Investigation of Exome-Wide Tumor Heterogeneity on Colorectal Tissue-Based Single Cells.

The progression of colorectal cancer is strongly influenced by environmental and genetic conditions. One of the key factors is tumor heterogeneity which is extensively studied by cfDNA and bulk sequencing methods; however, we lack knowledge regarding its effects at the single-cell level. Motivated by this, we aimed to employ an end-to-end single-cell sequencing workflow from tissue-derived sample isolation to exome sequencing.

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Stabilizing effect of HP-β-CD on infliximab in liquid formulations and a solid formulation produced by electrospinning.

The development of stable biopharmaceutical formulations, such as monoclonal antibodies, poses a great challenge in the pharmaceutical industry. This study investigated the stabilizing effect of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in liquid and solid formulations of infliximab during processing and storage. The solid formulation was produced by a scaled-up high-speed electrospinning method, resulting in a product suitable for reconstitution with excellent dissolution properties.

Insights into eye genetics and recent advances in ocular gene therapy.

The rapid advancements in the field of genetics have significantly propelled the development of gene therapies, paving the way for innovative treatments of various hereditary disorders. This review focuses on the genetics of ophthalmologic conditions, highlighting the currently approved ophthalmic gene therapy and exploring emerging therapeutic strategies under development. Inherited retinal dystrophies represent a heterogeneous group of genetic disorders that manifest across a broad spectrum from infancy to late middle age.

Occurrence and Time of Onset of Intraventricular Hemorrhage in Preterm Neonates: A Systematic Review and Meta-Analysis of Individual Patient Data.

Importance: Intraventricular hemorrhage (IVH) has been described to typically occur during the early hours of life (HOL); however, the exact time of onset is still unknown.

Objective: To investigate the temporal distribution of IVH reported in very preterm neonates.

Data Sources: PubMed, Embase, Cochrane Library, and Web of Science were searched on May 9, 2024.

High-efficiency base editing in the retina in primates and human tissues.

Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.

3D Finite Element Modeling of Femtosecond Laser Trabeculotomy.

Objectives: Femtosecond laser image guided high precision trabeculotomy (FLigHT) is a novel open-angle glaucoma treatment. The procedure non-invasively creates aqueous humor (AH) drainage channel from the anterior chamber (AC) to Schlemm's canal (SC) through the trabecular meshwork (TM) to decrease intraocular pressure (IOP). The purpose of this study was to develop a 3D finite element model (FEM) of the FLigHT procedure and to simulate clinical results for different drainage channel cross-sectional areas.

Misfolding PRSS1 variant p.Ala61Val in a case of suspected intrauterine pancreatitis.

Background/objectives: Genetic variants in PRSS1 encoding human cationic trypsinogen are associated with hereditary pancreatitis. The clinically frequent variants exert their pathogenic effect by increasing intrapancreatic trypsin activity, while a distinct subset of variants causes disease via mutation-induced trypsinogen misfolding and endoplasmic reticulum (ER) stress. Here, we report a novel misfolding PRSS1 variant.

Refractive Outcomes After Cataract Surgery-The Impact of Preoperative Visual Acuity, the Intraocular Lens Model, and the Surgeon's Experience: An Empirical Analysis of Hungarian and Kosovan Patients.

Phacoemulsification and intraocular lens (IOL) implantation comprise a standard procedure for cataract treatment. However, minimal refractive error remains a determinant of postoperative results. Our study aimed to evaluate the refractive outcomes and the impact of the surgeon's experience and the IOL model on Kosovan and Hungarian patients after cataract surgery.

Examination of the Corneal Endothelium in Patients With Congenital Aniridia With a PAX6 Mutation Using In Vivo Confocal Laser Scanning Microscopy.

Purpose: In PAX6 syndrome, it is still not clear, whether prenatally, parallel to the iris tissue developmental anomaly, there is neural ectodermal, neural crest, or mesodermal cell deposition at the corneal endothelium, affecting endothelial structure and function. In addition, because of the postnatal corneal inflammation and commonly appearing secondary glaucoma, progressive endothelial changes are expected. Our purpose was to study the corneal endothelium in subjects with PAX6 aniridia, using in vivo confocal laser scanning microscopy.

The current state-of-the art in pharmaceutical continuous film coating - A review.

In this decade, one of the major trends in the pharmaceutical industry is the adoption of continuous manufacturing. This requires the development of continuous equivalents of essential pharmaceutical processes such as film coating. The process of film coating is the last step of the processing of solid dosage forms and is critical because it determines the visual appearance of the end product, along with ensuring its stability and possibly even defining the rate of drug release.

High throughput in-line content uniformity measurement of tablets based on real-time UV imaging.

This paper presents a precursor of a novel, high-throughput, in-line system, which utilizes ultraviolet (UV) imaging in order to predict the active pharmaceutical ingredient (API) content of tablets in real-time, non-destructive manner. Pimobendan, cardiovascular drug used in veterinary medicine was chosen as a fluorescent model API. Two experiments were carried out using different measurement setups, where the tablets were moving at different speeds.

Strategies to Implement a Community-Based, Longitudinal Cohort Study: The Whole Communities-Whole Health Case Study.

This paper discusses the implementation of the Whole Communities-Whole Health (WCWH) initiative, which is a community-based, longitudinal cohort study. WCWH seeks to better understand the impact of location on family health and child development while also providing support for families participating in the study. Implementing a longitudinal study that is both comprehensive in the data it is collecting and inclusive in the population it is representing is what makes WCWH extremely challenging.

Continuous twin-screw melt granulation of drug-loaded electrospun fibers.

Electrospinning (ES) is a promising continuous formulation strategy to produce amorphous solid dispersions (ASDs) and thereby improve the dissolution of poorly water-soluble drugs. However, processing the electrospun material into solid dosage forms (e.g.

Digital PCR-based quantification of miR-181a in the cerebrospinal fluid aids patient stratification in pediatric acute lymphoblastic leukemia.

Despite remarkable improvements in the survival of pediatric acute lymphoblastic leukemia (ALL), sensitive detection and clinical management of central nervous system leukemia (CNSL) are still immensely challenging. Blast cells residing in the CNS but not circulating in the cerebrospinal fluid (CSF) remain undetected by current diagnostic methods, preventing a truly risk-adapted anti-leukemic treatment in this compartment. We examined the clinical applicability of the molecular marker microRNA (miR)-181a quantified in the cell-free CSF to evaluate the level of CNS involvement and to optimize patient stratification based on CNS status.

Air pollution exposure in vitrified oocyte donors and male recipient partners in relation to fertilization and embryo quality.

Background: Studies on air pollution and outcomes of in vitro fertilization (IVF) have focused on couples undergoing autologous IVF, in which it is challenging to disentangle maternal and paternal exposures during gametogenesis. We sought to evaluate the independent associations between air pollution exposure during oogenesis and spermatogenesis on fertilization and embryo quality in non-identified donor oocyte IVF cycles.

Methods: Our study included 500 oocyte donors and 915 male recipient partners who contributed 1,095 oocyte thaw cycles (2008-2019).

Prohibited Olympic Medalist with PIEZO1 VUS Who Claims Innocence.

Competitive athletes are often exposed to extreme physiological loading, resulting in over excessive mechanotransduction during their acute intensive training sessions and competitions. Individual differences in their genetics often affect how they cope with these challenges, as reflected in their high performances. Olympic Medalists are prohibited from providing atypical values in the Hematological Module of the Athlete Biological Passport.

Staphylococcal tricuspid valve infective endocarditis complicated by refractory sepsis and bilateral lung abscesses successfully treated with adjunctive mechanical aspiration.

•In bulky infective vegetations, response to antibiotic therapy can be unpredictable due to the size of vegetations and distal embolization.•Early surgery is indicated in complicated staphylococcal tricuspid valve endocarditis, but is associated with substantial risk, including early prosthetic valve endocarditis•Large-bore percutaneous mechanical aspiration provides early source control and limits valve destruction and serves as destination therapy or a bridge to more definitive surgery.

Automated tablet defect detection and the prediction of disintegration time and crushing strength with deep learning based on tablet surface images.

This paper presents novel measurement methods, where deep learning was used to detect tableting defects and determine the crushing strength and disintegration time of tablets on images captured by machine vision. Five different classes of defects were used and the accuracy of the real-time defect recognition performed with the deep learning algorithm YOLOv5 was 99.2 %.

Sperm penetration at the maturing metaphase I stage can trigger oocyte activation in a mouse model.

Research Question: Can spermatozoa penetrate maturing metaphase I (MI) oocytes, and render subsequent development following conventional IVF in a mouse model?

Design: ICR mice were used in this study. Metaphase II (MII) cumulus-oocyte complexes (COC) harvested 15 h after injection of human chorionic gonadotrophin (HCG) were used for IVF as the control group (Group 1). In the treatment group (Group 2), maturing MI COC harvested 7 h after HCG injection were used for IVF.

Custom integration of a magnetic-field monitoring system into a 32-channel MRI head coil.

Purpose: Customizing a Siemens 32-channel coil for use in a Philips 3T MRI system with incorporated magnetic field probes for collecting high-quality MRI and magnetic-field monitoring data concurrently.

Methods: The development process of the custom coil involved several (iterative) phases. Standard temporal SNR and B data were collected with the 32-channel Siemens and for reference the 32-channel/8-channel Philips head coils before and after the custom coil was made compatible with the 3T Philips Achieva system, and magnetic field probes were installed into it along with ancillary electronics around it.

Coronary Artery Dimensions on Computed Tomography Following the Neonatal Arterial Switch Operation for the Complete Transposition of the Great Arteries.

Coronary events are life-threatening long-term complications of the arterial switch operation for complete transposition of the great arteries. The aim of our study was to assess the dimensions of the reimplanted coronary arteries and their relationship with the various geometric characteristics to gain a better understanding of the involved mechanisms. Coronary computed tomography angiography (CCTA) scans of 78 asymptomatic pediatric patients were performed at the age of 10.