Overcoming Lot-to-Lot Variability in Protein Activity Using Epitope-Specific Calibration-Free Concentration Analysis.

Concentration determination is a fundamental hallmark of protein reagent characterization, providing a means to ensure reproducibility and unify measurements from various assays. However, lot-to-lot differences in protein activity often still occur, leading to uncertainty in the accuracy of downstream measurements. Here, we postulate that those differences are caused by a misrepresentation of the protein concentration as measured by traditional total protein techniques, which can include multiple types of inactive protein species.

Separation and Characterization of Plastic Waste Packaging Contaminated with Food Residues.

In this paper, we present the development of a novel processing technology to tackle hard-to-recycle plastic packaging waste contaminated with food residues. The proof-of-concept (POC) technology can effectively separate food residual amounts from plastic waste materials to a level acceptable for further re-use or recycling of the plastic packaging. To assess this technology, we have conducted spectroscopic, thermal, and calorimetric characterizations of the obtained fractions, such as cleaned mixed plastics (CMP), food waste with mixed plastics (FWMP), and a mixture of microplastics (MP).

COVID-VU - ENT-UK national survey of flexible nasendoscopy in the upper aerodigestive tract amidst the COVID-19 pandemic.

Background: Flexible nasendoscopy (FNE) is an invaluable multi-disciplinary tool for upper aerodigestive tract (UADT) examination. During the COVID-19 pandemic concerns were raised that FNE had the potential of generating aerosols resulting in human cross-contamination when performed on SARS-COV2 carriers. In the UK, and other European countries, national guidelines were issued restricting FNE to essential cases.

Seroprevalence of SARS-CoV-2 Antibodies in Children and Adults in St. Louis, Missouri, USA.

Reported coronavirus disease 2019 (COVID-19) case counts likely underestimate the true prevalence because mild or asymptomatic cases often go untested. Here, we use a sero-survey to estimate the seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the St. Louis, MO, metropolitan area in a symptom-independent manner.

A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2.

The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge.

Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2.

Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections and hundreds of thousands of deaths. Accordingly, an effective vaccine is of critical importance in mitigating coronavirus induced disease 2019 (COVID-19) and curtailing the pandemic. We developed a replication-competent vesicular stomatitis virus (VSV)-based vaccine by introducing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2).

Molluscum contagiosum virus MC80 sabotages MHC-I antigen presentation by targeting tapasin for ER-associated degradation.

The human specific poxvirus molluscum contagiosum virus (MCV) produces skin lesions that can persist with minimal inflammation, suggesting that the virus has developed robust immune evasion strategies. However, investigations into the underlying mechanisms of MCV pathogenesis have been hindered by the lack of a model system to propagate the virus. Herein we demonstrate that MCV-encoded MC80 can disrupt MHC-I antigen presentation in human and mouse cells.

Viral MHCI inhibition evades tissue-resident memory T cell formation and responses.

Tissue-resident memory CD8 T cells (Ts) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8 T cells, suggesting that these mechanisms may also apply to T-mediated protection. However, the effects of viral MHCI inhibition on the function and generation of Ts is unclear.

3-Dimensional fasciectomy: A highly efficacious common ground approach to Dupuytren's surgery.

Background: Numerous Dupuytren's fasciectomy techniques have been described, each associated with unique surgical challenges, complications and recurrence rates. We describe a common ground surgical approach to Dupuytren's disease; 3-dimensional fasciectomy (3DF). 3DF aims to address the potential contributors to the high recurrence rate of Dupuytren's disease and unite current limited fasciectomy practice that varies considerably between surgeons.

Management of Patients With High Baseline Hip Fracture Risk by FRAX Reduces Hip Fractures-A Post Hoc Analysis of the SCOOP Study.

The Screening for Osteoporosis in Older Women for the Prevention of Fracture (SCOOP) study was a community-based screening intervention in women aged 70 to 85 years in the United Kingdom. In the screening arm, licensed osteoporosis treatments were recommended in women identified to be at high risk of hip fracture using the FRAX risk assessment tool (including bone mineral density measurement). In the control arm, standard care was provided.

Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial.

Background: Despite effective assessment methods and medications targeting osteoporosis and related fractures, screening for fracture risk is not currently advocated in the UK. We tested whether a community-based screening intervention could reduce fractures in older women.

Methods: We did a two-arm randomised controlled trial in women aged 70-85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management.

Quantification of Lipid Filtration and the Effects on Cerebral Injury During Cardiopulmonary Bypass.

Background: Lipid microemboli (LME) are formed in pericardial suction blood which, when returned to the cardiopulmonary bypass (CPB) circuit, can pass through filter materials and are returned to the arterial cannula. LME have been observed to enter all major organs and have been associated with small capillary arteriolar dilatations in the brains of patients who have died after CPB. However, a causal relationship showing correlation between LME and organ dysfunction has not been demonstrated, or whether removal of LME results in improved organ function.

A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion.

The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the genus of the human subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology, because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified.

Does home oxygen therapy (HOT) in addition to standard care reduce disease severity and improve symptoms in people with chronic heart failure? A randomised trial of home oxygen therapy for patients with chronic heart failure.

Background: Home oxygen therapy (HOT) is commonly used for patients with severe chronic heart failure (CHF) who have intractable breathlessness. There is no trial evidence to support its use.

Objectives: To detect whether or not there was a quality-of-life benefit from HOT given as long-term oxygen therapy (LTOT) for at least 15 hours per day in the home, including overnight hours, compared with best medical therapy (BMT) in patients with severely symptomatic CHF.

Specifying the target difference in the primary outcome for a randomised controlled trial: guidance for researchers.

Background: Central to the design of a randomised controlled trial is the calculation of the number of participants needed. This is typically achieved by specifying a target difference and calculating the corresponding sample size, which provides reassurance that the trial will have the required statistical power (at the planned statistical significance level) to identify whether a difference of a particular magnitude exists. Beyond pure statistical or scientific concerns, it is ethically imperative that an appropriate number of participants should be recruited.

An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions.

During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes.

Reversing paclitaxel resistance in ovarian cancer cells via inhibition of the ABCB1 expressing side population.

The majority of deaths in ovarian cancer are caused by recurrent metastatic disease which is usually multidrug resistant. This progression has been hypothesised to be due in part to the presence of cancer stem cells, a subset of cells which are capable of self-renewal and are able to survive chemotherapy and migrate to distant sites. Side population (SP) cells, identified by the efflux of the DNA-binding dye Hoechst 33342 through ATP-binding cassette (ABC) transporters, are a known adult stem cell group and have been suggested as a cancer stem cell in various cancers.

Methods for specifying the target difference in a randomised controlled trial: the Difference ELicitation in TriAls (DELTA) systematic review.

Background: Randomised controlled trials (RCTs) are widely accepted as the preferred study design for evaluating healthcare interventions. When the sample size is determined, a (target) difference is typically specified that the RCT is designed to detect. This provides reassurance that the study will be informative, i.

Assessing methods to specify the target difference for a randomised controlled trial: DELTA (Difference ELicitation in TriAls) review.

Background: The randomised controlled trial (RCT) is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to the design and validity of a RCT is a calculation of the number of participants needed (the sample size). The value used to determine the sample size can be considered the 'target difference'.

Design of monodisperse and well-defined polypeptide-based polyvalent inhibitors of anthrax toxin.

The design of polyvalent molecules, presenting multiple copies of a specific ligand, represents a promising strategy to inhibit pathogens and toxins. The ability to control independently the valency and the spacing between ligands would be valuable for elucidating structure-activity relationships and for designing potent polyvalent molecules. To that end, we designed monodisperse polypeptide-based polyvalent inhibitors of anthrax toxin in which multiple copies of an inhibitory toxin-binding peptide were separated by flexible peptide linkers.

Use of methods for specifying the target difference in randomised controlled trial sample size calculations: Two surveys of trialists' practice.

Background: Central to the design of a randomised controlled trial (RCT) is a calculation of the number of participants needed. This is typically achieved by specifying a target difference, which enables the trial to identify a difference of a particular magnitude should one exist. Seven methods have been proposed for formally determining what the target difference should be.

Characterisation of human limbal side population cells isolated using an optimised protocol from an immortalised epithelial cell line and primary limbal cultures.

The challenges in limbal stem cell biology largely remain in the process of identification, isolation and expansion of these adult corneal epithelial stem cells of the eye. Due to the absence of specific limbal stem cell markers, identification and isolation of putative limbal stem cells is a complicated task. The side population assay is an isolation method that utilises the ability of stem cells to efflux the DNA-binding dye Hoechst 33342 (or other vital dyes) combined with dual wavelength flow cytometry and is a valuable strategy to enrich for limbal stem cells.

Inefficient exercise gas exchange identifies pulmonary hypertension in chronic thromboembolic obstruction following pulmonary embolism.

Introduction: Persistent obstruction in the pulmonary artery following acute pulmonary embolism (PE) can give rise to both chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease without PH (CTED). We hypothesised that cardiopulmonary exercise testing (CPET) may be able to differentiate patients with CTEPH and CTED following unresolved PE which may help guide patient assessment.

Materials And Methods: Fifteen patients with CTEPH and 15 with CTED all diagnosed after PE underwent CT pulmonary angiography, CPET and resting right heart catheterisation.