Iodinated PSMA Ligands as XFI Tracers for Targeted Cell Imaging and Characterization of Nanoparticles.

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes the development of small-molecule tracers for the well-known tumor marker prostate-specific membrane antigen (PSMA).

Proteomic profiling reveals ACSS2 facilitating metabolic support in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by genomic aberrations in oncogenes, cytogenetic abnormalities, and an aberrant epigenetic landscape. Nearly 50% of AML cases will relapse with current treatment. A major source of therapy resistance is the interaction of mesenchymal stroma with leukemic cells resulting in therapeutic protection.

Decoration of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) with N-oxides increases the T relaxivity of Gd-complexes.

High complex stability and longitudinal relaxivity of Gd-based contrast agents are important requirements for magnetic resonance imaging (MRI) because they ensure patient safety and contribute to measurement sensitivity. Charged and zwitterionic Gd-complexes of the well-known chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) provide an excellent basis for the development of safe and sensitive contrast agents. In this report, we describe the synthesis of DOTA-NOx, a DOTA derivative with four N-oxide functionalities via "click" functionalization of the tetraazide DOTAZA.

Risk-adjusted management in catheterization procedures for non-ST-segment elevation myocardial infarction: A standard operating procedure pilot study.

Background: The effects of standardized risk-adjusted periprocedural management of cardiac catheterization procedures in Non-ST segment elevation myocardial infarction (NSTEMI) remain unknown. We implemented a standard operating procedure (SOP) specifying risk assessment (RA, using National Cardiovascular Data Registry (NCDR) risk models) and risk-adjusted management (RM, e.g.

FAT1 expression in T-cell acute lymphoblastic leukemia (T-ALL) modulates proliferation and WNT signaling.

FAT atypical cadherin 1 (FAT1), a transmembrane protein, is frequently mutated in various cancer types and has been described as context-dependent tumor suppressor or oncogene. The FAT1 gene is mutated in 12-16% of T-cell acute leukemia (T-ALL) and aberrantly expressed in about 54% of T-ALL cases contrasted with absent expression in normal T-cells. Here, we characterized FAT1 expression and profiled the methylation status from T-ALL patients.

Knowledge of HbA1c and LDL-C treatment goals, subjective level of disease-related information and information needs in patients with atherosclerotic cardiovascular disease.

Background/hypothesis: Risk factor control of diabetes mellitus (DM) and especially dyslipidemia remains unsatisfactory in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to analyze the knowledge of low-density lipoprotein cholesterol (LDL-C) and glycated hemoglobin (HbA1c) treatment goals, subjective level of information, and information needs in very high-risk patients with ASCVD.

Methods: ASCVD patients (n = 210; 75 ± 9 years; 71.

An alternative CYB5A transcript is expressed in aneuploid ALL and enriched in relapse.

Background: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogenous malignancy with poor prognosis in relapsed adult patients. The genetic basis for relapse in aneuploid subtypes such as near haploid (NH) and high hyperdiploid (HeH) BCP-ALL is only poorly understood. Pathogenic genetic alterations remain to be identified.

Blazed grating enables highly decoupled optically variable devices fabricated by vibration-assisted diamond texturing.

Optically variable devices (OVDs) are well received for anti-counterfeiting and decorative applications. In this study, new strategies to develop highly decoupled OVDs were proposed and demonstrated based on the fast patterning of blazed gratings by vibration-assisted diamond texturing. A unique surface generation mechanism was revealed as a combined cutting and forming process.

Clinical efficacy and safety outcomes of bempedoic acid for LDL-C lowering therapy in patients at high cardiovascular risk: a systematic review and meta-analysis.

Objectives: Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients.

Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.

Concentric Scanning Strategies for Laser Powder Bed Fusion: Porosity Distribution in Practical Geometries.

Besides the optimisation of process parameters such as laser power or scan speed, the choice of the scan path represents a possibility to optimise the laser powder bed fusion process even further. The usual hatching strategy creates a homogeneous microstructure but makes it necessary to switch the laser off and on after each scan vector, which can slow down the fabrication. Moreover, the end of each scan vector is a location susceptible to the creation of keyhole pores.

National Cardiovascular Data Registry-Acute Kidney Injury (NCDR) vs. Mehran risk models for prediction of contrast-induced nephropathy and need for dialysis after coronary angiography in a German patient cohort.

Background: Contrast-induced nephropathy (CIN) is a major adverse event in patients undergoing coronary angiography. The Mehran risk model is the gold-standard for CIN risk prediction. However, its performance in comparison to more contemporary National Cardiovascular Data Registry-Acute Kidney Injury (NCDR-AKI) risk models remains unknown.

CXCR4 hyperactivation cooperates with TCL1 in CLL development and aggressiveness.

Aberrant CXCR4 activity has been implicated in lymphoma pathogenesis, disease progression, and resistance to therapies. Using a mouse model with a gain-of-function CXCR4 mutation (CXCR4) that hyperactivates CXCR4 signaling, we identified CXCR4 as a crucial activator of multiple key oncogenic pathways. CXCR4 hyperactivation resulted in an expansion of transitional B1 lymphocytes, which represent the precursors of chronic lymphocytic leukemia (CLL).

Dual-Laser PBF-LB Processing of a High-Performance Maraging Tool Steel FeNiCoMoVTiAl.

As part of an international research project (HiPTSLAM), the development and holistic processing of high-performance tool steels for AM is a promising topic regarding the acceptance of the laser powder bed fusion (PBF-LB) technology for functionally optimized die, forming and cutting tools. In a previous work, the newly developed maraging tool steel FeNiCoMoVTiAl was qualified to be processed by laser powder bed fusion (PBF-LB) with a material density of more than 99.9% using a suitable parameter set.

Painful legs and moving toes.

A 40-year-old woman reported involuntary and irregular movements of her left toes accompanied by pain. This arose following arthroscopy after a sprained left ankle. She had involuntary flexion-extension and abduction and adduction movements of the hallux and the other toes, with reduced pinprick sensation on the skin web between the left hallux and the second toe.

Introduction and spread of variegated squirrel bornavirus 1 (VSBV-1) between exotic squirrels and spill-over infections to humans in Germany.

The variegated squirrel bornavirus 1 (VSBV-1) is a recently discovered emerging viral pathogen which causes severe and eventually fatal encephalitis in humans after contact to exotic squirrels in private holdings and zoological gardens. Understanding the VSBV-1 epidemiology is crucial to develop, implement, and maintain surveillance strategies for the detection and control of animal and human infections. Based on a newly detected human encephalitis case in a zoological garden, epidemiological squirrel trade investigations and molecular phylogeny analyses of VSBV-1 with temporal and spatial resolution were conducted.

The potent AMPK inhibitor BAY-3827 shows strong efficacy in androgen-dependent prostate cancer models.

Purpose: 5' adenosine monophosphate-activated kinase (AMPK) is an essential regulator of cellular energy homeostasis and has been associated with different pathologies, including cancer. Precisely defining the biological role of AMPK necessitates the availability of a potent and selective inhibitor.

Methods: High-throughput screening and chemical optimization were performed to identify a novel AMPK inhibitor.

Modern NCDR and ACTION risk models outperform the GRACE model for prediction of in-hospital mortality in acute coronary syndrome in a German cohort.

Background And Purpose: Risk prediction with the Global Registry of Acute Coronary Events (GRACE) risk model is guideline-recommended in acute coronary syndrome (ACS) patients. However, the performance of more contemporary scores derived from ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and National Cardiovascular Data (NCDR) registries remains incompletely understood. We aimed to compare these models in German ACS patients.

Comparative Study of the Tempering Behavior of Different Martensitic Steels by Means of In-Situ Diffractometry and Dilatometry.

Martensitic steels are tempered to increase the toughness of the metastable martensite, which is brittle in the as-quenched state, and to achieve a more stable microstructure. During the tempering of steels, several particular overlapping effects can arise. Classical dilatometric investigations can only detect effects by monitoring the integral length change of the sample.

Treating Cancer by Spindle Assembly Checkpoint Abrogation: Discovery of Two Clinical Candidates, BAY 1161909 and BAY 1217389, Targeting MPS1 Kinase.

Inhibition of monopolar spindle 1 (MPS1) kinase represents a novel approach to cancer treatment: instead of arresting the cell cycle in tumor cells, cells are driven into mitosis irrespective of DNA damage and unattached/misattached chromosomes, resulting in aneuploidy and cell death. Starting points for our optimization efforts with the goal to identify MPS1 inhibitors were two HTS hits from the distinct chemical series "triazolopyridines" and "imidazopyrazines". The major initial issue of the triazolopyridine series was the moderate potency of the HTS hits.

Borna disease outbreak with high mortality in an alpaca herd in a previously unreported endemic area in Germany.

Borna disease virus 1 (BoDV-1) is the causative agent of Borna disease, an often fatal neurologic condition of domestic mammals, including New World camelids, in endemic areas in Central Europe. Recently, BoDV-1 gained further attention by the confirmation of fatal zoonotic infections in humans. Although Borna disease and BoDV-1 have been described already over the past decades, comprehensive reports of Borna disease outbreaks in domestic animals employing state-of-the-art diagnostic methods are missing.

Search for polyoma-, herpes-, and bornaviruses in squirrels of the family Sciuridae.

Background: Squirrels (family Sciuridae) are globally distributed members of the order Rodentia with wildlife occurrence in indigenous and non-indigenous regions (as invasive species) and frequent presence in zoological gardens and other holdings. Multiple species introductions, strong inter-species competition as well as the recent discovery of a novel zoonotic bornavirus resulted in increased research interest on squirrel pathogens. Therefore we aimed to test a variety of squirrel species for representatives of three virus families.

Uninterrupted anticoagulation during catheter ablation for atrial fibrillation: no difference in major bleeding and stroke between direct oral anticoagulants and vitamin K antagonists in an updated meta-analysis of randomised controlled trials.

Background: Periprocedural uninterrupted anticoagulation for catheter ablation of atrial fibrillation (AF) became standard after positive results of vitamin K antagonist (VKA) trials. Previous studies of uninterrupted direct oral anticoagulants (DOACs) vs. VKA have given controversial results.

Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor.

The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homologue IKKε are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKKε inhibitor BAY-985.