Current status of the development of dengue vaccines.

Dengue fever is caused by the mosquito-borne dengue virus (DENV), which is endemic in more than 100 countries. Annually, there are approximately 390 million dengue cases, with a small subset manifesting into severe illnesses, such as dengue haemorrhagic fever or dengue shock syndrome. Current treatment options for dengue infections remain supportive management due to the lack of an effective vaccine and clinically approved antiviral.

Identification and monitoring of cell heterogeneity from plasmid recombination during limonene production.

Detecting alterations in plasmid structures is often performed using conventional molecular biology. However, these methods are laborious and time-consuming for studying the conditions inducing these mutations, which prevent real-time access to cell heterogeneity during bioproduction. In this work, we propose combining both flow cytometry and fluorescence-activated cell sorting, integrated with mechanistic modelling to study conditions that lead to plasmid recombination using a limonene-producing microbial system as a case study.

Database of soil properties incorporating organic content from roots and soil organisms for regional slope stabilisation.

The effectiveness of using vegetation to reinforce slopes is influenced by the soil and vegetation characteristics. Hence, this study pioneers the construction of an extensive soil database using random forest machine learning and ordinary kriging methods, focusing on the influence of plant roots on the saturated and unsaturated properties of residual soils. Soil organic content, which includes contributions from both soil organisms and roots, functions as a key factor in estimating soil hydraulic and mechanical properties influenced by vegetation roots.

A phase 2 study of frontline pembrolizumab in follicular lymphoma.

Background: The tumor microenvironment (TME), including infiltrating T-cells, is thought to play a major role in the pathogenesis and prognosis of follicular lymphoma (FL) and may contribute to its widely varied disease course. We hypothesized that programmed death-1 inhibition may be most effective in untreated, immunocompetent FL patients. Thus, we developed a phase 2 study to evaluate the efficacy of pembrolizumab as the initial treatment for indolent B-cell lymphoma.

Clinical Relevance of Intensive Laboratory Monitoring With Standard Venetoclax Ramp-Up for Chronic Lymphocytic Leukemia: A Real-World Experience.

Purpose: Venetoclax is the standard of care for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) but requires intensive monitoring for optimal safety. Clinical relevance of intensive monitoring in practice is unknown, especially for patients with low or intermediate risk for tumor lysis syndrome (TLS).

Patients And Methods: A retrospective review was conducted to determine clinical significance of monitoring for TLS during standard ramp-up for patients with CLL/SLL.

Genotypic analysis of Shiga toxin-producing clonal complex 17 in England and Wales, 2014-2022.

Shiga toxin-producing (STEC) are zoonotic, gastrointestinal pathogens characterized by the presence of the Shiga toxin () gene. Historically, STEC O157:H7 clonal complex (CC) 11 has been the most clinically significant serotype; however, recently there has been an increase in non-O157 STEC serotypes, including STEC O103:H2 belonging to CC17. STEC O103:H2 is an STEC serotype frequently isolated in England, although little is known about the epidemiology, clinical significance, associated public health burden or evolutionary context of this strain.

Optimizing HMG-CoA Synthase Expression for Enhanced Limonene Production in through Temporal Transcription Modulation Using Optogenetics.

Overexpression of a single enzyme in a multigene heterologous pathway may be out of balance with the other enzymes in the pathway, leading to accumulated toxic intermediates, imbalanced carbon flux, reduced productivity of the pathway, or an inhibited growth phenotype. Therefore, optimal, balanced, and synchronized expression levels of enzymes in a particular metabolic pathway is critical to maximize production of desired compounds while maintaining cell fitness in a growing culture. Furthermore, the optimal intracellular concentration of an enzyme is determined by the expression strength, specific timing/duration, and degradation rate of the enzyme.

π-π Interactions Drive the Homotypic Phase Separation of the Prion-like Diatom Pyrenoid Scaffold PYCO1.

CO fixation in most unicellular algae relies on the pyrenoid, a biomolecular condensate, which sequesters the cell's carboxylase Rubisco. In the marine diatom Phaeodactylum tricornutum, the pyrenoid tandem repeat protein Pyrenoid Component 1 (PYCO1) multivalently binds Rubisco to form a heterotypic Rubisco condensate. PYCO1 contains prion-like domains and can phase-separate homotypically in a salt-dependent manner.

Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery.

Most (60%-80%) of the oral cavity invasive squamous cell carcinoma (OSCC) demonstrate molecular alterations in TP53. The presence of TP53 mutations in multiple organ systems has been associated with a more aggressive clinical course. This study aimed to classify OSCC into p53 wild-type OSCC and p53-abnormal OSCC using p53 immunohistochemistry and to determine if abnormal p53 status correlates with a higher risk of lymph node metastasis at the time of surgery.

p53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence-A Retrospective Study in a Longitudinal Cohort.

Grading of oral epithelial dysplasia (OED) can be challenging with considerable intraobserver and interobserver variability. Abnormal immunohistochemical staining patterns of the tumor suppressor protein, p53, have been recently shown to be potentially associated with progression in OED. We retrospectively identified 214 oral biopsies from 203 patients recruited in a longitudinal study between 2001 and 2008 with a diagnosis of reactive, nondysplastic lesions, low-grade lesions (mild OED and moderate OED) and high-grade lesions (HGLs; severe OED/carcinoma in situ).

ASTCT and USCLC Clinical Practice Recommendations for Allogeneic Stem Cell Transplant in Mycosis Fungoides and Sézary Syndrome.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach.

Does a subset of mature T-cell leukemias with features akin to T-cell prolymphocytic leukemia but lacking rearrangement of the represent peripheral T-cell lymphoma, NOS in a leukemic phase?

In the current WHO classification, a T-cell prolymphocytic leukemia (T-PLL) diagnosis requires lymphocytosis of >5 × 109/L, evidence of monoclonality, and or rearrangement. However, the 2019 consensus document suggested that in the absence of rearrangement of -family, the presence of abnormalities involving chromosome 11 (11q22.3; ATM), chromosome 8 (idic(8)(p11), t(8;8), trisomy 8q), 5, 12, 13, 22, or a complex karyotype, as well as involvement specific sites (e.

Immunogenicity of trivalent DNA vaccine candidate encapsulated in Chitosan-TPP nanoparticles against EV-A71 and CV-A16.

To develop a trivalent DNA vaccine candidate encapsulated in Chitosan-TPP nanoparticles against hand foot and mouth disease (HFMD) and assess its immunogenicity in mice. Trivalent plasmid carrying the VP1 and VP2 genes of EV-A71, VP1 gene of CV-A16 was encapsulated in Chitosan-TPP nanoparticles through ionic gelation. characterization and immunization studies of the CS-TPP-NPs (pIRES-VP121) were performed.

The Development of Epitope-Based Recombinant Protein Vaccines against SARS-CoV-2.

The COVID-19 pandemic continues to cause infections and deaths, which are attributable to the SARS-CoV-2 Omicron variant of concern (VOC). Moderna's response to the declining protective efficacies of current SARS-CoV-2 vaccines against Omicron was to develop a bivalent booster vaccine based on the Spike (S) protein from the Wuhan and Omicron BA.4/BA.

Imaging Biomarkers of Oral Dysplasia and Carcinoma Measured with In Vivo Endoscopic Optical Coherence Tomography.

Optical coherence tomography is a noninvasive imaging technique that provides three-dimensional visualization of subsurface tissue structures. OCT has been proposed and explored in the literature as a tool to assess oral cancer status, select biopsy sites, or identify surgical margins. Our endoscopic OCT device can generate widefield (centimeters long) imaging of lesions at any location in the oral cavity-but it is challenging for raters to quantitatively assess and score large volumes of data.

Identification and Validation of Peptides Specifying SARS-CoV-2 B-Cell Epitopes Eliciting Neutralizing Antibodies.

Vaccination is an effective means of inducing immune protection to prevent transmissible diseases. During the Covid-19 pandemic, immunizations using traditional and novel vaccine platforms such as the inactivated SARSCo-V-2 vaccine, adenoviral-vectored, and nucleic acid-based mRNA vaccines have been relatively successful in controlling the rates of infection and hospitalizations. Nevertheless, the danger posed by the emergence of SARS-CoV-2 variants would set the stage for the design of next generation vaccines.

Three-Dimension Epithelial Segmentation in Optical Coherence Tomography of the Oral Cavity Using Deep Learning.

This paper aims to simplify the application of optical coherence tomography (OCT) for the examination of subsurface morphology in the oral cavity and reduce barriers towards the adoption of OCT as a biopsy guidance device. The aim of this work was to develop automated software tools for the simplified analysis of the large volume of data collected during OCT. Imaging and corresponding histopathology were acquired in-clinic using a wide-field endoscopic OCT system.

Oral cancer detection and progression prediction using noninvasive cytology-based DNA ploidy approach.

Background: Despite the oral cavity being readily accessible, oral cancer (OC) remains a significant burden. The objective of this study is to develop a DNA ploidy-based cytology test for early detection of high-risk oral lesions.

Methods: This retrospective study was conducted using 569 oral brushing samples collected from 95 normal and 474 clinically abnormal mucosa with biopsy diagnosis of reactive, low-grade or high-grade precancer or cancers.

Adenovirus-mediated expression of MOAP-1, Bax and RASSF1A antagonizes chemo-drug resistance of human breast cancer cells expressing cancer stem cell markers.

Cancer is one of the major leading causes of mortality globally and chemo-drug-resistant cancers pose significant challenges to cancer treatment by reducing patient survival rates and increasing treatment costs. Although the mechanisms of chemoresistance vary among different types of cancer, cancer cells are known to share several hallmarks, such as their resistance to apoptosis as well as the ability of cancer stem cells to produce metastatic daughter cells that are resistant to chemotherapy. To address the issue of chemo-drug resistance in cancer cells, a tetracistronic expression construct, Ad-MBR-GFP, encoding adenovirus-mediated expression of MOAP-1, Bax, RASSSF1A, and GFP, was generated to investigate its potential activity in reducing or inhibiting the chemo-drug resistant activity of the human breast cancer cells, MCF-7-CR and MDA-MB-231.

B7-H3-Targeting Chimeric Antigen Receptors Epstein-Barr Virus-specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3-positive Solid Tumors.

Unlabelled: Encouraged by the observations of significant B7-H3 protein overexpression in many human solid tumors compared to healthy tissues, we directed our focus towards targeting B7-H3 using chimeric antigen receptor (CAR) T cells. We utilized a nanobody as the B7-H3-targeting domain in our CAR construct to circumvent the stability issues associated with single-chain variable fragment-based domains. In efforts to expand patient access to CAR T-cell therapy, we engineered our nanobody-based CAR into human Epstein-Barr virus-specific T cells (EBVST), offering a readily available off-the-shelf treatment.

Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice.

The protective efficacies of current licensed vaccines against COVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern (VOCs) which carried multiple mutations in the Spike (S) protein. Considering that these vaccines were developed based on the S protein of the original SARS-CoV-2 Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highly conserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strain and the Omicron VOC. Literature mining and bioinformatics were used to identify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S and membrane (M) proteins.

A retrospective review of the rate of sexually transmitted infections in adolescents after universal screening protocol implementation in an urban United States clinic.

Objective: Despite expanded guidelines, adolescent gonorrhea and chlamydia (GC/CT) screening rates remain low due to multiple psychosocial barriers and biases. This intervention aimed to improve screening and diagnosis rates at adolescent well visits by establishing a streamlined universal screening protocol for all patients ages 13-18 years old.

Methods: A universal sexually transmitted infection (STI) screening approach was introduced at an urban clinic affiliated with an academic medical center near Philadelphia, Pennsylvania (PA) in September 2018 for all adolescent well-visits.

Photosynthetic gas exchange, plant water relations and osmotic adjustment of three tropical perennials during drought stress and re-watering.

Planting vegetation on slopes is an effective way of improving slope stability while enhancing the aesthetic appearance of the landscape. However, plants growing on slopes are susceptible to natural drought stress (DS) conditions which commonly lead to water deficit in plant tissues that affect plant health and growth. This study investigated the photosynthetic gas exchange, plant water status and proline accumulation of three tropical perennials namely Clerodendrum paniculatum, Ipomoea pes-caprae and Melastoma malabathricum after being subjected to DS and re-watering (RW).