367 research outputs found
Experimental and numerical studies of inclined cables: free and parametrically-forced vibrations
Because of few experimental studies in the inclined cable literature, this paper is aimed at experimental modelling and investigating the linear free and nonlinear forced vibrations of sagged inclined cables, by discussing the relevant outcomes in the background of theoretical and numerical achievements. Attention is paid to the identification of cable hybrid modes due to system asymmetry, which gives rise to an avoidance phenomenon in the natural frequency spectrum, and to the investigation of some typical 3-D nonlinear dynamics involving the simultaneous parametric/external excitation due to a harmonically time-varying support movement. Large-amplitude out-of-plane/in-plane multi-modal interactions due to non-planar/planar internal resonances are experimentally observed and complemented by space-time numerical simulation of the associated, geometrically nonlinear, partial-differential equations of parametrically-forced cable motion. Overall, the experimental and numerical results highlight the fundamental linear/nonlinear dynamic characteristics of inclined cables, and the crucial role played by the asymmetry induced by cable inclination, in addition to the significant effects of cable sag and dynamic extensibility
Experimental and Analytical Investigation into the Effect of Ballasted Track on the Dynamic Response of Railway Bridges under Moving Loads
Ballasted tracks are among the most widespread railway track typologies. The ballast possesses multiple functions. Among them, it significantly affects the dynamic interaction between a rail bridge and a moving load in terms of damping and load distribution. These effects entail accurate modeling of the track-ballast-bridge interaction. The paper presents a finite-difference formulation of the governing equations of the track and the bridge, modeled as Euler-Bernoulli (EB) beams, and coupled by a distributed layer of springs representing the ballast. The two equations are solved under a moving load excitation using a Runge-Kutta family algorithm and the finite-difference method for the temporal and spatial discretization, respectively. The authors validated the mathematical model against the displacement response of a rail bridge with a ballasted substructure. In a first step, the modal parameters of the bridge, obtained from ambient vibration measurements, are used to estimate the bending stiffness of an equivalent EB beam representative of the tested bridge. In a second step, the authors estimated the coupling effect of the ballast by assessing the model sensitivity to the modeling parameters and optimizing the agreement with the experimental data. Comparing the bridge's experimental displacement responses highlights the ballast's significant effect on the load distribution and damping. The considerable difference between the damping estimated from output-only identification and that determined from the displacement response under moving load proves the dominant role of the ballast in adsorbing the vibrations transmitted to the bridge under the train passage and the different damping sources under high-amplitude excitation. The authors discuss the tradeoff between model accuracy and computational effort for a reliable estimation of ballasted tracks response under moving loads
Fibrous hamartoma of Infancy: An Italian multi-istitutional experience.
Fibrous hamartoma of infancy: an Italian multi-institutional experience.
Carretto E, Dall'Igna P, Alaggio R, Siracusa F, Granata C, Ferrari A, Cecchetto G.
Source
Division of Paediatric Surgery, Department of Paediatrics, University of Padua, Padua, Italy.
Abstract
BACKGROUND:
Fibrous hamartoma (FH) of infancy is a benign mesenchymal tumor, occurring as a superficial mass. Complete excision is curative.
OBJECTIVE AND METHODS:
The clinical features and treatment results of 18 children with FH are described.
RESULTS:
Local excision was the most common procedure. Surgery was radical in 10 patients, with microscopic residual disease in 6; all of them are alive with no evidence of disease 2 to 49 months after diagnosis. One patient, treated with a local reexcision for macroscopic residual disease (and chemotherapy for a synchronous desmoid fibromatosis) is well 83 months after diagnosis; the last patient, with a lesion of the labia majora, only underwent biopsy and is doing well, awaiting plastic surgery.
LIMITATIONS:
The results did not reach statistical significance due to difficulties in collecting cases.
CONCLUSIONS:
FH should be treated by complete excision; in our experience a nonradical excision was also able to achieve the cure. An aggressive approach should be avoided, as the overall prognosis is excellent.
PMID:
16635660
[PubMed - indexed for MEDLINE
Surgery in Malignant Germ Cell Tumors of Childhood. results of the Second Italian Cooperative Study TCG 98.
Congenital pancreatoblastoma: a case report
The literature describes 15 cases of congenital pancreatoblastoma (PB): 5 had prenatal diagnosis, none
had metastases at diagnosis, 7 were associated with BeckwitheWiedemann syndrome (BWS). In 13 cases
resection was radical, while in 2 there were macroscopic residues. Only one patient underwent
chemotherapy after distant recurrence. All children are alive except one who died because of problems
related to BWS. Our goal is to describe the approach adopted in an infant with congenital PB treated in
our center. After a prenatal third semester diagnosis of abdominal anechoic lesion, the radiological investigations
(ultrasound, MRI) performed at birth described a cystic lesion of unclear nature. We proceeded
to laparoscopic exploration, transformed into open approach after the detection of a lesion
located in the body of the pancreas; this lesion was resected, preserving the head and tail of pancreas.
The histological diagnosis showed a completely excised PB. After excluding metastatic lesions, we
decided to perform only careful follow-up without chemotherapy. The follow-up at 12 months is
negative. Although PB is a malignant tumor that requires a multidisciplinary treatment, the congenital
cases seem to have a less aggressive biological behavior. The treatment, therefore, in case of complete
resection, could be only surgical, followed by a careful follow-up. These forms are often associated with
congenital BWS, but in our case the patient did not have the typical characteristics of the syndrome
SURGERY IN MALIGNANT GERM CELL TUMORS OF CHILDHOOD. RESULTS OF THE SECOND ITALIAN COOPERATIVE STUDY TCG 98
Analysis of treatment and results of the patientsenrolled in the Italian TCG-98 Study, still open and comparison of data with those of the previous Studt TCG-9
Nationwide central diagnosis review for childhood solid tumors: From concept to realization of an Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) integrated project
NTRK3 overexpression in undifferentiated sarcomas with YWHAE and BCOR genetic alterations
The BCOR family of tumors includes a number of undifferentiated sarcomas, occurring in various age groups and anatomic sites, characterized by a spindle and round cell phenotype and diffuse immunoreactivity for BCOR. Prior RNA sequencing data revealed that NTRK3 was a top-upregulated gene in BCOR-CCNB3 sarcomas. In this study, we investigate a large cohort of tumors harboring BCOR/YWHAE genetic alterations for NTRK3 upregulation at both the mRNA and protein levels, compared with other sarcoma types. Pan-Trk immunohistochemistry was assessed for intensity and extent. A correlation between NTRK3 expression and the type of BCOR alteration and BCOR immunoreactivity was also performed. Most soft tissue undifferentiated round cell sarcomas with YWHAE or BCOR rearrangements or BCOR internal tandem duplications (ITD) showed NTRK3, but not NTRK1 or NTRK2, upregulation by RNA sequencing data analysis. Cytoplasmic pan-Trk immunoreactivity was also observed in most soft tissue round cell sarcomas with YWHAE rearrangements (100%), BCOR ITD (80%), and BCOR-CCNB3 fusions (67%), as well as clear cell sarcomas of kidney (75%), another BCOR family tumor, and ossifying fibromyxoid tumors with ZC3H7B-BCOR fusion (100%), with variable staining intensity and extent. Pan-Trk staining was also seen in solitary fibrous tumors (100%) and less frequently in synovial sarcoma and Ewing sarcoma, but rarely in other sarcomas tested. Tumors harboring rare fusion variants of BCOR, such as BCOR-CHD9, a novel fusion identified by targeted RNA sequencing, and KMT2D-BCOR, were also positive for pan-Trk staining and NTRK3 overexpression. In conclusion, NTRK3 upregulation resulting in pan-Trk overexpression is common in the BCOR family of tumors as well as in subsets of BCOR-expressing sarcomas through alternative mechanisms. The therapeutic implication of this finding awaits further investigation
PLEUROPULMONARY BLASTOMA: A DIFFERENTIAL DIAGNOSIS OF CHRONIC COUGH. LONG TERM SURVIVALAFTER MULTIMODAL AGGRESSIVE THERAPY
ITAL J PEDIATR 2006;32:122-125
CASE REPORT
CASO CLINICO
Pleuropulmonary blastoma: a differential diagnosis of chronic cough. Long-term survival after multimodal aggressive therapy
Blastoma pleuro-polmonare: rara diagnosi differenziale da tosse cronica.
Remissione a lungo termine dopo aggressiva terapia multimodale
P. D''ANGELO, V. MANZO*, S. VENEZIA*, R. ALAGGIO", E SIRACUSA*,
M. LO CURTO*
Unit\ue0 Operativa di Oncoematologia Pediatrica, Ospedale dei Bambini " G . Di Cristina",
Palermo; * Dipartimento Materno Infantile, Universit\ue0 di Palermo; ** Istituto di Anatomia
Patologica, Universit\ue0 di Padova
Summary
Pleuropulmonary blastoma (PPB) in childhood is a rare clinicopathologic entity distinct
from adult pneumoblastoma. This tumour may originate from the lung, the pleura, or the
mediastinum; it can metastasize and is usually associated with a poor outcome. We report
the case of a 5-year-old boy who developed PPB manifesting with respiratory distress. At
the standard x-ray and magnetic resonance imaging of the chest there was opacity covering
the entire right lung. The histological and immunohistological tests led to the diagnosis
of blastematous, malignant mesenchymatous PPB with pluridirectional differentiation.
Treatment consisted of preoperative chemotherapy to reduce tumour volume, complete
surgical resection of the residuai tumour mass, and post-surgical chemotherapy. Following
this approach, the child is alive in continuous complete remission 9 years after diagnosis.
Riassunto
II Blastoma Pleuro-Polmonare (BPP) infantile \ue8 un ''entit\ue0 clinico patologica ben distinta
dal Pneumoblastoma dell''adulto. Questo tumore pu\uf2 prendere origine dal polmone, dalla
pleura o dal mediastino; pu\uf2 metastatizzare e ha spesso una prognosi infausta. Riportiamo
il caso di un bambino di 5 anni, in cui il BPP si manifest\uf2 con un distress respiratorio;
la radiografia del torace e la Risonanza Magnetica hanno evidenziato una grossa
massa che occupava l''emitorace destro. L''esame istopatologico ha permesso di porre
diagnosi di BPP. Il paziente \ue8 stato trattato con chemioterapia, che ha ridotto il volume
della massa, con asportazione del tumore e chemioterapia post-operatoria; tale trattamento
ha consentito i''eradicazione della malattia; il paziente \ue8 in remissione completa
continua a 9 anni dalla diagnosi.
Introduction
Pleuropulmonary blastoma (PPB) is an extremely rare and aggressive malignancy
of childhood. It was originally described as a distinct entity by Manivel
et al. ''. Prior to its identification it was reported in the early literature by
Spencer as pulmonary blastoma or embryonic sarcoma 2.
It is characterized by primitive mesenchymal tissue and epithelial tubular
structures resembling the foetal lung. The eponymous PPB defines the paediatric
variety of pulmonary blastoma. In PPB, the dysembrionic neoplasm
shows blastematous and sarcomatous components and a lack of carcinomatous
components (which are instead present in adult pulmonary blastoma),
sometimes on previous dysplastic pulmonary conditions 3 . PPB is classified
in 3 subtypes: type I (cystic), type II (mixed solid and cystic) and type III
(solid)4.
Key words
Pleuropulmonary blastoma \u2022
Childhood lung cancer \u2022 Adjuvant
chemotherapy
Parole chiave
Blastoma pleuropolmonare \u2022
Tumore polmonare infantile \u2022
Chemioterapia post-operatoria
Submitted: March 16, 2005
Accepted: July 19, 2005
Correspondence:
Prof. Margherita Lo Curto
Dipartimento di Pediatria
Universit\ue0 di Palermo
Istituto Materno Infantile
via Cardinale Rampolla 1
Palermo, Italy
Tel. +39 091 6555476
E-mail:
[email protected].
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PLEUROPULMONARY BLASTOMA IN A CHILD
The predominant clinical features are cough, tachypnea,
fever, respiratory distress; secondary pneumothorax
5 and chest pain have also been reported 6. Since
these features are not specific, an infectious disease is
often erroneously diagnosed; hence, when eventually
detected, the neoplasm is often very large, may even involve
an entire hemithorax, and present metastases.
Despite the different therapeutic procedures - surgery,
chemotherapy and radiotherapy - prognosis is often
poor: Indolfi et al. 7 report 42% and Priest et al. 6 45%
of event free survival (EFS) at 2 years. Poor prognostic
factors are histological subtype II or III6 , a maximum
diameter greater than 5 cm 7 , failure to completely remove
the mass, extrapulmonary effusion such as pleura
or pericardium, metastases 8.
We report the case of a five-year-old child who, despite
the large tumour size at diagnosis and histological subtype
II, after a treatment with chemotherapy before and
after surgery, is in continuous complete remission
(CCR) nine years after the diagnosis.
Case report
A 5-year-old boy was admitted to our ward for hyporexia,
cough, shortness of breath, progressive thinning
and pallor in the previous 2 months. The physical
examination showed poor clinical conditions, tachydyspnea
(R.F. 45/min.), hypophonesis and reduction of
the physiologic vescicular murmure of the middle and
lower regions of the right lung, meteoric abdomen with
the liver margin 5 cm below the right costai margin.
The results of the laboratory investigations were Hb 8.5
g/dl, white blood cells 18.800/ul (N 68%, L 22%, M
6%, E 4%), platelets 611.000/u.l, VES (K.I.) 65, CRP
2.4 mg/dl; serum levels of copper 168 ixg/dl, ferritin
292 ng/dl, LDH 1.261 u/1, oc-FP 6.3 u/1.
Chest radiographs showed a bulky mass in the right
hemithorax displacing the mediastinum leftward and
the liver downward (Fig. 1).
The thoracic-abdominal ultrasound scan showed a
poorly confined voluminous mass, having diameters of
120 x 86 mm, with echogenic-hyperechogenic structure
and some hypo-anechogenic areas, arising in right
hemithorax and displacing the liver and right kidney
downwards.
A magnetic resonance imaging (MRI) of the thorax
showed a mass involving entirely the right hemitorax,
with a centrai hemorrhagic component that displaced
the mediastinum and the heart to the left.
The patient underwent surgical thoracotomy, which revealed
an unencapsulated mass with smooth surface
and tense-elastic consistency, entirely covered by pleura,
not adherent to the thoracic wall; since the conspicuous
extension of the mass did not allow resection, only
a biopsy was performed.
Microscopically, the biopsy specimen showed a predominantly
solid neoplasm with focal cysts. The tumour
contained mesenchymal elongated cells arranged
in sheets, and more primitive blastematous foci. There
Fig. 1. Posterior-anterior chest radiograph at presentation,
showing a bulky mass, displacing the mediastinum.
was no evidence of typical rhabdomyoblasts or cartilage.
Cysts exhibited an epithelial lining, with flattened
to columnar cells and an underlying layer of primitive
mesenchymal cells. The morphologic appearance was
consistent with a diagnosis of PPB type II. Immunostains
emphasized the doubl\ue9 component with a positive
staining for cytokeratin (MNF116, pancytokeratin) in
the epithelial component and a positive vimentin staining
in mesenchymal component. Occasionai spindle
cells were positive for desmin; oc-fetoprotein, S-100
protein, CD99, NB84A were negative in both the epithelial
and the stremai component.
In order to stage the disease the patient underwent total
body bone scan with "Tc-MDP, brain and abdominal
CT scan, and bone marrow aspirate; no metastatic
spread was detected, and a stage III was defined.
The child underwent chemotherapy with carboplatinum
(CBP) 400 mg/m2 + etoposide (VP16) 150 mg/m2 days
1, 2; vincristine (VCR) 1.5 mg/m2 + actinomycin-D
(ACT-D) 1.5 mg/m2 day 21 + ifosfamide (IFO) 1500
mg/m2 days 21-23, for overall 3 cycles; thereafter, 2 cycles
were scheduled, including VCR 1.5 mg/m2 + ACTD
1.5 mg/m2 day 1, doxorubicin 40 mg/m2 days 1-2 and
IFO 1500 mg/m2 days 1-3. The number of cycles were
established according to the features of imaging studies.
A chest x-ray survey showed a very good response
(Fig. 2) to chemotherapy. Six months after the diagnosis
complete resection of the tumour was performed
through a right posterior-lateral thoracotomy by the
fifth intercostal space. The tumour was capsulated and
located between the upper and middle lobe of the right
lung, displacing caudally the middle and lower pulmonary
lobes. The centrai zone of the mass was composed
of hyalinized fibrous stroma nodules and very
small fragments of blastomatosous tumoral tissue, at
about 2 cm from the resection borders. The neoplasm
was almost entirely necrotic.
123
P. D''ANGELO ET AL.
Fig. 2. Posterior-anterior chest radiograph, after chemotherapy,
before surgical excision.
After surgery the patient underwent 2 more cycles of
chemotherapy with CBP 400 mg/m2 + VP 16 150
mg/m2/day x 2 days.
There was clinical and imaging evidence of a progressive
normalisation of lung morphology and function.
The patient was monitored with clinical and radiological
investigations according to the following schedule:
chest radiograms every 3 months the first year, every 6
months the second and third year, every 12 months for
the 4t h, 5l h and 6* year; MRI at 1 and 3 years after withdrawal
of therapy.
Nine years after the diagnosis, the child is in continuous
complete remission.
Discussion
PPB in childhood is very rare. Our patient, as most of
those reported in the literature 5 8 , presented unspecific
respiratory symptoms; the x-ray revealed a large intrathoracic
mass, suggesting the need for further imaging
studies. It is important to emphasize the role of an
early imaging examination (x-ray, ultrasound scan, CT
or MRI) to detect as soon as possible the mass, in order
to proceed to more specific investigations to elucidate
the nature and staging of this malignant tumour. Radiographic
findings of pleuropulmonary blastoma are not
specific, especially when most of the neoplasm is cystic,
resembling the radiographic features of teratoma.
In this respect we note that PPB may initially manifest
with clinical and radiologie signs and symptoms of
pneumothorax 5 and may arise from other dysplastic
conditions; as a matter of fact, cystic pulmonary adenomatoid
malformation (CPAM) can be associated
with PPB, which is also described in association with
some congenital dysembriogenic abnormalities as cystic
nephroma 3 . The clinical and radiological presentation
in our patient showed mediastinal involvement;
the mass was not excisable at the first surgical look because
the neoplasm involved the pleura and was very
large. The histopathologic diagnosis was consistent
with type II PPB.
The features described usually correlate with a poor
prognosis 6 8 . The patient was submitted to intensive
multiagent neoadiuvant chemotherapy, which reduced
the tumour mass, making the complete surgical resection
feasible, and allowing eradication of the malignancy.
Such intensive multiagent chemotherapy is in most cases
necessary for the reduction and complete excision of
the tumor, which represents the most favourable factor
for long term survival.
In a recent report describing 11 patients 7 , two underwent
total excision of the tumour at diagnosis, and
were both alive without disease at 23 and 132 months
respectively, with no adjuvant chemotherapy administered
in the latter; another 3 patients remained disease
free, two after macroscopic total resection and polychemotherapy
and one after polychemotherapy and delayed
complete surgery.
The effectiveness of chemotherapy has also been reported
by other Authors 8 1\ub0. The choice of the antiblastic
agents used in our patients was due to their known
effectiveness on mesenchymal and epithelial tumors n.
Our patient was not treated with radiotherapy, which
has proven to be effective in few patients 1.
In conclusion, this case suggests that PPB may be taken
in consideration for the differential diagnosis in respiratory
distress. According to our experience and to
other literature reports, total remission of this condition
may be achieved with complete surgical excision (primary
or delayed) and intensive chemotherapy.
References
1 Manivel JC, Priest JR, Watterson J, Steiner M, Woods WG, Wick
MR. Pleuropulmonary blastoma: the so called pulmonary blastoma
of childhood. Cancer 1988;62:1516-26.
2 Spencer H. Pulmonary blastoma. J Pathol Bacteriol 1961 ;82:161-5.
3 Priest JR, Watterson J, Woods WG, Brid RI. Pleuropulmonary
blastoma: a marker forfamilial disease. J Pediatr 1996;128:220-4.
4 Dehner LP. Watterson J, Priest J. Pleuropulmonaiy blastoma. A
unique intrathorac\uecc-pulmonary neoplasm of childhood. In: Askin
FB, Langston C, Rosemberg HS, eds. Pulmonary disease: perspectives
in pediatrie pathology. Basel: Karger 1995, p. 214-26.
5 Guler E, Kutluk MT, Yalcin B, Cila A, Kale G, Buyukpamukcu
M. Pleuropulmonary blastoma in a child presenting with pneumothorax.
Tumori 2001;87:340-2.
6 Priest JR, McDermott MB, Bathia S, Watterson J, Manivel JC,
Dehner LP. Pleuropulmonary blastoma. A clinic-pathologic study
ofSOcases. Cancer 1997;80:146-61.
7 Indolfi P, Casale F, Carli M, Bisogno G, Ninfo V, Cecchetto G, et
al. Pleuropulmonary blastoma: management and prognosis of 11
cases. Cancer 2000;89:1396-401.
8 Romeo C, Impellizzeri P, Grosso M, Vitarelli E, Gentile C. Pleu-
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PLEUROPULMONARY BLASTOMA IN A CHILD
ropulmonary blastoma: long-term survival and literature review.
Med Pediatr Oncol 1999;33:372-6.
Parsons SK, Fishman SJ, Hoorntje LE, Jaramillo D, Marcus KC,
Perez-Atayde AR, et al. Aggressive multimodal treatment of pleuropulmonary
blastoma. Ann Thorac Surg 2001;72:939-42.
Ozkajnak MF, Ortega JA, Laug W, Gilsanz V, Isaacs H Jr. Role of
chemotherapy in pediatrie pulmonary blastoma. Med Pediatr Oncol
1990;18:53-6.
12
BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities
open10With the advent of next-generation sequencing, an increasing number of novel gene fusions and other abnormalities have emerged recently in the spectrum of EWSR1-negative small blue round cell tumors (SBRCTs). In this regard, a subset of SBRCTs harboring either BCOR gene fusions (BCOR-CCNB3, BCOR-MAML3), BCOR internal tandem duplications (ITD), or YWHAE-NUTM2B share a transcriptional signature including high BCOR mRNA expression, as well as similar histologic features. Furthermore, other tumors such as clear cell sarcoma of kidney (CCSK) and primitive myxoid mesenchymal tumor of infancy also demonstrate BCOR ITDs and high BCOR gene expression. The molecular diagnosis of these various BCOR genetic alterations requires an elaborate methodology including custom BAC fluorescence in situ hybridization (FISH) probes and reverse transcription polymerase chain reaction assays. As these tumors show high level of BCOR overexpression regardless of the genetic mechanism involved, either conventional gene fusion or ITD, we sought to investigate the performance of an anti-BCOR monoclonal antibody clone C-10 (sc-514576) as an immunohistochemical marker for sarcomas with BCOR gene abnormalities. Thus we assessed the BCOR expression in a pathologically and genetically well-characterized cohort of 25 SBRCTs, spanning various BCOR-related fusions and ITDs and YWHAE-NUTM2B fusion. In addition, we included related pathologic entities such as 8 CCSKs and other sarcomas with BCOR gene fusions. As a control group we included 20 SBRCTs with various (non-BCOR) genetic abnormalities, 10 fusion-negative SBRCTs, 74 synovial sarcomas, 29 rhabdomyosarcomas, and other sarcoma types. In addition, we evaluated the same study group for SATB2 immunoreactivity, as these tumors also showed SATB2 mRNA upregulation. All SBRCTs with BCOR-MAML3 and BCOR-CCNB3 fusions, as well as most with BCOR ITD (93%), and all CCSKs showed strong and diffuse nuclear BCOR immunoreactivity. Furthermore, all SBRCTs with YWHAE-NUTM2B also were positive. SATB2 stain was also positive in tumors with YWHAE-NUTM2B, BCOR-MAML3, BCOR ITD (75%), BCOR-CCNB3 (71%), and a subset of CCSKs (33%). In conclusion, BCOR immunohistochemical stain is a highly sensitive marker for SBRCTs and CCSKs with BCOR abnormalities and YWHAE-rearrangements and can be used as a useful diagnostic marker in these various molecular subsets. SATB2 immunoreactivity is also present in the majority of this group of tumors.openKao, Yc; Sung, Ys; Zhang, L; Jungbluth, Aa; Huang, Sc; Argani, P; Agaram, Np; Zin, A; Alaggio, R; Antonescu, CrKao, Yc; Sung, Ys; Zhang, L; Jungbluth, Aa; Huang, Sc; Argani, P; Agaram, Np; Zin, A; Alaggio, Rita; Antonescu, C
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