Characterization of extracellular vesicles released from MED4 at the steady state and under a light-dark cycle.

Bacterial extracellular vesicles (EVs) are vesicles secreted by bacteria into the extracellular environment. Containing DNA, RNA and proteins, EVs are implicated to mediate intercellular communications. The marine cyanobacterium , the most abundant photosynthetic organism in marine ecosystems, has been shown to generate EVs continuously during cell growth.

A comprehensive analysis framework for evaluating commercial single-cell RNA sequencing technologies.

This study examined nine prominent commercially available single-cell RNA sequencing (scRNA-seq) kits across four technology groups. Each kit was characterized using peripheral blood mononuclear cells (PBMCs) from a single donor, which enabled consistent assessment of factors such as analytical performance, protocol duration and cost. The Chromium Fixed RNA Profiling kit from 10× Genomics, with its probe-based RNA detection method, demonstrated the best overall performance.

Double Trouble: COVID-19 Infection Exacerbates Sickle Cell Crisis Outcomes in Hospitalized Patients-Insights from National Inpatient Sample 2020.

This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization.

Recombinant Newcastle disease viruses expressing immunological checkpoint inhibitors induce a pro-inflammatory state and enhance tumor-specific immune responses in two murine models of cancer.

Introduction: Tumor microenvironments are immunosuppressive due to progressive accumulation of mutations in cancer cells that can drive expression of a range of inhibitory ligands and cytokines, and recruitment of immunomodulatory cells, including myeloid-derived suppressor cells (MDSC), tumor-associated macrophages, and regulatory T cells (Tregs).

Methods: To reverse this immunosuppression, we engineered mesogenic Newcastle disease virus (NDV) to express immunological checkpoint inhibitors anti-cytotoxic T lymphocyte antigen-4 and soluble programmed death protein-1.

Results: Intratumoral administration of recombinant NDV (rNDV) to mice bearing intradermal B16-F10 melanomas or subcutaneous CT26LacZ colon carcinomas led to significant changes in the tumor-infiltrating lymphocyte profiles.

Per- and polyfluoroalkyl substances (PFAS) in Canadian municipal wastewater and biosolids: Recent patterns and time trends 2009 to 2021.

The concentrations of per- and polyfluoroalkyl substances (PFAS) were determined in raw influent, final effluent, and treated biosolids at Canadian wastewater treatment plants (WWTPs) to evaluate the fate of PFAS through liquid and solids trains of typical treatment process types used in Canada and to assess time trends of PFAS in wastewater between 2009 and 2021. Data for 42 PFAS in samples collected from 27 WWTP across Canada were used to assess current concentrations and 48 WWTPs were included in the time trends analysis. Although regulated and phased-out of production by industry since the early 2000s and late 2000s/early2010s, respectively, perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other long-chain PFAS continue to be widely detected in Canadian wastewater and biosolids.

Radiation proctitis with recurrent gastrointestinal bleeding complicated by cytomegalovirus.

Cytomegalovirus (CMV) usually causes infections with mild symptoms in immunocompetent individuals. However, in immunocompromised patients, these infections can be serious or life-threatening. Following initial infection, CMV typically becomes dormant but remains lifelong in the host.

Exploring the feasibility of a mental health application (JoyPop) for Indigenous youth.

Objective: The purpose of the current study was to explore the acceptability and feasibility of a resilience-focused mobile application, JoyPop™, for use with Indigenous youth.

Methods: A Haudenosaunee community-based research advisory committee co-developed the research project, in accordance with OCAP™ principles. Adopting a mixed-method approach, five youths from an immersion school used the JoyPop™ app for four consecutive weeks, as well as completed pre-test questions and weekly usage surveys.

Superior vena cava syndrome presenting as chylothorax.

Chylothorax caused by superior vena cava (SVC) syndrome is a rare but potentially life-threatening complication requiring a multidisciplinary diagnosis and management approach. We present a case of a 27-year-old female with end-stage renal disease who developed chylothorax secondary to SVC syndrome caused by venous stenosis from a tunneled hemodialysis (HD) catheter. The patient had a history of ongoing hemodialysis through a tunneled catheter placed in the right internal jugular vein approximately seven months before presentation.

2022 White Paper on Recent Issues in Bioanalysis: Enzyme Assay Validation, BAV for Primary End Points, Vaccine Functional Assays, Cytometry in Tissue, LBA in Rare Matrices, Complex NAb Assays, Spectral Cytometry, Endogenous Analytes, Extracellular Vesicles - Recommendations on Biomarkers/CDx, Flow Cytometry, Ligand-Binding Assays Development & Validation; Emerging Technologies; Critical Reagents Deep Characterization.

The 16 Workshop on Recent Issues in Bioanalysis (16 WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Exploring the relevance of a psychology-based resilience app (JoyPop™) for Indigenous youth.

Background: Despite facing challenges to mental wellness from ongoing multifold trauma, Indigenous youth continue to galvanize their resilience. One pathway undertaken is embracing technology. The JoyPop™ youth resilience mobile application (app) was invited by Six Nations of the Grand River (SN) leadership to consider its use with their reserve youth.

Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors.

Introduction: Anal dysplasia and anal cancer are major health problems. This study seeks to determine if inhibition of mTOR and/or PI3K pathways is effective at anal cancer prevention in mice with/without established precancerous lesions of the anus (anal dysplasia).

Methods: K14E6/E7 mice were entered into the study at 5 wk, 15 wk, or 25 wk of age.

Dehiscence and Deep Wound Infection After Spinal Cord Stimulator Implant Managed Without Explantation: A Case Report.

Deep infections of spinal cord stimulator devices usually result in explantation, as recommended by some professional societies. However, alternative options should be explored to avoid potential complications that are associated with explantation, and possibly additional procedures required in consideration of reimplantation. In this case, the patient presented with wound dehiscence after implantation.

Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models.

The artemisinin family of compounds is cytopathic in certain cancer cell lines that are positive for human papillomaviruses (HPV) and can potentially drive the regression of dysplastic lesions. We evaluated the efficacy of topical dihydroartemisinin (DHA) on cervical dysplasia and anal dysplasia in two papillomavirus mouse models: transgenic mice, which express HPV16 oncogenes; and immunodeficient NOD/SCID gamma (NSG) mice infected with papillomavirus (MmuPV1). Mice started treatment with DHA at 25 weeks of age () or 20 weeks post infection (MmuPV1-infected), when the majority of mice are known to have papillomavirus-induced low- to high-grade dysplasia.

Cytotoxicity of Metal-Based Photoactivated Chemotherapy (PACT) Compounds.

Metal-based compounds have been used to treat cancer for decades, with cisplatin being the most common and widely used. Photodynamic therapy (PDT) is another clinical modality used to fight cancer, which uses a photosensitizer (PS) that localizes in cancer tissues. This PS is activated by the illumination of the tumor with visible light.

Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8 T cell responses.

Dual blockade of the PD-1 and TIGIT coinhibitory receptors on T cells shows promising early results in cancer patients. Here, we studied the mechanisms whereby PD-1 and/or TIGIT blockade modulate anti-tumor CD8 T cells. Although PD-1 and TIGIT are thought to regulate different costimulatory receptors (CD28 and CD226), effectiveness of PD-1 or TIGIT inhibition in preclinical tumor models was reduced in the absence of CD226.

Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer.

Inhibitors of the programmed cell death-1 (PD-1/PD-L1) signaling axis are approved to treat non-small cell lung cancer (NSCLC) patients, based on their significant overall survival (OS) benefit. Using transcriptomic analysis of 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy from two large randomized clinical trials, we find a significant B cell association with extended OS with PD-L1 blockade, independent of CD8 T cell signals. We then derive gene signatures corresponding to the dominant B cell subsets present in NSCLC from single-cell RNA sequencing (RNA-seq) data.

Transcriptomic profiling of adjuvant colorectal cancer identifies three key prognostic biological processes and a disease specific role for granzyme B.

Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with a 5% 5-year survival rate for metastatic disease, yet with limited therapeutic advancements due to insufficient understanding of and inability to accurately capture high-risk CRC patients who are most likely to recur. We aimed to improve high-risk classification by identifying biological pathways associated with outcome in adjuvant stage II/III CRC.

Methods And Findings: We included 1062 patients with stage III or high-risk stage II colon carcinoma from the prospective three-arm randomized phase 3 AVANT trial, and performed expression profiling to identify a prognostic signature.

Using a Prime-Boost Vaccination Strategy That Proved Effective for High Resolution Epitope Mapping to Characterize the Elusive Immunogenicity of Survivin.

Survivin is a member of the inhibitor of apoptosis family of proteins and has been reported to be highly expressed in a variety of cancer types, making it a high priority target for cancer vaccination. We previously described a heterologous prime-boost strategy using a replication-deficient adenovirus, followed by an oncolytic rhabdovirus that generates unprecedented antigen-specific T cell responses. We engineered each vector to express a mutated version of full-length murine survivin.

Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis.

Vaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen.

HIV-1 Protease Inhibitors Slow HPV16-Driven Cell Proliferation through Targeted Depletion of Viral E6 and E7 Oncoproteins.

High-risk human papillomavirus strain 16 (HPV16) causes oral and anogenital cancers through the activities of two viral oncoproteins, E6 and E7, that dysregulate the host p53 and pRb tumor suppressor pathways, respectively. The maintenance of HPV16-positive cancers requires constitutive expression of E6 and E7. Therefore, inactivating these proteins could provide the basis for an anticancer therapy.

Microdissected "cuboids" for microfluidic drug testing of intact tissues.

As preclinical animal tests often do not accurately predict drug effects later observed in humans, most drugs under development fail to reach the market. Thus there is a critical need for functional drug testing platforms that use human, intact tissues to complement animal studies. To enable future multiplexed delivery of many drugs to one small biopsy, we have developed a multi-well microfluidic platform that selectively treats cuboidal-shaped microdissected tissues or "cuboids" with well-preserved tissue microenvironments.

Systematic Review of Clinician-Reported Barriers to Provision of Brief Advice for Alcohol Intake in Hospital Inpatient and Emergency Settings.

Hospital inpatient and emergency care settings provide frequent opportunities for clinicians to screen and provide brief interventions to patients who engage in the harmful use of alcohol. However, these services are not always provided, with several reasons given in different studies. We aimed to systematically review clinician-reported barriers in the provision of brief alcohol screening, brief advice, and intervention specific to hospital inpatient and emergency department (ED) settings.