Harnessing Viral-Specific T Cells: Expanding Therapeutic Strategies Across Diverse Populations.

Adoptive transfer of virus-specific T-cells (VSTs) has been utilized for managing viral diseases in immunocompromised patients, including those undergoing hematopoietic stem cell transplantation (HCT) and solid organ transplantation (SOT). Clinical trials targeting viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (Adv), and BK virus have demonstrated effective viral control without the toxicities associated with conventional antiviral therapies. This review explores the manufacturing, feasibility, safety, and efficacy of VSTs complemented by two case studies illustrating their real-world application.

TCF1 and LEF1 promote B-1a cell homeostasis and regulatory function.

B-1 cells are innate-like immune cells abundant in serosal cavities with antibodies enriched in bacterial recognition, yet their existence in humans has been controversial. The CD5 B-1a subset expresses anti-inflammatory molecules including IL-10, PDL1 and CTLA4 and can be immunoregulatory. Unlike conventional B cells that are continuously replenished, B-1a cells are produced early in life and maintained through self-renewal.

A Cloud-Based Platform for Harmonized COVID-19 Data: Design and Implementation of the Rapid Acceleration of Diagnostics (RADx) Data Hub.

Background: The COVID-19 pandemic exposed significant limitations in existing data infrastructure, particularly the lack of systems for rapidly collecting, integrating, and analyzing data to support timely and evidence-based public health responses. These shortcomings hampered efforts to conduct comprehensive analyses and make rapid, data-driven decisions in response to emerging threats. To overcome these challenges, the US National Institutes of Health launched the Rapid Acceleration of Diagnostics (RADx) initiative.

Targeting intestinal inflammation using locked nucleic acids delivered via lipid nanoparticles.

Locked nucleic acids are a third-generation antisense oligonucleotides with high binding affinity. A major limitation is the high dosages they require to achieve efficacy which may induce unwanted adverse effects. Here, we report the use of Lipid-based nanoparticles to deliver locked nucleic acids for treating intestinal inflammation in mice.

Early Post-Transplant Recipient Tissue Injury Predicts Allograft Function, Rejection, and Survival in Lung Transplant Recipients, Evidence from Cell-free DNA.

Background: Allograft injury in the early post-transplant period is a known risk factor of death after lung transplantation. However, the recipient tissue injury profile and its association with outcomes remain unexplored. This study leverages cell-free DNA (cfDNA) to test this association.

Preparing clinical research data for artificial intelligence readiness: insights from the National Institute of Diabetes and Digestive and Kidney Diseases data centric challenge.

Objectives: The success of artificial intelligence (AI) and machine learning (ML) approaches in biomedical research depends on the quality of the underlying data. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Data Centric Challenge was designed to address the challenge of making raw clinical research data AI ready, with a focus on type 1 diabetes studies available in the NIDDK Central Repository (NIDDK-CR). This paper aims to present a structured methodology for enhancing the AI readiness of clinical datasets.

CAR T cell therapy for children with rheumatic disease: the time is now.

Initial success with B cell-targeted chimeric antigen receptor (CAR) T cells for the treatment of systemic lupus erythematosus and other rheumatic diseases has generated enthusiasm for the broad application of this technology outside of the field of oncology. Paediatric patients with severe rheumatic diseases require lifelong therapy with a substantial toxicity burden and a high cost of care. Paradigm-shifting treatments, including CAR T cells, are desperately needed.

Early Outcomes of Primary Graft Dysfunction Comparing Donation After Circulatory and Brain Death Heart Transplantation: An Analysis of the UNOS Registry.

Background: Primary graft dysfunction (PGD) represents a leading cause of mortality in patients undergoing donation after brain death (DBD) orthotopic heart transplantation (OHT), requiring timely escalation to mechanical circulatory support. There is a lack of nationwide data regarding PGD after donation after circulatory death (DCD). Here, we evaluated the incidence and short-term outcomes of PGD following DCD.

Impact of the Composite Allocation Score on Lung Transplant Waitlist and Posttransplant Outcomes.

Background: On March 9, 2023, the Composite Allocation Score (CAS) was introduced for all lung transplantation (LT) candidates. We analyzed waitlist and posttransplant outcomes after CAS implementation.

Methods: Using the United Network for Organ Sharing registry (2022-2024), adult patients listed for isolated LT were divided into 2 eras: era 1 (pre-CAS: March 1, 2022-March 8, 2023) and era 2 (post-CAS: March 9, 2023-September 30, 2024).

Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft Failure.

Background: Despite treatment of major risk factors such as acute rejection (AR) and organizing pneumonia (OP) in lung transplant recipients, chronic lung allograft dysfunction (CLAD) still develops at high rates, suggesting that traditional methods of assessing response to treatment and resolution remain inadequate. It is unknown whether the degree of molecular allograft injury after treatment of AR/OP modulates the risk of CLAD and death.

Methods: To evaluate the association of molecular allograft injury after AR/OP with the incidence of CLAD/death, we conducted a multicenter prospective cohort study that included 93 patients who underwent lung transplantation between 2015 and 2022.

Impact of donor specific antibodies on longitudinal lung function and baseline lung allograft dysfunction.

Background: Lung transplantation offers life-saving benefits for patients with end-stage lung disease, however, long-term outcomes remain poor, with a median survival of 6.5 years. Identifying patients at risk for poor post-transplant lung function is crucial for improving outcomes.

Autologous HIV-specific T cell therapy targeting conserved epitopes is well-tolerated in six adults with HIV: an open-label, single-arm phase 1 study.

Novel cellular therapies may enable HIV control or cure. HIV-specific T cells targeting conserved immunogenic protein regions of HIV Gag/Pol and the entirety of HIV Nef, termed HST-NEETs, eliminate HIV infected cells in vitro. Here we enroll seven participants in an open-label, single-arm phase 1 study (NCT03485963) to evaluate the safety (primary endpoint) of two autologous administrations of HST-NEET products without prescribed lymphodepletion.

Donor-derived cell-free DNA is associated with the degree of immunosuppression in lung transplantation.

Donor-derived cell-free DNA (ddcfDNA) is increasingly used in clinical practice to monitor lung transplant patients for acute rejection (AR). However, its association with conventional approaches to monitor immunosuppression remains unclear. This multicenter observational cohort study examines the association of ddcfDNA with surrogate measures of immunosuppression.

Multi-Year Registry Study of Elapegademase Treatment in Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) Requiring Enzyme Replacement Therapy.

Purpose: The safety and tolerability of elapegademase (elapegademase-lvlr; Revcovi) a PEGylated recombinant adenosine deaminase (ADA), were demonstrated in two Phase 3 clinical trials in the U.S. and Japan in patients with ADA-deficient severe combined immunodeficiency (ADA-SCID).

Molecular criteria for pulmonary antibody-mediated rejection are associated with an increased risk of allograft failure.

Background: Current International Society for Heart and Lung Transplantation (ISHLT) criteria for pulmonary antibody-mediated rejection (AMR) is predicated on a constellation of clinical, laboratory and histopathological parameters, including the presence of donor-specific antibodies (DSA). However, molecular evidence of allograft injury is not considered. The aim of this study was to investigate if allograft injury on the molecular level, as measured by donor-derived cell-free DNA (dd-cfDNA), identifies DSA positive patients experiencing a form of AMR associated with increased risk of chronic lung allograft dysfunction (CLAD) or death.

IRF2BP2 deficiency: An important form of common variable immunodeficiency with inflammation.

Background: IRF2BP2 is a transcription factor that plays an important role in regulating immune pathways, angiogenesis, apoptosis, and cell differentiation. Defects in this gene have been implicated in immunodeficiency.

Objectives: To deepen the understanding of the clinical implications of IRF2BP2 variants, we sought to clinically characterize and functionally test 34 individuals with IRF2BP2 variants.

T Cell Immune Response to Influenza Vaccination When Administered Prior to and Following Autologous Chimeric Antigen Receptor-Modified T Cell Therapy.

Chimeric antigen receptor-modified T (CAR-T) cell therapies are gaining wider use in relapsed and refractory malignancies. However, data on vaccination in this population is lacking. We evaluated T cell responses in an established cohort of CAR-T recipients and healthy controls before and after 2019 to 2020 influenza vaccination.

Environmental drivers of spatial variation in tropical forest canopy height: Insights from NASA's GEDI spaceborne LiDAR.

Forest canopy height is a fundamental ecosystem property-influencing patterns of forest carbon storage and forest ecosystem responses to climate variability and change. Previous studies have analyzed environmental drivers influencing spatial variation in canopy height at landscape-to-regional scales; however, far less is known about the environmental determinants underlying regional and global scale variation in forest canopy height. Using the canopy height metrics products from Global Ecosystem Dynamics Investigation (GEDI), a space-borne Light Detection and Ranging (LiDAR) instrument specifically designed to characterize forest structure, we analyze the environmental correlates of spatial variation of global tropical forest canopy height.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Altered Purinergic Signaling and CD8+ T Cell Dysregulation in STAT3 GOF Syndrome.

Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants in STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, and immune dysregulation. In both primary human and mouse models of STAT3 GOF, CD8+ T cells have been implicated as pathogenic drivers of autoimmunity.

The 'Goldilocks Grub': reproductive responses to leafroller host development in , a parasitoid of the light brown apple moth.

Many parasitoids alter their reproductive behaviour in response to the quality of encountered hosts. They make adaptive decisions concerning whether to parasitise a potential host, the number of eggs laid on an accepted host, and the allocation of sex to their offspring. Here we present evidence that Farrugia (Hymenoptera: Bethylidae), a gregarious ectoparasitoid of larval tortricids, adjusts its reproductive response to the size and developmental stage of larvae of the light brown apple moth (LBAM), (Walker) (Lepidoptera: Tortricidae).