Designing Dual Compartment HIV Prevention Products: Women's Sensory Perceptions and Experiences of Suppositories for Rectal and Vaginal Use.

Dual compartment suppositories are being developed to prevent HIV and other sexually transmitted infections. Such products, for use in the rectum, the vagina, or both, could have a significant public health impact by decreasing global incidence of these diseases. In this study, 16 women each used two rheologically distinct suppositories in their vagina and rectum.

Explaining machine learning based diagnosis of COVID-19 from routine blood tests with decision trees and criteria graphs.

The sudden outbreak of coronavirus disease 2019 (COVID-19) revealed the need for fast and reliable automatic tools to help health teams. This paper aims to present understandable solutions based on Machine Learning (ML) techniques to deal with COVID-19 screening in routine blood tests. We tested different ML classifiers in a public dataset from the Hospital Albert Einstein, São Paulo, Brazil.

Oncolytic herpes simplex virus infects myeloma cells and .

Because most patients with multiple myeloma (MM) develop resistance to current regimens, novel approaches are needed. Genetically modified, replication-competent oncolytic viruses exhibit high tropism for tumor cells regardless of cancer stage and prior treatment. Receptors of oncolytic herpes simplex virus 1 (oHSV-1), NECTIN-1, and HVEM are expressed on MM cells, prompting us to investigate the use of oHSV-1 against MM.

Antibiotics as Major Disruptors of Gut Microbiota.

Advances in culture-independent research techniques have led to an increased understanding of the gut microbiota and the role it plays in health and disease. The intestine is populated by a complex microbial community that is organized around a network of metabolic interdependencies. It is now understood that the gut microbiota is vital for normal development and functioning of the human body, especially for the priming and maturation of the adaptive immune system.

Photobiology of the giant kelp Macrocystis pyrifera in the land-terminating glacier fjord Yendegaia (Tierra del Fuego): A look into the future?

The channel and fjord region of southern Chilean Patagonia hosts giant kelp forests (Macrocystis pyrifera) that have little known site-specific responses to diverse physical gradients. In this study, the functionality of the bio-optical, morphological and biochemical features of the kelps, that determine their light trapping and acclimation, were studied along a gradient of varying turbidity and light conditions at the land-terminating glacier of fjord Yendegaia in the Beagle Channel. These habitats are marked by glacial retreat, and M.

'I feel like a person has a right to use a product to protect themselves…': a qualitative study of the risk-benefit calculus on women's contraceptive use and choice.

Unlabelled: Background Reducing pregnancy risk requires a multidimensional approach to sexual and reproductive health product development. The purpose of this analysis is to identify, compare, and contrast women's pre-use beliefs and attitudes about three different forms of contraceptives: intravaginal rings; spermicide in conjunction with condoms; and oral contraceptive pills - and explore how those attitudes and beliefs, along with actual method-use experience, may affect potential choices in contraceptive method moving forward. The relationship of beliefs and attitudes to their risk-benefit calculations when using these methods was also considered.

Oncolytic HSV-Infected Glioma Cells Activate NOTCH in Adjacent Tumor Cells Sensitizing Tumors to Gamma Secretase Inhibition.

Purpose: To examine the effect of oncolytic herpes simplex virus (oHSV) on NOTCH signaling in central nervous system tumors.

Experimental Design: Bioluminescence imaging, reverse phase protein array proteomics, fluorescence microscopy, reporter assays, and molecular biology approaches were used to evaluate NOTCH signaling. Orthotopic glioma-mouse models were utilized to evaluate effects .

Satellite-derived mapping of kelp distribution and water optics in the glacier impacted Yendegaia Fjord (Beagle Channel, Southern Chilean Patagonia).

Giant kelp Macrocystis pyrifera is a brown alga with extensive global distribution, however, recent evidence suggests that its dynamics presents high degree of regional variability. In southern Chilean fjord region, largely unexplored kelp forests are currently being threatened by global change and human impacts. High-resolution satellite (Sentinel-2) imagery was used to describe temporal and spatial distribution patterns of kelp beds in Yendegaia Fjord (Beagle Channel) using Spectral Mixture Analysis (SMA), and to characterize water optical gradients of this habitat strongly influenced by river runoff from a melting glacier.

A Qualitative Study of the Contraceptive Effect on Women's Sexual Experiences: Beyond Hormonal Effects.

Objective: To elucidate the effects of the intravaginal ring, oral contraceptive pill (OCP), and spermicide plus condom on women's sexual experiences through an in-depth understanding of the physical characteristics of these contraceptive methods.

Methods: We conducted qualitative in-depth interviews with women (aged 18-45 years) who used up to three contraceptive methods (intravaginal ring, OCP, and spermicide plus condom). Women completed in-depth interviews after each 3-month use period.

Mapping of spatial and temporal variation of water characteristics through satellite remote sensing in Lake Panguipulli, Chile.

Central-southern Chile is characterized by a series of large lakes that originate in the Andes Mountains. This region is facing increasing anthropogenic impact, which threatens the oligotrophic status of these lakes. While monitoring programs are often based on a limited spatial and temporal coverage, remote sensing offers promising tools for large-scale observations improving our capacity to study comprehensively indicators of lake properties.

Oncolytic HSV therapy increases trametinib access to brain tumors and sensitizes them in vivo.

Background: Hyperactivation of the RAS-RAF-MEK-ERK signaling pathway is exploited by glioma cells to promote their growth and evade apoptosis. MEK activation in tumor cells can increase replication of ICP34.5-deleted herpes simplex virus type 1 (HSV-1), but paradoxically its activation in tumor-associated macrophages promotes a pro-inflammatory signaling that can inhibit virus replication and propagation.

Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus-1 with Integrin β1 Blocking Antibody OS2966.

Integrin β1 receptor, expressed on the surface of tumor cells and macrophages in the tumor microenvironment (TME), has been implicated in both tumor progression and resistance to multiple modalities of therapy. OS2966 is the first clinical-ready humanized monoclonal antibody to block integrin β1 and was recently orphan designated by the FDA Office of Orphan Products Development. Here, we tested therapeutic potential of OS2966-mediated integrin β1 blockade to enhance the efficacy of oncolytic herpes simplex virus-1 (oHSV) through evaluation of virus replication, tumor cell killing efficiency, effect on the antiviral signaling pathway, co-culture assays of oHSV-infected cells with macrophages, and bioluminescence imaging on mammary fat pad triple-negative breast cancer xenograft and subcutaneous and intracranial glioma xenografts.

PTEN expression by an oncolytic herpesvirus directs T-cell mediated tumor clearance.

Engineered oncolytic viruses are used clinically to destroy cancer cells and have the ability to boost anticancer immunity. Phosphatase and tensin homolog deleted on chromosome 10 loss is common across a broad range of malignancies, and is implicated in immune escape. The N-terminally extended isoform, phosphatase and tensin homolog deleted on chromosome 10 alpha (PTENα), regulates cellular functions including protein kinase B signaling and mitochondrial adenosine triphosphate production.

User evaluations offer promise for pod-intravaginal ring as a drug delivery platform: A mixed methods study of acceptability and use experiences.

Background: Effective HIV prevention requires efficient delivery of safe and efficacious drugs and optimization of user adherence. The user's experiences with the drug, delivery system, and use parameters are critical to product acceptability and adherence. Prevention product developers have the opportunity to directly control a drug delivery system and its impact on acceptability and adherence, as well as product efficacy.

Developing Online Recruitment and Retention Methods for HIV Prevention Research Among Adolescent Males Who Are Interested in Sex with Males: Interviews with Adolescent Males.

Background: Adolescent males interested in sex with males (AMSM) are an important audience for HIV prevention interventions, but they are difficult to reach due to their age and social stigma.

Objective: We aim to identify efficient methods to recruit and retain AMSM in online research.

Methods: Interviews with 14-to-18-year-old AMSM (N=16) were conducted at 2017 Pride events in Boston, MA and Providence, RI.

Reolysin and Histone Deacetylase Inhibition in the Treatment of Head and Neck Squamous Cell Carcinoma.

Oncolytic viruses (OVs) are emerging as powerful anti-cancer agents and are currently being tested for their safety and efficacy in patients. Reovirus (Reolysin), a naturally occurring non-pathogenic, double-stranded RNA virus, has natural oncolytic activity and is being tested in phase I-III clinical trials in a variety of tumor types. With its recent US Food and Drug Administration (FDA) orphan drug designation for several tumor types, Reolysin is a potential therapeutic agent for various cancers, including head and neck squamous cell carcinomas (HNSCCs), which have a 5-year survival of ∼55%.

User input in iterative design for prevention product development: leveraging interdisciplinary methods to optimize effectiveness.

The development of HIV-preventive topical vaginal microbicides has been challenged by a lack of sufficient adherence in later stage clinical trials to confidently evaluate effectiveness. This dilemma has highlighted the need to integrate translational research earlier in the drug development process, essentially applying behavioral science to facilitate the advances of basic science with respect to the uptake and use of biomedical prevention technologies. In the last several years, there has been an increasing recognition that the user experience, specifically the sensory experience, as well as the role of meaning-making elicited by those sensations, may play a more substantive role than previously thought.

Activation of the FcgammaReceptorIIIa on human natural killer cells leads to increased expression of functional interleukin-21 receptor.

Natural killer (NK) cells are innate immune effector cells that play a crucial role in immune surveillance and the destruction of cancer cells. NK cells express a low-affinity receptor for the Fc or constant region of immunoglobulin G (FcγRIIIa) and multiple cytokine receptors that respond to antibody-coated targets and cytokines in the tumor microenvironment. In the present work, microarray gene expression analysis revealed that the IL-21 receptor (IL-21R) was strongly upregulated following FcR stimulation.

RNA Nanoparticle-Based Targeted Therapy for Glioblastoma through Inhibition of Oncogenic miR-21.

Targeted inhibition of oncogenic miRNA-21 has been proposed to treat glioblastoma by rescuing tumor suppressors, PTEN and PDCD4. However, systemic delivery of anti-miR-21 sequences requires a robust and efficient delivery platform to successfully inhibit this druggable target. Three-way-junction (3WJ)-based RNA nanoparticles (RNP), artificially derived from pRNA of bacteriophage phi29 DNA packaging motor, was recently shown to target glioblastoma.

Humanized chondroitinase ABC sensitizes glioblastoma cells to temozolomide.

Background: Malignant gliomas (glioblastomas; GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extracellular matrix (ECM) interactions and are implicated in glioma growth and invasion.

Bortezomib Treatment Sensitizes Oncolytic HSV-1-Treated Tumors to NK Cell Immunotherapy.

Purpose: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy.

The combination of MLN2238 (ixazomib) with interferon-alpha results in enhanced cell death in melanoma.

The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity.

IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells.

Purpose: Alternative strategies to EGFR blockage by mAbs is necessary to improve the efficacy of therapy in patients with locally advanced or metastatic pancreatic cancer. One such strategy includes the use of NK cells to clear cetuximab-coated tumor cells, as need for novel therapeutic approaches to enhance the efficacy of cetuximab is evident. We show that IL-21 enhances NK cell-mediated effector functions against cetuximab-coated pancreatic tumor cells irrespective of KRAS mutation status.