Multi-Antigen Elephant Endotheliotropic Herpesvirus (EEHV) mRNA Vaccine Induces Humoral and Cell-Mediated Responses in Mice.

Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants in human care and the wild. It is the leading cause of death for young Asian elephants in North American and European zoos despite sensitive diagnostic tests and improved treatments. Thus, there is a critical need to develop an effective vaccine to prevent severe illness and reduce mortality from EEHV-HD.

Development and Evaluation of Five-in-One Vaccine Microneedle Array Patch for Diphtheria, Tetanus, Pertussis, Hepatitis B, and Type b: Immunological Efficacy and Long-Term Stability.

: The development of a five-in-one vaccine microneedle patch (five-in-one MN patch) aims to address challenges in administering vaccines against Diphtheria (DT), Tetanus (TT), Pertussis (wP), Hepatitis B (HBsAg), and type b (Hib). Combining multiple vaccines into a single patch offers a novel solution to improve vaccine accessibility, stability, and delivery efficiency, particularly in resource-limited settings. : The five-in-one MN patch consists of four distinct microneedle arrays: DT and TT vaccines are coated together on one array, while wP, HepB, and Hib vaccines are coated separately on individual arrays.

Inflammatory Monocytes Increase Prior to Detectable HIV-1 Rebound Viremia.

The persistence of HIV-1 proviruses in latently infected cells allows viremia to resume upon treatment cessation. To characterize the resulting immune response, we compare plasma proteomics and single-cell transcriptomics of peripheral blood mononuclear cells (PBMCs) before, during, and after detectable plasma viremia. We observe unique transcriptional signatures prior to viral rebound including a significant increase in CD16 monocytes with increased anti-viral gene expression.

The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup.

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup.

Anti-PD-1 amplifies costimulation in melanoma-infiltrating T1-like Foxp3 regulatory T cells to alleviate local immunosuppression.

Background: Immune checkpoint inhibitors targeting programmed cell death protein-1 (PD-1) are the first line of treatment for many solid tumors including melanoma. PD-1 blockade enhances the effector functions of melanoma-infiltrating CD8 T cells, leading to durable tumor remissions. However, 55% of patients with melanoma do not respond to treatment.

High organofluorine concentrations in municipal wastewater affect downstream drinking water supplies for millions of Americans.

Wastewater receives per- and polyfluoroalkyl substances (PFAS) from diverse consumer and industrial sources, and discharges are known to be a concern for drinking water quality. The PFAS family includes thousands of potential chemical structures containing organofluorine moieties. Exposures to a few well-studied PFAS, mainly perfluoroalkyl acids (PFAA), have been associated with increased risk of many adverse health outcomes, prompting federal drinking water regulations for six compounds in 2024.

Profiling lateral gene transfer events in the human microbiome using WAAFLE.

Lateral gene transfer (LGT), also known as horizontal gene transfer, facilitates genomic diversification in microbial populations. While previous work has surveyed LGT in human-associated microbial isolate genomes, the landscape of LGT arising in personal microbiomes is not well understood, as there are no widely adopted methods to characterize LGT from complex communities. Here we developed, benchmarked and validated a computational algorithm (WAAFLE or Workflow to Annotate Assemblies and Find LGT Events) to profile LGT from assembled metagenomes.

Fine-mapping causal tissues and genes at disease-associated loci.

Complex diseases often have distinct mechanisms spanning multiple tissues. We propose tissue-gene fine-mapping (TGFM), which infers the posterior inclusion probability (PIP) for each gene-tissue pair to mediate a disease locus by analyzing summary statistics and expression quantitative trait loci (eQTL) data; TGFM also assigns PIPs to non-mediated variants. TGFM accounts for co-regulation across genes and tissues and models uncertainty in cis-predicted expression models, enabling correct calibration.

System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans.

We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity.

The revised colorectal cancer screening guideline and screening burden at community health centers.

Colorectal cancer (CRC) is the third most common cancer among men and women combined, and the second leading cause of cancer death in the US. The revised USPSTF CRC screening recommendations increased CRC screening needs across health systems, which may create particular challenges for community health centers (CHCs) given their resource constraints. The objective of our study is to assess CRC screening rates across 10 CHCs in Massachusetts and estimate the additional increase in the number of average-risk screening-eligible individuals after the revision in guidelines.

A Bayesian active learning platform for scalable combination drug screens.

Large-scale combination drug screens are generally considered intractable due to the immense number of possible combinations. Existing approaches use ad hoc fixed experimental designs then train machine learning models to impute unobserved combinations. Here we propose BATCHIE, an orthogonal approach that conducts experiments dynamically in batches.

Evidence linking cadmium and/or lead exposure to immunomodulatory effects in mammals based upon an adverse outcome pathways approach, and research perspectives.

For decades, studies have shown how exposure to non-essential trace metals such as lead (Pb) and cadmium (Cd) largely impact global wildlife. Ecoimmunotoxicology has emerged in the past two decades and focuses on the effects of pollutants on the immune system of free-ranging organisms. Adverse outcome pathways (AOPs) represent a conceptual approach to explore the mechanistic linkage between a molecular initiating event and adverse outcomes, potentially at all biological levels of organisation.

Adjusting for Selection Bias Due to Missing Eligibility Criteria in Emulated Target Trials.

Target trial emulation (TTE) is a popular framework for observational studies based on electronic health records (EHR). A key component of this framework is determining the patient population eligible for inclusion in both a target trial of interest and its observational emulation. Missingness in variables that define eligibility criteria, however, presents a major challenge towards determining the eligible population when emulating a target trial with an observational study.

Melanoma toolkit for early detection for primary care clinicians: a 1-year follow-up on outcomes.

Introduction: Primary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope.

Methods: We have created a free, online, continuing education program (Melanoma Toolkit for Early Detection, MTED) that allows learners to choose from a variety of multimedia tools (image recognition, videos, written material, in-person seminars, self-tests, etc.

External validation of EncephalApp Stroop test to screen minimal hepatic encephalopathy patients with nonalcoholic cirrhosis.

Background: Neurocognitive impairment, including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, is one of the most common complications of all types of primary liver diseases, such as hepatitis B, biliary cholangitis, and autoimmune hepatitis. The EncephalApp Stroop test is a smartphone application-based test that is time-saving for MHE screening. However, neurocognitive impairment is different between alcoholic cirrhosis patients and nonalcoholic cirrhosis patients, so the cutoff value for MHE diagnosis might be inflated.

Does Asthma Affect the Risk of Developing Breast Cancer?

Background: The role of the immune system in cancer defense is likely underappreciated. While there has been longstanding interest in the role of atopic diseases in cancer, only a few studies have tested this hypothesis.

Methods: We analyzed data from 202,055 women participating in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) to explore whether asthma is associated with breast cancer.

Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma.

Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.

Extensive cervical lesion and treatment outcomes in women with HIV/HPV co-infection.

Background: Cervical cancer is a common cancer worldwide, with > 85% of deaths occurring in Lower- and Middle-Income Countries where resources for screening programs are limited. Women living with HIV (WLHIV) are at increased risk. HPV test-and-treat is a screening strategy where women with HPV are offered ablative treatment of the cervix to reduce the risk of invasive cancer.

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

Effects of a liquefied petroleum gas stove and fuel intervention on head circumference and length at birth: A multi-country household air pollution intervention network (HAPIN) trial.

Background: Air pollution may impair child growth and cognitive development, with potential markers including birth length and head circumference.

Methods: The Household Air Pollution Intervention Network (HAPIN) trial was an open label multi-country-randomized controlled trial, with 3200 pregnant women aged 18-34 years (9-19 weeks of gestation) randomly assigned in a 1:1 ratio to receive liquefied petroleum gas (LPG) stove intervention compared to women continuing to cook with solid fuels for 18 months. Particulate matter ≤ 2.

Improved Generalizability in Medical Computer Vision: Hyperbolic Deep Learning in Multi-Modality Neuroimaging.

Deep learning has shown significant value in automating radiological diagnostics but can be limited by a lack of generalizability to external datasets. Leveraging the geometric principles of non-Euclidean space, certain geometric deep learning approaches may offer an alternative means of improving model generalizability. This study investigates the potential advantages of hyperbolic convolutional neural networks (HCNNs) over traditional convolutional neural networks (CNNs) in neuroimaging tasks.

Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers of Cognitive Decline in People Living with HIV.

Background: This study examined the relationship between neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and cognition in people living with HIV (PLWH) at baseline and over time.

Methods: Plasma and clinical data were available from PLWH aged ≥45 years with HIV RNA <200 copies/mL enrolled in the AIDS Clinical Trials Group HAILO cohort study. We measured plasma NfL and GFAP using a single molecule array platform.

Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines.

Current COVID-19 vaccines are largely limited in their ability to induce broad, durable immunity against emerging viral variants. Design and development of improved vaccines utilizing existing platforms requires an in-depth understanding of the antigenic and immunogenic properties of available vaccines. Here we examined the antigenicity of two of the original COVID-19 vaccines, mRNA-1273 and NVX-CoV2373, by electron microscopy-based polyclonal epitope mapping (EMPEM) of serum from immunized non-human primates (NHPs) and clinical trial donors.

Structural equation modeling to evaluate the adult vaccine hesitancy scale for vaccines recommended during pregnancy.

Introduction: Acceptance of recommended vaccines is lower among pregnant people compared to non-pregnant adults, yet no tool has specifically measured prenatal vaccine hesitancy. We evaluated the performance of an existing adult Vaccine Hesitancy Scale (aVHS) in measuring vaccine hesitancy toward routinely recommended prenatal vaccines.

Methods: Between December 2021 and April 2022, we conducted a cross-sectional national online survey with 917 US postpartum adults 18-49 years old who had given birth in the past six months.