bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tympanic membrane retraction: An endoscopic evaluation of staging systems
Authors: James Adrian L. , Papsin Blake C. , Trimble Keith , Ramsden James , Sanjeevan Nadarajah , Bailie Neil , Chadha Neil K. 
Published: February 2012

AbstractObjectives/Hypothesis:The objectives of this work were to assess inter‐ and intraobserver variability of different staging systems for tympanic membrane (TM) retraction using otoendoscopy in children at risk of retraction from cleft palate, to compare hearing level with stage of retraction, and to propose optimum characteristics for monitoring TM retraction with endoscopy.Study Design:Cross‐sectional study.Methods:Endoscopic images of 245 TMs of children with cleft palate (mean age, 13.0 years) were assessed on two separate occasions by six observers using the Sade and Erasmus staging systems for pars tensa retraction and Tos system for pars flaccida retraction. Intra‐ and interobserver agreements were calculated. Extent of TM retraction was compared with hearing threshold. TMs with middle ear effusion, tympanostomy tubes, or perforation were excluded.Results:A total of 108 ear drums (44%) were rated as having pars tensa and/or flaccida retraction. Intraobserver agreement was fair to moderate (kappa = 0.3–0.37, P < .001) for the different staging systems and interobserver agreement slight to moderate (0.18–0.41 P < .001). Conductive hearing loss (four‐tone average air‐bone gap >25 dB HL) was present in 11 ears (15%). No correlation between hearing threshold and retraction stage was found. Isolated tensa retraction onto the promontory increased hearing threshold more than retraction involving the incus (P = .02; analysis of variance).Conclusions:Endoscopic image capture may provide a clear objective record of TM retraction, but current staging systems have unsatisfactory reliability when applied to such images, and retraction stage correlates poorly with hearing threshold. Modification of retraction assessment to improve validity and clinical relevance is proposed.
Validating the clinical assessment of eustachian tube dysfunction: The eustachian tube dysfunction questionnaire (ETDQ‐7)
Authors: McCoul Edward D. , Anand Vijay K. , Christos Paul J. 
Published: February 2012

AbstractObjectives/Hypothesis:Eustachian tube dysfunction (ETD) is a common condition that is associated with otologic and rhinologic symptoms. The complete assessment of ETD is limited without a valid symptom score. We developed and conducted initial validation of the seven‐item Eustachian Tube Dysfunction Questionnaire (ETDQ‐7), a disease‐specific instrument to assess symptoms with respect to ETD.Study Design:Validation study.Methods:The ETDQ‐7 was developed using standard survey methodology. The ETDQ‐7 was completed by a group of 50 consecutive adult patients diagnosed with ETD and 25 non‐ETD patients who served as a control group. Tympanometry was used as a criterion standard to distinguish the two groups. A subset of respondents repeated the ETDQ‐7 at a time point 4 weeks later.Results:Content validity for the ETDQ‐7 was established by focus group and review of the literature. Reliability testing indicated acceptable internal consistency for the entire instrument (Cronbach α = .71). The test–retest reliability indicated good correlation between the two questionnaires completed by the same patient 4 weeks apart (r = 0.78). The ETDQ‐7 was able to discriminate between patients with ETD and those without (P < .001), indicating excellent discriminant validity.Conclusions:The ETDQ‐7 is a valid and reliable symptom score for use in adult patients with ETD that may facilitate clinical practice by highlighting the impact of ETD. Further testing is needed to determine its usefulness in assessing treatment response.
Investigation of the role of the cerebellum in the myoclonic‐like movement disorder exhibited by tottering mice
Authors: Abbott Louise C. , Bump Melissa , Brandl Amy , De Laune Scarlett 
Published: February 2012

AbstractRecently it has been discovered that defects in neuronal ion channels can result in seizure disorders. The tottering mouse is a genetic animal model carrying a mutation in the α1A calcium channel subunit that causes these mice to exhibit generalized petit mal‐like epilepsy, cerebellar ataxia, and an intermittent movement disorder that has some characteristics similar to myoclonus or myoclonic epilepsy. We postulate that abnormal cerebellar Purkinje cell output to the deep cerebellar nuclei results in the intermittent movement disorder observed in these mice. The frequency and duration of seizure activity were measured in tottering mice before and 2 weeks after surgical or chemical lesioning of the cerebellum. Surgical lesions in the anterior cerebellar vermis of tottering mice produced significant reductions in seizure duration and frequency. Surgical lesioning of the posterior cerebellar vermis had no significant effect. Chemical lesions of the same cerebellar regions, using a locally applied neurotoxin, NMD‐L‐A, appear to produce effects similar to the surgical lesions. These data indicate that anterior vermal cerebellar output is important for production of the seizures associated with the intermittent movement disorder observed in tottering mice.
Charcot‐marie‐tooth disease presenting as a nonhealing ulcer in a 26‐year‐old man
Authors: Judhan Rudy J. , Maharaj Stefan R. , Perry Andrew , Dellon A. Lee , Maharaj Dale 
Published: February 2012

AbstractA 26‐year‐old man presented with a nonhealing ulcer on the plantar aspect of the left foot of five years duration. Initial investigations were unremarkable. It was only after careful neurological examination that an inherited neuropathy was suspected. This was confirmed by nerve conduction studies and serum electrophoresis. He subsequently underwent partial great toe amputation for the ulcer and underlying first phalangeal osteomyelitis with uneventful healing. Neuropathic ulcers are usually associated with several well‐known disorders including diabetes mellitus, tabes dorsalis, pernicious anemia, and sickle cell disease. A rarer cause is Charcot‐Marie‐Tooth Disease (CMTD). The report gives a review of CMTD and emphasizes that when faced with a nonhealing ulcer in the younger age group, such an underlying hereditary neuropathic cause must be considered. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.
Bilateral autologous breast reconstruction with deep inferior epigastric artery perforator flaps: Review of a single surgeon's early experience
Authors: Venkat Raghunandan , Lee Johnson C. , Rad Ariel N. , Manahan Michele A. , Rosson Gedge D. 
Published: February 2012

AbstractBackground:The purpose of this study is to describe the early experience of a single surgeon just out of training, including preoperative conditioning, surgical approach, and outcomes in bilateral deep inferior epigastric artery perforator (DIEP) flap breast reconstruction patients.Methods:We retrospectively reviewed 54 consecutive patients who underwent 108 DIEP flap breast reconstructions performed by a single surgeon over an initial 2.5‐year period.Results:There was 100% overall flap survival. The unplanned reoperation rate was 7.6% (n = 4). Minor complications including nonoperative infection, minor wound dehiscence, and donor site seroma occurred in 26% of patients (n = 14). Significant late complications were abdominal wall bulge (n = 1) and fat necrosis < 10% of volume (n = 1). Tissue expander explantation due to infection occurred in 25% of attempted staged patients (two of eight); this did not seem to compromise their oncologic treatment or final reconstruction outcome.Conclusion:This study demonstrates the efficacy of the DIEP flap for bilateral autologous breast reconstruction in the immediate, staged, and delayed settings. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.
Correlation imaging for multiscan MRI with parallel data acquisition
Authors: Li Yu , Dumoulin Charles 
Published: February 2012

AbstractA new approach to high‐speed magnetic resonance imaging (MRI) that uses all the data acquired in a multiscan imaging session is presented. This approach accelerates MRI data acquisition by statistically estimating correlation functions from images with different contrast and/or resolution. In multiscan MRI with parallel data acquisition, the estimation of correlation functions is dynamically improved as imaging proceeds. This allows imaging acceleration factors to be increased in subsequent scans, thereby reducing the total time of a multiscan MRI protocol. Furthermore, the correlation function estimates bring information about both coil sensitivity and anatomical structure into image reconstruction, thereby offering the ability to speed up MRI beyond the parallel imaging acceleration limit posed by a coil array alone. In this study, the feasibility of correlation imaging is demonstrated experimentally using brain and spine imaging protocols. The ability of correlation imaging to achieve an aggregate acceleration factor in excess of the number of coil elements in the phase encoding direction is also demonstrated. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Loss of bladder smooth muscle caveolae in the aging bladder
Authors: Lowalekar Samar K. , Cristofaro Vivian , Radisavljevic Ziv M. , Yalla Subbarao V. , Sullivan Maryrose P. 
Published: February 2012

AbstractAimsCaveolae are specialized regions of the cell membrane that modulate signal transduction and alterations in these structures affect bladder smooth muscle (BSM) contraction. Since bladder dysfunctions are common in the elderly, we evaluated the effect of aging on the morphology of caveolae and caveolin protein expression in BSM.MethodsCaveolar morphology (number, size, and depth) in BSM was determined from electron microscopy images of young (10 weeks), adult (6‐month old), and old (12‐month old) rat urinary bladders. Changes in expression levels of caveolin proteins with age were investigated by Western blot and immunofluorescence microscopy. Caveolin‐3 gene expression was determined by real‐time RT‐PCR in young and 19‐month‐old rat bladders.ResultsTwelve‐month‐old animals exhibited 50% fewer BSM caveolae compared to young (P < 0.01). The area of caveolae was significantly decreased at 6 and 12 months. Despite a decrease in the number of BSM caveolae at 12 months, the expression of caveolin‐1 and cavin‐1 were unaltered with age. In contrast, caveolin‐2 and caveolin‐3 protein expression and immunoreactivity were reduced in BSM at 6 and 12 months of age. Caveolin‐3 gene expression was also downregulated at 19 months compared to young animals.ConclusionBiological aging significantly decreases BSM caveolae number and morphology with associated selective alteration in caveolin protein expression. Since caveolae are protected membrane regions that regulate signal transduction, age‐related alterations in caveolae and caveolin protein expression could alter BSM contractility resulting in bladder dysfunctions of the elderly. Neurourol. Urodynam. 31:586–592, 2012. © 2012 Wiley Periodicals, Inc.
Finding off‐diagonal entries of the inverse of a large symmetric sparse matrix
Authors: Eastwood Shawn , Wan Justin W. L. 
Published: February 2012

SUMMARYThe method fast inverse using nested dissection (FIND) was proposed to calculate the diagonal entries of the inverse of a large sparse symmetric matrix. In this paper, we show how the FIND algorithm can be generalized to calculate off‐diagonal entries of the inverse that correspond to ‘short’ geometric distances within the computational mesh of the original matrix. The idea is to extend the downward pass in FIND that eliminates all nodes outside of each node cluster. In our advanced downwards pass, it eliminates all nodes outside of each ‘node cluster pair’ from a subset of all node cluster pairs. The complexity depends on how far (i,j) is from the main diagonal. In the extension of the algorithm, all entries of the inverse that correspond to vertex pairs that are geometrically closer than a predefined length limit l will be calculated. More precisely, let α be the total number of nodes in a two‐dimensional square mesh. We will show that our algorithm can compute O(α3 ∕ 2 + 2ε) entries of the inverse in O(α3 ∕ 2 + 2ε) time where l = O(α1 ∕ 4 + ε) and 0 ≤ ε ≤1 ∕ 4. Numerical examples are given to illustrate the efficiency of the proposed method. Copyright © 2012 John Wiley & Sons, Ltd.
Response to Comment on ‘Preconditioning of matrices partitioned in 2 × 2 block form: Eigenvalue estimates and Schwarz DD for mixed FEM’
Authors: Axelsson Owe , Blaheta Radim 
Published: February 2012

SUMMARYAs has been pointed out in a study by Cao, there is an erroneous omission in the study by Axelsson, Corollary 3.2 and Proposition 3.2, and the authors thank Zhi‐hao Cao for pointing this out.We mention, however, that these are side results and do not influence the major result of the paper ‘Preconditioning of matrices partitioned in 2 by 2 block form: Eigenvalue estimates and Schwarz DD for mixed FEM’.In this reply, we give a short background to the relations between inverses of saddle point matrices, thereby providing justified references to previous publications of the topic and present a corrected and extended version of Proposition 3.2. This gives an alternative presentation of the statements in the study by Cao, which might be useful for readers. Copyright © 2012 John Wiley & Sons, Ltd.
Guaranteed computable bounds on quantities of interest in finite element computations
Authors: Ainsworth Mark , Rankin Richard 
Published: February 2012

SUMMARYWe develop and compare a number of alternative approaches to obtain guaranteed and fully computable bounds on the error in quantities of interest of arbitrary order finite element approximations in the context of a linear second‐order elliptic problem. In each case, the bounds are fully computable and do not involve any unknown multiplicative factors. Guaranteed computable bounds are also obtained for the case when the Dirichlet boundary conditions are non‐homogeneous. This is achieved by taking account of the error incurred by the approximation of the Dirichlet data in the functional used to approximate the quantity of interest itself, which is found to generally give better results. Numerical examples are presented to show that the resulting estimators provide tight bounds with the effectivity index tending to unity from above. Copyright © 2012 John Wiley & Sons, Ltd.
Mediators of receptor tyrosine kinase activation in infantile fibrosarcoma: a Children's Oncology Group study
Authors: Gadd Samantha , Beezhold Patricia , Jennings Lawrence , George David , Leuer Katrin , Huang Chiang‐Ching , Huff Vicki , Tognon Cristina , Sorensen Poul HB , Triche Timothy , Coffin Cheryl M , Perlman Elizabeth J 
Published: February 2012

AbstractInfantile fibrosarcoma (IFS; also known as cellular congenital mesoblastic nephroma, CMN, when in the kidney) is a rare, undifferentiated tumour often characterized by the ETV6‐NTRK3 fusion transcript. Our goal was to identify downstream pathways, diagnostic markers and potential therapeutic targets for IFS/CMN. Global gene expression, reverse‐phase protein array and ETV6‐NTRK3 fusion analyses were performed on 14 IFS/CMN and compared with 41 other paediatric renal tumours. These analyses confirm significant receptor tyrosine kinase (RTK) activation, with evidence of PI3‐Akt, MAPK and SRC activation. In particular, GAB2 docking protein, STAT5‐pTyr‐694, STAT3‐pSer‐729 and YAP‐pSer‐127 were elevated, and TAZ‐pSer‐89 was decreased. This provides mRNA and proteomic evidence that GAB2, STAT activation and phosphorylation of the Hippo pathway transcription co‐activators YAP and TAZ contribute to the RTK signal transduction in IFS/CMN. All IFS/CMN tumours displayed a distinctive gene expression pattern that may be diagnostically useful. Unexpectedly, abundant ETV6‐NTRK3 transcript copies were present in only 7/14 IFS, with very low copy number in 3/14. An additional 4/14 were negative by RT‐PCR and absence of ETV6‐NTRK3 was confirmed by FISH for both ETV6 and NTRK3. Therefore, molecular mechanisms other than ETV6‐NTRK3 fusion are responsible for the development of some IFS/CMNs and the absence of ETV6‐NTRK3 fusion products should not exclude IFS/CMN as a diagnosis. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Frequent activating GNAS mutations in villous adenoma of the colorectum
Authors: Yamada Masayoshi , Sekine Shigeki , Ogawa Reiko , Taniguchi Hirokazu , Kushima Ryoji , Tsuda Hitoshi , Kanai Yae 
Published: February 2012

AbstractTo elucidate the role of GNAS mutations in colorectal tumourigenesis, we performed a mutation analysis in a total of 234 colorectal tumours, including adenomas, serrated lesions and adenocarcinomas. Activating GNAS mutations were found in 20 of the 24 villous adenomas (83%) but were absent in all the other tumours, except for one tubulovillous adenoma (3%) and two adenocarcinomas (3%). KRAS and BRAF mutations were always mutually exclusive. KRAS mutations were frequent in villous (67%) and tubulovillous (60%) adenomas but were rare or absent in tubular adenomas (6%) and serrated lesions, including hyperplastic polyps, sessile serrated polyps/sessile serrated lesions and traditional serrated adenomas (0‐9%). BRAF mutations were found in four villous adenomas (17%) and in the large majority of serrated lesions (81‐92%), but were absent in tubular and tubulovillous adenomas. Seventeen villous adenomas (71%) harboured GNAS mutations concomitantly with KRAS or BRAF mutations. Immunohistochemically, all the villous adenomas retained mismatch repair protein expression, suggesting that they are microsatellite‐stable. The current study showed that the presence of activating GNAS mutations, in association with KRAS or BRAF mutations, is a characteristic genetic feature of colorectal villous adenoma. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Neutrophil‐mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model
Authors: He Shuning , Lamers Gerda EM , Beenakker Jan‐Willem M , Cui Chao , Ghotra Veerander PS , Danen Erik HJ , Meijer Annemarie H , Spaink Herman P , Snaar‐Jagalska B Ewa 
Published: February 2012

AbstractInhibition of VEGF signalling effectively suppresses localized tumour growth but accelerates tumour invasiveness and micrometastasis by unknown mechanisms. To study the dynamic and reciprocal interactions between tumour cells and their microenvironment during these processes, we established a xenograft model by injecting tumour cells into the blood circulation of transparent zebrafish embryos. This reproducibly results in rapid simultaneous formation of a localized tumour and experimental micrometastasis, allowing time‐resolved imaging of both processes at single‐cell resolution within 1 week. The tumour vasculature was initiated de novo by remodelling of primitive endothelial cells into a functional network. Roles of myeloid cells in critical tumourigenesis steps such as vascularization and invasion were revealed by genetic and pharmaceutical approaches. We discovered that the physiological migration of neutrophils controlled tumour invasion by conditioning the collagen matrix and forming the metastatic niche, as detected by two‐photon confocal microscopy and second harmonic generation. Administration of VEGFR inhibitors blocked tumour vascularization and a localized tumour growth but enhanced migration of neutrophils, which in turn promoted tumour invasion and formation of micrometastasis. This demonstrates the in vivo cooperation between VEGF signalling and myeloid cells in metastasis and provides a new mechanism underlying the recent findings that VEGFR targeting can promote tumour invasiveness. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The dark side of a success story: microRNAs of the C19MC cluster in human tumours
Authors: Flor Inga , Bullerdiek Jörn 
Published: February 2012

AbstractMicroRNAs are a class of macromolecules of rapidly emerging significance for the pathogenesis of numerous human diseases, including cancer. Moreover, many of them hold great promise as valid biomarkers because of their high extracellular stability. Chromosome 19 harbours the largest cluster of microRNA genes known so far, which has developed in a very short time during mammalian evolution. Thus, in terms of evolution, gain of this cluster is an apparent success story. Nevertheless, we know very little about how functions of its microRNAs have contributed to this success and apparently, at least some of them can turn from Jekyll into Hyde and contribute to tumourigenesis. Recent work published in the Journal of Pathology by Fornari and colleagues, addressed here, reveals how members of that cluster are involved in the molecular pathogenesis of hepatocellular carcinomas. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Activation of protein kinase Cδ leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1
Authors: Johnson Charis L , Peat Jodi M , Volante Sonia N , Wang Rennian , McLean Carolyn A , Pin Christopher L 
Published: February 2012

AbstractPancreatic ductal adenocarcinoma (PDAC) has a 5 year survival rate post‐diagnosis of < 5%. Individuals with chronic pancreatitis (CP) are 20‐fold more likely to develop PDAC, making it a significant risk factor for PDAC. While the relationship for the increased susceptibility to PDAC is unknown, loss of the acinar cell phenotype is common to both pathologies. Pancreatic acinar cells can dedifferentiate or trans‐differentiate into a number of cell types including duct cells, β cells, hepatocytes and adipocytes. Knowledge of the molecular pathways that regulate this plasticity should provide insight into PDAC and CP. MIST1 (encoded by Bhlha15 in mice) is a transcription factor required for complete acinar cell maturation. The goal of this study was to examine the plasticity of acinar cells that do not express MIST1 (Mist1−/−). The fate of acinar cells from C57Bl6 or congenic Mist1−/− mice expressing an acinar specific, tamoxifen‐inducible Cre recombinase mated to Rosa26 reporter LacZ mice (Mist1CreERT/− R26r) was determined following culture in a three‐dimensional collagen matrix. Mist1CreERT/− R26r acini showed increased acinar dedifferentiation, formation of ductal cysts and transient increases in PDX1 expression compared to wild‐type acinar cells. Other progenitor cell markers, including Foxa1, Sox9, Sca1 and Hes1, were elevated only in Mist1−/− cultures. Analysis of protein kinase C (PKC) isoforms by western blot and immunofluorescence identified increased PKCε accumulation and nuclear localization of PKCδ that correlated with increased duct formation. Treatment with rottlerin, a PKCδ‐specific inhibitor, but not the PKCε‐specific antagonist εV1‐2, reduced acinar dedifferentiation, progenitor gene expression and ductal cyst formation. Immunocytochemistry on CP or PDAC tissue samples showed reduced MIST1 expression combined with increased nuclear PKCδ accumulation. These results suggest that the loss of MIST1 is a common event during PDAC and CP and events that affect MIST1 function and expression may increase susceptibility to these pathologies. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.