A
bstract
The nature of the QCD chiral phase transition in the limit of vanishing quark masses has remained elusive for a long time, since it cannot be simulated directly on the lattice and is ...strongly cutoff-dependent. We report on a comprehensive ongoing study using unimproved staggered fermions with
N
f
∈ 2, 8 mass-degenerate flavours on
N
τ
∈ {4
,
6
,
8} lattices, in which we locate the chiral critical surface separating regions with first-order transitions from crossover regions in the bare parameter space of the lattice theory. Employing the fact that it terminates in a tricritical line, this surface can be extrapolated to the chiral limit using tricritical scaling with known exponents. Knowing the order of the transitions in the lattice parameter space, conclusions for approaching the continuum chiral limit in the proper order can be drawn. While a narrow first-order region cannot be ruled out, we find initial evidence consistent with a second-order chiral transition in all massless theories with
N
f
≤ 6, and possibly up to the onset of the conformal window at 9 ≲
N
f
∗
≲ 12. A reanalysis of already published
O
(
a
)-improved
N
f
= 3 Wilson data on
N
τ
∈ 4
,
12 is also consistent with tricritical scaling, and the associated change from first to second-order on the way to the continuum chiral limit. We discuss a modified Columbia plot and a phase diagram for many-flavour QCD that reflect these possible features.
Prostate cancer (PCa) is the most common cancer in men. The androgen receptor (AR) has a pivotal role in the pathogenesis and progression of PCa. Many therapies targeting AR signaling have been ...developed over the years. AR signaling inhibitors (ARSIs), including androgen synthesis inhibitors and AR antagonists, have proven to be effective in castration-sensitive PCa (CSPC) and improve survival, but men with castration-resistant PCa (CRPC) continue to have a poor prognosis. Despite a good initial response, drug resistance develops in almost all patients with metastatic CRPC, and ARSIs are no longer effective. Several mechanisms confer resistance to ARSI and include AR mutations but also hyperactivation of other pathways, such as PI3K/AKT/mTOR. This pathway controls key cellular processes, including proliferation and tumor progression, and it is the most frequently deregulated pathway in human cancers. A significant interaction between AR and the PI3K/AKT/mTOR signaling pathway has been shown in PCa. This review centers on the current scene of different AR and PI3K signaling pathway inhibitors, either as monotherapy or in combination treatments in PCa, and the treatment outcomes involved in both preclinical and clinical trials. A PubMed-based literature search was conducted up to November 2022. The most relevant and recent articles were selected to provide essential information and current evidence on the crosstalk between AR and the PI3K signaling pathways. The ClinicalTrials.gov registry was used to report information about clinical studies and their results using the Advanced research tool, filtering for disease and target.
Prostate specific antigen (PSA) test is the most common, clinically validated test for the diagnosis of prostate cancer (PCa). While neoplastic lesions of the prostate may cause aberrant levels of ...PSA in the blood, the quantitation of free or complexed PSA poorly discriminates cancer patients from those developing benign lesions, often leading to invasive and unnecessary surgical procedures. Microenvironmental acidity increases exosome release by cancer cells. In this study we evaluated whether acidity, a critical phenotype of malignancy, could influence exosome release and increase the PSA expression in nanovesicles released by PCa cells. To this aim, we exploited Nanoparticle Tracking Analysis (NTA), an immunocapture-based ELISA, and nanoscale flow-cytometry. The results show that microenvironmental acidity induces an increased release of nanovesicles expressing both PSA and the exosome marker CD81. In order to verify whether the changes induced by the local selective pressure of extracellular acidity may correspond to a clinical pathway we used the same approach to evaluate the levels of PSA-expressing exosomes in the plasma of PCa patients and controls, including subjects with benign prostatic hypertrophy (BPH). The results show that only PCa patients have high levels of nanovesicles expressing both CD81 and PSA. This study shows that tumor acidity exerts a selective pressure leading to the release of extracellular vesicles that express both PSA and exosome markers. A comparable scenario was shown in the plasma of prostate cancer patients as compared to both BPH and healthy controls. These results suggest that microenvironmental acidity may represent a key factor which determines qualitatively and quantitatively the release of extracellular vesicles by malignant tumors, including prostate cancer. This condition leads to the spill-over of nanovesicles into the peripheral blood of prostate cancer patients, where the levels of tumor biomarkers expressed by exosomes, such as PSA-exosomes, may represent a novel, non-invasive clinical tool for the screening and early diagnosis of prostate cancer.
•PSA prostate-specific antigen (PSA) is a prostate cancer (PCa) specific marker.•Microenvironmental acidity increases exosome release by cancer cells.•Acidity induces expression of PSA by exosomes.•PCa patients had high levels of PSA-expressing exosomes.•Tumor acidity exerts a selective pressure leading to expression of PSA by exosomes, leading in turn to the spilling over of PSA-expressing exosomes in the blood of PCa patients.•The use of plasmatic PSA-exosomes may be a novel, non-invasive clinical tool for screening and early diagnosis of prostate cancer.
Vesical Imaging Reporting and Data System (VI-RADS) score is adopted to provide preoperative bladder cancer (BCa) staging. Repeated transurethral resection of bladder tumor (Re-TURBT) is recommended ...in most of high-risk non–muscle-invasive bladder cancers (HR-NMIBCs) due to possibility of persistent/understaged disease after initial TURBT. No diagnostic tools able to improve patient’s stratification for such recommendation exist.
To (1) prospectively validate VI-RADS for discriminating between NMIBC and muscle-invasive bladder cancer (MIBC) at TURBT, and (2) evaluate the accuracy of VI-RADS for identifying HR-NMIBC patients who could avoid Re-TURBT and detecting those at higher risk for understaging after TURBT.
Patients with BCa suspicion were offered multiparametric magnetic resonance imaging (mpMRI) before TURBT. According to VI-RADS, a cutoff of ≥3 to define MIBC was assumed. TURBT reports were compared with preoperative VI-RADS scores to assess accuracy of mpMRI for discriminating between NMIBC and MIBC. HR-NMIBC Re-TURBT reports were compared with preoperatively recorded VI-RADS scores to assess mpMRI accuracy in predicting Re-TURBT outcomes.
Multiparametric MRI of the bladder before TURBT.
Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated for mpMRI performance in patients undergoing TURBT and for HR-NMIBC patients candidate for Re-TURBT. Performance of mpMRI was assessed by receiver operating characteristic curve analysis. Ƙ statistics was used to estimate inter- and intrareader variability.
A total of 231 patients were enrolled. Multiparametric MRI showed sensitivity, specificity, PPV, and NPV for discriminating NMIBC from MIBC at initial TURBT of 91.9% (95% confidence interval CI: 82.2–97.3), 91.1% (95% CI: 85.8–94.9), 77.5% (95% CI: 65.8–86.7), and 97.1% (95% CI: 93.3–99.1), respectively. The area under the curve (AUC) was 0.94 (95% CI: 0.91–0.97). Among HR-NMIBC patients (n=114), mpMRI before TURBT showed sensitivity, specificity, PPV, and NPV of 85% (95% CI: 62.1–96.8), 93.6% (95% CI: 86.6–97.6), 74.5% (95% CI: 52.4–90.1), and 96.6% (95% CI: 90.5–99.3) respectively, to identify patients with MIBC at Re-TURBT. The AUC was 0.93 (95% CI: 0.87–0.97).
VI-RADS is accurate for discriminating between NMIBC and MIBC. Within HR-NMIBC cases, VI-RADS could, in future, improve the selection of patients who are candidate for Re-TURBT.
We investigated the accuracy of Vesical Imaging Reporting and Data System (VI-RADS) score to asses bladder cancer staging before transurethral resection of bladder tumors, and we explored the performance of VI-RADS score as a future preoperative predictive tool for the selection of high-risk non–muscle-invasive bladder cancer patients who are candidate for undergoing early repeated transurethral resection of the primary tumor site.
Vesical Imaging Reporting and Data System (VI-RADS) score is a novel imaging tool able to differentiate superficial from muscle-invasive bladder cancer before transurethral resection of bladder tumor (TURBT). Within the category of high-risk non–muscle-invasive bladder cancers, VI-RADS could differentiate those not needing repeated TURBT (Re-TURBT) from those who should definitely not miss Re-TURBT.
Numerical QCD is often extremely resource demanding and it is not rare to run hundreds of simulations at the same time. Each of these can last for days or even months and it typically requires a ...job-script file as well as an input file with the physical parameters for the application to be run. Moreover, some monitoring operations (i.e. copying, moving, deleting or modifying files, resume crashed jobs, etc.) are often required to guarantee that the final statistics is correctly accumulated. Proceeding manually in handling simulations is probably the most error-prone way and it is deadly uncomfortable and inefficient! BaHaMAS was developed and successfully used in the last years as a tool to automatically monitor and administrate simulations.
Abstract Context Prostate cancer (PCa) is the most common cancer in the adult male, and benign prostatic hyperplasia (BPH) represents the most frequent urologic diagnosis in elderly males. Recent ...data suggest that prostatic inflammation is involved in the pathogenesis and progression of both conditions. Objective This review aims to evaluate the available evidence on the role of prostatic inflammation as a possible common denominator of BPH and PCa and to discuss its possible clinical implication for the management, prevention, and treatment of both diseases. Evidence acquisition The National Library of Medicine Database was searched for the following Patient population, Intervention, Comparison, Outcome (PICO) terms: male, inflammation, benign prostatic hyperplasia, prostate cancer, diagnosis, progression, prognosis, treatment, and prevention. Basic and clinical studies published in the past 10 yr were reviewed. Additional references were obtained from the reference list of full-text manuscripts. Evidence synthesis The histologic signature of chronic inflammation is a common finding in benign and malignant prostate tissue. The inflammatory infiltrates are mainly represented by CD3+ T lymphocytes (70–80%, mostly CD4), CD19 or CD20 B lymphocytes (10–15%), and macrophages (15%). Bacterial infections, urine reflux, dietary factors, hormones, and autoimmune response have been considered to cause inflammation in the prostate. From a pathophysiologic standpoint, tissue damage associated with inflammatory response and subsequent chronic tissue healing may result in the development of BPH nodules and proliferative inflammatory atrophy (PIA). The loss of glutathione S-transferase P1 (GSTP1) may be responsible in patients with genetic predisposition for the transition of PIA into high-grade intraepithelial neoplasia (HGPIN) and PCa. Although there is growing evidence of the association among inflammatory response, BPH, and PCa, we can only surmise on the immunologic mechanisms involved, and further research is required to better understand the role of prostatic inflammation in the initiation of BPH and PCa. There is not yet proof that targeting prostate inflammation with a pharmacologic agent results in a lower incidence and progression or regression of either BPH or PCa. Conclusions Evidence in the peer-reviewed literature suggested that chronic prostatic inflammation may be involved in the development and progression of chronic prostatic disease, such as BPH and PCa, although there is still no evidence of a causal relation. Inflammation should be considered a new domain in basic and clinical research in patients with BPH and PCa.
Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement.
Patients with ...chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation.
Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies.
Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis‐like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation.
The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation.
Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically ...significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive.
Prostate cancer (PCa) is the most common worldwide diagnosed malignancy in male population. The diagnosis, the identification of aggressive disease, and the post-treatment follow-up needs a more ...comprehensive and holistic approach. Radiomics is the extraction and interpretation of images phenotypes in a quantitative manner. Radiomics may give an advantage through advancements in imaging modalities and through the potential power of artificial intelligence techniques by translating those features into clinical outcome prediction. This article gives an overview on the current evidence of methodology and reviews the available literature on radiomics in PCa patients, highlighting its potential for personalized treatment and future applications.
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