TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.

The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial.

Getting Back on Track: Meanings of Recovery After Critical Illness Caused by COVID-19.

Introduction: Being critically ill in need of intensive care, lead to a challenging way back after survival, so also for survivors of COVID-19. The process to recovery can be long.

Objectives: The aim of our qualitative study was to elucidate meanings of recovery for people who were once critically ill with COVID-19.

The effect of alemtuzumab on neurodegeneration in relapsing-remitting multiple sclerosis: A five-year prospective mono-center study.

Background: Relapsing-remitting multiple sclerosis (RRMS) is an inflammatory and neurodegenerative disease. After two or more short courses of alemtuzumab (ALZ), an immune reconstitution is achieved, which long-term results in reduced disease activity. We aimed to investigate the effect of ALZ on measures of neurodegeneration (i.

The scaffolding function of LSD1 controls DNA methylation in mouse ESCs.

Lysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation.

Association of serum glial fibrillary acidic protein with progression independent of relapse activity in multiple sclerosis.

Objective: Insidious disability worsening is a common feature in relapsing-remitting multiple sclerosis (RRMS). Many patients experience progression independent of relapse activity (PIRA) despite being treated with high efficacy disease-modifying therapies. We prospectively investigated associations of body-fluid and imaging biomarkers with PIRA.

Psychosocial Self-efficacy and its Association with Selected Potential Factors Among Adults with Type 1 Diabetes: A Cross-Sectional Survey Study.

Introduction: The management of type 1 diabetes, a non-preventable chronic disease, leads to a high physical and psychological burden on the individual. Digital health technology can improve a person's psychosocial self-efficacy and thereby contribute to improved diabetes self-care. The aim of this study was to explore associations between psychosocial self-efficacy and demographic-, disease specific-, well-being as well as digital health technology (DHT) related factors among adults with type 1 diabetes.

Exhaustive identification of genome-wide binding events of transcriptional regulators.

Genome-wide binding assays aspire to map the complete binding pattern of gene regulators. Common practice relies on replication-duplicates or triplicates-and high stringency statistics to favor false negatives over false positives. Here we show that duplicates and triplicates of CUT&RUN are not sufficient to discover the entire activity of transcriptional regulators.

Close relatives' perspective of critical illness due to COVID-19: Keeping in touch at a distance.

Aim: To elucidate the meaning of being a close relative of a critically ill person cared for in intensive care during the initial phase of the COVID-19 pandemic.

Design: A narrative inquiry design following the COREQ guidelines.

Methods: Individual interviews with fifteen close relatives of patients critically ill with COVID-19 were analysed using phenomenological hermeneutics.

A five-year observational prospective mono-center study of the efficacy of alemtuzumab in a real-world cohort of patients with multiple sclerosis.

Background: Alemtuzumab (ALZ) is a pulsed immune reconstitution therapy for multiple sclerosis (MS).

Objective: To assess basic characteristics, therapeutic effects, and prognostic biomarkers on clinical and imaging parameters of disease activity for relapsing-remitting MS (RRMS) patients selected for ALZ, in a real-world long-term setting.

Methods: Fifty-one RRMS patients [female = 31; mean age 36 (standard deviation 7.

The CUT&RUN suspect list of problematic regions of the genome.

Background: Cleavage Under Targets and Release Using Nuclease (CUT&RUN) is an increasingly popular technique to map genome-wide binding profiles of histone modifications, transcription factors, and co-factors. The ENCODE project and others have compiled blacklists for ChIP-seq which have been widely adopted: these lists contain regions of high and unstructured signal, regardless of cell type or protein target, indicating that these are false positives. While CUT&RUN obtains similar results to ChIP-seq, its biochemistry and subsequent data analyses are different.

The time-resolved genomic impact of Wnt/β-catenin signaling.

Wnt signaling orchestrates gene expression via its effector, β-catenin. However, it is unknown whether β-catenin binds its target genomic regions simultaneously and how this impacts chromatin dynamics to modulate cell behavior. Using a combination of time-resolved CUT&RUN against β-catenin, ATAC-seq, and perturbation assays in different cell types, we show that Wnt/β-catenin physical targets are tissue-specific, β-catenin "moves" on different loci over time, and its association to DNA accompanies changing chromatin accessibility landscapes that determine cell behavior.

Early Labour App: Developing a practice-based mobile health application for digital early labour support.

Background: Pregnant women in early labour have felt excluded from professional care, and their partners have been restricted from being involved in the birthing process. Expectant parents must be better prepared to deal with fear and stress during early labour. There is a need for evidence-based information and digital applications that can empower couples during childbirth.

β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer.

Intraepithelial lymphocytes (IEL) expressing γδ T-cell receptors (γδTCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic γδIELs.

Single-cell response to Wnt signaling activation reveals uncoupling of Wnt target gene expression.

Wnt signaling drives nuclear translocation of β-catenin and its subsequent association with the DNA-bound TCF/LEF transcription factors, which dictate target gene specificity by recognizing Wnt responsive elements across the genome. β-Catenin target genes are therefore thought to be collectively activated upon Wnt pathway stimulation. However, this appears in contrast with the non-overlapping patterns of Wnt target gene expression in several contexts, including early mammalian embryogenesis.

The four domains of the person-centred practice framework from the perspective of critical care nurses in intensive care units during a pandemic.

Objectives: The aim was to describe the Person-Centred Practice Framework's four domains (prerequisites, care environment, person-centred processes, and person-centred outcomes) through the perspectives of critical care nurses working in intensive care units during the second year of the COVID-19 pandemic. Furthermore, the aim was to investigate the relationships between prerequisites, care environment, person-centred processes, and person-centred outcomes.

Design/methods: A cross-sectional study involving questionnaires.

Moral Distress, Health and Intention to Leave: Critical Care Nurses' Perceptions During COVID-19 Pandemic.

Introduction: Moral distress increases the risk that critical care nurses will lose the ability to provide quality nursing care.

Aims: To describe person-related conditions and perceptions of moral distress, health and intention to leave among critical care nurses in intensive care units, and to examine the relationship between person-related conditions, moral distress, health and intention to leave.

Method: Cross-sectional, with 220 critical care nurses in 15 Swedish ICUs, and data gathered via a self-reported questionnaire.

A mobile application for early labour support -feasibility pilot study.

Background: Use of mobile applications (apps) are increasing during pregnancy but few of these are evidence-based or evaluated in research.

Aim: To examine the feasibility, including perceived usefulness and usability, and the preliminary effects of an app based on the Confident birth method.

Methods: A mixed-method approach, including 48 women, was used to evaluate acceptability, usability and to test study design and procedures.

Stress-sensitive dynamics of miRNAs and Elba1 in Drosophila embryogenesis.

Early-life stress can result in life-long effects that impact adult health and disease risk, but little is known about how such programming is established and maintained. Here, we show that such epigenetic memories can be initiated in the Drosophila embryo before the major wave of zygotic transcription, and higher-order chromatin structures are established. An early short heat shock results in elevated levels of maternal miRNA and reduced levels of a subgroup of zygotic genes in stage 5 embryos.

Teriflunomide Concentrations in Cerebrospinal Fluid and Plasma in Patients with Multiple Sclerosis: A Pharmacokinetic Study.

Background: Teriflunomide is a disease modifying treatment (DMT) approved for relapsing-remitting multiple sclerosis (RRMS) in adults and children. It reduces lymphocyte proliferation by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) and thereby the pyrimidine synthesis. Although most DMTs in multiple sclerosis (MS) modulate or inhibit the immune system in the periphery, the efficacy may improve if the agent also targets immune activity within the central nervous system (CNS), acts as a neuro-protective and enhances neuro-regeneration.

Measuring moral distress in Swedish intensive care: Psychometric and descriptive results.

Objectives: To investigate the construct validity and psychometric properties of the Swedish version of the Moral Distress Scale-Revised and to describe moral distress in an intensive care context.

Research Methodology/design: The Italian Moral Distress Scale-Revised was translated and semantically adjusted to the Swedish intensive care context. A web survey with 14 moral distress items, as well as three additional and eight background questions was answered by critical care nurses (N = 71) working in intensive care units during the second year of the coronavirus disease pandemic.

Learning in intensive care during the COVID-19 pandemic postgraduate critical care nursing students' experiences.

Objectives: This study explored postgraduate critical care nursing students' experiences of learning in the ICU during the COVID-19 pandemic and to understand these experiences in relation to self-directed learning and professional development.

Methods: An explorative qualitative design was used. Eight postgraduate critical care nursing students from two different universities were interviewed.

A new CUT&RUN low volume-urea (LoV-U) protocol optimized for transcriptional co-factors uncovers Wnt/β-catenin tissue-specific genomic targets.

Upon WNT/β-catenin pathway activation, stabilized β-catenin travels to the nucleus where it associates with the TCF/LEF transcription factors, constitutively bound to genomic Wnt-responsive elements (WREs), to activate target gene transcription. Discovering the binding profile of β-catenin is therefore required to unambiguously assign direct targets of WNT signaling. Cleavage under targets and release using nuclease (CUT&RUN) has emerged as prime technique for mapping the binding profile of DNA-interacting proteins.

Institutional Constraints as an Obstacle for Prioritizing Nursing Interventions During the COVID-19 Pandemic-Critical Care Nurses' Experiences.

Introduction: The demands of the pandemic such as staff shortages and limited resources combined with new guidelines regarding infection control may have required the prioritizing of nursing interventions.

Objectives: The aim of this study was to describe critical care nurses' experiences of prioritizing nursing interventions for patients with COVID-19 in intensive care units (ICUs) during the pandemic.

Method: A qualitative descriptive study was gathered from open-ended questions included in a cross-sectional online questionnaire.

Critical care nurses' perception of moral distress in intensive care during the COVID-19 pandemic - A pilot study.

Objectives: To describe critical care nurses' perception of moral distress during the second year of the COVID-19 pandemic.

Design/methods: A cross-sectional study involving a questionnaire was conducted. Participants responded to the Italian version of the Moral Distress Scale-Revised, which consists of 14 items divided in dimensions Futile care (three items), Ethical misconduct (five items), Deceptive communication (three items) and Poor teamwork (three items).