Detection of tumor antigens and tumor-antigen specific T cells in NSCLC patients: Correlation of the quality of T cell responses with NSCLC subtype.

Allogeneic cancer cell lines serve as universal source of tumor-associated antigens in cancer vaccines. Immunogenic high hydrostatic pressure-killed cancer cells derived from cell lines can be used for the generation of dendritic cell (DC)-based active cellular immunotherapy of non-small cell lung cancer (NSCLC). We investigated the expression of 12 known NSCLC tumor-associated antigens (TAA) (CEA, MAGE-A1, MAGE-A3, MAGE-A4, PRAME, hTERT, HER2, MUC1, Survivin, STEAP1, SOX2 and NY-ESO-1) in 6 NSCLC cell lines as candidates for the generation of DC-based lung cancer vaccine.

Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants.

Background: We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD; MIM: 312080). We then compared our new data to previous structural variant mutagenesis studies involving the Xq22 region of the human genome. The aggregate data from 159 sequenced join-points (discontinuous sequences in the reference genome that are joined during the rearrangement process) were studied.

Endoscopic or Surgical Myotomy in Patients with Idiopathic Achalasia.

Background: Pneumatic dilation and laparoscopic Heller's myotomy (LHM) are established treatments for idiopathic achalasia. Peroral endoscopic myotomy (POEM) is a less invasive therapy with promising early study results.

Methods: In a multicenter, randomized trial, we compared POEM with LHM plus Dor's fundoplication in patients with symptomatic achalasia.

Heterologous Cytomegalovirus and Allo-Reactivity by Shared T Cell Receptor Repertoire in Kidney Transplantation.

Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay.

Esophageal bypass surgery as a definitive repair of recurrent acquired benign bronchoesophageal fistula.

Background: Acquired benign bronchoesophageal fistula (BEF) is rare and develops as a complication of other diseases, mostly of inflammatory processes and traumas of the chest. The treatment of choice is a surgical repair, which is considered definitive and leads to successful outcomes. However, incidence of recurrence after the primary repair based on limited data is up to 10% and its treatment is challenging.

Enterovirus as trigger of coeliac disease: nested case-control study within prospective birth cohort.

Objective: To determine whether infection with human enterovirus or adenovirus, both common intestinal viruses, predicts development of coeliac disease.

Design: Case-control study nested within Norwegian birth cohort recruited between 2001 and 2007 and followed to September 2016.

Setting: Norwegian population.

Clinical relevance of human papillomavirus outside of oropharynx.

Purpose Of Review: The role of HPV in oropharyngeal cancer is well recognized. HPV DNA is also found in a fraction of head and neck tumors outside of oropharynx but its clinical importance is unknown. The purpose of this review is to sum up the present knowledge about the prevalence and possible impact of HPV presence in head and neck tumors in nonoropharyngeal sites.

Characterization of molecular mechanisms underlying the axonal Charcot-Marie-Tooth neuropathy caused by MORC2 mutations.

Mutations in MORC2 lead to an axonal form of Charcot-Marie-Tooth (CMT) neuropathy type 2Z. To date, 31 families have been described with mutations in MORC2, indicating that this gene is frequently involved in axonal CMT cases. While the genetic data clearly establish the causative role of MORC2 in CMT2Z, the impact of its mutations on neuronal biology and their phenotypic consequences in patients remains to be clarified.

Non-leukemic pediatric mixed phenotype acute leukemia/lymphoma: Genomic characterization and clinical outcome in a prospective trial for pediatric lymphoblastic lymphoma.

Rare cases of hematological precursor neoplasms fulfill the diagnostic criteria of mixed phenotype acute leukemia (MPAL), characterized by expression patterns of at least two hematopoietic lineages, for which a highly aggressive behavior was reported. We present a series of 11 pediatric non-leukemic MPAL identified among 146 precursor lymphoblastic lymphomas included in the prospective trial Euro-LBL 02. Paraffin-embedded biopsies of 10 cases were suitable for molecular analyses using OncoScan assay (n = 7), fluorescence in situ hybridization (FISH; n = 7) or both (n = 5).

Virus genotyping by massive parallel amplicon sequencing: adenovirus and enterovirus in the Norwegian MIDIA study.

Objectives: Direct genotyping of adenovirus or enterovirus from clinical material using polymerase chain reaction (PCR) followed by Sanger sequencing is often difficult due to the presence of multiple virus types in a sample, or due to varying efficacy of PCR amplifying the capsid gene on the background of foreign nucleic acids. Here we present a simple protocol for virus genotyping using massive parallel amplicon sequencing.

Methods: The protocol utilized a set of 16 tailed degenerate primers flanking the seventh hypervariable region of the adenovirus hexon gene and 9 tailed degenerate primers targeted to the proximal portion of the enterovirus VP1 gene.

UBTF Mutation Causes Complex Phenotype of Neurodegeneration and Severe Epilepsy in Childhood.

Introduction: Neurodegenerative diseases of childhood present with progressive decline in cognitive, social, and motor function and are frequently associated with seizures in different stages of the disease. Here we report a patient with severe progressive neurodegeneration with drug-resistant epilepsy of unknown etiology from the age of 2 years.

Methods And Results: Using whole exome sequencing, we found heterozygous missense de novo variant c.

A high-throughput pipeline for validation of antibodies.

Western blotting (WB) is widely used to test antibody specificity, but the assay has low throughput and precision. Here we used preparative gel electrophoresis to develop a capture format for WB. Fractions with soluble, size-separated proteins facilitated parallel readout with antibody arrays, shotgun mass spectrometry (MS) and immunoprecipitation followed by MS (IP-MS).

Siva-1 emerges as a tissue-specific oncogene beyond its classic role of a proapoptotic gene.

Siva-1 is a typical apoptotic protein commonly activated by the p53 tumor suppressor protein and should therefore participate in a barrier against the development of cancer. It has proapoptotic activities in various cell systems. Recent findings suggest that Siva-1 possesses several other apoptosis-independent functions and interacts with many other proteins not directly involved in apoptosis.

Complement activation is associated with more severe course of diarrhea-associated hemolytic uremic syndrome, a preliminary study.

Diarrhea-associated hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury secondary to enteric infection, typically Shiga toxin-producing Escherichia coli. Shiga toxin 2 is able to activate alternative complement pathways; therefore, the aim of the study was to analyze C3 as a predictor of clinical courses in patients with diarrhea-associated hemolytic uremic syndrome. We hypothesized that the patients with increased complement activation at admission suffered from a more severe course.

Widespread Expression of Hedgehog Pathway Components in a Large Panel of Human Tumor Cells and Inhibition of Tumor Growth by GANT61: Implications for Cancer Therapy.

The sonic Hedgehog/GLI signaling pathway (HH) is critical for maintaining tissue polarity in development and contributes to tumor stemness. Transcription factors GLI1⁻3 are the downstream effectors of HH and activate oncogenic targets. To explore the completeness of the expression of HH components in tumor cells, we performed a screen for all HH proteins in a wide spectrum of 56 tumor cell lines of various origin using Western blot analysis.

The bacteriome at the onset of type 1 diabetes: A study from four geographically distant African and Asian countries.

Objectives: Gut bacteriome profiling studies in type 1 diabetes (T1D) to date are mostly limited to populations of Europe, with two studies from China and one study each from Mexico and the USA. We therefore sought to characterize the stool bacteriome in children after onset of T1D along with age- and place-matched control subjects from four geographically distant African and Asian countries.

Methods: Samples were collected from 73 children and adolescents shortly after T1D onset (Azerbaijan 19, Jordan 20, Nigeria 14, Sudan 20) and 104 matched control subjects of similar age and locale.

Genetic diagnosis of steroid-resistant nephrotic syndrome in a longitudinal collection of Czech and Slovak patients: a high proportion of causative variants in NUP93.

Background: Steroid-resistant nephrotic syndrome (SRNS) has a heterogeneous spectrum of monogenic causes that substantially differ among populations. The aim of this study was to analyse the genetic aetiology of SRNS in Czech and Slovak paediatric patients.

Methods: We analysed clinical data from 74 patients (38 boys) with congenital (15%), infant (14%), and childhood-onset (71%) SRNS collected from the Czech Republic and Slovakia from 2000 to 2017 (inclusive).

Treatment of retinal capillary hemangioma using 810 nm infrared laser.

Aim: Presentation of the efficacy of infrared laser for the treatment of retinal capillary hemangioma (RCH).

Methods: The treatment and follow-up of nine eyes (fourteen tumors of different sizes and localizations) in seven patients (five children) with RCH. Infrared diode laser (810 nm) was used for modified transpupillary thermotherapy (TTT) in long exposition mode and power between 200 and 1200 mW with a beam diameter of 2 mm (indirect ophthalmoscope, +28 D or +40 D lens) or 0.

Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life.

Background: Epilepsy is a heterogeneous disease with a broad phenotypic spectrum and diverse genotypes. A significant proportion of epilepsies has a genetic aetiology. In our study, a custom designed gene panel with 112 genes known to be associated with epilepsies was used.

Glucocorticoids Reduce Aberrant O-Glycosylation of IgA1 in IgA Nephropathy Patients.

Background/aims: IgA nephropathy is associated with aberrant O-glycosylation of IgA1, which is recognized by autoantibodies leading to the formation of circulating immune complexes. Some of them, after deposition into kidney mesangium, trigger glomerular injury. In patients with active disease nonresponding to angiotensin-converting enzyme inhibitors or angiotensin II blockers, corticosteroids are recommended.

Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2.

Although mutations in more than 90 genes are known to cause CMT, the underlying genetic cause of CMT remains unknown in more than 50% of affected individuals. The discovery of additional genes that harbor CMT2-causing mutations increasingly depends on sharing sequence data on a global level. In this way-by combining data from seven countries on four continents-we were able to define mutations in ATP1A1, which encodes the alpha1 subunit of the Na,K-ATPase, as a cause of autosomal-dominant CMT2.

Neonatal Onset of Epilepsy of Infancy with Migrating Focal Seizures Associated with a Novel GABRB3 Variant in Monozygotic Twins.

Background: Recently, a study providing insight into mutational spectrum was published (Møller et al 2017). The authors report considerable pleiotropy even for single mutations and were not able to identify any genotype-phenotype correlations.

Methods: The proband (twin B) was referred for massively parallel sequencing of epilepsy-related gene panel because of hypotonia and neonatal seizures.

Quantitative CrAssphage real-time PCR assay derived from data of multiple geographically distant populations.

After its computational inference from human stool metagenomes, the CrAssphage has proven to be the most prevalent phage in the human gut, with presumably very wide geographic distribution. The currently available molecular assays do not sufficiently reflect the CrAssphage sequence variability. Here, we report a novel real-time PCR assay whose primers and probes are derived from data of multiple CrAssphage strains obtained from gut viral metagenomes of European, Asian, and African subjects.