Comparison of tumor-informed and tumor-naïve sequencing assays for ctDNA detection in breast cancer.

Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here, we compare detection of ctDNA in serial plasma samples from patients with breast cancer using different tumor-informed and tumor-naïve assays designed to detect structural variants (SVs), single nucleotide variants (SNVs), and/or somatic copy-number aberrations, by multiplex PCR, hybrid capture, and different depths of whole-genome sequencing.

[Parents as Co-Therapists in Home Treatment for Adolescents with Anorexia Nervosa - Factors and Mechanisms].

Caring for a child with anorexia nervosa (AN) puts a strain on many parents. At the same time, actively involving the parents in treatment to increase their skills tomanage the disorder is important, as it seems to improve the child's prognosis. Home treatment requires the parents to be particularly involved.

Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models.

Whole-genome sequencing (WGS) of circulating tumour DNA (ctDNA) is now a clinically important biomarker for predicting therapy response, disease burden and disease progression. However, the translation of ctDNA monitoring into vital preclinical PDX models has not been possible owing to low circulating blood volumes in small rodents. Here, we describe the longitudinal detection and monitoring of ctDNA from minute volumes of blood in PDX mice.

Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer.

Background: Identification of residual disease in patients with localized non-small cell lung cancer (NSCLC) following treatment with curative intent holds promise to identify patients at risk of relapse. New methods can detect circulating tumour DNA (ctDNA) in plasma to fractional concentrations as low as a few parts per million, and clinical evidence is required to inform their use.

Patients And Methods: We analyzed 363 serial plasma samples from 88 patients with early-stage NSCLC (48.

Characteristics, origin, and potential for cancer diagnostics of ultrashort plasma cell-free DNA.

Current evidence suggests that plasma cell-free DNA (cfDNA) is fragmented around a mode of 166 bp. Data supporting this view has been mainly acquired through the analysis of double-stranded cfDNA. The characteristics and diagnostic potential of single-stranded and damaged double-stranded cfDNA in healthy individuals and cancer patients remain unclear.

Motivation to Change in the Course of a Pilot Study of a Step-Down Treatment Approach of Inpatient and Anorexia Nervosa-Specific Home Treatment and Its Effects on Treatment Outcome.

Anorexia nervosa (AN) is a serious mental disorder that typically manifests in adolescence. Motivation to change is an important predictor for treatment outcome in adolescent AN, even though its development over the often long therapeutic process, with transitions between treatment settings, has not yet been studied. In this pilot study, the course of motivation to change and its effect on treatment outcome were investigated over the course of a step-down treatment approach during a 12-month observation period.

Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients.

Glioma-derived cell-free DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. We determined the glioma-derived DNA fraction in cerebrospinal fluid (CSF), plasma, and urine samples from patients using sequencing of personalized capture panels guided by analysis of matched tumor biopsies. By sequencing cfDNA across thousands of mutations, identified individually in each patient's tumor, we detected tumor-derived DNA in the majority of CSF (7/8), plasma (10/12), and urine samples (10/16), with a median tumor fraction of 6.

Adaptive servo-ventilation in patients with chronic heart failure and sleep disordered breathing: predictors of usage.

Purpose: Adaptive servo-ventilation (ASV) is a therapy designed for patients with central sleep apnea (CSA) and Cheyne Stokes respiration. The aim of this study was to find predictors of ASV usage in patients with CSA in a routine sleep clinic cohort.

Methods: In this retrospective study, consecutive patients in whom ASV therapy was initiated at the University Hospital Regensburg between 2011 and 2015, were analyzed.

'Therapists in action'-Home treatment in adolescent anorexia nervosa: A stepped care approach to shorten inpatient treatment.

Objective: It was the aim of this pilot study to apply a novel eating disorder (ED)-specific home treatment (HoT) to adolescents with anorexia nervosa (AN) and to investigate its feasibility, effects and safety.

Method: Twenty-two patients consecutively admitted to the hospital and fulfilling DSM-5 criteria for typical or atypical AN received HoT after 4-8 weeks of inpatient treatment. During the first two months of HoT, the patient and her family were visited on average three to four times per week, during the third and fourth months of HoT once or twice a week by a multi-professional team.

ctDNA monitoring using patient-specific sequencing and integration of variant reads.

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping.

Detection of ctDNA from Dried Blood Spots after DNA Size Selection.

Background: Recent advances in the study and clinical applications of circulating tumor DNA (ctDNA) are limited by practical considerations of sample collection. Whole-genome sequencing (WGS) is increasingly used for analysis of ctDNA, identifying copy-number alterations and fragmentation patterns. We hypothesized that low-depth/shallow WGS (sWGS) data may be generated from minute amounts of cell-free DNA, and that fragment-size selection may remove contaminating genomic DNA from small blood volumes.

Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors.

Background: Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.

Methods: Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine.

Results: Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.

Enhanced detection of circulating tumor DNA by fragment size analysis.

Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 patients with cancer using low-pass whole-genome sequencing (0.

Calcineurin Silencing in Dictyostelium discoideum Leads to Cellular Alterations Affecting Mitochondria, Gene Expression, and Oxidative Stress Response.

Calcineurin is involved in development and cell differentiation of the social amoeba Dictyostelium discoideum. However, since knockouts of the calcineurin-encoding genes are not possible in D. discoideum it is assumed that the phosphatase also plays a crucial role during vegetative growth of the amoebae.

The potential of volunteered geographic information to investigate peri-urbanization in the conservation zone of Mexico City.

Due to the availability of Web 2.0 technologies, volunteered geographic information (VGI) is on the rise. This new type of data is available on many topics and on different scales.

Polo-like kinase inhibitor volasertib marginally enhances the efficacy of the novel Fc-engineered anti-CD33 antibody BI 836858 in acute myeloid leukemia.

Acute myeloid leukemia (AML) is the second most common type of leukemia in adults. Incidence of AML increases with age with a peak incidence at 67 years. Patients older than 60 years have an unfavorable prognosis due to resistance to conventional chemotherapy.

Adaptive servo-ventilation and sleep quality in treatment emergent central sleep apnea and central sleep apnea in patients with heart disease and preserved ejection fraction.

Background: Reduced sleep quality is associated with impaired quality of life and increased mortality in patients with heart failure. The aim of this study was to observe changes in sleep fragmentation and sleep quality in patients with heart disease and preserved left ventricular ejection fraction (pEF) treated with adaptive servo-ventilation (ASV) therapy for treatment of emergent central sleep apnea (TECSA) or central sleep apnea (CSA).

Methods: 114 patients with structural heart disease and pEF introduced to ASV therapy between 2010 and 2015 were retrospectively analyzed.

Whom are we treating with adaptive servo-ventilation? A clinical post hoc analysis.

Background: Recent evidence has shown that adaptive servo-ventilation (ASV) is contraindicated in patients with predominant central sleep apnea (CSA) and reduced left ventricular ejection fraction (LVEF ≤45%). The objective of this study was to assess the clinical usage of ASV in patients at the time-point of the release of a safety warning by type of SDB, breathing pattern and LVEF.

Methods: Patients of a cardiac and a respirology sleep center, both in Germany, who received ASV therapy were contacted between May and October 2015.

Human and remote sensing data to investigate the frontiers of urbanization in the south of Mexico City.

The data presented here were originally collected for the article "Frontiers of Urbanization: Identifying and Explaining Urbanization Hot Spots in the South of Mexico City Using Human and Remote Sensing" (Rodriguez et al. 2017) [4]. They were divided into three databases (remote sensing, human sensing, and census information), using a multi-method approach with the goal of analyzing the impact of urbanization on protected areas in southern Mexico City.

Novel therapeutic approach to improve hematopoiesis in low risk MDS by targeting MDSCs with the Fc-engineered CD33 antibody BI 836858.

We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33HLA-DRLin, has a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it has an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS.

Decitabine enhances anti-CD33 monoclonal antibody BI 836858-mediated natural killer ADCC against AML blasts.

Acute myeloid leukemia (AML) is the most common type of acute leukemia, affecting older individuals at a median age of 67 years. Resistance to intensive induction chemotherapy is the major cause of death in elderly AML; hence, novel treatment strategies are warranted. CD33-directed antibody-drug conjugates (gemtuzumab ozogamicin) have been shown to improve overall survival, validating CD33 as a target for antibody-based therapy of AML.

Combined treatment of the immunoconjugate bivatuzumab mertansine and fractionated irradiation improves local tumour control in vivo.

Background And Purpose: To test whether BIWI 1 (bivatuzumab mertansine), an immunoconjugate of the humanized anti-CD44v6 monoclonal antibody BIWA 4 and the maytansinoid DM1, given simultaneously to fractionated irradiation improves local tumour control in vivo compared with irradiation alone.

Material And Methods: For growth delay, FaDu tumours were treated with 5 intravenous injections (daily) of phosphate buffered saline (PBS, control), BIWA 4 (monoclonal antibody against CD44v6) or BIWI 1 (bivatuzumab mertansine) at two different dose levels (50 μg/kg DM1 and 100 μg/kg DM1). For local tumour control, FaDu tumours received fractionated irradiation (5f/5d) with simultaneous PBS, BIWA 4 or BIWI 1 (two dose levels).