Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

Recommendations for mitochondria transfer and transplantation nomenclature and characterization.

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

Serum Biomarkers of Pulmonary Damage and Risk for Progression of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Objective: To investigate baseline and change of pulmonary damage biomarkers (serum Krebs von den Lungen 6 [KL-6], human surfactant protein D [hSP-D], and matrix metalloproteinase 7 [MMP-7]) with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression.

Methods: In the Korean Rheumatoid Arthritis Interstitial Lung Disease (KORAIL) cohort, a prospective cohort, we enrolled patients with RA and ILD confirmed by chest computed tomography imaging and followed annually. ILD progression was defined as worsening in physiological and radiological domains of the 2022 American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society guideline for progressive pulmonary fibrosis (PPF).

Neither Bone Marrow Aspirate Concentrate nor Platelet-Rich Plasma Improves Patient-Reported Outcomes After Surgical Management of Acetabular Labral Tears; However, Bone Marrow Aspirate Concentrate May Be Effective for Moderate Cartilage Damage: A Systematic Review.

Purpose: To (1) systematically assess which orthobiologic agents are being used in acetabular labral repairs and (2) report all available outcomes for patients undergoing operative management for labral repairs with orthobiologic agents.

Methods: The PubMed, Embase, and Cochrane databases were queried in August 2023. Articles were included if they used an orthobiologic agent during hip arthroscopy for acetabular labral repair and reported functional outcomes.

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.

Heat-Killed subsp. 557 Extracts Protect Chondrocytes from Osteoarthritis Damage by Reducing Inflammation: An In Vitro Study.

Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed subsp. 557 (LDL557) could significantly decrease OA progression.

Relationship Between Coronary Artery Calcium Score and Vulnerability of Culprit Plaque Assessed by OCT in Patients With Established Coronary Artery Disease.

Background: Coronary artery calcium score (CACS) is widely used for risk stratification. However, in patients with established coronary artery disease, its clinical implication and relationship with plaque vulnerability are unclear. We sought to correlate the CACS and plaque vulnerability assessed by optical coherence tomography.

Cryoballoon Pulmonary Vein Isolation With Versus Without Additional Right Atrial Linear Ablation for Persistent Atrial Fibrillation: The CRALAL Randomized Clinical Trial.

Background: Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with those with paroxysmal AF. We investigate whether additional linear ablation from the superior vena cava to the right atrial septum and cavotricuspid isthmus ablation improves the rhythm outcome of patients with persistent AF undergoing cryoballoon PVI (Cryo-PVI).

Methods: In this investigator-initiated, multicenter, randomized clinical trial, 289 patients with persistent AF refractory to antiarrhythmic drug therapy were randomized 1:1 to either Cryo-PVI with additional right atrium (RA) linear ablation or Cryo-PVI alone.

Factors Associated with Lamina Cribrosa Microvasculature Determined via Swept-Source Optical Coherence Tomography Angiography.

Prcis: The lamina cribrosa microvasculature reduction was associated with the posterior deformation of lamina cribrosa, as well as the functional deterioration, in all spectrums of open-angle glaucoma.

Purpose: To investigate the factors associated with the lamina cribrosa vessel density (LCVD) determined via swept-source optical coherence tomography angiography (SS-OCTA).

Materials And Methods: The optic nerve head (ONH) scan was obtained using SS-OCTA (PLEX Elite 9000; Carl Zeiss Meditec, Inc.

Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.

Background: Idiopathic interstitial pneumonias (IIPs), such as idiopathic pulmonary fibrosis and interstitial pneumonia with autoimmune features, present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF).

Methods: Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared with controls without lung disease (n=5).

Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration.

The use of adeno-associated viruses (AAVs) as donors for homology-directed repair (HDR)-mediated genome engineering is limited by safety issues, manufacturing constraints and restricted packaging limits. Non-viral targeted genetic knock-ins rely primarily on double-stranded DNA (dsDNA) and linear single-stranded DNA (lssDNA) donors. dsDNA is known to have low efficiency and high cytotoxicity, while lssDNA is challenging for scaled manufacture.

A Review of Contact Lens Regulations in the Asia Pacific Region.

The increased usage of nonrefractive cosmetic contact lenses in Asia and a trend toward increased online purchasing of both refractive and cosmetic contact lenses poses unique challenges in the management of contact lens-related complications. However, regulations have lagged behind this increased uptake in the community. This paper reviews regulations surrounding the manufacturing, import, and distribution of contact lenses in the Asia Pacific region and compares them with international regulations from the European Union and United States.

Autofluorescence Virtual Staining System for H&E Histology and Multiplex Immunofluorescence Applied to Immuno-Oncology Biomarkers in Lung Cancer.

We extend the capabilities of virtual staining from AF to a different disease and stain modality. Our work includes newly developed virtual stains for H&E and a multiplex immunofluorescence panel (DAPI, PanCK, PD-L1, CD3, and CD8) for non-small cell lung cancer, which reproduce the key features of real stains.

Regulatory T cells crosstalk with tumor cells and endothelium through lymphotoxin signaling.

Regulatory T cells (Tregs) with multifaceted functions suppress anti-tumor immunity by signaling surrounding cells. Here we report Tregs use the surface lymphotoxin (LT)α1β2 to preferentially stimulate LT beta receptor (LTβR) nonclassical NFκB signaling on both tumor cells and lymphatic endothelial cells (LECs) to accelerate tumor growth and metastasis. Selectively targeting LTβR nonclassical NFκB pathway inhibits tumor growth and migration in vitro.

Bivalent Omicron BA.1 vaccine booster increases memory B cell breadth and neutralising antibodies against emerging SARS-CoV-2 variants.

Background: Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine.

Risk of Contrast-Induced Acute Kidney Injury in Computed Tomography: A 16 Institutional Retrospective Cohort Study.

Objectives: Concern about contrast-induced acute kidney injury (CI-AKI) may delay the timely administration of contrast media for computed tomography (CT). The precise causative effect of iodinated contrast media on CI-AKI and its relevant risk factors remains an area of ongoing investigation. Therefore, this study aimed to determine the risk of CI-AKI following contrast-enhanced CT and its predisposing risk factors.

The Incidence of Popeye Deformity After Soft-Tissue Biceps Tenodesis Is Comparable to Biceps Anchor Tenodesis and Lower Than Biceps Tenotomy During Arthroscopic Rotator Cuff Repair.

Purpose: To compare clinical and radiologic outcomes between biceps anchor tenodesis (AT), biceps soft-tissue tenodesis (ST), and biceps tenotomy (TT) for patients with concomitant rotator cuff repair (RCR).

Methods: This retrospective study reviewed patients who underwent arthroscopic RCR for full-thickness rotator cuff tears with AT, ST, or TT with minimum 2-year follow-up. All biceps procedures were performed arthroscopically, and ST consisted of fixation to the transverse humeral ligament.

Lipid nanoparticle-mediated mRNA delivery to CD34 cells in rhesus monkeys.

Transplantation of ex vivo engineered hematopoietic stem cells (HSCs) can lead to robust clinical responses but carries risks of adverse events from bone marrow mobilization, chemotherapy conditioning and other factors. HSCs have been modified in vivo using lipid nanoparticles (LNPs) decorated with targeting moieties, which increases manufacturing complexity. Here we screen 105 LNPs without targeting ligands for effective homing to the bone marrow in mouse.

Fecal Microbiome Composition Correlates with Pathologic Complete Response in Patients with Operable Esophageal Cancer Treated with Combined Chemoradiotherapy and Immunotherapy.

: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer.