bluuebunny/crossref_metadata_2025 huggingface dataset:
An Italian Program of External Quality Control for Chromogranin A (CgA) Assay: State of the Art of Cga Measurement
Authors:   Italian Network for Quality Assessment of Tumor Biomarkers (INQAT) Group, Paradiso A. , Verderio P. , Pizzamiglio S. , Cortese M.E. , Marubini E. , Dittadi R. , Gion M. , De Appollonia L.
Published: January 2018

Chromogranin A (CgA) is a secretory protein produced by many neuroendocrine cells. Circulating levels of CgA have been found to be elevated in a variety of neuroendocrine tumors and may facilitate the diagnosis and management of patients with functioning as well as non-functioning forms. However, up to now the analytical methods used for assaying intact CgA and CgA-derived peptides in the circulation of patients have not been monitored in Italy by an external quality control program.

Within the framework of a Ministry of Health project an external quality control program was developed to investigate the state of the art of CgA determination in Italy and to monitor the performance of laboratories carrying out this assay. This paper deals primarily with the former of these aspects.

Every laboratory received the study protocol together with a questionnaire to be returned before receipt of the samples to be assayed. Serum and plasma samples obtained from a pool of routine specimens were prepared at three different concentrations of CgA, aliquoted, frozen at –80°C and mailed in dry ice to the participating laboratories. Of the 43 laboratories, 21 used IRMA, 21 used ELISA and one used RIA. There was a wide range in the time of kit utilization and the number of samples assayed per year, which indicated that the participating group was heterogeneous with regard to their experience in the determination of CgA. Most laboratories routinely used serum and plasma for IRMA and ELISA, respectively, and different data fitting approaches were employed. Further analyses will investigate the possible influence of these pre-analytical factors on laboratory performance.
Differential Expression Patterns of Irf3 and Irf7 in Pediatric Lymphoid Disorders
Authors: Park H.S. , Kim Y.J. , Bae Y.K. , Lee N.H. , Lee Y.J. , Hah J.O. , Park T.I. , Lee K.S. , Park J.B. , Kim H.S.
Published: January 2018

Interferon regulatory factors (IRFs) are multifunctional transcriptional factors. To define the role of IRFs in lymphoid disorders, we determined the expression patterns of IRF3 and IRF7 by immunohistochemistry in 5 normal lymph nodes, 12 reactive hyperplastic lymph nodes, and 27 pediatric lymphomas. IRF3 was prominently expressed in the nuclei of the histiocytes, and was expressed very weakly in the cytoplasm of most of the lymphocytes of the normal lymph nodes. However, IRF7 was expressed strongly in the nuclei of over 50% of the lymphocytes throughout the normal lymph nodes, but the histiocytes and fibroblasts were spared. In the reactive hyperplastic lymph nodes, the number of IRF3- and IRF7-positive cells in the nuclei was elevated. In the lymphomas, the number of IRF3-positive cells in the nucleus appeared to have decreased, and the cells were scattered throughout the lymphoma tissue in no specific pattern. However, in most cases the number of IRF7-positive cells was elevated.

These results suggested that IRF3 was activated principally in the histiocytes and T cells under inflammatory conditions, but IRF3 activation was attenuated in cases of lymphoma. However, the number of IRF7-positive cells was found to be elevated in the reactive hyperplastic lymph nodes and pediatric lymphoma.
FHIT Oncosuppressor Gene Expression Profile in Human Anal Cancers
Authors: Zucchini C. , Concu M. , Martini F. , Morelli C. , Salfi N. , Carinci P. , Tognon M. , Caramelli E.
Published: January 2018

The FHIT gene, a member of the histidine triad gene family, is a tumor suppressor gene exhibiting deletions in the majority of human cancers. Aberrant transcripts of this gene have been found in about 50% of esophageal, stomach and colon carcinomas. Little is known about the molecular mechanisms involved in malignant transformation of the lining cells of the anus. In this study FHIT gene expression was investigated in this particular kind of human cancer. FHIT expression was comparatively analyzed at the mRNA level, by RT-PCR, in squamous anal cancers, normal anal tissue and peripheral blood samples. cDNA analyses showed variability in FHIT transcripts, without apparent effects on the predicted amino acid sequence. These different FHIT mRNAs could represent transcripts from an alternative splicing event. Our data indicate that the FHIT mRNA detected in anal cancers and in normal samples is heterogeneous. Immunohistochemical data suggest that the Fhit protein is expressed only in a fraction of the tumor cells, while it is strongly expressed in the epithelial cells of glands of the normal anal mucosa. The absence or poor expression of the Fhit protein in anal cancers suggests a role for this tumor suppressor gene product, as a risk factor, in the onset of this human cancer, as reported before for other human gastrointestinal tumors.
Involvement of NK Cells against Tumors and Parasites
Authors: Papazahariadou M. , Athanasiadis G.I. , Papadopoulos E. , Symeonidou I. , Hatzistilianou M. , Castellani M.L. , Bhattacharya K. , Shanmugham L.N. , Conti P. , Frydas S.
Published: January 2018

Host resistance against pathogens depends on a complex interplay of innate and adaptive immune mechanisms. Acting as an early line of defence, the immune system includes activation of neutrophils, tissue macrophages, monocytes, dendritic cells, eosinophils and natural killer (NK) cells. NK cells are lymphoid cells that can be activated without previous stimulation and are therefore like macrophages in the first line of defence against tumor cells and a diverse range of pathogens. NK cells mediate significant activity and produce high levels of proinflammatory cytokines in response to infection. Their cytotoxicity production is induced principally by monocyte-, macrophage- and dendritic cell-derived cytokines, but their activation is also believed to be cytokine-mediated. Recognition of infection by NK cells is accomplished by numerous activating and inhibitory receptors on the NK cells’ surface that selectively trigger the cytolytic activity in a major histocompability complex-independent manner. NK cells have trypanocidal activity of fibroblast cells and mediate direct destruction of extracellular epimastigote and trypomastigote forms of T. cruzi and T. lewisi in vitro; moreover, they kill plasmodia-infected erythrocytes directly through cell-cell interaction. This review provides a more detailed analysis of how NK cells recognize and respond to parasites and how they mediate cytotoxicity against tumor cells. Also the unique role of NK cells in innate immunity to infection and the relationship between parasites and carcinogenesis are discussed.
Interchangeability and Diagnostic Accuracy of Two Assays for Total and Free Prostate-Specific Antigen: Two not Always Related Items
Authors: Dittadi R. , Franceschini R. , Fortunato A. , Zancan M. , Barichello M. , Tasca A. , Giavarina D. , Peloso L. , Soffiati G. , Gion M.
Published: January 2018

The variation between different PSA assays seems to influence the interpretation of individual PSA values and the clinical decisions about prostate cancer. One reason for this variability could be the different reactivity of antibodies for the various molecular forms of serum PSA; as a result, samples containing the same amount of tPSA but different proportions of fPSA can produce very different values. In this study, serum samples were collected prospectively from 152 consecutive patients referred to 2 institutions (Regional Hospital, Venice, 90 subjects; San Bortolo Hospital, Vicenza, 62 subjects) for PSA elevation and/or symptoms. Serum samples were assessed according to the manufacturers’ instructions on the following 2 analyzers: the Immulite 2000 assay (Diagnostic Products Corporation, Los Angeles, USA), which measures tPSA and fPSA, and the ADVIA Centaur (Bayer Diagnostics, Tarrytown, USA), which assays tPSA and cPSA. cPSA values were transformed into fPSA by the equation fPSA=tPSA-cPSA. When taking Immulite tPSA and f/tPSA values as 100%, ADVIA Centaur values were 92.6% and 122%, respectively, which means that 20% of patients would be classified differently according to the traditional biopsy cutoff. In conclusion, there are considerable differences between the 2 methods, which could affect clinical decisions.
Evaluation of Serum CA 125 Levels in Patients with Pelvic Pain Related to Endometriosis
Authors: Maiorana A. , Cicerone C. , Niceta M. , Alio L.
Published: January 2018

The aim of the study was to investigate the clinical value of the serum CA 125 level for diagnosing and determining the severity of endometriosis and pelvic pain associated with endometriosis. Eighty-six women who underwent operative laparoscopy were enrolled. Sixty-nine women with endometriosis and 17 without endometriosis participated in this study. In all of the patients, endometriosis was diagnosed and classified into stages according to the Revised American Fertility Society (R-AFS) classification. The mean serum CA 125 levels were determined in each patient. We also investigated the relationship between serum CA 125 concentration and the intensity of dysmenorrhea and dyspareunia in the study group. The mean serum CA 125 levels of women with endometriosis were higher than those of the control group (p<0.050). However, the mean serum CA 125 levels were higher in stage IV than in other stages of endometriosis according to the R-AFS classification. On the other hand, the percentage of patients with serum CA 125 levels >35 U/mL was elevated in the subgroups with severe dyspareunia and severe dysmenorrhea versus the asymptomatic subgroup but the differences had no statistical significance. In conclusion, CA 125 serum levels were related to endometriosis and R-AFS score in the evaluated patient series. No correlation was found between serum levels of CA 125 and pelvic pain in patients with endometriosis.
Localization and Activity of iNOS in Normal Human Lung Tissue and Lung Cancer Tissue
Authors: Speranza L. , De Lutiis M.A. , Shaik Y.B. , Felaco M. , Patruno A. , Tetè A. , Mastrangelo F. , Madhappan B. , Castellani M.L. , Conti F. , Vecchiet J. , Theoharides T.C. , Conti P. , Grilli A.
Published: January 2018

Inducible nitric oxide synthase (iNOS) is one of three enzymes generating nitric oxide (NO) from the amino acid L-arginine. iNOS-derived NO plays an important role in several physiological and pathophysiological conditions. NO is a free radical which produces many reactive intermediates that account for its bioactivity. In the human lung, the alveolar macrophage is an important producer of cytokines and this production may be modified by NO. Moreover, high concentrations of NO have been shown to increase nuclear factor KB (NF-kB) activation. Recent investigations of NO expression in tumor tissue indicated that, at least for certain tumors, NO may mediate one or more roles during the growth of human cancer. We have studied iNOS in two tissue groups: normal human lung tissue and human lung cancer tissue. We localized iNOS in these tissues by immunohistochemistry and tested the mRNA expression by RT-PCR, the protein level by Western blot, and the protein activity by radiometric analysis. The results demonstrate different expression, localization and activity of iNOS in normal versus tumor tissue. This is suggestive of a role for NO production from iNOS in human lung cancer because high concentrations of this short molecule may transform to highly reactive compounds such as peroxynitrite (ONOO-); moreover, through the upregulator NF-kB, they can induce a chronic inflammatory state representing an elevated risk for cell transformation to cancer.
(AC) Dinucleotide Repeat Polymorphism in Intron 1 of Human EGFR Shows Ethnic Specificities and High Evidence for Association with Breast Cancer
Authors: Kharrat N. , Al'Fadhli S. , Rebaï M. , Aifa M.S. , Kallel I. , Khabir A. , Sellami-Boudawara T. , Frikha M. , Rebaï A.
Published: January 2018

A polymorphic AC repeat in intron 1 of the EGFR gene was genotyped on 352 healthy individuals and 118 women with breast cancer sampled from the Kuwaiti and Tunisian populations. We compared allele frequencies in these populations with published data on various ethnic groups. We found very close similarity between Tunisian and Kuwaiti populations for both allelic and genotypic frequencies and in both control and patient groups. Our analysis revealed clear interethnic differences between populations; in Europeans, allele 16 occurred predominantly, whereas in Tunisia and Kuwait allele 17 was the most frequent and allele 20 predominated in Asians. One hundred twenty-three healthy women, matched with the 118 breast cancer patients, were used as controls to test for associations between AC repeat and cancer risk. Strong evidence for such an association was found for allele 18 when considered alone (χ2=27.04, corrected p=0.0000016, OR=3.94) or with longer alleles (>17 repeats) (χ2=20.21, p=0.0005, OR=2.30). This contrasts with Asian populations where allele 16 was identified as the risk allele, showing allele heterogeneity depending on ethnicity.
Assessment of the Biological Variation of Plasma Tissue Inhibitor of Metalloproteinases-1
Authors: Frederiksen C.B. , Lomholt A.F. , Lottenburger T. , Davis G.J. , Dowell B.L. , Blankenstein M.A. , Christensen I.J. , Brünner N. , Nielsen H.J.
Published: January 2018

Background

Tissue inhibitor of metalloproteinases-1 (TIMP-1) measurements in plasma may be useful for the early detection and prognosis of colorectal cancer (CRC). Data on analytical performance and normal intra- and interindividual biological variation are required in order to interpret the utility of TIMP-1 in CRC. The aim of this study was to establish the biological and analytical variation of plasma TIMP-1 in volunteers.

Material and methods

Three separate studies were undertaken. 1: Plasma was collected from 23 volunteers 6 times within a 3-week period, first in September 2004 (round [R] 1), then repeated in May 2005 (R2) and May 2006 (R3) in the same group of individuals. TIMP-1 levels were determined by the MAC15 ELISA assay and with the Abbott ARCHITECT i2000 Immunoanalyzer. 2: Circadian variation was evaluated in plasma collected 7 times within a 24-hour period (n=16). 3: Effects of physical exercise were evaluated in plasma collected before and after bicycling (n=14). In studies 2 and 3 TIMP-1 levels were determined with the MAC15 ELISA assay only.

Results

A significant correlation between TIMP-1 MAC15 and ARCHITECT i2000 was shown (rs=0.78, p<0.002), with consistently higher levels being detected by the ARCHITECT i2000. Median levels of TIMP-1 (ARCHITECT) at 8 a.m. in each round were 74.9 ng/mL (range 65.7–89.9) (R1), 87.3 ng/mL (range 72.7–127.9) (R2), and 81.9 ng/mL (range 66.8–113.6) (R3). The within-subject variation was 10.7%, the variation between rounds was 7.4%, and the intraclass correlation was 46.2%. Comparison between the 3 rounds and time of collection showed that TIMP-1 values decreased by 11% after storage for more than 16 months (p=0.0002). A systematic circadian variation in plasma TIMP-1 levels was not observed (p=0.17). No significant variation of plasma TIMP-1 was found in relation to physical exercise (p=0.92 [global test]).

Conclusion

Levels of plasma TIMP-1 in volunteers show limited circadian, day-to-day, week-to-week and season-to-season variation. In addition, physical exercise has no impact on plasma TIMP-1 levels. Possible storage-dependent decreases in plasma TIMP-1 levels warrant further investigation.
Identification of αB-Crystallin, a Biomarker of Renal Cell Carcinoma by SELDI-TOF MS
Authors: Holcakova J. , Hernychova L. , Bouchal P. , Brozkova K. , Zaloudik J. , Valik D. , Nenutil R. , Vojtesek B.
Published: January 2018

Spectrometric-based surface-enhanced laser desorption/ionization ProteinChip (SELDI-TOF) facilitates rapid and easy analysis of protein mixtures and is often exploited to define potential diagnostic markers from sera. However, SELDI-TOF is a relatively insensitive technique and unable to detect circulating proteins at low levels even if they are differentially expressed in cancer patients. Therefore, we applied this technology to study tissues from renal cell carcinomas (RCC) in comparison to healthy controls. We found that different biomarkers are identified from tissues than those previously identified in serum, and that serum markers are often not produced by the tumors themselves at detectable levels, reflecting the nonspecific nature of many circulating biomarkers. We detected and characterized αB-crystallin as an overexpressed protein in RCC tissues and showed differential expression by immunohistochemistry. We conclude that SELDI-TOF is more useful for the identification of biomarkers that are synthesized by diseased tissues than for the identification of serum biomarkers and identifies a separate set of markers. We suggest that SELDI-TOF should be used to screen human cancer tissues to identify potential tissue-specific proteins and simpler and more sensitive techniques can then be applied to determine their validity as biomarkers in biological fluids.
Parallel Assessment of Circulatory Cell-Free DNA by PCR and Nucleosomes by ELISA in Breast Tumors
Authors: Seefeld M. , El Tarhouny S. , Fan A.X.C. , Hahn S. , Holzgreve W. , Zhong X.Y.
Published: January 2018

Objectives

In order to assess the potential biomolecules for breast cancer, we analyzed in parallel the levels of cell-free glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and cell-free nucleosomes in serum samples from patients with benign and malignant breast tumors. The levels of cell-free DNA obtained by quantitative PCR were compared with those obtained by enzyme-linked immunosorbent assay (ELISA).

Methods

Twenty-three patients with benign breast tumors, 27 patients with breast cancer, and 32 age-matched healthy women were recruited. The amounts of serum nucleosomes were analyzed by ELISA and the levels of cell-free GAPDH were measured by real-time quantitative PCR. The correlation between nucleosome and cell-free GAPDH levels was examined using the Spearman rank test.

Results

The levels of cell-free GAPDH were significantly higher in the serum samples of patients with benign and malignant breast tumors than in those of the control group (median 37,966 GE/mL, range 3,802–130,104 versus 11,770 GE/mL, range 2,198–73,522, p=0.035 and median 40,698 GE/mL, range 3,644–192,482 versus 11,770 GE/mL range 2,198–73,522, p=0.001). The concentration of cell-free GAPDH correlated significantly with the quantities of nucleosomes in serum samples (r=0.451, p=0.000). There was, however, no significant difference between healthy individuals and women with benign breast tumors or breast cancer in terms of nucleosomes determined by ELISA.

Conclusion

Our data suggest that the cell-free serum GAPDH DNA assayed by quantitative PCR is a better biomarker than nucleosomes assayed by ELISA in patients with breast tumors.
Immunohistochemical Expression of p53 and Ki67 in Colorectal Adenomas and Prediction of Malignancy and Development of New Polyps
Authors: Vernillo R. , Lorenzi B. , Banducci T. , Minacci C. , Vindigni C. , Fei A. Lucenti , Lorenzi M.
Published: January 2018

The aim of this study was to investigate the immunohistochemical expression of p53 and Ki67 in colorectal adenomas in order to clarify their significance as indicators of malignancy and development of new polyps. Seventy-eight polyps were removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and 22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at 3-year follow-up). We tested the association between p53 and Ki67 expression and various clinicopathological variables, and regression analysis was performed to identify the risk factors for malignancy and development of new adenomas. A significant correlation between the grade of atypia and p53 immunoreactivity was observed. Ki67 expression was not related to atypia and no correlation was found between p53 and Ki67 immunoreactivity. Regression analysis showed that size (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to malignant transformation, whereas the number of synchronous primary polyps emerged as the only predictive factor of development of new adenomas, although without statistical significance. The expression of biological markers may be in future added to the currently examined features of polyps; however, further studies are needed to better define their predictive value.
Brain Irradiation-Induced Lymphocytosis Predicts Response in Cancer Patients with Brain Metastases
Authors: Lissoni P. , Meregalli S. , Curreri S. , Messina G. , Brivio F. , Fumagalli L. , Colciago M. , Gardani G.
Published: January 2018

Lymphocytopenia is one of the main toxicities of radiotherapy and its severity is related to the irradiation dose. The occurrence of lymphocytopenia depends on the body site of radiotherapy; it is most pronounced with pelvic irradiation, whereas the effect of brain irradiation on the lymphocyte count is to be elucidated. This preliminary study was performed to evaluate changes in lymphocyte number occurring during brain irradiation in cancer patients with brain metastases. The study included 50 patients who received brain radiotherapy for single or multiple brain metastases at a total dose of 30 Gy. Overall, no significant changes in mean lymphocyte number occurred during brain radiotherapy. However, when lymphocyte variations were assessed in relation to the clinical response of brain metastases, a significant increase in the mean number of lymphocytes was found in patients who achieved objective regression of brain metastases on brain irradiation. The mean lymphocyte number decreased in nonresponding patients, albeit without a statistically significant difference with respect to the pretreatment values. The results of this study show that the efficacy of radiotherapy in the treatment of brain metastases is associated with a significant increase in mean lymphocyte number. Therefore, evidence of brain irradiation-induced lymphocytosis may predict the efficacy of radiotherapy.
Association of Elevated IGFBP-1 with Increased IGF-II Concentration in Patients with Carcinoma of the Liver
Authors: Nedić O. , Malenković V. , Đukanović B. , Baričević I.
Published: January 2018

Insulin-like growth factors (IGFs) are mitogens for numerous types of cells including cancer cells. The aim of this work was to analyze some of the components of the IGF system to assess which could be potential clinical biomarkers for monitoring patients diagnosed with liver cancer. Compared to healthy persons, patients with liver cancer had a lower concentration of IGF-I and a higher concentration of IGFBP-1, whereas the concentrations of IGF-II and IGFBP-3 remained unchanged. The IGF-I:IGFBP-3 ratio decreased in patients with cancer, while the IGF-II:IGFBP-1 ratio was not altered. Patients with primary carcinoma and those scheduled for surgery had lower IGF-I and higher IGF-II and IGFBP-1 concentrations than patients with secondary carcinoma and those not eligible for surgery. It may be postulated that a liver with primary cancer is induced to increase IGF-II and IGFBP-1 synthesis more than a liver involved in metastatic response. Similarly, in patients eligible for liver surgery an increase in IGF-II may reflect a gradual change in the concentration associated with a different stage of disease. As increased synthesis of certain IGFBPs is necessary to compensate decreased production of the others or increased IGF production, determination of serum IGF-II, IGFBP-1 and their ratio may aid in estimating the compensatory capacity of the liver affected by cancer.
Association of Interleukin-6 –174G>C Promoter Polymorphism with Risk of Cervical Cancer
Authors: Gangwar Ruchika , Mittal Balraj , Mittal Rama Devi
Published: January 2018

Background

The etiology of cervical cancer is associated with excessive–inflammation-mediated tumorigenesis. Interleukin-6 ( IL-6), a multifunctional cytokine, regulates inflammation and various physiological processes. We therefore aimed to evaluate the association of the IL-6 –174G>C polymorphism with predisposition to cervical cancer.

Materials and methods

The present case-control study comprised 160 histopathologically confirmed cases of cervical cancer and 200 healthy controls. Polymorphism for the IL-6 gene was genotyped by amplification refractory mutation system (ARMS) polymerase chain reaction (PCR).

Results

We observed a significant association of the IL-6 –174CC genotype with risk of cervical cancer (OR=3.16; p=0.014). An increased risk of developing stage I tumors was found in individuals with a heterozygous (GC) genotype (OR=3.63, p=0.003). In a case-only analysis, the risk was further increased in patients consuming tobacco products (OR=3.14; p=0.033).

Conclusion

The CC genotype in the IL-6 promoter region may confer a high risk of cervical cancer, which is further modulated in patients who are tobacco users.
Haptoglobin Genotypes in Nasopharyngeal Carcinoma
Authors: Lee Ching-Chih , Lin Hon-Yi , Hung Shih-Kai , Li Dian-Kun , Ho Hsu-Chueh , Lee Moon-Sing , Tung Ya-Ting , Chou Pesus , Su Yu-Chieh
Published: January 2018

Aim

Haptoglobin polymorphisms are associated with different cancers; however, the occurrence of nasopharyngeal carcinoma (NPC) in relation to haptoglobin polymorphisms has not been reported. In this study, the distribution of haptoglobin genotypes among patients with NPC was investigated and the prognostic significance of haptoglobin genotypes was further analyzed.

Material and methods

Haptoglobin genotypes were analyzed using polymerase chain reaction and electrophoresis. The genotypes were determined in the sera of 49 NPC patients and in 134 controls.

Results

The haptoglobin genotypes of patients with NPC were as follows: Hp 1–1, 2%; Hp 2–1, 39%; Hp 2–2, 59%. The frequency of the Hp 2–2 genotype was much higher in NPC patients than in control individuals (p=0.044). Furthermore, NPC patients with the Hp 2–2 genotype had advanced T stages (p=0.001) and larger primary tumor volumes (p=0.035) than those with Hp 2–1 or 1–1.

Conclusion

An increased frequency of the Hp 2–2 genotype was associated with NPC. The Hp 2 allele was also overexpressed in NPC patients. NPC patients with the Hp 2–2 genotype had advanced T stage and a larger primary tumor volume. Hp 2–2 may be a negative prognostic factor in NPC.
20–25% Lower Concentrations of Total and Free Prostate-Specific Antigen (PSA) after Calibration of PSA Assays to the WHO Reference Materials – Analysis of 1098 Patients in Four Centers
Authors: Stephan Carsten , Bangma Chris , Vignati Giulio , Bartsch Georg , Lein Michael , Jung Klaus , Philippe Marianne , Semjonow Axel , Catalona William J.
Published: January 2018

Aim

To examine the potential clinical implications of the recalibration of total prostate-specific antigen (PSA) and free PSA (fPSA) assays to the World Health Organization (WHO) standard materials.

Material and methods

Data from 1098 patients with or without clinically detected prostate cancer (PCa) from four independent cohort studies were compared using commercial assays calibrated to the traditional Hybritech® PSA (PSA-Hyb) and fPSA (fPSA-Hyb) standards and to the WHO 96/670 (PSA-WHO) and 96/668 (fPSA-WHO) standards. The Access® Immunoassay System (Beckman Coulter, Inc.) was used in all studies.

Results

All studies showed 20% to 25% lower PSA and fPSA test results with the WHO-standardized assays. No significant change in %fPSA (fPSA/PSA × 100) was observed. Continuing to use the traditional clinical PSA cutoffs obtained with the Hybritech standard after changing to the PSA-WHO standard could result in up to one-third of prostate cancer cases being missed. Conclusions: Manufacturers should fully inform laboratories about a calibration change and its clinical impact. Laboratory reports for PSA measurements should indicate the assay's manufacturer and which calibration standard was used to avoid misleading information concerning PCa risk
Molecular detection methods of human papillomavirus (HPV)
Authors: Zaravinos Apostolos , Mammas Ioannis N. , Sourvinos George , Spandidos Demetrios A.
Published: January 2018

Human papillomavirus (HPV) testing can identify women at risk of cervical cancer. Currently, molecular detection methods are the gold standard for identification of HPV. The three categories of molecular assays that are available are based on the detection of HPV DNA and include (1) non-amplified hybridization assays, such as Southern transfer hybridization (STH), dot blot hybridization (DB) and in situ hybridization (ISH); (2) signal amplified hybridization assays, such as hybrid capture assays (HC2); (3) target amplification assays, such as polymerase chain reaction (PCR) and in situ PCR. STH requires large amounts of DNA, is laborious and not reproducible, while ISH has only moderate sensitivity for HPV. The sensitivity of the HC2 assay is similar to that of PCR-based assays, with high sensitivity being achieved by signal rather than target amplification. PCR-based detection is both highly sensitive and specific. Since PCR can be performed on very small amounts of DNA, it is ideal for use on specimens with low DNA content. In the future, with the advance of technology, viral DNA extraction and amplification systems will become more rapid, more sensitive, and more automated.
Expression of MRP1, BCRP, LRP and ERCC1 as prognostic factors in non-small cell lung cancer patients receiving postoperative cisplatin-based chemotherapy
Authors: Li Xiao-Qin , Li Jian , Shi Shun-Bing , Chen Ping , Yu Li-Chao , Bao Qian-Lei
Published: January 2018

The development of resistance to chemotherapy is one of the major obstacles in the treatment of non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic value of multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP), and excision repair cross-complementing 1 (ERCC1) in NSCLC patients receiving cisplatin-based adjuvant chemotherapy (cisplatin plus vinorelbine or gemcitabine) after tumor resection. We used semiquantitative reverse-transcription polymerase chain reaction to detect the expression of MRP1, BCRP, LRP and ERCC1 mRNA in surgical resection specimens of 60 patients with stage IB through IIIA NSCLC. The expression level of each gene was analyzed in relation to clinicopathological factors, tumor-free survival (TFS), and overall survival. The results showed that stage IIIA (p=0.011), N1 and N2 status (p=0.008), high expression of MRP1 (p=0.034) and LRP (p=0.018) were associated with shorter TFS. Stage IIIA (p=0.0105), N1 and N2 status (p=0.009), high expression of MRP1 (p=0.021) and ERCC1 (p=0.012) were related to a shorter overall survival. Cox multivariate analyses revealed that early stage (p=0.013 and p=0.024), negative lymph node status (p=0.006 and p=0.011), and low MRP1 expression (p=0.022 and p=0.035) were independent predictors of favorable TFS and overall survival, respectively. Additionally, ERCC1 (p=0.019) was an independent predictor of favorable overall survival.
Accuracy of urine telomerase activity to detect bladder cancer in symptomatic patients
Authors: Casadio Valentina , Bravaccini Sara , Gunelli Roberta , Nanni Oriana , Zoli Wainer , Amadori Dino , Calistri Daniele , Silvestrini Rosella
Published: January 2018

Telomerase activity assessment in voided urine is an important noninvasive tool for bladder cancer diagnosis. In a previous case-control study we verified that this method can detect tumor cells in urine with high sensitivity and specificity, but few data are still available on its accuracy to detect tumors in patients with symptomatic urinary tract diseases. Following recently published guidelines on bladder cancer, we aimed to define the diagnostic accuracy of urine telomerase levels in symptomatic patients. Telomerase activity, expressed in arbitrary enzymatic units (AEUs), was evaluated in urine collected from 515 patients: 197 with urinary tract symptoms and 318 with a first diagnosis of bladder cancer. Telomerase repeat amplification protocol (TRAP) sensitivity ranged from 93% to 61% and specificity varied from 42% to 88% at the different AEU cutoff values. At the cutoff of 50, the sensitivity was 87% (95% CI 83–91), the specificity was 70% (95% CI 63–75), and the overall accuracy, in terms of true positives and true negatives, was 80%. Sensitivity did not vary in relation to tumor grade or stage at diagnosis, or to patient age. Our results indicate that urine telomerase activity is a good marker for the early diagnosis of bladder tumors in symptomatic patients, a subset which represents an “at-risk” population requiring close surveillance.
Evaluation of PD-L1/PD-1 on circulating tumor cells in patients with advanced non-small cell lung cancer
Authors: Kallergi Galatea , Vetsika Eleni-Kyriaki , Aggouraki Despoina , Lagoudaki Eleni , Koutsopoulos Anastasios , Koinis Filippos , Katsarlinos Panagiotis , Trypaki Maria , Messaritakis Ippokratis , Stournaras Christos , Georgoulias Vassilis , Kotsakis Athanasios
Published: January 2018

Background:

Circulating tumor cells (CTCs) could escape from the immune system through the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis leading to the development of metastasis. The current study investigated the expression of PD-1/PD-L1 on CTCs isolated from non-small cell lung cancer (NSCLC) patients treated with chemotherapy.

Patients and methods:

CTCs were isolated from 30 chemo-naïve stage IV NSCLC patients before and after front-line chemotherapy using the ISET filtration platform. CTCs were detected by Giemsa and immunofluorescence (IF) staining. Samples were analyzed with the ARIOL system.

Results:

Giemsa staining revealed that 28 (93.3%) out of 30 and 9 (81.8%) out of 11 patients had detectable CTCs at baseline and after the third chemotherapy cycle, respectively. Cytokeratin (CK)+/CD45- CTCs by IF could be detected in 17 of 30 (56.7%) patients at baseline and in 8 of 11 (72.7%) after the third chemotherapy cycle. Spearman analysis revealed a significant correlation ( p = 0.001) between Giemsa-positive and IF-positive (CK+/CD45-) CTCs. At baseline, PD-1 and PD-L1 expression was observed in 53% and in 47% CK-positive patients, respectively. After the third treatment cycle the corresponding numbers were 13% and 63% respectively. Median progression-free survival (PFS) was significantly shorter in patients with >3 PD-1(+) CTCs at baseline compared with those with <3 PD-1(+) CTCs ( p = 0.022) as well as in patients with >1 Giemsa-positive tumor cells ( p = 0.025).

Conclusion:

PD-1(+) and PD-L1(+) CTCs could be detected before and after front-line chemotherapy in patients with metastatic NSCLC. The presence of high PD-1(+) CTC numbers before treatment is associated with a poor patient clinical outcome.
Neurocognitive Deficits Associated With ADHD in Athletes: A Systematic Review
Authors: Poysophon Poyrung , Rao Ashwin L.
Published: January 2018

Context:

Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder and is frequently diagnosed in young adults. Emerging studies suggest a relationship between ADHD and concussion.

Objective:

To determine whether athletes with ADHD are at increased risk for neurocognitive deficits related to concussion risk, symptom reporting, and recovery.

Data Sources:

A comprehensive search of PubMed, CINAHL, PsychInfo, and Cochrane Library databases was performed. Studies conducted between 2006 and 2017 were reviewed, although only those between 2013 and 2017 met inclusion criteria.

Study Selection:

Studies that examined neurocognitive deficits in adolescent and young adult athletes aged 15 to 19 years who had ADHD and reported using notable neuropsychological evaluation tools were included.

Study Design:

Systematic review.

Level of Evidence:

Level 2.

Results:

A total of 17 studies met the inclusion criteria. The prevalence of ADHD in athletes varied between 4.2% and 8.1%. Overall, athletes with ADHD demonstrated lower scores on neurocognitive testing such as the ImPACT (Immediate Post-Concussion Assessment and Cognitive Test), increased risk for concussion, and increased symptom reporting. There was no evidence that treatment with stimulant medication changed these risks.

Conclusion:

ADHD is associated with increased neurocognitive deficits in athletes, although pathophysiology remains unclear. Evidence for stimulant treatment in athletes with ADHD continues to be sparse.
Topographic Analysis of the Distal Femoral Condyle Articular Cartilage Surface: Adequacy of the Graft from Opposite Condyles of the Same or Different Size for the Osteochondral Allograft Transplantation
Authors: Yanke Adam B. , Urita Atsushi , Shin Jason J. , Cvetanovich Greg L. , Moran Erin K. , Bach Bernard R. , Cole Brian J. , Inoue Nozomu , Verma Nikhil N.
Published: January 2018

Objective

To analyze the topography of the opposite condyle to treat focal femoral condyle articular defects with an osteochondral allograft (OCA).

Design

Three groups were created: Group 1, same condyle with same width; Group 2, opposite condyle with same width; Group 3, opposite condyle with different width. Computed tomography (CT) of 22 cadaveric femoral hemi-condyles was used to create 3-dimensional CT models that were exported into point-cloud models. Three zones of the donor condyle (anterior, middle, and posterior) were quantified. Four defect sizes were created (15, 18, 23, 25 mm) at the weight-bearing region. The defect was moved throughout each donor condyle zone and the least distance was calculated, defined as the shortest distance between the defect and the donor condyle.

Results

The mean least distance increased with larger defect size in all groups, yet there was a less than 0.2 mm difference in the least distance among defect sizes. The 15, 18, and 23 mm defect models in Group 1 exhibited greater least distances at the anterior than middle and posterior zones. The 15 mm defect model exhibited greater least distance at the anterior zone than posterior zone in Group 3. However, there was a less than 0.05 mm difference in the mean least distance between zones. There was no significant difference in the least distance between groups.

Conclusion

OCAs from opposite condyles yield similar topographic matching to OCAs from the same condyles, suggesting that opposite condyles can be utilized. Clinical correlation and outcomes are necessary.
Investigating the Relationship Between Self-Perceived Moral Superiority and Moral Behavior Using Economic Games
Authors: Tappin Ben M. , McKay Ryan T.
Published: January 2018

Most people report that they are superior to the average person on various moral traits. The psychological causes and social consequences of this phenomenon have received considerable empirical attention. The behavioral correlates of self-perceived moral superiority (SPMS), however, remain unknown. We present the results of two preregistered studies (Study 1, N = 827; Study 2, N = 825), in which we indirectly assessed participants’ SPMS and used two incentivized economic games to measure their engagement in moral behavior. Across studies, SPMS was unrelated to trust in others and to trustworthiness, as measured by the trust game, and unrelated to fairness, as measured by the dictator game. This pattern of findings was robust to a range of analyses, and, in both studies, Bayesian analyses indicated moderate support for the null over the alternative hypotheses. We interpret and discuss these findings and highlight interesting avenues for future research on this topic.
Brexit, Trump, and the Polarizing Effect of Disillusionment
Authors: Maher Paul J. , Igou Eric R. , van Tilburg Wijnand A. P.
Published: January 2018

We investigate experiences of disillusionment as a source of political polarization. Disillusioning experiences motivate a search for meaning, and we propose that people respond by seeking reassurance in political ideologies, reflected in political polarization. We first tested this hypothesis in the context of two major political events: the European Union (EU) membership referendum in the United Kingdom and the 2016 U.S. presidential election. In Study 1, disillusionment stemming from the EU referendum outcome led “remain” supporters to express more extreme political views. In Study 2, we measured political stance and disillusionment before and after the U.S. presidential election. Political polarization occurred among Clinton supporters, and this was mediated by increased disillusionment levels. In Study 3, we manipulated disillusionment and found that disillusioned participants expressed stronger support for diverging forms of political activism. Consistent with our approach, this effect was mediated by epistemic motivations. Implications regarding the effect of political polarization in society are discussed.
Changing Deep-Rooted Implicit Evaluation in the Blink of an Eye: Negative Verbal Information Shifts Automatic Liking of Gandhi
Authors: Van Dessel Pieter , Ye Yang , De Houwer Jan
Published: January 2018

It is often assumed that, once established, spontaneous or implicit evaluations are resistant to immediate change. Recent research contradicts this theoretical stance, showing that a person’s implicit evaluations of an attitude object can be changed rapidly in the face of new counterattitudinal information. Importantly, it remains unknown whether such changes can also occur for deep-rooted implicit evaluations of well-known attitude objects. We address this question by examining whether the acquisition of negative information changes implicit evaluations of a well-known positive historic figure: Mahatma Gandhi. We report three experiments showing rapid changes in implicit evaluations of Gandhi as measured with an affect misattribution procedure and evaluative priming task but not with an implicit association test (IAT). These findings suggest that implicit evaluations based on deep-rooted representations are subjective to rapid changes in the face of expectancy-violating information while pointing to limitations of the IAT for assessing such changes.
The Gradual Move Toward Gender Equality: A 7-Year Latent Growth Model of Ambivalent Sexism
Authors: Huang Yanshu , Osborne Danny , Sibley Chris G.
Published: January 2018

Sexist ideologies maintain and reinforce gender inequality, yet the stability of these belief systems is unknown. We addressed this oversight by examining changes in men’s and women’s hostile sexism (HS) and benevolent sexism (BS)—complementary gender-based belief systems, respectively, rooted in punitive and protective (albeit restrictive) attitudes toward women—using seven annual waves of longitudinal panel data ( N = 15,626). Autoregressive cross-lagged models examined the rank-order stability of BS and HS, whereas latent growth models examined mean-level changes in both ideologies for men and women from 2009 to 2016. Results indicated that both BS and HS demonstrated high levels of rank-order stability across time for men and women. Nevertheless, women and men experienced mean-level curvilinear decreases in HS characterized by initial sharp declines that decelerated over time. Conversely, women’s mean-level BS initially declined slowly before gradually accelerating, whereas men’s mean-level HS decreased linearly. Together, these results indicate that sexism decreased over time.
Characterizing Pediatric Non–Malarial Fever and Identifying the At-Risk Child in Rural Malawi
Authors: Kortz Teresa Bleakly , Blair Alden , Scarr Ellen , Mguntha Andrew Masozi , Bandawe Gama , Schell Ellen , Rankin Sally , Baltzell Kimberly
Published: January 2018

Objective. To characterize children with non–malarial fever at risk of nonrecovery or worsening in rural Malawi. Methods. This is a subgroup analysis of patients ≤14 years of age from a prospective cohort study in non–malarial fever subjects (temperature ≥37.5°C, or fever within 48 hours, and malaria negative) in southern Malawi cared for at a mobile clinic during the 2016 dry (August to September) or wet (November to December) season. Data collection included chart review and questionnaires; 14-day follow-up was conducted. We conducted univariate descriptive statistics on cohort characteristics, bivariate analyses to examine associations between characteristics and outcomes, and multivariate logistic regressions to explore factors associated with nonrecovery. Results. A total of 2893 patients were screened, 401 were enrolled, 286 of these were children, and 280 children completed follow-up. Eighty-seven percent reported symptom resolution, 12.9% reported no improvement, and there were no deaths or hospitalizations. No improvement was associated with dry season presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a 4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] = 1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI = 1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion. Outcomes were generally excellent in this rural, outpatient pediatric cohort, though risk factors for nonrecovery included food insecurity, access to a standing clinic, and seasonality. Ideally, this study will inform clinic- and policy-level changes aimed at ameliorating the modifiable risk factors in Malawi and throughout rural Africa.
“Aliens Ministering to Aliens”: Reformed Church in America Missionaries among Chinese in the Philippines
Authors: White Chris
Published: January 2018

This article reviews the two decades after RCA missionaries were forced out of China, revealing that the church’s “China mission” was not abandoned, but simply changed geographic focus to overseas Chinese in the Philippines. Although the RCA continued a ministry targeting Chinese from South Fujian, where they had worked since 1842, they faced many new challenges in the Philippines that were quite inconsistent with their experience in China. A major point of contention for missionaries was balancing their relationship with the United Church of Christ in the Philippines (UCCP) and Chinese churches that refused to join this ecumenical organization.
Clinical characteristic and intraoperative findings of uterine perforation patients in using of intrauterine devices (IUDs)
Authors: Sun Xin , Xue Min , Deng Xinliang , Lin Yun , Tan Ying , Wei Xueli
Published: January 2018

Background

Intrauterine devices (IUDs) are the most popular form of contraception used worldwide; however, IUD is not risk-free. IUD migrations, especially uterine perforations, were frequently occurred in patients. The aim of this study was to investigate the clinical characteristics and intraoperative findings in patients with migrated IUDs.

Results

29 cases of uterine perforation associated with migrated IUDs and 69 control patients were followed between January 2008 to March 2015. Patients who used IUDs within first 6 months from the last delivery experienced a characteristically high rate of the perforation of the uterine wall. A significantly larger number of IUD insertion associated with uterine perforation were performed in rural hospitals or operated at a lower level health care system. There was no clear difference in the age and presented symptoms in patients between two groups. Majority of contraceptive intrauterine devices was the copper-releasing IUDs. Furthermore, patients who used V-shaped IUD showed significantly higher incidence of pelvic adhesions when compared with the users of O-shaped IUDs.

Conclusions

Unique clinical characteristics of IUD migration were identified in patients with uterine perforation. Hysteroscopy and/or laparoscopy were the effective approaches to remove the migrated IUDs. Improving operating skills is required at the lower level of health care system.