Molecular pathology : MP最新文献

{"title":"Immunohistochemical prognostic index for breast cancer in young women.","authors":"I Guerra,&nbsp;J Algorta,&nbsp;R Díaz de Otazu,&nbsp;A Pelayo,&nbsp;J Fariña","doi":"10.1136/mp.56.6.323","DOIUrl":"https://doi.org/10.1136/mp.56.6.323","url":null,"abstract":"<p><strong>Aims: </strong>Women under 35 years of age comprise a small proportion of patients with breast cancer, but determining their prognosis can be difficult. This prospective, multivariate study looked at several factors with the aim of obtaining a useful index to evaluate the prognosis of these women.</p><p><strong>Methods: </strong>In total, 108 patients below 35 years of age affected by invasive ductal carcinoma without distant metastasis were studied. The mean duration of the follow up period was six years. Histopathological (tumour size, histological grade, and lymph node stage) and immunohistochemical (c-erbB-2, p53, oestrogen receptor, and progesterone receptor) factors were measured in all patients, and the Nottingham prognostic index (NPI) was then calculated. An immunohistochemical prognostic index (IHPI) was created using the arithmetic sum of the four individual immunohistochemical factors.</p><p><strong>Results: </strong>In univariate assessment of survival, all the studied factors yielded a significant association with either overall survival or disease free survival, except for c-erbB-2 and p53 with disease free survival. In univariate calculation of risk, all the factors gave significant results; however, in multivariate analysis only tumour size, histological grade, and progesterone receptor were significant. Both NPI and IHPI correlated significantly with prognosis. In multivariate regression analysis, IHPI correlated with tumour size and there was a significant interaction between both variables.</p><p><strong>Conclusion: </strong>IHPI is very useful in determining the prognosis of tumours < or = 2 cm and of moderate use for tumours > 2, although it has no use in tumours > 5 cm.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 6","pages":"323-7"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.6.323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24099118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear beta catenin as a potential prognostic and diagnostic marker in patients with colorectal cancer from Hong Kong.","authors":"S C C Wong,&nbsp;E S F Lo,&nbsp;A K C Chan,&nbsp;K C Lee,&nbsp;W L Hsiao","doi":"10.1136/mp.56.6.347","DOIUrl":"https://doi.org/10.1136/mp.56.6.347","url":null,"abstract":"<p><strong>Aims: </strong>To study the expression of nuclear beta catenin in patients with colorectal cancer, colorectal adenoma, and colorectal polyps to elucidate its role in carcinogenesis, and its potential for prognosis and diagnosis.</p><p><strong>Methods: </strong>The expression of nuclear beta catenin was studied by immunohistochemistry using paraffin wax embedded specimens. Sixty specimens each of colorectal carcinoma, colorectal adenoma, colorectal polyp, and normal colorectal specimens were analysed. The potential for prognosis was assessed by correlating nuclear beta catenin expression in 60 and 75 patients with colorectal cancer with lymph node metastasis and survival, respectively. The diagnostic capacity was explored by comparing nuclear beta catenin expression in 60 patients with colorectal cancer with other cytokeratin 20 (CK20) positive adenocarcinomas, namely: 30 colonic mucinous adenocarcinomas, 30 gastric adenocarcinomas, 27 pancreatic adenocarcinomas, and 12 ovarian mucinous adenocarcinomas.</p><p><strong>Results: </strong>Nuclear beta catenin expression was highly associated with progression of colorectal tissue from normal epithelial tissue, polyps, adenomas, to carcinomas (r = 0.875; p < 0.0001). Nineteen patients with colorectal adenoma who subsequently developed colorectal carcinoma had higher nuclear beta catenin expression than those with colorectal adenomas alone (p < 0.0001). Moreover, those patients with colorectal cancer and high nuclear beta catenin expression had a higher incidence of lymph node metastasis (chi(2) = 16.99; p < 0.005) and shorter overall survival (p < 0.0001). Finally, nuclear beta catenin expression in colorectal adenocarcinomas was significantly higher than in other CK20 positive adenocarcinomas.</p><p><strong>Conclusions: </strong>Nuclear beta catenin expression is a potential prognostic factor in patients with colorectal cancer, and together with CK20, it could be used to identify colorectal carcinoma in the Hong Kong population.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 6","pages":"347-52"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.6.347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24099122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of cDNA microarray gene expression data obtained from linearly amplified RNA.","authors":"S D Jenson,&nbsp;R S Robetorye,&nbsp;S D Bohling,&nbsp;J A Schumacher,&nbsp;J W Morgan,&nbsp;M S Lim,&nbsp;K S J Elenitoba-Johnson","doi":"10.1136/mp.56.6.307","DOIUrl":"https://doi.org/10.1136/mp.56.6.307","url":null,"abstract":"<p><strong>Background: </strong>DNA microarray technology has permitted the analysis of global gene expression profiles for several diseases, including cancer. However, standard hybridisation and detection protocols require micrograms of mRNA for microarray analysis, limiting broader application of this technology to small excisional biopsies, needle biopsies, and/or microdissected tissue samples. Therefore, linear amplification protocols to increase the amount of RNA have been developed. The correlation between the results of microarray experiments derived from non-amplified RNA and amplified samples needs to be evaluated in detail.</p><p><strong>Methods: </strong>Total RNA was amplified and replicate hybridisation experiments were performed with linearly amplified (aRNA) and non-amplified mRNA from tonsillar B cells and the SUDHL-6 cell line using cDNA microarrays containing approximately 4500 genes. The results of microarray differential expression using either source of RNA (mRNA or aRNA) were also compared with those found using real time quantitative reverse transcription polymerase chain reaction (QRT-PCR).</p><p><strong>Results: </strong>Microarray experiments using aRNA generated reproducible data displaying only small differences to data obtained from non-amplified mRNA. The quality of the starting total RNA template and the concentration of the promoter primer used to synthesise cDNA were crucial components of the linear amplification reaction. Approximately 80% of selected upregulated and downregulated genes identified by microarray analysis using linearly amplified RNA were confirmed by QRT-PCR using non-amplified mRNA as the starting template.</p><p><strong>Conclusions: </strong>Linear RNA amplification methods can be used to generate high fidelity microarray expression data of comparable quality to data generated by microarray methods that use non-amplified mRNA samples.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 6","pages":"307-12"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.6.307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24099838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancer.","authors":"F Bataille,&nbsp;P Rümmele,&nbsp;W Dietmaier,&nbsp;D Gaag,&nbsp;F Klebl,&nbsp;A Reichle,&nbsp;P Wild,&nbsp;F Hofstädter,&nbsp;A Hartmann","doi":"10.1136/mp.56.5.286","DOIUrl":"https://doi.org/10.1136/mp.56.5.286","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the usefulness of molecular markers in predicting histopathological and clinical response to preoperative high dose chemotherapy (HDCT) and survival of patients with advanced gastric cancer.</p><p><strong>Methods: </strong>In a phase II trial, 25 patients with metastatic gastric cancer received preoperative tandem HDCT consisting of etoposide, cisplatin, and mitomycin, followed by autologous bone marrow transplantation to achieve surgical resectability. Samples before and after treatment, from normal and tumour tissue, were characterised histopathologically, and both p53 and BAX expression was analysed by immunohistochemistry. Pretreatment formalin fixed, paraffin wax embedded samples from normal and tumour tissue were microdissected, and the extracted DNA was preamplified using improved primer extension preamplification polymerase chain reaction. Detection of microsatellite instability (MSI) or loss of heterozygosity (LOH) was performed using markers for p53, BAX, BAT25, BAT26, D2S123, D17S250, and APC. Exons 5-9 of the p53 gene were sequenced directly on ABI 373.</p><p><strong>Results: </strong>Four parameters were significantly associated with response to chemotherapy and prolonged overall survival: positive p53 immunostaining, positive p53 mutation status before chemotherapy, strong histological regression induced by preoperative HDCT, and surgical treatment. Patients's sex or age, tumour location or stage, lymph node status, Lauren classification, MSI, or LOH did not influence duration of survival significantly in this high risk population.</p><p><strong>Conclusion: </strong>Positive p53 immunostaining and p53 mutation status in pretreatment tumour biopsies might be useful molecular predictors of response and prognosis in patients with advanced gastric cancer treated by preoperative HDCT.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 5","pages":"286-92"},"PeriodicalIF":0.0,"publicationDate":"2003-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.5.286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40828274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular heterogeneity of meningioma with INI1 mutation.","authors":"P Rieske,&nbsp;M Zakrzewska,&nbsp;S Piaskowski,&nbsp;D Jaskólski,&nbsp;B Sikorska,&nbsp;W Papierz,&nbsp;K Zakrzewski,&nbsp;P P Liberski","doi":"10.1136/mp.56.5.299","DOIUrl":"https://doi.org/10.1136/mp.56.5.299","url":null,"abstract":"<p><strong>Background: </strong>INI1 (hSNF5) mutations are linked to rhabdoid tumours, but mutations in meningiomas with hot spot mutations in position 377 have also been reported.</p><p><strong>Aims: </strong>To analyse the INI1 gene in meningioma.</p><p><strong>Methods: </strong>Exons 1, 4, 5, and 9 of the INI1 gene were analysed by the polymerase chain reaction and direct sequencing in 80 meningiomas. For all cases, western blotting of the INI1 protein was performed.</p><p><strong>Results: </strong>Only one of the 80 samples showed a cytosine insertion in codon 376. This mutation changed the open reading frame in almost the whole exon 9 and resulted in a longer hSNF5 protein. Complex analysis of the above described tumour sample by western blotting, DNA sequencing, and loss of heterozygosity (LOH) analysis showed that this particular meningioma consisted of heterogeneic cellular components. One of these components had a mutated INI1 gene, whereas in the other component INI1 was intact.</p><p><strong>Conclusions: </strong>INI1 mutation is a rare event in the molecular pathology of meningiomas. It is possible for the INI1 gene to be mutated in only a proportion of meningioma cells.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 5","pages":"299-301"},"PeriodicalIF":0.0,"publicationDate":"2003-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.5.299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40828276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential deletions of chromosome 3p are associated with the development of uterine cervical carcinoma in Indian patients.","authors":"S Dasgupta,&nbsp;S B Chakraborty,&nbsp;A Roy,&nbsp;S Roychowdhury,&nbsp;C K Panda","doi":"10.1136/mp.56.5.263","DOIUrl":"https://doi.org/10.1136/mp.56.5.263","url":null,"abstract":"<p><strong>Background: </strong>Deletions in chromosome 3 occur frequently in uterine cervical carcinoma (CA-CX). The common consensus regions deleted during CA-CX development are not well defined, and have not been correlated with tumour progression.</p><p><strong>Aims: </strong>To define specific regions of chromosome 3 deleted during development of CA-CX and to correlate these with clinicopathological data.</p><p><strong>Methods: </strong>Deletion mapping of chromosome 3 was done in seven cervical intraepithelial neoplasia (CIN) and 43 primary CA-CX samples using 20 highly polymorphic microsatellite markers.</p><p><strong>Results: </strong>Deletions of chromosome 3 were significantly associated with tumour progression. High frequencies (33-53%) of loss of heterozygosity (LOH) were found in 3p26.1, 3p22.3, 3p21.2, and 3p13, suggesting the location of putative tumour suppressor genes (TSGs) in these regions. Among these four regions, deletions in 3p21.2 were suggested to occur early during CA-CX development. A significant correlation was found between LOH at 3p26.1 and 3p22.3 with tumour progression from stage I/IIB to stage III/IV. No association was found with the highly deleted regions and human papillomavirus positivity, parity, or menopausal status. Microsatellite size alteration was seen in only seven of the samples. However, rare biallelic alterations were seen in and around the highly deleted regions. Loss of normal copy of chromosome 3 and interstitial alterations in chromosome 3p were seen in some samples.</p><p><strong>Conclusion: </strong>These four regions on chromosome 3p may be differentially deleted during specific stages of CA-CX development. The putative TSGs located in these regions may have a cumulative effect on tumour progression.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 5","pages":"263-9"},"PeriodicalIF":0.0,"publicationDate":"2003-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.5.263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40828386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The type and quality of paraffin wax is important when constructing tissue microarrays.","authors":"J Dennis,&nbsp;J Westra,&nbsp;A Bell,&nbsp;K Montgomery,&nbsp;K Oien","doi":"10.1136/mp.56.5.306","DOIUrl":"https://doi.org/10.1136/mp.56.5.306","url":null,"abstract":"","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 5","pages":"306"},"PeriodicalIF":0.0,"publicationDate":"2003-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.5.306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40828279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of cysteine dioxygenase (EC 1.13.11.20) and sulfite oxidase in the human lung: a potential role for sulfate production in the protection from airborne xenobiotica.","authors":"J Millard, R B Parsons, R H Waring, A C Williams, D B Ramsden","doi":"10.1136/mp.56.5.270","DOIUrl":"10.1136/mp.56.5.270","url":null,"abstract":"<p><strong>Aims: </strong>The lung is one of the major sites of phase I cytochrome P450 enzyme and phase II sulfotransferase expression, which together are thought to act as an enzymic barrier against the unimpeded transfer of airborne xenobiotics into the lung parenchyma and systemic circulation. Sulfate for conjugation is produced primarily from the oxidation of cysteine, begun by cysteine dioxygenase (CDO), and completed with the conversion of sulfite to sulfate via sulfite oxidase (SO). Little is known about the site of expression of these two enzymes in the alveoli of the human lung.</p><p><strong>Methods: </strong>Antibodies and oligonucleotide probes raised against both CDO and SO were used for immunohistochemistry and in situ hybridisation, respectively, to investigate the expression of CDO and SO in human lung alveoli.</p><p><strong>Results: </strong>CDO and SO were expressed in alveolar epithelial cells, which is also the site of expression of cytochrome P450 1B1.</p><p><strong>Conclusions: </strong>These results demonstrate that the two key enzymes in sulfate production are expressed in the same locale as phase I and phase II enzymes, and that these two enzymes may be involved in the production of sulfate for the maintenance of a metabolic barrier against the entry of airborne xenobiotics and the synthesis of important structural proteins and proteoglycans.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 5","pages":"270-4"},"PeriodicalIF":0.0,"publicationDate":"2003-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187337/pdf/mp56000270.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40828387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor revision of immunoglobulin heavy chain genes in human MALT lymphomas.","authors":"D Lenze,&nbsp;A Greiner,&nbsp;C Knörr,&nbsp;I Anagnostopoulos,&nbsp;H Stein,&nbsp;M Hummel","doi":"10.1136/mp.56.5.249","DOIUrl":"https://doi.org/10.1136/mp.56.5.249","url":null,"abstract":"<p><strong>Background/aims: </strong>Rearrangement of immunoglobulin gene segments, leading to B cells with functional receptors, is thought to be largely restricted to developing immature B cells in bone marrow. However, accumulating evidence suggests that mature B cells occasionally modify their antigen specificity by VH segment replacements during the germinal centre reaction to enhance antigen affinity, or to overcome self reactive antigen receptors. Although malignant B cells maintain the features of their normal counterparts in most instances, to date, such replacements have not been described for human B cell lymphomas.</p><p><strong>Methods: </strong>Rearranged immunoglobulin heavy chain genes from two extranodal marginal zone B cell lymphomas were amplified, cloned, and sequenced. Sequences with identical CDR3 regions were selected and aligned to each other and public databases.</p><p><strong>Results: </strong>VH replacements were seen in two extranodal marginal zone B cell lymphomas. In line with the hypothesis that in mature B cells these replacements are associated with active somatic hypermutation, in addition to VH replacement, different mutation patterns were seen in the revised VH portions. In the remaining common 3'-VH regions, these mutations could be used to establish a phylogenetic relation between the sequences, rendering the possibility of artefactual chimaeric polymerase chain reaction products very unlikely.</p><p><strong>Conclusions: </strong>These results support the view that VH replacements are a further mechanism for reshaping antigen affinity and specificity, and indicate that these receptor modifications are not restricted to normal and reactive germinal centre B cells, but may also occur in close association with the development of malignant B cell lymphomas.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 5","pages":"249-55"},"PeriodicalIF":0.0,"publicationDate":"2003-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.5.249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40828384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological and genetic analysis of 65 patients with a clinical suspicion of X linked hyper-IgM.","authors":"K C Gilmour,&nbsp;D Walshe,&nbsp;S Heath,&nbsp;G Monaghan,&nbsp;S Loughlin,&nbsp;T Lester,&nbsp;G Norbury,&nbsp;C M Cale","doi":"10.1136/mp.56.5.256","DOIUrl":"https://doi.org/10.1136/mp.56.5.256","url":null,"abstract":"<p><strong>Background: </strong>X linked hyper-IgM (XHIM) is a primary immunodeficiency caused by mutations in the tumour necrosis factor superfamily 5 gene, TNFSF5, also known as the CD40 ligand (CD40L) gene. Patients often present with recurrent infections, and confirmation of a diagnosis of XHIM enables appropriate therapeutic interventions, including replacement immunoglobulin, antibiotics, and bone marrow transplantation.</p><p><strong>Aim: </strong>To review and optimise the institution's diagnostic strategy for XHIM.</p><p><strong>Method: </strong>Samples from 65 boys were referred to this centre for further investigation of suspected XHIM. The results, which included a flow cytometric whole blood assay for CD40L expression followed by mutation analysis in selected patients, were reviewed.</p><p><strong>Results: </strong>Twenty one patients failed to express CD40L and TNFSF5 mutations were found in 20 of these patients. In contrast, no TNFSF5 mutations were found in 16 patients with weak expression of CD40L. Interestingly, one quarter of patients with confirmed XHIM who had TNFSF5 mutations had low concentrations of IgG, IgA, and IgM. Most of the remaining patients with XHIM had the classic pattern of normal or raised IgM with low concentrations of IgA and IgG.</p><p><strong>Conclusions: </strong>This study demonstrates the usefulness of the whole blood staining method as a rapid screen to select patients for subsequent TNFSF5 mutation analysis, and shows the benefits of a unified protein/genetic diagnostic strategy.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 5","pages":"256-62"},"PeriodicalIF":0.0,"publicationDate":"2003-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.5.256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40828385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}