Integrating advanced analytical methods to assess epigenetic marks affecting response to hypomethylating agents in higher risk myelodysplastic syndrome.

Background: Patients with higher-risk (HR) myelodysplastic syndrome (MDS), ineligible for allogeneic hematopoietic stem cell transplantation (alloHSCT), require prompt therapeutic interventions, such as treatment with hypomethylating agents (HMAs) to restore normal DNA methylation patterns, mainly of oncosuppressor genes, and consequently to delay disease progression and increase overall survival (OS). However, response assessment to HMA treatment relies on conventional methods with limited capacity to uncover a wide spectrum of underlying molecular events.

Methods: We implemented liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess 5' methyl-2' deoxycytidine (5mdC), 5' hydroxy-methyl-2'-deoxycytidine (5hmdC) levels and global adenosine/thymidine ([dA]/[T]) ratio in bone marrow aspirates from twenty-one HR MDS patients, pre- and post-HMA treatment.

Survival and quality of life in patients with lower risk myelodysplastic syndromes exposed to erythropoiesis-stimulating agents: an observational cohort study.

Background: In our previous study on erythropoiesis-stimulating agent (ESA) treatment in lower risk myelodysplastic syndromes from the European MDS (EUMDS) Registry, we showed that patients treated with ESAs had longer survival compared with patients who receive red blood cell transfusion (RBCT). In this study, with a longer follow up time and more patients included, we aimed to assess long-term effects on survival and health-related quality of life (HRQoL) of exposure to ESAs with or without RBCT in patients with lower risk myelodysplastic syndromes.

Methods: The EUMDS Registry is a non-interventional, longitudinal, real-world registry prospectively enrolling newly diagnosed patients older than 18 years with lower risk (International Prognostic Scoring System low or intermediate-1) myelodysplastic syndromes from 16 European countries and Israel.

Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients.

Proteasome inhibitors (PIs) constitute the most common type of induction treatment for multiple myeloma. Interactions between the proteasome, autophagy, and reactive oxygen species (ROS) have been shown in the past, thus emphasizing the need for a better understanding of the underlying pathophysiology. For this study, bone marrow mononuclear cells from 110 myeloma patients were collected at different disease stages.

Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.

Real-world treatment patterns and health care resource use for patients with myelofibrosis: results from the METER study.

Myelofibrosis (MF), a myeloproliferative neoplasm, was most commonly treated with hydroxyurea (HU) before approval of ruxolitinib (RUX), now the standard of care. Factors that influence real-world MF treatment patterns are not well understood. The METER study was a multi-country, retrospective chart review of MF treatment patterns, treatment effectiveness, and health care resource utilization.

R4Alz-R: a cutting-edge tool for spotting the very first and subtle signs of aging-related cognitive impairment with high accuracy.

The accurate diagnosis of aging-related neurocognitive disorders as early as possible, even in a phase that is characterized by the absence of clinical symptoms, is nowadays the holy grail of the neurosciences. R4Alz-R is a novel cognitive tool designed to objectively detect the subtle cognitive changes that emerge as the very first result of the aging processes and could be developed and broadened in a continuum from healthy aging to subjective cognitive impairment (SCI) and mild cognitive impairment (MCI), before reaching some type of dementia. The goal of the present study was to examine whether the R4Alz-R battery has the potential to detect these subtle changes.

To Drink or Not to Drink? Investigating Alcohol's Impact on Prostate Cancer Risk.

Background/objectives: Prostate cancer (PCa) is a significant global health issue. The relationship between alcohol consumption and PCa risk has been the subject of extensive research, yet findings remain inconsistent. This review aims to clarify the association between alcohol intake and PCa risk, its aggressiveness, and the potential metabolic pathways involved in PCa onset.

MicroRΝΑ analysis in patients with myelodysplastic neoplasms. Possible implications in risk stratification.

MiRNAs have been identified as participants in leukemogenesis by controlling several cellular functions, such as differentiation, proliferation, and apoptosis. Their role in myelodysplastic neoplasms (MDS) pathogenesis is researched due to implementations in early identification, classification, and therapeutical options. IPSS-R, being the most widely used MDS classification, underestimates early biological events that can alter the disease's prognosis.

Breakage and detachment of the rigid cystoscope's distal tip: an unusual case of urological instrument malfunction.

Herein, we describe an unusual case of cystoscope damage during a planned laser cystolithotripsy in a 65-year-old male with a previous history of radical prostatectomy for prostate cancer and subsequent serial urethral dilations for bladder neck contracture. Upon crossing the penile urethra without exerting significant pressure, we noticed the cystoscope's distal metallic tip detachment. Therefore, we re-introduced another 22Fr cystoscope and removed the broken part with alligator forceps.

A Multilayer Architecture towards the Development and Distribution of Multimodal Interface Applications on the Edge.

Today, Smart Assistants (SAs) are supported by significantly improved Natural Language Processing (NLP) and Natural Language Understanding (NLU) engines as well as AI-enabled decision support, enabling efficient information communication, easy appliance/device control, and seamless access to entertainment services, among others. In fact, an increasing number of modern households are being equipped with SAs, which promise to enhance user experience in the context of smart environments through verbal interaction. Currently, the market in SAs is dominated by products manufactured by technology giants that provide well designed off-the-shelf solutions.

The seasonal distribution of immune thrombotic thrombocytopenic purpura is influenced by geography: Epidemiologic findings from a multi-center analysis of 719 disease episodes.

Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included.

Subjective Cognitive Impairment Can Be Detected from the Decline of Complex Cognition: Findings from the Examination of Remedes 4 Alzheimer's (R4Alz) Structural Validity.

Unlabelled: R4Alz is utilized for the early detection of minor neurocognitive disorders. It was designed to assess three main dimensions of cognitive-control abilities: working-memory capacity, attentional control, and executive functioning.

Objectives: To reveal the cognitive-control dimensions that can differentiate between adults and older adults with healthy cognition, people with subjective cognitive impairment, and people diagnosed with mild cognitive impairment by examining the factorial structure of the R4Alz tool.

Fetal hemoglobin induction in azacytidine responders enlightens methylation patterns related to blast clearance in higher-risk MDS and CMML.

Background: As new treatment options for patients with higher-risk myelodysplastic syndromes are emerging, identification of prognostic markers for hypomethylating agent (HMA) treatment and understanding mechanisms of their delayed and short-term responses are essential. Early fetal hemoglobin (HbF) induction has been suggested as a prognostic indicator for decitabine-treated patients. Although epigenetic mechanisms are assumed, responding patients' epigenomes have not been thoroughly examined.

Ixazomib plus daratumumab and dexamethasone: Final analysis of a phase 2 study among patients with relapsed/refractory multiple myeloma.

Novel therapies have improved outcomes for multiple myeloma (MM) patients, but most ultimately relapse, making treatment decisions for relapsed/refractory MM (RRMM) patients increasingly challenging. We report the final analysis of a single-arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexamethasone (IDd; NCT03439293). Sixty-one RRMM patients (ixazomib/daratumumab-naïve; 1-3 prior therapies) were enrolled to receive IDd (28-day cycles) until disease progression/unacceptable toxicity.

Inflammatory profile of lower risk myelodysplastic syndromes.

The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs).

Dense Multi-Scale Graph Convolutional Network for Knee Joint Cartilage Segmentation.

In this paper, we propose a dense multi-scale adaptive graph convolutional network () method for automatic segmentation of the knee joint cartilage from MR images. Under the multi-atlas setting, the suggested approach exhibits several novelties, as described in the following. First, our models integrate both local-level and global-level learning simultaneously.

Autophagy and oxidative stress modulation mediate Bortezomib resistance in prostate cancer.

Proteasome inhibitors such as Bortezomib represent an established type of targeted treatment for several types of hematological malignancies, including multiple myeloma, Waldenstrom's macroglobulinemia, and mantle cell lymphoma, based on the cancer cell's susceptibility to impairment of the proteasome-ubiquitin system. However, a major problem limiting their efficacy is the emergence of resistance. Their application to solid tumors is currently being studied, while simultaneously, a wide spectrum of hematological cancers, such as Myelodysplastic Syndromes show minimal or no response to Bortezomib treatment.