Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.

Background: B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.

Progression of Heart Failure in People with Type 2 Diabetes in Germany: An Analysis Using German Health Insurance Claims Data.

Individuals with type 2 diabetes (T2D) show high risk of heart failure (HF). Left ventricular ejection fraction is a major factor for disease progression. In Germany, no recent longitudinal data are available.

Dysferlin Enables Tubular Membrane Proliferation in Cardiac Hypertrophy.

Background: Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies but can result in heart failure if left untreated. Here, we hypothesized that the membrane fusion and repair protein dysferlin is critical for the integrity of the transverse-axial tubule (TAT) network inside cardiomyocytes and contributes to the proliferation of TAT endomembranes during pressure overload-induced cardiac hypertrophy.

Methods: Stimulated emission depletion and electron microscopy were used to localize dysferlin in mouse and human cardiomyocytes.

The Multifaceted Actions of PVP-Curcumin for Treating Infections.

Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP-curcumin as a photosensitizer for antimicrobial photodynamic therapy (aPDT) as well as its potential to act as an adjuvant in antibiotic drug therapy.

The intricacies of isomiRs: from classification to clinical relevance.

MicroRNAs (miRNAs) and isoforms of their archetype, called isomiRs, regulate gene expression via complementary base-pair binding to messenger RNAs (mRNAs). The partially evolutionarily conserved isomiR sequence variations are differentially expressed among tissues, populations, and genders, and between healthy and diseased states. Aiming towards the clinical use of isomiRs as diagnostic biomarkers and for therapeutic purposes, several challenges need to be addressed, including (i) clarification of isomiR definition, (ii) improved annotation in databases with new standardization (such as the mirGFF3 format), and (iii) improved methods of isomiR detection, functional verification, and in silico analysis.

Paul Glaucoma Implant following Congenital Cataract Surgery in a Pediatric Cohort.

: The aim of this study was to evaluate the short-term efficacy and safety of the Paul Glaucoma Implant (PGI) in pediatric eyes diagnosed with glaucoma following congenital cataract surgery (GFCS). : A retrospective, single-center, descriptive study was conducted on consecutive children diagnosed with GFCS who underwent PGI implantation between July 2022 and November 2023 at the University Medical Center Mainz. The primary outcome measure was the reduction in IOP at the last follow-up visit.

Experimental capture of miRNA targetomes: disease-specific 3'UTR library-based miRNA targetomics for Parkinson's disease.

The identification of targetomes remains a challenge given the pleiotropic effect of miRNAs, the limited effects of miRNAs on individual targets, and the sheer number of estimated miRNA-target gene interactions (MTIs), which is around 44,571,700. Currently, targetome identification for single miRNAs relies on computational evidence and functional studies covering smaller numbers of targets. To ensure that the targetome analysis could be experimentally verified by functional assays, we employed a systematic approach and explored the targetomes of four miRNAs (miR-129-5p, miR-129-1-3p, miR-133b, and miR-873-5p) by analyzing 410 predicted target genes, both of which were previously associated with Parkinson's disease (PD).

Phosphate Restriction Prevents Metabolic Acidosis and Curbs Rise in FGF23 and Mortality in Murine Folic Acid-Induced AKI.

Significance Statement: Patients with AKI suffer a staggering mortality rate of approximately 30%. Fibroblast growth factor 23 (FGF23) and phosphate (P i ) rise rapidly after the onset of AKI and have both been independently associated with ensuing morbidity and mortality. This study demonstrates that dietary P i restriction markedly diminished the early rise in plasma FGF23 and prevented the rise in plasma P i , parathyroid hormone, and calcitriol in mice with folic acid-induced AKI (FA-AKI).

Exploring Patient Demographics and Presence of Retinal Vascular Disease in Paracentral Acute Middle Maculopathy.

Purpose: To investigate the sociodemographic profile, the association with retinal vascular diseases (RVD) and systemic comorbidities, and visual outcomes of patients with paracentral acute middle maculopathy (PAMM) in a large, ethnically diverse single-center cohort.

Design: Retrospective cohort study.

Methods: Electronic health record query for all patients presenting with PAMM at Moorfields Eye Hospital, London, was completed.

Effect of serum creatinine difference between the Jaffe and the enzymatic method on kidney disease detection and staging.

Background: Serum creatinine (SCr), mainly determined by the Jaffe or an enzymatic method, is the central marker to assess kidney function. Deviations between these two methods may affect the diagnosis and staging of acute kidney injury (AKI) and chronic kidney disease (CKD).

Methods: The results of the first parallel SCr measurement (Jaffe and enzymatic method) of adult in- and outpatients in the same serum sample at the University Hospital Essen (Essen, Germany) between 2020-2022 were retrospectively evaluated.

A foundation model for generalizable disease detection from retinal images.

Medical artificial intelligence (AI) offers great potential for recognizing signs of health conditions in retinal images and expediting the diagnosis of eye diseases and systemic disorders. However, the development of AI models requires substantial annotation and models are usually task-specific with limited generalizability to different clinical applications. Here, we present RETFound, a foundation model for retinal images that learns generalizable representations from unlabelled retinal images and provides a basis for label-efficient model adaptation in several applications.

Retinal Optical Coherence Tomography Features Associated With Incident and Prevalent Parkinson Disease.

Background And Objectives: Cadaveric studies have shown disease-related neurodegeneration and other morphological abnormalities in the retina of individuals with Parkinson disease (PD); however, it remains unclear whether this can be reliably detected with in vivo imaging. We investigated inner retinal anatomy, measured using optical coherence tomography (OCT), in prevalent PD and subsequently assessed the association of these markers with the development of PD using a prospective research cohort.

Methods: This cross-sectional analysis used data from 2 studies.

Brain Maturation Patterns on Normalized FLAIR MR Imaging in Children and Adolescents.

Background And Purpose: Signal analysis of FLAIR sequences is gaining momentum for studying neurodevelopment and brain maturation, but FLAIR intensity varies across scanners and needs to be normalized. This study aimed to establish normative values for standardized FLAIR intensity in the pediatric brain.

Materials And Methods: A new automated algorithm for signal normalization was used to standardize FLAIR intensity across scanners and subjects.

A draft human pangenome reference.

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels.

Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues.

Molecular mechanisms of organismal and cell aging remain incompletely understood. We, therefore, generated a body-wide map of noncoding RNA (ncRNA) expression in aging (16 organs at ten timepoints from 1 to 27 months) and rejuvenated mice. We found molecular aging trajectories are largely tissue-specific except for eight broadly deregulated microRNAs (miRNAs).

Long-Term Efficacy and Safety of Modified Canaloplasty Versus Trabeculectomy in Open-Angle Glaucoma.

Background: To evaluate the long-term efficacy and safety of modified canaloplasty versus trabeculectomy in open-angle glaucoma.

Methods: In total, 210 subjects with open-angle glaucoma were included. 70 were treated with Mitomycin C-augmented modified canaloplasty with enhanced subconjunctival filtration and 140 with Mitomycin C-augmented trabeculectomy.

Mechanistic Insights of the LEMD2 p.L13R Mutation and Its Role in Cardiomyopathy.

Background: Nuclear envelope proteins play an important role in the pathogenesis of hereditary cardiomyopathies. Recently, a new form of arrhythmic cardiomyopathy caused by a homozygous mutation (p.L13R) in the inner nuclear membrane protein LEMD2 was discovered.

Assessing Differences in Attitudes toward Occupational Safety and Health Measures for Infection Control between Office and Assembly Line Employees during the COVID-19 Pandemic in Germany: A Cross-Sectional Analysis of Baseline Data from a Repeated Employee Survey.

In our study, we investigated possible differences across occupational groups regarding employees’ perceived work-related risk of infection with SARS-CoV-2, attitudes toward technical, organisational, and personal occupational safety and health (OSH) measures for infection control, and factors associated with this attitude. We analysed baseline data (10 August to 25 October 2020) from a repeated standardised online survey distributed at a worldwide leading global supplier of technology and services in Germany. 2144 employees (32.