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Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The hum

Molecular profiling reveals low- and high-grade forms of primary melanoma

PURPOSE: For primary melanomas, tumor thickness, mitotic rate and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma that predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early st

Canonical BMP signaling is dispensable for hematopoietic stem cell function in both adult and fetal liver hematopoiesis, but essential to preserve colon architecture.

Numerous publications have described the importance of Bone Morphogenetic Protein (BMP) signaling in the specification of hematopoietic tissue in developing embryos. Here we investigate the full role of canonical BMP signaling in both adult and fetal liver hematopoiesis using conditional knockout strategies, since conventional disruption of components of the BMP signaling pathway result in early d

Swedish CDKN2A mutation carriers do not present the atypical mole syndrome phenotype.

Phenotypic characteristics were examined in melanoma-prone southern Swedish CDKN2A (p16-113insArg/p14ARF-128insSer) mutation families, in relation to the CDKN2A genotype, nevi, clinically atypical nevi (CAN) and melanoma. Individuals from eight melanoma-prone families, with index patients carrying the CDKN2A mutation, were offered skin examinations and genotyping (CDKN2A and MC1R). Ninety-three in

Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmo Preventive Project).

Aims Orthostatic hypotension (OH) has been linked to increased mortality and incidence of cardiovascular disease in various risk groups, but determinants and consequences of OH in the general population are poorly studied. Methods and results Prospective data of the Swedish 'Malmö Preventive Project' (n = 33 346, 67.3% men, mean age 45.7 +/- 7.4 years, mean follow-up 22.7 +/- 6.0 years) were analy

Sources and Diagnostics for Attosecond Science

Ultrafast science refers to physical events that happen on the femtosecond (1 fs=10^-15 s) and attosecond (1 as=10^-18 s) timescales. Generation of attosecond pulses is usually achieved by interacting high-intensity femtosecond pulses with matter (typically gases), in a process called high-order harmonic generation (HHG). Under the correct conditions, this process leads to the creation of sub-fs p

Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis.

Background: Genetic polymorphisms associated with common aetiologically complex diseases have recently been identified through genome-wide association studies. Direct-to-consumer genetic testing for such polymorphisms, with provision of absolute genetic risk estimates, is marketed by several commercial companies. Polymorphisms associated with atrial fibrillation (AF) have shown relatively large r

Blood Biomarker Levels to Aid Discovery of Cancer-Related Single-Nucleotide Polymorphisms: Kallikreins and Prostate Cancer.

Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding beta-microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis tha

Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy.

AIMS/HYPOTHESIS: Our aim was to study whether glycaemic control differs between individuals with latent autoimmune diabetes in adults (LADA) and patients with type 2 diabetes, and whether it is influenced by time on insulin therapy. METHODS: We performed a retrospective study of 372 patients with LADA (205 men and 167 women; median age 54 years, range 35-80 years) from Swedish cohorts from Skåne (

Stratified Genetic Analysis Reveals Sex Differences In MPO-ANCA-associated Vasculitis

OBJECTIVE: To identify and genetically characterize subgroups of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) based on sex and ANCA subtype.METHODS: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for ass

Urban Cemeteries and the Aesthetics of Care

Even though urban cemeteries in Sweden today can be seen as making space for different memorial practices, they are also a materialization of certain cultural and religious norms (Kjaersgaard & Venbrux, 2016), which sometimes are expressed as functional and aesthetic values. In this respect, the urban cemetery has an abiding attitude to change in building on past traditions and designs to addr

Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing

Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartment and we investigated stromal cell regulation principles based on the RNA velocity analysis using s

Parallel motion vision pathways in the brain of a tropical bee

Spatial orientation is a prerequisite for most behaviors. In insects, the underlying neural computations take place in the central complex (CX), the brain’s navigational center. In this region different streams of sensory information converge to enable context-dependent navigational decisions. Accordingly, a variety of CX input neurons deliver information about different navigation-relevant cues.

Evaluation of genetic demultiplexing of single-cell sequencing data from model species

Single-cell sequencing (sc-seq) provides a species agnostic tool to study cellular processes. However, these technologies are expensive and require sufficient cell quantities and biological replicates to avoid artifactual results. An option to address these problems is pooling cells from multiple individuals into one sc-seq library. In humans, genotype-based computational separation (i.e., demulti