VLST: Virtual Lung Screening Trial for Lung Cancer Detection Using Virtual Imaging Trial.

Importance: The efficacy of lung cancer screening can be significantly impacted by the imaging modality used. This Virtual Lung Screening Trial (VLST) addresses the critical need for precision in lung cancer diagnostics and the potential for reducing unnecessary radiation exposure in clinical settings. Objectives: To establish a virtual imaging trial (VIT) platform that accurately simulates real-world lung screening trials (LSTs) to assess the diagnostic accuracy of CT and CXR modalities. Design Setting and Participants: Utilizing computational models and machine learning algorithms, we created a diverse virtual patient population. The cohort, designed to mirror real-world demographics, was assessed using virtual imaging techniques that reflect historical imaging technologies. Main Outcomes and Measures: The primary outcome was the difference in the Area Under the Curve (AUC) for CT and CXR modalities across lesion types and sizes. Results: The study analyzed 298 CT and 313 CXR simulated images from 313 virtual patients, with a lesion-level AUC of 0.81 (95% CI: 0.78-0.84) for CT and 0.55 (95% CI: 0.53-0.56) for CXR. At the patient level, CT demonstrated an AUC of 0.85 (95% CI: 0.80-0.89), compared to 0.53 (95% CI: 0.47-0.60) for CXR. Subgroup analyses indicated CT's superior performance in detecting homogeneous lesions (AUC of 0.97 for lesion-level) and heterogeneous lesions (AUC of 0.71 for lesion-level) as well as in identifying larger nodules (AUC of 0.98 for nodules > 8 mm). Conclusion and Relevance: The VIT platform validated the superior diagnostic accuracy of CT over CXR, especially for smaller nodules, underscoring its potential to replicate real clinical imaging trials. These findings advocate for the integration of virtual trials in the evaluation and improvement of imaging-based diagnostic tools.

Development and Application of a Virtual Imaging Trial Framework for Longitudinal Quantification of Emphysema in CT.

Pulmonary emphysema is a progressive lung disease that requires accurate evaluation for optimal management. This task, possible using quantitative CT, is particularly challenging as scanner and patient attributes change over time, negatively impacting the CT-derived quantitative measures. Efforts to minimize such variations have been limited by the absence of ground truth in clinical data, thus necessitating reliance on clinical surrogates, which may not have one-to-one correspondence to CT-based findings. This study aimed to develop the first suite of human models with emphysema at multiple time points, enabling longitudinal assessment of disease progression with access to ground truth. A total of 14 virtual subjects were modeled across three time points. Each human model was virtually imaged using a validated imaging simulator (DukeSim), modeling an energy-integrating CT scanner. The models were scanned at two dose levels and reconstructed with two reconstruction kernels, slice thicknesses, and pixel sizes. The developed longitudinal models were further utilized to demonstrate utility in algorithm testing and development. Two previously developed image processing algorithms (CT-HARMONICA, EmphysemaSeg) were evaluated. The results demonstrated the efficacy of both algorithms in improving the accuracy and precision of longitudinal quantifications, from 6.1±6.3% to 1.1±1.1% and 1.6±2.2% across years 0-5. Further investigation in EmphysemaSeg identified that baseline emphysema severity, defined as >5% emphysema at year 0, contributed to its reduced performance. This finding highlights the value of virtual imaging trials in enhancing the explainability of algorithms. Overall, the developed longitudinal human models enabled ground-truth based assessment of image processing algorithms for lung quantifications.

Quantitative accuracy of lung function measurement using parametric response mapping: A virtual imaging study.

Parametric response mapping (PRM) is a voxel-based quantitative CT imaging biomarker that measures the severity of chronic obstructive pulmonary disease (COPD) by analyzing both inspiratory and expiratory CT scans. Although PRM-derived measurements have been shown to predict disease severity and phenotyping, their quantitative accuracy is impacted by the variability of scanner settings and patient conditions. The aim of this study was to evaluate the variability of PRM-based measurements due to the changes in the scanner types and configurations. We developed 10 human chest models with emphysema and air-trapping at end-inspiration and end-expiration states. These models were virtually imaged using a scanner-specific CT simulator (DukeSim) to create CT images at different acquisition settings for energy-integrating and photon-counting CT systems. The CT images were used to estimate PRM maps. The quantified measurements were compared with ground truth values to evaluate the deviations in the measurements. Results showed that PRM measurements varied with scanner type and configurations. The emphysema volume was overestimated by 3 ± 9.5 % (mean ± standard deviation) of the lung volume, and the functional small airway disease (fSAD) volume was underestimated by 7.5±19 % of the lung volume. PRM measurements were more accurate and precise when the acquired settings were photon-counting CT, higher dose, smoother kernel, and larger pixel size. This study demonstrates the development and utility of virtual imaging tools for systematic assessment of a quantitative biomarker accuracy.

Characterization of the broad-spectrum antibacterial activity of bacteriocin-like inhibitory substance-producing probiotics isolated from fermented foods.

Antimicrobial peptides, such as bacteriocin, produced by probiotics have become a promising novel class of therapeutic agents for treating infectious diseases. Selected lactic acid bacteria (LAB) isolated from fermented foods with probiotic potential were evaluated for various tests, including exopolysaccharide production, antibiotic susceptibility, acid and bile tolerance, antibacterial activity, and cell adhesion and cytotoxicity to gastric cell lines. Six selected LAB strains maintained their high viability under gastrointestinal conditions, produced high exopolysaccharides, showed no or less cytotoxicity, and adhered successfully to gastric cells. Furthermore, three strains, Weissella confusa CYLB30, Lactiplantibacillus plantarum CYLB47, and Limosilactobacillus fermentum CYLB55, demonstrated a strong antibacterial effect against drug-resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica serovar Choleraesuis, Enterococcus faecium, and Staphylococcus aureus. Whole genome sequencing was performed on these three strains using the Nanopore platform; then, the results showed that all three strains did not harbor genes related to toxins, superantigens, and acquired antimicrobial resistance, in their genome. The bacteriocin gene cluster was found in CYLB47 genome, but not in CYLB30 and CYLB55 genomes. In SDS-PAGE, the extract of CYLB30 and CYLB47 bacteriocin-like inhibitory substance (BLIS) yielded a single band with a size of less than 10 kDa. These BLIS inhibited the growth and biofilm formation of drug-resistant P. aeruginosa and methicillin-resistant S. aureus (MRSA), causing membrane disruption and inhibiting adhesion ability to human skin HaCaT cells. Moreover, CYLB30 and CYLB47 BLIS rescued the larvae after being infected with P. aeruginosa and MRSA infections. In conclusion, CYLB30 and CYLB47 BLIS may be potential alternative treatment for multidrug-resistant bacteria infections.

An integrated and multi-functional droplet-based microfluidic platform for digital DNA amplification.

Digital DNA amplification is a powerful method for detecting and quantifying rare nucleic acids. In this study, we developed a multi-functional droplet-based platform that integrates the traditional digital DNA amplification workflow into a one-step device. This platform enables efficient droplet generation, transition, and signal detection within a 5-min timeframe, distributing the sample into a uniform array of 4 × 104 droplets (variation <2%) within a chamber. Subsequent in-situ DNA amplification, fluorescence detection, and signal analysis were carried out. To assess the platform's performance, we quantitatively detected the human epidermal growth factor receptor (EGFR) mutation and human papillomavirus (HPV) mutation using digital polymerase chain reaction (dPCR) and digital loop-mediated isothermal amplification (dLAMP), respectively. The fluorescence results exhibited a positive, linear, and statistically significant correlation with target DNA concentrations ranging from 101 to 105 copies/µL, demonstrating the capability and feasibility of the integrated device for dPCR and dLAMP. This platform offers high-throughput droplet generation, eliminates droplet fusion and transition, is user-friendly, reduces costs compared to current methods, and holds potential for thermocycling and isothermal nucleic acid quantification with high sensitivity and accuracy.

Development and Application of a Virtual Imaging Trial framework for Airway Quantifications via CT.

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of death worldwide, characterized by emphysema and bronchitis. Airway measurements reflect the severity of bronchitis and other airway-related diseases. Airway structures can be objectively evaluated with quantitative computed tomography (CT). The accuracy of such quantifications is limited by the spatial resolution and image noise characteristics of the imaging system and can be potentially improved with the emerging photon-counting CT (PCCT) technology. This study evaluated the quantitative performance of PCCT against energy-integrating CT (EICT) systems for airway measurements, and further identified optimum CT imaging parameters for such quantifications. The study was performed using a novel virtual imaging framework by developing the first library of virtual patients with bronchitis. These virtual patients were developed based on CT images of confirmed COPD patients with varied bronchitis severity. The human models were virtually imaged at 6.3 and 12.6 mGy dose levels using a scanner-specific simulator (DukeSim), synthesizing clinical PCCT and EICT scanners (NAEOTOM Alpha, FLASH, Siemens). The projections were reconstructed with two algorithms and kernels at different matrix sizes and slice thicknesses. The CT images were used to quantify clinically relevant airway measurements ("Pi10" and "WA%") and compared against their ground truth values. Compared to EICT, PCCT provided more accurate Pi10 and WA% measurements by 63.1% and 68.2%, respectively. For both technologies, sharper kernels and larger matrix sizes led to more reliable bronchitis quantifications. This study highlights the potential advantages of PCCT against EICT in characterizing bronchitis utilizing a virtual imaging platform.

A web-based clinical pedagogy program to promote professional development for nurse preceptors: A quasi-experimental study.

OBJECTIVE: To examine the effectiveness of a web-based clinical pedagogy program on nurse preceptors' clinical teaching competency, self-efficacy, and attitudes toward web-based learning in comparison to face-to-face course. BACKGROUND: Preceptorship is a dynamic educational process that requires designing, and implementing various teaching strategies, evaluation, assessment and feedback. Web-based learning has been recognized as an effective learning approach for nursing professional development. DESIGN: A prospective quasi-experimental approach with two-group pre-test and post-test repeated measures was adopted. METHODS: The web-based clinical pedagogy program was provided to the preceptors in the experimental group, while control group received the face-to-face preceptorship course. Clinical Teaching Competence Inventory (CTCI), Preceptor Self-efficacy Assessment Instrument (PSEQ), and Attitudes toward Web-based Continuing Learning Survey (AWCLS) were used to evaluate preceptors' learning outcomes. Data were collected at three time points - before, immediately after the learning program, and after 6 months of the clinical teaching experience. RESULTS: A total of 150 nurses (75 participants/group) were recruited from a tertiary hospital in Singapore from July 2018 to June 2020. The results from the repeated measures analysis of covariance showed that there was a significant interaction effect (group x time) on the overall CTCI score after adjusting for covariate (F = 5.390, p = 0.005). However, there were no significant interaction effect (group x time) on PSEQ (F = 2.693, p = 0.070) and overall AWCLS score (F = 1.341, p = 0.264) between the two groups across the three time points. CONCLUSION: The web-based clinical pedagogy program produced outcomes comparable to the face-to-face program in terms of preceptors' clinical teaching competence and self-efficacy. The innovative and cost-effective web-based clinical pedagogy program provided professional development and the flexibility to accommodate preceptors' busy work schedules. Online learning has become increasingly popular during the COVID-19 pandemic and the web-based clinical pedagogy program was implemented when face-to-face workshop was not feasible.

Perspectives of nurse preceptors on a web-based clinical pedagogy program and clinical teaching: A descriptive qualitative study.

Nurse preceptors are key stakeholders in providing quality clinical education. This study aimed to explore the perspectives of nurse preceptors on a web-based clinical pedagogy program and clinical teaching. A descriptive qualitative design was adopted. The program was made accessible to the nurse preceptors who were assigned nursing students from July 2019 to June 2020. Upon completion of clinical teaching, a total of 19 nurse preceptors participated in four focus group discussions. The discussions were audio recorded and transcribed verbatim, and thematic analysis was conducted. Five themes, with 11 subthemes, emerged: (i) Undergoing the process of self-awareness and development; (ii) Mastering newly acquired skills to refine own teaching approach; (iii) Implementing consistent evaluation and constructive feedback; (iv) Dual roles and responsibilities of preceptor; and (v) Benefits and barriers of the program. This study highlighted the knowledge and skills preceptors gained through the program which gave them newfound confidence and facilitated their clinical teaching and evaluation. As the shift towards online learning progresses, web-based learning can be a useful platform for professional development of nurse preceptors.

Singapore Basic Cardiac Life Support and Automated External Defibrillation Guidelines 2021.

Basic Cardiac Life Support and Automated External Defibrillation (BCLS+AED) refers to the skills required in resuscitating cardiac arrest casualties. On recognising cardiac arrest, the rescuer should call for '995' for Emergency Ambulance and immediately initiate chest compressions. Good-quality chest compressions are performed with arms extended, elbows locked, shoulders directly perpendicular over the casualty's chest, and the heel of the palm placed on the lower half of the sternum. The rescuer compresses hard and fast at 4-6 cm depth for adults at a compression rate of 100-120 per minute, with complete chest recoil after each compression. Two quick ventilations of 400-600 mL each can be delivered via a bag-valve-mask after every 30 chest compressions. Alternatively, a trained, able and willing rescuer can provide mouth-to-mouth ventilation. Cardiopulmonary resuscitation should be stopped only when the casualty wakes up, the emergency team takes over care, or when an automated external defibrillator prompts for heart rhythm analysis or delivery of a shock.

Life Support Course for Nurses: beyond competency training.

The Life Support Course for Nurses (LSCN) equips nurses with the resuscitation skills needed to be first responders in in-hospital cardiac arrests. Previous published articles on the LSCN were mainly focused on the development of the LSCN in Singapore, as well as nurses' confidence level, defibrillation experience and outcomes, the perceived barriers faced by nurses and the usefulness of the course. This paper highlights the importance of two key learning methodologies in the LSCN: deep learning and reflection.

A Clinical Teaching Blended Learning Program to Enhance Registered Nurse Preceptors' Teaching Competencies: Pretest and Posttest Study.

BACKGROUND: Clinical nursing education provides opportunities for students to learn in multiple patient care settings, receive appropriate guidance, and foster the development of clinical competence and professionalism. Nurse preceptors guide students to integrate theory into practice, teach clinical skills, assess clinical competencies, and enhance problem-solving and critical thinking skills. Previous research has indicated that the teaching competencies of nurse preceptors can be transferred to students' clinical learning to enhance their clinical competencies. OBJECTIVE: This study aimed to develop a clinical teaching blended learning (CTBL) program with the aid of web-based clinical pedagogy (WCP) and case-based learning for nurse preceptors and to examine the effectiveness of the CTBL program on nurse preceptors' clinical teaching competencies, self-efficacies, attitudes toward web-based learning, and blended learning outcomes. METHODS: A quasi-experimental single-group pretest and posttest design was adopted. A total of 150 nurse preceptors participated in the CTBL program, which was conducted from September 2019 to December 2019. A set of questionnaires, including the clinical teaching competence inventory, preceptor self-efficacy questionnaire, attitudes toward web-based continuing learning survey, and e-learning experience questionnaire, was used to assess the outcomes before and after the CTBL program. RESULTS: Compared with the baseline, the participants had significantly higher total mean scores and subdomain scores for clinical teaching competence (mean 129.95, SD 16.38; P<.001), self-efficacy (mean 70.40, SD 9.35; P<.001), attitudes toward web-based continuing learning (mean 84.68, SD 14.76; P<.001), and blended learning outcomes (mean 122.13, SD 14.86; P<.001) after the CTBL program. CONCLUSIONS: The CTBL program provides a comprehensive coverage of clinical teaching pedagogy and assessment strategies. The combination of the WCP and case-based approach provides a variety of learning modes to fit into the diverse learning needs of the preceptors. The CTBL program allows the preceptors to receive direct feedback from the facilitators during face-to-face sessions. Preceptors also gave feedback that the web-based workload is manageable. This study provides evidence that the CTBL program increases the clinical teaching competencies and self-efficacies of the preceptors and promotes positive attitudes toward web-based learning and better blended learning outcomes. The health care organization can consider the integration of flexible learning and intellect platforms for preceptorship education.

Targeted destruction of cancer stem cells using multifunctional magnetic nanoparticles that enable combined hyperthermia and chemotherapy.

Cancer stem cells (CSCs) have been implicated in cancer recurrence and therapy resistance. Therefore, a CSC-targeted therapy that disrupts the maintenance and survival of CSCs may offer an effective approach in killing tumor cells in primary tumors and preventing the metastasis caused by CSCs. Nanoparticles (NPs)-based thermotherapy and/or chemotherapy are promising therapeutic methods for cancer treatment. Methods: A silica-based multifunctional NP system was present, which encapsulated a chemotherapeutic agent and magnetic cores and coated with a specific antibody against the lung CSCs. The efficacy of this novel therapeutic strategy was systematically studied both in vitro and in vivo by simultaneous activating the combined thermotherapy and chemotherapy via CSC-targeted NPs. Results: These NPs were systematically administered and activated for targeted chemotherapy and thermotherapy by using an externally applied alternating magnetic field (AMF). The antibody-modified NPs targeted to lung CSCs with enhanced cellular uptake in vitro and extended accumulation in tumor in vivo. Up to 98% of lung CSCs was killed in vitro with 30-min application of AMF, due to the combined effects of hyperthermia and chemotherapeutic drug treatment. In in vivo models, this combined therapy significantly suppressed tumor growth and metastasis in lung CSC xenograft-bearing mice, with minimal side effects and adverse effects. Conclusion: With good biocompatibility and targeting capability, the nanodrug delivery system may offer a promising clinical platform for the combined thermotherapy and chemotherapy. This work demonstrated the feasibility of developing multifunctional nanomedicine targeting CSCs for effective cancer treatment.

A web-based clinical pedagogy program to enhance registered nurse preceptors' teaching competencies - An innovative process of development and pilot program evaluation.

BACKGROUND: Registered Nurse Preceptors guide students to integrate theory into practice, assess clinical competencies, and enhance problem-solving skills. Researches have indicated that the teaching competencies of nurse preceptors can be transferred to students' clinical learning. OBJECTIVES: The aims of the study are to develop a web-based clinical pedagogy (WCP) program for Registered Nurse Preceptors and conduct pilot program evaluation. DESIGN: A three-step process was applied to integrate the theoretical framework, evidence from the systematic review, and content validity by the experts and pilot test with the Registered Nurse Preceptors in the content and technical development of the program. The WCP program has unique features including use of dashboard, interactive videos, consultation with experts, discussion forum and backend data analysis. RESULTS: A committee of six content experts evaluated the comprehensiveness, appropriateness, and relevancy of the program. The item-Content Validity Index (CVI) score ranged from 0.83 to 1.00 and the scale-CVI score was 0.87, which indicated that the WCP program had a strong content validity. Ten nurse preceptors were invited to use the WCP program. Preceptors shared that the website was easy to use and navigate. They commented that the videos in each module are beneficial for nurses to understand the real situation in the clinical setting. This feature also makes the website more interactive. Feedback from preceptors was subsequently used to further refine the program. DISCUSSION AND CONCLUSION: The WCP program is an evidence-based program that provides a comprehensive coverage on clinical teaching pedagogy and assessment strategies. The unique web-based technology and interactive features provide a platform for nurse preceptors to discuss clinical encounters with peers and consult experts. The flexible and resource-rich nature of web-based learning encourages nurses to use it for continuing education.

Pretreatment Prediction of Adaptive Radiation Therapy Eligibility Using MRI-Based Radiomics for Advanced Nasopharyngeal Carcinoma Patients.

Background and purpose: Adaptive radiotherapy (ART) can compensate for the dosimetric impacts induced by anatomic and geometric variations in patients with nasopharyngeal carcinoma (NPC); Yet, the need for ART can only be assessed during the radiation treatment and the implementation of ART is resource intensive. Therefore, we aimed to determine tumoral biomarkers using pre-treatment MR images for predicting ART eligibility in NPC patients prior to the start of treatment. Methods: Seventy patients with biopsy-proven NPC (Stage II-IVB) in 2015 were enrolled into this retrospective study. Pre-treatment contrast-enhanced T1-w (CET1-w), T2-w MR images were processed and filtered using Laplacian of Gaussian (LoG) filter before radiomic features extraction. A total of 479 radiomics features, including the first-order (n = 90), shape (n = 14), and texture features (n = 375), were initially extracted from Gross-Tumor-Volume of primary tumor (GTVnp) using CET1-w, T2-w MR images. Patients were randomly divided into a training set (n = 51) and testing set (n = 19). The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied for radiomic model construction in training set to select the most predictive features to predict patients who were replanned and assessed in the testing set. A double cross-validation approach of 100 resampled iterations with 3-fold nested cross-validation was employed in LASSO during model construction. The predictive performance of each model was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC). Results: In the present cohort, 13 of 70 patients (18.6%) underwent ART. Average AUCs in training and testing sets were 0.962 (95%CI: 0.961-0.963) and 0.852 (95%CI: 0.847-0.857) with 8 selected features for CET1-w model; 0.895 (95%CI: 0.893-0.896) and 0.750 (95%CI: 0.745-0.755) with 6 selected features for T2-w model; and 0.984 (95%CI: 0.983-0.984) and 0.930 (95%CI: 0.928-0.933) with 6 selected features for joint T1-T2 model, respectively. In general, the joint T1-T2 model outperformed either CET1-w or T2-w model alone. Conclusions: Our study successfully showed promising capability of MRI-based radiomics features for pre-treatment identification of ART eligibility in NPC patients.

Electrotaxis of tumor-initiating cells of H1975 lung adenocarcinoma cells is associated with both activation of stretch-activated cation channels (SACCs) and internal calcium release.

The metastatic potential of cancer cells is related to their migratory ability, which is influenced by in vivo microenvironment possessing specific physiochemical factors including electric properties. In the present study, we isolated two different subsets of lung adenocarcinoma H1975 cells, as side population (SP) and main population (MP). SP cells were demonstrated to have cancer stem cell characteristics. Using a microscale device to provide physiological direct-current electric field (dcEF), we investigated the electrotactic responses of the SP and MP cells. The results showed that both SP and MP cells exhibited enhanced cathodal migration ability with actin reorganization and transient intracellular calcium ions ([Ca2+]i) increase under dcEF stimulation. For SP cells, the treatment of either stretch-activated cation channels (SACCs) inhibitor or the blockage of intracellular Ca2+ release could partially inhibited dcEF-activated [Ca2+]i increase, and the concomitant treatment led to a complete inhibition. For MP cells, SACCs activation was entirely responsible for EF-activated increase of [Ca2+]i. All these results suggested that that intracellular Ca2+ activation may be associated with cancer cell tumorigenicity and metastasis.

Synthesis of 3-(2-Olefinbenzyl)-4H-chromen-4-one through Cyclobenzylation and Catalytic C-H Bond Functionalization Using Palladium(II).

An efficient strategy for synthesizing 3-(2-olefinbenzyl)-4H-chromen-4-one in two steps was developed. The first step is a cyclobenzylation reaction between (E)-3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one and benzyl bromide to produce homoisoflavonoid. The second step involves intermolecular Pd-catalyzed π-chelating-assisted C-H bond olefination. Using the C-2/C-3 double bond of chromone, palladium-catalyzed aryl C-H bond activation can be functionalized to generate ortho-olefination derivatives in moderate to high yields.

Basic Cardiac Life Support: 2016 Singapore Guidelines.

Basic Cardiac Life Support (BCLS) or cardiopulmonary resuscitation (CPR) refers to the skills required (without use of equipment) in the resuscitation of cardiac arrest individuals. On recognising cardiac arrest, chest compressions should be initiated. Good quality compressions are with arms extended, elbows locked, shoulders directly over the casualty's chest and heel of the palm on the lower half of the sternum. The rescuer pushes hard and fast, compressing 4-6 cm deep for adults at 100-120 compressions per minute with complete chest recoil. Two quick mouth-to-mouth ventilations (each 400-600 mL tidal volume) should be delivered after every 30 chest compressions. Chest compression-only CPR is recommended for lay rescuers, dispatcher-assisted CPR and those unable or unwilling to give ventilations. CPR should be stopped when the casualty wakes up, an emergency team takes over casualty care or if an automated external defibrillator prompts for analysis of heart rhythm or delivery of shock.

Seventeen years of life support courses for nurses: where are we now?

The Life Support Course for Nurses (LSCN) equips nurses with the resuscitation skills to be first responders in in-hospital cardiac arrests. Seventeen years after the initiation of the LSCN, a confidential cross-sectional Qualtrics™ survey was conducted in May 2016 on LSCN graduands to assess the following: confidence in nurse-initiated resuscitation post-LSCN; defibrillation experience and outcomes; and perceived barriers and usefulness of the LSCN. The majority of respondents reported that the course was useful and enhanced their confidence in resuscitation. Skills retention can be enhanced by organising frequent team-based resuscitation training. Resuscitation successes should be publicised to help overcome perceived barriers.

Development of Novel Piezoelectric Biosensor Using PZT Ceramic Resonator for Detection of Cancer Markers.

A novel biosensor based on piezoelectric ceramic resonator was developed for direct detection of cancer markers in the study. For the first time, a commercially available PZT ceramic resonator with high resonance frequency was utilized as transducer for a piezoelectric biosensor. A dual ceramic resonators scheme was designed wherein two ceramic resonators were connected in parallel: one resonator was used as the sensing unit and the other as the control unit. This arrangement minimizes environmental influences including temperature fluctuation, while achieving the required frequency stability for biosensing applications. The detection of the cancer markers Prostate Specific Antigen (PSA) and α-Fetoprotein (AFP) was carried out through frequency change measurement. The device showed high sensitivity (0.25 ng/ml) and fast detection (within 30 min) with small samples (1 µl), which is compatible with the requirements of clinical measurements. The results also showed that the ceramic resonator-based piezoelectric biosensor platform could be utilized with different chemical interfaces, and had the potential to be further developed into biosensor arrays with different specificities for simultaneous detection of multiple analytes.

Chemoresistant lung cancer stem cells display high DNA repair capability to remove cisplatin-induced DNA damage.

BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor responsible for the recurrence of lung cancer as they are highly resistant to conventional chemotherapy. However, the underlying mechanisms are still unclear. EXPERIMENTAL APPROACH: We examined the cellular response of a human LCSC line to treatment with cisplatin, a DNA-damaging anticancer drug that is used extensively in the clinic. We compared the response to cisplatin of LCSCs and differentiated LCSCs (dLCSCs) by determining the viability of these cells, and their ability to accumulate cisplatin and to implement genomic and transcription-coupled DNA repair. We also investigated the transcription profiles of genes related to drug transport and DNA repair. KEY RESULTS: LCSCs were found to be more stem-like, and more resistant to cisplatin-induced cytotoxicity than dLCSCs, confirming their drug resistance properties. LCSCs accumulated less cisplatin intracellularly than dLCSCs and showed less DNA damage, potentially due to their ability to down-regulate AQP2 and CTR1. The results of the transcription-coupled repair of cisplatin-DNA cross-links indicated a higher level of repair of DNA damage in LCSCs than in dLCSCs. In addition, LCSCs showed a greater ability to repair cisplatin-DNA interstrand cross-links than dLCSCs; this involved the activation of various DNA repair pathways. CONCLUSIONS AND IMPLICATIONS: Our results further clarify the mechanism of cisplatin resistance in LCSCs in terms of reduced cisplatin uptake and enhanced ability to implement DNA repairs. These findings may aid in the design of the next-generation of platinum-based anticancer drugs.