Therapeutic approaches of diametaphyseal radius fractures in children.

Background: There are clear standards for when to operate on both distal epiphyseal and diaphyseal forearm fractures in children. However, paediatric surgeons are often faced with fractures in the transition zone between metaphysis and diaphysis. This aim of the study is to compare different treatment approaches for diametaphyseal forearm fractures, to classify different types of these fractures, and to define further assessment parameters and treatment recommendations.

Systematic P2Y receptor survey identifies P2Y11 as modulator of immune responses and virus replication in macrophages.

The immune system is in place to assist in ensuring tissue homeostasis, which can be easily perturbed by invading pathogens or nonpathogenic stressors causing tissue damage. Extracellular nucleotides are well known to contribute to innate immune signaling specificity and strength, but how their signaling is relayed downstream of cell surface receptors and how this translates into antiviral immunity is only partially understood. Here, we systematically investigated the responses of human macrophages to extracellular nucleotides, focusing on the nucleotide-sensing GPRC receptors of the P2Y family.

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.

Proteomic Analysis of Effects of Spironolactone in Heart Failure With Preserved Ejection Fraction.

Background: The TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) suggested clinical benefits of spironolactone treatment among patients with heart failure with preserved ejection fraction enrolled in the Americas. However, a comprehensive assessment of biologic pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction has not been performed.

Methods: We conducted aptamer-based proteomic analysis utilizing 5284 modified aptamers to 4928 unique proteins on plasma samples from TOPCAT participants from the Americas (n=164 subjects with paired samples at baseline and 1 year) to identify proteins and pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction.

Selective Requirement of MYB for Oncogenic Hyperactivation of a Translocated Enhancer in Leukemia.

In acute myeloid leukemia (AML) with inv(3)(q21;q26) or t(3;3)(q21;q26), a translocated enhancer drives oncogenic expression of . We generated an EVI1-GFP AML model and applied an unbiased CRISPR/Cas9 enhancer scan to uncover sequence motifs essential for transcription. Using this approach, we pinpointed a single regulatory element in the translocated enhancer that is critically required for aberrant expression.

Search for Rare or Forbidden Decays of the D^{0} Meson.

We present a search for nine lepton-number-violating and three lepton-flavor-violating neutral charm decays of the type D^{0}→h^{'-}h^{-}ℓ^{'+}ℓ^{+} and D^{0}→h^{'-}h^{+}ℓ^{'±}ℓ^{∓}, where h and h^{'} represent a K or π meson and ℓ and ℓ^{'} an electron or muon. The analysis is based on 468  fb^{-1} of e^{+}e^{-} annihilation data collected at or close to the ϒ(4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory. No significant signal is observed for any of the twelve modes, and we establish 90% confidence level upper limits on the branching fractions in the range (1.

Handling Artificially Terminated Events in Electropenetrography Data.

Electropenetrography a.k.a.

Rationale and Design of the CONCERT-HF Trial (Combination of Mesenchymal and c-kit Cardiac Stem Cells As Regenerative Therapy for Heart Failure).

Rationale: Autologous bone marrow mesenchymal stem cells (MSCs) and c-kit cardiac progenitor cells (CPCs) are 2 promising cell types being evaluated for patients with heart failure (HF) secondary to ischemic cardiomyopathy. No information is available in humans about the relative efficacy of MSCs and CPCs and whether their combination is more efficacious than either cell type alone.

Objective: CONCERT-HF (Combination of Mesenchymal and c-kit Cardiac Stem Cells As Regenerative Therapy for Heart Failure) is a phase II trial aimed at elucidating these issues by assessing the feasibility, safety, and efficacy of transendocardial administration of autologous MSCs and CPCs, alone and in combination, in patients with HF caused by chronic ischemic cardiomyopathy (coronary artery disease and old myocardial infarction).

TIME Trial: Effect of Timing of Stem Cell Delivery Following ST-Elevation Myocardial Infarction on the Recovery of Global and Regional Left Ventricular Function: Final 2-Year Analysis.

Rationale: The TIME trial (Timing in Myocardial Infarction Evaluation) was the first cell therapy trial sufficiently powered to determine if timing of cell delivery after ST-segment-elevation myocardial infarction affects recovery of left ventricular (LV) function.

Objective: To report the 2-year clinical and cardiac magnetic resonance imaging results and their modification by microvascular obstruction.

Methods And Results: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells versus placebo in 120 patients with anterior ST-segment-elevation myocardial infarctions resulting in LV dysfunction.

Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy.

Purpose Of Review: Here, we discuss a recently developed experimental strategy for discovering small molecules with potential to prevent and treat skeletal muscle atrophy.

Recent Findings: Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression, which generate complex but measurable patterns of positive and negative changes in skeletal muscle mRNA levels (a.k.

Salinipostins A-K, long-chain bicyclic phosphotriesters as a potent and selective antimalarial chemotype.

Despite significant advances in antimalarial chemotherapy over the past 30 years, development of resistance to frontline drugs remains a significant challenge that limits efforts to eradicate the disease. We now report the discovery of a new class of antimalarials, salinipostins A-K, with low nanomolar potencies and high selectivity indices against mammalian cells (salinipostin A: Plasmodium falciparum EC50 50 nM, HEK293T cytotoxicity EC50 > 50 μM). These compounds were isolated from a marine-derived Salinospora sp.

Measurement of branching fractions and charge asymmetries in B decays to an eta meson and a K* meson.

We present measurements of branching fractions and charge asymmetries for the decays B-->etaK*, where K* indicates a spin 0, 1, or 2 Kpi system. The data sample corresponds to 344x10(6) BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy e+ e- collider at SLAC. We measure the branching fractions (in units of 10(-6): B(B0-->etaK*0(892))=16.

Model selection based on structural similarity-method description and application to water solubility prediction.

A method is introduced that allows one to select, for a given property and compound, among several prediction methods the presumably best-performing scheme based on prediction errors evaluated for structurally similar compounds. The latter are selected through analysis of atom-centered fragments (ACFs) in accord with a k nearest neighbor procedure in the two-dimensional structural space. The approach is illustrated with seven estimation methods for the water solubility of organic compounds and a reference set of 1876 compounds with validated experimental values.

Dose effects and density-dependent regulation of two microparasites of Daphnia magna.

Individual hosts constitute a limited resource for parasites, suggesting that density-dependent effects may play a role in within-host growth and parasite regulation. This hypothesis has been tested for several helminth parasites, but not for microparasites. We therefore examined dose-response patterns for the microparasitic bacterium Pasteuria ramosa and the fungus Metschnikowiella biscuspidata infecting the planktonic crustacean Daphnia magna.

Characterization of a new AMPA receptor radioligand, [3H]2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid.

(RS)-2-Amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA), which is a potent and selective agonist at (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptors, has previously been shown to desensitize AMPA receptors to a much lower degree than AMPA itself. We now report the synthesis of [3H]ACPA (32.5 Ci/mmol), the neurochemical and pharmacological characterization of [3H]ACPA binding, and a comparison of the distribution of [3H]ACPA, [3H]AMPA, and [3H](S)-5-fluorowillardiine binding sites in rat brain.

Analysis of K-ras gene mutations in rare pancreatic and ampullary tumours.

Objective: Mutation of the K-ras oncogene is a frequent event in pancreatic ductal carcinogenesis and it is believed to occur at an early stage in the development of pancreatic cancer. However, little is known of the role of K-ras mutations in rare pancreatic epithelial neoplasms, endocrine tumours or other non-epithelial tumours of the pancreas. Furthermore, limited data are available regarding the role of K-ras mutations in the pathogenesis of ampullary tumours.

Absence of K-ras mutations in the pancreatic parenchyma of patients with chronic pancreatitis.

Background: Human pancreatic cancers exhibit a high frequency of K-ras mutations.

Methods: In this study we used oligonucleotide specific hybridization to compare the frequency of K-ras mutations in genomic DNA samples prepared from 21 normal pancreatic tissues, 26 chronic pancreatitis tissues, and 24 pancreatic cancers.

Results: None of the DNA samples from normal or chronic pancreatitis tissues exhibited a K-ras mutation at codons 12 or 13 of K-ras.