pinecone/core-2020-05-10-deduplication huggingface dataset:
GATA3 : a promising marker for metastatic breast carcinoma in serous effusion specimens

Background\ud
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The utility of GATA3 as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. \ud
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Methods\ud
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Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from breast (30), female genital tract (13), gastrointestinal tract (7), lung adenocarcinoma (9), pancreas (1), kidney (1) and bladder (1). The breast carcinoma cases included 15 ductal carcinomas, 8 lobular carcinomas and in 7 the histology sub-type was not available. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and GCDFP-15 to compare sensitivity with GATA3. \ud
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Results\ud
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Positive nuclear staining for GATA3 was present in 90% (27/30) of metastatic breast carcinoma specimens. All non-breast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases showed weak positivity of benign lymphoid cells. Staining results were unambiguous as all positive cases showed intense nuclear staining in >50% of tumor cells. Mammaglobin (57%; 17/30) and GCDFP-15 (33%; 10/30) were less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only one additional case to those stained with GATA3. \ud
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Conclusions\ud
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GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a consideration
Optimizing detection of RET and PPARg rearrangements in thyroid neoplastic cells using a home-brew tetracolor probe

BACKGROUND Fluorescence in situ hybridization (FISH) to identify specific DNA target sequences in the nuclei of nondividing cells of numerous solid neoplasms has contributed to the introduction of molecular cytogenetics as a useful adjunct to cytology, leading recently to the "marriage" of the 2 disciplines. Numerous cancer molecular markers can now be investigated using different technical approaches, at both the gene and expression levels, in biopsies of various suspected cancers, including differentiated thyroid carcinoma. The limited amount of bioptic material is often insufficient to carry out multiple tests, and optimizing handling of the biopsy is desirable. METHODS We have developed a home-brew tetracolor break-apart probe able to simultaneously identify the 2 most common genetic alterations in differentiated thyroid carcinoma: RET/PTC variants in papillary thyroid carcinoma and PAX8/PPARg fusion and variants in follicular thyroid carcinoma. RESULTS The probe had 100% specificity, 99.5% sensitivity, and >= 3% cutoff. The probe was tested on RET/PTC and PAX8/PPARg RT-PCR positive controls, and feasibility was assessed in 368 thyroid nodule fine-needle aspirations (FNA). In the latter analysis, 24 FNAs had split RET signal, and 9 had split PPARg signal. FISH analysis of available surgically removed nodules confirmed the sensitivity of FISH in detecting abnormal clones and oligoclones. CONCLUSIONS The home-brew tetracolor probe showed high feasibility, optimizing the use of the biological material in relation to the available molecular tests and maximizing the FISH experimental and slide-scoring times. This probe may be considered an alternative to RT-PCR when recovery and quality of RNA amplification from FNA are insufficient
The role of liquid-based cytology and ancillary techniques in pleural and pericardic effusions: An institutional experience

"Epub ahead of print 2015 Jan. 14"BACKGROUND:
Fine-needle aspiration cytology (FNAC) of serous membrane effusions may fulfil a challenging role in the diagnostic analysis of both primary and metastatic disease. From this perspective, liquid-based cytology (LBC) represents a feasible and reliable method for empowering the performance of ancillary techniques (ie, immunocytochemistry and molecular testing) with high diagnostic accuracy.
METHODS:
In total, 3171 LBC pleural and pericardic effusions were appraised between January 2000 and December 2013. They were classified as negative for malignancy (NM), suspicious for malignancy (SM), or positive for malignancy (PM).
RESULTS:
The cytologic diagnoses included 2721 NM effusions (2505 pleural and 216 pericardic), 104 SM effusions (93 pleural and 11 pericardic), and 346 PM effusions (321 pleural and 25 pericardic). The malignant pleural series included 76 unknown malignancies (36 SM and 40 PM effusions), 174 metastatic lesions (85 SM and 89 PM effusions), 14 lymphomas (3 SM and 11 PM effusions), 16 mesotheliomas (5 SM and 11 SM effusions), and 3 myelomas (all SM effusions). The malignant pericardic category included 20 unknown malignancies (5 SM and 15 PM effusions), 15 metastatic lesions (1 SM and 14 PM effusions), and 1 lymphoma (1 PM effusion). There were 411 conclusive immunocytochemical analyses and 47 molecular analyses, and the authors documented 88% sensitivity, 100% specificity, 98% diagnostic accuracy, 98% negative predictive value, and 100% positive predictive value for FNAC.
CONCLUSIONS:
FNAC represents a primary diagnostic tool for effusions and a reliable approach with which to determine the correct follow-up. Furthermore, LBC is useful for ancillary techniques, such as immunocytochemistry and molecular analysis, with feasible diagnostic and predictive utility
HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status

BACKGROUND: Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. 
METHODS: Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. 
RESULTS: A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). 
CONCLUSIONS: A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results. Cancer (Cancer Cytopathol) 2015. (c) 2015 American Cancer Society.Financial support for the Canadian Cervical Cancer Screening Trial was provided by the Canadian Institutes of Health Research (CIHR) (grant MCT-54063 to Dr. Franco). The Democratic Republic of Congo's Cervical Screening Study was funded by the Program for Appropriate Technology in Health (grant to Dr. Sangwa-Lugoma). The Brazilian Investigation into Nutrition and Cervical Cancer Prevention study received funding from the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (grant to Dr. Cardoso). Additional support for the work performed in rereading Papanicolaou tests was provided by a CIHR team grant (83320 to Dr. Franco). Additional support for human papillomavirus testing and genotyping was provided by the above CIHR team grant and the Reseau FRQS SIDA-MI
Histologic and Clinical Follow-up of Thyroid Fine Needle Aspirates in Pediatric Patients

BACKGROUND

Although fine-needle aspiration (FNA) has an important role in evaluating thyroid nodules in adults, there is little published information regarding its utility in the pediatric population.
METHODS

A retrospective analysis of thyroid FNAs for patients who were 18 years old or younger at 2 institutions was conducted. Aspirates were retrospectively categorized with the Bethesda System for Reporting Thyroid Cytopathology. These diagnoses were then correlated with either final histopathology or clinical follow-up.
RESULTS

A total of 186 thyroid FNA samples from 154 patients (122 females and 32 males), who ranged in age from 9 months to 18 years (median, 16 years; mean, 14 years), were identified. FNA was performed to evaluate 1 to 3 nodules for each patient. Aspirates were classified as follows: nondiagnostic (n = 27), benign (n = 114), atypia of undetermined significance (AUS; n = 21), follicular neoplasm (FN; n = 8), suspicious for malignancy (n = 3), and malignant (n = 13). Sixty-one samples had a histologic correlation, 68 were followed clinically for ≥2 years, and 57 either had no follow-up or were followed for <2 years. For statistical purposes, FNA diagnoses of suspicious and malignant were considered positive, and benign lesions were considered negative. The accuracy was 99%, and the sensitivity and specificity were 94% and 100%, respectively. The risk of malignancy, not including papillary microcarcinoma, was 2% for benign aspirates, 21% for AUS, 57% for FN, and 100% for suspicious or malignant aspirates.
CONCLUSIONS

This analysis demonstrates that FNA is a sensitive and highly specific modality for evaluating thyroid nodules in pediatric patients. Each diagnostic category can facilitate communication and guide appropriate management
Can the careHPV test performed in mobile units replace cytology for screening in rural and remote areas?

BACKGROUND
Human papillomavirus (HPV) DNA testing can be crucial for women who have limited access to traditional screening. The current study compared the results obtained through HPV DNA testing with those obtained through cytology-based screening. 

METHODS
A total of 3068 women aged 18 to 85 years were enrolled in an opportunistic cervical cancer screening program developed by the Barretos Cancer Hospital and performed by a team of health professionals working within a mobile unit from March to December 2012, followed by statistical analyses. For each patient, 2 different cervical samples were collected and preserved in a careHPV assay and SurePath medium, respectively. 

RESULTS
High-risk HPV (hr-HPV) DNA was detected in 10.0% of women, with the majority (86.7%) demonstrating no abnormal Papanicolaou test results. The following cytological samples were found to be hr-HPV positive: 8.2% of the normal samples; 39.4% of the samples with atypical squamous/glandular cells of undetermined significance; 38.5% of the samples with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion; 55.3% of the samples with low-grade squamous intraepithelial lesions; and 100% of the samples with high-grade squamous intraepithelial lesions. Colposcopy examinations were performed among 33.4% of the women with positive results on at least 1 of the tests (HPV DNA positive and/or cytology with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion or high-grade squamous intraepithelial lesions), and 59.5% of these women underwent biopsies. Among these samples, 18.2% were confirmed as cervical intraepithelial neoplasia. 

CONCLUSIONS
The careHPV test was demonstrated to be a feasible alternative to primary screening in low-resource settings accessed through the use of mobile units.Adriana T. Lorenzi was supported (via a scholarship) by CNPq process no. 573799/2008-3 and FAPESP process no. 2008/57889-1 through the National HPV Research and Technology Institute of São Paulo, Brazil (INCT-HPV)info:eu-repo/semantics/publishedVersio
High Apoptotic Index in Urine Cytology Is Associated with High-Grade Urothelial Carcinoma

BACKGROUND

The significance of apoptosis and its association with high-grade urothelial carcinoma (HGUC) in urine cytology has yet to be determined.
METHODS

A computerized search of the study laboratory information system was performed over a 3-year period for all urine cytology specimens processed using the SurePath liquid-based preparation technique. Only those cases with correlating surgical pathology obtained within 6 months after the urine cytologic samples were included in the current study. Cases from ileal conduit samples were excluded. A semiquantitative numerical scoring system (apoptotic index) was used to assess the amount of pyknosis or karyorrhexis, with 0 indicating none, 1 indicating < 10 per 10 high-power fields, 2 indicating 10 to 30 per 10 high-power fields, and 3 indicating > 30 per 10 high-power fields. Statistical analysis using the Pearson chi-square test was performed.
RESULTS

A total of 228 cases including 105 benign cases, 79 cases of HGUC, and 44 cases of low-grade urothelial carcinoma (LGUC) diagnosed on follow-up surgical pathology were selected. A score of 0 was observed in 70 benign, 11 HGUC, and 8 LGUC cases; a score of 1 was observed in 31 benign, 21 HGUC, and 23 LGUC cases; a score of 2 was observed in 3 benign, 27 HGUC, and 9 LGUC cases; and a score of 3 was observed in 1 benign, 20 HGUC, and 4 LGUC cases.
CONCLUSIONS

Excluding ileal conduit urine specimens, the finding of a high apoptotic index (score ≥ 2) with the presence of pyknosis or karyorrhexis in ≥10 per 10 high-power fields in the urine cytology appears to be significantly associated with HGUC (P<.05)
BMP4 expression in the adult rat brain

Bone morphogenetic protein-4 (BMP4) is a member of the transforming
growth factor β (TGF- β) superfamily and plays important roles in multiple
biological events. Although BMP4 expression has been well described in the
early development of central nervous system (CNS), little information is
available for its expression in the adult CNS. We, thus, investigated BMP4
expression in the adult rat CNS using immunohistochemistry. BMP4 is
intensely expressed in most neurons and their dendrites. In addition, intense
BMP4 expression was also observed in the neuropil of the gray matters
where high plasticity is reported, such as the molecular layer of the
cerebellum and the superficial layer of the superior colliculus. Furthermore,
we found that astrocytes also express BMP4 protein. These data indicate that
BMP4 is more widely expressed throughout the adult CNS than previously
reported, and its continued abundant expression in the adult brain strongly
supports the idea that BMP4 plays pivotal roles also in the adult brain
Identification of Molecular Markers of Bipolar Cells in the Murine Retina

Retinal bipolar neurons serve as relay interneurons that connect rod and cone photoreceptor cells to amacrine and ganglion cells. They exhibit diverse morphologies essential for correct routing of photoreceptor cell signals to specific postsynaptic amacrine and ganglion cells. The development and physiology of these interneurons have not been completely defined molecularly. Despite previous identification of genes expressed in several bipolar cell subtypes, molecules that mark each bipolar cell type still await discovery. In this report, novel genetic markers of murine bipolar cells were found. Candidates were initially generated by using microarray analysis of single bipolar cells and mining of retinal serial analysis of gene expression (SAGE) data. These candidates were subsequently tested for expression in bipolar cells by RNA in situ hybridization. Ten new molecular markers were identified, five of which are highly enriched in their expression in bipolar cells within the adult retina. Double-labeling experiments using probes for previously characterized subsets of bipolar cells were performed to identify the subtypes of bipolar cells that express the novel markers. Additionally, the expression of bipolar cell genes was analyzed in Bhlhb4 knockout retinas, in which rod bipolar cells degenerate postnatally, to delineate further the identity of bipolar cells in which novel markers are found. From the analysis of Bhlhb4 mutant retinas, cone bipolar cell gene expression appears to be relatively unaffected by the degeneration of rod bipolar cells. Identification of molecular markers for the various subtypes of bipolar cells will lead to greater insights into the development and function of these diverse interneurons
The Transcriptome of Retinal Müller Glial Cells

Müller glial cells are the major type of glia in the mammalian retina. To identify the molecular machinery that defines Müller glial cell identity and function, single cell gene expression profiling was performed on Affymetrix microarrays. Identification of a cluster of genes expressed at high levels suggests a Müller glia core transcriptome, which likely underlies many of the functions of Müller glia. Expression of components of the cell cycle machinery and the Notch pathway, as well as of growth factors, chemokines, and lipoproteins might allow communication between Müller glial cells and the neurons that they support, including modulation of neuronal activity. This approach revealed a set of transcripts that were not previously characterized in (Müller) glia; validation of the expression of some of these genes was performed by in situ hybridization. Genes expressed exclusively by Müller glia were identified as novel markers. In addition, a novel BAC transgenic mouse that expresses Cre in Müller glia cells was generated. The molecular fingerprint of Müller glia provides a foundation for further studies of Müller glia development and function in normal and diseased states
Distribution and neurochemical characterization of neurons expressing GIRK channels in the rat brain

El pdf del artículo es la versión pre-print.-- et al.G-protein inwardly rectifying potassium (GIRK) channels mediate the synaptic actions of numerous neurotransmitters in the mammalian brain and play an important role in the regulation of neuronal excitability in most brain regions through activation of various G-protein-coupled receptors such as the serotonin 5-HT1A receptor. In this report we describe the localization of GIRK1, GIRK2, and GIRK3 subunits and 5-HT1A receptor in the rat brain, as assessed by immunohistochemistry and in situ hybridization. We also analyze the co-expression of GIRK subunits with the 5-HT1A receptor and cell markers of glutamatergic, γ-aminobutyric acid (GABA)ergic, cholinergic, and serotonergic neurons in different brain areas by double-label in situ hybridization. The three GIRK subunits are widely distributed throughout the brain, with an overlapping expression in cerebral cortex, hippocampus, paraventricular nucleus, supraoptic nucleus, thalamic nuclei, pontine nuclei, and granular layer of the cerebellum. Double-labeling experiments show that GIRK subunits are present in most of the 5-HT1A receptor-expressing cells in hippocampus, cerebral cortex, septum, and dorsal raphe nucleus. Similarly, GIRK mRNA subunits are found in glutamatergic and GABAergic neurons in hippocampus, cerebral cortex, and thalamus, in cholinergic cells in the nucleus of vertical limb of the diagonal band, and in serotonergic cells in the dorsal raphe nucleus. These results provide a deeper knowledge of the distribution of GIRK channels in different cell subtypes in the rat brain and might help to elucidate their physiological roles and to evaluate their potential involvement in human diseases.Funded by: Spanish Ministry of Education. Grant Numbers: SAF2004-02784, SAF-2006-10243; Basque Government. Grant Numbers: Saiotek-PE06UN12, IT-261-07.Peer reviewe
Gradual morphogenesis of retinal neurons in the peripheral retinal margin of adult monkeys and humans

The adult mammalian retina has been for long considered to lack neurogenerative capacity. However, retinal stem/progenitor cells which can originate retinal neurons in vitro have been recently reported in the ciliary body of adult mammals. Here we have explored the possibility of retinal neurogenesis occurring in vivo in adult monkeys and humans. We have found the presence of cells expressing molecular markers of neural and retinal progenitors in the non-laminated retinal margin and ciliary body pars plana of mature primates. By means of imunohistochemistry and electron microscopy we have also observed photoreceptors and other retinal cell types in different stages of morphological differentiation along the peripheral retinal margin. These findings allow us to extend to primates the idea of neurogenesis aimed at retinal cell turnover throughout life.Grant sponsor: Ministerio de Educación y Ciencia; Grant number: BFU2006-00957/BFI; Grant sponsor: Ministerio de Sanidad y Consumo; Grant number: RETICS RD07/0062/0012; Grant sponsor: ONCE; Grant sponsor: Fundaluce (to N.C.); Grant sponsor: Generalitat Valenciana; Grant number: GV06/197 (to J.M.-N)
Stem cells for ischemic brain injury: a critical review

No effective therapy is currently available to promote recovery following ischemic stroke. Stem cells have been proposed as a potential source of new cells to replace those lost due to central nervous system injury, as well as a source of trophic molecules to minimize damage and promote recovery. We undertook a detailed review of data from recent basic science and preclinical studies to investigate the potential application of endogenous and exogenous stem cell therapies for treatment of cerebral ischemia. To date, spontaneous endogenous neurogenesis has been observed in response to ischemic injury, and can be enhanced via infusion of appropriate cytokines. Exogenous stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke-injured brain. Stem cells from multiple sources cells also exhibit neuroprotective properties that may ameliorate stroke deficits. In many cases, functional benefits observed are likely independent of neural differentiation, although the exact mechanisms remain poorly understood. Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to demonstrate definitively the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. Thus careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggests that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury.status: publishe