The Utility of Kapandji Technique in Closed Reduction and Percutaneous Pinning Of Completely Displaced Pediatric Supracondylar Fracture of Humerus: Technical Note.

The standard treatment for displaced pediatric supracondylar fracture of humer us (PSCFH) is closed reduction and percutaneous pinning under image intensifier guidance. This technical note describes Kapandji intrafocal pinning technique (KIPT) for achieving optimal fracture reduction and stable fixation in Gartland Type III or IV extension type PSCFH. In KIPT, a K wire was introduced into the fracture site from the posterior aspect, fracture manipulation was done by levering with wire reducing the posterior displacement of the distal fragment and the wire was fixed to the anterior cortex of the proximal fragment.

Enhancing human phenotype ontology term extraction through synthetic case reports and embedding-based retrieval: A novel approach for improved biomedical data annotation.

With the increasing utilization of exome and genome sequencing in clinical and research genetics, accurate and automated extraction of human phenotype ontology (HPO) terms from clinical texts has become imperative. Traditional methods for HPO term extraction, such as PhenoTagger, often face limitations in coverage and precision. In this study, we propose a novel approach that leverages large language models (LLMs) to generate synthetic sentences with clinical context, which were semantically encoded into vector embeddings.

Synthesis and biological assessment of benzimidazole-acrylonitrile-1,2,3-triazole derivatives as α-glucosidase inhibitors.

In the pursuit of developing potent α-glucosidase inhibitors for managing diabetes, a series of novel benzimidazole-acrylonitrile-1,2,3-triazole derivatives were designed. Sixteen derivatives (12a-p) were synthesized by varying substituents on the phenyl ring of the N-phenylacetamide moiety. Among these, compound 12m emerged as highly effective against α-glucosidase, displaying an IC value of 6.

3D chromatin hubs as regulatory units of identity and survival in human acute leukemia.

Cancer progression involves genetic and epigenetic changes that disrupt chromatin 3D organization, affecting enhancer-promoter interactions and promoting growth. Here, we provide an integrative approach, combining chromatin conformation, accessibility, and transcription analysis, validated by in silico and CRISPR-interference screens, to identify relevant 3D topologies in pediatric T cell leukemia (T-ALL and ETP-ALL). We characterize 3D hubs as regulatory centers for oncogenes and disease markers, linking them to biological processes like cell division, inflammation, and stress response.

Genome-informed Discovery of Monchicamides A-K: Cyanobactins from the Microcoleaceae Cyanobacterium LEGE 16532.

Genome mining has emerged as an important tool for the discovery of natural products and is particularly effective for the swift identification of ribosomally synthesized and post-translationally modified peptides (RiPPs). Among RiPPs, cyanobactins have gained attention due to their diverse structures and bioactive properties. Here, we explored the Microcoleaceae cyanobacterium LEGE 16532 strain and identified the biosynthetic gene cluster (BGC), which was predicted to encode cyanobactin-like molecules.

The Biological Effects of Magnesium-Based Implants on the Skeleton and Their Clinical Implications in Orthopedic Trauma Surgery.

Magnesium (Mg)-based implants have evolved as a promising innovation in orthopedic trauma surgery, with the potential to revolutionize the treatment of bone diseases, including osteoporotic fractures and bone defects. Available clinical studies mostly show excellent patient outcomes of resorbable Mg-based implants, without the need for subsequent implant removal. However, the occurrence of radiolucent zones around Mg-based implants seems to be a noticeable drawback for a more widespread clinical use.

Transglutaminase 2 is an RNA-binding protein: experimental verification and characterisation of a novel transglutaminase feature.

Transglutaminase 2 (TG2) is a uniquely versatile protein with diverse catalytic activities, such as transglutaminase, protein disulfide isomerase, GTPase and protein kinase, and participates in several biological processes. According to information available in the RBP2GO database, TG2 can act as an RNA-binding protein (RBP). RBPs participate in posttranscriptional gene expression regulation, therefore influencing the function of RNA, whereas RNA molecules can also modulate the biological activity of RBPs.

An umbrella review on how digital health intervention co-design is conducted and described.

Co-design has been suggested to improve intervention effectiveness and sustainability. However, digital health intervention co-design is inconsistently reported. This umbrella review aims to synthesize what is known about co-design of digital health interventions.

Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors.

Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors.

Impaired Wnt/Planar Cell Polarity Signaling in Yellow Nail Syndrome.

Background: Yellow nail syndrome (YNS) is a rare disorder characterized by a triad of yellow dystrophic nails, lymphedema, and chronic lung disease. Most patients present in adulthood, with only a few congenital or familial cases described. The cause of YNS remains largely unknown, although defects in lymphatic vessel development are suggested to play a significant role.

Colloidal AInSe (A = K, Rb, Cs) Nanocrystals with Tunable Crystal and Band Structures.

Wide band gap AInSe (A = K, Rb, Cs) is an important interlayer material for improving the efficiency of Cu(In,Ga)(S,Se) (CIGS) solar cells. Compared to high-vacuum deposition and solid-state synthesis, a less energy-intensive method is of interest for its fabrication. Herein, we present the rapid, low-temperature colloidal synthesis of AInSe nanocrystals that opens a pathway for convenient solution processing.

Pharmacokinetics/pharmacodynamics of glucocorticoids: modeling the glucocorticoid receptor dynamics and dose/response of commonly prescribed glucocorticoids.

Background And Purpose: The main features of the dynamics of the glucocorticoid receptor (GR) have been known for 50 years: 1) in the absence of glucocorticoid (G), the receptor is localized entirely in the cytoplasm; 2) upon G binding, GR is converted into a tightly bound G form and is rapidly imported into the nucleus where it can bind DNA and modulate transcription; 3) nuclear export of GR is very slow; and 4) the nuclear form of GR can recycle through an unbound form, back to the bound transcription modulating form without leaving the nucleus.

Experimental Approach: A kinetic model that captures these features is presented, a set of model parameters for dexamethasone is derived, and the clinical implication for the commonly used glucocorticoids is discussed.

Key Results: At the high concentrations normally used to describe G pharmacodynamics, the model reduces to the standard Michaelis-Menten equation with a that is a function of 4 model parameters.

The Safety of Recently Approved Therapeutics in Age-Related Macular Degeneration.

Recent developments in treatments for both forms of advanced age-related macular degeneration (AMD) have led to the approval of multiple agents and modalities within the last few years. Five new medications for both neovascular AMD (nAMD) and geographic atrophy (GA) secondary to nonexudative AMD (neAMD) have been FDA-approved within the last 5 years, along with a new device designed for sustained drug delivery for nAMD. In nAMD, the newest agents approved by the FDA are brolucizumab (Novartis Pharmaceuticals, Basel, Switzerland), faricimab (F.

Mixed methods systematic review: Using a cultural validity assessment to evaluate prevention programs for Indigenous students.

Implementing culturally appropriate school-based prevention programs with Indigenous students that leverage culture as a protective factor has the potential to revitalize and sustain cultural connections that have historically and systematically been destroyed in the United States. However, there is a dearth of literature synthesizing the effectiveness of school-based prevention programs that have been implemented with Indigenous students across contexts. As such, we conducted a mixed method systematic review to (a) evaluate school-based prevention programs with quantitative and/or qualitative data, (b) assess the use of Indigenous research methods, and (c) examine cultural and community validity.

[Academics in ophthalmology : An analysis of the gender distribution at German university hospitals and the Clinician Scientist Program].

Background: The number of female ophthalmologists has risen steadily in recent years. The aim of this study is to investigate the gender ratios, subspecialties, and academic degrees of ophthalmologists at German university hospitals. Additionally, the study analyzes the proportion of women in science programs such as the Clinician Scientist Program.

Biologically defined neuronal synuclein disease as a tool to advance drug development.

In a recent Viewpoint article (. 2024;81:789‒90), Okubadejo et al. raised concerns regarding two recent proposals for biological definitions and staging systems for synucleinopathies (the Neuronal Synuclein Disease Integrated Staging System and SynNeurGe system).

Approaches to ensure an equitable and fair admissions process for medical training.

There has been considerable discussion of how best to address racial and ethnic disparities in health outcomes, both globally and specifically in the United States. Increasing diversity among future clinicians and physician-scientists has been identified as a key strategy for addressing and correcting health disparities among underrepresented populations. Increasingly, medical schools, the institutions that train clinicians, have embraced the practice of holistic review for evaluating applicants and virtually all medical schools have reported contributing to a diverse physician workforce as an important aspect of their educational mission.

Mining of antioxidant sesquiterpene lactones from the aerial parts of Saussurea involucrata with feature-based molecular network strategy.

Sesquiterpene lactones (SLs) are a class of natural products with diverse structural scaffoldings and biological activities, making them intriguing objects in the fields of pharmaceutical industry, drug development, and pharmacology. Herein, fifteen SLs, including eleven undescribed SLs compounds sauruintones A-K (1-8 and 13-15), were isolated and identified from the aerial parts of Saussurea involucrata. Their structures were characterized by using mass spectrometry, spectroscopic methods, computational calculations, and single crystal X-ray diffraction.

Measuring the Burden of Epilepsy Hospitalizations in CDKL5 Deficiency Disorder.

Background: Information on the hospital service use among individuals with CDKL5 Deficiency Disorder, an ultrarare developmental epileptic encephalopathy, is limited, evidence of which could assist with service planning. Therefore, using baseline and longitudinal data on 379 genetically verified individuals in the International CDKL5 Disorder Database, we aimed to investigate rates of seizure-related and other hospitalizations and associated length of stay in this cohort.

Methods: Outcome variables were lifetime count of family-reported hospitalizations and average length of stay both for seizure- (management and/or investigative) and non-seizure-related causes.

Neurofilament Light Chain as a Discriminator of Disease Activity Status in MOG Antibody-Associated Disease.

Background And Objectives: In patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), acute disease activity is generally identified through medical history, neurologic examination, and imaging. However, these may be insufficient for detecting disease activity in specific conditions. This study aimed to investigate the dynamics of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) after clinical attacks and to assess their utility in discriminating attacks from remission in patients with MOGAD.

Cerebral Hemodynamic Responses to Disease-Modifying and Curative Sickle Cell Disease Therapies.

Background And Objectives: Sickle cell disease (SCD) is a hemoglobinopathy resulting in hemoglobin-S production, hemolytic anemia, and elevated stroke risk. Treatments include oral hydroxyurea, blood transfusions, and hematopoietic stem cell transplantation (HSCT). Our objective was to evaluate the neurologic relevance of these therapies by characterizing how treatment-induced changes in hemoglobin (Hb) affect brain health biomarkers.

Intranasal influenza-vectored vaccine expressing pneumococcal surface protein A protects against Influenza and Streptococcus pneumoniae infections.

Streptococcus pneumoniae and influenza A virus (IAV) are significant agents of pneumonia cases and severe respiratory infections globally. Secondary bacterial infections, particularly by Streptococcus pneumoniae, are common in IAV-infected individuals, leading to critical outcomes. Despite reducing mortality, pneumococcal vaccines have high production costs and are serotype specific.

Replicating RNA vaccine confers durable immunity against Crimean Congo hemorrhagic fever virus challenge in mice.

Spread by Hyalomma genus ticks, Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic disease endemic throughout Southern and Eastern Europe, Asia, and Africa. To date, there are no widely approved vaccines for CCHFV and treatment for disease is largely supportive. Due to this lack of intervention, the WHO lists CCHFV as a high-priority pathogen.

Designing strong inducible synthetic promoters in yeasts.

Inducible promoters are essential for precise control of target gene expression in synthetic biological systems. However, engineering eukaryotic promoters is often more challenging than engineering prokaryotic promoters due to their greater mechanistic complexity. In this study, we describe a simple and reliable approach for constructing strongly inducible synthetic promoters with minimum leakiness in yeasts.