Angular two-photon interference and angular two-qubit states

Using angular-position-orbital-angular-momentum entangled photons, we study angular two-photon interference in a scheme in which entangled photons are made to pass through apertures in the form of double angular slits, and using this scheme, we demonstrate an entangled two-qubit state that is based on the angular-position correlations of entangled photons. The entanglement of the two-qubit state is quantified in terms of concurrence. These results provide an additional means for preparing entangled quantum states for use in quantum information protocols

Novel histological scoring for predicting disease outcome in primary sclerosing cholangitis

Background Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease that may lead to liver cirrhosis or cholangiocarcinoma. Liver histology and fibrosis stage are predictive markers of disease progression, and histological cirrhosis is defined as a significant endpoint. PSC-specific histological scoring methods are lacking at present. We aimed to develop a tailored classification system for PSC, the PSC histoscore, based on histological features associated with disease progression. Methods In total, 300 PSC patients diagnosed between 1988 and 2018 were enrolled; their data were collected from the PSC registry (Helsinki University Hospital), and liver specimens were obtained from the Biobank of Helsinki. Five histological features included in the adapted Nakanuma scoring system and three additional parameters typical for PSC histology were evaluated and compared with the clinical and laboratory data. A compound endpoint consisting of liver transplantation, development of cholangiocarcinoma, or death was used as outcome measurement. Results Stage (fibrosis, bile duct loss, ductular reaction, and chronic cholestasis) and grade (portal inflammation, portal edema, hepatitis activity, and cholangitis activity) parameters were found to be independent predictive risk factors for the compound endpoint (P < 0.001). High disease grade (2-6) and stage (2-4) better correlated with clinical endpoints when evaluated with the PSC histoscore system compared to the adapted Nakanuma classification. The risk for disease progression in sequential endoscopic retrograde cholangiography (ERC) examinations was increased with elevated total PSC histoscores. Conclusion The PSC histoscore is a novel histological classification system for PSC. Our findings support the applicability of liver histology as a marker for disease progression.Peer reviewe

A prospective randomised study of dense Infinity cytological brush versus regularly used brush in pancreaticobiliary malignancy

Peer reviewe

Surveillance of primary sclerosing cholangitis with ERC and brush cytology : risk factors for cholangiocarcinoma

Objective: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to bile duct strictures and fibrosis, and predisposing to cholangiocarcinoma (CCA). Biliary dysplasia is a known precursor of CCA. In our unit, PSC patients undergo regular surveillance with ERC and brush cytology (BC), and liver transplantation is an option in case with biliary dysplasia. We evaluated the risk factors for biliary dysplasia and CCA based on ERC imaging, BC and liver function tests. Patients and methods: Seven hundred and eighty-eight ERCs were performed with BC for 447 PSC patients. ERC images were evaluated using the modified Amsterdam score, neutrophilic inflammation was assessed in BC, and liver function tests were collected. Ploidy analysis with DNA flow cytometry was performed in cases with advanced PSC or previous suspicious BC/aneuploidy. The endpoint was either a benign disease course (follow-up for >= 2.4 years after the latest ERC), benign histology, biliary dysplasia or CCA. Results: Benign disease course was seen in 424/447 (including 23 cases with biliary dysplasia), and CCA in 17 (3.8%) patients. Gallbladder carcinoma/carcinoma in situ was diagnosed in three patients. Advanced ERC findings, male gender, suspicious BC, aneuploidy in flow cytometry, inflammation, and elevation of ALP, bilirubin, ALT, AST, GGT, CEA and CA19-9 represented significant risk factors for CCA in univariate analysis. Conclusions: PSC patients with advanced bile duct disease and elevated liver enzymes, CEA or CA19-9, inflammation or suspicious BC are most likely to develop CCA. These patients may benefit from surveillance with BC if early liver transplantation is possible.Peer reviewe

Adapt locally and act globally: strategy to maintain high chemoreceptor sensitivity in complex environments

In bacterial chemotaxis, several types of receptors form mixed clusters. Receptor adaptation is shown to depend on the receptor's own conformational state rather than on the cluster's global activity, enabling cells to differentiate stimuli in complex environments

Automated image analysis of keratin 7 staining can predict disease outcome in primary sclerosing cholangitis

Background and AimsPrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that obstructs the bile ducts and causes liver cirrhosis and cholangiocarcinoma. Efficient surrogate markers are required to measure disease progression. The cytokeratin 7 (K7) load in a liver specimen is an independent prognostic indicator that can be measured from digitalized slides using artificial intelligence (AI)-based models. MethodsA K7-AI model 2.0 was built to measure the hepatocellular K7 load area of the parenchyma, portal tracts, and biliary epithelium. K7-stained PSC liver biopsy specimens (n = 295) were analyzed. A compound endpoint (liver transplantation, liver-related death, and cholangiocarcinoma) was applied in Kaplan-Meier survival analysis to measure AUC values and positive likelihood ratios for each histological variable detected by the model. ResultsThe K7-AI model 2.0 was a better prognostic tool than plasma alkaline phosphatase, the fibrosis stage evaluated by Nakanuma classification, or K7 score evaluated by a pathologist based on the AUC values of measured variables. A combination of parameters, such as portal tract volume and area of K7-positive hepatocytes analyzed by the model, produced an AUC of 0.81 for predicting the compound endpoint. Portal tract volume measured by the model correlated with the histological fibrosis stage. ConclusionsThe K7 staining of histological liver specimens in PSC provides significant information on disease outcomes through objective and reproducible data, including variables that cannot be measured by a human pathologist. The K7-AI model 2.0 could serve as a prognostic tool for clinical endpoints and as a surrogate marker in drug trials.Peer reviewe

Chronic cholestasis detection by a novel tool : automated analysis of cytokeratin 7-stained liver specimens

Background The objective was to build a novel method for automated image analysis to locate and quantify the number of cytokeratin 7 (K7)-positive hepatocytes reflecting cholestasis by applying deep learning neural networks (AI model) in a cohort of 210 liver specimens. We aimed to study the correlation between the AI model's results and disease progression. The cohort of liver biopsies which served as a model of chronic cholestatic liver disease comprised of patients diagnosed with primary sclerosing cholangitis (PSC). Methods In a cohort of patients with PSC identified from the PSC registry of the University Hospital of Helsinki, their K7-stained liver biopsy specimens were scored by a pathologist (human K7 score) and then digitally analyzed for K7-positive hepatocytes (K7%area). The digital analysis was by a K7-AI model created in an Aiforia Technologies cloud platform. For validation, values were human K7 score, stage of disease (Metavir and Nakunuma fibrosis score), and plasma liver enzymes indicating clinical cholestasis, all subjected to correlation analysis. Results The K7-AI model results (K7%area) correlated with the human K7 score (0.896; p < 2.2e(- 16)). In addition, K7%area correlated with stage of PSC (Metavir 0.446; p < 1.849e(- 10) and Nakanuma 0.424; p < 4.23e(- 10)) and with plasma alkaline phosphatase (P-ALP) levels (0.369, p < 5.749e(- 5)). Conclusions The accuracy of the AI-based analysis was comparable to that of the human K7 score. Automated quantitative image analysis correlated with stage of PSC and with P-ALP. Based on the results of the K7-AI model, we recommend K7 staining in the assessment of cholestasis by means of automated methods that provide fast (9.75 s/specimen) quantitative analysis.Peer reviewe

Metabolic profile of liver damage in non-cirrhotic virus C and autoimmune hepatitis : A proton decoupled P-31-MRS study

Purpose: To study liver P-31 MRS, histology, transient elastography, and liver function tests in patients with virus C hepatitis (HCV) or autoimmune hepatitis (AIH) to test the hypothesis that P-31 MR metabolic profile of these diseases differ. Materials and methods: 25 patients with HCV (n = 12) or AIH (n = 13) underwent proton decoupled P-31 MRS spectroscopy performed on a 3.0 T MR imager. Intensities of phosphomonoesters (PME) of phosphoethanolamine (PE) and phosphocholine (PC), phosphodiesters (PDE) of glycerophosphoethanolamine( GPE) and glycerophosphocholine (GPC), and gamma, alpha and beta resonances of adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide phosphate (NADPH) were determined. Liver stiffness was measured by transient elastography. Inflammation and fibrosis were staged according to METAVIR from biopsy samples. Activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALT) and thromboplastin time (TT) were determined from serum samples. Results: PME had a stronger correlation with AST (z = 1.73, p = 0.04) and ALT (z = 1.77, p = 0.04) in HCV than in AIH patients. PME, PME/PDE, PE/GPE correlated positively and PDE negatively with inflammatory activity. PE, PC and PME correlated positively with liver function tests. Conclusion: P-31-MRS suggests a more serious liver damage in HCV than in AIH with similar histopathological findings. P-31-MRS is more sensitive in detecting inflammation than fibrosis in the liver. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Mechanical Faraday effect for orbital angular momentum-carrying beams

When linearly polarised light is transmitted through a spinning window, the plane of polarisation is rotated. This rotation arises through a phase change that is applied to the circularly polarised states corresponding to the spin angular momentum (SAM). Here we show an analogous effect for the orbital angular momentum (OAM), where a differential phase between the positive and negative modes (±ℓ) is observed as a rotation of the transmitted image. For normal materials, this rotation is on the order of a micro radian, but by using a slow-light medium, we show a rotation of a few degrees. We also note that, within the bounds of our experimental parameters, this rotation angle does not exceed the scale of the spatial features in the beam profile

Suspicious brush cytology is an indication for liver transplantation evaluation in primary sclerosing cholangitis

AIM To investigate markers for high-grade dysplasia for the optimal timing of liver transplantation in patients with primary sclerosing cholangitis (PSC). METHODS Earlier data support a dysplasia-carcinoma sequence, even low-to high-grade dysplasia, in PSC-associated cholangiocarcinoma (CCA). Surveillance using endoscopic retrograde cholangiography (ERC) and brush cytology aims to detect cases of biliary dysplasia, and liver transplantation is an option in cases with suspicion of malignancy in brushing. This study investigated markers to identify patients with high-grade biliary dysplasia for optimal timing in early liver transplantation. Patients undergoing surveillance using ERC and brush cytology during 2008-2014 and who were diagnosed with biliary dysplasia in explanted liver or CCA until February 2016 were included in the study. Demographic data, cholangiography findings, laboratory values, cytological morphology and DNA ploidy were analysed. RESULTS Thirty PSC patients had biliary neoplasia in the explanted liver during the study period. Sixteen of these patients had low-grade dysplasia, 10 patients had high-grade dysplasia, and 4 patients had CCA. Fifteen PSC patients diagnosed with CCA were not transplanted. Patients with low-grade dysplasia were younger. Alkaline phosphatase or carcinoembryonic antigen values did not differ between groups during surveillance, but carbohydrate antigen 19-9 was higher in CCA patients. No difference in PSC duration, ERC scores, suspicious cytology, or ploidy analysis was found between groups. No difference was observed between fibrosis stage in explanted livers. Low-and high-grade dysplasia could not be differentiated before liver transplantation based on liver enzymes, tumour markers, ERC scores, brush cytology or DNA ploidy. CONCLUSION Repeated suspicion of neoplasia in brush cytology should be an indication for evaluations of liver transplantation prior to the development of CCA.Peer reviewe