CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses

It is well established that Ly6C(hi) monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6C(hi) monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6C(hi) monocytes consist of two distinct subpopulations (CXCR4(hi) and CXCR4(lo) subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4(hi) subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4(lo) monocytes. We propose that the CXCR4(hi) subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The Role Complexities in Advance Care Planning for End-of-Life Care—Nursing Students’ Perception of the Nursing Profession

Nurses’ perceptions of being responsible for advance care planning (ACP) vary greatly across different studies. It could, however, affect their involvement in advance care planning and patients’ quality of death. Recent studies on this topic have mostly focused on advance directives but not ACP and nurses in the ward setting. This study aimed to assess the perception of Hong Kong nursing undergraduates of the nurse’s role in advance care planning and examine its associations with knowledge, attitude, and experience. A cross-sectional 57-item survey was delivered to nursing undergraduates between June and August 2020. The chi-squared test or Fisher’s exact test were used for univariate analysis. The multiple logistic regression model was used for multivariate analysis. A total of 469 participants were assessed for eligibility; 242 of them were included in the data analysis, with a response rate of 97.6%. The majority of respondents—77.3% (95% CI: 72.0–82.6%)—perceived having a role in ACP, but large discrepancies were found between their perception of their role regarding different aspects of ACP. Participants who had a better knowledge status (p = 0.029) or supported the use of ACP (p &lt; 0.001) were more likely to have a positive perception of their role in ACP. A negative correlation was found between the experience of life threat and positive role perception (p &lt; 0.001). Through strengthening training, the role clarity of nursing undergraduates could be achieved, maximizing their cooperation with and implementation of ACP in their future nursing career. The enhancement of end-of-life education could also be undertaken to fill nursing undergraduates’ knowledge gap in this area and change their attitudes

Effects of Music on Patients Undergoing a C-clamp Procedure After Percutaneous Coronary Interventions

Aim: This paper reports a study to determine the effect of music on physiological parameters and level of pain in patients undergoing application of a C-clamp after percutaneous coronary interventions. Background: Most percutaneous coronary interventions are performed through the femoral artery. In order to stop bleeding and achieve homeostasis, a C-clamp is used after percutaneous coronary interventions. However, the experience is painful for patients and they inevitably suffer discomfort. Pain may lead to stress responses and may affect the physical and mental health of patients. One potential beneficial practice is having the patient listen to relaxing music, which might have the effect of reducing situational discomfort and pain. Methods: A randomized controlled study was conducted during the period September 2004 to March 2005. Forty-three people (20 experimental and 23 control) were recruited from the intensive care units of two acute care hospitals in Hong Kong. Physiological and psychological variables were collected at baseline and at 15, 30 and 45 minutes. Results: In the music group, there were statistically significant reductions (P = 0.001) in heart rate, respiratory rate, and oxygen saturation than the control participants at 45 minutes. In the music group, statistically significant reductions (P = 0.001) in systolic blood pressure, heart rate, respiratory rate and oxygen saturation were found at the four time points, but not in the control group. No statistically significant differences were found at baseline comparison of the two groups, but statistically significant differences in pain scores were found at 45 minutes for participants in the music group compared with the control group (P = 0.003). Participants in the control group showed statistically significant increases in pain at 45 minutes compared with baseline (P \u3c 0.001). Conclusions: The benefits of preventing physiological reactions to pain were demonstrated. Music is a simple, safe and effective method of reducing potentially harmful physiological and psychological responses arising from pain. (PsycINFO Database Record (c) 2016 APA, all rights reserved

Conditional Knockout of Hypoxia-Inducible Factor 1-Alpha in Tumor-Infiltrating Neutrophils Protects against Pancreatic Ductal Adenocarcinoma

Large numbers of neutrophils infiltrate tumors and comprise a notable component of the inflammatory tumor microenvironment. While it is established that tumor cells exhibit the Warburg effect for energy production, the contribution of the neutrophil metabolic state to tumorigenesis is unknown. Here, we investigated whether neutrophil infiltration and metabolic status promotes tumor progression in an orthotopic mouse model of pancreatic ductal adenocarcinoma (PDAC). We observed a large increase in the proportion of neutrophils in the blood and tumor upon orthotopic transplantation. Intriguingly, these tumor-infiltrating neutrophils up-regulated glycolytic factors and hypoxia-inducible factor 1-alpha (HIF-1α) expression compared to neutrophils from the bone marrow and blood of the same mouse. This enhanced glycolytic signature was also observed in human PDAC tissue samples. Strikingly, neutrophil-specific deletion of HIF-1α (HIF-1αΔNφ) significantly reduced tumor burden and improved overall survival in orthotopic transplanted mice, by converting the pro-tumorigenic neutrophil phenotype to an anti-tumorigenic phenotype. This outcome was associated with elevated reactive oxygen species production and activated natural killer cells and CD8+ cytotoxic T cells compared to littermate control mice. These data suggest a role for HIF-1α in neutrophil metabolism, which could be exploited as a target for metabolic modulation in cancer

Revealing the millipede and other soil-macrofaunal biodiversity in Hong Kong using a citizen science approach

Soil biodiversity plays important roles in nutrient recycling in both the environment and agriculture. However, they are generally understudied worldwide. To reveal the diversity of soil macrofauna in Hong Kong, here we initiated a citizen science project involving university, non-governmental organisations and secondary school students and teachers. It is envisioned that the citizen science approach used in this study could be used as a demonstration to future biodiversity sampling and monitoring studies.Throughout a year of monitoring and species sampling across different localities in Hong Kong, 150 soil macrofaunal morphospecies were collected. Eighty five of them were further identified by morphology and DNA barcoding was assigned to each identified morphospecies, yielding a total of 646 DNA barcodes, with new millipede sequences deposited to the GenBank. The soil macrofauna morphospecies in Hong Kong found in this study are mainly dominated by millipedes (23 out of 150) and oligochaetes (15 out of 150). Amongst the twenty three identified millipedes, two polyxenid millipedes, Monographis queenslandica Huynh & Veenstra, 2013 and Alloproctoides remyi Marquet and Condé, 1950 are first recorded in Hong Kong. Information has been curated on an online platform and database (http://biodiversity.sls.cuhk.edu.hk/millipedes). A postcard summarising the findings of millipedes in Hong Kong has also been made as a souvenir and distributed to citizen participants. The identified macrofauna morphospecies and their 646 DNA barcodes in this study established a solid foundation for further research in soil biodiversity