A heterozygous CEBPA mutation disrupting the bZIP domain in a RUNX1 and SRSF2 mutational background causes MDS disease progression.

Myelodysplastic syndrome disease (MDS) is caused by the successive acquisition of mutations and thus displays a variable risk for progression to AML. Mutations in CEBPA are commonly associated with a high risk of disease progression, but whether they are causative for AML development is unclear. To analyse the molecular basis of disease progression we generated MDS patient-derived induced pluripotent stem cells from a low risk male patient harbouring RUNX1/SRSF2 mutations.

Predicting memory decline from left temporal lobe epilepsy surgery using preoperative fMRI: a multicenter study.

Objective: While fMRI language laterality has been used to predict verbal memory after epilepsy surgery, supporting evidence is not yet definitive. The FMRI in Anterior Temporal Epilepsy Surgery (FATES) project was a prospective observational cohort study at 10 US epilepsy centers, performed to determine whether a multivariable model including fMRI language laterality can predict verbal memory outcome 6 months after left temporal lobe epilepsy surgery.

Methods: This analysis includes 70 adults who underwent left temporal lobe epilepsy surgeries including hippocampal resection for treatment of epilepsy.

Predicting seizure onset zones from interictal intracranial EEG using functional connectivity and machine learning.

Functional connectivity (FC) analyses of intracranial EEG (iEEG) signals can potentially improve the mapping of epileptic networks in drug-resistant focal epilepsy. However, it remains unclear whether FC-based metrics provide additional value beyond established epilepsy biomarkers such as epileptic spikes and high-frequency oscillations (HFOs). Using interictal iEEG data from 26 patients, we estimated FC across eight frequency bands (4-290 Hz) using amplitude envelope correlation (AEC) and phase locking value (PLV).

Behavioral and neural effects of temporoparietal high-definition transcranial direct current stimulation in logopenic variant primary progressive aphasia: a preliminary study.

Background: High-definition-tDCS (HD-tDCS) is a recent technology that allows for localized cortical stimulation, but has not yet been investigated as an augmentative therapy while targeting the left temporoparietal cortex in logopenic variant PPA (lvPPA). The changes in neuronal oscillatory patterns and resting-state functional connectivity in response to HD-tDCS also remains poorly understood.

Objective: We sought to investigate the effects of HD-tDCS with phonologic-based language training on language, cognition, and resting-state functional connectivity in lvPPA.

The genomic analysis of patients with musculoskeletal metastases from an unknown origin.

Background: A subgroup of patients present with musculoskeletal (MSK) metastases but no detectable primary tumour. An inability to employ disease-specific treatment means this cohort's median survival is just 6-10 months. We present a novel, prospective, pilot study investigating the role of targeted Next Generation Sequencing (NGS) of metastases in these 'Cancer of Unknown Primary' (CUP) patients, reporting on diagnostic, therapeutic and prognostic benefits.

The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project.

Background: The 100,000 Genomes Project established infrastructure for Whole Genome Sequencing (WGS) in the United Kingdom.

Methods: A retrospective study of cancer patients recruited to the 100,000 Genomes Project by the West Midlands Genomics Medicine Centre, evaluating clinical relevance of results.

Results: After excluding samples with no sequencing data (1678/4851; 34.

Gamma amplitude-envelope correlations are strongly elevated within hyperexcitable networks in focal epilepsy.

Methods to quantify cortical hyperexcitability are of enormous interest for mapping epileptic networks in patients with focal epilepsy. We hypothesize that, in the resting state, cortical hyperexcitability increases firing-rate correlations between neuronal populations within seizure onset zones (SOZs). This hypothesis predicts that in the gamma frequency band (40-200 Hz), amplitude envelope correlations (AECs), a relatively straightforward measure of functional connectivity, should be elevated within SOZs compared to other areas.

Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1.

AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis.

T1-/T2-weighted ratio reveals no alterations to gray matter myelination in temporal lobe epilepsy.

Short-range functional connectivity in the limbic network is increased in patients with temporal lobe epilepsy (TLE), and recent studies have shown that cortical myelin content correlates with fMRI connectivity. We thus hypothesized that myelin may increase progressively in the epileptic network. We compared T1w/T2w gray matter myelin maps between TLE patients and age-matched controls and assessed relationships between myelin and aging.

Large-scale brain networks and intra-axial tumor surgery: a narrative review of functional mapping techniques, critical needs, and scientific opportunities.

In recent years, a paradigm shift in neuroscience has been occurring from "localizationism," or the idea that the brain is organized into separately functioning modules, toward "connectomics," or the idea that interconnected nodes form networks as the underlying substrates of behavior and thought. Accordingly, our understanding of mechanisms of neurological function, dysfunction, and recovery has evolved to include connections, disconnections, and reconnections. Brain tumors provide a unique opportunity to probe large-scale neural networks with focal and sometimes reversible lesions, allowing neuroscientists the unique opportunity to directly test newly formed hypotheses about underlying brain structural-functional relationships and network properties.

Mapping and decoding cortical engagement during motor imagery, mental arithmetic, and silent word generation using MEG.

Accurate quantification of cortical engagement during mental imagery tasks remains a challenging brain-imaging problem with immediate relevance to developing brain-computer interfaces. We analyzed magnetoencephalography (MEG) data from 18 individuals completing cued motor imagery, mental arithmetic, and silent word generation tasks. Participants imagined movements of both hands (HANDS) and both feet (FEET), subtracted two numbers (SUB), and silently generated words (WORD).

Responsive Neurostimulation of the Anterior Thalamic Nuclei in Refractory Genetic Generalized Epilepsy: A Case Series.

Genetic generalized epilepsies (GGEs) are thought to represent disorders of thalamocortical networks. There are currently no well-established non-pharmacologic treatment options for patients with drug-resistant GGE. NeuroPace's Responsive Neurostimulation (RNS) System was approved by the United States Food and Drug Administration to treat focal seizures with up to two ictal foci.

Late dominance of the right hemisphere during narrative comprehension.

PET and fMRI studies suggest that auditory narrative comprehension is supported by a bilateral multilobar cortical network. The superior temporal resolution of magnetoencephalography (MEG) makes it an attractive tool to investigate the dynamics of how different neuroanatomic substrates engage during narrative comprehension. Using beta-band power changes as a marker of cortical engagement, we studied MEG responses during an auditory story comprehension task in 31 healthy adults.

Anti-seizure medication treatment trials prior to pre-surgical evaluation.

Purpose: Our study evaluates patterns of anti-seizure medication (ASM) usage prior to pre-surgical evaluation in drug resistant epilepsy (DRE).

Methods: We conducted a retrospective study of patients with DRE presenting for pre-surgical evaluation from 1/1/2017 to 12/31/2018. We abstracted demographic data, ASM usage, MRI and EEG findings, and distance from home to our center.

Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells.

Acute myeloid leukaemia (AML) cells interact and modulate components of their surrounding microenvironment into their own benefit. Stromal cells have been shown to support AML survival and progression through various mechanisms. Nonetheless, whether AML cells could establish beneficial metabolic interactions with stromal cells is underexplored.

Phase Ib study of eltrombopag and azacitidine in patients with high-risk myelodysplastic syndromes and related disorders (the ELASTIC study).

Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of <150 × 10 /l received eltrombopag ranging from 25 to 300 mg.

Prediction of Naming Outcome With fMRI Language Lateralization in Left Temporal Epilepsy Surgery.

Background And Objectives: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery.

A retrospective observational research study to describe the real-world use of bosutinib in patients with chronic myeloid leukemia in the United Kingdom and the Netherlands.

Objectives: To describe the real-world effectiveness and safety of bosutinib in patients with chronic myeloid leukemia (CML).

Methods: This was a multi-center, retrospective, non-interventional chart review study conducted in 10 hospitals in the United Kingdom and the Netherlands.

Results: Eighty-seven patients were included.

Molecular Basis of Hematological Disease Caused by Inherited or Acquired RUNX1 Mutations.

The transcription factor RUNX1 is essential for correct hematopoietic development; in its absence in the germ line, blood stem cells are not formed. RUNX1 orchestrates dramatic changes in the chromatin landscape at the onset of stem cell formation, which set the stage for both stem self-renewal and further differentiation. However, once blood stem cells are formed, the mutation of the RUNX1 gene is not lethal but can lead to various hematopoietic defects and a predisposition to cancer.

Models of care for chronic myeloid leukemia patients during the COVID-19 pandemic in the United Kingdom: Changes in patient attitudes to remote consultations and future implications.

The ongoing COVID-19 pandemic has presented numerous challenges to the provision of patient care within hematology. We undertook a questionnaire-based study investigating the experiences and opinions of patients with chronic myeloid leukemia (CML) in the UK in relation to the different models of follow-up care received during the pandemic. One hundred fifty-four patients completed the online questionnaire.