Metadata for Data dIscoverability aNd Study rEplicability in obseRVAtional Studies (MINERVA): Development and Pilot of a Metadata List and Catalogue in Europe.

Purpose: Metadata for data dIscoverability aNd study rEplicability in obseRVAtional studies (MINERVA), a European Medicines Agency-funded project (EUPAS39322), defined a set of metadata to describe real-world data sources (RWDSs) and piloted metadata collection in a prototype catalogue to assist investigators from data source discoverability through study conduct.

Methods: A list of metadata was created from a review of existing metadata catalogues and recommendations, structured interviews, a stakeholder survey, and a technical workshop. The prototype was designed to comply with the FAIR principles (findable, accessible, interoperable, reusable), using MOLGENIS software.

Elevated TFPI is a prognostic factor in hepatocellular carcinoma: Putative role of miR-7-5p and miR-1236-3p.

Background: Primary liver cancer is the third leading cause of cancer related deaths worldwide, and the disease is associated with high incidence rate of thrombosis. Studies indicate that Tissue Factor Pathway Inhibitor (TFPI) plays a role in cancer development. We aimed to study its expression, clinical role and regulation by micro RNAs (miRNAs) in hepatocellular carcinoma (HCC).

Interleukin-13 Treatment of Living Lung Tissue Model Alters the Metabolome and Proteome-A Nano-DESI MS Metabolomics and Shotgun Proteomics Study.

Asthma is a chronic respiratory disease with one of the largest numbers of cases in the world; thus, constant investigation and technical development are needed to unravel the underlying biochemical mechanisms. In this study, we aimed to develop a nano-DESI MS method for the in vivo characterization of the cellular metabolome. Using air-liquid interface (ALI) cell layers, we studied the role of Interleukin-13 (IL-13) on differentiated lung epithelial cells acting as a lung tissue model.

Coagulation factor V in breast cancer: a p53-regulated tumor suppressor and predictive marker for treatment response to chemotherapy.

Background: Patients with cancer are at an increased risk of developing coagulation complications, and chemotherapy treatment increases the risk. Tumor progression is closely linked to the hemostatic system. Breast cancer tumors express coagulation factor V (FV), an essential factor in blood coagulation.

Revisiting the ownership effect in adults with and without autism.

Self-owned items are better remembered than other-owned items; this ownership effect reflects privileged processing of self-related information. The size of this ownership effect has been shown to decrease in neurotypical adults as the number of autistic traits increases, and is reduced in autistic adults. However, emerging evidence has questioned the reliability of these findings.

Treating a Case of First-Episode Psychosis to Uncover Undiagnosed Obsessive Compulsive Disorder: A Case Report.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric condition characterized by the presence of obsessions, compulsions, or both. Historically OCD was associated with good insight. However, there are more categories to the degrees of insight in OCD patients, namely good, fair, poor, absent, or delusional beliefs.

Prognosis of CRT-treated and CRT-untreated unselected population with LBBB in Stockholm County.

Aims: Left bundle branch block (LBBB) might be the first finding of cardiovascular diseases but also the prerequisite for cardiac resynchronization therapy (CRT) in heart failure (HF) with reduced ejection fraction (HFrEF). The prognosis for patients with LBBB and the implications of CRT in an unselected real-world setting are the focus of our study.

Methods And Results: A central electrocardiogram (ECG) database and national registers have been screened to identify patients with LBBB.

An increase in the cytosolic concentration of free calcium ions activates the neutrophil NADPH-oxidase provided that the free fatty acid receptor 2 has been allosterically modulated.

Signals generated by free fatty acid receptor 2 (FFA2R) can activate the neutrophil NADPH-oxidase without involvement of any orthosteric FFA2R agonist. The initiating signals may be generated by P2YR, the receptor for ATP. An FFA2R specific allosteric modulator (PAM; Cmp58) was required for this response and used to investigate the mechanism by which signals generated by ATP/P2YR activate an FFA2R dependent process.

The allosterically modulated FFAR2 is transactivated by signals generated by other neutrophil GPCRs.

Positive allosteric modulators for free fatty acid receptor 2 (FFAR2/GPR43), that affect receptor function through binding to two distinct allosteric binding sites, were used to determine the correlation between the responses induced in neutrophils by two distinct activation modes; FFAR2 was activated either by the orthosteric agonist propionate or by a receptor transactivation mechanism that activated FFAR2 from the cytosolic side of the neutrophil plasma membrane by signals generated by the neutrophil PAFR (receptor for platelet activating factor), P2Y2R (receptor for ATP), FPR1 (receptor for fMLF) and FPR2 (receptor for WKYMVM). We show that the transactivation signals that activate FFAR2 in the absence of any orthosteric agonist were generated downstream of the signaling G protein that couple to PAFR and P2Y2R. This transactivation of allosterically modulated FFAR2s, by signals generated by PAFR/P2Y2R, represents a novel mechanism by which a G protein coupled receptor can be activated.

The ketone body acetoacetate activates human neutrophils through FFAR2.

Neutrophils express many surface receptors that sense environmental changes. One such sensor is FFAR2 (free fatty acid receptor 2), a receptor that detects gut microbiota-derived short-chain fatty acids. As such, FFAR2 has been regarded as a molecular link between metabolism and inflammation.

The Effects of Periostin Expression on Fibroid-Like Transition of Myometrial Cells.

Fibroids, benign tumors of the myometrium, are the most common tumors in women and are associated with spontaneous abortion, preterm birth, placenta abruption, and infertility, among others. The incidence of fibroids in reproductive aged women is 20-89%. Fibroids are characterized by high production of extracellular matrix (ECM), particularly collagens, which play a role in their growth.

G protein coupled pattern recognition receptors expressed in neutrophils: Recognition, activation/modulation, signaling and receptor regulated functions.

Neutrophils, the most abundant white blood cell in human blood, express receptors that recognize damage/microbial associated pattern molecules of importance for cell recruitment to sites of inflammation. Many of these receptors belong to the family of G protein coupled receptors (GPCRs). These receptor-proteins span the plasma membrane in expressing cells seven times and the down-stream signaling rely in most cases on an activation of heterotrimeric G proteins.

Phenol-soluble modulin α and β display divergent roles in mice with staphylococcal septic arthritis.

Phenol-soluble modulin α (PSMα) is identified as potent virulence factors in Staphylococcus aureus (S. aureus) infections. Very little is known about the role of PSMβ which belongs to the same toxin family.

Registered nurses' experiences of caring for patients in hospitals transitioning from curative to palliative care: A qualitative study.

The aim of this study was twofold: to illuminate registered nurses' experiences of palliative care and of caring for patients transitioning from curative to palliative care in hospitals. A qualitative descriptive design was used. Group interviews were conducted with 11 registered nurses in three different hospital settings.

Potential Use of Supercharging Agents for Improved Mass Spectrometric Analysis of Monoclonal Antibodies and Antibody-Drug Conjugates.

The addition of supercharging (SC) reagents in electrospray ionization coupled mass spectrometry (ESI-MS) has demonstrated several advantages for protein analysis such as reduced required mass range of the instrument, narrowed charge-state distribution, increased sensitivity, and adduct suppression. The potential use of SC reagents to improve analyses of larger and complex protein molecules such as monoclonal antibodies and antibody-drug conjugates (ADCs) has not been previously reported. In this study, the effect of seven SC reagents (-nitrobenzyl alcohol (-NBA), dimethyl sulfoxide (DMSO), -nitroanisole (-NA), propane sultone (PS), ethylene carbonate (EC), propylene carbonate (PC), and sulfolane) on ESI-MS acquired spectra of deglycosylated, intact, and reduced trastuzumab and a vcMMAE-trastuzumab ADC was investigated under denaturing conditions.

Structural Determinants in the -Derived Phenol-Soluble Modulin α2 Peptide Required for Neutrophil Formyl Peptide Receptor Activation.

Highly pathogenic strains produce phenol-soluble modulins (PSMs), which are -formylated peptides. Nanomolar concentrations of PSMα2 are recognized by formyl peptide receptor 2 (FPR2), but unlike the prototypic FPR2 agonist WKYMVM, PSMα2 is a biased signaling agonist. The truncated N-terminal PSMα2 variant, consisting of the five N-terminal residues, is no longer recognized by FPR2, showing that the C-terminal part of PSMα2 confers FPR2 selectivity, whereas the N-terminal part may interact with the FPR1 binding site.

Successive extreme climatic events lead to immediate, large-scale, and diverse responses from fish in the Arctic.

The warming trend of the Arctic is punctuated by several record-breaking warm years with very low sea ice concentrations. The nature and reversibility of marine ecosystem responses to these multiple extreme climatic events (ECEs) are poorly understood. Here, we investigate the ecological signatures of three successive bottom temperature maxima concomitant with surface ECEs between 2004 and 2017 in the Barents Sea across spatial and organizational scales.

Antipsychotic treatment patterns in Alzheimer's disease patients with agitation: a cohort study using the UK clinical practice research datalink.

Objectives: There is a lack of robust epidemiological evidence on antipsychotic (AP) use in patients with agitation in Alzheimer's disease (AD). Authors studied AP use in patients with AD and agitation and compared their use with patients with other or no neuropsychiatric symptoms (NPS).

Methods: A retrospective cohort study in the UK Clinical Practice Research Datalink, included patients with AD between January 1, 2015, and December 31, 2017.

A Feasibility Study on the Identification of Potential Biomarkers in Pulmonary Embolism Using Proteomic Analysis.

Acute pulmonary embolism (PE) is a common emergency with a high morbidity and mortality. Most clinical presentations are non-specific and there is a lack of suitable biomarkers for PE. For example, the traditional D-dimer tests shows a rather high sensitivity for PE, but yet a rather low positive predictive value due to its lack of specificity.

Plasma-derived extracellular vesicles from myocardial infarction patients inhibits tumor necrosis factor-alpha induced cardiac cell death.

Rationale: Extracellular vesicles (EVs) derived exogenously from pluripotent stem cells or endogenously from healthy human serum exert cardioprotective effects after injury. However role of endogenous EVs from myocardial infarction (MI) patients not well understood in this settings.

Methods And Results: The EVs from plasma of MI patients with preserved or reduced left ventricular ejection fraction (LVEF) and healthy controls (HC) were purified and characterized by flow cytometry, mass spectrometry (MS) and transmission electron microscopy (TEM).

Social processes in academic-community partnership in health care. A grounded theory study.

Background: International and national guidelines state that palliative care should be offered to everyone who needs it. To promote the implementation of palliative care in nursing homes, a partnership collaboration was initiated with the goal of implementing high quality palliative care. The partnership consisted of three partner groups: a project group from a non-profit organisation providing health care, managers at the nursing homes and an academic partner.

Allosteric receptor modulation uncovers an FFA2R antagonist as a positive orthosteric modulator/agonist in disguise.

A novel receptor crosstalk activation mechanism, through which signals generated by the agonist-occupied P2YR (the neutrophil receptor for ATP) activate allosterically modulated free fatty acid 2 receptor (FFA2R) without the involvement of any FFA2R agonist, was used to determine the inhibitor profiles of two earlier-described, FFA2R-specific antagonists, CATPB and GLPG0974. These antagonists have been shown to have somewhat different receptor-interaction characteristics at the molecular/functional level, although both are recognized by the orthosteric site in FFA2R. The antagonists inhibited neutrophil activation induced by ATP, an activation occurred only in the presence of either of the two positive allosteric FFA2R modulators (PAMs) AZ1729 and Cmp58.

Clinical Hypnosis in Medical Care: A Mixed-Method Feasibility Study.

Background: Preoperative hypnosis has shown promising effects in controlling side effects from breast cancer surgery, but the feasibility and effects are largely unknown outside the US.

Methods: A mixed-methods approach was applied involving a large-scale population survey and a small-scale pilot study. The survey assessed attitudes toward hypnosis in a representative sample from the general population (n = 1049), while the pilot study involved interviews with 5 women who received hypnosis prior to mastectomy/lumpectomy.