Liquid biopsy guides successful molecular targeted therapy of an inoperable pediatric brainstem neoplasm.

Midline CNS tumors are occasionally inaccessible for surgical biopsies. In these instances, cell-free DNA (cfDNA) may serve as a viable alternative for molecular analysis and identification of targetable mutations. Here, we report a young child with an inoperable brainstem tumor in whom a stereotactic biopsy was deemed unsafe.

Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen: A Nonrandomized Controlled Trial.

Importance: Medulloblastoma recurrence in patients who have previously received irradiation has a dismal prognosis and lacks a standard salvage regimen.

Objective: To evaluate the response rate of pediatric patients with medulloblastoma recurrence using an antiangiogenic metronomic combinatorial approach (Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial [MEMMAT]).

Design, Setting, And Participants: This phase 2, investigator-initiated, multicenter nonrandomized controlled trial assessed 40 patients with relapsed or refractory medulloblastoma without a ventriculoperitoneal shunt who were younger than 20 years at original diagnosis.

Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation.

Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism.

Supratentorial CNS-PNETs in children; a Swedish population-based study with molecular re-evaluation and long-term follow-up.

Background: Molecular analyses have shown that tumours diagnosed as supratentorial primitive neuro-ectodermal tumours of the central nervous system (CNS-PNETs) in the past represent a heterogenous group of rare childhood tumours including high-grade gliomas (HGG), ependymomas, atypical teratoid/rhabdoid tumours (AT/RT), CNS neuroblastoma with forkhead box R2 (FOXR2) activation and embryonal tumour with multi-layered rosettes (ETMR). All these tumour types are rare and long-term clinical follow-up data are sparse. We retrospectively re-evaluated all children (0-18 years old) diagnosed with a CNS-PNET in Sweden during 1984-2015 and collected clinical data.

Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a "MEMMAT-like" Metronomic Antiangiogenic Approach.

Medulloblastoma (MB) recurrence is usually incurable despite intensive therapy including high-dose chemotherapy. An evolving alternative approach to conventional chemotherapy aims at interfering with tumor angiogenesis at different levels. We report on a novel combinatorial metronomic antiangiogenic approach.

DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study.

Aims: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort.

Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry.

Background: The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features.

Methods: Data prospectively accumulated over a 4-year period in the Swedish Childhood Cancer Registry from patients aged 0-18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines.

Improving forest management by implementing best suitable timber harvesting methods.

Efficient forest operations are required for the provision of biodiversity and numerous ecosystem services, such as wood production, carbon sequestration, protection against natural hazards and recreation. In numerous countries, under difficult terrain conditions, the costs of forest management and harvesting are not covered by timber revenue. One possible option to increase the cost-effectiveness of the forestry sector is the application of state-of-the-art harvesting and extraction techniques, so-called best suitable harvesting methods.

Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1).

Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Surgical biopsy is rarely performed prior to treatment in the setting of NF1, resulting in a paucity of tumor genomic information. To define the molecular landscape of NF1-associated LGGs (NF1-LGG), we integrated clinical data, histological diagnoses, and multi-level genetic/genomic analyses on 70 individuals from 25 centers worldwide.

HeProMo: A decision support tool to estimate wood harvesting productivities.

In the field of forestry, one of the most economically important ecosystem service is the provision of timber. The need to calculate the economic effects of forest management in the short, medium, and long term is increasing. Forest operations or timber harvesting, which comprises felling, processing, and transport of trees or timber, are responsible for a large part of the costs and environmental impacts associated to forest management or enterprises.

Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors.

Background: Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses.

Methods: Clinical, genetic, and treatment data of 143 patients from 13 European countries were analyzed (2009-2017).

Preparation of colloidal molecules with temperature-tunable interactions from oppositely charged microgel spheres.

The self-assembly of small colloidal clusters, so-called colloidal molecules, into crystalline materials has proven extremely challenging, the outcome often being glassy, amorphous states where positions and orientations are locked. In this paper, a new type of colloidal molecule is therefore prepared, assembled from poly(N-isopropylacrylamide) (PNIPAM)-based microgels that due to their well documented softness and temperature-response allow for greater defect tolerance compared to hard spheres and for convenient in situ tuning of size, volume fraction and inter-particle interactions with temperature. The microgels (B) are assembled by electrostatic adsorption onto oppositely charged, smaller-sized microgels (A), where the relative size of the two determines the valency (n) of the resulting core-satellite ABn-type colloidal molecules.

A Droplet-Based Microfluidics Route to Temperature-Responsive Colloidal Molecules.

Small clusters of spherical colloids that mimic real molecules, so-called colloidal molecules, hold great promise as building blocks in bottom-up routes to new materials. However, their typical hard sphere nature has hampered their assembly into ordered structures, largely due to a lack of control in the interparticle interactions. To provide easy external control of the interactions, the present work focuses on the preparation of colloidal molecules from temperature-responsive microgel particles that undergo a transition from a soft repulsive to a short-range attractive state as their characteristic volume phase transition temperature (VPTT) is crossed.

Diagnostics and treatment of diffuse intrinsic pontine glioma: where do we stand?

Introduction: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines.

Methods: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively.

Label-free enrichment of primary human skeletal progenitor cells using deterministic lateral displacement.

Skeletal stem cells (SSCs) are present in bone marrow (BM) and offer great potential for bone regenerative therapies. However, in the absence of a unique marker, current sorting approaches remain challenging in the quest for simple strategies to deliver SSCs with consistent regeneration and differentiation capacities. Microfluidics offers the possibility to sort cells marker-free, based on intrinsic biophysical properties.

Empirical validation of an agent-based model of wood markets in Switzerland.

We present an agent-based model of wood markets and show our efforts to validate this model using empirical data from different sources, including interviews, workshops, experiments, and official statistics. Own surveys closed gaps where data was not available. Our approach to model validation used a variety of techniques, including the replication of historical production amounts, prices, and survey results, as well as a historical case study of a large sawmill entering the market and becoming insolvent only a few years later.

Microfluidics-Based Approaches to the Isolation of African Trypanosomes.

African trypanosomes are responsible for significant levels of disease in both humans and animals. The protozoan parasites are free-living flagellates, usually transmitted by arthropod vectors, including the tsetse fly. In the mammalian host they live in the bloodstream and, in the case of human-infectious species, later invade the central nervous system.

Cerebellar mutism syndrome in children with brain tumours of the posterior fossa.

Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete.

Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN.

Background: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear.

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease.

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG.

Sorting cells by their dynamical properties.

Recent advances in cell sorting aim at the development of novel methods that are sensitive to various mechanical properties of cells. Microfluidic technologies have a great potential for cell sorting; however, the design of many micro-devices is based on theories developed for rigid spherical particles with size as a separation parameter. Clearly, most bioparticles are non-spherical and deformable and therefore exhibit a much more intricate behavior in fluid flow than rigid spheres.

Immunotherapy in atypical teratoid-rhabdoid tumors: Data from a survey of the HGG-Immuno Group.

Background Aims: Atypical rhabdoid/teratoid tumors (AT/RT) are the most common brain tumors in infants and associated with a dismal prognosis. Although intensification of first-line therapy has resulted in improvement of overall survival, novel treatment strategies are needed. Because immunotherapy has resulted in remarkable results in several adult tumor entities, incorporation of immunotherapy into AT/RT treatment offers a novel alternative.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features.