Background & Aims: Acinar cells produce digestive enzymes that impede transcriptomic characterization of the exocrine pancreas. Thus, single-cell RNA-sequencing studies of the pancreas underrepresent acinar cells relative to histological expectations, and a robust approach to capture pancreatic cell responses in disease states is needed. We sought to innovate a method that overcomes these challenges to accelerate study of the pancreas in health and disease.
View Article and Find Full Text PDFUnder chronic stress, cells must balance competing demands between cellular survival and tissue function. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), hepatocytes cooperate with structural and immune cells to perform crucial metabolic, synthetic, and detoxification functions despite nutrient imbalances. While prior work has emphasized stress-induced drivers of cell death, the dynamic adaptations of surviving cells and their functional repercussions remain unclear.
View Article and Find Full Text PDFBackground: As Artificial Intelligence and social robots are increasingly used in health and social care, it is imperative to explore the training needs of the workforce, factoring in their cultural background.
Objectives: Explore views on perceived training needs among professionals around the world and how these related to country cultures.
Design: Cross-sectional, descriptive, mixed-methods international online survey.
Appl Radiat Isot
September 2023
The absolute intensity for the 803-keV γ ray of Po was evaluated by α-γ coincidence technique. A liquid sample with a known amount of Po embedded in scintillation fluid was measured in a coincidence-based system that comprises a Liquid Scintillator (LS) detector and a High-Purity Germanium (HPGe) detector. A photo-reflector assembly that contains the Po sample provides 100% efficiency for detecting the α particles.
View Article and Find Full Text PDFAppl Radiat Isot
August 2023
A ground-level prototype system for low-background measurements was developed and tested. The system consists of a high-purity germanium (HPGe) detector used for detecting γ rays and coupled to a liquid scintillator (LS) used for detecting α and β particles. Both detectors are surrounded by shielding materials and anti-cosmic detectors ("veto") used to suppress background events.
View Article and Find Full Text PDFBackground: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality.
Objectives: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID.
Aim: This qualitative study aimed to examine the motivations and challenges encountered by Israeli nurses during their journey to achieve a doctoral degree (PhD).
Background: The increasing numbers of nurses studying for a doctoral degree may contribute to improving nursing education, expanding the body of knowledge and promoting the status of nursing as a research profession. However, many countries have reported a shortage in nurses with doctoral degrees.
Aim: This study explored the views of an international sample of registered nurses and midwives working in health and social care concerning socially assistive robots (SARs), and the relationship between dimensions of culture and rejection of the idea that SARs had benefits in these settings.
Methods: An online survey was used to obtain rankings of (among other topics) the extent to which SARs have benefits for health and social care. It also asked for free text responses regarding any concerns about SARs.
The small GTPase family is well-studied in cancer and cellular physiology. With 162 annotated human genes, the family has a broad expression throughout cells of the body. Members of the family have multiple exons that require splicing.
View Article and Find Full Text PDFHematol Oncol Clin North Am
October 2022
Germline genetic variants implicated in increasing lifetime risk of pancreatic cancer (PDAC) have been identified in ∼4% to 10% of cases. Clinical features such as family history have poor sensitivity in identifying carriers of these risk variants. Genetic testing for these germline variants has potential to guide risk assessment and surveillance recommendations in high-risk individuals to promote prevention and early detection measures.
View Article and Find Full Text PDFAim: To explore the views of an international sample of nursing and midwifery managers concerning attributes that they associate with compassionate management.
Method: A cross-sectional online survey. Using a snowballing sampling method, 1217 responses were collected from nursing and midwifery managers in 17 countries.
The absolute intensity for the 'prompt' 140.5 keV gamma-ray of Mo was evaluated using the β-γ coincidence technique. A liquid sample of Mo was prepared from aMo/Tc generator and measured in a 4παβ(LS)-γ(HPGe) system that comprises a Liquid Scintillator (LS) detector and a High-Purity Germanium (HPGe) detector.
View Article and Find Full Text PDFIntroduction: Despite the importance of compassionate leadership in health care, many of the existing publications do not account for the effect of culture. The aim of this study is to explore the views of nursing and midwifery managers from different countries in relation to the definition, advantages, and importance of compassion.
Methodology: A cross-sectional, descriptive, exploratory online survey was conducted across 17 countries, containing both closed and open-ended questions.
The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains dismal. Multiple genome-wide association studies (GWAS) have implicated the nuclear receptor NR5A2 in modulating PDAC risk, but mechanisms for this association are not understood. NR5A2 is a transcription factor that maintains acinar cell identity, and heterozygous loss of Nr5a2 in mice accelerates oncogenic Kras-driven formation of pancreatic intraepithelial neoplasia (PanIN), a PDAC precursor derived from acinar cells.
View Article and Find Full Text PDFAim: To explore nursing and midwifery managers' views regarding obstacles to compassion-giving across country cultures.
Background: The benefit of compassionate leadership is being advocated, but despite the fact that health care is invariably conducted within culturally diverse workplaces, the interconnection of culture, compassion and leadership is rarely addressed. Furthermore, evidence on how cultural factors hinder the expression of compassion among nursing and midwifery managers is lacking.
Pancreatic ductal adenocarcinoma is an aggressive cancer with limited treatment options. Approximately 10% of cases exhibit familial predisposition, but causative genes are not known in most families. We perform whole-genome sequence analysis in a family with multiple cases of pancreatic ductal adenocarcinoma and identify a germline truncating mutation in the member of the RAS oncogene family-like 3 (RABL3) gene.
View Article and Find Full Text PDFSelenium, an essential micronutrient known for its cancer prevention properties, is incorporated into a class of selenocysteine-containing proteins (selenoproteins). Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish.
View Article and Find Full Text PDFBackground: Compassion is considered the cornerstone of nursing practice. However, the recent failures in delivering high-quality compassionate nursing care in the UK's National Health Service have brought the topic of compassion to the attention of the public, service providers, policy makers and academics.
Aim: The aim of this study was to explore the nurses' views and experiences of a number of compassion-related issues in nursing and describe similarities and differences at an international level as well as from the different nursing roles of the participating nurses.
The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development.
View Article and Find Full Text PDFThe Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signalling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 (also known as YAP) develop enlarged livers and are prone to liver tumour formation.
View Article and Find Full Text PDFNCOA4 is a selective cargo receptor for the autophagic turnover of ferritin, a process critical for regulation of intracellular iron bioavailability. However, how ferritinophagy flux is controlled and the roles of NCOA4 in iron-dependent processes are poorly understood. Through analysis of the NCOA4-FTH1 interaction, we demonstrate that direct association via a key surface arginine in FTH1 and a C-terminal element in NCOA4 is required for delivery of ferritin to the lysosome via autophagosomes.
View Article and Find Full Text PDFCannabinoids (CB) modulate adult hematopoietic stem and progenitor cell (HSPCs) function, however, impact on the production, expansion, or migration of embryonic HSCs is currently uncharacterized. Here, using chemical and genetic approaches targeting CB-signaling in zebrafish, we show that CB receptor (CNR) 2, but not CNR1, regulates embryonic HSC development. During HSC specification in the aorta-gonad-mesonephros (AGM) region, CNR2 stimulation by AM1241 increased runx1;cmyb(+) HSPCs, through heightened proliferation, whereas CNR2 antagonism decreased HSPC number; FACS analysis and absolute HSC counts confirmed and quantified these effects.
View Article and Find Full Text PDFGenetic control of hematopoietic stem and progenitor cell (HSPC) function is increasingly understood; however, less is known about the interactions specifying the embryonic hematopoietic niche. Here, we report that 17β-estradiol (E2) influences production of runx1+ HSPCs in the AGM region by antagonizing VEGF signaling and subsequent assignment of hemogenic endothelial (HE) identity. Exposure to exogenous E2 during vascular niche development significantly disrupted flk1+ vessel maturation, ephrinB2+ arterial identity, and specification of scl+ HE by decreasing expression of VEGFAa and downstream arterial Notch-pathway components; heat shock induction of VEGFAa/Notch rescued E2-mediated hematovascular defects.
View Article and Find Full Text PDFThe liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development.
View Article and Find Full Text PDFObjectives: The objective of this study was to determine the relationship between specific genetic alterations and malignant transformation in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.
Methods: Quantitative meta-analysis was conducted of studies through October 2010 that adhered to the 1996 World Health Organization guidelines for distinguishing adenoma and borderline IPMN versus carcinoma in surgically resected specimens using a random-effects model. We developed a 6-point scoring system to assess study quality.