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Background: Team reflexivity and peer feedback in daily clinical work can improve patient safety. However, teams do not always engage in reflection after patient care. A reason could be that team members may lack skills in engaging in team reflection. This study explores the use of interprofessional team-based simulations to encourage and equip teams for reflective conversations in the real-world clinical practice., Methods: This was a prospective, explorative study of team members' perceptions of the use of in situ simulation-based scenarios with critically ill patient cases to train team-based reflections and peer feedback. The study took place in two neurological wards. Prior to the intervention, a 1-day observation in each ward and semi-structured short interviews with physicians and nurses were conducted., Results: A total of 94 staff members, 57 nurses, 8 nurse assistants and 29 physicians participated in the in situ simulation scenarios. All team members showed appreciation of the safe learning environment. The authors found that the simulations and the debriefing structure provided an opportunity for training of team reflexivity and feedback. The team members evaluated the simulation-based training very positively, and their initial reaction indicated that they found peer feedback useful for the individual and the team. This approach allowed them to reflect on their own clinical practice., Conclusion: The simulation-based training scenarios and the debriefing structure promoted team members' team reflexivity and peer feedback skills. The method is feasible and could be used in other specialties and situations. The team members' reactions to feedback were positive, and based on their reflections, there is a potential to increase both individual and team skills as well as improve patient treatment., (© 2024. The Author(s).)

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent., Significance: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483., (©2022 The Authors; Published by the American Association for Cancer Research.)

Large-scale efforts to identify breast cancer (BC) risk alleles have historically taken place among women of European ancestry. Recently, there are new efforts to verify if these alleles increase risk in African American (AA) women as well. We investigated the effect of previously reported AA breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African-enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case-control, case-series and race-nested approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.420, p = 0.005). Our results suggest that an ancestry-specific Duffy-null allele and differential prevalence of a polymorphic gene variant of ANKLE1 may play a role in TNBC breast cancer outcomes. These findings present opportunities for therapeutic potential and future studies to address race-specific differences in TNBC risk and disease outcome.

Background: The purpose of this paper is to describe a development project in which simulation was used to improve the telephone-based conversations between nurses in an emergency department (ED) and physicians from different specialties taking care of acutely ill patients., Methods: A needs analysis consisting of observations and interviews was conducted and a one-day simulation-based interprofessional team training course was developed. Observations of phone conversations pre-course, three and six months after the course were conducted in the clinical setting with 20 participants in each point of time. A 14-item evaluation tool was used to record how many information pieces were communicated., Results: Five courses were conducted for 66 nurses/nurse assistants and 17 physicians. 9 out of the 14 items were reported significantly more after the course. Item that were not reported in the pre-measurement, increased to around 20% reporting three months after the course but then fell to close to 0% again after six months., Conclusions: The patterns of retention and decrease of the effect could be an indicator for norms, values and beliefs held by professions about what constitutes their task., (© 2020 The Authors.)

Background: Up to 40% of lung adenocarcinoma have been reported to lack ataxia-telangiectasia mutated (ATM) protein expression. We asked whether ATM-deficient lung cancer cell lines are sensitive to poly-ADP ribose polymerase (PARP) inhibitors and determined the mechanism of action of olaparib in ATM-deficient A549 cells., Methods: We analysed drug sensitivity data for olaparib and talazoparib in lung adenocarcinoma cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) project. We deleted ATM from A549 lung adenocarcinoma cells using CRISPR/Cas9 and determined the effects of olaparib and the ATM/Rad3-related (ATR) inhibitor VE-821 on cell viability., Results: IC 50 values for both olaparib and talazoparib positively correlated with ATM mRNA levels and gene amplification status in lung adenocarcinoma cell lines. ATM mutation was associated with a significant decrease in the IC 50 for olaparib while a similar trend was observed for talazoparib. A549 cells with deletion of ATM were sensitive to ionising radiation and olaparib. Olaparib induced phosphorylation of DNA damage markers and reversible G2 arrest in ATM-deficient cells, while the combination of olaparib and VE-821 induced cell death., Conclusions: Patients with tumours characterised by ATM-deficiency may benefit from treatment with a PARP inhibitor in combination with an ATR inhibitor.

Objective: To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations., Background: Breast cancer (BC) mortality is higher in African American (AA) compared to White American (WA) women; this disparity is partly explained by 2-fold higher TNBC incidence., Methods: We used a surgically maintained biospecimen cohort of 2884 BC cases. Subsets of the total (760 AA; 962 WA; 910 West African/Ghanaian; 252 East African/Ethiopian) were analyzed for genotypes of candidate alleles. A subset of 417 healthy controls were also genotyped, to measure associations with overall BC risk and TNBC., Results: TNBC frequency was highest in Ghanaian and AA cases (49% and 44% respectively; P < 0.0001) and lowest in Ethiopian and WA cases (17% and 24% respectively; P < 0.0001). TNBC cases had higher West African ancestry than non-TNBC (P < 0.0001). Frequency of the Duffy-null allele (rs2814778; an African ancestral variant adopted under selective pressure as protection against malaria) was associated with TNBC-specific risk (P < 0.0001), quantified West African Ancestry (P < 0.0001) and was more common in AA, Ghanaians, and TNBC cases. Additionally, rs4849887 was significantly associated with overall BC risk, and both rs2363956 and rs13000023 were associated with TNBC-specific risk, although none as strongly as the Duffy-null variant., Conclusions: West African ancestry is strongly correlated with TNBC status, as well as germline variants related to BC risk. The Duffy-null allele was associated with TNBC risk in our cohort.

Introduction: Voltage-gated calcium channels (VGCC) have been found to be differentially expressed in several different tumor types, but their role in tumor growth, malignant invasion, metastases and impact on clinical outcomes has not been clarified., Materials and Methods: From a cohort database of 193 patients with early-stage NSCLC, 163 formalin-fixed paraffin-embedded specimens were available for analysis to construct tissue microarrays. Cav3.1 protein expression was detected using fluorescence immunohistochemistry, and quantified using automated image acquisition and analysis., Results: Among the cohort of 193 NSCLC patients, adenocarcinoma (53.9%) and squamous cell carcinoma (SCC) (30.1%) were the most common histologies. There was no difference between SCC and non-SCC subtypes in overall survival (OS) or relapse-free survival (RFS); 74.2 vs 90.1 months ( p = 0.543) and 48.8 vs 52.6 months ( p = 0.766), respectively. T-type VGCC 3.1 (Cav3.1) overexpression was assessed by tissue microarray immunohistochemistry analysis from 163 available patient samples. Eighteen (11.0%) NSCLC primaries were found to have Cav3.1 overexpression levels, and were significantly associated with SCC histology ( p < 0.001), larger tumor size ( p < 0.001) and later stage disease at diagnosis ( p = 0.019). Median OS was 48.6 vs 106.7 months for Cav3.1 overexpressing and non-overexpressing patients, respectively ( p = 0.032). Regression analysis revealed a significantly negative effect for Cav3.1 overexpression on RFS (Hazard ratio [HR] = 2.02, p = 0.048)., Conclusions: Cav3.1 overexpression is a potential biomarker for poorer patient outcomes. These results bring supportive evidence for calcium channels inducing an aggressive phenotype in NSCLC and potentially may serve as a therapeutic target in overexpressing tumors., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

Background: Respiratory rate is among the first vital signs to change in deteriorating patients. The aim was to investigate the agreement between respiratory rate measurements by three different methods., Methods: This prospective observational study included acutely admitted adult patients in a medical ward. Respiratory rate was measured by three methods: a standardised approach over 60 s while patients lay still and refrained from talking, by ward staff and by a wireless electronic patch (SensiumVitals). The Bland-Altman method was used to compare measurements and three breaths per minute (BPM) was considered a clinically relevant difference., Results: We included 50 patients. The mean difference between the standardised approach and the electronic measurement was 0.3 (95% CI: -1.4 to 2.0) BPM; 95% limits of agreement were -11.5 (95% CI: -14.5 to -8.6) and 12.1 (95% CI: 9.2 to 15.1) BPM. Removal of three outliers with huge differences lead to a mean difference of -0.1 (95% CI: -0.7 to 0.5) BPM and 95% limits of agreement of -4.2 (95% CI: -5.3 to -3.2) BPM and 4.0 (95% CI: 2.9 to 5.0) BPM. The mean difference between staff and electronic measurements was 1.7 (95% CI: -0.5 to 3.9) BPM; 95% limits of agreement were -13.3 (95% CI: -17.2 to -9.5) BPM and 16.8 (95% CI: 13.0 to 20.6) BPM., Conclusion: A concerning lack of agreement was found between a wireless monitoring system and a standardised clinical approach. Ward staff's measurements also seemed to be inaccurate., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

MicroRNAs (miRNAs) are small non-coding RNAs that function in transcriptional and post-transcriptional regulation of gene expression. Several miRNAs have been implicated in regulating prostate cancer (PCa) progression. Deregulations of miRNA regulatory networks have been reported in ERG positive PCa, which accounts for ~50 % of PCa and have been suggested to affect tumor aggressiveness. The function of miR338-3p, its prognostic significance, and its association with ERG positive PCa has not been fully investigated. Using microarray expression profiling, we identified miRNA338-3p as among the top deregulated miRNAs associated with ERG status in PCa. We investigated miR338-3p function using in vitro and in vivo experimental models and its expression was assessed and validated in clinical samples and a public cohort of localized and metastatic prostate cancer. miR338-3p was significantly down-regulated with disease progression from benign prostate tissue to primary and metastatic lesions. In localized disease, patients with lower miR338-3p expression levels showed increased association to biochemical recurrence and several adverse pathological parameters compared to patients with higher miRNA338-3p tissue expression levels. Using in vitro PCa cell models, overexpression of miR338-3p resulted in a decrease in cell invasion and expression of chemokine signalling genes CXCL12, CXCR4, and CXCR7. In vivo, orthotropic implantation of PC3 cells stably expressing miR338-3p was associated with a significant decrease in tumor weights compared to control cells. miR338-3p has anti-proliferative and anti-invasive properties. It affects CXCR4 axis, and its down-regulation is associated with adverse clinical outcomes in PCa patients.

Purpose: The present study examined the effects of 15 weeks of soccer training and two different swimming training protocols on bone turnover in sedentary middle-aged women., Methods: Eighty-three premenopausal mildly hypertensive women [age: 45 ± 6 (± SD) years, height: 165 ± 6 cm, weight: 80.0 ± 14.1 kg, body fat: 42.6 ± 5.7 %, systolic blood pressure/diastolic blood pressure: 138 ± 6/85 ± 3 mmHg] were randomized into soccer training (SOC, n = 21), high-intensity intermittent swimming (HS, n = 21), moderate-intensity swimming (MS, n = 21) intervention groups, and a control group (C, n = 20). The training groups completed three sessions per week for 15 weeks. DXA scans were performed and resting blood samples were drawn pre- and post-intervention., Results: In SOC, plasma osteocalcin, procollagen type I N propeptide and C-terminal telopeptide increased (P < 0.05) by 37 ± 15, 52 ± 23 and 42 ± 18 %, respectively, with no changes in MS, HS and C. The intervention-induced increase in SOC was larger (P < 0.05) than in MS, HS and C. In SOC, leg BMC increased (P < 0.05) by 3.1 ± 4.5 %, with a larger increase in SOC than in C. Femoral shaft and trochanter bone mineral density (BMD) increased (P < 0.05) by 1.7 ± 1.9 and 2.4 ± 2.9 %, respectively, in SOC, with a greater (P < 0.05) change in SOC than in MS and C, whereas total body and total leg BMD did not change in any of the groups., Conclusion: In conclusion, 15 weeks of soccer training with sedentary middle-aged women caused marked increases in bone turnover markers, with concomitant increases in leg bone mass. No changes in bone formation and resorption markers were seen after prolonged submaximal or high-intensity intermittent swimming training. Thus, soccer training appears to provide a powerful osteogenic stimulus in middle-aged women.

Background: The purpose of this study is to evaluate symptom relief, patient satisfaction, and safety of permanent mesh following Nissen fundoplication and hiatal hernia repair., Methods: Patients who underwent Nissen fundoplication and hiatal hernia repair with permanent mesh (Crurasoft; Davol, Inc, Bard, Warwick, RI) between 2005 and 2011 were identified. A retrospective chart review was conducted. Long-term follow-up data were obtained via telephone interviews using a modified 5-point Likert scale., Results: Forty-one patients were identified. Twenty-six patients (63%) had complete follow-up data. Mean follow-up period was 65 months (14 to 96 months). Symptomatic improvement occurred in 23 patients (88%). Twenty-three patients (88%) reported overall satisfaction with the procedure as either excellent or good, and 23 of 26 patients (89%) would undergo surgery again. Three patients (12%) reported hernia recurrence. There were no mesh erosions., Conclusion: The use of permanent (Crurasoft; Davol, Inc) mesh resulted in symptom improvement as well as patient satisfaction, and no mesh erosions were seen., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: ERG-gene rearrangement defines a distinct molecular subtype of PCA with potential biological and clinical implications. To identify a molecular signature reflective of the downstream effects of ERG-mediated transcriptional regulation with prognostic implication in patients with prostate cancer (PCA)., Material and Methods: We used a singular value decomposition (SVD) bioinformatics approach to re-analyse gene expression data previously generated from 46 prostate tumours, and identified an ERG-like gene signature. The signature was validated on several patient cohorts and individual genes were correlated to ERG expression and PCA progression., Results: An ERG-like 10-gene signature was identified and validated in PCA cohorts of the physician health study (p115) (n = 110) in addition to three independent public datasets, and was significantly associated with disease progression, biochemical recurrence and PCA-specific mortality. Patients with the ERG-like signature were significantly associated with disease recurrence on univariate (hazard ratio [HR] 2.6; 95% confidence interval [CI]:1.3-5.2; P = 0.004) and multivariate analysis (HR 2.3; 95% CI:1.1-4.6, P = 0.016) compared with patients without this signature. Within the group of patients with Gleason score (GS) 6 and 7 PCA, the signature added prognostic value beyond GS and identified patients at higher risk of cancer deaths more accurately than GS alone or in combination with ERG status. Protein expression of the 10 genes were significantly associated with ERG and disease progression regardless of ERG status., Conclusion: The characterized ERG-like signature was reflective of aggressive features of ERG-mediated transcription and was prognostically robust. The combination of this signature with clinicopathological variables should be validated prospectively to explore its clinical utility in stratifying patients with PCA and in identifying those at higher risk of metastatic and lethal disease., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objectives: • To investigate the effects of different folic acid concentrations on the growth and invasiveness of prostate cancer cell lines. • To determine if observed changes are correlated with changes in levels of the potential prostate cancer biomarker, sarcosine, a byproduct of folate metabolism., Materials and Methods: • The prostate cancer cell lines PC-3, LNCaP and DU145 were cultured in media containing 4, 20 or 100 nm of folic acid and assayed for growth over 9 days by counting viable cells at 3-day intervals, or for invasion by passage through a Matrigel-coated transwell membrane. • Cells grown in the different folic acid media were collected and subjected to metabolomic analysis by gas chromatography and mass spectrometry to measure levels of intracellular sarcosine., Results: • The results show that higher levels of folic acid can increase cell growth in PC-3 and LNCaP prostate cancer cell lines, and may also increase the invasive capacity of PC-3, LNCaP and DU145 cells. • We did not observe a correlation between increased invasion from higher folic acid concentrations and levels of sarcosine, but there were significant changes in other metabolites in cells grown in higher levels of folic acid., Conclusion: • These findings suggest that folic acid has an important and potentially negative role in prostate cancer progression., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Tropoelastin is the monomeric form of elastin, a major polymeric protein of the extracellular elastic matrix of vertebrate tissues with properties of extensibility and elastic recoil. Mammalian and avian species contain a single gene for tropoelastin. A tropoelastin gene has also previously been identified in amphibians. In contrast, two tropoelastin genes with different tissue expression patterns have been described in teleosts. While general characteristics of tropoelastins, such as alternating arrangements of hydrophobic and crosslinking domains, are conserved across a wide phylogenetic range, sequences of these domains are highly variable, particularly when amphibian and teleost tropoelastins are included. For this reason exon-to-exon correspondence is not clear, and overall alignment of tropoelastin sequences across all species is not possible. An exception to this is the C-terminal exon, whose coding sequence has been very well-conserved across all species described to date. In mammalians this C-terminal domain has been shown to be important for interactions with cells and other matrix-associated proteins involved in matrix assembly. Here we identify and characterize a second tropoelastin gene in the frog with several unusual characteristics, the most striking of which is truncation of the C-terminal domain, deleting normally conserved sequence motifs. We demonstrate that, in spite of the absence of these motifs, both frog tropoelastin genes are expressed and incorporated into the elastic matrix, although with differential tissue localizations.

Non-canonical Wnt signaling is an important regulator of gastrulation in Xenopus. In particular, it has been implicated in the control of convergent extension movements. Convergent extension in the gastrula occurs primarily in the dorsal tissue of the marginal zone, and explants of this tissue will continue to undergo these movements in isolation. This observation has led to an assay to examine convergent extension movements that is unique to the Xenopus system, and is described herein.

Vertebrate gastrulation requires coordination of mesoderm specification with morphogenetic movements. While both of these processes require FGF signaling, it is not known how mesoderm specification and cell movements are coordinated during gastrulation. The related Sprouty and Spred protein families are recently discovered regulators of receptor tyrosine kinase signaling. We identified two genes for each family in Xenopus tropicalis: Xtsprouty1, Xtsprouty2, Xtspred1, and Xtspred2. In gain- and loss-of-function experiments we show that XtSprouty and XtSpred proteins modulate different signaling pathways downstream of the FGF receptor (FGFR), and consequently different developmental processes. Notably, XtSproutys inhibit morphogenesis and Ca(2+) and PKCdelta signaling, leaving MAPK activation and mesoderm specification intact. In contrast, XtSpreds inhibit MAPK activation and mesoderm specification, with little effect on Ca(2+) or PKCdelta signaling. These differences, combined with the timing of their developmental expression, suggest a mechanism to switch FGFR signal interpretation to coordinate mesoderm formation and cell movements during gastrulation.