Atypical B-Cell Acute Lymphoblastic Leukemia with iAMP21 in the Context of Constitutional Ring Chromosome 21: A Case Report and Review of the Genetic Insights.

Recent studies have demonstrated the association between constitutional ring chromosome 21 (r(21)c) and the development of B-cell acute lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21). iAMP21 acts as a driver which is often accompanied by secondary alterations that influence disease progression. Here, we report an atypical case of iAMP21 B-ALL with a unique molecular profile in the context of r(21)c.

Comprehensive detection of alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach.

Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer with high cure rate, but poses a significant medical challenge in adults and relapsed patients. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype, with approximately half of cases characterized by overexpression and frequent concomitant deletions. To address the need for efficient, rapid, and cost-effective detection of alterations, we developed a novel RT-qPCR technique combining SYBR Green and highresolution melting analysis on a single plate.

Assessing the Adoption of One Health Approaches in National Plans to Combat Health Threats: The Pilot of a One Health Conceptual Framework in Armenia.

Due to several factors, such as environmental and climate changes, the risk of health threats originating at the human-animal-environment interface, including vector-borne diseases (VBDs) and zoonoses, is increasing. Low-resource settings struggle to counter these multidimensional risks due to their already-strained health systems and are therefore disproportionally affected by the impact caused by these changes. Systemic approaches like One Health (OH) are sought to strengthen prevention and preparedness strategies by addressing the drivers of potential threats with a multidisciplinary and multisectoral approach, considering the whole system at the human-animal-environment interface.

Methotrexate & rheumatoid arthritis associated atherosclerosis: A narrative review of multidisciplinary approach for risk modification by the international board of experts.

Rheumatoid arthritis (RA) is an idiopathic, autoimmune connective tissue disorder that primarily affects the synovial joints, causing symmetric, erosive-deforming polyarthritis. It is also associated with extra-articular manifestations, particularly cardiovascular (CV) diseases (CVD). CV risk modification in RA remains unsolved despite recent advances in the management of RA.

Cytogenetic Assessment and Risk Stratification in Myelofibrosis with Optical Genome Mapping.

Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow.

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia.

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce.

Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer.

Broxbam, also known as N-hydroxy-4-{1-methoxy-4-[4'-(3'-bromo-4',5'-dimethoxyphenyl)-oxazol-5'-yl]-2-phenoxy} butanamide, is a novel chimeric inhibitor that contains two distinct pharmacophores in its molecular structure. It has been previously demonstrated to inhibit the activity of histone deacetylases (HDAC) and tubulin polymerisation, two critical components required for cancer growth and survival. In the present study, the potential suitability of broxbam for the treatment of liver cancer was investigated.

A Single-Run Next-Generation Sequencing (NGS) Assay for the Simultaneous Detection of Both Gene Mutations and Large Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes (MDS) and Related Myeloid Neoplasms.

Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms are clonal disorders that share most of their cytogenetic and molecular alterations. Despite the increased knowledge of the prognostic importance of genetics in these malignancies, next-generation sequencing (NGS) has not been incorporated into clinical practice in a validated manner, and the conventional karyotype remains mandatory in the evaluation of suspected cases. However, non-informative cytogenetics might lead to an inadequate estimation of the prognostic risk.

[Peculiarities of sonoelastographic imaging of thyroid papillary cancer in presence of autoimmune thyroiditis].

Aim: To determine the features of visualization of papillar thyroid cancer (PTC) in presence of autoimmune thyroiditis (AIT) according to sonoelastography data.

Materials And Methods: 155 patients were examined (75 PTC, 30 AIT, 20 PTC in presence of AIT and 30 with diffuse parenchymal changes) and 30 patients of the control group. Among patients with PTC 68 (90.

RNA Sequencing Analysis for the Identification of a PCM1/PDGFRB Fusion Gene Responsive to Imatinib.

The platelet-derived growth factor receptor β (PDGFRB) gene translocations lead to a spectrum of chronic myeloid neoplasms, frequently associated with eosinophilia. Clinical heterogeneity is associated with a molecular one. Here, we report a novel case of a patient harboring a t(5;8)(q33;p22) translocation, resulting in the PCM1/PDGFRB fusion.

Loss of Axon Bifurcation in Mesencephalic Trigeminal Neurons Impairs the Maximal Biting Force in Npr2-Deficient Mice.

Bifurcation of axons from dorsal root ganglion (DRG) and cranial sensory ganglion (CSG) neurons is mediated by a cGMP-dependent signaling pathway composed of the ligand C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2 and the cGMP-dependent protein kinase I (cGKI). Here, we demonstrate that mesencephalic trigeminal neurons (MTN) which are the only somatosensory neurons whose cell bodies are located within the CNS co-express Npr2 and cGKI. Afferents of MTNs form Y-shaped branches in rhombomere 2 where the ligand CNP is expressed.

Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade.

Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP)-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, neurons in dorsal root ganglia (DRG) and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction.

The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord.

A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI ( and ) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice.

Principles of protein targeting to the nucleolus.

The nucleolus is the hallmark of nuclear compartmentalization and has been shown to exert multiple roles in cellular metabolism besides its main function as the place of rRNA synthesis and assembly of ribosomes. Nucleolar proteins dynamically localize and accumulate in this nuclear compartment relative to the surrounding nucleoplasm. In this study, we have assessed the molecular requirements that are necessary and sufficient for the localization and accumulation of peptides and proteins inside the nucleoli of living cells.

A genetic strategy for the analysis of individual axon morphologies in cGMP signalling mutant mice.

One of the many physiological functions of cyclic guanosine 3',5' monophosphate (cGMP) signalling is the regulation of a specific mode of axonal branching. The bifurcation of axons from dorsal root ganglion (DRG) neurons at the dorsal root entry zone of the embryonic spinal cord is triggered by a cGMP -signalling pathway comprising the ligand C-type natriuretic peptide (CNP), the cGMP-producing natriuretic peptide receptor 2 (Npr2), and the cGMP-dependent protein kinase Iα (cGKIα). Absence of any of these components causes a loss of bifurcation and sensory axons instead only turn in either a rostral or a caudal direction.

Respiratory syncytial virus infection in recipients of allogeneic stem-cell transplantation: a retrospective study of the incidence, clinical features, and outcome.

Background: Respiratory syncytial virus (RSV) is a common cause of serious respiratory infections in hematopoietic stem-cell transplant (HSCT) recipients. We aimed to determine the frequency, risk factors, and outcome of RSV infection in allo-HSCT recipients.

Design And Methods: Data were collected from 275 allo-HSCT recipients and identified 32 patients (11.

Cell entry of arginine-rich peptides is independent of endocytosis.

Arginine-rich peptides are a subclass of cell-penetrating peptides that are taken up by living cells and can be detected freely diffusing inside the cytoplasm and nucleoplasm. This phenomenon has been attributed to either an endocytic mode of uptake and a subsequent release from vesicles or to direct membrane penetration (transduction). To distinguish between both possibilities, we have blocked endocytic pathways suggested to be involved in uptake of cell-penetrating peptides.

Influenza vaccination in hematopoietic SCT recipients.

Influenza is a potentially serious infection after hematopoietic SCT (HSCT). Vaccination is the main prophylactic approach in individuals at an increased risk for severe influenza disease or post-influenza complications. No controlled study on the efficacy of influenza vaccination has been performed in HSCT recipients and also studies evaluating the antibody response are limited by their small sizes and by that vaccinations have been performed at varying times after HSCT.

Evaluation of immune responses to seasonal influenza vaccination in healthy volunteers and in patients after stem cell transplantation.

Background: Influenza causes significant morbidity and mortality in immunocompromised stem cell transplantation (SCT) recipients. Measurement of cellular and humoral immunological responses might increase our understanding of how to estimate a protective response to influenza vaccination.

Methods: Eighteen healthy subjects and 14 SCT patients tested before and 4 weeks after influenza vaccination were included in the study.

Novel complex t(V;9;22) rearrangements in three cases with chronic myeloid leukemia and a rare translocation in a case with classical Philadelphia chromosome.

The fusion gene BCR/ABL arises in connection with a complex translocation event in 2-10% of cases with chronic myeloid leukemia (CML). Due to causative treatment with Imatinib most cases with variant rearrangements show no specific prognostic significance, though the events of therapy resistance remain to be studied. Herein we report on three CML cases with complex chromosomal aberrations not observed before, involving chromosomal regions such as 1p32, 2q11 and 6q12.

Equine arteritis virus is delivered to an acidic compartment of host cells via clathrin-dependent endocytosis.

Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae. Infection by EAV requires the release of the viral genome by fusion with the respective target membrane of the host cell. We have investigated the entry pathway of EAV into Baby Hamster Kidney cells (BHK).

Live-cell analysis of cell penetration ability and toxicity of oligo-arginines.

Cell penetrating peptides (CPPs) are useful tools to deliver low-molecular-weight cargoes into cells; however, their mode of uptake is still controversial. The most efficient CPPs belong to the group of arginine-rich peptides, but a systematic assessment of their potential toxicity is lacking. In this study we combined data on the membrane translocation abilities of oligo-arginines in living cells as a function of their chain length, concentration, stability and toxicity.

Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT.

Late occurring CMV disease is an important problem after allogeneic SCT and has been associated with poor CMV-specific immunity. We conducted a prospective study of 58 patients studied at 3-6 months after allo-SCT, to base the antiviral therapy on monitoring of CMV-specific immunity. Reactivation of CMV was measured by quantitative PCR, and intracellular IFN-gamma production was analysed by FACS and enzyme-linked immunospot.