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Sarah Gabri?l Joachim Blocher Pierre Dorny Emmanuel Nji Abatih Erich Schmutzhard Michaeli Ombay Bartholomayo Mathias Andrea Sylvia Winkler 《PLoS neglected tropical diseases》2012,6(10)
Background
Neurocysticercosis (NCC) is the most common cause of acquired epilepsy in Taenia solium endemic areas, primarily situated in low-income countries. Diagnosis is largely based upon the “Del Brutto diagnostic criteria” using the definitive/probable/no NCC diagnosis approach. Neuroimaging and specific T. solium cysticercosis antibody detection results are at the mainstay of this diagnosis, while antigen detection in serum has never been included. This study aimed at evaluating the addition of antigen detection as a major diagnostic criterion, especially in areas where neuroimaging is absent.Methods
The B158/B60 monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating cysticercus antigen was carried out retrospectively on serum samples collected during a hospital-based study from 83 people with epilepsy (PWE) in an endemic area.Results
The addition of antigen results as a major criterion allowed the correct diagnosis of definitive NCC in 10 out of 17 patients as opposed to 0/17 without antigen results in the absence of neuroimaging. A sensitivity of 100% and a specificity of 84% were determined for the diagnosis of active NCC using antigen ELISA. While the use of a higher cutoff improves the specificity of the test to 96%, it decreases its sensitivity to 83%.Conclusions
In areas where neuroimaging is absent, NCC diagnosis according to the existing criteria is problematic. Taking into account its limitations for diagnosis of inactive NCC, antigen detection can be of added value for diagnosing NCC in PWE by supporting diagnostic and treatment decisions. Therefore, we recommend a revision of the “Del Brutto diagnostic criteria” for use in resource poor areas and suggest the inclusion of serum antigen detection as a major criterion. 相似文献3.
Mehrnoosh Doroudchi Oleg Yegorov Tom Baumgartner Anne-Elen Kernaleguen Gaelle Breton Michel L. Ndongala Mohamed-Rachid Boulassel Jean-Pierre Routy Nicole F. Bernard Rafick-Pierre Sékaly Bader Yassine-Diab 《PloS one》2012,7(11)
Objective
To determine the function and phenotype of CD8+ T-cells targeting consensus and autologous sequences of entire HIV-1 Nef protein.Methods
Multiparameter flow cytometry-based analysis was used to evaluate the responses of two treatment naïve HIV-infected individuals, during primary and the chronic phases of infection.Results
A greater breadth and magnitude of CD8 IFN-γ responses to autologous compared to clade-B consensus peptides was observed in both subjects. Cross recognition between autologous and consensus peptides decreased in both subjects during progression from primary to chronic infection. The frequencies of TEMRA and TEM CD8+ T-cells targeting autologous peptides were higher than those targeting consensus peptides and were more polyfunctional (IFN-γ+ Gr-B+ CD107a+).Conclusions
Our data indicate superior sensitivity and specificity of autologous peptides. The functional and maturational aspects of “real” versus “cross-recognized” responses were also found to differ, highlighting the importance of a sequence-specific approach towards understanding HIV immune response. 相似文献4.
Claudia List Weihong Qi Eva Maag Bruno Gottstein Norbert Müller Ingrid Felger 《PLoS neglected tropical diseases》2010,4(8)
Background
Production of native antigens for serodiagnosis of helminthic infections is laborious and hampered by batch-to-batch variation. For serodiagnosis of echinococcosis, especially cystic disease, most screening tests rely on crude or purified Echinococcus granulosus hydatid cyst fluid. To resolve limitations associated with native antigens in serological tests, the use of standardized and highly pure antigens produced by chemical synthesis offers considerable advantages, provided appropriate diagnostic sensitivity and specificity is achieved.Methodology/Principal Findings
Making use of the growing collection of genomic and proteomic data, we applied a set of bioinformatic selection criteria to a collection of protein sequences including conceptually translated nucleotide sequence data of two related tapeworms, Echinococcus multilocularis and Echinococcus granulosus. Our approach targeted alpha-helical coiled-coils and intrinsically unstructured regions of parasite proteins potentially exposed to the host immune system. From 6 proteins of E. multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30 amino acids in length were designed. These peptides were chemically synthesized, spotted on microarrays and screened for reactivity with sera from infected humans. Peptides reacting above the cut-off were validated in enzyme-linked immunosorbent assays (ELISA). Peptides identified failed to differentiate between E. multilocularis and E. granulosus infection. The peptide performing best reached 57% sensitivity and 94% specificity. This candidate derived from Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera from patients infected either with E. multilocularis or E. granulosus.Conclusions/Significance
This study provides proof of principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform. Our data showed that a single peptide cannot provide sufficient diagnostic sensitivity whereas pooling several peptide antigens improved sensitivity; thus combinations of several peptides may lead the way to new diagnostic tests that replace, or at least complement conventional immunodiagnosis of echinococcosis. Our strategy could prove useful for diagnostic developments in other pathogens. 相似文献5.
Dros J Maarsingh OR van der Windt DA Oort FJ ter Riet G de Rooij SE Schellevis FG van der Horst HE van Weert HC 《PloS one》2011,6(1):e16481
Background
The diagnostic approach to dizzy, older patients is not straightforward as many organ systems can be involved and evidence for diagnostic strategies is lacking. A first differentiation in diagnostic subtypes or profiles may guide the diagnostic process of dizziness and can serve as a classification system in future research. In the literature this has been done, but based on pathophysiological reasoning only.Objective
To establish a classification of diagnostic profiles of dizziness based on empirical data.Design
Cross-sectional study.Participants and Setting
417 consecutive patients of 65 years and older presenting with dizziness to 45 primary care physicians in the Netherlands from July 2006 to January 2008.Methods
We performed tests, including patient history, and physical and additional examination, previously selected by an international expert panel and based on an earlier systematic review. We used the results of these tests in a principal component analysis for exploration, data-reduction and finally differentiation into diagnostic dizziness profiles.Results
Demographic data and the results of the tests yielded 221 variables, of which 49 contributed to the classification of dizziness into six diagnostic profiles, that may be named as follows: “frailty”, “psychological”, “cardiovascular”, “presyncope”, “non-specific dizziness” and “ENT”. These explained 32% of the variance.Conclusions
Empirically identified components classify dizziness into six profiles. This classification takes into account the heterogeneity and multicausality of dizziness and may serve as starting point for research on diagnostic strategies and can be a first step in an evidence based diagnostic approach of dizzy older patients. 相似文献6.
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Jean T. Coulibaly Yves K. N'Gbesso Stefanie Knopp Nicaise A. N'Guessan Kigbafori D. Silué Govert J. van Dam Eliézer K. N'Goran Jürg Utzinger 《PLoS neglected tropical diseases》2013,7(3)
Background
The Kato-Katz technique is widely used for the diagnosis of Schistosoma mansoni, but shows low sensitivity in light-intensity infections. We assessed the accuracy of a commercially available point-of-care circulating cathodic antigen (POC-CCA) cassette test for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration.Methodology
A 3-week longitudinal survey with a treatment intervention was conducted in Azaguié, south Côte d''Ivoire. Overall, 242 preschoolers (age range: 2 months to 5.5 years) submitted two stool and two urine samples before praziquantel administration, and 86 individuals were followed-up posttreatment. Stool samples were examined with duplicate Kato-Katz thick smears for S. mansoni. Urine samples were subjected to POC-CCA cassette test for S. mansoni, and a filtration method for S. haematobium diagnosis.Principal Findings
Before treatment, the prevalence of S. mansoni, as determined by quadruplicate Kato-Katz, single CCA considering ‘trace’ as negative (t−), and single CCA with ‘trace’ as positive (t+), was 23.1%, 34.3% and 64.5%, respectively. Using the combined results (i.e., four Kato-Katz and duplicate CCA(t−)) as diagnostic ‘gold’ standard, the sensitivity of a single Kato-Katz, a single CCA(t−) or CCA(t+) was 28.3%, 69.7% and 89.1%, respectively. Three weeks posttreatment, the sensitivity of a single Kato-Katz, single CCA(t−) and CCA(t+) was 4.0%, 80.0% and 84.0%, respectively. The intensity of the POC-CCA test band reaction was correlated with S. mansoni egg burden (odds ratio = 1.2, p = 0.04).Conclusions/Significance
A single POC-CCA cassette test appears to be more sensitive than multiple Kato-Katz thick smears for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration. The POC-CCA cassette test can be recommended for the rapid identification of S. mansoni infections before treatment. Additional studies are warranted to determine the usefulness of POC-CCA for assessing drug efficacy and monitoring the impact of control interventions. 相似文献8.
Natanael P. Leit?o Jr Milene C. Vallejo Palloma M. Concei??o Zoilo P. Camargo Rosane Hahn Rosana Puccia 《PLoS neglected tropical diseases》2014,8(8)
Background
Paracoccidioides brasiliensis and P. lutzii cause paracoccidioidomycosis (PCM). P. brasiliensis main diagnostic antigen is glycoprotein gp43, and its peptide sequence is 81% identical with a P. lutzii ortholog here called Plp43. P. lutzii (“Pb01-like”) apparently predominates in Midwestern/Northern Brazil, where high percentages of false-negative reactions using P. brasiliensis antigens have recently been reported. The aim of this work was to produce recombinant Plp43 to study its antigenic identity with gp43.Methodology
We expressed rPlp43 as a secreted major component in Pichia pastoris and studied its reactivity in immunoblot with PCM patients'' sera from Southwestern and Midwestern Brazil.Principal Findings
We showed that rPlp43 is not glycosylated and bears glucanase activity. The protein did not react with anti-gp43 monoclonal antibodies in immunoblot, suggesting absence of the corresponding gp43 epitopes. Nevertheless, common epitope(s) might exist, considering that gp43-positive PCM sera recognized rPlp43 in immunoblot, while gp43-negative sera (33 out of 51) from patients resident in Midwestern Brazil were also rPlp43-negative. Two genotyped P. lutzii were from patients with gp43-negative sera, suggesting that non-reactive sera are from patients infected with this species.Conclusion
Our data suggest that gp43 and Plp43 bear one or only a few common epitopes and that gp43 cannot be used in diagnosis of PCM patients infected with P. lutzii probably because Plp43 is poorly expressed during infection. 相似文献9.
Hongzhe Zhou Yunbo Wang Wei Wang Junying Jia Yuan Li Qiyu Wang Yanfang Wu Jie Tang 《PloS one》2009,4(6)
Background
Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach.Methodology/Principal Findings
In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1) and one mouse self-antigen (TNF-alpha) as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system.Conclusions/Significance
We developed an efficient and universal method for generating surrogate or therapeutic antibodies against “difficult antigens” to facilitate the development of therapeutic antibodies. 相似文献10.
Objectives
Metabolic disturbances are well-known risk factors for atherosclerosis, but it remains unclear which cardiometabolic components are the predominant determinants. This study aimed to compare and identify the key determinants of carotid atherosclerosis in asymptomatic middle-aged and elderly Chinese.Methods
A community-based cross-sectional study including 3,162 apparently healthy residents aged 37–75 years was performed from July 2008 to June 2010 in Guangzhou, China. Carotid artery intima-media thickness (IMT) was assessed by B-mode ultrasound, and increased IMT was defined as IMT>1.00 mm. Obesity indices, blood pressure, fasting blood lipids, glucose and uric acid levels were determined. Principal components factor analysis was used to extract common factors underlying 11 metabolic factors.Results
Four common factors, defined as “adiposity,” “blood lipids,” “triglycerides/uric acid (TG/UA)” (in men) or “triglycerides/uric acid/glucose (TG/UA/Glu)” (in women), and “blood pressure,” were retained for both sexes. After adjustment for potential covariates, the “adiposity” factor showed the strongest positive association with increased IMT in men. Comparing the extreme quartiles, ORs (95% CI) of increased IMT were 4.64 (2.04–10.59) at the CCA and 2.37 (1.54–3.64) at the BIF), followed by “blood pressure”, the corresponding OR (95% CI) was 2.85 (1.37–5.90) at the CCA. Whereas, the four common factors showed comparable and weak relationship with increased IMTs, the ORs for quartile 4 vs. quartile 1 varied from 0.89 to 3.59 in women.Conclusions
Among the metabolic factors, “adiposity” and “blood pressure” play predominant roles in the presence of carotid atherosclerosis in men, but no key factor is identified in women. 相似文献11.
Nathella Pavan Kumar Rathinam Sridhar Luke E. Hanna Vaithilingam V. Banurekha Thomas B. Nutman Subash Babu 《PloS one》2014,9(10)
Background
Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.Aims/Methodology
To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.Results
We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.Conclusions
Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets. 相似文献12.
Background
Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.Objective
To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.Design
Markov decision model.Data Sources
Published data.Target Population
Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.Time Horizon
The 5 years after initial evaluation for OSAS.Perspective
Societal.Interventions
Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.Outcomes measures
Quality of life, survival and costs for each screening strategy.Results of base-case analysis
Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.Results of sensitivity analysis
Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.Conclusions
CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care. 相似文献13.
Yunxian Zhou 《PloS one》2014,9(9)
Background and Purpose
Transnational nurse migration is a growing phenomenon. This study explored the experiences of China-educated nurses working in Australia.Design
Using a constructivist grounded theory method, 46 in-depth interviews were conducted with 28 China-educated nurses in two major cities in Australia.Results
The core category emerged was “reconciling different realities”. Three phases of reconciling were conceptualised: realising, struggling, and reflecting. Realising refers to an awareness of the discrepancies between different realities. Struggling reflects the dilemma of the “middle position” and how being situated as “the other” is experienced. Reflecting is the process of making sense of the experience and rationalising the gains and losses associated with immigration.Conclusions
This study produced a theoretical understanding of the experience of China-educated nurses working in Australia. The findings not only inform Chinese nurses who wish to migrate but contribute to the implementation of more effective support services for immigrant nurses. 相似文献14.
Zhenhua Hu Jian Gao Danye Zhang Qing Liu Limei Yan Lili Gao Juanjuan Liu Dawo Liu Shulan Zhang Bei Lin 《PloS one》2013,8(2)
Objectives
To measure Lewis y antigen and CD44 antigen expression in epithelial ovarian carcinoma and to correlate the levels of these antigens with clinical response to chemotherapy.Methods
The study cases included 34 cases of ovarian carcinoma with resistance to chemotherapeutic drugs, 6 partially drug-sensitive cases, and 52 drug-sensitive cases (92 total).Results
The rates of expression of Lewis y antigen and CD44 antigen were significantly greater in the drug-resistant group than that in the partially-sensitive or sensitive groups. Surgical stage, residual tumor size and expression of CD44 and Lewis y antigen in ovarian carcinoma tissues were independent risk factors for chemotherapeutic drug resistance.Conclusions
Over-expression of Lewis y and CD44 antigen are strong risk factors for chemotherapeutic drug resistance in ovarian carcinoma patients. 相似文献15.
LA Tchuem Tchuenté CJ Kueté Fouodo RI Kamwa Ngassam L Sumo C Dongmo Noumedem CM Kenfack NF Gipwe ED Nana JR Stothard D Rollinson 《PLoS neglected tropical diseases》2012,6(7):e1758
Background
The Kato-Katz is the most common diagnostic method for Schistosoma mansoni infection. However, the day-to-day variability in host egg-excretion and its low detection sensitivity are major limits for its use in low transmission zones and after widespread chemotherapy. We evaluated the accuracy of circulating cathodic antigen (CCA) urine-assay as a diagnostic tool of S. mansoni. In comparison, a low sensitive CCA test (CCA-L) was assessed.Methodology
The study was conducted in three settings: two foci with single S. mansoni infections (settings A and B), and one mixed S. mansoni – S. haematobium focus (setting C). Stool and urine samples were collected from school-children on three consecutive days. Triplicate Kato-Katz readings were performed per stool sample. Each urine sample was tested with one CCA and only the first urine sample was subjected to CCA-L. Urine samples were also examined for S. haematobium eggs using the filtration method and for microhaematuria using urine reagent strips. Overall, 625 children provided three stool and three urine samples.Principal Findings
Considering nine Kato-Katz thick smears as ‘reference’ diagnostic test, the prevalence of S. mansoni was 36.2%, 71.8% and 64.0% in settings A, B and C, respectively. The prevalence of S. haematobium in setting C was 12.0%. The sensitivities of single Kato-Katz, CCA and CCA-L from the first stool or urine samples were 58%, 82% and 46% in setting A, 56.8%, 82.4% and 68.8% in setting B, and 49.0%, 87.7% and 55.5% in setting C. The respective specificities were 100%, 64.7% and 100%; 100%, 62.3% and 91.3%; and 100%, 42.5% and 92.0%. Mixed infection with S. haematobium did not influence the CCA test results for S. mansoni diagnosis.Conclusions/Significance
Urine CCA revealed higher sensitivity than CCA-L and triplicate Kato-Katz, and produced similar prevalence as nine Kato-Katz. It seems an attractive method for S. mansoni diagnosis. 相似文献16.
Peiliang Geng Jianjun Li Ning Wang Juanjuan Ou Ganfeng Xie Chen Liu Xiaoxin Zhao Lisha Xiang Yunmei Liao Houjie Liang 《PloS one》2015,10(8)
Background
Published data on the association between PSCA rs2294008 polymorphism and cancer risk have implicated inconclusive results. To determine the relationship and to precisely assess the effect size estimate of the association, we performed a meta-analysis.Methods
We searched published literature in Embase and PubMed databases using the search terms “PSCA”, “prostate stem cell antigen”, “variants”, “polymorphism”, “polymorphisms”, and “cancer”. A total of 21 eligible articles were retrieved, with 27, 197 cancer cases and 48, 237 controls.Results
On the whole, we found the association between PSCA rs2294008 polymorphism and cancer risk was statistically significant: TT vs CC: OR = 1.18, 95% CI, 1.10 to 1.27; TT + CT vs CC: OR = 1.08, 95% CI, 1.05 to 1.10; TT vs CT + CC: OR = 1.14, 95% CI, 1.07 to 1.21; T vs C: OR = 1.10, 95% CI, 1.06 to 1.14; CT vs CC: OR = 1.10, 95% CI, 1.06 to 1.13. Stratified analyses in cancer type and ethnicity showed similar results.Conclusions
Based on the statistical evidence, we can draw a conclusion that the rs2294008 polymorphism of PSCA gene is likely to play a role in cancer carcinogenesis, especially in gastric cancer and bladder cancer. 相似文献17.
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Richard Kwizera Joyce Nguna Agnes Kiragga Jesca Nakavuma Radha Rajasingham David R. Boulware David B. Meya 《PloS one》2014,9(7)
Background
Cryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva.Methods
We screened HIV-infected, antiretroviral therapy naïve persons with symptomatic meningitis (n = 130) and asymptomatic persons with CD4+<100 cells/µL entering into HIV care (n = 399) in Kampala, Uganda. The diagnostic performance of testing saliva was compared to serum/plasma cryptococcal antigen as the reference standard.Results
The saliva lateral flow assay performance was overall more sensitive in symptomatic patients (88%) than in asymptomatic patients (27%). The specificity of saliva lateral flow assay was excellent at 97.8% in the symptomatic patients and 100% in asymptomatic patients. The degree of accuracy of saliva in diagnosing cryptococcosis and the level of agreement between the two sample types was better in symptomatic patients (C-statistic 92.9, κ-0.82) than in asymptomatic patients (C-statistic 63.5, κ-0.41). Persons with false negative salvia CrAg tests had lower levels of peripheral blood CrAg titers (P<0.001).Conclusion
There was poor diagnostic performance in testing saliva for cryptococcal antigen, particularly among asymptomatic persons screened for preemptive treatment of cryptococcosis. 相似文献19.
Stijn Rogé Liesbeth Van Nieuwenhove Magali Meul Annick Heykers Annette Brouwer de Koning Nicolas Bebronne Yves Guisez Philippe Büscher 《PLoS neglected tropical diseases》2014,8(7)
Background
Screening tests for gambiense sleeping sickness, such as the CATT/T. b. gambiense and a recently developed lateral flow tests, are hitherto based on native variant surface glycoproteins (VSGs), namely LiTat 1.3 and LiTat 1.5, purified from highly virulent trypanosome strains grown in rodents.Methodology/Principal Findings
We have expressed SUMO (small ubiquitin-like modifier) fusion proteins of the immunogenic N-terminal part of these antigens in the yeast Pichia pastoris. The secreted recombinant proteins were affinity purified with yields up to 10 mg per liter cell culture.Conclusions/Significance
The diagnostic potential of each separate antigen and a mixture of both antigens was confirmed in ELISA on sera from 88 HAT patients and 74 endemic non-HAT controls. Replacement of native antigens in the screening tests for sleeping sickness by recombinant proteins will eliminate both the infection risk for the laboratory staff during antigen production and the need for laboratory animals. Upscaling production of recombinant antigens, e.g. in biofermentors, is straightforward thus leading to improved standardisation of antigen production and reduced production costs, which on their turn will increase the availability and affordability of the diagnostic tests needed for the elimination of gambiense HAT. 相似文献20.
Jadwiga Nowak-Sadzikowska Tomasz Skóra Bogumi?a Szyszka-Charewicz Jerzy Jakubowicz 《Reports of Practical Oncology and Radiotherapy》2016,21(1):31-36