Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer

Background and aims: Chromosomal instability (CIN) is recognised as a hallmark of cancer and is caused by a spindle assembly checkpoint disorder or chromosome mis-segregation during mitosis. Although the recent identification of human shugoshin (hSgo1), an important player in proper chromosome segregation, has suggested the involvement of hSgo1 in colorectal tumourigenesis, little is known about how it is involved. The aim of this study was to obtain information about the status of hSgo1 in human colorectal cancer. Method and results: Among the 46 colorectal cancer cases, hSgo1 mRNA expression was decreased in the tumour tissue in comparison with the corresponding normal tissue (p = 0.032). Human Sgo1-downregulated tumours (tumour to normal mucosa ratio<0.5) had preferential location on the left side large bowel rather than on the right side (p = 0.012), and a higher variation of centromere numbers revealed by fluorescence in situ hybridisation (FISH). To assess the effects of hSgo1 downregulation, hSgo1 knockdown was performed by transfecting the diploid HCT116 cell line with a short hairpin RNA expression vector. hSgo1 knockdown cells proliferated slowly because of both G2/M arrest and apoptosis (p<0.001), and markers of CIN in the form of aneuploidy (p<0.001) and micronuclei (p<0.005) were later observed in hSgo1 knockdown cells. Increased centrosome amplification (p<0.05), the presence of binucleated cells and mitotic catastrophes were also noted in hSgo1 knockdown cells. Conclusions: These findings suggest that hSgo1-downregulated colorectal cancers have a clinicopathological character of CIN, and hSgo1 downregulation leads to CIN in colorectal cancer cells.
A Clinical Analysis of Patients with Premature Ovarian Failure: Compliance with Hormonal Treatment

조기폐경은 40세 이전에 폐경이 되는 것으로, 빈도는 약 1% 정도로 보고되고 있다. 일반적으로 폐경은 호르몬 감 소와 관련된 많은 퇴행성 변화를 일으키며, 40세 이전의 여 성에서 폐경을 겪는 경우, 이러한 노화 과정에 보다 더 취 약할 수 있다. 이의 원인으로는 염색체 이상이나 방사선치 료, 항암치료, 수술 등으로 인한 의인성 원인 및 감염, 자가 면역질환, 대사이상, 흡연 등이 알려져 있으나, 대부분은 원 인 불명인 경우가 많다. 조기폐경의 경우 다양한 정도의 에스트로겐 결핍 증상을 보일 수 있으며, 영구적인 폐경과 달리 난소 기능이 일부 호전되는 경우도 있어, 5-10%에서 는 자연 임신 가능성이 있을 수 있고, 일부에서는 난자 공여 를 통해 임신을 하기도 한다. 이러한 조기폐경 여성에서 는 심혈관계 질환, 신경학적인 질환, 정신과학적인 질환 및 골다공증뿐 아니라 기타 퇴행성 변화가 일어날 가능성이 높 고, 전체적인 사망률도 증가할 수 있는 것으로 알려져 있으 며, 특히 폐경이 되는 시점이 빠를수록 이러한 위험도는 증 ISSN 1226-8704 http://dx.doi. org/10.6118/jksm.2013. 19.2. 87 J Korean Soc Menopause 2013;19:87-92
Toll-like receptors as targets in chronic liver diseases

Toll-like receptors (TLRs) recognise pathogen-associated molecular patterns (PAMPs) to detect the presence of pathogens. In addition to their role in innate immunity, TLRs also play a major role in the regulation of inflammation, even under sterile conditions such as injury and wound healing. This involvement has been suggested to depend, at least in part, on the ability of TLRs to recognise several endogenous TLR ligands termed damage-associated molecular patterns (DAMPs). The liver not only represents a major target of bacterial PAMPs in many disease states but also upregulates several DAMPs following injury. Accordingly, TLR-mediated signals have been implicated in a number of chronic liver diseases. Here, we will summarise recent findings on the role TLRs and TLR ligands in the pathophysiology of liver fibrosis and cirrhosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease and hepatocellular carcinoma, and highlight the potential role of TLR agonists, antagonists and probiotics for the treatment of chronic liver disease.
Comparing optical-flow based methods for quantification of myocardial deformations on RT3D ultrasound

Quantitative analysis of cardiac motion is of great clinical interest in assessing ventricular function. Real-time 3-D (RT3D) ultrasound transducers provide valuable three-dimensional information, from which quantitative measures of cardiac function can be extracted. Such analysis requires segmentation and visual tracking of the left ventricular endocardial border. Previously, we presented a method based on four-dimensional optical flow motion estimation for temporal tracking of ventricular borders in RT3D ultrasound. A myocardial displacement field and dynamic cardiac metrics were computed by interpolating the boundary tracking results. In this paper, we propose three additional methods for deriving dynamic cardiac information from tracking ventricular surfaces and demonstrate these methods on a clinical dataset
Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue

Background: The antitumoral immune response is one determinant of colorectal cancer (CRC) outcome. Recent work suggests that Foxp3+CD25+CD4+ regulatory T cells (T4reg) might hamper effective immunosurveillance of emerging cancer cells and impede effective immune responses to established tumours. In this descriptive study, we analysed blood and tissue regulatory T cell populations in patients with CRC. Methods: Blood and tissue regulatory Foxp3+ T cells from 40 patients with CRC were compared to regulatory Foxp3+ T cells from normal colonic tissue and from blood of 26 healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3+ T cell populations. Correlations were sought with the tumour stage and with micro-invasive status. The suppressive capacity of regulatory Foxp3+ T cells was assessed by their effect on CD4+CD25− T cell proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells. Results: We found a significant increase of CD8+CD25+Foxp3+ cells (T8reg) in blood and CRC tissue; their phenotype was close to that of T4reg. T8reg cells infiltrating CRC were activated, as suggested by increased cytoxic T lymphocyte-associated antigen-4, glucocorticoid-induced tumour necrosis factor-related protein, and transforming growth factor (TGF)β1 expression compared to T8reg from normal autologous colonic tissue. Moreover, T8reg were able to suppress CD4+CD25− T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumour-infiltrating T8reg have strong suppressive capacities. T8reg numbers correlated with the tumour stage and with micro-invasive status. Finally, interleukin 6 and TGFβ1 synergistically induced the generation of CD8+CD25+Foxp3+ T cells ex vivo. Conclusions: We have identified a new regulatory T cell population (CD8+Foxp3+) in colorectal tumours. After isolation from cancer tissue these CD8+Foxp3+ cells demonstrated strong immunosuppressive properties in vitro. These data suggest that these cells may contribute to tumoral immune escape and disease progression.
An upper bound for the half-removal time of neutrophils from circulation.

To the editor: In the 5 May 2016 issue of Blood , Silvestre-Roig et al[1][1] explored the phenotypic heterogeneity and the versatility of neutrophils, a heterogeneity established in part by an adaptable neutrophil lifespan. As noted by the authors, the classical understanding of the neutrophil
Hyperspectral imaging system for quantitative identification and discrimination of fluorescent labels in the presence of autofluorescence

Multivariate data analysis applied to hyperspectral images offers the unique opportunity to dramatically increase the amount of information gained from a single biological sample. Numerous fluorescent tags can be used to perform multiple studies in parallel from a single hyperspectral image scan. Highly spatially and spectrally overlapping fluorophores can be separated even amidst a large autofluorescence background with the use of multivariate curve resolution methods. The results of two biological samples with multiple fluorescent labels are shown and compared to a traditional filter-based multispectral system. These examples illustrate the combined power of the hyperspectral microscope hardware and the multivariate image analysis software for biomedical imaging. This technique has the potential to be applied to a broad array of biological applications where fluorescent tags are a central and ubiquitous tool, and to biomedical areas that focus on the discovery and identification of weak, broad spectrum native fluorescence
Eficácia do regime terapêutico empregando a associação de pantoprazol, claritromicina e amoxicilina, durante uma semana, na erradicação do Helicobacter pylori em pacientes com úlcera péptica

AIM: This is an open label, multicenter trial to determine the efficacy of the association of pantoprazole, clarithromycin and amoxicillin to eradicate Helicobacter pylory in patients with peptic ulcer. MATERIAL AND METHODS: Seventy-one patients (36 females, 35 males, average age 41.9 years) from three Brazilian university centers (located in the cities of Belo Horizonte and Porto Alegre), with peptic ulcers confirmed by endoscopy, and infections by H. pylory proven by at least two diagnostic testings were admitted in the trial. An association of pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1.0 g was administered to patients twice daily for 7 days. RESULTS: By the end of treatment all patients were examined for digestive symptoms, presence of adverse events, and treatment adherence. Sixty days after the end of the treatment a new endoscopy with biopsies and respiratory function testing with 13C-urea breath test was performed in order to determine the eradication rates of that microorganism. Patients showing negative results at least in the 13C-urea breath test and in one other test (urease or histology) were considered H. pylory-negative. By the end of the trial, 60/69 (87%, CI 95% = 78.9-94.8) patients had the H. pylory eradicated in the per protocol analysis and 60/71 (84.5%, CI 95% = 76-92.9) in the intention-to-treat analysis. One patient was withdrawn from the trial due to a diarrhea. Twelve (16.9%) patients showed adverse symptoms that were deemed as mild symptoms. CONCLUSION: Our conclusion is that the association of pantoprazole, amoxicillin and clarithromycin administered during 7 days is an effective and well-tolerated alternative as regards the eradication of H. pylory in patients with peptic ulcer in Brazil.
Results from the first three rounds of the Scottish demonstration pilot of FOBT screening for colorectal cancer

Objectives: To assess the effects of the first three rounds of a pilot colorectal screening programme based on guaiac faecal occult blood testing (gFOBT) and their implications for a national population-based programme. Methods: A demonstration pilot programme was conducted in three Scottish NHS Boards. Residents aged between 50 and 69 years registered on the Community Health Index were included in the study. Results: In the first round, the uptake was 55.0%, the positivity rate was 2.07% and the cancer detection rate was 2.1/1000 screened. In the second round, these were 53.0%, 1.90% and 1.2/1000, respectively, and in the third round, 55.3%, 1.16% and 0.7/1000, respectively. In the first round, the positive predictive value of the gFOBT was 12.0% for cancer and 36.5% for adenoma; these fell to 7.0% and 30.3% in the second round and were maintained at 7.5% and 29.1% in the third round. The percentage of screen-detected cancers diagnosed at Dukes’ stage A was 49.2% in the first round, 40.1% in the second round and 36.3% in the third round. Conclusions: These results are compatible with those of previous randomised trials done in research settings, demonstrating that population-based colorectal cancer screening is feasible in Scotland and should lead to a comparable reduction in disease-specific mortality.
Bivalirudin: treatment effect versus side effect.

Alexopoulos et al. [1] presented interesting data showing that in “real-life” scenario, there are no differences in one-month outcome between bivalirudinand no bivalirudin-treated patients. When talking about bivalirudin efficacy, we have to consider two distinct features: treatment effect (antithrombotic action) and side effect (bleeding events). In HORIZONS-AMI trial, there was a reduction in cardiac mortality in the bivalirudin group that can only partly be attributed to prevention of bleeding [2]. Notwithstanding, in EUROMAX trial, there was a substantial decline in bleeding events which did not transfer into survival benefit [3]. Repeatedly, however, there was a higher incidence of stent thrombosis and a trend toward a higher incidence of myocardial infarction [3,4], despite investigators’ attempts to prevent it by prolonging bivalirudin infusion to 4 h following PCI. So actually, in terms of treatment effect, the study proved the drug not to be so efficacious. Bleeding events are independently associated with a worse long-term prognosis across a wide spectrum of patients with coronary artery disease and the risk of death progresses with increasing severity of bleeding [5,6]. However, in this instance, it would seem that we have decreased the risk of side effects (excellent safety profile) at the trade-off of increasing the risk of thrombotic events – events that, one would expect, should decline using antithrombotic agent [7]. In addition, the cost of bivalirudin far exceeds that of standard treatment, thereby calling into question the ancillary benefits of the drug that would justify its use in place of the conventional regimen. Accordingly, we emphasize caution when talking about therapeutic effect. Until then, findings should be considered signals warranting further investigation.
Increased ergothioneine tissue concentrations in carriers of the Crohn’s disease risk-associated 503F variant of the organic cation transporter OCTN1

Accumulating evidence suggests that genetic susceptibility to Crohn’s disease (CD) is driven by loss-of-function mutations in established risk genes such as IBD5 , NOD2/CARD15 , ATG16L1 or IL23R conferring defects in the innate immune response.1 2 Within the IBD5 locus, a coding variant of the organic cation transporter OCTN1 ( SLC22A4 ) has been associated with the risk of CD in Caucasian populations.3 4 However, the causal involvement of OCTN1 in CD pathogenesis is unclear, because the OCTN1 variant is in linkage disequilibrium with other IBD5 alleles, in particular with a promoter variant of the carnitine transporter OCTN2 ( SLC22A5 ). 3 We have previously demonstrated that the food ingredient ergothioneine (ET), not arising from mammalian metabolism or intestinal flora, represents the key substrate of OCTN15 and that the CD risk-associated variant 503F (1672T) exhibits a …
MiR-23a Regulates the Vasculogenesis of Coronary Artery Disease by Targeting Epidermal Growth Factor Receptor.

OBJECTIVE Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. We aimed to investigate the correlation between the levels of circulating miR-23a and the expression of epidermal growth factor receptor (EGFR) in the pathogenesis of patients with coronary heart disease to further explore the mechanism involved in its vasculogenesis. METHOD Three different cohorts, including 13 acute myocardial infarction (AMI) patients, 176 angina pectoris patients, and 127 control subjects, were enrolled to investigate the expression levels of circulating miR-23a in patients with myocardial ischemia and also the relationship between plasma miR-23a and severity of coronary stenosis. Plasma miR-23a levels of participants were examined by real-time quantitative PCR. Simultaneously, plasma cardiac troponin I (cTnI) concentrations were measured by ELISAs. We further detected the correlation of miR-23a and EGFR by molecular and animal assays. RESULT MiR-23a was enriched in not only diseased endothelial progenitor cells (EPCs) but also in the plasma of patients with coronary artery disease (CAD). Besides, we found out miR-23a was able to suppress EGFR expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-23a to the 3'-UTR of EGFR mRNA. Knockdown of miR-23a not only restored EGFR levels and angiogenic activities of diseased EPCs in vitro, but further promoted blood flow recovery in ischemic limbs of mice. CONCLUSION Circulating miR-23a may be a new biomarker for CAD and as a potential diagnostic tool. And increased miR-23a level may be used to predict the presence and severity of coronary lesions in patients with CAD.
Epac‐Rap1‐activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction

INTRODUCTION Rap1, a member of Ras superfamily of small GTP-binding proteins, is involved in cardiovascular biology in numerous ways. It is an evolutionary conserved regulator of adhesion, polarity, differentiation and growth. AIMS Our aim was to analyze Rap1-activated rat bone marrow mesenchymal stem cells (MSCs) for their potential role in adhesion and cardiac differentiation. METHODS Myocardial infarction (MI) was produced in Sprague Dawley (SD) rats through occlusion of the left anterior descending coronary artery. MSCs were treated with 8-pCPT-2'-O-Me-cAMP (CPT) to activate Rap1. Normal (untreated) and CPT-treated MSCs were transplanted through intramyocardial injection in respective groups. Cardiac function was assessed by echocardiography at 2 and 4 weeks after cell transplantation. Histological analysis was performed to observe changes at tissue level. RESULTS Homing of CPT-treated MSCs was significantly (***P<.001) higher as compared to normal MSCs in the infarcted hearts. This may be due to increase in the gene expression of some of the cell adhesion molecules as evident by qRT-PCR analysis. Significant (***P<.001) improvement in the restoration of heart function in terms of left ventricular diastolic and systolic internal diameters (LVIDd, LVIDs), % ejection fraction, % fraction shortening and end-systolic and end-diastolic volumes were observed in CPT-treated MSCs as compared to the MI model. Histological analyses showed significant (***P<.001) reduction in scar formation in the CPT-treated group. Differentiation of treated MSCs into functional cardiomyocytes was evident through immunohistochemical staining. LV wall thickness was also preserved significantly (***P<.001). Blood vessel formation was more pronounced in CPT-treated group although both cell therapy groups showed significant increase as compared to MI model. CONCLUSION Our findings showed that pharmacological activation of Epac-Rap1 improves cardiac function through better survival, adhesion and differentiation of transplanted cells. Transplantation of these MSCs in the infarct area restored functional myocardium.
A method for quantitative evaluation of statistical shape models using morphometry

We introduce a novel method for the evaluation of statistical shape models (SSM) that allows for quantifying the model quality wrt. global and local shape properties. The construction of SSM requires the identification of corresponding landmarks across a set of training shapes. Establishing such correspondence is a delicate matter and demands for automatic methods in a 3D setting. Conversely, the model quality needs to be evaluated to be able to compare different SSM in terms of specificity and generalization ability and to further improve the process of establishing correspondence. These well-known quantitative evaluation measures can be analyzed using various distance functions. The problem with popular landmark based metrics however is that the shape similarity of both the generated SSM and the actual object is disregarded. Evaluation of various models reveals that this can significantly corrupt the quality measures of the respective SSM, whereas the proposed method provides feasible results.
Comparison of anti‐mutated citrullinated vimentin, anti‐cyclic citrullinated peptides, anti‐glucose‐6‐phosphate isomerase and anti‐keratin antibodies and rheumatoid factor in the diagnosis of rheumatoid arthritis in Chinese patients

To evaluate the diagnostic value of anti‐mutated citrullinated vimentin antibodies (anti‐MCV), anti‐cyclic citrullinated peptides antibodies (anti‐CCP), anti‐glucose‐6‐phosphate isomerase antibodies (anti‐GPI) and anti‐keratin antibodies (AKA) and rheumatoid factor (RF) in rheumatoid arthritis (RA).
Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy

Background: Screening for colorectal cancer (CRC) is widely accepted, but there is no consensus on the preferred strategy. We conducted a randomised trial comparing participation and detection rates (DR) per screenee of guaiac-based faecal occult blood test (gFOBT), immunochemical FOBT (FIT), and flexible sigmoidoscopy (FS) for CRC screening. Methods: A representative sample of the Dutch population (n = 15 011), aged 50–74 years, was 1:1:1 randomised prior to invitation to one of the three screening strategies. Colonoscopy was indicated for screenees with a positive gFOBT or FIT, and for those in whom FS revealed a polyp with a diameter ⩾10 mm; adenoma with ⩾25% villous component or high grade dysplasia; serrated adenoma; ⩾3 adenomas; ⩾20 hyperplastic polyps; or CRC. Results: The participation rate was 49.5% (95% confidence interval (CI) 48.1 to 50.9%) for gFOBT, 61.5% (CI, 60.1 to 62.9%) for FIT and 32.4% (CI, 31.1 to 33.7%) for FS screening. gFOBT was positive in 2.8%, FIT in 4.8% and FS in 10.2%. The DR of advanced neoplasia was significantly higher in the FIT (2.4%; OR, 2.0; CI, 1.3 to 3.1) and the FS arm (8.0%; OR, 7.0; CI, 4.6 to 10.7) than the gFOBT arm (1.1%). FS demonstrated a higher diagnostic yield of advanced neoplasia per 100 invitees (2.4; CI, 2.0 to 2.8) than gFOBT (0.6; CI, 0.4 to 0.8) or FIT (1.5; CI, 1.2 to 1.9) screening. Conclusion: This randomised population-based CRC-screening trial demonstrated superior participation and detection rates for FIT compared to gFOBT screening. FIT screening should therefore be strongly preferred over gFOBT screening. FS screening demonstrated a higher diagnostic yield per 100 invitees than both FOBTs.
GERD: How to Have a Better Day

Gastroesophageal reflux disease (GERD) is a highly prevalent disorder in all Western countries and, in recent years, the prevalence has substantially increased in developing countries. In parallel, there is a remarkable increase of GERD-related fatal and nonfatal complications although these complications are rare on a global scale. GERD is defined by the augmented exposure of esophageal mucosa to acidic gastric content. This is associated with relevant symptoms or mucosal lesions. Symptoms do not include the typical acid-related symptoms (heartburn, acid regurgitation) but a number of atypical symptoms and even disturbances of sleep. There is now emerging evidence that impairment of sleep quality of patients with GERD is an important factor for the reduced quality of life in these patients. On the other hand, sleep and sleep disturbances are linked to the mechanisms that determine the severity of reflux. A number of other factors may contribute to the manifestation of GERD. Nutritional factors are believed to aggravate acidic reflux either by delaying gastric emptying or diminishing the pressure of the lower esophageal sphincter. However, lifestyle modifications such as dietary modifications are believed important but rarely sufficient for the long-term management. Sleeping with an elevated head is a widely used advice that is not easy to follow and has not been proven effectively with regard to the long-term outcome. Thus, medication is usually necessary for symptom control. Reduction of acid secretion with proton pump inhibitors is now mainstream treatment and 8-week complete remission rates (healing of lesions and control of symptoms) are above 80%.
Clusters of paracortical plasmacytoid dendritic cells in lupus lymphadenitis.

[Figure][1] A 56-year-old woman with a history of systemic lupus erythematosus presented with enlarged right axillary lymph nodes, the largest measuring 2.3 cm. The patient underwent an excisional biopsy. The lymph nodes showed follicular and paracortical hyperplasia with prominent clusters