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.

The impact of radiofrequency thermocoagulation on brain connectivity in drug-resistant epilepsy: Insights from stereo-electroencephalography and cortico-cortical evoked potentials.

Objective: To investigate whether local lesions created by stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) affect distant brain connectivity and excitability in patients with focal, drug-resistant epilepsy (DRE).

Methods: Ten patients with focal DRE underwent SEEG implantation and subsequently 1 Hz bipolar repetitive electrical stimulation (RES) for 30 s before and after RFTC. Root mean square (RMS) of cortico-cortical evoked potentials (CCEPs) was calculated for 15 ms to 300 ms post-stimulation with baseline correction.

Association Between Blood Type and Mortality Among Severely Injured Patients Enrolled in the Pragmatic Randomized Optimal Platelet and Plasma Ratios Trial.

Introduction: Previous studies suggested that type O blood may be associated with increased mortality and/or thrombotic complications among trauma patients. The purpose of this analysis was to evaluate the relationship between endogenous blood type, mortality, and complications among patients receiving massive transfusions, using data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial.

Materials And Methods: This was a secondary analysis of the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial that included patients with the reported blood type (A, AB, B, or O) data.

In vivo 9.4 Tesla MRI of a patient with drug-resistant epilepsy: Technical report.

Purpose: In resective epilepsy surgery for drug-resistant focal epilepsy (DRE), good seizure outcome is strongly associated with visualization of an epileptogenic lesion on MRI. Standard clinical MRI (≤ 3 Tesla (T)) may fail to detect subtle lesions. 7T MRI enhances detection and delineation, the potential benefits of increasing field strength to 9.

Nitrogen Enriched Tröger's Base Polymers of Intrinsic Microporosity for Heterogeneous Catalysis.

Heterogeneous catalysis is significantly enhanced by the use of highly porous polymers with specific functionalities, such as basic groups, which accelerate reaction rates. Polymers of intrinsic microporosity (PIMs) provide a unique platform for catalytic reactions owing to their high surface areas and customizable pore structures. We herein report a series of Tröger's base polymers (TB-PIMs) with enhanced basicity, achieved through the incorporation of nitrogen-containing groups into their repeat units, such as triazine and triphenylamine.

Increased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation.

In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.

Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency.

Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies.

Analysis of time to regulatory approval in an exception from informed consent trial in trauma patients.

Background: The interactive media-based approach to community consultation and public disclosure (CC/PD), a key step when conducting exception from informed consent (EFIC) clinical trials, is intended to be completed in 4 months. This analysis characterizes the process, from initiation of CC/PD activities to institutional review board approval, to better understand the barriers and how these can be mitigated.

Methods: This is a retrospective post hoc analysis of data collected as part of the CC/PD campaigns conducted for a large trial involving up to 90 trauma centers in the United States.

Mitochondrial protective potential of fucoxanthin in brain disorders.

Mitochondrial dysfunction is a common feature of brain disorders. Mitochondria play a central role in oxidative phosphorylation; thus changes in energy metabolism in the brain have been reported in conditions such as Alzheimer's disease, Parkinson's disease, and stroke. In addition, mitochondria regulate cellular responses associated with neuronal damage such as the production of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), and apoptosis.

Objective outcome prediction in depression through functional MRI brain network dynamics.

Research Purpose: Subjective clinical decision-making in major depressive disorder (MDD) may result in low treatment effectiveness. This study aims to identify objective predictors of MDD outcome using resting-state functional MRI scans, acquired from 25 MDD patients at baseline. Over a year, patients were assessed every 3 months, labeled as positive or negative outcome (change in depression severity).

Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors.

Malignant rhabdoid tumor (MRT) is one of the most aggressive childhood cancers for which no effective treatment options are available. Reprogramming of cellular metabolism is an important hallmark of cancer, with various metabolism-based drugs being approved as a cancer treatment. In this study, we use patient-derived tumor organoids (tumoroids) to map the metabolic landscape of several pediatric cancers.

A bioprinted and scalable model of human tubulo-interstitial kidney fibrosis.

Chronic kidney disease (CKD) affects more than 10% of the global population. As kidney function negatively correlates with the presence of interstitial fibrosis, the development of new anti-fibrotic therapies holds promise to stabilize functional decline in CKD patients. The goal of the study was to generate a scalable bioprinted 3-dimensional kidney tubulo-interstitial disease model of kidney fibrosis.

Low-Intensity Resistance Exercise in Cardiac Rehabilitation: A Narrative Review of Mechanistic Evidence and Clinical Implications.

Cardiac rehabilitation, a multi-component intervention designed to mitigate the impact of cardiovascular disease, often underutilises low-intensity resistance exercise despite its potential benefits. This narrative review critically examines the mechanistic and clinical evidence supporting the incorporation of low-intensity resistance exercise into cardiac rehabilitation programmes. Research indicates that low-intensity resistance exercise induces hypertrophic adaptations by maximising muscle fibre activation through the size principle, effectively recruiting larger motor units as it approaches maximal effort.

Virtual Reality to Improve Sleep Quality in Patients Suffering from Painful Diabetic Polyneuropathy: A Proof of Concept Study.

: Sleep disturbance is often observed in the context of chronic pain. We hypothesize that, by providing an immersive Virtual Reality (VR) experience with a serious game to chronic pain patients an hour before bedtime, attention can be diverted from the pain condition, consequently leading to improved sleep quality. The aim is to evaluate the efficacy of VR compared to usual care in reducing the number of awakenings during the night and increasing sleep efficiency in patients suffering from painful diabetic polyneuropathy (PDPN).

Postoperative Radiotherapy for pT1- and pT2-Classified Squamous Cell Carcinoma of the External Auditory Canal.

Background: There is no consensus regarding the indication for postoperative radiotherapy (PORT) for T1- and T2-classified squamous cell carcinoma (SCC) of the external auditory canal (EAC) even with negative surgical margins. This study aimed to evaluate whether PORT provides additional benefits for these cases.

Methods: We collected retrospective data from fourteen international hospitals, including resected pT1- and pT2-classified EAC SCC with negative surgical margins.

How Inclusive Are Patient Decision Aids for People with Limited Health Literacy? An Analysis of Understandability Criteria and the Communication about Options and Probabilities.

Objective: Patient decision aids (PtDAs) can support shared decision making. We aimed to explore how inclusive PtDAs are for people with limited health literacy (LHL) by analyzing 1) the understandability of PtDAs using established criteria, 2) how options and probabilities of outcomes are communicated, and 3) the extent to which risk communication (RC) guidelines are followed.

Methods: In a descriptive document analysis, we analyzed Dutch PtDAs available in 2021 that met the International Patient Decision Aid Standards.

Heterogeneity and Penumbra of White Matter Hyperintensities in Small Vessel Diseases Determined by Quantitative MRI.

Background: White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease.

HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia.

KMT2A::MLLT3 acute myelomonocytic leukemia (AML) comes in two clinically and biologically different subtypes. One is characterized by inferior outcome, older age, and MECOM oncogene expression. The other is mainly observed in children and young adults, associates with better clinical outcome, but lacks MECOM.

Preparing the future combat surgeon: a survey of the military general surgery trainee GME experience.

Introduction: Graduate medical education (GME) lacks a standardized military training program for general surgery residents, and concern exists that they may not be prepared to serve as combat surgeons on training completion. The purpose of this study was to assess military surgery trainee satisfaction with their programs. Our hypothesis was that military residents were not completely confident to care for combat casualties on completion of current GME training.

A semi-permeable insert culture model for the distal part of the nephron with human and mouse tubuloid epithelial cells.

Tubuloids are advanced in vitro models obtained from adult human or mouse kidney cells with great potential for modelling kidney function in health and disease. Here, we developed a polarized human and mouse tubuloid epithelium on cell culture inserts, namely Transwell™ filters, as a model of the distal nephron with an accessible apical and basolateral side that allow for characterization of epithelial properties such as leak-tightness and epithelial resistance. Tubuloids formed a leak-tight and confluent epithelium on Transwells™ and the human tubuloids were differentiated towards the distal part of the nephron.