Sexual Violence Trends before and after Rollout of COVID-19 Mitigation Measures, Kenya.

COVID-19 mitigation measures such as curfews, lockdowns, and movement restrictions are effective in reducing the transmission of SARS-CoV-2; however, these measures can enable sexual violence. We used data from the Kenya Health Information System and different time-series approaches to model the unintended consequences of COVID-19 mitigation measures on sexual violence trends in Kenya. We found a model-dependent 73%-122% increase in reported sexual violence cases, mostly among persons 10-17 years of age, translating to 35,688 excess sexual violence cases above what would have been expected in the absence of COVID-19-related restrictions.

Evaluation of myCOPD Digital Self-management Technology in a Remote and Rural Population: Real-world Feasibility Study.

Background: Chronic obstructive pulmonary disease (COPD) is a common, costly, and incurable respiratory disease affecting 1.2 million people in the United Kingdom alone. Acute COPD exacerbations requiring hospitalization place significant demands on health services, and the incidence of COPD in poor, remote, and rural populations is up to twice that of cities.

COVID-19 and the multidisciplinary care of patients with lung cancer: an evidence-based review and commentary.

Delivering lung cancer care during the COVID-19 pandemic has posed significant and ongoing challenges. There is a lack of published COVID-19 and lung cancer evidence-based reviews, including for the whole patient pathway. We searched for COVID-19 and lung cancer publications and brought together a multidisciplinary group of stakeholders to review and comment on the evidence and challenges.

Rumor surveillance in support of minimally invasive tissue sampling for diagnosing the cause of child death in low-income countries: A qualitative study.

In low-and middle-income countries, determining the cause of death of any given individual is impaired by poor access to healthcare systems, resource-poor diagnostic facilities, and limited acceptance of complete diagnostic autopsies. Minimally invasive tissue sampling (MITS), an innovative post-mortem procedure based on obtaining tissue specimens using fine needle biopsies suitable for laboratory analysis, is an acceptable proxy of the complete diagnostic autopsy, and thus could reduce the uncertainty of cause of death. This study describes rumor surveillance activities developed and implemented in Bangladesh, Mali, and Mozambique to identify, track and understand rumors about the MITS procedure.

Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with Zr-oxine PET-CT.

Background: MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution.

Retrospective response analysis of BAP1 expression to predict the clinical activity of systemic cytotoxic chemotherapy in mesothelioma.

Introduction BRCA1 associated protein-1 (BAP1) is a key tumor driver in mesothelioma and a potential biomarker predicting response to several targeted therapies in clinical testing. Whether it also modulates response to cytotoxic chemotherapy is undetermined. This study used retrospective response analysis of BAP1 expression in archival tumor biopsies taken from patients in the MS01 trial (NCT00075699).

Genetically modified mesenchymal stromal cells in cancer therapy.

The cell therapy industry has grown rapidly over the past 3 decades, and multiple clinical trials have been performed to date covering a wide range of diseases. The most frequently used cell is mesenchymal stromal cells (MSCs), which have been used largely for their anti-inflammatory actions and in situations of tissue repair and although they have demonstrated a good safety profile, their therapeutic efficacy has been limited. In addition to these characteristics MSCs are being used for their homing and engraftment properties and have been genetically modified to enable targeted delivery of a variety of therapeutic agents in both malignant and nonmalignant conditions.

Cryopreservation of human mesenchymal stromal cells expressing TRAIL for human anti-cancer therapy.

Background Aims: Mesenchymal stromal cells (MSCs) are being extensively researched for cell therapy and tissue engineering. We have engineered MSCs to express the pro-apoptotic protein tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and are currently preparing this genetically modified cell therapy for a phase 1/2a clinical trial in patients with metastatic lung cancer. To do this, we need to prepare a cryopreserved allogeneic MSCTRAIL cell bank for further expansion before patient delivery.

CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity.

Although squamous cell carcinomas (SqCCs) of the lungs, head and neck, oesophagus, and cervix account for up to 30% of cancer deaths, the mechanisms that regulate disease progression remain incompletely understood. Here, we use gene transduction and human tumor xenograft assays to establish that the tumour suppressor Cell adhesion molecule 1 (CADM1) inhibits SqCC proliferation and invasion, processes fundamental to disease progression. We determine that the extracellular domain of CADM1 mediates these effects by forming a complex with HER2 and integrin α6β4 at the cell surface that disrupts downstream STAT3 activity.

Mesenchymal stromal cell delivery of full-length tumor necrosis factor-related apoptosis-inducing ligand is superior to soluble type for cancer therapy.

Background Aims: Mesenchymal stromal cell (MSC) delivery of pro-apoptotic tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an attractive strategy for anticancer therapy. MSCs expressing full-length human TRAIL (flT) or its soluble form (sT) have previously been shown to be effective for cancer killing. However, a comparison between the two forms has never been performed, leaving it unclear which approach is most effective.

Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma.

Malignant pleural mesothelioma is a rare but devastating cancer of the pleural lining with no effective treatment. The tumour is often diffusely spread throughout the chest cavity, making surgical resection difficult, while systemic chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate into tumour stroma, making them good candidates to deliver anticancer therapies.

Primed infusion with delayed equilibrium of Gd.DTPA for enhanced imaging of small pulmonary metastases.

Objectives: To use primed infusions of the magnetic resonance imaging (MRI) contrast agent Gd.DTPA (Magnevist), to achieve an equilibrium between blood and tissue (eqMRI). This may increase tumor Gd concentrations as a novel cancer imaging methodology for the enhancement of small tumor nodules within the low signal-to-noise background of the lung.

Stem Cell Implants for Cancer Therapy: TRAIL-Expressing Mesenchymal Stem Cells Target Cancer Cells In Situ.

Purpose: Tumor-specific delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), an apoptosis-inducing peptide, at effective doses remains challenging. Herein we demonstrate the utility of a scaffold-based delivery system for sustained therapeutic cell release that capitalizes on the tumor-homing properties of mesenchymal stem cells (MSCs) and their ability to express genetically-introduced therapeutic genes.

Methods: Implants were formed from porous, biocompatible silk scaffolds seeded with full length TRAIL-expressing MSCs (FLT-MSCs).

β-Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial-mesenchymal transition.

Human lung cancers, including squamous cell carcinoma (SCC) are a leading cause of death and, whilst evidence suggests that basal stem cells drive SCC initiation and progression, the mechanisms regulating these processes remain unknown. In this study we show that β-catenin signalling regulates basal progenitor cell fate and subsequent SCC progression. In a cohort of preinvasive SCCs we established that elevated basal cell β-catenin signalling is positively associated with increased disease severity, epithelial proliferation and reduced intercellular adhesiveness.

Mesenchymal stem cells as vectors for lung disease.

Stem cells divide asymmetrically, leading to self-renewal and the production of a daughter cell committed to differentiation. This property has engendered excitement as to the use of these cells for treatments. The majority of the work with stem cells has used the relatively accessible and well-characterized adult bone marrow stem cell compartment.

Circadian orchestration of the hepatic proteome.

Circadian rhythms are essential to health. Their disruption is associated with metabolic diseases in experimental animals and man. Local metabolic rhythms represent an output of tissue-based circadian clocks.

Optimising ovine cerebrospinal fluid preparation for two-dimensional gel electrophoresis.

Biomarkers for neurodegenerative disorders are potentially present in cerebrospinal fluid (CSF) and can be detected using proteomic technologies. Since CSF is high in salt and low in protein, its study by proteomic methods requires appropriate sample preparation. In this study, we applied four different sample treatments to the same ovine CSF sample.