Outcomes after laser enucleation of the prostate with and without significant storage symptoms.

Objective: To test for differences in recovery of lower urinary tract symptoms (LUTS) between patients with storage-positive vs -negative symptoms after laser enucleation of the prostate (LEP).

Patients And Methods: Consecutive storage-positive (severe storage symptoms, International Prostate Symptom Score [IPSS] storage subscore >8) vs storage-negative patients treated with LEP (November 2017-September 2022) within our tertiary-care database were identified. Mixed linear models tested for changes in IPSS and quality of life (QoL) at 1, 3 and 12 months after LEP.

Paragraph: a graph-based structural variant genotyper for short-read sequence data.

Accurate detection and genotyping of structural variations (SVs) from short-read data is a long-standing area of development in genomics research and clinical sequencing pipelines. We introduce Paragraph, an accurate genotyper that models SVs using sequence graphs and SV annotations. We demonstrate the accuracy of Paragraph on whole-genome sequence data from three samples using long-read SV calls as the truth set, and then apply Paragraph at scale to a cohort of 100 short-read sequenced samples of diverse ancestry.

Detection of Novel Fusion Transcript VTI1A-CFAP46 in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is now the second-highest cause of cancer death worldwide. Recent studies have discovered a wide range of somatic mutations in HCC. These mutations involve various vital signaling pathways such as: Wnt/-Catenin, p53, telome-rase reverse transcriptase (TERT), chromatin remodeling, RAS/MAPK signaling, and oxidative stress.

ExpansionHunter: a sequence-graph-based tool to analyze variation in short tandem repeat regions.

Summary: We describe a novel computational method for genotyping repeats using sequence graphs. This method addresses the long-standing need to accurately genotype medically important loci containing repeats adjacent to other variants or imperfect DNA repeats such as polyalanine repeats. Here we introduce a new version of our repeat genotyping software, ExpansionHunter, that uses this method to perform targeted genotyping of a broad class of such loci.

Screening for late-onset Pompe disease in western Denmark.

Objective: Late-onset Pompe disease (LOPD) is a rare autosomal recessively inherited metabolic myopathy caused by reduced activity of the lysosomal enzyme alpha-glucosidase. In a previous screening study at two large neuromuscular university clinics in Denmark, three patients with LOPD were identified out of 103 patients screened. No systematic screening has been performed at the other neurological departments in the western part of Denmark.

Developmental validation of the MiSeq FGx Forensic Genomics System for Targeted Next Generation Sequencing in Forensic DNA Casework and Database Laboratories.

Human DNA profiling using PCR at polymorphic short tandem repeat (STR) loci followed by capillary electrophoresis (CE) size separation and length-based allele typing has been the standard in the forensic community for over 20 years. Over the last decade, Next-Generation Sequencing (NGS) matured rapidly, bringing modern advantages to forensic DNA analysis. The MiSeq FGx™ Forensic Genomics System, comprised of the ForenSeq™ DNA Signature Prep Kit, MiSeq FGx™ Reagent Kit, MiSeq FGx™ instrument and ForenSeq™ Universal Analysis Software, uses PCR to simultaneously amplify up to 231 forensic loci in a single multiplex reaction.

Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications.

Unlabelled: : We describe Manta, a method to discover structural variants and indels from next generation sequencing data. Manta is optimized for rapid germline and somatic analysis, calling structural variants, medium-sized indels and large insertions on standard compute hardware in less than a tenth of the time that comparable methods require to identify only subsets of these variant types: for example NA12878 at 50× genomic coverage is analyzed in less than 20 min. Manta can discover and score variants based on supporting paired and split-read evidence, with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs.

The evolutionary dynamics of major regulators for sexual development among Hymenoptera species.

All hymenopteran species, such as bees, wasps and ants, are characterized by the common principle of haplodiploid sex determination in which haploid males arise from unfertilized eggs and females from fertilized eggs. The underlying molecular mechanism has been studied in detail in the western honey bee Apis mellifera, in which the gene complementary sex determiner (csd) acts as primary signal of the sex determining pathway, initiating female development by csd-heterozygotes. Csd arose from gene duplication of the feminizer (fem) gene, a transformer (tra) ortholog, and mediates in conjunction with transformer2 (tra2) sex-specific splicing of fem.

Comparative analysis of the transcriptome across distant species.

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly.

De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements.

Deep sequencing of mammalian DNA methylomes has uncovered a previously unpredicted number of discrete hypomethylated regions in intergenic space (iHMRs). Here, we combined whole-genome bisulfite sequencing data with extensive gene expression and chromatin-state data to define functional classes of iHMRs, and to reconstruct the dynamics of their establishment in a developmental setting. Comparing HMR profiles in embryonic stem and primary blood cells, we show that iHMRs mark an exclusive subset of active DNase hypersensitive sites (DHS), and that both developmentally constitutive and cell-type-specific iHMRs display chromatin states typical of distinct regulatory elements.

Lessons learned from lethal cardiac injury by nuss repair of pectus excavatum in a 16-year-old.

This report investigates cardiac injury and arrest during a Nuss repair of severe pectus excavatum in a 16-year-old boy in 2006. The injuries of the right atrial auricle and the right ventricle were sutured, and the patient was resuscitated. Ultimately he died on the 11th day of progressive malignant cerebral edema and respiratory distress syndrome despite cerebral decompression and hypothermia.

Prostate cancer may trigger paraneoplastic limbic encephalitis: a case report and a review of the literature.

We present a case of a previously healthy and active 64-year-old man who experienced a rapid neuropsychiatric decline. All tests for metabolic causes, neuroinfection, intracranial infarction or tumor were negative. By the means of magnetic resonance imaging, electroencephalography and the anti-Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer.

STAR: ultrafast universal RNA-seq aligner.

Motivation: Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases.

Results: To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure.

Landscape of transcription in human cells.

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function.

The two different effects of the potential neuroprotective compound minocycline on AMPA-type glutamate receptors.

Background: Minocycline has demonstrated neuroprotective effects in experimental neurodegenerative diseases. The aim of this study was to investigate if there is any direct interaction between minocycline and the AMPA-type receptor channels, and to elucidate the underlying molecular pharmacological mechanisms.

Methods: The patch-clamp technique was used combined with an ultrafast solution exchange system to investigate the interaction of minocycline with recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing GluR2L504Y).

Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.

Many animal species use a chromosome-based mechanism of sex determination, which has led to the coordinate evolution of dosage-compensation systems. Dosage compensation not only corrects the imbalance in the number of X chromosomes between the sexes but also is hypothesized to correct dosage imbalance within cells that is due to monoallelic X-linked expression and biallelic autosomal expression, by upregulating X-linked genes twofold (termed 'Ohno's hypothesis'). Although this hypothesis is well supported by expression analyses of individual X-linked genes and by microarray-based transcriptome analyses, it was challenged by a recent study using RNA sequencing and proteomics.

Synthetic spike-in standards for RNA-seq experiments.

High-throughput sequencing of cDNA (RNA-seq) is a widely deployed transcriptome profiling and annotation technique, but questions about the performance of different protocols and platforms remain. We used a newly developed pool of 96 synthetic RNAs with various lengths, and GC content covering a 2(20) concentration range as spike-in controls to measure sensitivity, accuracy, and biases in RNA-seq experiments as well as to derive standard curves for quantifying the abundance of transcripts. We observed linearity between read density and RNA input over the entire detection range and excellent agreement between replicates, but we observed significantly larger imprecision than expected under pure Poisson sampling errors.

The reality of pervasive transcription.

Despite recent controversies, the evidence that the majority of the human genome is transcribed into RNA remains strong.

New Berlin-Buch "reversed Nuss," endoscopic pectus carinatum repair using eight-hole stabilizers, submuscular CO2, and presternal Nuss bar compression: first results in 35 patients.

Introduction: Since 2001 we minimized access (2.9-4.7 cm) for universally applicable endoscopic hybrid carinatum technique with two transsternal Willital bars in 173 endoscopic hybrid (EH) patients with very satisfactory results.

Changes in extracellular pH affect glycine receptor channels expressed in HEK 293 cells.

Glycine receptors are expressed throughout the central nervous system working for inhibitory neurotransmission. Since fluctuations of the blood pH value occur under certain physiological and pathological conditions, we investigated the influence of the extracellular pH on glycine homomeric and heteromeric receptor functions using patch clamp in combination with the fast agonist application technique. Our results demonstrated that both alpha1 homomeric and alpha 1 beta heteromeric glycine receptors were remarkably inhibited under acidic extracellular pH.

The interaction of the neuroprotective compounds riluzole and phenobarbital with AMPA-type glutamate receptors: a patch-clamp study.

Background: Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors is a promising pharmacological strategy in the treatment of neurodegenerative diseases. The aim of the study is to elucidate if there are direct interactions of riluzole and phenobarbital with AMPA-type receptor channels and to determinethe molecular pharmacological mechanisms.

Methods: The patch-clamp technique was used combining an ultrafast solution exchange system to investigate the interaction of riluzole and phenobarbital with recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing GluR2L504Y).

Synaptic currents and transmitter responses in human NT2 neurons differentiated in aggregate culture.

Postmitotic neurons were generated from the human NT2 teratocarcinoma cell line in a novel cell aggregate differentiation procedure. The NT2 model neurons express punctate immunoreactivity for synapsin and for cell markers related to GABAergic and glutamatergic neurotransmission. Using the outside-out patch-clamp configuration, we characterized the kinetics of currents elicited by a rapid application of the amino acid neurotransmitters.

Analysis of neuroprotective effects of valproic acid on primary motor neurons in monoculture or co-cultures with astrocytes or Schwann cells.

Chronic dysregulation of the intracellular Ca(2+) homeostasis (excitotoxicity) is thought to contribute to the development of motor neuron diseases. Valproic acid (VPA) is widely used as an antiepileptic drug and acts mainly by inhibition of sodium channels and by enhancing the level of the inhibitory neurotransmitter gamma-aminobutyric acid. Neuroprotective capacities of VPA are supposed to arise also from the inhibition of histone deacetylases.

Laparoscopic approach to ovarian mass in children and adolescents: already a standard in therapy.

Introduction: Functional cysts, ovarian torsion, and benign neoplasms are the most common ovarian masses among young adolescents. The laparoscopic approach to giant ovarian cysts in the pediatric population maybe difficult due the limited working space and the high risk of spillage. In this paper, we evaluate the role of laparoscopic surgery in the treatment of adnexal disease occurring in young girls.

Molecular mechanisms of interaction between the neuroprotective substance riluzole and GABA(A)-receptors.

The antiepileptic drug riluzole is used as a therapeutic agent in amyotrophic lateral sclerosis due to its neuroprotective effects. Besides presynaptic inhibition of GABAergic and preferentially glutamatergic transmission, it also potentiates postsynaptic GABA(A)-receptor function. We investigated the postsynaptic effects of riluzole on GABA(A)-receptor channels by use of the patch-clamp technique.