MicroRNA-199a-5p may be a diagnostic biomarker of primary ITP.

There is no diagnostic test for primary immune thrombocytopenia (ITP). Certain microRNAs have shown to have diagnostic potential in ITP. We validated 12 microRNAs identified from two previous studies to find a diagnostic biomarker.

The Value of Bone Marrow Assessment by FDG PET/CT, Biopsy and Aspirate in the Upfront Evaluation of Mantle Cell Lymphoma: A Nationwide Cohort Study.

Background: Assessment of bone marrow infiltration (BMI) is part of the initial staging of mantle cell lymphoma (MCL), although BMI evaluated by biopsy (BMB) is not considered significant in the MIPI scales, and standardized recommendations remain lacking.

Objectives: To evaluate the accuracy and prognostic impact of BMI assessed by PET/CT and BMB in a large series of MCL patients.

Methods: We deconstructed the IPI-NCCN, MIPI, and MIPI-c indices and considered BMI as positive if indicated by a BMB, PET/CT scan, or a combination of both.

Landscape of antisense genes in the human genome and identification of new human hepatic antisense RNAs by long-read sequencing.

Background: Protein-coding genes have been considered the functional part of the genome, although they represent only 2% of the genome. In contrast, more than 90% of the genome produces non-coding RNA (ncRNA), including antisense (AS) genes, a type of long non-coding genes (encoding transcripts > 200 nucleotides) located on the opposite strand of coding genes. Therefore, antisense RNA (asRNA) can be complementary to the counterpart sense RNA, supporting a regulatory role with potential pathogenic consequences, as their deregulation has been associated with cardiovascular disease, cancer, and diabetes.

Pacritinib prevents inflammation-driven myelofibrosis-like phenotype in a miR-146a murine model.

Chronic proinflammatory signaling is a characteristic trait in myeloproliferative neoplasms (MPN), particularly myelofibrosis (MF). Aberrant inflammatory signaling, particularly from NF-κB pathway, exacerbates the progression of MPN. Previously, we identified a critical role of miR-146a, a negative regulator of the TLR/NF-κB axis, in MF development.

Analysis of AlphaFold and molecular dynamics structure predictions of mutations in serpins.

Serine protease inhibitors (serpins) include thousands of structurally conserved proteins playing key roles in many organisms. Mutations affecting serpins may disturb their conformation, leading to inactive forms. Unfortunately, conformational consequences of serpin mutations are difficult to predict.

Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively.

miR-146a mice model reveals that NF-κB inhibition reverts inflammation-driven myelofibrosis-like phenotype.

Emerging evidence shows the crucial role of inflammation (particularly NF-κB pathway) in the development and progression of myelofibrosis (MF), becoming a promising therapeutic target. Furthermore, tailoring treatment with currently available JAK inhibitors (such as ruxolitinib or fedratinib) does not modify the natural history of the disease and has important limitations, including cytopenias. Since recent studies have highlighted the role of miR-146a, a negative regulator of the NF-κB pathway, in the pathogenesis of MF; here we used miR-146a (KO) mice, a MF-like model lacking driver mutations, to investigate whether pharmacological inhibition of JAK/STAT and/or NF-κB pathways may reverse the myelofibrotic phenotype of these mice.

Germline assessment for alloHSCT candidates over 50 years: A 'Fast-Track' screening in myeloid neoplasms.

Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN.

Factor XI in Carriers of Antiphospholipid Antibodies: Elevated Levels Associated with Symptomatic Thrombotic Cases, While Low Levels Linked to Asymptomatic Cases.

Antiphospholipid syndrome (APS) is a thromboinflammatory disorder caused by circulating antiphospholipid autoantibodies (aPL) and characterized by an increased risk of thrombotic events. The pathogenic mechanisms of these antibodies are complex and not fully understood, but disturbances in coagulation and fibrinolysis have been proposed to contribute to the thrombophilic state. This study aims to evaluate the role of an emerging hemostatic molecule, FXI, in the thrombotic risk of patients with aPL.

Suramin, a drug for the treatment of trypanosomiasis, reduces the prothrombotic and metastatic phenotypes of colorectal cancer cells by inhibiting hepsin.

Unlabelled: Recently, our group identified serine-protease hepsin from primary tumor as a biomarker of metastasis and thrombosis in patients with localized colorectal cancer. We described hepsin promotes invasion and thrombin generation of colorectal cancer cells in vitro and in vivo and identified venetoclax as a hepsin inhibitor that suppresses these effects. Now, we aspire to identify additional hepsin inhibitors, aiming to broaden the therapeutic choices for targeted intervention in colorectal cancer.

Venetoclax is a potent hepsin inhibitor that reduces the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells.

Hepsin is a type II transmembrane serine protease and its expression has been linked to greater tumorigenicity and worse prognosis in different tumors. Recently, our group demonstrated that high hepsin levels from primary tumor were associated with a higher risk of metastasis and thrombosis in localized colorectal cancer patients. This study aims to explore the molecular role of hepsin in colorectal cancer.

Recommendations for the future management of thrombocytopenia in patients with liver cirrhosis: A modified RAND/UCLA appropriateness method.

Objective: The lack of consensus and specific guidelines, and the introduction of new treatments in thrombocytopenia management in liver cirrhosis patients, required a series of recommendations by experts to improve knowledge on this disease. This study's aim was to improve the knowledge around thrombocytopenia in liver cirrhosis patients, in order to contribute to the generation of future evidence to improve the management of this disease.

Patients And Methods: A modified version of the RAND/UCLA appropriateness method was used.

Usefulness and Limitations of Multiple Ligation-Dependent Probe Amplification in Antithrombin Deficiency.

Multiplex ligation-dependent probe amplification (MLPA) identifies genetic structural variants in in 5% of cases with antithrombin deficiency (ATD), the most severe congenital thrombophilia. Our aim was to unravel the utility and limitations of MLPA in a large cohort of unrelated patients with ATD (N = 341). MLPA identified 22 structural variants (SVs) causing ATD (6.

Platelet transcriptome analysis in patients with germline RUNX1 mutations.

Background: Germline mutations in RUNX1 can cause a familial platelet disorder that may lead to acute myeloid leukemia, an autosomal dominant disorder characterized by moderate thrombocytopenia, platelet dysfunction, and a high risk of developing acute myeloid leukemia or myelodysplastic syndrome. Discerning the pathogenicity of novel RUNX1 variants is critical for patient management.

Objectives: To extend the characterization of RUNX1 variants and evaluate their effects by transcriptome analysis.

Validation of immunofluorescence analysis of blood smears in patients with inherited platelet disorders.

Background: Inherited platelet disorders (IPDs) are rare diseases characterized by reduced blood platelet counts and/or impaired platelet function. Recognizing IPDs is advisable but often challenging. The diagnostic tools include clinical evaluation, platelet function tests, and molecular analyses.

Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients.

Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases.

Two SERPINC1 variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays.

Antithrombin deficiency, the most severe congenital thrombophilia, might be underestimated, as some pathogenic variants are not detected by routine functional methods. We have identified 2 new SERPINC1 variants, p.Glu227Lys and p.

Src-related thrombocytopenia: a fine line between a megakaryocyte dysfunction and an immune-mediated disease.

Src-related thrombocytopenia (SRC-RT) is a rare autosomal dominant, inherited platelet disorder resulting from the p.E527K heterozygous germline gain-of-function variant of Src. To date, genetic diagnosis of the disease has only been reported in 7 patients from 3 unrelated families.

Validation of a Virtual Assistant for Improving Medication Adherence in Patients with Comorbid Type 2 Diabetes Mellitus and Depressive Disorder.

Virtual assistants are programs that interact with users through text or voice messages simulating a human-based conversation. The development of healthcare virtual assistants that use messaging platforms is rapidly increasing. Still, there is a lack of validation of these assistants.

Expanding the genetic spectrum of TUBB1-related thrombocytopenia.

β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying 6 β1-tubulin variants, p.

Inherited Platelet Disorders: An Updated Overview.

Platelets play a major role in hemostasis as ppwell as in many other physiological and pathological processes. Accordingly, production of about 10 platelet per day as well as appropriate survival and functions are life essential events. Inherited platelet disorders (IPDs), affecting either platelet count or platelet functions, comprise a heterogenous group of about sixty rare diseases caused by molecular anomalies in many culprit genes.

Role of Thrombopoietin Receptor Agonists in Inherited Thrombocytopenia.

In the last decade, improvements in genetic testing have revolutionized the molecular diagnosis of inherited thrombocytopenias (ITs), increasing the spectrum of knowledge of these rare, complex and heterogeneous disorders. In contrast, the therapeutic management of ITs has not evolved in the same way. Platelet transfusions have been the gold standard treatment for a long time.