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Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer : patient-level meta-analysis of randomised trials

BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials.METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast c

Transcriptomic subtyping of malignant peripheral nerve sheath tumours highlights immune signatures, genomic profiles, patient survival and therapeutic targets

Background: Malignant peripheral nerve sheath tumour (MPNST) is an aggressive orphan disease commonly affecting adolescents or young adults. Current knowledge of molecular tumour biology has been insufficient for development of rational treatment strategies. We aimed to discover molecular subtypes of potential clinical relevance. Methods: Fresh frozen samples of MPNSTs (n = 94) and benign neurofib

Impact of the gut microbiome on immunological responses to COVID-19 vaccination in healthy controls and people living with HIV

Although mRNA SARS-CoV-2 vaccines are generally safe and effective, in certain immunocompromised individuals they can elicit poor immunogenic responses. Among these individuals, people living with HIV (PLWH) have poor immunogenicity to several oral and parenteral vaccines. As the gut microbiome is known to affect vaccine immunogenicity, we investigated whether baseline gut microbiota predicts immu

Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion.

Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 sec

Characterization of Human Invasive Isolates of Listeria monocytogenes in Sweden 1986-2007

Since 1986, 68% of the Listeria monocytogenes isolates from human cases of invasive listeriosis in Sweden are available for retrospective Studies. The aim of the present Study was to characterize 601 human invasive isolates of L. monocytogenes in Sweden from 1986 to 2007 by using serotyping and pulsed-field gel electrophoresis. Since 1996, serovar 4b was permanently reduced to the second or third

Association of Genes in the NF-kappa B Pathway with Antibody-Positive Primary Sjogren's Syndrome

Primary Sjogren's syndrome (SS) is a systemic autoimmune inflammatory disease characterized by focal lymphocytic infiltrates in the lachrymal and salivary glands and autoantibodies against the SSA/Ro and SSB/La antigens. Experimental studies have shown an activation of NF-B in primary SS. NF-B activation results in inflammation and autoimmunity and is regulated by inhibitory and activating protein

Towards more flexible enterprise information systems

The aim of this paper is to present the software development techniques used to build the EIS Patterns development framework, which is a testbed for a series of techniques that aim at giving more flexibility to EIS in general. Some of these techniques are customizations or extensions of practices created by the agile software development movement, while others represent new proposals. This paper a

UWB Systems for Wireless Sensor Networks

Wireless sensor networks are emerging as an important area for communications. They enable a wealth of new applications including surveillance, building control, factory automation, and in-vehicle sensing. The sensor nodes have to operate under severe constraints on energy consumption and form factor, and provide the ability for precise self-location of the nodes. These requirements can be fulfill

Novel Role of the Antimicrobial Peptide LL-37 in the Protection of Neutrophil Extracellular Traps against Degradation by Bacterial Nucleases

Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defence mechanism. They consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs) which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within NETs is still unknown because it lo

Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo

Activation of Th1 lymphocytes, IFN-gamma production and macrophage activation are crucial in defense against Mycobacteria. In developing countries, Th2 activation and IL-4 production have been associated in vitro with tuberculosis and with poor clinical outcome after treatment. Serological markers of Th1 [soluble lymphocyte activation gene (LAG)-3] and Th2 (IgE, soluble CD30, and CCL22/macrophage-

Emphysema diagnosis using X-ray dark-field imaging at a laser-driven compact synchrotron light source

In early stages of various pulmonary diseases, such as emphysema and fibrosis, the change in X-ray attenuation is not detectable with absorption-based radiography. To monitor the morphological changes that the alveoli network undergoes in the progression of these diseases, we propose using the dark-field signal, which is related to small-angle scattering in the sample. Combined with the absorption

Hunting for Protein Markers of Hypoxia by Combining Plasma Membrane Enrichment with a New Approach to Membrane Protein Analysis

Nontransient hypoxia is strongly associated with malignant lesions, resulting in aggressive behavior and resistance to treatment. We present an analysis of mRNA and protein expression changes in neuroblastoma cell lines occurring upon the transition from normoxia to hypoxia. The correlation between mRNA and protein level changes was poor, although some known hypoxia-driven genes and proteins corre

Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets

Environmental factors interact with the genome throughout life to determine gene expression and, consequently, tissue function and disease risk. One such factor that is known to play an important role in determining long-term metabolic health is diet during critical periods of development. Epigenetic regulation of gene expression has been implicated in mediating these programming effects of early

Analysis of the Response of AGATA Detectors at GSI

In 2012 and 2014 the γ-ray tracking spectrometer AGATA was operated at the SIS/FRS facility at GSI in Darmstadt, Germany. The performance of the array is discussed, outlining some important aspects of the offline data processing and analysis. Relying on the data obtained from measurements with standard γ-ray sources, a first estimate of the photopeak efficiency and peak-to-total (P/T) is presented

Urinary Extracellular Vesicles of Podocyte Origin and Renal Injury in Preeclampsia

Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We furth

The role of RANK-ligand inhibition in cancer : the story of denosumab

The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-b

Severe carpal tunnel syndrome potentially needing surgical treatment in a general population.

Purpose: To estimate the prevalence of severe carpal tunnel syndrome (CTS) that potentially needs surgical treatment in a general population. Methods: A health-status questionnaire was mailed to a random general population sample of 3,000 subjects (ages, 25-74 y). The responders who reported numbness and/or tingling in the median nerve distribution in the hands were asked to attend a clinical eval

The neuropeptide substance P is a critical mediator of burn-induced acute lung injury

The classical tachykinin substance P (SP) has numerous potent neuroimmunomodulatory effects on all kinds of airway functions. Belonging to a class of neuromediators targeting not only residential cells but also inflammatory cells, studying SP provides important information on the bidirectional linkage between how neural function affects inflammatory events and, in turn, how inflammatory responses