Natural Killer Cells and Liver Fibrosis

In the 40 years since the discovery of natural killer (NK) cells, it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue-resident NK cells with distinct phenotypical and functional characteristics have been identified. Here, we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects

Different expression of cyclooxygenase-2 (COX-2) in selected nonmelanocytic human cutaneous lesions

The aim of our study was to elucidate the possible involvement of COX-2 in the development and/or progression of nonmelanocytic skin lesions. To evaluate the usefulness of that enzyme as a potential molecular marker, we examined the intensity and spatial distribution of COX-2 expression in selected types of such tumors using the same immunohistochemical procedure as in our earlier studies of melanocytic cancers. We examined 20 benign epithelial lesions, 11 precancerous lesions, 21 basal cell carcinomas (BCC), 14 squamous cell carcinomas (SCC) and eight fibromas. The levels of COX-2 expression detected in benign lesions and in normal skin were comparable. Elevated expression of this protein may play a role in the development of SCC, as indicated by strong immunostaining both in SCCs and precancerous lesions. Significantly stronger staining in SCCs compared to BCCs may indicate a role of COX-2 in cancer malignancy and serve as an indicator useful for differential diagnostics of the two types of cancer. Strong staining in all skin layers of SCC may help in detecting cancer cells infiltrating surrounding skin layers. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 3, pp. 381–388

Podejrzenie nowotworu pęcherzykowego czy nowotwór pęcherzykowy? Dylemat patologa i chirurga

  Introduction: Cytological material obtained from Fine Needle Aspiration Biopsy (FNAB) does not permit us to distinguish between follicular carcinomas, adenomas, and hyperplastic nodules. The limitations of the method are: lack of possibility to assess the presence of tumour capsule, eventual capsular invasion, and angioinvasion. An unequivocal conclusion of whether what we have to deal with is a neoplastic or benign lesion is possible only after histopathological examination. The aim of the study was to confirm justification for using the term “Suspicious for Follicular Neoplasm” (SFN) in cytological diagnostics of thyroid carcinoma. Material and methods: Three hundred and fifty-two primary SFN FNAB diagnoses (diagnostic category IV [DC IV] — according to Bethesda System) obtained from 2010 to 2015 in the Institute of Oncology in Gliwice were analysed, and their correlation with histopathological diagnoses was verified. Results: In the Institute of Oncology in Gliwice, 352 primary SFN diagnoses (diagnostic category IV [DC IV] — according to Bethesda System) were established. Surgical treatment was undertaken after first FNAB in six cases, giving confirmation of a neoplasm in five cases, one of which was a follicular carcinoma. Second FNAB performed in 90 patients confirmed DC IV diagnosis in 53 cases. Third FNAB concerned 26 patients, providing another 14 diagnoses of DC IV. 26 out of 352 patients were subjected to surgery, and then histopathological examination confirmed a neoplasm in 19 cases (which comprises 73%), five of which were carcinomas. Conclusions: High positive predictive value PPV = 73% of SFN diagnosis justifies undertaking surgical treatment in any case of this diagnosis. (Endokrynol Pol 2016; 67 (1): 17–22)    Wstęp: Materiał cytologiczny biopsji aspiracyjnej cienkoigłowej (BAC) tarczycy nie pozwala na zróżnicowanie raków pęcherzykowych, gruczolaków i guzków rozrostowych. Ograniczeniem metody jest brak możliwości określenia obecności torebki guza, jej ewentualnego nacieku oraz angioinwazji. Jednoznaczne rozstrzygnięcie czy mamy do czynienia ze zmianą nowotworową czy łagodną jest możliwe dopiero po badaniu histopatologicznym. Celem pracy było uzasadnienie celowości używania terminu „podejrzenie nowotworu pęcherzykowego” w diagnostyce cytologicznej raka tarczycy. Materiał i metody: Poddano analizie 352 wyniki BAC tarczycy wykonanych w Instytucie Onkologii (IO) w Gliwicach w latach 2010–2015 i ich korelację z rozpoznaniem histopatologicznym. Wyniki: W IO rozpoznanie podejrzenie nowotworu pęcherzykowego (grupa IV wg Systemu Bethesda) postawiono pierwotnie w 352 przypadkach. Leczenie operacyjne podjęto po pierwszej BAC w 6 przypadkach uzyskując potwierdzenie nowotworu w 5 przypadkach w tym jednego raka pęcherzykowego. Powtórna BAC przeprowadzona u 90 pacjentów potwierdziła rozpoznanie grupy IV w 53 przypadkach. Trzecią BAC przeprowadzono u 26 chorych, uzyskując kolejnych 14 rozpoznań grupy IV. Leczeniu operacyjnemu poddano 26 pacjentów na 352 rozpoznania nowotworu pęcherzykowego, uzyskując potwierdzenie nowotworu w 19 przypadkach, co stanowi 73% w tym raka 5 razy. Wnioski: Wysoka dodatnia wartość predykcyjna PPV = 73% rozpoznania „podejrzenie nowotworu pęcherzykowego” uzasadnia podjęcie leczenia operacyjnego w każdym przypadku tego rozpoznania. (Endokrynol Pol 2016; 67 (1): 17–22)

Kliniczne znaczenie rozpoznania zmiany pęcherzykowej bliżej nieokreślonej (grupa III wg Systemu Bethesda) w biopsji aspiracyjnej cienkoigłowej (BAC)

  Introduction: Follicular Lesion of Undetermined Significance (FLUS) belongs to the most controversial category of the Bethesda System. The aim of the study was to specify the risk of malignancy in patients with FLUS diagnosis in the material from the Institute of Oncology in Gliwice. This is the first Polish study specifying the risk of malignant neoplasm presence when Fine-Needle Aspiration Biopsy (FNAB) results in a report of diagnostic category III (DC III). Material and methods: Three hundred and ninety-five primary DC III diagnoses from FNABs of the thyroid gland performed from 2010 to 2015 were analysed. Correspondence of DC III with diagnoses from repeated FNABs and histopathology reports was evaluated. Results: From 395 DC III patients, 27 were treated surgically for clinical indications, receiving six diagnoses of cancer. Repeat FNAB was performed in 180 cases, and primary diagnosis was confirmed in 41 cases. In the second FNAB there was one diagnosis of “Papillary Thyroid Carcinoma” and one “Suspicious for Papillary Thyroid Carcinoma”. From eight patients treated surgically in these series prior cytological cancer diagnosis was confirmed in two cases. Forty-six patients were subjected to third and subsequent FNABs; in one case the diagnosis was “Suspicious for Malignancy”. In the analysed material the risk of cancer in patients with FLUS is 2.78%. Taking into account all 56 subsequent FNABs in which the primary diagnosis was confirmed, the risk decreases to 2.43%. Conclusions: The diagnosis of FLUS in the absence of clinical indications is not a basis for surgical treatment. (Endokrynol Pol 2016; 67 (1): 12–16)    Wstęp: Zmiana pęcherzykowa bliżej nieokreślona (grupa III) należy do najbardziej kontrowersyjnej kategorii systemu Bethesda. Brak jest polskich opracowań określających stopień ryzyka wystąpienia nowotworu złośliwego po rozpoznaniu zmiany z grupy III. Celem pracy było określenie ryzyka złośliwości po rozpoznaniu zmiany pęcherzykowej bliżej nieokreślonej w materiale Centrum Onkologii w Gliwicach. Materiał i metody: Analizie poddano 395 rozpoznań z grupy III BAC tarczycy wykonanych w latach 2010–2015. Oceniono zgodność pierwotnego rozpoznania grupy III z rozpoznaniami z kolejnych BAC i wynikami badań histopatologicznych. Wyniki: Na 395 rozpoznań grupy III zoperowano ze wskazań klinicznych 27 pacjentów i rozpoznano 6 raków. Ponowną BAC wykonano w 180 przypadkach i pierwotne rozpoznanie potwierdzono w 41 przypadkach. Po drugiej BAC 2-krotnie rozpoznano raka brodawkowatego lub jego podejrzenie. U 8 operowanych w tej serii potwierdzono wcześniejsze cytologiczne rozpoznanie raka u 2. Trzecią i kolejne BAC wykonano u 46 pacjentów i w jednym przypadku podejrzewano raka. Ryzyko raka w zmianie pęcherzykowej bliżej nieokreślonej w analizowanym materiale wynosi 2,78%. Uwzględniając wszystkie powtórnie wykonane 56 BAC, w których potwierdzono pierwotne rozpoznanie grupy III, ryzyko maleje do 2,43%. Wnioski: Rozpoznanie zmiany pęcherzykowej bliżej nieokreślonej przy braku wskazań klinicznych nie jest podstawą do wszczęcia postępowania chirurgicznego. (Endokrynol Pol 2016; 67 (1): 12–16)

Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells

Background & AimsThe differentiation of stem cells to hepatocyte-like cells (HLC) offers the perspective of unlimited supply of human hepatocytes. However, the degree of differentiation of HLC remains controversial. To obtain an unbiased characterization, we performed a transcriptomic study with HLC derived from human embryonic and induced stem cells (ESC, hiPSC) from three different laboratories.MethodsGenome-wide gene expression profiles of ESC and HLC were compared to freshly isolated and up to 14days cultivated primary human hepatocytes. Gene networks representing successful and failed hepatocyte differentiation, and the transcription factors involved in their regulation were identified.ResultsGene regulatory network analysis demonstrated that HLC represent a mixed cell type with features of liver, intestine, fibroblast and stem cells. The “unwanted” intestinal features were associated with KLF5 and CDX2 transcriptional networks. Cluster analysis identified highly correlated groups of genes associated with mature liver functions (n=1057) and downregulated proliferation associated genes (n=1562) that approach levels of primary hepatocytes. However, three further clusters containing 447, 101, and 505 genes failed to reach levels of hepatocytes. Key TF of two of these clusters include SOX11, FOXQ1, and YBX3. The third unsuccessful cluster, controlled by HNF1, CAR, FXR, and PXR, strongly overlaps with genes repressed in cultivated hepatocytes compared to freshly isolated hepatocytes, suggesting that current in vitro conditions lack stimuli required to maintain gene expression in hepatocytes, which consequently also explains a corresponding deficiency of HLC.ConclusionsThe present gene regulatory network approach identifies key transcription factors which require modulation to improve HLC differentiation

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

A Conceptual Framework for the Design of Energy-Efficient Vertical Green Façades

This research aims to develop a conceptual framework for a design support model for energy-efficient vertical green façade systems with a focus on their thermal and shading performance. The model applies forecasting and backcasting methods based on an extensive literature review and analysis by the authors, with a particular focus on the energy efficiency parameters of vertical green façades. The key parameters are related to the location (climate, surroundings, orientation of the façade), system type (air gap dimensions, irrigation, structure, and substrate type) and plant characteristics (leaf area index, leaf absorptivity, foliage thickness, stomatal resistance, typical leaf dimensions, leaf emissivity, transmission coefficient, radiation attenuation) determined from actual data collected from buildings. This holistic approach changes the perception of a user and an architect while facilitating the design process. The method’s limitations result from the scarcity of comparative experimental studies. However, the proposed model can be customised for specific conditions, with an increasing number of studies testing energy efficiency parameters comparatively. The article emphasises the vital importance of vertical green façades for built environment decarbonisation and links it to a new conceptual framework to encourage designers to make greater use of vertical green systems that are fully integrated into building energy strategies

A Conceptual Framework for the Design of Energy-Efficient Vertical Green Façades

This research aims to develop a conceptual framework for a design support model for energy-efficient vertical green façade systems with a focus on their thermal and shading performance. The model applies forecasting and backcasting methods based on an extensive literature review and analysis by the authors, with a particular focus on the energy efficiency parameters of vertical green façades. The key parameters are related to the location (climate, surroundings, orientation of the façade), system type (air gap dimensions, irrigation, structure, and substrate type) and plant characteristics (leaf area index, leaf absorptivity, foliage thickness, stomatal resistance, typical leaf dimensions, leaf emissivity, transmission coefficient, radiation attenuation) determined from actual data collected from buildings. This holistic approach changes the perception of a user and an architect while facilitating the design process. The method’s limitations result from the scarcity of comparative experimental studies. However, the proposed model can be customised for specific conditions, with an increasing number of studies testing energy efficiency parameters comparatively. The article emphasises the vital importance of vertical green façades for built environment decarbonisation and links it to a new conceptual framework to encourage designers to make greater use of vertical green systems that are fully integrated into building energy strategies

Additional file 1: of Prognostic significance of RBP2-H1 variant of JARID1B in melanoma

Raw data on JARID1B expression and patients’ overall survival including the main tumor characteristics. (XLS 26 kb