Follow-up of iatrogenic aorto-coronary "Dunning" dissections by cardiac computed tomography imaging

Background: Iatrogenic aorto-coronary dissections following percutaneous coronary interventions (PCI) represent a rare but potentially life threatening complication. This restrospective and observational study aims to describe our in-house experience for timely diagnostics and therapy including cardiovascular imaging to follow-up securely high-risk patients with Dunning dissections. Methods: Dunning dissections (DD) occurred during clinical routine PCIs, which were indicated according to current ESC guidelines. Diagnostic assessment, treatment and follow-up were based on coronary angiography with PCI or conservative treatment and cardiac computed tomography (cCTA) imaging. Results: A total of eight patients with iatrogenic DD were included. Median age was 69 years (IQR 65.8–74.5). Patients revealed a coronary multi-vessel-disease in 75% with a median SYNTAX-II-score of 35.3 (IQR 30.2–41.2). The most common type of DD was type III (50%), followed by type I (38%) and type II (13%). In most patients (88%) the DD involved the right coronary arterial ostium. 63% were treated by PCI, the remaining patients were treated conservatively. 88% of patients received at least one cCTA within 2 days, 50% were additionally followed-up by cCTA within a median of 6 months (range: 4–8 months) without any residual. Conclusion: Independently of the type of DD (I-III) it was demonstrated that cCTA represents a valuable imaging modality for detection and follow-up of patients with DDs

2-[1-(1-Naphth­yl)-1H-1,2,3-triazol-4-yl]pyridine

In the crystal structure of the title compound, C17H12N4, the angle between the naphthalene and 1H-1,2,3-triazole ring systems is 71.02 (4)° and that between the pyridine and triazole rings is 8.30 (9)°

Lymphocyte Subsets Show Different Response Patterns to In Vivo Bound Natalizumab—A Flow Cytometric Study on Patients with Multiple Sclerosis

Natalizumab is an effective monoclonal antibody therapy for the treatment of relapsing- remitting multiple sclerosis (RRMS) and interferes with immune cell migration into the central nervous system by blocking the α4 subunit of very-late activation antigen-4 (VLA-4). Although well tolerated and very effective, some patients still suffer from relapses in spite of natalizumab therapy or from unwanted side effects like progressive multifocal leukoencephalopathy (PML). In search of a routine-qualified biomarker on the effectiveness of natalizumab therapy we applied flow cytometry and analyzed natalizumab binding to α4 and α4 integrin surface levels on T-cells, B-cells, natural killer (NK) cells, and NKT cells from 26 RRMS patients under up to 72 weeks of therapy. Four-weekly infusions of natalizumab resulted in a significant and sustained increase of lymphocyte-bound natalizumab (p<0.001) which was paralleled by a significant decrease in detectability of the α4 integrin subunit on all lymphocyte subsets (p<0.001). We observed pronounced natalizumab accumulations on T and B cells at single measurements in all patients who reported clinical disease activity (n = 4). The natalizumab binding capacity of in vitro saturated lymphocytes collected during therapy was strongly diminished compared to treatment-naive cells indicating a therapy-induced reduction of α4. Summing up, this pilot study shows that flow cytometry is a useful method to monitor natalizumab binding to lymphocytes from RRMS patients under therapy. Investigating natalizumab binding provides an opportunity to evaluate the molecular level of effectiveness of natalizumab therapy in individual patients. In combination with natalizumab saturation experiments, it possibly even provides a means of studying the feasability of patient-tailored infusion intervals. A routine-qualified biomarker on the basis of individual natalizumab saturation on lymphocyte subsets might be an effective tool to improve treatment safety

Measurement of neutrino and antineutrino neutral-current quasielasticlike interactions on oxygen by detecting nuclear deexcitation γ rays

Neutrino- and antineutrino-oxygen neutral-current quasielastic-like interactions are measured at Super-Kamiokande using nuclear de-excitation $\gamma$-rays to identify signal-like interactions in data from a $14.94 \ (16.35)\times 10^{20}$protons-on-target exposure of the T2K neutrino (antineutrino) beam. The measured flux-averaged cross sections on oxygen nuclei are$\langle \sigma_{\nu {\rm -NCQE}} \rangle = 1.70 \pm 0.17 ({\rm stat.}) ^{+ {\rm 0.51}}_{- {\rm 0.38}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$with a flux-averaged energy of 0.82 GeV and$\langle \sigma_{\bar{\nu} {\rm -NCQE}} \rangle = 0.98 \pm 0.16 ({\rm stat.}) ^{+ {\rm 0.26}}_{- {\rm 0.19}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$ with a flux-averaged energy of 0.68 GeV, for neutrinos and antineutrinos, respectively. These results are the most precise to date, and the antineutrino result is the first cross section measurement of this channel. They are compared with various theoretical predictions. The impact on evaluation of backgrounds to searches for supernova relic neutrinos at present and future water Cherenkov detectors is also discussed

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Measurement of the muon neutrino charged-current cross sections on water, hydrocarbon and iron, and their ratios, with the T2K on-axis detectors

We report a measurement of the flux-integrated νμ charged-current cross sections on water, hydrocarbon, and iron in the T2K on-axis neutrino beam with a mean neutrino energy of 1.5 GeV. The measured cross sections on water, hydrocarbon, and iron are σH2OCC=(0.840±0.010(stat.)+0.10−0.08(syst.))×10−38cm2/nucleon, σCHCC=(0.817±0.007(stat.)+0.11−0.08(syst.))×10−38cm2/nucleon, and σFeCC=(0.859±0.003(stat.)+0.12−0.10(syst.))×10−38cm2/nucleon, respectively, for a restricted phase space of induced muons: θμ0.4 GeV/c in the laboratory frame. The measured cross section ratios are σH2OCC/σCHCC=1.028±0.016(stat.)±0.053(syst.)⁠, σFeCC/σH2OCC=1.023±0.012(stat.)±0.058(syst.)⁠, and σFeCC/σCHCC=1.049±0.010(stat.)±0.043(syst.)⁠. These results, with an unprecedented precision for the measurements of neutrino cross sections on water in the studied energy region, show good agreement with the current neutrino interaction models used in the T2K oscillation analyses

Constraint on the matter-antimatter symmetry-violating phase in neutrino oscillations

The charge-conjugation and parity-reversal (CP) symmetry of fundamental particles is a symmetry between matter and antimatter. Violation of this CP symmetry was first observed in 19641, and CP violation in the weak interactions of quarks was soon established2. Sakharov proposed3 that CP violation is necessary to explain the observed imbalance of matter and antimatter abundance in the Universe. However, CP violation in quarks is too small to support this explanation. So far, CP violation has not been observed in non-quark elementary particle systems. It has been shown that CP violation in leptons could generate the matter–antimatter disparity through a process called leptogenesis4. Leptonic mixing, which appears in the standard model’s charged current interactions5,6, provides a potential source of CP violation through a complex phase δCP, which is required by some theoretical models of leptogenesis7,8,9. This CP violation can be measured in muon neutrino to electron neutrino oscillations and the corresponding antineutrino oscillations, which are experimentally accessible using accelerator-produced beams as established by the Tokai-to-Kamioka (T2K) and NOvA experiments10,11. Until now, the value of δCP has not been substantially constrained by neutrino oscillation experiments. Here we report a measurement using long-baseline neutrino and antineutrino oscillations observed by the T2K experiment that shows a large increase in the neutrino oscillation probability, excluding values of δCP that result in a large increase in the observed antineutrino oscillation probability at three standard deviations (3σ). The 3σ confidence interval for δCP, which is cyclic and repeats every 2π, is [−3.41, −0.03] for the so-called normal mass ordering and [−2.54, −0.32] for the inverted mass ordering. Our results indicate CP violation in leptons and our method enables sensitive searches for matter–antimatter asymmetry in neutrino oscillations using accelerator-produced neutrino beams. Future measurements with larger datasets will test whether leptonic CP violation is larger than the CP violation in quarks