Disease diagnostics using machine learning of B cell and T cell receptor sequences.

Clinical diagnosis typically incorporates physical examination, patient history, various laboratory tests, and imaging studies but makes limited use of the human immune 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 MAchine Learning for Immunological Diagnosis, 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.

High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads.

In serology, each sample is typically tested individually, one antigen at a time. This is costly and time consuming. Serology techniques should ideally allow recurrent measurements in parallel in small sample volumes and be inexpensive and fast.

Rapid Sterilization of Clinical Apheresis Blood Products using Ultra-High Dose Rate Radiation.

Background And Objectives: Apheresis platelets products and plasma are essential for medical interventions, but both still have inherent risks associated with contamination and viral transmission. Platelet products are vulnerable to bacterial contamination due to storage conditions, while plasma requires extensive screening to minimize virus transmission risks. Here we investigate rapid irradiation to sterilizing doses for bacteria and viruses as an innovative pathogen reduction technology.

Implementation and early outcomes with Pathogen Reduced Cryoprecipitated Fibrinogen Complex.

Objectives: Cryoprecipitated antihemophilic factor (cryo) has been used for fibrinogen replacement in actively bleeding patients, dysfibrinogenemia, and hypofibrinogenemia. Cryo has a shelf life of 4 to 6 hours after thawing and a long turnaround time in issuing the product, posing a major limitation of its use. Recently, the US Food and Drug Administration approved Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex [IFC]) for the treatment of bleeding associated with fibrinogen deficiency, which can be stored at room temperature and has a shelf life of 5 days after thawing.

Measuring the effectiveness of online search ads on blood donor recruitment and donation.

Background: Acutely highlighted during the COVID-19 pandemic, the tenuousness of the blood supply continues to be a lynchpin of the most important medical procedures. Online advertisements have become a mainstay in donor recruitment. We set out to determine the effectiveness of online search ads and variations thereof on blood donations with an emphasis on first-time donors.

Germline-encoded specificities and the predictability of the B cell response.

Antibodies result from the competition of B cell lineages evolving under selection for improved antigen recognition, a process known as affinity maturation. High-affinity antibodies to pathogens such as HIV, influenza, and SARS-CoV-2 are frequently reported to arise from B cells whose receptors, the precursors to antibodies, are encoded by particular immunoglobulin alleles. This raises the possibility that the presence of particular germline alleles in the B cell repertoire is a major determinant of the quality of the antibody response.

Hepatitis E virus seropositivity in an ethnically diverse community blood donor population.

Background And Objectives: Hepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion-associated HEV infections.

Materials And Methods: We screened 10,002 randomly selected donations over an 8-month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT-qPCR).

Targeting repetitive laboratory testing with electronic health records-embedded predictive decision support: A pre-implementation study.

Introduction: Unnecessary laboratory testing contributes to patient morbidity and healthcare waste. Despite prior attempts at curbing such overutilization, there remains opportunity for improvement using novel data-driven approaches. This study presents the development and early evaluation of a clinical decision support tool that uses a predictive model to help providers reduce low-yield, repetitive laboratory testing in hospitalized patients.

Implementation strategy for complete pathogen reduction technology treated apheresis platelet inventory.

Background: Bacterial contamination in platelets remain a major public health concern, which prompted the US Food and Drug Administration guidance for bacterial contamination mitigation. Pathogen reduction technology (PRT) is one mitigation strategy that has shown success in Europe over the last decade. Therefore, our center sought to transition from a dual system of bacterial culturing (BacT) and PRT to full PRT.

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.

Factors associated with first-time and repeat blood donation: Adverse reactions and effects on donor behavior.

Background: Blood centers have a dual mission to protect donors and patients; donor safety is paramount to maintaining an adequate blood supply. Elucidating donor factors associated with adverse reactions (AR) is critical to this mission.

Study Design/methods: A retrospective cohort analysis of whole blood donors from 2003 to 2020 was conducted at a single blood center in northern California.

Differential Peripheral Blood Glycoprotein Profiles in Symptomatic and Asymptomatic COVID-19.

Glycosylation is the most common form of post-translational modification of proteins, critically affecting their structure and function. Using liquid chromatography and mass spectrometry for high-resolution site-specific quantification of glycopeptides coupled with high-throughput artificial intelligence-powered data processing, we analyzed differential protein glycoisoform distributions of 597 abundant serum glycopeptides and nonglycosylated peptides in 50 individuals who had been seriously ill with COVID-19 and in 22 individuals who had recovered after an asymptomatic course of COVID-19. As additional comparison reference phenotypes, we included 12 individuals with a history of infection with a common cold coronavirus, 16 patients with bacterial sepsis, and 15 healthy subjects without history of coronavirus exposure.

Regulation of the BCR signalosome by the class II peptide editor, H2-M, affects the development and repertoire of innate-like B cells.

The non-classical Major Histocompatibility Complex class II (MHCII) protein, H2-M, edits peptides bound to conventional MHCII in favor of stable peptide/MHCII (p/MHCII) complexes. Here, we show that H2-M deficiency affects B-1 cell survival, reduces cell renewal capacity, and alters immunoglobulin repertoire, allowing for the selection of cells specific for highly abundant epitopes, but not low-frequency epitopes. H2-M-deficient B-1 cells have shorter CDR3 length, higher content of positively charged amino acids, shorter junctional regions, less mutation frequency, and a skewed clonal distribution.

How do I implement pathogen-reduced platelets?

Background: Several risk mitigation steps have improved the safety of platelets in regard to bacterial contamination, but this continues to be a concern today. A Food and Drug Administration (FDA) Guidance issued in December 2018 aims to further limit this risk. The guidance offers multiple pathways for compliance, and hospital blood banks will have to collaborate with blood donor centers to assess various factors before deciding which method is most appropriate for them.

Use of Outpatient-Derived COVID-19 Convalescent Plasma in COVID-19 Patients Before Seroconversion.

Background: Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings.

Efficient Identification of High-Titer Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Plasma Samples by Pooling Method.

Context.—: The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has elicited a surge in demand for serologic testing to identify previously infected individuals. In particular, antibody testing is crucial in identifying COVID-19 convalescent plasma, which has been approved by the Food and Drug Administration under the Emergency Use Authorization for use as passive immunotherapy for hospitalized patients infected with COVID-19.

Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues.

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens.

Molecular epidemiology of Cryptosporidium spp. in an agricultural area of northern Vietnam: A community survey.

The purpose of this study was to investigate the occurrence of Cryptosporidium infection and the potential for transmission of Cryptosporidium spp. between animals and humans in northern Vietnam. A total of 2715 samples (2120 human diarrheal samples, 471 human non-diarrheal samples, and 124 animal stool samples) were collected through our community survey in an agricultural area.

A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice.

The development of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines, and ferritin-based vaccines have been investigated in humans in two separate clinical trials.

Molecular epidemiology of spp. in northern Vietnam: Potential transmission between animals and humans.

spp. is detected frequently in humans and animals. Although many studies have been conducted on the epidemiology of giardiasis, there is a scarcity of information on the genetic diversity and the dynamics of transmission of spp.

Identifying correlations between donor demographics and isohemagglutinin titers as a potential method to screen for low-titer group O whole blood.

Background: With more hospitals using low-titer group O whole blood in trauma resuscitation, having an efficient screening method for low-titer donors is critical. Our blood center uses an automated screen for high-titer isohemagglutinins in our platelet donations while collecting detailed donor demographic information. Using this data, we can identify key demographics often associated with titer status, thereby helping develop a donor-triaging method for titering.