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Neuroendocrine markers, which could indicate for aggressive variants of prostate cancer and Ki67 (a well-known marker in oncology for defining tumor proliferation), have already been associated with clinical outcome in prostate cancer. The aim of this study was to investigate the prognostic value of those markers in primary prostate cancer patients.

The mechanisms that underlie the regulation of enzymatic reactions by biomolecular condensates and how they scale with compartment size remain poorly understood. Here we use intrinsically disordered domains as building blocks to generate programmable enzymatic condensates of NADH-oxidase (NOX) with different sizes spanning from nanometers to microns. These disordered domains, derived from three distinct RNA-binding proteins, each possessing different net charge, result in the formation of condensates characterized by a comparable high local concentration of the enzyme yet within distinct environments. We show that only condensates with the highest recruitment of substrate and cofactor exhibit an increase in enzymatic activity. Notably, we observe an enhancement in enzymatic rate across a wide range of condensate sizes, from nanometers to microns, indicating that emergent properties of condensates can arise within assemblies as small as nanometers. Furthermore, we show a larger rate enhancement in smaller condensates. Our findings demonstrate the ability of condensates to modulate enzymatic reactions by creating distinct effective solvent environments compared to the surrounding solution, with implications for the design of protein-based heterogeneous biocatalysts., (© 2024. The Author(s).)

Bifidobacteria are early colonizers of the human gut and play central roles in human health and metabolism. To thrive in this competitive niche, these bacteria evolved the capacity to use complex carbohydrates, including mammalian N-glycans. Herein, we elucidated pivotal biochemical steps involved in high-mannose N-glycan utilization by Bifidobacterium longum. After N-glycan release by an endo-β-N-acetylglucosaminidase, the mannosyl arms are trimmed by the cooperative action of three functionally distinct glycoside hydrolase 38 (GH38) α-mannosidases and a specific GH125 α-1,6-mannosidase. High-resolution cryo-electron microscopy structures revealed that bifidobacterial GH38 α-mannosidases form homotetramers, with the N-terminal jelly roll domain contributing to substrate selectivity. Additionally, an α-glucosidase enables the processing of monoglucosylated N-glycans. Notably, the main degradation product, mannose, is isomerized into fructose before phosphorylation, an unconventional metabolic route connecting it to the bifid shunt pathway. These findings shed light on key molecular mechanisms used by bifidobacteria to use high-mannose N-glycans, a perennial carbon and energy source in the intestinal lumen., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The objective of this study was to evaluate the application of a biodegradable film, based on grape seed flour extract, for raisin packaging. Physico-chemical characteristics (moisture, total soluble solids, total acidity, pH), total phenolic content and antioxidant activity were evaluated during 182 days of storage at 20 °C, compared to a poly(ethylene) film packaging. After 182 days, the use of biodegradable film increased raisin moisture and pH, decreased total soluble solids and total acidity of raisin compared to the use of poly(ethylene) film. The total phenolic content and antioxidant activity of raisin packed in the biodegradable film were 60.0 and 51.8% higher, respectively, than in poly(ethylene) film. The results showed that the biodegradable film based on seed flour extract is a potential material for active packaging due its contribution to the maintenance of the antioxidant activity of raisin and can be used for their conservation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Comprehensive genomic studies have delineated key driver mutations linked to disease progression for most cancers. However, corresponding transcriptional changes remain largely elusive because of the bias associated with cross-study analysis. Here, we overcome these hurdles and generate a comprehensive prostate cancer transcriptome atlas that describes the roadmap to tumor progression in a qualitative and quantitative manner. Most cancers follow a uniform trajectory characterized by upregulation of polycomb-repressive-complex-2, G2-M checkpoints, and M2 macrophage polarization. Using patient-derived xenograft models, we functionally validate our observations and add single-cell resolution. Thereby, we show that tumor progression occurs through transcriptional adaption rather than a selection of pre-existing cancer cell clusters. Moreover, we determine at the single-cell level how inhibition of EZH2 - the top upregulated gene along the trajectory - reverts tumor progression and macrophage polarization. Finally, a user-friendly web-resource is provided enabling the investigation of dynamic transcriptional perturbations linked to disease progression., (© 2021. The Author(s).)

Introduction: We aimed to present the safety profile of robotic radical prostatectomy (RARP) performed in a single center of medium surgical volume since its introduction and identify predictors of postoperative complications., Methods: We prospectively collected clinical data from 317 consecutive patients undergoing RARP between August 2011 and November 2019 in a medium-volume center. Surgical procedures were performed by a single experienced surgeon. Complications were collected according to the Martin criteria for reporting and the Clavien-Dindo classification for rating. Preoperative, intraoperative, and postoperative data were analyzed and compared with available literature., Results: A total of 102 complications were observed in 96 (30.3%) patients and were minor in 84.4% of cases (Clavien grade 1 and 2). Transfusion rate was 1.3%. Complications of grade 4b or 5 did not occur. The most frequent complications were urinary retention (7.3%) and anastomotic leak (5.9%). At multivariate analysis, the nerve-sparing technique was an independent predictor of complications (odds ratio [OR] 0.55, p=0.02)., Conclusions: The study shows that a high safety profile may be achieved in a medium-volume hospital. The nerve-sparing technique was a predictor of complications. Further studies are needed to define the current relationship between surgical volume and perioperative outcome for RARP.

Agaricus blazei, Auricularia fuscosuccinea and Pleurotus albidus mycelia were obtained in solid-state cultivation (SSC), using grains (brown rice, canjica corn and wheat) as raw material. Colonized grain flours were analysed for their nutritional, physical and physico-chemical characteristics and biological activity in vitro. Wheat flour with P. albidus showed higher values for protein (18.34 g/100 g), ergosterol (0.60 mg/g), mycelial biomass (183 mg/g) and total amino acids (58.34 mg/g). Corn flour with A. fuscosuccinea showed the highest total phenolic content (2.38 mg GAE/g), antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) (8.90 μmol TEAC/g) and 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (16.52 μmol TEAC/g) assay. Wheat flour with P. albidus were more effective at inhibiting of pancreatic lipase (74.5%) and of α-glucosidase (98.2%). In conclusion, grains colonized by macrofungi mycelia through SSC can enrich the nutritional value and the biological activity of the flours, which presents a potential for functional foods., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Five years after the first state-of-the-art report on Commercial Visual Analytics Systems we present a reevaluation of the Big Data Analytics field. We build on the success of the 2012 survey, which was influential even beyond the boundaries of the InfoVis and Visual Analytics (VA) community. While the field has matured significantly since the original survey, we find that innovation and research-driven development are increasingly sacrificed to satisfy a wide range of user groups. We evaluate new product versions on established evaluation criteria, such as available features, performance, and usability, to extend on and assure comparability with the previous survey. We also investigate previously unavailable products to paint a more complete picture of the commercial VA landscape. Furthermore, we introduce novel measures, like suitability for specific user groups and the ability to handle complex data types, and undertake a new case study to highlight innovative features. We explore the achievements in the commercial sector in addressing VA challenges and propose novel developments that should be on systems' roadmaps in the coming years.

Background: Five-year survival in patients with localized prostate cancer (PCa) is nearly 100%, but metastatic disease still remains incurable. Clinical management of metastatic patients has become increasingly complex as novel therapeutic strategies have emerged. This study aims at evaluating the impact of the first metastatic progression on the outcome of PCa patients treated with curative intent., Methods: The analysis was conducted using data of 913 cases of localized PCa diagnosed between 2000 and 2014. All patients were treated with curative surgery (N = 382) or radiotherapy (N = 531) with or without adjuvant therapy. All metastases were radiologically documented. The prognostic impact of the first site of metastasis on metastasis-free survival (MFS) and PCa-specific survival (PCaSS) was investigated by univariate and multivariate analyses., Results: One hundred and thirty-six (14.9%) patients developed a metastatic hormone-sensitive PCa and had a median PCaSS of 50.4 months after first metastatic progression. Bone (N = 50, 36.8%) and LN or locoregional (N = 52, 38.2%) metastases occurred more frequently with a median PCaSS of 39.7 and 137 months respectively (p < 0.0001). Seven patients developed visceral metastasis only (5.1%; liver, lung, brain) and 27 (19.9%) concurrent metastases; this last group was associated with the worst survival with a median value of only 17 months. Thus, each subgroup exhibited a survival after metastasis significantly different from each other. In multivariate analysis the site of the first metastasis was an independent prognostic factor for PCaSS along with Gleason score at diagnosis. The correlation between survival and first site of metastasis was confirmed separately for each therapy subgroup. Median metastasis-free survival from primary diagnosis to first metastasis was not correlated with the first site of metastasis., Conclusions: In non-metastatic PCa patients treated with curative intent, the PCa-specific survival time depends on the time after metastatic progression rather than the time from diagnosis to metastasis. Moreover, the site of first metastasis is an independent prognostic factor for PCaSS. Our data confirm that the first metastatic event may confer a differential prognostic impact and may help in identifying patient at high risk of death supporting the treatment-decision making process following metastatic progression.