Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms.

Background: Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear.

Endovascular robotics: technical advances and future directions.

Endovascular interventions excel in treating cardiovascular diseases in a minimally invasive manner, showing improved outcomes over open techniques. However, challenges related to precise navigation - still relying on 2D fluoroscopy - persist. This review examines the role of robotics, highlighting commercial and research platforms, while exploring emerging trends like MRI compatibility, enhanced navigation, and autonomy.

Robotic Laser Tissue Soldering for Atraumatic Soft Tissue Fusion Guided by Fluorescent Nanothermometry.

Minimally invasive surgical techniques, including endoscopic and robotic procedures, continue to revolutionize patient care, for their ability to minimize surgical trauma, thus promoting faster recovery and reduced hospital stays. Yet, the suturing of soft tissues ensuring damage-free tissue bonding during these procedures remains challenging due to missing haptics and the fulcrum effect. Laser tissue soldering has potential in overcoming these issues, offering atraumatic seamless tissue fusion.

MethScore as a new comprehensive DNA methylation-based value refining the prognosis in acute myeloid leukemia.

Background: Changes in DNA methylation are common events in the pathogenesis of acute myeloid leukemia (AML) and have been repeatedly reported as associated with prognosis. However, studies integrating these numerous and potentially prognostically relevant DNA methylation changes are lacking. Therefore, we aimed for an overall evaluation of these epigenetic aberrations to provide a comprehensive NGS-based approach of DNA methylation assessment for AML prognostication.

Attenuated cell cycle and DNA damage response transcriptome signatures and overrepresented cell adhesion processes imply accelerated progression in patients with lower-risk myelodysplastic neoplasms.

Patients with myelodysplastic neoplasms (MDS) are classified according to the risk of acute myeloid leukemia transformation. Some lower-risk MDS patients (LR-MDS) progress rapidly despite expected good prognosis. Using diagnostic samples, we aimed to uncover the mechanisms of this accelerated progression at the transcriptome level.

Towards an Action Recognition Framework for Endovascular Surgery.

Objective knowledge about instrument manoeuvres in endovascular surgery is essential for evaluating surgical skills and developing advanced technologies for cathlab routines. To the recent day, endovascular navigation has been exclusively assessed in laboratory scenarios. By contrast, information contained in available fluoroscopy data from clinical cases has been disregarded.

ABC transporters are predictors of treatment failure in acute myeloid leukaemia.

Introduction: To date, no chemoresistance predictors are included in acute myeloid leukaemia (AML) prognostic scoring systems to distinguish responding and refractory AML patients prior to chemotherapy. ABC transporters have been described as altering AML chemosensitivity; however, a relevant study investigating their role at various molecular levels was lacking.

Methods: Gene expression, genetic variants, methylation and activity of ABCA2, ABCA5, ABCB1, ABCB6, ABCC1, ABCC3 and ABCG2 were analysed in AML blasts and healthy myeloblasts.

A novel germline hyperactivating JAK2 mutation L604F.

Somatic JAK2 mutations are the main molecular cause of the vast majority of polycythemia vera (PV) cases. According to a recent structural model, the prevalent acquired V617F mutation improves the stability of the JAK2 dimer, thereby enhancing the constitutive JAK2 kinase activity. Germline JAK2 mutations usually do not largely alter JAK2 signaling, although they may modulate the impact of V617F.

Expression of circular RNAs in myelodysplastic neoplasms and their association with mutations in the splicing factor gene SF3B1.

Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells.

In-Vivo Validation of a Novel Robotic Platform for Endovascular Intervention.

Objective: In-vivo validation on animal setting of a pneumatically propelled robot for endovascular intervention, to determine safety and clinical advantage of robotic cannulations compared to manual operation.

Methods: Robotic assistance and image-guided intervention are increasingly used for improving endovascular procedures with enhanced navigation dexterity and accuracy. However, most platforms developed in the past decade still present inherent limitations in terms of altered clinical workflow, counterintuitive human-robot interaction, and a lack of versatility.

RUNX1 mutations contribute to the progression of MDS due to disruption of antitumor cellular defense: a study on patients with lower-risk MDS.

Patients with lower-risk myelodysplastic syndromes (LR-MDS) have a generally favorable prognosis; however, a small proportion of cases progress rapidly. This study aimed to define molecular biomarkers predictive of LR-MDS progression and to uncover cellular pathways contributing to malignant transformation. The mutational landscape was analyzed in 214 LR-MDS patients, and at least one mutation was detected in 137 patients (64%).

Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes.

Background/aim: Prediction of response to azacitidine (AZA) treatment is an important challenge in hematooncology. In addition to protein coding genes (PCGs), AZA efficiency is influenced by various noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular RNAs (circRNAs), and transposable elements (TEs).

Materials And Methods: RNA sequencing was performed in patients with myelodysplastic syndromes or acute myeloid leukemia before AZA treatment to assess contribution of ncRNAs to AZA mechanisms and propose novel disease prediction biomarkers.

A validation study of potential prognostic DNA methylation biomarkers in patients with acute myeloid leukemia using a custom DNA methylation sequencing panel.

Background: Multiple studies have reported the prognostic impact of DNA methylation changes in acute myeloid leukemia (AML). However, these epigenetic markers have not been thoroughly validated and therefore are still not considered in clinical practice. Hence, we aimed to independently verify results of selected studies describing the relationship between DNA methylation of specific genes and their prognostic potential in predicting overall survival (OS) and event-free survival (EFS).

Somatic Mutations in Oncogenes Are in Chronic Myeloid Leukemia Acquired Deregulated Base-Excision Repair and Alternative Non-Homologous End Joining.

Somatic mutations are a common molecular mechanism through which chronic myeloid leukemia (CML) cells acquire resistance to tyrosine kinase inhibitors (TKIs) therapy. While most of the mutations in the kinase domain of BCR-ABL1 can be successfully managed, the recurrent somatic mutations in other genes may be therapeutically challenging. Despite the major clinical relevance of mutation-associated resistance in CML, the mechanisms underlying mutation acquisition in TKI-treated leukemic cells are not well understood.

μRALP and Beyond: Micro-Technologies and Systems for Robot-Assisted Endoscopic Laser Microsurgery.

Laser microsurgery is the current gold standard surgical technique for the treatment of selected diseases in delicate organs such as the larynx. However, the operations require large surgical expertise and dexterity, and face significant limitations imposed by available technology, such as the requirement for direct line of sight to the surgical field, restricted access, and direct manual control of the surgical instruments. To change this status quo, the European project μRALP pioneered research towards a complete redesign of current laser microsurgery systems, focusing on the development of robotic micro-technologies to enable endoscopic operations.

Progress in robotics for combating infectious diseases.

The world was unprepared for the COVID-19 pandemic, and recovery is likely to be a long process. Robots have long been heralded to take on dangerous, dull, and dirty jobs, often in environments that are unsuitable for humans. Could robots be used to fight future pandemics? We review the fundamental requirements for robotics for infectious disease management and outline how robotic technologies can be used in different scenarios, including disease prevention and monitoring, clinical care, laboratory automation, logistics, and maintenance of socioeconomic activities.

Low Plasma Citrate Levels and Specific Transcriptional Signatures Associated with Quiescence of CD34 Progenitors Predict Azacitidine Therapy Failure in MDS/AML Patients.

To better understand the molecular basis of resistance to azacitidine (AZA) therapy in myelodysplastic syndromes (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), we performed RNA sequencing on pre-treatment CD34 hematopoietic stem/progenitor cells (HSPCs) isolated from 25 MDS/AML-MRC patients of the discovery cohort (10 AZA responders (RD), six stable disease, nine progressive disease (PD) during AZA therapy) and from eight controls. Eleven MDS/AML-MRC samples were also available for analysis of selected metabolites, along with 17 additional samples from an independent validation cohort. Except for two patients, the others did not carry isocitrate dehydrogenase (IDH)1/2 mutations.

An MR-Safe Endovascular Robotic Platform: Design, Control, and Ex-Vivo Evaluation.

Objective: Cardiovascular diseases are the most common cause of global death. Endovascular interventions, in combination with advanced imaging technologies, are promising approaches for minimally invasive diagnosis and therapy. More recently, teleoperated robotic platforms target improved manipulation accuracy, stabilisation of instruments in the vasculature, and reduction of patient recovery times.

Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients.

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34 cells were assessed by whole-genome microarrays.

LncRNA Profiling Reveals That the Deregulation of H19, WT1-AS, TCL6, and LEF1-AS1 Is Associated with Higher-Risk Myelodysplastic Syndrome.

Background: myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder with an incompletely known pathogenesis. Long noncoding RNAs (lncRNAs) play multiple roles in hematopoiesis and represent a new class of biomarkers and therapeutic targets, but information on their roles in MDS is limited.

Aims: here, we aimed to characterize lncRNAs deregulated in MDS that may function in disease pathogenesis.

Circular RNAs in Hematopoiesis with a Focus on Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Circular RNAs (circRNAs) constitute a recently recognized group of noncoding transcripts that function as posttranscriptional regulators of gene expression at a new level. Recent developments in experimental methods together with rapidly evolving bioinformatics approaches have accelerated the exploration of circRNAs. The differentiation of hematopoietic stem cells into a broad spectrum of specialized blood lineages is a tightly regulated process that depends on a multitude of factors, including circRNAs.

Preclinical Performance Evaluation of a Robotic Endoscope for Non-Contact Laser Surgery.

Despite great efforts, transoral robotic laser surgery has not been established clinically. Patient benefits are yet to be proven to accept shortcomings of robotic systems. In particular, laryngeal reachability and transition from microscope to accurate endoscopic laser ablation have not been achieved.

Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome.

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers of the disease. We aimed to characterize the expression profiles of circulating sncRNAs of MDS patients and to search for specific RNAs applicable as potential biomarkers.

Stereo vision-based tracking of soft tissue motion with application to online ablation control in laser microsurgery.

Recent research has revealed that image-based methods can enhance accuracy and safety in laser microsurgery. In this study, non-rigid tracking using surgical stereo imaging and its application to laser ablation is discussed. A recently developed motion estimation framework based on piecewise affine deformation modeling is extended by a mesh refinement step and considering texture information.