580 research outputs found
Особливості змісту права громадян на екологічну безпеку
В статье сделан анализ содержания права граждан на экологическую безопасность, определяется момент, с которого право на экологическую безопасность считается нарушенным
Nonperturbative confinement in quantum chromodynamics:III. Improved gluon propagator
An ansatz is introduced for the three‐gluon vertex that is consistent with the Slavnov–Taylor identity in Landau gauge. It is shown that the gluon has a confining infrared singularity; but there is also a tachyon, indicating an insufficiency either of quarkless QCD or at least of our approximation to it
Granulocyte concentrates: Prolonged functional capacity during storage in the presence of phenotypic changes
Background Granulocyte transfusion has been proposed as a bridging therapy for patients with prolonged p
Theorizing Practice and Practising Theory: Outlines for an Actor-Relational-Approach in Planning
Pulsed radiofrequency or anterior neurectomy for anterior cutaneous nerve entrapment syndrome (ACNES) (the PULSE trial): study protocol of a randomized controlled trial
Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I
Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem
cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency
of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset
have improved outcome, suggesting to administer such therapy as early as possible. Given that
the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases
Efficacy of MSC for steroid-refractory acute GVHD associates with MSC donor age and a defined molecular profile
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Integrated Analyses of Copy Number Variations and Gene Expression in Lung Adenocarcinoma
Numerous efforts have been made to elucidate the etiology and improve the treatment of lung cancer, but the overall five-year survival rate is still only 15%. Identification of prognostic biomarkers for lung cancer using gene expression microarrays poses a major challenge in that very few overlapping genes have been reported among different studies. To address this issue, we have performed concurrent genome-wide analyses of copy number variation and gene expression to identify genes reproducibly associated with tumorigenesis and survival in non-smoking female lung adenocarcinoma. The genomic landscape of frequent copy number variable regions (CNVRs) in at least 30% of samples was revealed, and their aberration patterns were highly similar to several studies reported previously. Further statistical analysis for genes located in the CNVRs identified 475 genes differentially expressed between tumor and normal tissues (p<10−5). We demonstrated the reproducibility of these genes in another lung cancer study (p = 0.0034, Fisher's exact test), and showed the concordance between copy number variations and gene expression changes by elevated Pearson correlation coefficients. Pathway analysis revealed two major dysregulated functions in lung tumorigenesis: survival regulation via AKT signaling and cytoskeleton reorganization. Further validation of these enriched pathways using three independent cohorts demonstrated effective prediction of survival. In conclusion, by integrating gene expression profiles and copy number variations, we identified genes/pathways that may serve as prognostic biomarkers for lung tumorigenesis
Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare fatal autorecessive disease. Halter et al. report outcomes from all known haematopoietic stem cell transplantations worldwide from sibling or unrelated donors for MNGIE between 2005 and 2011. In some of the recipients, correction of the underlying metabolic defect results in gradual clinical improvemen
Multicenter Comparison of Molecular Tumor Boards in The Netherlands:Definition, Composition, Methods, and Targeted Therapy Recommendations
Background Molecular tumor boards (MTBs) provide rational, genomics-driven, patient-tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. Materials and Methods MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision-making method, reporting, and registration of the MTBs was completed through on-site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Results Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type-specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). Conclusion MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a "Dutch MTB model" for an optimal, collaborative, and nationally aligned MTB workflow. Implications for Practice Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing
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