Design of a Golden Gate Cloning Plasmid for the Generation of a Chimeric Virus-Like Particle-Based Subunit Vaccine Against Porcine Circovirus Type 2.

Porcine circovirus type 2 (PCV2) is a pervasive pathogen in the swine industry, leading to a spectrum of disorders known as porcine circovirus associated diseases (PCVAD). The PCV2 Cap protein contains critical antigenic epitopes and is the primary target for vaccine development. Current vaccines include inactivated viral particles and virus-like particles (VLPs), with experimental vaccines exploring various innovative approaches.

Minimally invasive techniques for the management of benign thyroid nodules: Efficacy and impact on quality of life of percutaneous ethanol injection. Results from a high-resolution thyroid nodule unit.

Background And Objective: The high incidence of thyroid nodular disease has raised concerns on the therapeutic management of benign thyroid nodules. The development of minimally invasive techniques is an alternative to surgery and has a low rate of complications. Our objective was to evaluate the safety and efficacy profile of percutaneous ethanol injections (PEI) with ethanol aspiration of symptomatic cystic and predominantly cystic thyroid nodules (cystic component > 50%) treated in the thyroid nodule high-resolution unit (TNHRU) of Hospital de Tortosa Verge de la Cinta Hospital, Tarragona, Spain.

Role of Immunotherapy in Conjunction With the Surgical Treatment of Breast Cancer: Preoperative and Postoperative Applications.

Breast cancer is one of the most common cancers in the world. Since the appearance of molecular medicine, the perspective of breast cancer treatment has changed, making it more successful in comparison with the treatment during previous years. Numerous ongoing trials are exploring the capacity of immunotherapy, mainly in immune checkpoint inhibitors (ICIs), in conjunction with conventional therapies or with antibody-drug conjugates (ADCs).

Functional structure of a high resolution thyroid nodule unit. Economic impact and results of its implementation in an Endocrinology department.

Background And Objective: The high incidence of nodular thyroid pathology has led to growing concern about the economic impact that this pathology represents on the healthcare system. There are conclusive data about the cost-effectiveness of high-resolution units for nodular thyroid pathology; however, their implementation is not homogeneous in the Endocrinology and Nutrition services of our country. The objective of the present study was to evaluate the economic impact of the implementation of the high-resolution thyroid nodule unit (HRTNU) in our center.

Widespread human exposure to ledanteviruses in Uganda: A population study.

Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas.

Conditioned Cooperative training for semi-supervised weapon detection.

Violent assaults and homicides occur daily, and the number of victims of mass shootings increases every year. However, this number can be reduced with the help of Closed Circuit Television (CCTV) and weapon detection models, as generic object detectors have become increasingly accurate with more data for training. We present a new semi-supervised learning methodology based on conditioned cooperative student-teacher training with optimal pseudo-label generation using a novel confidence threshold search method and improving both models by conditional knowledge transfer.

CrimeNet: Neural Structured Learning using Vision Transformer for violence detection.

The state of the art in violence detection in videos has improved in recent years thanks to deep learning models, but it is still below 90% of average precision in the most complex datasets, which may pose a problem of frequent false alarms in video surveillance environments and may cause security guards to disable the artificial intelligence system. In this study, we propose a new neural network based on Vision Transformer (ViT) and Neural Structured Learning (NSL) with adversarial training. This network, called CrimeNet, outperforms previous works by a large margin and reduces practically to zero the false positives.

Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa.

The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 and 488 HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections.

Infection with HIV-1 subtype D among acutely infected Ugandans is associated with higher median concentration of cytokines compared to subtype A.

Objective: The observation that HIV-1 subtype D progresses faster to disease than subtype A prompted us to examine cytokine levels early after infection within the predominant viral subtypes that circulate in Uganda and address the following research questions: (1) Do cytokine levels vary between subtypes A1 and D? (2) Do cytokine profiles correlate with disease outcomes?

Methods: To address these questions, HIV-1 subtypes were determined by population sequencing of the HIV-1 gene and 37 plasma cytokine concentrations were evaluated using V-Plex kits on Meso Scale Discovery platform in 65 recent sero-converters.

Results: HIV-1 subtype D () infections exhibited significantly higher median plasma concentrations of IL-5, IL-16, IL-1α, IL-7, IL-17A, CCL11 (Eotaxin-1), CXCL10 (IP-10), CCL13 (MCP-4) and VEGF-D compared to subtype A1 () infections. We also found that IL-12/23p40 and IL-1α were associated with faster CD4T cell count decline, while bFGF was associated with maintenance of CD4+ counts above 350 cells/microliter.

Characterization of Near Full-Length Transmitted/Founder HIV-1 Subtype D and A/D Recombinant Genomes in a Heterosexual Ugandan Population (2006-2011).

Detailed characterization of transmitted HIV-1 variants in Uganda is fundamentally important to inform vaccine design, yet studies on the transmitted full-length strains of subtype D viruses are limited. Here, we amplified single genomes and characterized viruses, some of which were previously classified as subtype D by sub-genomic pol sequencing that were transmitted in Uganda between December 2006 to June 2011. Analysis of 5' and 3' half genome sequences showed 73% (19/26) of infections involved single virus transmissions, whereas 27% (7/26) of infections involved multiple variant transmissions based on predictions of a model of random virus evolution.

Acute Kidney Injury and Organ Dysfunction: What Is the Role of Uremic Toxins?

Acute kidney injury (AKI), defined as an abrupt increase in serum creatinine, a reduced urinary output, or both, is experiencing considerable evolution in terms of our understanding of the pathophysiological mechanisms and its impact on other organs. Oxidative stress and reactive oxygen species (ROS) are main contributors to organ dysfunction in AKI, but they are not alone. The precise mechanisms behind multi-organ dysfunction are not yet fully accounted for.

HIV-1 Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity.

The ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and the assembly of new virions may also play a role in establishing and spreading viral infection in a new host. We examined Ugandan viruses from newly infected patients and focused on the contribution of the genes to replication capacity.

Real-time gun detection in CCTV: An open problem.

Object detectors have improved in recent years, obtaining better results and faster inference time. However, small object detection is still a problem that has not yet a definitive solution. The autonomous weapons detection on Closed-circuit television (CCTV) has been studied recently, being extremely useful in the field of security, counter-terrorism, and risk mitigation.

Prevalence of viral load suppression, predictors of virological failure and patterns of HIV drug resistance after 12 and 48 months on first-line antiretroviral therapy: a national cross-sectional survey in Uganda.

Objectives: We implemented the WHO cross-sectional survey protocol to determine rates of HIV viral load (VL) suppression (VLS), and weighted prevalence, predictors and patterns of acquired drug resistance (ADR) in individuals with virological failure (VF) defined as VL ≥1000 copies/mL.

Methods: We enrolled 547 and 1064 adult participants on first-line ART for 12 (±3) months (ADR12) and ≥48 months (ADR48), respectively. Dried blood spots and plasma specimens were collected for VL testing and genotyping among the VFs.

Expression of Breast Cancer-Related Epitopes Targeting the IGF-1 Receptor in Chimeric Human Parvovirus B19 Virus-Like Particles.

Breast cancer is a worldwide health problem, and the complexity of the disease, as well as the lack of treatment specificity, generates an urgent need for developing prophylactic and therapeutic measures. Searching for novel epitope-based approaches able to induce tumour immunity, we designed virus-like particles (VLPs) derived from Human parvovirus B19 assembled of chimeric VP2 proteins displaying two epitopes from the insulin-like growth factor-1 receptor (IGF-1R). Here, we present the generation of two chimeric VP2s that retain the stability, solubility and conditions of purification and assembly of the native VP2.

Phylogeography of HIV-1 suggests that Ugandan fishing communities are a sink for, not a source of, virus from general populations.

Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to the general population (GP), the transmission dynamics are not completely understood. We earlier found most HIV-1 transmissions to occur within FCs of Lake Victoria. Here, we test the hypothesis that HIV-1 transmission in FCs is isolated from networks in the GP.

Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection.

Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 genome sequences from longitudinal samples. Recombinant genomes rapidly replace transmitted/founder (T/F) lineages, with a median half-time of 27 days, increasing the genetic complexity of the viral population.

Assessment of Carrot Callus as Biofactories of an Atherosclerosis Oral Vaccine Prototype.

Atherosclerosis is a pathology leading to cardiovascular diseases with high epidemiologic impact; thus, new therapies are required to fight this global health issue. Immunotherapy is a feasible approach to treat atherosclerosis and given that genetically engineered plants are attractive hosts for vaccine development; we previously proved that the plant cell is able to synthesize a chimeric protein called CTB:p210:CETPe, which is composed of the cholera toxin B subunit (CTB) as immunogenic carrier and target epitopes from the cholesteryl ester transfer protein (CETP) and apolipoprotein B100 (p210). Since CTB:p210:CETPe was expressed in tobacco at sufficient levels to evoke humoral responses in mice, its expression in carrot was explored in the present study looking to develop a vaccine in a safe host amenable for oral delivery; avoiding the purification requirement.

Do microRNAs play a role in the activity of plant-based vaccines?

An important trend in vaccinology is the development of oral vaccines based on genetically modified plants. Areas covered: Several studies have suggested that dietary microRNAs from plants and other organisms are bioavailable upon oral ingestion exerting biological events in the host such as the modulation of gene expression in several cell types. Since oral plant-based vaccines rely on whole cells as vaccine delivery vehicles, miRNAs could play a role in the immunogenic activity of this type of vaccine.

Expression of the VP40 antigen from the Zaire ebolavirus in tobacco plants.

The plant cell is able to produce the VP40 antigen from the Zaire ebolavirus , retaining the antigenicity and the ability to induce immune responses in BALB/c mice. The recent Ebola outbreak evidenced the need for having vaccines approved for human use. Herein we report the expression of the VP40 antigen from the Ebola virus as an initial effort in the development of a plant-made vaccine that could offer the advantages of being cheap and scalable, which is proposed to overcome the rapid need for having vaccines to deal with future outbreaks.

Use of Dried Blood Spots to Elucidate Full-Length Transmitted/Founder HIV-1 Genomes.

Background: Identification of HIV-1 genomes responsible for establishing clinical infection in newly infected individuals is fundamental to prevention and pathogenesis research. Processing, storage, and transportation of the clinical samples required to perform these virologic assays in resource-limited settings requires challenging venipuncture and cold chain logistics. Here, we validate the use of dried-blood spots (DBS) as a simple and convenient alternative to collecting and storing frozen plasma.

Progress and future opportunities in the development of vaccines against atherosclerosis.

Atherosclerosis represents a serious global health problem that demands new therapeutic and prophylactic interventions. Considering that atherosclerosis has autoimmune and inflammatory components, immunotherapy is a possible focus to treat this disease. Areas covered: Based on the analysis of the current biomedical literature, this review describes the status on the development of vaccines against atherosclerosis.

HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection.

Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, most of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T cell cross-reactivity in patients with acute HIV-1 clade B infection.