The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities.

Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, MM remains incurable, and better risk stratification as well as new therapies are therefore highly needed. The proteome of MM has not been systematically assessed before and holds the potential to uncover insight into disease biology and improved prognostication in addition to genetic and transcriptomic studies.

Prediction of Clinically Significant Prostate Cancer by a Specific Collagen-related Transcriptome, Proteome, and Urinome Signature.

Background And Objective: While collagen density has been associated with poor outcomes in various cancers, its role in prostate cancer (PCa) remains elusive. Our aim was to analyze collagen-related transcriptomic, proteomic, and urinome alterations in the context of detection of clinically significant PCa (csPCa, International Society of Urological Pathology [ISUP] grade group ≥2).

Methods: Comprehensive analyses for PCa transcriptome (n = 1393), proteome (n = 104), and urinome (n = 923) data sets focused on 55 collagen-related genes.

Artificial Targets: a versatile cell-free platform to characterize CAR T cell function .

Cancer immunotherapies using chimeric antigen receptor (CAR) T cells have tremendous potential and proven clinical efficacy against a number of malignancies. Research and development are emerging to deepen the knowledge of CAR T cell efficacy and extend the therapeutic potential of this novel therapy. To this end, functional characterization of CAR T cells plays a central role in consecutive phases across fundamental research and therapeutic development, with increasing needs for standardization.

The Atherosclerotic Profile of a Young Symptomatic Population between 19 and 49 Years: Coronary Computed Tomography Angiography or Coronary Artery Calcium Score?

(1) Background: Whether coronary computed tomography angiography (CTA) or the coronary artery calcium score (CACS) should be used for diagnosis of coronary heart disease, is an open debate. The aim of our study was to compare the atherosclerotic profile by coronary CTA in a young symptomatic high-risk population (age, 19-49 years) in comparison with the coronary artery calcium score (CACS). (2) Methods: 1137 symptomatic high-risk patients between 19-49 years (mean age, 42.

Coronary Artery Dimensions in Endurance Athletes by Computed Tomography Angiography: A Quantitative Analysis.

(1) Background: The athlete's heart may develop permanent vessel enlargement. The purpose of our study was to define normal values for coronary artery dimensions of endurance athletes by coronary computed tomography angiography (CTA). (2) Methods: Ninety-eight individuals (56.

The Effect of Vitamin D on Coronary Atherosclerosis: A Propensity Score Matched Case-Control Coronary CTA Study.

Background: Vitamin D supplementation may be associated with lower cardiovascular (CV) events, but the data are controversial. It remains speculative whether vitamin D supplementation has a direct effect on coronary atherosclerosis. We therefore set out to assess the influence of vitamin D supplementation on the coronary atherosclerosis profile quantified by coronary computed tomography angiography (CTA) in a retrospective case-control cohort study.

Full or intensity-reduced high-dose melphalan and single or double autologous stem cell transplant with or without bortezomib consolidation in patients with newly diagnosed multiple myeloma.

Objective: A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression-free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed.

Methods: Following induction therapy and high-dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35-day cycles of bortezomib consolidation (1.

Comprehensive CRISPR-Cas9 screens identify genetic determinants of drug responsiveness in multiple myeloma.

The introduction of new drugs in the past years has substantially improved outcome in multiple myeloma (MM). However, the majority of patients eventually relapse and become resistant to one or multiple drugs. While the genetic landscape of relapsed/ resistant multiple myeloma has been elucidated, the causal relationship between relapse-specific gene mutations and the sensitivity to a given drug in MM has not systematically been evaluated.

[Preparing for a pandemic].

On 16 March 2020 the government of Bavaria declared a state of emergency due to the coronavirus disease 2019 (COVID-19) pandemic. This confronted all clinics with completely new and difficult challenges. In accordance with the official requirements, pandemic officers were appointed at the Kempten Clinic and a clinical management team was established.

Smoking and obesity predict high-risk plaque by coronary CTA in low coronary artery calcium score (CACS).

Background: The AHA recommends statins in patients with CACS>100 AU. However in patients with low CACS (1-99 AU), no clear statement is provided, leaving the clinician in a grey-zone. High-risk plaque (HRP) criteria by coronary CTA are novel imaging biomarkers indicating a higher a-priori cardiovascular (CV) risk, which could help for decision-making.

Click Chemistry in Ultra-high Vacuum - Tetrazine Coupling with Methyl Enol Ether Covalently Linked to Si(001).

The additive-free tetrazine/enol ether click reaction was performed in ultra-high vacuum (UHV) with an enol ether group covalently linked to a silicon surface: Dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate molecules were coupled to the enol ether group of a functionalized cyclooctyne which was adsorbed on the silicon (001) surface via the strained triple bond of cyclooctyne. The reaction was observed at a substrate temperature of 380 K by means of X-ray photoelectron spectroscopy (XPS). A moderate energy barrier was deduced for this click reaction in vacuum by means of density functional theory based calculations, in good agreement with the experimental results.

Kinetics of Renal Function during Induction in Newly Diagnosed Multiple Myeloma: Results of Two Prospective Studies by the German Myeloma Study Group DSMM.

Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD).

Gender Differences in the Atherosclerosis Profile by Coronary CTA in Coronary Artery Calcium Score Zero Patients.

: The coronary artery calcium score (CACS) is a powerful tool for cardiovascular risk stratification. Coronary computed tomography angiography (CTA) allows for a more distinct analysis of atherosclerosis. The aim of the study was to assess gender differences in the atherosclerosis profile of CTA in patients with a CACS of zero.

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells.

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2.

Combined XPS and DFT investigation of the adsorption modes of methyl enol ether functionalized cyclooctyne on Si(001).

The reaction of methyl enol ether functionalized cyclooctyne on the silicon (001) surface was investigated by means of X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT). Three different groups of final states were identified; all of them bind on Si(001) via the strained triple bond of cyclooctyne but they differ in the configuration of the methyl enol ether group. The majority of molecules adsorbs without additional reaction of the enol ether group; the relative contribution of this configuration to the total coverage depends on substrate temperature and coverage.

The effect of omega-3 fatty acids on coronary atherosclerosis quantified by coronary computed tomography angiography.

Background & Aims: Data on the effects omega-3 fatty acids on coronary artery disease (CAD) are contradictory. While a recent metanalysis could not show improved cardiovascular outcomes, anti-atherogenic mechanisms are well known.

Objective: Aim was to assess the influence of Omega-3 polyunsaturated long-chain fatty acids (PUFA) supplementation on coronary atherosclerosis quantified by coronary computed tomography angiography (CTA).

Coronary atherosclerosis profile in patients with end-stage liver disease prior to liver transplantation due to alcoholic fatty liver: a coronary CTA study.

Objectives: To assess the coronary atherosclerosis profile by coronary computed tomography angiography (CTA) in patients with end-stage liver disease (ESLD) due to alcohol-related liver disease (ARLD) evaluated for liver transplantation (LT), in a retrospective matched case-controlled cohort study.

Methods: One hundred forty patients (age 60.6 years ± 9.

Differences in coronary vasodilatory capacity and atherosclerosis in endurance athletes using coronary CTA and computational fluid dynamics (CFD): Comparison with a sedentary lifestyle.

Background: The aim was to assess the effect of endurance exercise on coronary vasodilatory capacity and atherosclerosis by coronary computed tomography angiography (CTA) and computational fluid dynamic (CFD) modelling.

Methods: 100 subjects (age 56.2y±11, 29 females) who underwent coronary CTA were included into this retrospectively matched cohort study.

Autologous stem cell transplantation in multiple myeloma patients: utilization patterns and hospital effects.

Evidence on volume outcome associations for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) is limited. We investigated ASCT utilization patterns and volume outcome associations in the German National Registry for Stem Cell Transplants (DRST). MM patients with an upfront ASCT between 1998 and 2014 registered in the DRST were included.

c-MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide-dexamethasone in myeloma.

Objectives: In the TOURMALINE-MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib-lenalidomide-dexamethasone (IRd) showed different magnitudes of progression-free survival (PFS) benefit vs placebo-Rd according to number and type of prior therapies, with greater benefit seen in patients with >1 prior line of therapy or 1 prior line of therapy without stem cell transplantation (SCT).

Methods: RNA sequencing data were used to investigate the basis of these differences.

Results: The PFS benefit of IRd vs placebo-Rd was greater in patients with tumors expressing high c-MYC levels (median not reached vs 11.