pinecone/core-2020-05-10-deduplication huggingface dataset:
Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia

BACKGROUND: Cytarabine (cytosine arabinoside, ara-C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara-C, are considerable and may cause difficulties during chemotherapy. Single nucleotide polymorphisms (SNPs) can play a significant role in modifying nucleoside-drug pharmacokinetics and pharmacodynamics and thus the development of adverse effects. Our aim was to determine whether polymorphisms in genes encoding transporters and enzymes responsible for the metabolism of ara-C are associated with toxicity and clinical outcome in a patient population with childhood ALL. PROCEDURE: We studied 8 SNPs in the CDA, DCK, DCTD, SLC28A3, and SLC29A1 genes in 144 patients with childhood acute lymphoblastic leukemia treated according to ALLIC BFM 1990, 1995 and 2002 protocols. RESULTS: DCK rs12648166 and DCK rs4694362 SNPs were associated with hematologic toxicity (OR = 2.63, CI 95% = 1.37-5.04, P = 0.0036 and OR = 2.53, CI 95% = 1.34-4.80, P = 0.0044, respectively). CONCLUSIONS: Our results indicate that DCK polymorphisms might be  important genetic risk factors for hematologic toxicity during ALL treatment with ara-C. Individualized chemotherapy based on genetic profiling may help to optimize ara-C dosing, leading to improvements in clinical outcome and reduced toxicity. Pediatr Blood Cancer 2014;9999:1-7(c) 2015 Wiley Periodicals, Inc
Mature and Immature Teratoma: A Report From the Second Italian Pediatric Study

Background. Teratomas demonstrate a benign clinical behavior, however they may recur with malignant components or as teratoma, and in a small group of patients prognosis could be fatal. After the ®rst Italian study, we collected cases of teratoma, alongside the protocol\ud
for malignant germ cell tumors. Procedure. Patients with teratoma were collected from 2004 to 2014. Teratomas were classi®ed according to the WHO classi®cations, as mature and immature. Patients with pathological aFP and/or bHCG, and those with a\ud
malignant germ cell component were not included. Results. The study enrolled 219 patients (150 mature, 69 immature teratomas) with a median age at diagnosis of 42 months. The primary sites involved were: 118 gonadal and 101 extragonadal teratomas. Two females with ovarian teratoma had a positive family history. Complete and incomplete surgeries were performed in 85% and 9% of cases. Seventeen events occurred: six females had a second\ud
metachronous tumor (5 contralateral ovarian teratoma, 1 adrenal neuroblastoma) and 11 teratomas relapsed/progressed (3 mature, 8 immature teratomas). Two patients died, one of progressive immature teratoma and one of surgical complications. At a median follow up of 68 months, the event-free, relapse-free, and overall survival rates were 90.6%, 94.3%, 98.6%, respectively. Conclusions. Teratomas show a good prognosis, especially the mature ones: surgery and follow-up remain the standard approach. Incomplete surgery in\ud
immature teratoma is the group at greatest risk of relapse. Bilateral ovarian tumors are a possibility, and the rare family predisposition to ovarian mature teratoma warrants further analyses
Preclinical assessments of the MEK inhibitor PD-0325901 in a mouse model of neurofibromatosis type 1.

Background: Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes affected individuals to formation of benign neurofibromas, peripheral nerve tumors that can be associated with significant morbidity. Loss of the NF1 Ras-GAP protein causes increased Ras-GTP, and we previously found that inhibiting MEK signaling downstream of Ras can shrink established neurofibromas in a genetically engineered murine model. Procedures: We studied effects of MEK inhibition using 1.5 mg/kg/day PD-0325901 prior to neurofibroma onset in the Nf1 flox/flox;Dhh-Cre mouse model. We also treated mice with established tumors at 0.5 and 1.5 mg/kg/day dosees of PD-0325901. We monitored tumor volumes using MRI and volumetric measurements, and measured pharmacokinetic and pharmacodynamic endpoints. Results: Early administration significantly delayed neurofibroma development as compared to vehicle controls. When treatment was discontinued neurofibromas grew, but no rebound effect was observed and neurofibromas remained significantly smaller than controls. Low dose treatment of mice with PD-0325901 resulted in neurofibroma shrinkage equivalent to that observed at higher doses. Tumor cell proliferation decreased, although less than at higher doses with drug. Tumor blood vessels per area correlated with tumor shrinkage. Conclusions: Neurofibroma development was not prevented by MEK inhibition, beginning at 1 month of age, but tumor size was controlled by early treatment. Moreover, treatment with PD-0325901 at very low doses may shrink neurofibromas while minimizing toxicity. These studies highlight how genetically engineered mouse models can guide clinical trial design
Cognitive dysfunction in children with brain tumors at diagnosis

Background: Survivors of brain tumors have a high risk for a wide range of cognitive problems. These dysfunctions are caused by the lesion itself and its surgical removal, as well as subsequent treatments (chemo- and/or radiation therapy). Multiple recent studies have indicated that children with brain tumors (BT) might already exhibit cognitive problems at diagnosis, i.e., before the start of any medical treatment. The aim of the present study was to \ud
investigate the baseline neuropsychological profile in children with BT compared to children with an oncological diagnosis not involving the central nervous system (CNS).  \ud
Methods: Twenty children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1 to 16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient’s age. Furthermore, the child and his/her parent(s) completed self-report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as \ud
surgery, chemotherapy or irradiation. Groups were comparable with regard to age, gender and socioeconomic status. \ud
Results:  Compared to the control group, patients with BTs performed significantly worse in tests of working memory, verbal memory and attention (effect sizes between 0.28 and 0.47). In contrast, the areas of perceptual reasoning, processing speed and verbal comprehension were preserved at the time of measurement.  \ud
Conclusion: Our results highlight the need for cognitive interventions early in the treatment process in order to minimize or prevent academic difficulties as patients return to school
Nosocomial outbreak of hepatitis B virus infection in a pediatric hematology and oncology unit in South Africa : epidemiological investigation and measures to prevent further transmission

BACKGROUND : Hospital-acquired hepatitis B virus (HBV) infection has been well described and continues to occur worldwide. Recent nosocomial outbreaks have been linked to unsafe injection practices, use of multi-dose vials, and poor staff compliance with
standard precautions. This report describes a nosocomial outbreak that occurred in a
paediatric haematology and oncology unit of a large academic hospital, the epidemiological investigation of the outbreak, and preventive measures implemented
to limit further in-hospital transmission.
METHODS :Outbreak investigation including contact tracing and HBV screening were initiallycarried out on all patients seen by the unit during the same period as the first three
cases. Routine screening for the entire patient population of the unit was initiated in
February 2013 when it was realised that numerous patients may have been
exposed.
RESULTS : Forty-nine cases of HBV infection were confirmed in 408 patients tested between July 2011 and October 2013. Phylogenetic analysis of the HBV preC/C gene
nucleotide sequences revealed that all tested outbreak strains clustered together.
Most (67%) patients were HBeAg positive. The cause of transmission could not be
established. Preventive measures targeted three proposed routes. HBV screening
and vaccination protocols were started in the unit.
CONCLUSIONS : The high number of HBeAg positive patients, together with suspected lapses in infection prevention and control measures, are believed to have played a major role in the transmission. Measures implemented to prevent further in-hospital
transmission were successful. On-going HBV screening and vaccination
programmes in paediatric haematology and oncology units should become standard
of care.http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1545-50172016-11-30hb201
Chemotherapy Responsiveness in a Patient With Multiply Relapsed Ameloblastic Fibro-Odontosarcoma of the Maxilla

Ameloblastic fibro-odontosarcoma (AFOS) is an extremely rare malignant odontogenic tumor. Complete surgical excision is the treatment of choice. Deaths due to disease recurrence and/or progression are documented. Here, we report the case of a 15-year-old female with multiple recurrent AFOS. She responded to chemotherapy with ifosfamide and doxorubicin consolidated by stereotactic reirradiation using cyberknife and remained in complete remission 14 months from the end of reirradiation therapy. Chemotherapy with ifosfamide and doxorubicin should be considered in advanced cases of AFOS. (C) 2015 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc
Preclinical Evidence for the Use of Sunitinib Malate in the Treatment of Plexiform Neurofibromas

Plexiform neurofibromas (pNF) are pathognomonic nerve and soft tissue tumors of neurofibromatosis type I (NF1), which are highly resistant to conventional chemotherapy and associated with significant morbidity/mortality. Disruption of aberrant SCF/c-Kit signaling emanating from the pNF microenvironment induced the first ever objective therapeutic responses in a recent phase 2 trial. Sunitinib malate is a potent, highly selective RTK inhibitor with activity against c-Kit, PDGFR, and VEGFR, which have also been implicated in the pathogenesis of these lesions. Here, we evaluate the efficacy of sunitinib malate in a preclinical Krox20;Nf1flox/− pNF murine model.
Experimental Design

Proliferation, β-hexosaminidase release (degranulation), and Erk1/2 phosphorylation were assessed in sunitinib treated Nf1+/− mast cells and fibroblasts, respectively. Krox20;Nf1flox/− mice with established pNF were treated sunitinib or PBS-vehicle control for a duration of 12 weeks. pNF metabolic activity was monitored by serial [18F]DG-PET/CT imaging.
Results

Sunitinib suppressed multiple in vitro gain-in-functions of Nf1+/− mast cells and fibroblasts and attenuated Erk1/2 phosphorylation. Sunitinib treated Krox20;Nf1flox/− mice exhibited significant reductions in pNF size, tumor number, and FDG uptake compared to control mice. Histopathology revealed reduced tumor cellularity and infiltrating mast cells, markedly diminished collagen deposition, and increased cellular apoptosis in sunitinib treated pNF.
Conclusions

Collectively, these results demonstrate the efficacy of sunitinib in reducing tumor burden in Krox20;Nf1flox/− mice. These preclinical findings demonstrate the utility of inhibiting multiple RTKs in pNF and provide insights into the design of future clinical trials
The N-terminal domain of human GATA1 prevents dyserythropoietic anemia and megakaryocyte dysplasia in vivo

We describe a child with dyserythropoietic anemia, thrombocytosis, functional platelet defect, and megakaryocyte dysplasia. We show that (i) this constellation of hematopoietic abnormalities was due to a germline mutation within the 5′ untranslated region (5′UTR) of globin transcription factor 1 (GATA1); (ii) the mutation impaired a 5′UTR GATA1 splicing site, with promoted production of the shortened GATA1 isoform lacking the N-terminus; and (iii) expression of the GATA1 N-terminus is restricted to erythroblasts and megakaryocytes in normal marrow, consistent with the patient's abnormal erythropoiesis and megakaryopoiesis. Our findings provide insights into the clinically relevant in vivo function of the N-terminal domain of GATA1 in human hematopoiesis
Allergic-like reactions to asparaginase: Atypical allergies without asparaginase inactivation

Background: Asparaginase is an important component of pediatric acute lymphoblastic leukemia (ALL) therapy. Unfortunately, this treatment is hampered by hypersensitivity reactions. In general, allergies – regardless of severity – cause complete inactivation of the drug. However, we report atypical allergic reactions without inactivation of asparaginase, here called allergic-like reactions. Procedure: Patients with an allergic-like reaction, who were treated according to the Dutch Childhood Oncology Group ALL-11 or the CoALL 08–09 protocol, were described. The reactions were identified by continual measurement of asparaginase activity levels. Characteristics, including timing of occurrence, symptoms, grade, and the presence of antiasparaginase antibodies, were compared to those of real allergies. Results: Fourteen allergic-like reactions occurred in nine patients. Five reactions were to PEGasparaginase and nine to Erwinia asparaginase. Allergic-like reactions occurred relatively late after the start of infusion compared to real allergies. Antibodies were absent in all but one patient with an allergic-like reaction, while they were detected in all patients with a real allergy. Symptoms and grade did not differ between the groups. Asparaginase was continued with the same formulation in six patients of whom four finished treatment with adequate activity levels. Conclusions: In conclusion, allergic-like reactions occur relatively late after the start of infusion and without antibodies. Despite these clinical differences, allergic-like reactions can only be distinguished from real allergies by continually measuring asparaginase activity levels. If clinically tolerated, formulations should not be switched in case of allergic-like reactions. Moreover, failure to recognize these reactions may lead to a less favorable prognosis if asparaginase therapy is terminated unnecessarily
A neonate with a unique non-Down syndrome transient proliferative megakaryoblastic disease

Transient myeloproliferative disorder (TMD) is a leukemia type that occurs typically in newborns. In Down syndrome, TMD is referred to as transient abnormal myelopoiesis (TAM).32 Recently, transientness has also been reported in acute myeloid leukemia patients with germline trisomy 21 mosaicism, and even in cases with somatic trisomy 21, with or without GATA1 mutations.  \ud
TMD cases without trisomy 21 are rare, and recurrent genetic aberrations that aid in clinical decision-making are scarcely described. We describe here a TMD patient without trisomy 21 or GATA1 mutation in whom single-nucleotide polymorphism analysis of leukemic blasts revealed a novel combined submicroscopic deletion (5q31.1-5q31.3 and 8q23.2q24)
Lifestyle and emotional well-being in men and women with type 2 diabetes (e-VitaDM-4; ZODIAC-48)

Contains fulltext :
                  169733.pdf (publisher's version ) (Open Access)BACKGROUND: Whether lifestyle is associated with well-being in patients with type 2 diabetes (T2D) is largely unknown. Uncovering and clarifying associations between these constructs may lead to new strategies for improving both. OBJECTIVES: The aim was to investigate the relationship between lifestyle and well-being, focussing on gender differences. METHODS: This cross-sectional study included 1085 patients with T2D that participated in the e-Vita part of the Zwolle outpatient diabetes project integrating available care (ZODIAC) study. Patients were included from May 2012 until September 2014 from 52 general practices. Emotional well-being was assessed with the World Health Organization-5 well-being index (WHO-5). Lifestyle information on body mass index, smoking, physical activity and alcohol use was extracted from self-reported questionnaires. Multiple linear regression analyses were used. RESULTS: After adjustment for other lifestyle factors, physical activity, smoking and drinking 22-35 alcohol consumptions per week were associated with the WHO-5 score in men and physical activity and smoking were associated with the WHO-5 score in women. In the fully adjusted analyses for the total study population, physical activity and smoking were still associated with the WHO-5 score (b = 1.1, P < .001 and b =-3.1, P = .018, respectively). In the fully adjusted analyses stratified to gender only physical activity was associated with the WHO-5 score (in men: b =0.8, P = .006, in women: b = 1.4, P = .001). CONCLUSION: This study shows a negative, non-clinically relevant association between smoking and emotional well-being in the total population with T2D and a positive, non-clinically relevant association between physical activity and emotional well-being in both men and women with T2D
Malignant ovarian germ cell tumors in pediatric patients: The\ud
AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica)\ud
study

Objective: Malignant ovarian germ cell tumors (MOGCT) carry an excellent prognosis, and the\ud
treatment aims to achieve results with the least possible treatment-related morbidity. The aim of\ud
this study was to assess the outcomes of pediatric patients with MOGCT.\ud
Methods: Patients were treated according to their stage: surgery and surveillance for stage I;\ud
a modified bleomycin–etoposide–cisplatin (BEP) regimen for stages II (three cycles), III, and IV\ud
(three cycles) with surgery on residual disease.\ud
Results: Seventy-seven patients were enrolled (median age 11.8 years), 26 with dysgerminoma\ud
(Dysg), 13 with immature teratoma and elevated serum alpha-fetoprotein levels (IT+AFP), and 38\ud
with nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage III, 5 stage IV.\ud
Among evaluable patients in stage I (5-year event-free survival [EFS] 72.1% [95% CI: 56.4–92.1%];\ud
5-year overall survival [OS] 100%), seven relapsed (three patients with Dysg and four patients\ud
with Non-Dysg) and were rescuedwith chemotherapy (plus surgery in three patients). Among the\ud
evaluable patients with stages II–IV, 48 (98%) achieved complete remission after chemotherapy\ud
± surgery, one (IT + AFP, stage IV) had progressive disease. In the whole series (median follow-up\ud
80 months), the 5-year OS and EFS were 98.5% (95% CI: 95.6–100%) and 84.5% (95% CI: 76.5–\ud
93.5%).\ud
Conclusions:We confirm the excellent outcome for MOGCT. Robust data are lacking on surgical\ud
staging, surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most appropriate\ud
BEP regimen. As pediatric oncologists,we support the role of surveillance after proper surgical\ud
staging providing cases are managed by experts at specialized pediatric centers
On the effect of the fiber orientation on the flexural stiffness of injection molded short fiber reinforced polycarbonate plates

The through-thickness fiber orientation distribution of injection molded polycarbonate
plates was experimentally determined by light reflection microscopy and
manual digitization of polished cross sections. Fiber length distribution was determined
by pyrolysis tests followed by image analysis. A statistical analysis was done
to determine the confidence limits of the fiber orientation results. The fiber orientation
distribution was described by using second-order orientation tensors. The throughthickness
stiffness variations were determined by the orientation averaging approach.
This layer stiffness distribution was used to simulate the behavior of beams subjected
to three point bending with a FEM Ansys model. The results were compared
with experimentally determined flexural stiffness both in the flow direction and in the
transverse flow direction. The effect of flow rate and melt-temperature on stiffness
and fiber orientation is discussed
Isothermal and Non-Isothermal Consolidation of Carbon Fiber Towpregs

Published by Wiley for the Society of Plastics Engineers (SPE).The purpose of this work is to establish and validate a model to predict the isothermal and non-isothermal consolidation behavior of unidirectional towpregs, made of carbon fibers and a thermoplastic polymer. A Finite Difference Method program was devised based on a set of analytical expressions developed in a previous work. The program allows the determination of pressure-displacement curves at constant press closing speed and fixed or variable molding temperature, allowing comparison with experimental data obtained in the same conditions. There was good agreement between theoretical predictions and experimental results for both the isothermal and non-isothermal consolidation. However, in the former case, the agreement was limited to low closing speeds and long pre-heating times. In the latter case these limitations did not exist, showing that the non-isothermal model is a good tool for the optimization of the consolidation process
Fracture behavior of polyetherimide (PEI) and\ud
interlaminar fracture of CF/PEI laminates at elevated\ud
temperatures

To investigate the effects of environmental temperature\ud
on fracture behavior of a polyetherimide (PEI) thermoplastic polymer and its carbon fiber (CF/PEI) composite,experimental and numerical studies were performed on compact tension (CT) and double cantilever beam (DCB) specimens under mode-I loading. The numerical analyses were based on 2-D large deformation finite element\ud
analyses (FEA). Elevated temperatures greatly released\ud
the crack tip triaxiality (constraint) and promoted matrix\ud
deformation due to low yield strength and enhanced\ud
ductility of the PEI matrix, which resulted in the greater\ud
plane-strain fracture toughness of the bulk PEI polymer\ud
and the interlaminar fracture toughness of its composite\ud
during delamination propagation with increasing temperature.Furthermore, the high triaxiality was developed\ud
around the delamination front tip in the DCB specimen,\ud
which accounted for the poor translation of matrix\ud
toughness to the interlaminar fracture toughness by\ud
suppressing the matrix deformation and reducing the\ud
plastic energy dissipated in the plastic zone. Especially,\ud
at delamination initiation, the weakened fiber/matrix adhesion at elevated temperatures led to premature failure\ud
of fiber/matrix interface, suppressing matrix deformation\ud
and preventing the full utilization of matrix toughness.\ud
Consequently, low interlaminar fracture toughness\ud
was obtained at elevated temperatures
Structure-property relationships in glass-reinforced polyamide, part 1: The effects of fiber content

We present the results of an extensive study of the performance of injection-molded glass-fiber reinforced polyamide 66 with glass content between 0 and 40% and based on two chopped glass products both sized with polyamide compatible sizing. Mechanical properties generally improved with increasing glass content, modulus linearly, strength with a maximum at 40-50% glass content, and impact showing an initial decrease from the resin value with a minimum at 4% glass content before increasing at higher glass contents. Residual fiber length decreased linearly with increasing glass content. Interfacial strength was found to be in the range of 30-36 MPa, and no significant differences in dry as molded performance was found between the 123D and 173X sizings. Conditioning these composites in either boiling water or water/glycol mixtures leads to a dramatic drop in both tensile modulus and tensile strength. This is most likely due to the high level of matrix plasticization. After conditioning, the 173X sized glass delivered a significantly higher level of tensile elongation at all fiber contents. Excellent agreement was obtained between the experimental data and the theoretical predictions of the rule of mixtures model for modulus and the Kelly-Tyson model for strength over the range of fiber concentrations studied