Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus.

Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC.

Profiling of VEGF Receptors and Immune Checkpoints in Recurrent Respiratory Papillomatosis.

Objectives: Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) infection of the aerodigestive tract that significantly impacts quality-of-life including the ability to communicate and breathe. Treatment was traditionally limited to serial ablative procedures in the O.R.

In situ vaccination via tissue-targeted cDC1 expansion enhances the immunogenicity of chemoradiation and immunotherapy.

Even with the prolific clinical use of next-generation cancer therapeutics, many tumors remain unresponsive or become refractory to therapy, creating a medical need. In cancer, DCs are indispensable for T cell activation, so there is a restriction on cytotoxic T cell immunity if DCs are not present in sufficient numbers in the tumor and draining lymph nodes to take up and present relevant cancer antigens. To address this bottleneck, we developed a therapeutic based on albumin fused with FMS-related tyrosine kinase 3 ligand (Alb-Flt3L) that demonstrated superior pharmacokinetic properties compared with Flt3L, including significantly longer half-life, accumulation in tumors and lymph nodes, and cross-presenting-DC expansion following a single injection.

Comparison of corneal tomographic parameters between Hispanic and non-Hispanic patients.

Purpose: To compare corneal tomographic parameters between Hispanic White and non-Hispanic White patients using Pentacam data.

Methods: This retrospective study evaluated preoperative Pentacam data from 641 patients 50 years or older who underwent surgery for senile cataract and self-identified as Hispanic or non-Hispanic White. Patients of non-White race or multiethnic groups, or a history of surgery, trauma, or any abnormality of the cornea or anterior segment were excluded.

Development and anticancer properties of Up284, a spirocyclic candidate ADRM1/RPN13 inhibitor.

Bortezomib has been successful for treatment of multiple myeloma, but not against solid tumors, and toxicities of neuropathy, thrombocytopenia and the emergence of resistance have triggered efforts to find alternative proteasome inhibitors. Bis-benzylidine piperidones such as RA190 covalently bind ADRM1/RPN13, a ubiquitin receptor that supports recognition of polyubiquitinated substrates of the proteasome and their subsequent deububiqutination and degradation. While these candidate RPN13 inhibitors (iRPN13) show promising anticancer activity in mouse models of cancer, they have suboptimal drug-like properties.

Organoid modeling of lung-resident immune responses to SARS-CoV-2 infection.

Tissue-resident immunity underlies essential host defenses against pathogens, but analysis in humans has lacked model systems where epithelial infection and accompanying resident immune cell responses can be observed . Indeed, human primary epithelial organoid cultures typically omit immune cells, and human tissue resident-memory lymphocytes are conventionally assayed without an epithelial infection component, for instance from peripheral blood, or after extraction from organs. Further, the study of resident immunity in animals can be complicated by interchange between tissue and peripheral immune compartments.

Detection of SARS-CoV-2 Antibodies in Immunoglobulin Products.

Background: For patients with primary antibody deficiency, the first line of therapy is replacement with immunoglobulin (Ig) products. Prior to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, Ig products did not contain antibodies with specificity for this virus, and there have been limited data on the antibodies present in the Ig products in current use.

Objective: To quantitatively examine SARS-CoV-2 antibodies in current Ig products.

Bilateral retinal vasculitis associated with cold agglutinin disease treated with obinutuzumab and infliximab.

Purpose: To describe the clinical course and management of a patient with bilateral retinal vasculitis associated with cold agglutinin disease (CAD) treated with obinutuzumab and infliximab.

Observations: A 69-year-old Hispanic woman was referred to a tertiary Uveitis Clinic with progressively worsening blurry vision, right eye (OD) worse than left eye (OS). Past ocular history was significant for epiretinal membranes in both eyes (OU).

Comparison of Ocular Biometric Parameters Between Hispanic and Non-Hispanic Ethnicities in White Adults Undergoing Cataract Surgery.

Objectives: To compare ocular biometric parameters between Hispanic and non-Hispanic White adult patients undergoing cataract surgery.

Methods: We included 433 adult patients undergoing surgery for senile cataract. Only patients with race and ethnicities of Hispanic and non-Hispanic White were included.

Localization of Salmonella and albumin-IL-2 to the tumor microenvironment augments anticancer T cell immunity.

Background: For centuries, microbial-based agents have been investigated as a therapeutic modality for the treatment of cancer. In theory, these methods would be cheap to produce, broadly applicable in a wide array of cancer types, and could synergize with other cancer treatment strategies. We aimed to assess the efficacy of combining microbial-based therapy using Salmonella SL7207 with interleukin-2 (IL-2), a potent immunostimulatory agent, in the treatment of murine colon carcinoma.

Disease diagnostics using machine learning of immune receptors.

Clinical diagnosis typically incorporates physical examination, patient history, and various laboratory tests and imaging studies, but makes limited use of the human system's own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop , an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences.

Albumin and interferon-β fusion protein serves as an effective vaccine adjuvant to enhance antigen-specific CD8+ T cell-mediated antitumor immunity.

Background: Type I interferons (IFN) promote dendritic cells maturation and subsequently enhance generation of antigen-specific CD8 +T cell for the control of tumor. Using type I interferons as an adjuvant to vaccination could prove to be a potent strategy. However, type I interferons have a short half-life.

Repeatability and reproducibility of a handheld quantitative G6PD diagnostic.

Background: The introduction of novel short course treatment regimens for the radical cure of Plasmodium vivax requires reliable point-of-care diagnosis that can identify glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. While deficient males can be identified using a qualitative diagnostic test, the genetic make-up of females requires a quantitative measurement. SD Biosensor (Republic of Korea) has developed a handheld quantitative G6PD diagnostic (STANDARD G6PD test), that has approximately 90% accuracy in field studies for identifying individuals with intermediate or severe deficiency.

Mass Spectrometry-Cleavable Protein N-Terminal Tagging Strategy for System-Level Protease Activity Profiling.

Proteolysis is one of the most important protein post-translational modifications (PTMs) that influences the functions, activities, and structures of nearly all proteins during their lifetime. To facilitate the targeted identification of low-abundant proteolytic products, we devised a strategy incorporating a novel biotinylated reagent PFP (pentafluorophenyl)-Rink-biotin to specifically target, enrich and identify proteolytic N-termini. Within the PFP-Rink-biotin reagent, a mass spectrometry (MS)-cleavable feature was designed to assist in the unambiguous confirmation of the enriched proteolytic N-termini.

Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells.

The phospholipid phosphatidylserine (PS) is naturally maintained on the cytoplasmic side of the plasma membrane. Independent of apoptosis, PS is redistributed to the surface of CD8 T cells in response to TCR-mediated activation. Annexin V (AnnV) is a protein known to bind PS with high affinity and has been effectively utilized to anchor antigen to the surface of CD8 T cells.

Augmenting the Activity of Chlorhexidine for Decolonization of from Porcine skin.

readily colonizes skin and efficiently spreads among patients in healthcare settings worldwide. Given the capacity of this drug-resistant fungal pathogen to cause invasive disease with high mortality, hospitals frequently employ chlorhexidine bathing to reduce skin colonization. Using an ex vivo skin model, we show only a mild reduction in following chlorhexidine application.

In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice.

Chirality and asymmetry increase the potency of candidate ADRM1/RPN13 inhibitors.

Bortezomib and the other licensed 20S proteasome inhibitors show robust activity against liquid tumors like multiple myeloma, but have disappointed against solid tumors including ovarian cancer. Consequently, interest is mounting in alternative non-peptide based drugs targeting the proteasome's 19S regulatory particle subunit, including its ubiquitin receptor RPN13. RA183 and RA375 are more potent analogs of the prototypic inhibitor of RPN13 (iRPN13) called RA190, and they show promise for the treatment of ovarian cancer.

Development of a Novel Mouse Model of Spontaneous High-Risk HPVE6/E7-Expressing Carcinoma in the Cervicovaginal Tract.

Current preclinical models for cervical cancer lack important clinical and pathologic features. To improve upon these models, we aimed to develop a novel, spontaneous HPV16-expressing carcinoma model that captures major aspects of HPV-associated cancer in the female genital tract. This novel preclinical model features (i) expression of HPV oncogenes E6 and E7 in the tumors in female reproductive tract of mice, (ii) spontaneous progression through high-grade squamous intraepithelial lesion (HSIL) to carcinoma, and (iii) flexibility to model cancers from different high-risk HPV genotypes.

Validation of the Ottawa Troponin Pathway.

Background: The Ottawa Troponin Pathway (OTP) was developed to improve Non-ST elevation myocardial infarction (NSTEMI) diagnosis accuracy using 3-h serial conventional troponin I (TnI) measurements. We sought to validate the OTP in patients with TnI values >99th percentile upper reference limit (>45 ng/L).

Methods: We conducted a health records review in adult patients with NSTEMI symptoms with at least two serial TnI and at least one >45 ng/L at two emergency departments (EDs).

A novel pseudovirus-based mouse model of SARS-CoV-2 infection to test COVID-19 interventions.

Background: The spread of SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19), has been characterized as a worldwide pandemic. Currently, there are few preclinical animal models that suitably represent infection, as the main point of entry to human cells is via human angiotensin-converting enzyme 2 (ACE2) which is not present in typical preclinical mouse strains. Additionally, SARS-CoV-2 is highly virulent and unsafe for use in many research facilities.

Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL/lpr mouse autoimmune model.

Autoimmune diseases are driven largely by a pathogenic cytokine milieu produced by aberrantly activated lymphocytes. Many cytokines, including interferon gamma (IFN-γ), utilize the JAK/STAT pathway for signal propagation. Suppressor of Cytokine Signaling-1 (SOCS1) is an inducible, intracellular protein that regulates IFN-γ signaling by dampening JAK/STAT signaling.