Loss of the Inv(16) Oncogene Eliminates Leukemia from the Blood and Spleen, but not the Bone Marrow.

Inversion of chromosome 16 [inv(16)] is one of the most common chromosomal rearrangements in Acute Myeloid Leukemia (AML) and generates the fusion gene , which initiates leukemogenesis. Patients with inv(16) at diagnosis invariably have the rearrangement at relapse, leading to the assumption that is required after leukemic transformation. However, this has yet to be shown experimentally.

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

Stabilizing Schottky-to-Ohmic Switching in HfO-Based Ferroelectric Films via Electrode Design.

The discovery of ferroelectric phases in HfO-based films has reignited interest in ferroelectrics and their application in resistive switching (RS) devices. This study investigates the pivotal role of electrodes in facilitating the Schottky-to-Ohmic transition (SOT) observed in devices consisting of ultrathin epitaxial ferroelectric HfYO (YHO) films deposited on LaSrMnO-buffered Nb-doped SrTiO (NbSTO|LSMO) with Ti|Au top electrodes. These findings indicate combined filamentary RS and ferroelectric switching occurs in devices with designed electrodes, having an ON/OFF ratio of over 100 during about 10 cycles.

Gastroesophageal reflux disease is associated with a more severe interstitial lung disease in systemic sclerosis in the EUSTAR cohort.

Objectives: Gastroesophageal reflux disease (GERD) is frequent in systemic sclerosis (SSc) and could predict progression of interstitial lung disease (ILD). We aimed to analyse (1) the prevalence of GERD among SSc-ILD patients, (2) its association with disease characteristics and (3) predictive factors for ILD progression in SSc-ILD patients with GERD.

Methods: SSc patients from the EUSTAR database with ILD were included.

Hydrogel injection molded complex macroencapsulation device geometry improves long-term cell therapy viability and function in the rat omentum transplant site.

Insulin-secreting allogeneic cell therapies are a promising treatment for type 1 diabetes, with the potential to eliminate hypoglycemia and long-term complications of the disease. However, chronic systemic immunosuppression is necessary to prevent graft rejection, and the acute risks associated with immunosuppression limit the number of patients who can be treated with allogeneic cell therapies. Islet macroencapsulation in a hydrogel biomaterial is one proposed method to reduce or eliminate immune suppression; however, macroencapsulation devices suffer from poor oxygen transport and limited efficacy as they scale to large animal model preclinical studies and clinical trials.

Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1-HER3 signaling.

Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer.

Vestibular Implant Surgery: How to Deal With Obstructed Semicircular Canals-A Diagnostic and Surgical Guide.

Background: A vestibular implant can partially restore vestibular function by providing motion information through implanted electrodes. During vestibular implantation, various obstructions of the semicircular canals, such as protein deposits, fibrosis, and ossification, can be encountered. The objective was to explore the relationship between preoperative imaging and intraoperative findings of semicircular canal obstruction and to develop surgical strategies for dealing with obstructions of the semicircular canal(s) in patients eligible for vestibular implantation.

Clinical relevance of calprotectin in patients with perianal fistulas in Crohn's disease and cryptoglandular fistulas.

Background And Aims: Previous literature suggests that faecal calprotectin (FC) discriminates Crohn's disease perianal fistulas from cryptoglandular fistulas, irrespective of luminal disease. This study aims to prospectively validate this and analyse if increased local fistula calprotectin levels are associated with fistula characteristics.

Methods: In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anaesthesia were included.

Pre-Clinical Assessment of Bupivacaine-Loaded Poly(ester urea) Thin Films for Controlled Drug Release and Effective Pain Management After Surgery.

Safe, effective pain management remains one of the biggest challenges following surgical procedures. Despite widespread recognition of this problem and advances in the mechanistic understanding of pain signaling, post-surgical pain is often undermanaged, with opioid use remaining the clinical standard. As an alternative to current oral, systemic treatments, a degradable bupivacaine-loaded poly(ester urea) (PEU) thin film has been developed to deliver bupivacaine directly to the site of injury over an extended duration.

A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding.

The SARS-CoV-2 nucleocapsid protein is indispensable for viral RNA genome processing. Although the N-terminal domain (NTD) is suggested to mediate specific RNA-interactions, high-resolution structures with viral RNA are still lacking. Available hybrid structures of the NTD with ssRNA and dsRNA provide valuable insights; however, the precise mechanism of complex formation remains elusive.

Interfacial vs confinement effects in the anisotropic frequency-dependent dielectric, THz and IR response of nanoconfined water.

We investigate the anisotropic frequency-dependent dielectric, THz and IR response of liquid water confined between two planar graphene sheets with force-field- and density-functional-theory-based molecular dynamics simulations. Using spatially resolved anisotropic spectra, we demonstrate the critical role of the volume over which the spectral response is integrated when reporting spatially averaged electric susceptibilities. To analyze the spectra, we introduce a unique decomposition into bulk, interfacial, and confinement contributions, which reveals that confinement effects on the spectra occur only for systems with graphene separation below 1.

The Europa Imaging System (EIS) Investigation.

The Europa Imaging System (EIS) consists of a Narrow-Angle Camera (NAC) and a Wide-Angle Camera (WAC) that are designed to work together to address high-priority science objectives regarding Europa's geology, composition, and the nature of its ice shell. EIS accommodates variable geometry and illumination during rapid, low-altitude flybys with both framing and pushbroom imaging capability using rapid-readout, 8-megapixel (4k × 2k) detectors. Color observations are acquired using pushbroom imaging with up to six broadband filters.

Facilitating comprehensive child health monitoring within REDCap - an open-source code for real-time Z-score assessments.

Background: Monitoring of somatic development through the assessment of anthropometric variables such as weight, height, and BMI is vital for evaluating the physical development and nutritional status of children. This approach aids in the early identification of somatic developmental disorders, enabling timely medical interventions. It traditionally relies on Z-scores, which compare anthropometric variables with reference standards.

Probabilistic photonic computing with chaotic light.

Biological neural networks effortlessly tackle complex computational problems and excel at predicting outcomes from noisy, incomplete data. Artificial neural networks (ANNs), inspired by these biological counterparts, have emerged as powerful tools for deciphering intricate data patterns and making predictions. However, conventional ANNs can be viewed as "point estimates" that do not capture the uncertainty of prediction, which is an inherently probabilistic process.

Performance of the EULAR Systemic sclerosis Impact of Disease (ScleroID) questionnaire as a patient-reported outcome measure for patients with diffuse systemic sclerosis.

Objective: Systemic sclerosis Impact of Disease (ScleroID) is the first comprehensive patient-reported outcome measure (PROM) specifically developed for systemic sclerosis (SSc). We investigated the performance of ScleroID in patients with diffuse cutaneous SSc (dcSSc), as a prerequisite for its use in randomised controlled trials (RCTs) testing potentially disease-modifying drugs.

Methods: All patients with dcSSc from the large, multicentric, ScleroID cohort were included.

Targeting IL-1/IRAK1/4 signaling in Acute Myeloid Leukemia Stem Cells Following Treatment and Relapse.

Therapies for acute myeloid leukemia (AML) face formidable challenges due to relapse, often driven by leukemia stem cells (LSCs). Strategies targeting LSCs hold promise for enhancing outcomes, yet paired comparisons of functionally defined LSCs at diagnosis and relapse remain underexplored. We present transcriptome analyses of functionally defined LSC populations at diagnosis and relapse, revealing significant alterations in IL-1 signaling.

A Modular Genetic Approach to Newborn Screening from Spinal Muscular Atrophy to Sickle Cell Disease-Results from Six Years of Genetic Newborn Screening.

Background/objectives: Genetic newborn screening (NBS) has already entered the phase of common practice in many countries. In Germany, spinal muscular atrophy (SMA), severe combined immunodeficiency (SCID) and sickle cell disease (SCD) are currently a mandatory part of NBS. Here, we describe the experience of six years of genetic NBS including the prevalence of those three diseases in Germany.

Evaluating the reproducibility of a deep learning algorithm for the prediction of retinal age.

Recently, a deep learning algorithm (DLA) has been developed to predict the chronological age from retinal images. The Retinal Age Gap (RAG), a deviation between predicted age from retinal images (Retinal Age, RA) and chronological age, correlates with mortality and age-related diseases. This study evaluated the reliability and accuracy of RA predictions and analyzed various factors that may influence them.

Dose-dependency of a combined EPA:DHA mixture on incorporation, washout, and protein synthesis in C2C12 myotubes.

We demonstrate divergent incorporation and washout patterns for EPA and DHA following high and low-dose EPA+DHA incubation in C2C12 myotubes, with higher concentrations favoring n-3 PUFA incorporation. Lower n-3 PUFA concentrations increased MPS without further upregulating the mTORC1 signaling pathway. Our study provides novel insights into the temporal incorporation and washout dynamics of EPA and DHA and, specifically, their combined effect on MPS, thereby advancing knowledge regarding dietary n-3 PUFA prescription to promote skeletal muscle health in humans.