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To determine the capability of Gadolinium-free arterial spin labelling (ASL) sequences as novel, contrast-free, non-invasive alternative perfusion imaging method to differentiate prostate cancer (PCA) from benign prostate tissue compared to conventional DCE MRI.Thirty men with histologically confirmed PCA were included in this prospectively enrolled single center cohort study. All patients received multiparametric MRI (T2, DWI, DCE) at 3 T with additional ASL of the PCA lesion. Primary endpoint was differentiability of PCA versus benign prostate tissue by signal intensities (SI) and contrast ratios (CR) in ASL in comparison to DCE. For DCE also Signal-Enhancement-Ratio (SER) of native and early contrast enhancement SI was assessed. Secondary objectives were differences regarding PCA localisation in peripheral (PZ) or transition zone (TZ) and PCA detection.In both, ASL and DCE, average SI of PCA differed significantly from SI in benign tissue in the TZ and PZ (p 0,01, respectively). ASL had significantly higher CR discerning PCA and benign tissue in PZ and TZ (PZ = 5.19; TZ = 6.45) compared to DCE SI (PZ = 1.61; TZ = 1.43) and DCE SER (PZ = 1.59; TZ = 1.43) (p 0.01, respectively). In subjective evaluation, PCA could be detected in ASL in 28 patients, compared to 29 in DCE.ASL had significantly higher CR differentiating PCA from benign tissue in PZ and TZ compared to DCE. Visual detection of PCA does not differ significantly between the two sequences. As perfusion gadolinium-based contrast media is seen more critical in the last few years, ASL seems to be a promising alternative to DCE in PCA detection.

Efficient data storage and query processing systems play a vital role in many different research areas. Blockchain technology and distributed ledgers attract massive attention and trigger multiple projects in various industries. Nevertheless, blockchain still lacks the features of a Database Management System (DBMS or simply databases), such as high throughput, low latency, and high capacity. For that purpose, there have been many proposed approaches for handling data storage and query processing solutions in the blockchain. This paper presents a complete overview of many different DBMS types and how these systems can be used to implement, enhance, and further improve blockchain technology. More concretely, we give an overview of 10 transactional, an extensive overview of 14 analytical, 9 hybrids, i.e., translytical, and 13 blockchain DBMSs. We explain how database technology has influenced the development of blockchain technology by unlocking different features, such as Atomicity, Consistency, Isolation, and Durability (ACID), transaction consistency, rich queries, real-time analysis, and low latency. Using a relaxation approach analogous to the one used to prove the Consistency, Availability, Partition tolerance (CAP)-theorem, we postulate a “Decentralization, Consistency, and Scalability (DCS)-satisfiability conjecture” and give concrete strategies for achieving the relaxed DCS conditions. We also provide an overview of the different DBMSs, emphasizing their architecture, storage manager, query processing, and implementation.

This is a data article from the original publication "Reasons for missing clinically significant prostate cancer by targeted magnetic resonance imaging/ultrasound fusion-guided biopsy" [1]. From January 2014 to April 2019 a sample collective of 785 patients with 3T multiparametric magnetic resonance imaging (mp-MRI) of the prostate and subsequent combined systematic biopsy (SB) and magnetic resonance imaging/ultrasound (US) fusion-guided biopsy (TB) was retrospectively analyzed. Prostate cancer (PCa) detection by TB and/or additional SB was analyzed.

Exaggerated PI3K/AKT signaling abrogates B cell tolerance and results in autoimmunity. P2RY8 is a repressor of AKT-mediated B cell activation that also restrains cell migration. Here we identified a de novo, novel P2RY8 missense variant in a child with severe lupus nephritis, an ultrarare variant in a proband with antiphospholipid syndrome, and a less rare missense variant in six lupus patients. These variants impaired protein expression and function, leading to increased AKT and ERK activity and cell migration, and diminished follicular confinement. By contrast, P2RY8 overexpression restrained plasma cell (PC) development and reinforced negative selection of DNA-reactive developing mouse B cells. Remarkably, P2RY8 was downregulated in most SLE patients. Environmental factors including TLR7 ligation and DNA damage caused P2RY8 downregulation. Low P2RY8 correlated with lupus nephritis and increased PC and double negative B cells, suggesting that loss of P2RY8-mediated immunological tolerance contributes to lupus pathogenesis.

Background: The Rotterdam European Randomized Study of Screening for Prostate Cancer risk calculators (ERSPC-RCs) help to avoid unnecessary transrectal ultrasound-guided systematic biopsies (TRUS-Bx). Multivariable risk stratification could also avoid unnecessary biopsies following multiparametric magnetic resonance imaging (mpMRI). Objective: To construct MRI-ERSPC-RCs for the prediction of any- and high-grade (Gleason score ≥3 + 4) prostate cancer (PCa) in 12-core TRUS-Bx ± MRI-targeted biopsy (MRI-TBx) by adding Prostate Imaging Reporting and Data System (PI-RADS) and age as parameters to the ERSPC-RC3 (biopsy-naïve men) and ERSPC-RC4 (previously biopsied men). Design, setting, and participants: A total of 961 men received mpMRI and 12-core TRUS-Bx ± MRI-TBx (in case of PI-RADS ≥3) in five institutions. Data of 504 biopsy-naïve and 457 previously biopsied men were used to adjust the ERSPC-RC3 and ERSPC-RC4. Outcome measurements and statistical analysis: Logistic regression models were constructed. The areas under the curve (AUCs) of the original ERSPC-RCs and MRI-ERSPC-RCs (including PI-RADS and age) for any- and high-grade PCa were compared. Decision curve analysis was performed to assess the clinical utility of the MRI-ERSPC-RCs. Results and limitations: MRI-ERSPC-RC3 had a significantly higher AUC for high-grade PCa compared with the ERSPC-RC3: 0.84 (95% confidence interval [CI] 0.81–0.88) versus 0.76 (95% CI 0.71–0.80, p < 0.01). Similarly, MRI-ERSPC-RC4 had a higher AUC for high-grade PCa compared with the ERSPC-RC4: 0.85 (95% CI 0.81–0.89) versus 0.74 (95% CI 0.69–0.79, p < 0.01). Unlike for the MRI-ERSPC-RC3, decision curve analysis showed clear net benefit of the MRI-ERSPC-RC4 at a high-grade PCa risk threshold of ≥5%. Using a ≥10% high-grade PCa risk threshold to biopsy for the MRI-ERSPC-RC4, 36% biopsies are saved, missing low- and high-grade PCa, respectively, in 15% and 4% of men who are not biopsied. Conclusions: We adjusted the ERSPC-RCs for the prediction of any- and high-grade PCa in 12-core TRUS-Bx ± MRI-TBx. Although the ability of the MRI-ERSPC-RC3 for biopsy-naïve men to avoid biopsies remains questionable, application of the MRI-ERSPC-RC4 in previously biopsied men in our cohort would have avoided 36% of biopsies, missing high-grade PCa in 4% of men who would not have received a biopsy. Patient summary: We have constructed magnetic resonance imaging-based Rotterdam European Randomized study of Screening for Prostate Cancer (MRI-ERSPC) risk calculators for prostate cancer prediction in transrectal ultrasound-guided biopsy and MRI-targeted biopsy by incorporating age and Prostate Imaging Reporting and Data System score into the original ERSPC risk calculators. The MRI-ERSPC risk calculator for previously biopsied men could be used to avoid one-third of biopsies following MRI. The magnetic resonance imaging-based Rotterdam European Randomized Study of Screening for Prostate Cancer (MRI-ERSPC) risk calculators include age and Prostate Imaging Reporting and Data System as parameters, and predict (Gleason ≥3 + 4) prostate cancer in transrectal ultrasound-guided systematic biopsy and MRI-targeted biopsy. The MRI-ERSPC risk calculator could help avoid one-third of biopsies following MRI in previously biopsied men.

Purpose Reproducibility of quantitative perfusion analysis of DCE requires a standardized AIF acquisition. However, there are many different approaches for AIF assessment so that the absolute values of perfusion parameters may vary depending on the used method. This study analyzes the influence of the method of AIF determination on quantitative DCE-MRI. Methods In this retrospective, single-center, cohort study three different methods of AIF determination in 50 consecutive patients with multiparametric MRI of the prostate were conducted. As a reference, AIF was selected manually by defining a region of interest in an artery manually (AIFm). The second method (AIFa), based on an automated algorithm and the third, population-derived AIFp where then compared. Primary endpoint were differences in the performance of the perfusion parameters Ktrans, ve and kep regarding the AIF acquisition methods, secondary endpoints consisted of the evaluation of differences in the peripheral and transition zone of the prostate (PZ, TZ). Results In all three methods, Ktrans, ve, and kep were significantly higher in PZ than in TZ with Ktrans showing least overlapping. There were no significant differences for Ktrans determined with AIFm and AIFa (0.3 ± 0.2 min−1 for PZ for both and 0.5 ± 0.3 min−1 for TZ in AIFm and 0.4 ± 0.3 min−1 in AIFa), while there were great differences between AIFa and AIFp and AIFm and AIFp (0.1 ± 0.03 min−1 for TZ and PZ in AIFp). Spearman test demonstrated good correlation of values for Ktrans and kep in all 3 methods (ρ ≥ 0.76). AIFa showed a success rate of 98% in finding the artery. Conclusion AIFa is a recommendable user-independent automatical method to determine quantitative perfusion parameters allowing an objective measurement and saving interactive time for the radiologist. AIFp may be applied as second alternative method.

Purpose To evaluate image quality and diagnostic value of multiparametric prostate MRI (mpMRI) in patients with total hip replacement (THR) at 1.5 and 3 Tesla. Methods In this retrospective multicenter cohort study patients with uni- or bilateral THR and 1.5 T or 3 T mpMRI were included. Seventy consecutive, standard-of-care examinations per field strength were evaluated regarding their diagnostic value. The overall diagnostic value and prostate imaging quality score (PI-QUAL) were assessed. Artifact severity in the localizer and mpMRI sequences (T2w, DWI, DCE) was scored on a 3-point scale. Correlation between diagnostic value and artifacts was analysed. Moreover, a subgroup analysis focussed on image quality at different 3 T scanner generations. Results 140 consecutive patients (mean age 72, median PSA value 8.3 ng/ml) were included. When comparing 1.5 T to 3 T examinations, no significant differences were observed regarding the artifact severity of DWI and the localizer and the overall diagnostic value of the images. There was a strong correlation between the diagnostic value, PI-QUAL score, and artifact severity in the localizer and DWI. T2w and DCE sequences showed overall low artifacts. Significant improvement in image quality for 3 T at the latest scanner generation was observed, especially for DWI (p Conclusions MpMRI of patients with THR can be conducted at both field strengths without significant differences in artifacts. The localizer might be useful as an early forecasting feature for diagnostic value and particularly for contrast medium application decision. Patients with THR could benefit from technically advanced scanner generation and rs/ptx-EPI DWI sequences.

This study prospectively evaluates objective image quality (IQ), subjective IQ, and PI-RADS scoring of prostate MRI at 3.0T (3T) and 1.5T (1.5T) within the same patients.Sixty-three consecutive patients (64±9years) were prospectively included in this non-inferiority trial, powered at 80% to demonstrate a ≤10% difference in signal-to-noise (SNR) and contrast-to-noise ratio (CNR) of T2-weighted and diffusion-weighted imaging (T2WI, DWI) at 1.5T compared to 3T. Secondary endpoints were analysis of subjective IQ and PI-RADS v2 scoring.All patients received multi-parametric prostate MRI on a 3T (T2WI, DWI, DCE) and bi-parametric MRI (T2WI, DWI) on a 1.5T scanner using body coils, respectively. SNR and CNR of T2WI were similar at 1.5T and 3T (p=0.7-1), but of DWI significantly lower at 1.5T (p0.01). Subjective IQ was significantly better at 3T for both, T2WI and DWI (p0.01). PI-RADS scores were comparable for both field strengths (p=0.05-1). Inter-reader agreement was excellent for subjective IQ assessment and PI-RADS scoring (k=0.9-1).Prostate MRI at 1.5T can reveal comparable objective image quality in T2WI, but is inferior to 3T in DWI and subjective IQ. However, similar PI-RADS scoring and thus diagnostic performance seems feasible independent of the field strength even without an endorectal coil.

The chromosome 15q13.3 region has been implicated in epilepsy, intellectual disability and neuropsychiatric disorders, especially schizophrenia. Deficiency of the acetylcholine receptor gene CHRNA7 and the partial duplication, CHRFAM7A, may contribute to these phenotypes and we sought to comprehensively analyze these genes in genetic generalized epilepsy. We analyzed using DHPLC, Sanger sequencing and long range PCR, 174 probands with genetic generalized epilepsy with or without intellectual disability or psychosis, including 8 with the recurrent 15q13.3 microdeletion. We searched CHRNA7 and CHRFAM7A for single sequence variants, small copy number variants, and the common 2-bp deletion in CHRFAM7A. We identified two novel and one reported missense variants. The common 2-bp deletion was not enriched in patients compared to controls. Our data suggest that missense mutations in CHRNA7 contribute to complex inheritance in genetic generalized epilepsy in a similar fashion to the 15q13.3 microdeletion. They do not support a pathogenic role for the common 2-bp CHRFAM7A deletion. Refereed/Peer-reviewed

Objectives To compare prostate specific membrane antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) and computed tomography (CT) alone for the detection of biochemical recurrence of prostate cancer (PCa) and effect on treatment. Methods This retrospective study included 59 patients with recently recorded biochemical recurrence of PCa (mean PSA 1.96 ± 1.64 ng/mL) after radical prostatectomy. Patients received PET/CT with either 68Ga-PSMA-11 (n = 36) or 18F-PSMA-1007 (n = 23). PET/CT and CT images were evaluated separately in regard to PCa lesion count, type, and localisation by two physicians. Histopathology, follow-up imaging and PSA levels after salvage irradiation served as reference standard. A McNemar test was used to compare detection rates. Changes in therapeutic approaches based on staging differences between CT alone and PET/CT were assessed in a virtual multidisciplinary tumour board. Results There were 142 lesions in 50 of 59 patients. PSMA PET/CT detected 141 lesions (99.3 %) in 50 patients (84.7 %), while CT detected 72 lesions (50.7 %) in 29 patients (49.2 %). A significantly higher detection rate of PSMA PET/CT was observed on a lesion-based analysis (p Conclusion PSMA PET/CT is superior to CT alone in detecting biochemical recurrence in PCa patients after radical prostatectomy and offered additional therapeutic options in a substantial number of patients.