The data on the expression of stem cell markers CD44, CD24, and ALDH1A1 in the breast tissue of cancer-free women is very limited and no previous studies have explored the agreement between ...pathologist and computational assessments of these markers. We compared the immunohistochemical (IHC) expression assessment for CD44, CD24, and ALDH1A1 by an expert pathologist with the automated image analysis results and assessed the homogeneity of the markers across multiple cores pertaining to each woman.
We included 81 cancer-free women (399 cores) with biopsy-confirmed benign breast disease in the Nurses' Health Study (NHS) and NHSII cohorts. IHC was conducted with commercial antibodies CD44 (Dako, Santa Clara, CA, USA) 1:25 dilution; CD24 (Invitrogen, Waltham, MA, USA) 1:200 dilution and ALDH1A1 (Abcam, Cambridge, United Kingdom) 1:300 dilution. For each core, the percent positivity was quantified by the pathologist and Definiens Tissue Studio. Correlations between pathologist and computational scores were evaluated with Spearman correlation (for categorical positivity: 0, >0-<1, 1-10, >10-50, and >50%) and sensitivity/specificity (for binary positivity defined with 1 and 10% cut-offs), using the pathologist scores as the gold standard. Expression homogeneity was examined with intra-class correlation (ICC). Analyses were stratified by core normal terminal duct-lobular units (TDLUs), benign lesions and tissue type (epithelium, stroma).
Spearman correlation between pathologist and Definiens ranged between 0.40-0.64 for stroma and 0.66-0.68 for epithelium in normal TDLUs cores and between 0.24-0.60 for stroma and 0.61-0.64 for epithelium in benign lesions. For stroma, sensitivity and specificity ranged between 0.92-0.95 and 0.24-0.60, respectively, with 1% cut-off and between 0.43-0.88 and 0.73-0.85, respectively, with 10% cut-off. For epithelium, 10% cut-off resulted in better estimates for both sensitivity and specificity. ICC between the cores was strongest for CD44 for both stroma and epithelium in normal TDLUs cores and benign lesions (range 0.74-0.80). ICC for CD24 and ALDH1A ranged between 0.42-0.63 and 0.44-0.55, respectively.
Our findings show that computational assessments for CD44, CD24, and ALDH1A1 exhibit variable correlations with manual assessment. These findings support the use of computational platforms for IHC evaluation of stem cell markers in large-scale epidemiologic studies. Pilot studies maybe also needed to determine appropriate cut-offs for defining staining positivity.
To evaluate effects of prematurity on early optic nerve (ON) development and the usefulness of ON parameters as indicators of central nervous system (CNS) development and pathology.
Prospective, ...cross-sectional, longitudinal study.
Forty-four preterm infants undergoing retinopathy of prematurity (ROP) screening and 52 term infants.
We analyzed ON from portable handheld spectral-domain optical coherence tomography (SD-OCT) images (Bioptigen, Inc, Research Triangle Park, NC) of 44 preterm and 52 term infants. The highest-quality ON scan from either eye was selected for quantitative analysis. Longitudinal analysis was performed at 31-36 weeks and 37-42 weeks postmenstrual age (PMA). Preterm ON parameters also were assessed for correlation with indicators of cognitive, language, and motor development and CNS pathology.
Vertical cup diameter (vCD), vertical disc diameter (vDD), vertical cup-to-disc ratio (vCDR), cup depth, and indicators of neurocognitive development and CNS pathology.
At 37-42 weeks PMA, preterm infants had larger vCD and vCDR than term infants (908 vs. 700 μm P<0.001 and 0.68 vs. 0.53 μm P<0.001, respectively), whereas cup depth and vDD were not significantly different. Longitudinal changes (n = 26 preterm eyes; mean interval, 4.7 weeks) in vDD and in vCDR were an increase of 74 μm (P = 0.008) and decrease of 0.05 (P = 0.015), respectively. In preterm infants (n = 44), periventricular leukomalacia was associated with larger vCD (1084 vs. 828 μm; P = 0.005) and vCDR (0.85 vs. 0.63; P<0.001), posthemorrhagic hydrocephalus was associated with shallower cup (331 vs. 456 μm; P = 0.030), and clinical magnetic resonance imaging was associated with larger vCDR (0.73 vs. 0.64; P = 0.023). In 23 preterm infants with Bayley Scales of Infant Development scores, larger vCDR was associated with lower cognitive scores (P = 0.049).
This is the first analysis of ON parameters in premature infants using SD-OCT. It demonstrated that by age of term birth, vCD and vCDR are larger in preterm infants who were screened for ROP than in term infants. In this prospective pilot study, ON parameters in these preterm infants associate weakly with CNS pathology and future cognitive development. Future prospective studies with larger numbers are necessary before further conclusions can be made.
The cultivation of college students’ intercultural communication competence (ICC) for sustainable development is a hot research topic in English foreign language (EFL) education. What competencies ...are they required to have, and how to cultivate them in EFL education? The study is based on Byram’s model of ICC for cultivating students’ ICC for their sustainable development. To this end, an empirical study was conducted by constructing an intercultural comparative teaching mode called Input-Comparison-Output (ICO) in the research by integrating Chinese culture into EFL education for cultivating students’ ICC among Chinese college students. The study emphasizes the importance of the Chinese culture as the native culture by comparing similarities and differences with the targeted culture in EFL education. There are some existing research works on English and its culture, but few of them focus on the role and integration of Chinese culture in China’s EFL teaching. In order to seek some evidence of the function of the Chinese culture as the first culture in EFL education, the authors constructed the ICO intercultural mode, and 58 participants were recruited and divided into two groups randomly as the controlled group and experimental group in the empirical study. Some research methods were used in the study, such as questionnaires, term papers, statistical analyses and interviews. The data were collected through the Star of Questionnaire, the automatic assessing system of the I-write Platform, Excel and WeChat videos. Quantitative and qualitative statistics were adopted to assess the students’ changes of attitudes towards the integration of the Chinese culture into the course and academic development in the research. The ICO intercultural mode creates a novel teaching mode of cultural comparison between first culture and targeted culture, breaking down the traditional monocultural teaching one in the EFL teaching. The results of the research show that the integration of the Chinese culture into the EFL course is important, which can promote the students’ ICC thanks to the application of the ICO intercultural mode in the course. The initiative findings can be used as references for further intercultural teaching in EFL education.
The novel coronavirus pneumonia COVID-19 is characterized by all age susceptibility, which imposes a dramatic threat to the human species all over the world. According to current available data, the ...cytokine storm appears to be the most life-threatening symptom of severe COVID-19 cases accompanied with lung fibrosis. Galectin-3 (Gal-3), a member of soluble β-galactoside-binding lectin families, has been implicated as a key regulator in various inflammation conditions in addition to its well-documented roles in cancer. The pro-inflammatory activity of Gal-3 in the inflammatory response and lung fibrosis of COVID-19 has been proposed by emerging studies, which suggested that inhibition of Gal-3 may represent a novel treatment approach for COVID-19 patients. Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis. ICC accounts for 10–25% of primary liver cancers with limited therapeutic options, which has higher incidence in Asian countries, particularly in China. Cancer patients, including ICC patients, are highly vulnerable to COVID-19 due to their impaired immune system. It is thus undoubtedly a challenge for our oncology department to establish effective treatment strategies under the influence of the COVID-19 crisis. According to our management procedures in the COVID-19 era, emergency treatment will be applied to ICC patients who are under life-threatening conditions, despite the COVID-19 infection. To the best of our knowledge, the modulatory function of Gal-3 in ICC is still barely explored to date. In order to evaluate the therapeutic potential of Gal-3 for ICC patients or those comprised with COVID-19, we herein report our preliminary investigation into roles of Gal-3 in ICC. Our results exhibited that the expression of Gal-3 was significantly up-regulated in ICC tissues, and a significant correlation was observed between its overexpression and malignant progression of ICC cells. We further discussed the activity and possible molecular mechanisms of Gal-3 in ICC, which may pave the ways for further exploring the possibility of Gal-3 as a potential therapeutic target for treating ICC patients or those with COVID-19-related conditions.
Objectives
The intra-class correlation coefficient (ICC) is a measure of intra-subject clustering effects. A priori estimates of the ICC and the associated design effect (DE) are required for sample ...size estimation in clustered studies, and should be considered during their analysis, too. We aimed to determine the clustering effects of carious lesions, apical lesions, periodontal bone loss, and periodontal pocketing, assessed in clinical or radiographic examinations.
Methods
A subsample of patients (
n
= 175) enrolled in the fifth German Oral Health Study provided data on clinically determined carious teeth (i.e., with untreated carious lesions, WHO method) as well as teeth with periodontal pocketing (i.e., with maximum probing-pocket-depths ≥ 4 mm). A sample of panoramic radiographs (
n
= 85) from randomly chosen patients, examined from 2010 to 2017 at the Charité dental hospital, provided data on radiographically determined carious teeth (i.e., with lesions extending into dentine or enamel), teeth with apical lesions (determined by dentists via majority vote), and teeth with periodontal bone loss (≥ 20% of root-length). The ICC and its 95% confidence interval (95% CI) were determined.
Results
There were 3839 and 1961 teeth assessed in clinical and radiographic evaluations, respectively. For clinically or radiographically determined carious lesions, the ICC (95% CI) was 0.20 (0.16–0.24) or 0.19 (0.14–0.25), respectively. For clinical pocketing or radiographic bone loss, the ICC was 0.40 (0.35–0.46) or 0.30 (0.24–0.38), respectively. The lowest ICC was found for apical lesions at 0.08 (0.06–0.13).
Conclusions
The ICC varied between assessment methods and conditions. Clustered trials should account for this during study planning and data analysis.
Clinical relevance
Within the limitations of this study, and considering the risk of selection bias and the limited sample sizes of both datasets, clustering effects were substantial but varied between dental conditions. Studies not accounting for this during planning and analysis may yield misleading estimates if clustering is present.
The objective of this study was to evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differentiating combined hepatocellular cholangiocarcinomas (CHCs) from hepatocellular ...carcinomas (HCCs) and intrahepatic cholangiocarcinomas (ICCs).
Thirty-three patients with pathologically confirmed CHC and matched control subjects with pathologically confirmed HCC (n = 30) or ICC (n = 32) who underwent preoperative CEUS from January 2005 to December 2015 were enrolled in this study. The CEUS images of the hepatic lesions were subjectively analyzed in consensus by two radiologists. The diagnostic performances were evaluated by ROC analysis.
In the arterial phase, hyperenhancement was more common in CHCs (76%) and HCCs (100%) than in ICCs (22%), whereas in the late phase marked washout was more common in CHCs (76%) and ICCs (100%) than in HCCs (10%). Using marked washout in the late phase to differentiate CHC from HCC, the area under the ROC curve (AUC) was 0.829, and the sensitivity, specificity, and accuracy were 78%, 90%, and 83%, respectively. Using hyperenhancement in the arterial phase followed by marked washout in the late phase to distinguish CHC from ICC, the AUC value was 0.663, and the sensitivity, specificity, and accuracy were 55%, 78%, and 66%.
Although the imaging features of CHC, HCC, and ICC on CEUS may overlap, CEUS could be used in the differential diagnosis of CHC from HCC and ICC.
Abstract Repetitive falls degrade the quality of life of elderly people and of patients suffering of various neurological disorders. In order to prevent falls while walking, one should rely on ...relevant early indicators of impaired dynamic balance. The local dynamic stability (LDS) represents the sensitivity of gait to small perturbations: divergence exponents (maximal Lyapunov exponents) assess how fast a dynamical system diverges from neighbor points. Although numerous findings attest the validity of LDS as a fall risk index, reliability results are still sparse. The present study explores the intrasession and intersession repeatability of gait LDS using intraclass correlation coefficients (ICC) and standard error of measurement (SEM). Ninety-five healthy individuals performed 5 min treadmill walking in two sessions separated by 9 days. Trunk acceleration was measured with a 3D accelerometer. Three time scales were used to estimate LDS: over 4–10 strides ( λ4–10 ), over one stride ( λ1 ) and over one step ( λ0.5 ). The intrasession repeatability was assessed from three repetitions of either 35 strides or 70 strides taken within the 5 min tests. The intersession repeatability compared the two sessions, which totalized 210 strides. The intrasession ICCs (70-strides estimates/35-strides estimates) were 0.52/0.18 for λ4–10 and 0.84/0.77 for λ1 and λ0.5 . The intersession ICCs were around 0.60. The SEM results revealed that λ0.5 measured in medio-lateral direction exhibited the best reliability, sufficient to detect moderate changes at individual level (20%). However, due to the low intersession repeatability, one should average several measurements taken on different days in order to better approximate the true LDS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In times of economic stringency, the prerequisite for the provision of healthcare services differentiated by complexity is identified in the right patients' allocation. Since access to high-intensity ...care units is restricted, it is necessary both to promptly diagnose patients who are at risk of rapid clinical deterioration or death and to define criteria to identify the correct allocation of patients based on clinical-care needs. Although the so-called "early warning scores" were used by healthcare professionals to alert medical staff, nowadays, they can also be used as decision rules for managing patient admissions, increasing their effective usefulness. The procedure for assessing the complexity of care profiles needs to be based on a multidisciplinary approach. The primary objective of scientific research was to determine the intensity of care (clinical instability and care dependence) of the patients allocated in different settings of the medical area. To correctly frame the phenomenon, the main methods and strategies developed for different care models were discussed. In the Italian healthcare organization, the indicators, methodologies and tools to evaluate the clinical-care complexity were identified and subsequently applied. In conclusion, the findings and proposals for improvement actions are shown.
Background
Hepatitis B virus (HBV) infection is one of the most common risk factors for intrahepatic cholangiocarcinoma (ICC). However, there is no direct evidence of a causal relationship between ...HBV infection and ICC. In this study, we attempted to prove that ICC may originate from hepatocytes through a pathological study involving ICC tissue-derived organoids.
Method
The medical records and tumor tissue samples of 182 patients with ICC after hepatectomy were collected. The medical records of 182 patients with ICC were retrospectively analyzed to explore the prognostic factors. A microarray of 182 cases of ICC tumor tissue and 6 cases of normal liver tissue was made, and HBsAg was stained by immunohistochemistry (IHC) to explore the factors closely related to HBV infection. Fresh ICC tissues and corresponding adjacent tissues were collected to make paraffin sections and organoids. Immunofluorescence (IF) staining of factors including HBsAg, CK19, CK7, Hep-Par1 and Albumin (ALB) was performed on both fresh tissues and organoids. In addition, we collected adjacent nontumor tissues of 6 patients with HBV (+) ICC, from which biliary duct tissue and normal liver tissue were isolated and RNA was extracted respectively for quantitative PCR assay. In addition, the expression of HBV-DNA in organoid culture medium was detected by quantitative PCR and PCR electrophoresis.
Results
A total of 74 of 182 ICC patients were HBsAg positive (40.66%, 74/182). The disease-free survival (DFS) rate of HBsAg (+) ICC patients was significantly lower than that of HBsAg (−) ICC patients (
p
= 0.0137). IF and IHC showed that HBsAg staining was only visible in HBV (+) ICC fresh tissues and organoids, HBsAg expression was negative in bile duct cells in the portal area. Quantitative PCR assay has shown that the expression of HBs antigen and HBx in normal hepatocytes were significantly higher than that in bile duct epithelial cells. Combined with the IF and IHC staining, it was confirmed that HBV does not infect normal bile duct epithelial cells. In addition, IF also showed that the staining of bile duct markers CK19 and CK7 were only visible in ICC fresh tissue and organoids, and the staining of hepatocyte markers Hep-Par1 and ALB was only visible in normal liver tissue fresh tissue. Real-time PCR and WB had the same results. High levels of HBV-DNA were detected in the culture medium of HBV (+) organoids but not in the culture medium of HBV (−) organoids.
Conclusion
HBV-related ICC might be derived from hepatocytes. HBV (+) ICC patients had shorter DFS than HBV (−) ICC patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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