Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients

OBJECTIVE: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. METHODS: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. RESULTS: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. CONCLUSION: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients

Influence of Hypericum perforatum extract and its single compounds on amyloid-beta mediated toxicity in microglial cells

As immunocompetent cells of the brain, microglia are able to counteract the damaging effects of amyloid-beta in Alzheimer's disease by phagocytosis-mediated clearance of protein aggregates. The survival and health of microglia are therefore crit. for attenuating and preventing neurodegenerative diseases. In a microglial cell line pretreated with St. John's wort (Hypericum perforatum L.) ext. (HPE), the cell death evoked by treatment with amyloid-beta (25-35) and (1-40) was attenuated significantly in a dose-dependent manner. Investigation of the single compds. in the ext. revealed that the flavanols (+)-catechin and (-)-epicatechin increase cell viability slightly, whereas the flavonol quercetin and its glycosides rutin, hyperosid and quercitrin showed no effect on cell viability. In contrast, at the same concn., the flavonoids reduced the formation of amyloid-induced reactive oxygen species in microglia, indicating that improvement of cell viability by the catechins is not correlated to the antioxidant activity. No influence of HPE on the capacity of microglia to phagocytose sub-toxic concns. of fibrillar amyloid-beta (1-40) was obsd. Other expts. showed that HPE, (+)-catechin and (-)-epicatechin can alter cellular membrane fluidity and thereby may have a beneficial effect on cell health. Our findings provide in vitro evidence that treatment esp. with the complex plant ext. HPE may restore or improve microglial viability and thereby attenuate amyloid-beta mediated toxicity in Alzheimer's disease

Hyperforin is a modulator of inducible nitric oxide synthase and phagocytosis in microglia and macrophages

Upon activation, microglia, the immunocompetent cells in the brain, get highly phagocytic and release pro-inflammatory mediators like nitric oxide (NO). Excessive NO prodn. is pivotal in neurodegenerative disorders, and there is evidence that abnormalities in NO prodn. and inflammatory responses may at least support a range of neuropsychiatric disorders, including depression. Although exts. of St. John's wort (Hypericum perforatum L.) have been used for centuries in traditional medicine, notably for the treatment of depression, there is still considerable lack in scientific knowledge about the impact on microglia. We used N11 and BV2 mouse microglia, as well as RAW 264.7 macrophages to investigate the effects of St. John's wort ext. and constituents thereof on NO prodn. Moreover, flow cytometry and fluorescence microscopy were employed to analyze the influence on phagocytosis, transcription factor activation states, and cell motility. We found that exts. of St. John's wort efficiently suppress lipopolysaccharide-induced NO release and identified hyperforin as the responsible compd., being effective at concns. between 0.25 and 0.75 micro M. The reduced NO prodn. was mediated by diminished inducible nitric oxide synthase expression on the mRNA and protein level. In addn., at similar concns., hyperforin reduced zymosan phygocytosis to 20-40% and putatively acted by downregulating the CD206 macrophage mannose receptor and modulation of cell motility. We found that the obsd. effects correlate with a suppression of the activated state of Nf-kappaB and phospho-CREB, while c-JUN, STAT1, and HIF-1alpha activity and cyclooxygenase-2 expression remained unaffected by hyperforin. These results reveal that hyperforin influences pro-inflammatory and immunol. responses of microglia that are involved in the progression of neuropathol. disorders

Shared Tasks as Tutorials: A Methodical Approach

In this paper, we discuss the benefits and challenges of shared tasks as a teaching method. A shared task is a scientific event and a friendly competition to solve a research problem, the task. In terms of linking research and teaching, shared-task-based tutorials fulfill several faculty desires: they leverage students' interdisciplinary and heterogeneous skills, foster teamwork, and engage them in creative work that has the potential to produce original research contributions. Based on ten information retrieval (IR) courses at two universities since 2019 with shared tasks as tutorials, we derive a domain-neutral process model to capture the respective tutorial structure. Meanwhile, our teaching method has been adopted by other universities in IR courses, but also in other areas of AI such as natural language processing and robotics