Value of T2 Mapping MRI for Prostate Cancer Detection and Classification.

Currently, multi-parametric prostate MRI (mpMRI) consists of a qualitative T <sub>2</sub> , diffusion weighted, and dynamic contrast enhanced imaging. Quantification of T <sub>2</sub> imaging might further standardize PCa detection and support artificial intelligence solutions. To evaluate the value of T <sub>2</sub> mapping to detect prostate cancer (PCa) and to differentiate PCa aggressiveness. Retrospective single center cohort study. Forty-four consecutive patients (mean age 67 years; median PSA 7.9 ng/mL) with mpMRI and verified PCa by subsequent targeted plus systematic MR/ultrasound (US)-fusion biopsy from February 2019 to December 2019. Standardized mpMRI at 3 T with an additionally acquired T <sub>2</sub> mapping sequence. Primary endpoint was the analysis of quantitative T <sub>2</sub> values and contrast differences/ratios (CD/CR) between PCa and benign tissue. Secondary objectives were the correlation between T <sub>2</sub> values, ISUP grade, apparent diffusion coefficient (ADC) value, and PI-RADS, and the evaluation of thresholds for differentiating PCa and clinically significant PCa (csPCa). Mann-Whitney test, Spearman's rank (r <sub>s</sub> ) correlation, receiver operating curves, Youden's index (J), and AUC were performed. Statistical significance was defined as P < 0.05. Median quantitative T <sub>2</sub> values were significantly lower for PCa in PZ (85 msec) and PCa in TZ (75 msec) compared to benign PZ (141 msec) or TZ (97 msec) (P < 0.001). CD/CR between PCa and benign PZ (51.2/1.77), respectively TZ (19.8/1.29), differed significantly (P < 0.001). The best T <sub>2</sub> -mapping threshold for PCa/csPCa detection was for TZ 81/86 msec (J = 0.929/1.0), and for PZ 110 msec (J = 0.834/0.905). Quantitative T <sub>2</sub> values of PCa did not correlate significantly with the ISUP grade (r <sub>s</sub> = 0.186; P = 0.226), ADC value (r <sub>s</sub> = 0.138; P = 0.372), or PI-RADS (r <sub>s</sub> = 0.132; P = 0.392). Quantitative T <sub>2</sub> values could differentiate PCa in TZ and PZ and might support standardization of mpMRI of the prostate. Different thresholds seem to apply for PZ and TZ lesions. However, in the present study quantitative T <sub>2</sub> values were not able to indicate PCa aggressiveness. 2 TECHNICAL EFFICACY: Stage 2

First results from the CERN Axion Solar Telescope (CAST)

Hypothetical axion-like particles with a two-photon interaction would be produced in the Sun by the Primakoff process. In a laboratory magnetic field (``axion helioscope'') they would be transformed into X-rays with energies of a few keV. Using a decommissioned LHC test magnet, CAST has been running for about 6 months during 2003. The first results from the analysis of these data are presented here. No signal above background was observed, implying an upper limit to the axion-photon coupling < 1.16 10^{-10} GeV^-1 at 95% CL for m_a <~0.02 eV. This limit is comparable to the limit from stellar energy-loss arguments and considerably more restrictive than any previous experiment in this axion mass range.Comment: 4 pages, accepted by PRL. Final version after the referees comment

Equivocal pi-rads three lesions on prostate magnetic resonance imaging: Risk stratification strategies to avoid mri-targeted biopsies

We aimed to investigate the relation between largest lesion diameter, prostate-specific antigen density (PSA-D), age, and the detection of clinically significant prostate cancer (csPCa) using first-time targeted biopsy (TBx) in men with Prostate Imaging—Reporting and Data System (PI-RADS) 3 index lesions. A total of 292 men (2013–2019) from two referral centers were included. A multivariable logistic regression analysis was performed. The discrimination and clinical utility of the built model was assessed by the area under the receiver operation curve (AUC) and decision curve analysis, respectively. A higher PSA-D and higher age were significantly related to a higher risk of detecting csPCa, while the largest index lesion diameter was not. The discrimination of the model was 0.80 (95% CI 0.73–0.87). When compared to a biopsy-all strategy, decision curve analysis showed a higher net benefit at threshold probabilities of ≥2%. Accepting a missing ≤5% of csPCa diagnoses, a risk-based approach would result in 34% of TBx sessions and 23% of low-risk PCa diagnoses being avoided. In men with PI-RADS 3 index lesions scheduled for first-time TBx, the balance between the number of TBx sessions, the detection of low-risk PCa, and the detection of csPCa does not warrant a biopsy-all strategy. To minimize the risk of missing the diagnosis of csPCa but acknowledging the need of avoiding unnecessary TBx sessions and overdiagnosis, a risk-based approach is advisable

Disruption of the Autophagy-Lysosome Pathway Is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis

Variant late-infantile neuronal ceroid lipofuscinosis, a fatal lysosomal storage disorder accompanied by regional atrophy and pronounced neuron loss in the brain, is caused by mutations in the CLN6 gene. CLN6 is a non-glycosylated endoplasmic reticulum (ER)-resident membrane protein of unknown function. To investigate mechanisms contributing to neurodegeneration in CLN6 disease we examined the nclf mouse, a naturally occurring model of the human CLN6 disease. Prominent autofluorescent and electron-dense lysosomal storage material was found in cerebellar Purkinje cells, thalamus, hippocampus, olfactory bulb and in cortical layer II to V. Another prominent early feature of nclf pathogenesis was the localized astrocytosis that was evident in many brain regions and the more widespread microgliosis. Expression analysis of mutant Cln6 found in nclf mice demonstrated synthesis of a truncated protein with a reduced half-life. Whereas the rapid degradation of the mutant Cln6 protein can be inhibited by proteasomal inhibitors, there was no evidence for ER stress or activation of the unfolded protein response in various brain areas during postnatal development. Age-dependent increases in LC3-II, ubiquitinated proteins, and neuronal p62-positive aggregates were observed, indicating a disruption of the autophagy-lysosome degradation pathway of proteins in brains of nclf mice, most likely due to defective fusion between autophagosomes and lysosomes. These data suggest that proteasomal degradation of mutant Cln6 is sufficient to prevent the accumulation of misfolded Cln6 protein, whereas lysosomal dysfunction impairs constitutive autophagy promoting neurodegeneration

A compact and cost-effective hard X-ray free-electron laser driven by a high-brightness and low-energy electron beam

We present the first lasing results of SwissFEL, a hard X-ray free-electron laser (FEL) that recently came into operation at the Paul Scherrer Institute in Switzerland. SwissFEL is a very stable, compact and cost-effective X-ray FEL facility driven by a low-energy and ultra-low-emittance electron beam travelling through short-period undulators. It delivers stable hard X-ray FEL radiation at 1-Å wavelength with pulse energies of more than 500 μJ, pulse durations of ~30 fs (root mean square) and spectral bandwidth below the per-mil level. Using special configurations, we have produced pulses shorter than 1 fs and, in a different set-up, broadband radiation with an unprecedented bandwidth of ~2%. The extremely small emittance demonstrated at SwissFEL paves the way for even more compact and affordable hard X-ray FELs, potentially boosting the number of facilities worldwide and thereby expanding the population of the scientific community that has access to X-ray FEL radiation

The search for solar axions in the CAST experiment

The CAST (CERN Axion Solar Telescope) experiment at CERN searches for solar axions with energies in the keV range. It is possible that axions are produced in the core of the sun by the interaction of thermal photons with virtual photons of strong electromagnetic fields. In this experiment, the solar axions can be reconverted to photons in the transversal field of a 9 Tesla superconducting magnet. At both ends of the 10m-long dipole magnet three different X-ray detectors were installed, which are sensitive in the interesting photon energy range. Preliminary results from the analysis of the 2004 data are presented: g$_{a\gamma}<0.9\times10^{-10}$ GeV$^{-1}$ at 95% C.L. for axion masses m$_{a} <$ 0.02 eV. At the end of 2005, data started to be taken with a buffer gas in the magnet pipes in order to extend the sensitivity to axion masses up to 0.8 eV.The CAST (CERN Axion Solar Telescope) experiment at CERN searches for solar axions with energies in the keV range. It is possible that axions are produced in the core of the sun by the interaction of thermal photons with virtual photons of strong electromagnetic fields. In this experiment, the solar axions can be reconverted to photons in the transversal field of a 9 Tesla superconducting magnet. At both ends of the 10m-long dipole magnet three different X-ray detectors were installed, which are sensitive in the interesting photon energy range. Preliminary results from the analysis of the 2004 data are presented: g$_{a\gamma}<0.9\times10^{-10}$ GeV$^{-1}$ at 95% C.L. for axion masses m$_{a} <$ 0.02 eV. At the end of 2005, data started to be taken with a buffer gas in the magnet pipes in order to extend the sensitivity to axion masses up to 0.8 eV

Search for solar axions: CAST

The CERN Axion Solar Telescope (CAST) is searching for axions produced in the Sun's core by the Primakoff process. CAST is using a decommissioned Large Hadron Collider (LHC) test magnet where axions could be converted back into X-rays with energies up to 10 keV. Analysis of the 2003 data showed no signal above background implying an upper limit for the axion-photon coupling constant gagg < 1.16 X 10 ^-10 GeV exp -1 at 95% C.L. for ma . 0.02 eV [1]. The higher quality 2004 data is presently under analysis. CAST Phase II is scheduled to start in late 2005. This will be the first step in extending CAST's sensitivity to axion rest masses up to ~ 1 eV

An Essential Role for Katanin p80 and Microtubule Severing in Male Gamete Production

Katanin is an evolutionarily conserved microtubule-severing complex implicated in multiple aspects of microtubule dynamics. Katanin consists of a p60 severing enzyme and a p80 regulatory subunit. The p80 subunit is thought to regulate complex targeting and severing activity, but its precise role remains elusive. In lower-order species, the katanin complex has been shown to modulate mitotic and female meiotic spindle dynamics and flagella development. The in vivo function of katanin p80 in mammals is unknown. Here we show that katanin p80 is essential for male fertility. Specifically, through an analysis of a mouse loss-of-function allele (the Taily line), we demonstrate that katanin p80, most likely in association with p60, has an essential role in male meiotic spindle assembly and dissolution and the removal of midbody microtubules and, thus, cytokinesis. Katanin p80 also controls the formation, function, and dissolution of a microtubule structure intimately involved in defining sperm head shaping and sperm tail formation, the manchette, and plays a role in the formation of axoneme microtubules. Perturbed katanin p80 function, as evidenced in the Taily mouse, results in male sterility characterized by decreased sperm production, sperm with abnormal head shape, and a virtual absence of progressive motility. Collectively these data demonstrate that katanin p80 serves an essential and evolutionarily conserved role in several aspects of male germ cell development

Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation

A novel method for quantifying the similarity between phenotypes by the use of ontologies can be used to search for candidate genes, pathway members, and human disease models on the basis of phenotypes alone