bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the Blind Spot Enlarged in Early Glaucoma?
Authors: Meyer J.H. , Guhlmann M. , Funk J. 
Published: April 2018

Purpose We investigated whether the blind spot is larger in early “preperimetric” glaucoma with already deeply excavated optic discs than in normal persons. Methods We examined eight eyes of five patients with definite glaucomatous optic disc cupping but normal visual fields. Ten eyes of five normal healthy volunteers, with normal central excavation, served as controls. With SLO-perimetry we measured the differential light sensitivity 0.5-1.0° outside the disc margins, “within” the center (Goldmann V stimulus) and along the horizontal meridian of the optic discs. Optic disc topography was documented with the Heidelberg Retina Tomograph (HRT). Results Differential light sensitivities adjacent to the optic discs did not differ in the two groups (normal 8.3dB, early glaucoma 8.4dB). Goldmann IV stimuli presented on the horizontal meridian of optic discs with glaucomatous cupping were seen up to 0.7° centrally (i.e., towards the center) of the disc margin. In the control group this distance was significantly greater (1.3°). The light differential thresholds with stimulus presentation in the disc center (Goldmann V) were significantly higher in the glaucoma group (0±2.8dB) than in the normal controls (6.6±1.3dB), though disc size was the same in both groups. Conclusions Blind spots of normal discs seem to be smaller than those of deeply excavated discs in eyes with early glaucoma, possibly because there is more light scattering by the normal disc surface towards the adjacent functioning retina.
Estrogen and Progesterone Measurement and its Quality Control in Breast Cancer: A Reappraisal
Authors: Piffanelli Adriano , Giovannini Gloria , Pelizzola Dario , De Bortoli Michele 
Published: April 2018

This article illustrates the two main methods for routine measurement of cytoplasmic estrogen receptor status in neoplastic biopsy. The first is the Dextran Coated Charcoal Technique (D.C.C. Assay) which is still the method of choice in the majority of clinical laboratories for its simplicity, reproducibility and low cost. The second is a more advanced technique based on the specific binding, enzimatically displayed, of commercially available antiestrogen monoclonal antibodies (Enzyme Immuno Assay - ABBOTT). The sui generis characteristics of endocrine sensitivity assessment on tumor tissues and the importance of decision-making connected with the assay justify rigorous quality assurance schemes. The quality control design proposed by the Italian Committee concerned the evaluation of several lyophilized preparations with scalar receptor content; this permits the identification through linear regression analysis of systematic and non-systematic errors. The Italian Committee has currently connected 50 labs from most regions of the country.
Tissue Polypeptide Antigen (Tpa) Modifications in Hepatic Cirrhosis, Aggressive Chronic Hepatitis, Persistent Chronic Hepatitis, and in Minimal Pathology
Authors: Sabbatani S. , Monti M. , Fini A. 
Published: April 2018

A total of 104 patients with various liver diseases were studied. Hepatic biopsy was performed and the AST, ALT and TPA in serum were measured. Higher levels of TPA, AST and ALT were found in CAH and LC, lower in CPH and MHP. High serum TPA values, usually suggesting the possibility of neoplasm, should be considered with attention. A follow-up with periodic TPA assays (in addition to AST and ALT) is suggested in patients with acute hepatitis, in order to predict further possible complications such as CAH and LC.
CA 15.3 and CEA Plasma Level Monitoring in Patients with Breast Cancer
Authors: Martoni A. , Ercolino L. , Bellanova B. , Zanichelli L. , Canova N. , Pannuti F. 
Published: April 2018

CA 15.3 and CEA were determined in the serum of 217 patients with early and advanced breast carcinoma. CA 15.3 was high (> 30 U/ml) in 1/6 (17%) patients with stage III primary tumor, in 4/77 (5%) patients without clinical signs of disease after mastectomy, in 67/102 (65%) patients with advanced disease in progression, and in 13/32 (41%) patients with advanced disease not in progression and undergoing therapy. The corresponding incidences of pathological CEA values (> 2.5 ng/ml) were 33, 8, 55 and 14%>. The combination of the two markers brings about a certain improvement in the sensitivity for recognising patients with advanced disease in progression (79/102 = 77%). The presence of high values of CA 15.3 is statistically correlated to the prevalent site of metastases (bone and viscera > soft tissues). Monitoring the two markers during antitumor therapy in 36 patients showed good accordance (56%) between CA 15.3 changes and response to therapy. The decrease of the marker in patients who achieved partial remission was statistically significant. In conclusion, CA 15.3 is more sensitive than CEA in recognising patients with advanced disease in progression and gives better accordance with the response to therapy. The simultaneous use of the two markers may be useful in the follow-up of operated patients and in monitoring the disease during treatment.
Pattern Analysis of Serum alpha-fetoprotein in the Early Diagnosis of Hepatocellular Carcinoma in Liver Cirrhosis
Authors: Arrigoni A. , Andriulli A. , Gindro T. , Piantino P. , Capussotti L. , Rizzetto M. 
Published: April 2018

In a surveillance program for hepatocellular carcinoma (HCC), serum alpha-fetoprotein (AFP) was determined every 4 months in 164 patients with liver cirrhosis. Ultrasonography (US) was performed yearly or as dictated by abnormal AFP levels. During a follow-up of 32.5 ± 20.8 months HCC was identified by US in 16 patients. In 9 of them the AFP levels rose steadily over 4 months, increasing 7, 8 and 12 months in 3 cases before the lesion became detectable by US. In 4 patients tumors developed despite persistently normal AFP levels. Nine more patients showed abnormal fluctuations of AFP but HCC was not detected. AFP sensitivity was higher at a low cutoff point (40 ng/ml) while specificity of the test appeared higher at the 200 ng/ml cutoff point. An AFP value rising steeply over a few months appeared more reliable than a fixed preset threshold in indicating carcinomatous transformation. Screening for AFP can be expected to uncover about 3/4 of HCC developing in cirrhotics with few false-positive reactions. The test may have a unique role in identifying a subset of liver tumors whose early expression is AFP production.
Molecular Profile, Tissue Distribution and Prognostic Evaluation of a Human Melanoma-Carcinoma Antigen Recognized by the Murine Monoclonal Antibody B1.1
Authors: Natali P.G. , Nicotra M.R. , Nuti M. , Bigotti G. , Calabrò A. , Schlom J. , Giacomini P. 
Published: April 2018

Using the murine monoclonal antibody (MoAb) B1.1 we have analyzed the immunochemical profile and the tissue distribution of a human melanoma associated antigen (MAA) carrying an epitope shared by the 180 kd CEA. Results of this study have demonstrated that the epitope expressed by the MAA is carried by a distinct set of molecules of 110-140 kd. Similarly to the 180 kd CEA molecules synthesized by carcinomas, the expression of the melanoma associated CEA like components (MA-CEA) is upregulated by IFN-α. The tissue distribution of MA-CEA is not restricted to malignant primary and metastatic melanocytic lesions but is found also at low levels in 64% of benign nevi. No circulating CEA was found in patients bearing widespread metastatic disease of MA-CEA positive lesions. Preliminary clinical evaluation of stage I melanoma patients bearing MoAb Bl. l positive lesions has not shown a significative prognostic association of this phenotypic marker with clinical course of the disease.
PNA: A Marker of Neoplastic Progression and Differentiation in the Gastrointestinal Tract
Authors: Grigolato P. , Benetti A. , Berenzi A. , Villanacci V. , Tardanico R. 
Published: April 2018

We examined 35 cases of stomach carcinoma and 40 cases of colonic carcinoma with PNA associated with peroxidase (peanut agglutinin, lectin which binds to the terminal disaccharide galactose β (1, 3)-N-acetil-galacto-samine). In this way evaluation of the functional aspects of the normal-neoplastic sequence was undertaken. This method was carried out for histological and ultrastructural investigations. The results obtained in both cases showed a different reactivity in the evolution of neoplastic disease: in fact, positivity in dysplasia is finely granular intracytoplasmic, whereas in well-differentiated neoplastic transformation such a reactivity is preferentially localized along the cellular membranes, with restoration of gross positivity in the cytoplasm for the poorly-differentiated neoplasm. We therefore believe PNA to be a marker not only of neoplastic progression but of differentiation as well: we also hypothesize it to reveal glycoprotein groups with possible antigenic power, involved in immunologic interactions between tumor and host.
Intraoperative Radioimmunolocalization of Colorectal Cancer: A Review
Authors: Aprile C. 
Published: April 2018

Although intraoperative radioimmunolocalization (IORIL) is gaining wider acceptance, several limits inhibit a more extensive clinical use. In this paper the following topics will be discussed: 1) the clinical approach, that is, the combined use of immunoscintigraphy and IORIL after a single MAb administration or the use of non-imaging 125 I MAb; 2) the detector type and its collimation and shielding; 3) the nuclides employed, and 4) the background problem. The clinical results of our and other groups show a sensitivity that is generally higher than 0.75 with a high positive predictive value. The detection rate of occult lesions is in the order of 20% of all explored sites. However, the current state of detector and MAb technology do not allow to achieve better results; probably the results can be improved by the use of bispecific MAb or the avidin-biotin system.
Evaluation of Cytokeratin 19 Serum Fragments (Cyfra 21–1) in Patients with Lung Cancer: Results of a Multicenter Trial
Authors: Bombardieri E. , Seregni E. , Bogni A. , Ardit S. , Belloli S. , Busetto A. , Caniello B. , Castelli M. , Cianetti A. , Correale M. , De Angelis G. , Gandolfo G.M. , Gion M. , Macchia V. , Mione R. , Navaglia F. , Onetto M. , Paganuzzi M. , Pecchio F. , Plebani M. , Rapellino M. , Ruggeri G. , Vannini P. , Vitelli G. , Zamperlin A. 
Published: April 2018

Recently, a new immunometric assay (Cyfra 21–1) was developed to measure serum concentrations of a soluble fragment of cytokeratin subunit 19. With this method, supplied by Boehringer Mannheim (EIA Test Cyfra 21–1), an Italian multicenter trial was performed in patients with lung cancer. Cyfra 21–1 serum levels were determined in 568 normal subjects (blood donors), 607 patients with non-malignant diseases (491 respiratory diseases) and 730 patients with malignancies. In the latter group 584 had lung cancer. All these 584 patients had pathologically confirmed disease; 314 were epidermoid tumors, 166 adenocarcinomas, 88 small cell cancers and 16 large cell cancers. In the 568 healthy blood donors the mean Cyfra 21–1 value was 0.91 ng/ml (SD 0.47 ng/ml; range 0.05–2.90 ng/ml). A threshold of 1.9 ng/ml was chosen as the upper limit of normality. High levels of Cyfra21–1 were observed in patients with chronic hepatitis (positivity rate: 17/51–33.3%) and with pancreatitis (positivity rate 5/16 - 31.3%). In 114 out of 491 (23.2%) patients with respiratory diseases Cyfra 21–1 showed values greater than 1.9 ng/ml. The overall sensitivity (all stages) of Cyfra 21–1 in lung cancer was 65.6% (383/584). When the histology was considered the highest positivity rates were found in patients with squamous cell tumors (226/314; 72%) followed by adenocarcinomas (105/166; 63%). In patients with SCLC the global sensitivity was 52.3% (46/88). Higher sensitivity of Cyfra 21–1 was observed from stage I to stage IV (53.9% vs 85.7%; Chisquare: p < 0.01). When comparing patients in whom curative resections were possible (up to stage IIIa) with patients suffering from inoperable tumors, a significant difference in Cyfra 21–1 positivies was found (59% vs 81.5%; Chi square p < 0.01).
The Role of Carcinoembryonic Antigen (CEA) and Neuron-Specific Enolase (NSE) Evaluation in Pericardial Fluid for the Recognition of Malignant Pericarditis
Authors: Szturmowicz M. , Tomkowski W. , Fijalkowska A. , Burakowski J. , Sakowicz A. , Filipecki S. 
Published: April 2018

This study was designed to assess the value of tumor marker evaluation in pericardial fluid for the recognition of malignant pericarditis. Thirty-six patients with signs and symptoms of large pericardial effusion entered the study. Pericardiocentesis with pericardial fluid drainage was performed in all of them. CEA and NSE levels were evaluated in the pericardial fluid and compared to pericardial fluid cytology. The median CEA value in malignant effusions was 80 ng/ml (range 0-305 ng/ml) and in non-malignant ones 1.26 ng/ml (range 0.2-18.4 ng/ml), p<0.01. The sensitivity of CEA elevation above 5 ng/ml for the recognition of malignant pericarditis was 73% and the specificity was 90%. Pericardial fluid cytology was positive in 22 of 26 patients with malignant pericarditis (85%). CEA exceeding 5 ng/ml or positive cytology were seen in 96% of the patients with malignant pericarditis. The median NSE value in malignant pericardial effusions was 41.8 μg/l (range 2-172 μg/l) and in non-malignant ones 5.85 μg/l (range 1-83.9 μg/l), p<0.3. For the differential diagnosis of large pericardial effusions we would recommend simultaneous cytologic examination of pericardial fluid and CEA assessment. NSE measurement in hemorrhagic pericardial fluid is of limited value.
miR-148b-3p functions as a tumor suppressor in GISTs by directly targeting KIT
Authors: Wang Yu , Li Jun , Kuang Dong , Wang Xiaoyan , Zhu Yuanli , Xu Sanpeng , Chen Yaobing , Cheng Henghui , Zhao Qiu , Duan Yaqi , Wang Guoping 
Published: April 2018

Abstract
Background
Gain-of-function mutations and overexpression of KIT are characteristic features of gastrointestinal stromal tumor (GIST). Dysregulation in miRNA expression may lead to KIT overexpression and tumorigenesis.

Methods
miRNA microarray analysis and real-time PCR were used to determine the miRNA expression profiles in a cohort of 69 clinical samples including 50 CD117IHC+/KITmutation GISTs and 19 CD117IHC−/wild-type GISTs. GO enrichment and KEGG pathway analyses were performed to reveal the predicted targets of the dysregulated miRNAs. Of the dysregulated miRNAs whose expression was inversely correlated with that of KIT miRNAs were predicted by bioinformatics analysis and confirmed by luciferase reporter assay. Cell counting kit-8 (CCK-8) and flow cytometry were used to measure the cell proliferation, cycle arrest and apoptosis. Wound healing and transwell assays were used to evaluate migration and invasion. A xenograft BALB/c nude mouse model was applied to investigate the tumorigenesis in vivo. Western blot and qRT-PCR were used to investigate the protein and mRNA levels of KIT and its downstream effectors including ERK, AKT and STAT3.

Results
Of the six miRNAs whose expression was inversely correlated with that of KIT, we found that miR-148b-3p was significantly downregulated in the CD117IHC+/KITmutation GIST cohort. This miRNA was subsequently found to inhibit proliferation, migration and invasion of GIST882 cells. Mechanistically, miR-148b-3p was shown to regulate KIT expression through directly binding to the 3’-UTR of the KIT mRNA. Restoration of miR-148b-3p expression in GIST882 cells led to reduced expression of KIT and the downstream effectors proteins ERK, AKT and STAT3. However, overexpression of KIT reversed the inhibitory effect of miR-148b-3p on cell proliferation, migration and invasion. Furthermore, we found that reduced miR-148b-3p expression correlated with poor overall survival (OS) and disease-free survival (DFS) in GIST patients.

Conclusion
miR-148b-3p functions as an important regulator of KIT expression and a potential prognostic biomarker for GISTs.
Automated Renal Cancer Grading Using Nuclear Pleomorphic Patterns
Authors: Holdbrook Daniel Aitor , Singh Malay , Choudhury Yukti , Kalaw Emarene Mationg , Koh Valerie , Tan Hui Shan , Kanesvaran Ravindran , Tan Puay Hoon , Peng John Yuen Shyi , Tan Min-Han , Lee Hwee Kuan 
Published: April 2018

Purpose Nuclear pleomorphic patterns are essential for Fuhrman grading of clear cell renal cell carcinoma (ccRCC). Manual observation of renal histopathologic slides may lead to subjective and inconsistent assessment between pathologists. An automated, image-based system that classifies ccRCC slides by quantifying nuclear pleomorphic patterns in an objective and consistent interpretable fashion can aid pathologists in histopathologic assessment. Methods In the current study, histopathologic tissue slides of 59 patients with ccRCC who underwent surgery at Singapore General Hospital were assembled retrospectively. An automated image classification pipeline detects and analyzes prominent nucleoli in ccRCC images to classify them as either low (Fuhrman grade 1 and 2) or high (Fuhrman grade 3 and 4). The pipeline uses machine learning and image pixel intensity–based feature extraction techniques for nuclear analysis. We trained classification systems that concurrently analyze different permutations of multiple prominent nucleoli image patches. Results Given the parameters for feature combination and extraction, we present experimental results across various configurations for the classification of a given ccRCC histopathologic image. We also demonstrate that the image score used by the pipeline, termed fraction value, is correlated ( R = 0.59) with an existing multigene assay–based scoring system that has previously been demonstrated to be a strong indicator of prognosis in patients with ccRCC. Conclusion The current method provides an objective and fully automated way by which to process pathologic slides. The correlation study with a multigene assay–based scoring system also allows us to provide quantitative interpretation for already established nuclear pleomorphic patterns in ccRCC. This method can be extended to other cancers whose corresponding grading systems use nuclear pattern information.
Conserved and divergent functions of Pax6 underlie species-specific neurogenic patterns in the developing amniote brain
Authors: Yamashita Wataru , Takahashi Masanori , Kikkawa Takako , Gotoh Hitoshi , Osumi Noriko , Ono Katsuhiko , Nomura Tadashi 
Published: April 2018

ABSTRACT
The evolution of unique organ structures is associated with changes in conserved developmental programs. However, characterizing the functional conservation and variation of homologous transcription factors (TFs) that dictate species-specific cellular dynamics has remained elusive. Here, we dissect shared and divergent functions of Pax6 during amniote brain development. Comparative functional analyses revealed that the neurogenic function of Pax6 is highly conserved in the developing mouse and chick pallium, whereas stage-specific binary functions of Pax6 in neurogenesis are unique to mouse neuronal progenitors, consistent with Pax6-dependent temporal regulation of Notch signaling. Furthermore, we identified that Pax6-dependent enhancer activity of Dbx1 is extensively conserved between mammals and chick, although Dbx1 expression in the developing pallium is highly divergent in these species. Our results suggest that spatiotemporal changes in Pax6-dependent regulatory programs contributed to species-specific neurogenic patterns in mammalian and avian lineages, which underlie the morphological divergence of the amniote pallial architectures.
Distinct 3′ UTRs regulate the life-cycle-specific expression of two TCTP paralogs in Trypanosoma brucei
Authors: Jojic Borka , Amodeo Simona , Bregy Irina , Ochsenreiter Torsten 
Published: April 2018

ABSTRACT
The translationally controlled tumor protein (TCTP; also known as TPT1 in mammals) is highly conserved and ubiquitously expressed in eukaryotes. It is involved in growth and development, cell cycle progression, protection against cellular stresses and apoptosis, indicating the multifunctional role of the protein. Here, for the first time, we characterize the expression and function of TCTP in the human and animal pathogen, Trypanosoma brucei. We identified two paralogs (TCTP1 and TCTP2) that are differentially expressed in the life cycle of the parasite. The genes have identical 5′ untranslated regions (UTRs) and almost identical open-reading frames. The 3′UTRs differ substantially in sequence and length, and are sufficient for the exclusive expression of TCTP1 in procyclic- and TCTP2 in bloodstream-form parasites. Furthermore, we characterize which parts of the 3′UTR are needed for TCTP2 mRNA stability. RNAi experiments demonstrate that TCTP1 and TCTP2 expression is essential for normal cell growth in procyclic- and bloodstream-form parasites, respectively. Depletion of TCTP1 in the procyclic form cells leads to aberrant cell and mitochondrial organelle morphology, as well as enlarged, and a reduced number of, acidocalcisomes.
Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application
Authors: Müller Cristina , Domnanich Katharina A , Umbricht Christoph A , van der Meulen Nicholas P 
Published: April 2018

Currently, different radiometals are in use for imaging and therapy in nuclear medicine: 68Ga and 111In are examples of nuclides for positron emission tomography (PET) and single photon emission computed tomography (SPECT), respectively, while 177Lu and 225Ac are used for β−- and α-radionuclide therapy. The application of diagnostic and therapeutic radionuclides of the same element (radioisotopes) would utilize chemically-identical radiopharmaceuticals for imaging and subsequent treatment, thereby enabling the radiotheranostic concept. There are two elements which are of particular interest in this regard: Scandium and Terbium. Scandium presents three radioisotopes for theranostic application. 43Sc (T1/2 = 3.9 h) and 44Sc (T1/2 = 4.0 h) can both be used for PET, while 47Sc (T1/2 = 3.35 d) is the therapeutic match—also suitable for SPECT. Currently, 44Sc is most advanced in terms of production, as well as with pre-clinical investigations, and has already been employed in proof-of-concept studies in patients. Even though the production of 43Sc may be more challenging, it would be advantageous due to the absence of high-energetic γ-ray emission. The development of 47Sc is still in its infancy, however, its therapeutic potential has been demonstrated preclinically. Terbium is unique in that it represents four medically-interesting radioisotopes. 155Tb (T1/2 = 5.32 d) and 152Tb (T1/2 = 17.5 h) can be used for SPECT and PET, respectively. Both radioisotopes were produced and tested preclinically. 152Tb has been the first Tb isotope that was tested (as 152Tb-DOTATOC) in a patient. Both radionuclides may be of interest for dosimetry purposes prior to the application of radiolanthanide therapy. The decay properties of 161Tb (T1/2 = 6.89 d) are similar to 177Lu, but the coemission of Auger electrons make it attractive for a combined β−/Auger electron therapy, which was shown to be effective in preclinical experiments. 149Tb (T1/2 = 4.1 h) has been proposed for targeted α-therapy with the possibility of PET imaging. In terms of production, 161Tb and 155Tb are most promising to be made available at the large quantities suitable for future clinical translation. This review article is dedicated to the production routes, the methods of separating the radioisotopes from the target material, preclinical investigations and clinical proof-of-concept studies of Sc and Tb radionuclides. The availability, challenges of production and first (pre)clinical application, as well as the potential of these novel radionuclides for future application in nuclear medicine, are discussed.