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Genetic Predisposition to Sporadic and Familial Multiple Myeloma

Multiple Myeloma (MM) is the second most common hematological malignancy. It is defined by an uncontrolled growth of plasma cells, usually in the bone marrow. Clinically it is complicated by hypercalcemia, renal failure, anaemia, and bone pain. Although recent advances in the treatment have extended survival and quality-of-life considerably, MM remains a fatal disease.Since the 1920’s MM has been

Guest-protein incorporation into solvent channels of a protein host crystal (hostal)

Soaking small molecules into the solvent channels of protein crystals is the most common method of obtaining crystalline complexes with ligands such as substrates or inhibitors. The solvent channels of some protein crystals are large enough to allow the incorporation of macromolecules, but soaking of protein guests into protein crystals has not been reported. Such protein host crystals (here given

RNA modifications and post-transcriptional control in cancer and stem cells

Splicing and translation are two of the key steps of post-transcriptional regulation of gene expression. Their tight regulation is essential for development, whereas their deregulation is involved in cancer pathogenesis. Nevertheless, many of the molecular mechanisms controlling these processes are still unknown. Hence, the main aim of this thesis is to elucidate novel regulatory mechanisms that a

High level of protection against COVID-19 after two doses of BNT162b2 vaccine in the working age population–first results from a cohort study in Southern Sweden

Background: Vaccine effectiveness against COVID-19 needs to be assessed in diverse real-world population settings. Methods: A cohort study of 805,741 residents in Skåne county, Southern Sweden, aged 18–64 years, of whom 26,587 received at least one dose of the BNT162b2 vaccine. Incidence rates of COVID-19 were estimated in sex- and age-adjusted analysis and stratified in two-week periods with subs

Culturing patient-derived malignant hematopoietic stem cells in engineered and fully humanized 3D niches

Human malignant hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) niches, which remain challenging to explore due to limited in vivo accessibility and constraints with humanized animal models. Several in vitro systems have been established to culture patient-derived HSPCs in specific microenvironments, but they do not fully recapitulate the complex features of native bone

Intracavitary Electron FLASH Radiotherapy in a Canine Cancer Patient With Oral Malignant Melanoma

PURPOSE/OBJECTIVE(S): Studies of electron FLASH radiotherapy (FLASH-RT) in companion animals are being conducted at several institutions. High energy electron beams are generally suitable for treatment of superficial cancers, but of limited use for deep-seated tumors. In this case report, the feasibility of intracavitary electron FLASH-RT is demonstrated.MATERIALS/METHODS: A canine cancer patient

Beta and Alpha Particle Autoradiography

utoradiography is defined as technologies and methods used to produce a two-dimensional image of the distribution of activity in, or on, a thin and solid sample that is in close proximity to the detector. The images are usually formed by charged particles (α or β±), and image characteristics are determined both by the detector and the properties of the particles detected. This method is not widely

Role of FLT3 in Acute Myeloid Leukemia: Molecular mechanisms and Therapeutic opportunities

Acute myeloid leukemia (AML) is a highly heterogeneous blood disease which is characterized by different mutations and chromosomal rearrangements. Nearly 60% of genetic alterations have been found in AML patients involve in signaling pathways including signaling of tyrosine kinase receptor FLT3. FLT3 mutations emerged as one of the most common mutations in AML which represent around 35% of all AML

Heparin-binding protein in lower airway samples as a biomarker for pneumonia

Objectives: Ventilator-associated pneumonia (VAP) is difficult to diagnose using clinical criteria and no biomarkers have yet been proved to be sufficiently accurate. The use of the neutrophil-derived Heparin-binding protein (HBP) as a biomarker for pneumonia was investigated in this exploratory case–control study in two intensive care units at a tertiary referral hospital. Methods: Patients with

3D Engineering of Human Hematopoietic Niches in Perfusion Bioreactor

The hematopoietic microenvironment, also referred to as hematopoietic niche, is a functional three-dimensional (3D) unit of the bone marrow (BM) that planar culture systems cannot recapitulate. Existing limitations of 2D protocols are driving the development of advanced 3D methodologies, capable of superior modeling of the native organization and interactions between hematopoietic cells and their

Potential relationship between eGFRcystatin C /eGFRcreatinine -ratio and glomerular basement membrane thickness in diabetic kidney disease

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomeru- lar basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle-molecules such as cyst

Use of Melatonin Is Associated With Lower Risk of Colorectal Cancer in Older Adults

INTRODUCTION: Preclinical evidence suggests that melatonin may affect cellular pathways involved in colorectal cancer (CRC). We sought to test whether melatonin use was associated with decreased risk of CRC using population-based data.METHODS: We performed a nationwide cohort study using a new-user study design. We identified a total of 58,657 incident melatonin users aged 50 years and older from

Targeting Alveolar Repair in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is a fatal interstitial lung disease with limited therapeutic options. Current evidence suggests that IPF may be initiated by repeated epithelial injury in the distal lung followed by abnormal wound healing responses which occur due to intrinsic and extrinsic factors. Mechanisms contributing to chronic damage of the alveolar epithelium in IPF include dysregulated cell

Sustained and controlled delivery of doxorubicin from an in-situ setting biphasic hydroxyapatite carrier for local treatment of a highly proliferative human osteosarcoma

Doxorubicin (DOX) is a cornerstone drug in the treatment of osteosarcoma. However, achieving sufficient concentration in the tumor tissue after systemic administration with few side effects has been a challenge. Even with the most advanced nanotechnology approaches, less than 5% of the total administered drug gets delivered to the target site. Alternatives to increase the local concentration of DO

High-titer GAD65 autoantibodies detected in adult diabetes patients using a high efficiency expression vector and cold GAD65 displacement.

Adult type 2 diabetes patients with GAD65 autoantibodies (GADA) are known as latent autoimmune diabetes in adults (LADA). It has been suggested that GADA in LADA patients preferentially bind to the N-terminal end of GAD65. Using the N-terminal end extension of (35)S-GAD65 generated by the pEx9 plasmid, we tested the hypothesis that GADA in LADA patients preferentially react with (35)S-GAD65 from t

Pharmacogenetic implications for eight common blood pressure-associated single-nucleotide polymorphisms.

OBJECTIVE:: We aimed to test whether eight common recently identified single-nucleotide polymorphisms (SNPs), strongly associated with blood pressure (BP) in the population, also have impact on the degree of BP reduction by antihypertensive agents with different mechanisms. METHODS:: In 3863 Swedish hypertensive patients, we related number of unfavorable alleles of each SNP (i.e. alleles associa

Decrease in sick leave among patients with rheumatoid arthritis in the first 12 months after start of treatment with tumour necrosis factor antagonists: a population-based controlled cohort study.

OBJECTIVE: /st> To investigate the effect of tumour necrosis factor (TNF) antagonist treatment of patients with rheumatoid arthritis (RA) on sick leave (SL) and disability pension (DP) in a population-based setting in southern Sweden. METHODS: /st> All patients with RA in the South Swedish Arthritis Treatment Group register living in the county of Skåne (population 1.2 million), who started their