT

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

PMID:38593797 | DOI:10.1016/j.stem.2024.03.008

J Environ Manage. 2024 Apr 8;358:120815. doi: 10.1016/j.jenvman.2024.120815. Online ahead of print.

ABSTRACT

The present research study investigates the performance of pyrolysis oils recycled from waste tires as a collector in coal flotation. Three different types of pyrolysis oils (namely, POT₁, POT₂, and POT₃) were produced through a two-step pressure pyrolysis method followed by an oil rolling process. The characteristics of POTs were adjusted using various oil-modifying additives such as mineral salts and organic solvents. The chemical structure of POTs was explored by employing necessary instrumental analysis techniques, including microwave-assisted acid digestion (MAD), inductively coupled plasma atomic emission spectroscopy (ICP-AES), Fourier-transform infrared spectroscopy (FT-IR), and gas chromatography-mass spectrometry (GC-MS). The collecting performance of POTs in coal flotation was evaluated using an experimental design based on Response Surface Methodology (RSM), considering the ash content and yield of the final concentrate. The effect of the type and dosage of POTs was evaluated in conjunction with other important operating variables, including the dosage of frother, dosage of depressant, and the type of coal. Results of POTs characterization revealed that the pyrolysis oils were a complex composition of light and heavy hydrocarbon molecules, including naphthalene, biphenyl, acenaphthylene, fluorene, and pyrene. Statistical analysis of experimental results showed that among different POTs, POT₁ exhibited remarkable superiority, achieving not only a 15% higher coal recovery but also a 12% lower ash content. The outstanding performance of POT₁ was attributed to its unique composition, which includes a concentrated presence of carbon chains within the optimal range for efficient flotation. Additionally, the FT-IR spectra of POT₁ reveal specific functional groups, including aromatic and aliphatic compounds, greatly enhancing its interaction with coal surfaces, as confirmed by contact angle measurement. This research provides valuable insights into the specific carbon chains and functional groups that contribute to the effectiveness of POT as a collector, facilitating the optimization of coal flotation processes and underscoring the environmental advantages of employing pyrolysis oils as sustainable alternatives in the mining industry.

PMID:38593739 | DOI:10.1016/j.jenvman.2024.120815

J Environ Manage. 2024 Apr 8;358:120810. doi: 10.1016/j.jenvman.2024.120810. Online ahead of print.

ABSTRACT

The rise in oil trade and transportation has led to a continuous increase in the risk of oil spills, posing a serious worldwide concern. However, there is a lack of numerical models for predicting oil spill transport in freshwater, especially under icy conditions. To tackle this challenge, we developed a prediction system for oil with ice modeling by coupling the General NOAA Operational Modeling Environment (GNOME) model with the Great Lakes Operational Forecast System (GLOFS) model. Taking Lake Erie as a pilot study, we used observed drifter data to evaluate the performance of the coupled model. Additionally, we developed six hypothetical oil spill cases in Lake Erie, considering both with and without ice conditions during the freezing, stable, and melting seasons spanning from 2018 to 2022, to investigate the impacts of ice cover on oil spill processes. The results showed the effective performance of the coupled model system in capturing the movements of a deployed drifter. Through ensemble simulations, it was observed that the stable season with high-concentration ice had the most significant impact on limiting oil transport compared to the freezing and melting seasons, resulting in an oil-affected open water area of 49 km² on day 5 with ice cover, while without ice cover it reached 183 km². The stable season with high-concentration ice showed a notable reduction in the probability of oil presence in the risk map, whereas this reduction effect was less prominent during the freezing and melting seasons. Moreover, negative correlations between initial ice concentration and oil-affected open water area were consistent, especially on day 1 with a linear regression R-squared value of 0.94, potentially enabling rapid prediction. Overall, the coupled model system serves as a useful tool for simulating oil spills in the world’s largest freshwater system, particularly under icy conditions, thus enhancing the formulation of effective emergency response strategies.

PMID:38593738 | DOI:10.1016/j.jenvman.2024.120810