Advances in RNA editing in hematopoiesis and associated malignancies.

Adenosine-to-inosine (A-to-I) RNA editing is a prevalent RNA modification essential for cell survival. The process is catalyzed by the Adenosine Deaminase Acting on RNA (ADAR) enzyme family that converts adenosines in double-stranded RNAs (dsRNAs) into inosines, which are read as guanosines during translation. Deep sequencing has helped to reveal that A-to-I editing occurs across various types of RNAs to affect their functions.

Integrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody response.

Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.

Protection of β2GPI-Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation.

Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI.

Babesiosis and Sickle Red blood Cells: Loss of Deformability, Heightened Osmotic fragility, and Hypervesiculation.

Babesiosis in sickle cell disease (SCD) is marked by severe anemia but the underlying red blood cell (RBC) rheological parameters remain largely undefined. Here, we describe altered RBC deformability from both primary (host RBC sickle hemoglobin mediated) and secondary changes (Babesia parasite infection mediated) to the RBC membrane using wild type AA, sickle trait AS and sickle SS RBCs. Our ektacytometry (LORRCA) analysis demonstrates that the changes in the host RBC bio-mechanical properties, pre- and post- Babesia infection, reside on a spectrum of severity, with wild type infected AA cells, despite showing a significant reduction of deformability under both shear and osmolarity gradients, exhibiting only a mild phenotype; compared to infected AS RBCs which show median changes in deformability and infected SS RBCs which exhibit the most dramatic impact of infection on cellular rheology, including an increase in Point of Sickling values.

Frontline treatment of follicular lymphoma: What will it take to change current practice?

Follicular lymphoma is the most common subtype of indolent lymphoma. Despite multiple trials over the past decade showing improved progression-free survival with new first-line therapeutic strategies -such as anti-CD20 maintenance therapy and new glycoengineered anti-CD20 antibodies- no standardized approach has been widely adopted in routine clinical practice. Several factors may explain this, including the increased incidence of infectious adverse events associated with these therapies, particularly during the COVID-19 pandemic, and the lack of overall survival benefit despite long-term follow-up.

Factor XIII: Driving (Cross-)Links in Hemostasis, Thrombosis, and Disease.

Blood clots are complex structures composed of blood cells and proteins held together by the structural framework provided by an insoluble fibrin network. Factor (F)XIII is a protransglutaminase essential for stabilizing the fibrin network. Activated FXIII(a) introduces novel covalent crosslinks within and between fibrin and other plasma and cellular proteins, and thereby promotes fibrin biochemical and mechanical integrity.

IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoid malignancy with limited treatment options. To discover new treatment targets for T-PLL, we performed high-throughput drug sensitivity screening on 30 primary patient samples ex-vivo. After screening over 2'800 unique compounds, we found T-PLL to be more resistant to most drug classes, including chemotherapeutics, compared to other blood cancers.

14-3-3 promotes sarcolemmal expression of cardiac Ca1.2 and nucleates isoproterenol-triggered channel superclustering.

The L-type Ca channel (Ca1.2) is essential for cardiac excitation-contraction coupling. To contribute to the inward Ca flux that drives Ca-induced-Ca-release, Ca1.

Structure Protects Function: A Multilevel Engineered Surface Modification Renders the Surface of Titanium Dental Implants Resistant to Bacterial Colonization.

The global dental implant market is projected to reach $9.5 billion by 2032, growing at a 6.5% compound annual growth rate due to the rising prevalence of dental diseases.

Prenatal tests in Brazil: prevalence and associated factors according to the Brazilian National Health Survey.

Objective: To analyze the prevalence of prenatal tests of pregnant women and factors associated with variation in this prevalence in the years of the Brazilian National Health Survey 2013 and 2019.

Method: A cross-sectional study, carried out with women who underwent prenatal care, interviewed in the Brazilian National Health Survey 2013 (n = 1,851) and 2019 (n = 2,729).

Results: The most prevalent tests were urine and blood, and the least prevalent were syphilis and HIV.

Daytime DNase-I Administration Protects Mice From Ischemic Stroke Without Inducing Bleeding or tPA-Induced Hemorrhagic Transformation, Even With Aspirin Pretreatment.

Background: Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes of tPA resistance, influenced by thrombus composition and timing, are not fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes and reperfusion resistance, contribute to thrombosis.

Transient Ischemic Attack in Women: Real-World Hospitalization Incidence, Outcomes, and Risk of Hemorrhage and Stroke.

Background: Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women.

Methods: This was a retrospective cohort study of the 2016 to 2021 Nationwide Readmissions Database in the United States.

Triatoma venosa and Panstrongylus geniculatus challenge the certification of interruption of vectorial Trypanosoma cruzi transmission by Rhodnius prolixus in eastern Colombia.

Reactivation of Trypanosoma cruzi transmission by native vectors with different domiciliation capabilities is a major concern for Chagas disease control programs. T. cruzi transmission via intra-domestic Rhodnius prolixus was certified as interrupted by the Pan American Health Organization in Miraflores municipality (Boyacá, Colombia) in 2019.

Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation.

Adaptation to existence outside the womb is a key event in the life of a mammal. The absence of macrophages in rats with a homozygous mutation in the colony-stimulating factor 1 receptor (Csf1r) gene (Csf1rko) severely compromises pre-weaning somatic growth and maturation of organ function. Transfer of wild-type bone marrow cells (BMT) at weaning rescues tissue macrophage populations permitting normal development and long-term survival.

The link between the atherogenic index of plasma and the risk of hypertension: Analysis from NHANES 2017-2020.

Background: The atherogenic index of plasma (AIP) is a newly identified metabolic marker for atherosclerosis. However, there are inconsistent conclusions regarding the relationship between AIP and hypertension.

Methods: The study subjects were sourced from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020.

Synbiotics effects of d-tagatose and Lactobacillus rhamnosus GG on the inflammation and oxidative stress reaction of Gallus gallus based on the genus of cecal bacteria and their metabolites.

Backgrounds: Abuse of feed supplement can cause oxidative stress and inflammatory responses in Gallus gallus. Synbiotics are composed of prebiotics and probiotics and it possess huge application potentials in the treatment of animal diseases.

Methods: This study examined the effect of d-tagatose on the probiotic properties of L.

Impact of nutritional status and pulmonary function on short- and long-term overall survival in hemodialysis patients.

Background: End-stage renal disease (ESRD) patients frequently experience protein-energy wasting (PEW), which increases their morbidity and mortality rates.

Objective: This study explores the effects of nutritional status and pulmonary function on the short- and long-term mortality of ESRD patients undergoing hemodialysis.

Materials And Methods: 67 consecutive ESRD patients on maintenance hemodialysis were included in the study.

Deep learning based analysis of G3BP1 protein expression to predict the prognosis of nasopharyngeal carcinoma.

Background: Ras-GTPase-activating protein (GAP)-binding protein 1 (G3BP1) emerges as a pivotal oncogenic gene across various malignancies, notably including nasopharyngeal carcinoma (NPC). The use of automated image analysis tools for immunohistochemical (IHC) staining of particular proteins is highly beneficial, as it could reduce the burden on pathologists. Interestingly, there have been no prior studies that have examined G3BP1 IHC staining using digital pathology.

Generalized functional varying-index coefficient model for dynamic synergistic gene-environment interactions with binary longitudinal traits.

The genetic basis of complex traits involves the function of many genes with small effects as well as complex gene-gene and gene-environment interactions. As one of the major players in complex diseases, the role of gene-environment interactions has been increasingly recognized. Motivated by epidemiology studies to evaluate the joint effect of environmental mixtures, we developed a functional varying-index coefficient model (FVICM) to assess the combined effect of environmental mixtures and their interactions with genes, under a longitudinal design with quantitative traits.

Correction: Severe, but not moderate asthmatics share blood transcriptomic changes with post-traumatic stress disorder and depression.

[This corrects the article DOI: 10.1371/journal.pone.

A safe-enhanced fully closed-loop artificial pancreas controller based on deep reinforcement learning.

Patients with type 1 diabetes and their physicians have long desired a fully closed-loop artificial pancreas (AP) system that can alleviate the burden of blood glucose regulation. Although deep reinforcement learning (DRL) methods theoretically enable adaptive insulin dosing control, they face numerous challenges, including safety and training efficiency, which have hindered their clinical application. This paper proposes a safe and efficient adaptive insulin delivery controller based on DRL.

A Granzyme B-Cleavable T Cell-Targeted Bispecific Cell Vesicle Connector for Reversing New-Onset Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disorder in which pancreatic β-cells are destroyed by CD8 T cells. Anti-CD3 antibody effectively treats early-stage T1D when β-cell autoantibodies are detected but before symptoms appear. However, it impairs the immune system temporarily, exposing individuals to infection.

Label-Free and Sequence-Independent Isothermal Amplification Strategy for the Simultaneous Detection of Genomic 5-Methylcytosine and 5-Hydroxymethylcytosine.

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are crucial epigenetic modifications in eukaryotic genomic DNA that regulate gene expression and are associated with the occurrence of various cancers. Here, we combined bisulfite conversion with 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperridinium tetrafluoroborate (ACTBF, TCI) oxidation to develop a label-free and sequence-independent isothermal amplification (BTIA) assay for a genome-wide 5mC and 5hmC analysis. The BTIA strategy can distinguish 5mC and 5hmC signatures from other bases with high sensitivity and good specificity, avoiding sophisticated chemical modifications and expensive protein labeling.