Clinical characteristics and serological profiles of Lyme disease in children: a 15-year retrospective cohort study in Switzerland.

Background: Lyme disease (LD) is caused by and is the most common tickborne disease in the northern hemisphere. Although classical characteristics of LD are well-known, the diagnosis and treatment are often delayed. Laboratory diagnosis by serological testing is recommended for most LD manifestations.

Bayesian semiparametric inference in longitudinal metabolomics data.

The article is motivated by an application to the EarlyBird cohort study aiming to explore how anthropometrics and clinical and metabolic processes are associated with obesity and glucose control during childhood. There is interest in inferring the relationship between dynamically changing and high-dimensional metabolites and a longitudinal response. Important aspects of the analysis include the selection of the important set of metabolites and the accommodation of missing data in both response and covariate values.

EZH2 inhibition enhances T cell immunotherapies by inducing lymphoma immunogenicity and improving T cell function.

T cell-based immunotherapies have demonstrated effectiveness in treating diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) but predicting response and understanding resistance remains a challenge. To address this, we developed syngeneic models reflecting the genetics, epigenetics, and immunology of human FL and DLBCL. We show that EZH2 inhibitors reprogram these models to re-express T cell engagement genes and render them highly immunogenic.

First-in-class transactivator-free, doxycycline-inducible IL-18-engineered CAR-T cells for relapsed/refractory B cell lymphomas.

Although chimeric antigen receptor (CAR) T cell therapy has revolutionized type B cancer treatment, efficacy remains limited in various lymphomas and solid tumors. Reinforcing conventional CAR-T cells to release cytokines can improve their efficacy but also increase safety concerns. Several strategies have been developed to regulate their secretion using minimal promoters that are controlled by chimeric proteins harboring transactivators.

Surface tension enables induced pluripotent stem cell culture in commercially available hardware during spaceflight.

Low Earth Orbit (LEO) has emerged as a unique environment for evaluating altered stem cell properties in microgravity. LEO has become increasingly accessible for research and development due to progress in private spaceflight. Axiom Mission 2 (Ax-2) was launched as the second all-private astronaut mission to the International Space Station (ISS).

Emergency Medicaid enrollment after traumatic injury predicts long-term health care utilization.

Background: Injured patients have high rates of uninsurance, which is associated with worse outcomes. Insurance linkage programs that connect patients to Medicaid coverage can prevent catastrophic costs for patients. Less is known about the long-term impact of insurance enrollment.

Identifying the Mechanisms of a Peripherally Limited Exercise Phenotype in Patients With Heart Failure With Preserved Ejection Fraction.

Background: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation.

Methods: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO, and muscle oxygen diffusive conductance.

Genetic ablation of adhesion ligands mitigates rejection of allogeneic cellular immunotherapies.

Allogeneic cellular immunotherapies hold promise for broad clinical implementation but face limitations due to potential rejection of donor cells by the host immune system. Silencing of beta-2 microglobulin (B2M) expression is commonly employed to evade T cell-mediated rejection by the host, although the absence of B2M is expected to trigger missing-self responses by host natural killer (NK) cells. Here, we demonstrate that genetic deletion of the adhesion ligands CD54 and CD58 in B2M-deficient chimeric antigen receptor (CAR) T cells and multi-edited induced pluripotent stem cell (iPSC)-derived CAR NK cells reduces their susceptibility to rejection by host NK cells in vitro and in vivo.

Nonterpenoid Chemical Diversity of Cannabis Phenotypes Predicts Differentiated Aroma Characteristics.

The recent increase in legality of . has led to interest in developing new varieties with unique aromatic or effect-driven traits. Selectively breeding plants for the genetic stability and consistency of their secondary metabolite profiles is one application of phenotyping.

Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.

Epilepsy is a common neurological disorder characterized by abnormal activity of neuronal networks, leading to seizures. The racetam class of anti-seizure medications bind specifically to a membrane protein found in the synaptic vesicles of neurons called synaptic vesicle protein 2 (SV2) A (SV2A). SV2A belongs to an orphan subfamily of the solute carrier 22 organic ion transporter family that also includes SV2B and SV2C.

Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.

Methods: In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone.

Randomized study of induction with bendamustine-rituximab ± bortezomib and maintenance with rituximab ± lenalidomide for MCL.

Although initial therapy of mantle cell lymphoma (MCL) is not standardized, bendamustine plus rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance after induction is often used. Thus, the open-label, randomized phase 2 ECOG-ACRIN Cancer Research Group E1411 trial was designed to test 2 questions: (1) does addition of bortezomib to BR induction (BVR) and/or (2) addition of lenalidomide to rituximab (LR) maintenance improve progression-free survival (PFS) in patients with treatment-naïve MCL? From 2012 to 2016, 373 previously untreated patients, 87% aged ≥60 years, were enrolled in this trial.

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

Background: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial.

Purpose: To clarify associations of sex hormones with these outcomes.

Data Sources: Systematic literature review to July 2019, with bridge searches to March 2024.

Association of a device-based remote management heart failure pathway with outcomes: TriageHF Plus real-world evaluation.

Aims: Clinical pathways have been shown to improve outcomes in patients with heart failure (HF). Although patients with HF often have a cardiac implantable electronic device, few studies have reported the utility of device-derived risk scores to augment and organize care. TriageHF Plus is a device-based HF clinical pathway (DHFP) that uses remote monitoring alerts to trigger structured telephone assessment for HF stability and optimization.

Defining primary refractory large B-cell lymphoma.

Patients with large B-cell lymphoma (LBCL) that fail to achieve a complete response (CR) or who relapse early after anthracycline-containing immunochemotherapy (IC) have a poor prognosis and are commonly considered to have "primary refractory disease." However, different definitions of primary refractory disease are used in the literature and clinical practice. In this study, we examined variation in the time to relapse used to define refractory status and association with survival outcomes in patients with primary refractory LBCL in a single-center prospective cohort with validation in an independent multicenter cohort.

Clinical and Genetic Analysis of Patients With TK2 Deficiency.

Objectives: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive disorder that stems from a perturbation of the mitochondrial DNA maintenance. Nucleoside treatment has recently shown promise as a disease-modifying therapy. TK2d was initially associated with rapidly progressive fatal myopathy in children featuring mitochondrial DNA depletion.