A robust deep learning workflow to predict CD8 + T-cell epitopes.

Background: T-cells play a crucial role in the adaptive immune system by triggering responses against cancer cells and pathogens, while maintaining tolerance against self-antigens, which has sparked interest in the development of various T-cell-focused immunotherapies. However, the identification of antigens recognised by T-cells is low-throughput and laborious. To overcome some of these limitations, computational methods for predicting CD8 + T-cell epitopes have emerged.

A systems approach evaluating the impact of SARS-CoV-2 variant of concern mutations on CD8+ T cell responses.

T cell recognition of SARS-CoV-2 antigens after vaccination and/or natural infection has played a central role in resolving SARS-CoV-2 infections and generating adaptive immune memory. However, the clinical impact of SARS-CoV-2-specific T cell responses is variable and the mechanisms underlying T cell interaction with target antigens are not fully understood. This is especially true given the virus' rapid evolution, which leads to new variants with immune escape capacity.

Evaluating performance of existing computational models in predicting CD8+ T cell pathogenic epitopes and cancer neoantigens.

T cell recognition of a cognate peptide-major histocompatibility complex (pMHC) presented on the surface of infected or malignant cells is of the utmost importance for mediating robust and long-term immune responses. Accurate predictions of cognate pMHC targets for T cell receptors would greatly facilitate identification of vaccine targets for both pathogenic diseases and personalized cancer immunotherapies. Predicting immunogenic peptides therefore has been at the center of intensive research for the past decades but has proven challenging.

HLA-dependent variation in SARS-CoV-2 CD8 T cell cross-reactivity with human coronaviruses.

The conditions and extent of cross-protective immunity between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and common-cold human coronaviruses (HCoVs) remain open despite several reports of pre-existing T cell immunity to SARS-CoV-2 in individuals without prior exposure. Using a pool of functionally evaluated SARS-CoV-2 peptides, we report a map of 126 immunogenic peptides with high similarity to 285 MHC-presented peptides from at least one HCoV. Employing this map of SARS-CoV-2-non-homologous and homologous immunogenic peptides, we observe several immunogenic peptides with high similarity to human proteins, some of which have been reported to have elevated expression in severe COVID-19 patients.

Potential CD8+ T Cell Cross-Reactivity Against SARS-CoV-2 Conferred by Other Coronavirus Strains.

While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory to related pathogens cross-reactive against SARS-CoV-2 can influence the disease outcome in COVID-19. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated an map of public and private CD8+ T cell epitopes between coronaviruses. We observed 794 predicted SARS-CoV-2 epitopes of which 52% were private and 48% were public.

Communicating marine climate change impacts in the Caribbean and Pacific regions.

The scientific literature on marine and coastal climate change has proliferated in recent decades. Translating and communicating this evidence in a timely, and accessible manner, is critical to support adaptation, but little is being done to summarise the latest science for decision makers. For Small Island Developing States (SIDS), which are highly vulnerable to marine and coastal climate change impacts, there is an urgent need to make the latest science readily available to inform national policy, leverage climate funding and highlight their vulnerability for international reports and climate negotiations.

Application of Modeling Approaches to Explore Vaccine Adjuvant Mode-of-Action.

Novel adjuvant technologies have a key role in the development of next-generation vaccines, due to their capacity to modulate the duration, strength and quality of the immune response. The AS01 adjuvant is used in the malaria vaccine RTS,S/AS01 and in the licensed herpes-zoster vaccine (Shingrix) where the vaccine has proven its ability to generate protective responses with both robust humoral and T-cell responses. For many years, animal models have provided insights into adjuvant mode-of-action (MoA), generally through investigating individual genes or proteins.

Magnetic sphincter augmentation: Optimal patient selection and referral care pathways.

Outcomes associated with magnetic sphincter augmentation (MSA) in patients with gastroesophageal reflux disease (GERD) have been reported, however the optimal population for MSA and the related patient care pathways have not been summarized. This Minireview presents evidence that describes the optimal patient population for MSA, delineates diagnostics to identify these patients, and outlines opportunities for improving GERD patient care pathways. Relevant publications from MEDLINE/EMBASE and guidelines were identified from 2000-2018.

Magnetic Sphincter Augmentation Superior to Proton Pump Inhibitors for Regurgitation in a 1-Year Randomized Trial.

Background & Aims: Regurgitative gastroesophageal reflux disease (GERD) refractive to medical treatment is common and caused by mechanical failure of the anti-reflux barrier. We compared the effects of magnetic sphincter augmentation (MSA) with those of proton-pump inhibitors (PPIs) in a randomized trial.

Methods: Patients with moderate to severe regurgitation (assessed by the foregut symptom questionnaire) despite once-daily PPI therapy (n = 152) were randomly assigned to groups given twice-daily PPIs (n = 102) or laparoscopic MSA (n = 50) at 20 sites, from July 2015 through February 2017.

Laparoscopic magnetic sphincter augmentation versus double-dose proton pump inhibitors for management of moderate-to-severe regurgitation in GERD: a randomized controlled trial.

Background And Aims: GERD patients frequently complain of regurgitation of gastric contents. Medical therapy with proton-pump inhibitors (PPIs) is frequently ineffective in alleviating regurgitation symptoms, because PPIs do nothing to restore a weak lower esophageal sphincter. Our aim was to compare effectiveness of increased PPI dosing with laparoscopic magnetic sphincter augmentation (MSA) in patients with moderate-to-severe regurgitation despite once-daily PPI therapy.

Characterization of Primary Organic Aerosol from Domestic Wood, Peat, and Coal Burning in Ireland.

An aerosol chemical speciation monitor (ACSM) was deployed to study the primary nonrefractory submicron particulate matter emissions from the burning of commercially available solid fuels (peat, coal, and wood) typically used in European domestic fuel stoves. Organic mass spectra (MS) from burning wood, peat, and coal were characterized and intercompared for factor analysis against ambient data. The reference profiles characterized in this study were used to estimate the contribution of solid fuel sources, along with oil combustion, to ambient pollution in Galway, Ireland using the multilinear engine (ME-2).

Outcomes of magnetic sphincter augmentation - A community hospital perspective.

Background: Magnetic sphincter augmentation (MSA) is FDA approved for the surgical treatment of GERD. While multiple reports from academic settings exist, we report the early experience from two community-based health systems.

Methods: The first 102 post-trial cases of MSA were reviewed.

Viscoelasticity of Tendons Under Transverse Compression.

Tendons are highly anisotropic and also viscoelastic. For understanding and modeling their 3D deformation, information is needed on their viscoelastic response under off-axis loading. A study was made, therefore, of creep and recovery of bovine digital extensor tendons when subjected to transverse compressive stress of up to ca.

An adhesive elastomeric supramolecular polyurethane healable at body temperature.

In this paper, we report the synthesis and healing ability of a non-cytotoxic supramolecular polyurethane network whose mechanical properties can be recovered efficiently (>99%) at the temperature of the human body (37 °C). Rheological analysis revealed an acceleration in the drop of the storage modulus above 37 °C, on account of the dissociation of the supramolecular polyurethane network, and this decrease in viscosity enables the efficient recovery of the mechanical properties. Microscopic and mechanical characterisation has shown that this material is able to recover mechanical properties across a damage site with minimal contact required between the interfaces and also demonstrated that the mechanical properties improved when compared to other low temperature healing elastomers or gel-like materials.

Transverse Compression of Tendons.

A study was made of the deformation of tendons when compressed transverse to the fiber-aligned axis. Bovine digital extensor tendons were compression tested between flat rigid plates. The methods included: in situ image-based measurement of tendon cross-sectional shapes, after preconditioning but immediately prior to testing; multiple constant-load creep/recovery tests applied to each tendon at increasing loads; and measurements of the resulting tendon displacements in both transverse directions.

Spontaneous chylous ascites, chylomediastinum and bilateral chylothoraces encountered during laparoscopic incarcerated paraesophageal hernia repair.

Chylous ascites is an accumulation of milky lipid-rich lymph in the peritoneal cavity. Spontaneous chyle leak is a rare occurrence, often associated with malignancy or cirrhosis. This is a report of spontaneous chylous ascites, chylomediastinum and chylothoraces encountered in the setting of an incarcerated paraesophageal hernia.

Single-site Nissen fundoplication versus laparoscopic Nissen fundoplication.

Background: Advances in minimally invasive surgery have led to the emergence of single-incision laparoscopic surgery (SILS). The purpose of this study is to assess the feasibility of SILS Nissen fundoplication and compare its outcomes with traditional laparoscopic Nissen fundoplication.

Methods: This is a retrospective study of 33 patients who underwent Nissen fundoplication between January 2009 and September 2010.

Public awareness, concerns, and priorities about anthropogenic impacts on marine environments.

Numerous international bodies have advocated the development of strategies to achieve the sustainability of marine environments. Typically, such strategies are based on information from expert groups about causes of degradation and policy options to address them, but these strategies rarely take into account assessed information about public awareness, concerns, and priorities. Here we report the results of a pan-European survey of public perceptions about marine environmental impacts as a way to inform the formation of science and policy priorities.

Single-incision laparoscopic Ladd's procedure for intestinal malrotation.

Introduction: The potential of single-incision laparoscopic surgery (SILS) as a less invasive and more cosmetically appealing technique has prompted the expansion of its adoption. SILS has been shown to be a safe and feasible alternative to traditional multiport cholecystectomy, appendectomy, colectomy, and many other laparoscopic procedures. The objective of this study is to provide an initial report of the feasibility of correcting intestinal malrotation via a single-incision laparoscopic transumbilical approach.

Single-incision laparoscopic appendectomy versus traditional three-port laparoscopic appendectomy: an analysis of outcomes at a single institution.

Background: Questions have emerged as to whether single-incision laparoscopy has reproducible or superior patient outcomes compared with traditional laparoscopy. A retrospective review comparing single-incision laparoscopic (SILS) appendectomy and traditional multiport laparoscopic (MP) appendectomy was conducted to assess the safety and feasibility of the less invasive laparoscopic technique.

Methods: All SILS and MP appendectomies performed by three surgeons at a single institution during 43 months were reviewed.

Comparison of outcomes for single-incision laparoscopic inguinal herniorrhaphy and traditional three-port laparoscopic herniorrhaphy at a single institution.

Background: Evidence in the literature regarding the potential of single-incision laparoscopic (SILS) inguinal herniorrhaphy currently is limited. A retrospective comparison of SILS and traditional multiport laparoscopic (MP) inguinal hernia repair was conducted to assess the safety and feasibility of the minimally invasive laparoscopic technique.

Methods: All laparoscopic inguinal hernia repairs performed by three surgeons at a single institution during 4 years were reviewed.

An automated algorithm for consolidating dates of diagnosis from multiple sources.

Background: Multiple dates of diagnosis are often received from different reporting sources at a central cancer registry. Resolving these inconsistencies can be a labor-intensive task. To our knowledge, no algorithms for the consolidation of diagnosis dates have been published.

Genetic basis of resistance to fall armyworm (Lepidoptera: Noctuidae) and southwestern corn borer (Lepidoptera: Crambidae) leaf-feeding damage in maize.

Leaf-feeding damage by first generation larvae of fall armyworm, Spodopter frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), and southwestern corn borer, Diatraea grandiosella Dyar (Lepidoptera: Crambidae), cause major economic losses each year in maize, Zea mays L.

The integrity of welded interfaces in ultra-high molecular weight polyethylene: Part 2--interface toughness.

In Part 2 of a study of welding of ultra-high molecular weight polyethylene (UHMWPE), experiments were conducted to measure the interfacial fracture energy of butt welds, for various welding times and temperatures above the melting point. Their toughness was investigated at 37 degrees C in terms of their fracture energy, obtained by adapting the essential work of fracture (EWF) method. However, a proportion of the welded samples (generally decreasing with increasing welding time or temperature) failed in dual ductile/brittle mode, hence invalidating the EWF test.

The integrity of welded interfaces in ultra high molecular weight polyethylene: Part 1-Model.

The difficulty of eradicating memory of powder-particle interfaces in UHMWPE for bearing surfaces for hip and knee replacements is well-known, and 'fusion defects' have been implicated frequently in joint failures. During processing the polymer is formed into solid directly from the reactor powder, under pressure and at temperatures above the melting point, and two types of inter-particle defect occur: Type 1 (consolidation-deficient) and Type 2 (diffusion-deficient). To gain quantitative information on the extent of the problem, the formation of macroscopic butt welds in this material was studied, by (1) modelling the process and (2) measuring experimentally the resultant evolution of interface toughness.