An image-based screen for secreted proteins involved in breast cancer G0 cell cycle arrest.

Secreted proteins regulate the balance between cellular proliferation and G0 arrest and therefore play important roles in tumour dormancy. Tumour dormancy presents a significant clinical challenge for breast cancer patients, where non-proliferating, G0-arrested cancer cells remain at metastatic sites, below the level of clinical detection, some of which can re-enter proliferation and drive tumour relapse. Knowing which secreted proteins can regulate entry into and exit from G0 allows us to manipulate their signalling to prevent tumour relapse.

Comparison of Quality of Life after Robotic, Video-Assisted, and Open Surgery for Lung Cancer.

Post-operative quality of life (QOL) has become crucial in choosing operative approaches in thoracic surgery. However, compared to VATS and thoracotomy, QOL results post-RATS are limited. We compared QOL before and after RATS and between RATS, VATS, and thoracotomy.

Optimizing the Cell Painting assay for image-based profiling.

In image-based profiling, software extracts thousands of morphological features of cells from multi-channel fluorescence microscopy images, yielding single-cell profiles that can be used for basic research and drug discovery. Powerful applications have been proven, including clustering chemical and genetic perturbations on the basis of their similar morphological impact, identifying disease phenotypes by observing differences in profiles between healthy and diseased cells and predicting assay outcomes by using machine learning, among many others. Here, we provide an updated protocol for the most popular assay for image-based profiling, Cell Painting.

Hand hygiene with hand sanitizer versus handwashing: what are the planetary health consequences?

In order to reduce the transmission of pathogens, and COVID-19, WHO and NHS England recommend hand washing (HW) and/or the use of hand sanitizer (HS). The planetary health consequences of these different methods of hand hygiene have not been quantified. A comparative life cycle assessment (LCA) was carried out to compare the environmental impact of the UK population practising increased levels of hand hygiene during the COVID-19 pandemic for 1 year.

Impact of the TNM staging system for thymoma.

Background: Masaoka-Koga staging system remains the most frequently applied clinical staging system for thymic malignancy. However, the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposed a tumor-node-metastasis (TNM) staging system in 2014. This study aims to evaluate its impact on stage distribution, clinical implementation, and prognosis for thymomas.

Risks and rewards of the surgical treatment of lung cancer in octogenarians.

Objectives: Surgeons will face an increasing number of octogenarians with lung cancer potentially curable by surgery. The goal of this study was to evaluate short- and long-term outcomes after lung resection.

Methods: We performed a single-centre study of consecutive patients ≥80 years old, surgically treated for suspected lung cancer between 2009 and 2016.

Maintaining safe lung cancer surgery during the COVID-19 pandemic in a global city.

Background: SARS-CoV-2 has challenged health service provision worldwide. This work evaluates safe surgical pathways and standard operating procedures implemented in the high volume, global city of London during the first wave of SARS-CoV-2 infection. We also assess the safety of minimally invasive surgery(MIS) for anatomical lung resection.

Quality of Life in Octogenarians After Lung Resection Compared to Younger Patients.

Introduction: To evaluate postoperative outcome and quality of life (QOL), comparing patients <80 years old to patients ≥ 80.

Patients And Methods: EORTC questionnaires, QLQ-C30 and QLQ-LC13 was used to assess QOL, in patients after surgery. Results were evaluated according to 3 age groups: <70, 70 to 79, and ≥80.

New N1/N2 classification and lobe specific lymphatic drainage: Impact on survival in patients with non-small cell lung cancer treated with surgery.

Objective: to validate the proposed N descriptor revision on a large cohort of patients and assess the impact of tumour location on the distribution pattern of lymph node metastases for patients with NSCLC.

Methods: This is a retrospective review of a consecutive series of patients who had anatomical lung resections. Systematic lymph node dissection was done for all patients.

A Novel Screening Approach for the Dissection of Cellular Regulatory Networks of NF-κB Using Arrayed CRISPR gRNA Libraries.

CRISPR/Cas9 is increasingly being used as a tool to prosecute functional genomic screens. However, it is not yet possible to apply the approach at scale across a full breadth of cell types and endpoints. In order to address this, we developed a novel and robust workflow for array-based lentiviral CRISPR/Cas9 screening.

Modeling Dose and Schedule Effects of AZD2811 Nanoparticles Targeting Aurora B Kinase for Treatment of Diffuse Large B-cell Lymphoma.

Barasertib (AZD1152), a pro-drug of the highly potent and selective Aurora B kinase inhibitor AZD2811, showed promising clinical activity in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients administered as a 4-day infusion. To improve potential therapeutic benefit of Aurora B kinase inhibition, a nanoparticle formulation of AZD2811 has been developed to address limitations of repeated intravenous infusion. One of the challenges with the use of nanoparticles for chronic treatment of tumors is optimizing dose and schedule required to enable repeat administration to sustain tumor growth inhibition.

Effect of a patient-information video on the preoperative anxiety levels of cataract surgery patients.

Purpose: To assess whether a cataract surgery patient-information video reduces patients' preoperative anxiety levels.

Setting: Leeds Teaching Hospitals NHS Trust, UK.

Design: Prospective controlled trial of an intervention to reduce anxiety for first-eye elective cataract surgery patients.

Retrospective Observational Study into the Early Causes of Death Following Surgery for NSCLC.

Introduction: Respiratory failure has historically been the major cause of mortality after elective lung resections. With improved intubation using fiber-optic scopes, better preoperative respiratory risk assessment, more advanced anesthetic single lung ventilation, and minimally invasive surgical technique, this may have changed. Our objective was to assess the main causes of mortality over the past 10 years in patients undergoing elective lung surgery in a major UK center.

Characterization and Validation of a Human 3D Cardiac Microtissue for the Assessment of Changes in Cardiac Pathology.

Pharmaceutical agents despite their efficacy to treat disease can cause additional unwanted cardiovascular side effects. Cardiotoxicity is characterized by changes in either the function and/or structure of the myocardium. Over recent years, functional cardiotoxicity has received much attention, however morphological damage to the myocardium and/or loss of viability still requires improved detection and mechanistic insights.

Prognostic factors including lymphovascular invasion on survival for resected non-small cell lung cancer.

Objectives: The aim of this study was to report on the influence of tumor lymphovascular invasion on overall survival and in patients with resected non-small cell lung cancer and identify prognostic factors for survival.

Methods: This is a retrospective observational study of a consecutive series of patients who had surgical resection of non-small cell lung cancer in a single institution. The study covers a 3-year period.

How accurate is the clinical and radiological evaluation of orbital lesions in comparison to surgical orbital biopsy?

Aims: The purpose of the present study is to determine the overall and disease-related accuracy of clinical and radiological diagnosis when compared to the histology result of the surgical orbital biopsy.

Methods: A retrospective case notes analysis of patients who underwent surgical orbital biopsy during a 12-year period involving more than 100 orbital lesions. The accuracy of clinical and radiological diagnosis was compared with histological diagnosis.

Inhibiting PI3Kβ with AZD8186 Regulates Key Metabolic Pathways in PTEN-Null Tumors.

PTEN-null tumors become dependent on the PI3Kβ isoform and can be targeted by molecules such as the selective PI3Kβ inhibitor AZD8186. However, beyond the modulation of the canonical PI3K pathway, the consequences of inhibiting PI3Kβ are poorly defined. To determine the broader impact of AZD8186 in PTEN-null tumors, we performed a genome-wide RNA-seq analysis of PTEN-null triple-negative breast tumor xenografts treated with AZD8186.

Optimizing Therapeutic Effect of Aurora B Inhibition in Acute Myeloid Leukemia with AZD2811 Nanoparticles.

Barasertib (AZD1152), a highly potent and selective aurora kinase B inhibitor, gave promising clinical activity in elderly acute myeloid leukemia (AML) patients. However, clinical utility was limited by the requirement for a 7-day infusion. Here we assessed the potential of a nanoparticle formulation of the selective Aurora kinase B inhibitor AZD2811 (formerly known as AZD1152-hQPA) in preclinical models of AML.

From the Cover: High-Throughput Imaging of Cardiac Microtissues for the Assessment of Cardiac Contraction during Drug Discovery.

Cardiotoxicity is a common cause of attrition in preclinical and clinical drug development. Current in vitro approaches have two main limitations, they either are limited to low throughput methods not amendable to drug discovery or lack the physiological responses to allow an integrated risk assessment. A human 3D cardiac microtissue containing human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), cardiac endothelial cells and cardiac fibroblast were used to assess their suitability to detect drug induced changes in cardiomyocyte contraction.

A lateral costal artery complicating video-assisted thorascopic surgery (VATS) pleurectomy.

The lateral costal artery is a rare variant arising from the internal thoracic artery (ITA). It has been associated with steel syndrome after coronary artery bypass using the ITA as a conduit. Clinically, it is under-reported in the literature.

New-onset atrial fibrillation after anatomic lung resection: predictive factors, treatment and follow-up in a UK thoracic centre.

Objectives: Postoperative atrial fibrillation (POAF) increases morbidity, hospital stay and healthcare expenditure. This study aims to determine the perioperative factors correlating with POAF as well as to evaluate both treatment strategies and AF persistence beyond discharge.

Methods: The records of all patients undergoing anatomical lung resection over a 1-year period were retrospectively reviewed.

Are there recognized prognostic factors for patients undergoing pulmonary metastasectomy for colorectal carcinoma?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether there is a specific subgroup of patients that would benefit from pulmonary metastasectomy for colorectal carcinoma (CRC). A total of 524 papers were identified using the reported search, of which 1 meta-analysis, 1 systematic review and 17 retrospective studies represented the best evidence to answer the clinical question.