Browsing by Subject "STAGE"

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  • Ranta, Jukka; Airaksinen, Manu; Kirjavainen, Turkka; Vanhatalo, Sampsa; Stevenson, Nathan J. (2021)
    Objective To develop a non-invasive and clinically practical method for a long-term monitoring of infant sleep cycling in the intensive care unit. Methods Forty three infant polysomnography recordings were performed at 1-18 weeks of age, including a piezo element bed mattress sensor to record respiratory and gross-body movements. The hypnogram scored from polysomnography signals was used as the ground truth in training sleep classifiers based on 20,022 epochs of movement and/or electrocardiography signals. Three classifier designs were evaluated in the detection of deep sleep (N3 state): support vector machine (SVM), Long Short-Term Memory neural network, and convolutional neural network (CNN). Results Deep sleep was accurately identified from other states with all classifier variants. The SVM classifier based on a combination of movement and electrocardiography features had the highest performance (AUC 97.6%). A SVM classifier based on only movement features had comparable accuracy (AUC 95.0%). The feature-independent CNN resulted in roughly comparable accuracy (AUC 93.3%). Conclusion Automated non-invasive tracking of sleep state cycling is technically feasible using measurements from a piezo element situated under a bed mattress. Significance An open source infant deep sleep detector of this kind allows quantitative, continuous bedside assessment of infant's sleep cycling.
  • Ng, Wai Tong; But, Barton; Choi, Horace C. W.; de Bree, Remco; Lee, Anne W. M.; Lee, Victor H. F.; Lopez, Fernando; Mäkitie, Antti A.; Rodrigo, Juan P.; Saba, Nabil F.; Tsang, Raymond K. Y.; Ferlito, Alfio (2022)
    Introduction: Nasopharyngeal carcinoma (NPC) is endemic to Eastern and South-Eastern Asia, and, in 2020, 77% of global cases were diagnosed in these regions. Apart from its distinct epidemiology, the natural behavior, treatment, and prognosis are different from other head and neck cancers. With the growing trend of artificial intelligence (AI), especially deep learning (DL), in head and neck cancer care, we sought to explore the unique clinical application and implementation direction of AI in the management of NPC. Methods: The search protocol was performed to collect publications using AI, machine learning (ML) and DL in NPC management from PubMed, Scopus and Embase. The articles were filtered using inclusion and exclusion criteria, and the quality of the papers was assessed. Data were extracted from the finalized articles. Results: A total of 78 articles were reviewed after removing duplicates and papers that did not meet the inclusion and exclusion criteria. After quality assessment, 60 papers were included in the current study. There were four main types of applications, which were auto-contouring, diagnosis, prognosis, and miscellaneous applications (especially on radiotherapy planning). The different forms of convolutional neural networks (CNNs) accounted for the majority of DL algorithms used, while the artificial neural network (ANN) was the most frequent ML model implemented. Conclusion: There is an overall positive impact identified from AI implementation in the management of NPC. With improving AI algorithms, we envisage AI will be available as a routine application in a clinical setting soon.
  • Jensen, Christina T.; Ahsberg, Josefine; Sommarin, Mikael N. E.; Strid, Tobias; Somasundaram, Rajesh; Okuyama, Kazuki; Ungerback, Jonas; Kupari, Jussi; Airaksinen, Matti S.; Lang, Stefan; Bryder, David; Soneji, Shamit; Karlsson, Goran; Sigvardsson, Mikael (2018)
    To understand the developmental trajectories in early lymphocyte differentiation, we identified differentially expressed surface markers on lineage-negative lymphoid progenitors (LPs). Single-cell polymerase chain reaction experiments allowed us to link surface marker expression to that of lineage-associated transcription factors (TFs) and identify GFRA2 and BST1 as markers of early B cells. Functional analyses in vitro and in vivo as well as single-cell gene expression analyses supported that surface expression of these proteins defined distinct subpopulations that include cells from both the classical common LPs (CLPs) and Fraction A compartments. The formation of the GFRA2-expressing stages of development depended on the TF EBF1, critical both for the activation of stage-specific target genes and modulation of the epigenetic landscape. Our data show that consecutive expression of Ly6D, GFRA2, and BST1 defines a developmental trajectory linking the CLP to the CD19(+) progenitor compartment.
  • Almangush, Alhadi; Youssef, Omar; Pirinen, Matti; Sundström, Jari; Leivo, Ilmo; Mäkitie, Antti A. (2019)
    Tumour budding has emerged as a promising prognostic marker in many cancers. We systematically reviewed all studies that evaluated tumour budding in diagnostic biopsies. We conducted a systematic review of PubMed, MEDLINE, Scopus, Web of Science and Cochrane library for all articles that have assessed tumour budding in diagnostic (i.e. pretreatment or pre-operative) biopsies of any tumour type. Two independent researchers screened the retrieved studies, removed duplicates, excluded irrelevant studies and extracted data from the eligible studies. A total of 13 reports comprising 11 cohorts were found to have studied tumour budding in diagnostic biopsies. All these reports showed that evaluation of tumour budding in diagnostic biopsies was easily applicable. A strong association was observed between tumour budding score in diagnostic biopsies and corresponding surgical samples. Evaluation of tumour budding in diagnostic biopsies had a significant prognostic value for lymph node metastasis and patient survival. In all studies, tumour budding was a valuable marker of tumour aggressiveness and can be evaluated in technically satisfactory diagnostic biopsies. Thus, the assessment of tumour budding seems to identify the behaviour of cancer, and therefore to facilitate treatment planning.
  • Morales, Juliana; Malles, Aaron; Kimble, Marrell; de la Vega, Pura Rodriguez; Castro, Grettel; Nieder, Alan M.; Barengo, Noel C. (2019)
    Background: Scientific evidence on the effect of health insurance on racial disparities in urinary bladder cancer patients' survival is scant. The objective of our study was to determine whether insurance status modifies the association between race and bladder cancer specific survival during 2007-2015. Methods: The 2015 database of the cancer surveillance program of the National Cancer Institute (n = 39,587) was used. The independent variable was race (White, Black and Asian Pacific Islanders (API)), the main outcome was cancer specific survival. Health insurance was divided into uninsured, any Medicaid and insured. An adjusted model with an interaction term for race and insurance status was computed. Unadjusted and adjusted Cox regression analysis were applied. Results: Health insurance was a statistically significant effect modifier of the association between race and survival. Whereas, API had a lower hazard of death among the patients with Medicaid insurance (HR 0.67; 95% CI 0.48-0.94 compared with White patients, no differences in survival was found between Black and White urinary bladder carcinoma patients (HR 1.24; 95% CI 0.95-1.61). This may be due a lack of power. Among the insured study participants, Blacks were 1.46 times more likely than Whites to die of bladder cancer during the 5-year follow-up (95% CI 1.30-1.64). Conclusions: While race is accepted as a poor prognostic factor in the mortality from bladder cancer, insurance status can help to explain some of the survival differences across races.
  • Witjes, Julia J.; Smits, Loek P.; Pekmez, Ceyda T.; Prodan, Andrei; Meijnikman, Abraham S.; Troelstra, Marian A.; Bouter, Kristien E. C.; Herrema, Hilde; Levin, Evgeni; Holleboom, Adriaan G.; Winkelmeijer, Maaike; Beuers, Ulrich H.; van Lienden, Krijn; Aron-Wisnewky, Judith; Mannisto, Ville; Bergman, Jacques J.; Runge, Jurgen H.; Nederveen, Aart J.; Dragsted, Lars O.; Konstanti, Prokopis; Zoetendal, Erwin G.; de Vos, Willem; Verheij, Joanne; Groen, Albert K.; Nieuwdorp, Max (2020)
    The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of .Conclusion:Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.
  • Almangush, Alhadi; Leivo, Ilmo; Siponen, Maria; Sundquist, Elias; Mroueh, Rayan; Mäkitie, Antti A.; Soini, Ylermi; Haglund, Caj; Nieminen, Pentti; Salo, Tuula (2018)
    It is of great clinical importance to identify simple prognostic markers from preoperative biopsies that could guide treatment planning. Here, we compared tumor budding (B), depth of invasion (D), and the combined scores (i.e., budding and depth of invasion (BD) histopathologic model) in preoperative biopsies and the corresponding postoperative specimens of oral tongue squamous cell carcinoma (OTSCC). Tumor budding and depth of invasion were evaluated in the pre- and postoperative samples from 100 patients treated for OTSCC. Sensitivity and specificity statistics were used. Our results showed statistically significant (P <0.001) relationship between pre- and postoperative BD scores. There was an agreement between the pre- and postoperative BD model scores in 83 cases (83%) with 57.1% sensitivity (95% CI 39.4 to 73.7%) and 96.9% specificity (95% CI 89.3 to 99.6%). Our findings suggest that the BD model, analyzed from representative biopsies, could be used for the treatment planning of OTSCC.
  • Salvador-Martinez, Irepan; Salazar-Ciudad, Isaac (2017)
    The increase in complexity in an embryo over developmental time is perhaps one of the most intuitive processes of animal development. It is also intuitive that the embryo becomes progressively compartmentalized over time and space. In spite of this intuitiveness, there are no systematic attempts to quantify how this occurs. Here, we present a quantitative analysis of the compartmentalization and spatial complexity of Ciona intestinalis over developmental time by analyzing thousands of gene expression spatial patterns from the ANISEED database. We measure compartmentalization in two ways: as the relative volume of expression of genes and as the disparity in gene expression between body parts. We also use a measure of the curvature of each gene expression pattern in 3D space. These measures show a similar increase over time, with the most dramatic change occurring from the 112-cell stage to the early tailbud stage. Combined, these measures point to a global pattern of increase in complexity in the Ciona embryo. Finally, we cluster the different regions of the embryo depending on their gene expression similarity, within and between stages. Results from this clustering analysis, which partially correspond to known fate maps, provide a global quantitative overview about differentiation and compartmentalization between body parts at each developmental stage. (C) 2017 Elsevier B.V. All rights reserved.
  • Olenius, Tobias; Koskenvuo, Laura; Koskensalo, Selja; Lepisto, Anna; Böckelman, Camilla (2022)
    Background Colorectal cancer (CRC) incidence in Finland has risen steadily. Given development in cancer treatments in recent decades, disease-specific data on the long-term prognosis of patients may be obsolete. Thus, this study aimed to report 5-year disease-specific survival (DSS) and relative survival based on tumour spread and site among CRC patients diagnosed between 1991 and 2015 in Finland. Material and methods We conducted a population-based registry study among 59 465 CRC patients identified from the Finnish Cancer Registry. Results The 5-year DSS for all CRC patients was 56.7% [95% confidence interval (CI) 56.3-57.1%] for 1991 through 2015. Tumour site-specific survival has improved for the period 2006-2015 versus 1991-2005 for right-sided colon cancer from 54.8% (95% CI 53.8-55.8%) to 59.9% (95% CI 58.7-61.1%), for left-sided colon cancer from 54.1% (95% CI 52.9-55.3%) to 61.0% (95% CI 59.8-62.2%) and for rectal cancer from 53.6% (95% CI 52.2-55.0%) to 62.3% (95% CI 61.3-63.3%). The 5-year relative survival for the period 2006 through 2015 was 93.6% for localised disease (stage I); 84.2% for locally advanced tumour invading adjacent structures (stage II); 68.2% for regional disease with regional lymph node metastases (stage III); and 14.0% for metastatic disease (stage IV). Conclusions This study confirms that survival for CRC has improved in recent decades in Finland, mirroring observations from other Western countries. However, the classification of tumour spread within the Finnish Cancer Registry differs slightly from the TNM classification, thereby limiting the generalisability of these results.
  • Hermunen, Kethe; Soveri, Leena-Maija; Boisen, Mogens Karsbol; Mustonen, Harri K.; Dehlendorff, Christian; Haglund, Caj H.; Johansen, Julia Sidenius; Osterlund, Pia (2020)
    Background In colorectal cancer (CRC) patients, guidelines only recommend measurement of preoperative carcinoembryonic antigen (CEA), although postoperative CEA may be more informative. However, the sensitivity of both preoperative and postoperative CEA in identifying relapse is limited. We studied whether CA19-9, YKL-40, C-reactive protein (CRP) and interleukin (IL)-6 add prognostic information combined with postoperative CEA. Material and methods This post-hoc analysis included 147 radically resected stage II (n = 38), III (n = 91) and IV (n = 18) CRC patients treated with adjuvant 5-fluorouracil (5-FU)-based therapy in the phase III LIPSYT study (ISRCTN98405441). We collected postoperative blood samples a median of 48 days after surgery. We analysed relapses, sensitivity, positive predictive value (PPV) and disease-free (DFS) and overall survival (OS) by bootstrap, Kaplan-Meier and adjusted Cox-models in the elevated vs. normal biomarker groups. Results Elevated postoperative CEA associated with impaired DFS (HR 7.23; CI(95%)3.85-13.58), impaired OS (HR 7.16; CI(95%)3.76-13.63), and more relapses (HR 7.9; CI(95%)3.4-18.2); but sensitivity for CEA in finding relapses was only 31% (CI(95%)21-48%). Normal CEA combined with an elevated YKL-40 or elevated CRP showed more relapses (HR for YKL-40 2.13 [CI(95%)1.10-4.13], HR for CRP 3.14 [CI(95%)1.21-8.16]), impaired DFS (HR 2.18 [CI(95%)1.12-4.24] or 3.23 [CI(95%)1.34-7.82]), and impaired OS (2.33 [CI(95%)1.24-4.40] or 2.68 [CI(95%)1.12-6.44]). Elevated CEA combined with a concomitantly elevated CA19-9, YKL-40, CRP or IL-6 showed a respective PPV of 100, 90, 100, and 100%. Conclusion In radically operated stage II to IV CRC patients who received adjuvant 5-FU-based chemotherapy, a postoperatively elevated CEA alone or in combination with CA19-9, YKL-40, CRP, or IL-6, or a normal CEA combined with an elevated YKL-40 or with an elevated CRP, may indicate patients at high risk of relapse.
  • Van Hemelrijck, Mieke; Ji, Xi; Helleman, Jozien; Roobol, Monique J.; van der Linden, Wim; Nieboer, Daan; Bangma, Chris H.; Frydenberg, Mark; Rannikko, Antti; Lee, Lui S.; Gnanapragasam, Vincent J.; Kattan, Mike W.; Trock, Bruce; Ehdaie, Behfar; Carroll, Peter; Filson, Christopher; Kim, Jeri; Logothetis, Christopher; Morgan, Todd; Klotz, Laurence; Pickles, Tom; Hyndman, Eric; Moore, Caroline M.; Gnanapragasam, Vincent; Van Hemelrijck, Mieke; Dasgupta, Prokar; Bangma, Chris; Roobol, Monique; Villers, Arnauld; Valdagni, Riccardo; Perry, Antoinette; Hugosson, Jonas; Rubio-Briones, Jose; Bjartell, Anders; Hefermehl, Lukas; Shiong, Lee Lui; Frydenberg, Mark; Kakehi, Yoshiyuki; Byung Ha Chung; van der Kwast, Theo; Obbink, Henk; Hulsen, Tim; de Jonge, Cees; Kattan, Mike; Xinge, Ji; Muir, Kenneth; Lophatananon, Artitaya; Fahey, Michael; Steyerberg, Ewout (2019)
    Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Balkhed, Wile; Åberg, Fredrik O.; Nasr, Patrik; Ekstedt, Mattias; Kechagias, Stergios (2022)
    Background and Aims The presence of advanced hepatic fibrosis is the prime marker for the prediction of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Blood-based non-invasive tests (NITs) have been developed to evaluate fibrosis and identify patients at risk. Current guidelines propose monitoring the progression of NAFLD using repeated NITs at 2-3-year intervals. The aim of this study was to evaluate the association of changes in NITs measured at two time points with the progression of NAFLD. Methods We retrospectively included NAFLD patients with NIT measurements in whom the baseline hepatic fibrosis stage had been assessed by biopsy or transient elastography (TE). Subjects underwent follow-up visits at least 1 year from baseline to evaluate the progression of NAFLD. NAFLD progression was defined as the development of end-stage liver disease or fibrosis progression according to repeat biopsy or TE. The following NITs were calculated at baseline and follow-up: Fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet ratio index (APRI) and dynamic aspartate-to-alanine aminotransferase ratio (dAAR). Results One hundred and thirty-five patients were included with a mean follow-up of 12.6 +/- 8.5 years. During follow-up, 41 patients (30%) were diagnosed with progressive NAFLD. Change in NIT scores during follow-up was significantly associated with disease progression for all NITs tested except for NFS. However, the diagnostic precision was suboptimal with area under the receiver operating characteristics 0.56-0.64 and positive predictive values of 0.28-0.36 at sensitivity fixed at 90%. Conclusions Change of FIB-4, NFS, APRI, and dAAR scores is only weakly associated with disease progression in NAFLD. Our findings do not support repeated measurements of these NITs for monitoring the course of NAFLD.
  • Kröger, Björn; Lintulaakso, Kari (2017)
    RNames ( is an open access relational database linking stratigraphic units with each other that are considered to be time-equivalent or time overlapping. RNames is also a tool to correlate among stratigraphic units. The structure of the database allows for a wide range of queries and applications. Currently three algorithms are available, which calculate a set of correlation tables with Ordovician stratigraphic units time binned into high-resolution chronostratigraphic slices (Global Ordovician Stages, Stage Slices, Time Slices). The ease of availability of differently binned stratigraphic units and the potential to create new schemes are the main advantages and goals of RNames. Different timebinned stratigraphic units can be matched with other databases and allow for simultaneous up-to-date analyses of stratigraphically constrained estimates in various schemes. We exemplify these new possibilities with our compiled Ordovician data and analyse fossil collections of the Paleobiology Database based on the three different binning schemes. The presented diversity curves are the first sub-stage level, global, marine diversity curves for the Ordovician. A comparison among the curves reveals that differences in time slicing have a major effect on the shape of the curve. Despite uncertainties in Early and Late Ordovician diversities, our calculations confirm earlier estimates that Ordovician diversification climaxed globally during the Darriwilian stage.
  • Jetsu, Lauri (2021)
    Constant orbital period ephemerides of eclipsing binaries give the computed eclipse epochs (C). These ephemerides based on the old data cannot accurately predict the observed future eclipse epochs (O). Predictability can be improved by removing linear or quadratic trends from the O - C data. Additional companions in an eclipsing binary system cause light-time travel effects that are observed as strictly periodic O - C changes. Recently, Hajdu et al. estimated that the probability of detecting the periods of two new companions from the O - C data is only 0.00005. We apply the new discrete chi-square method to 236 yr of O - C data of the eclipsing binary Algol (beta Persei). We detect the tentative signals of at least five companion candidates having periods between 1.863 and 219.0 yr. The weakest one of these five signals does not reveal a "new" companion candidate, because its 680.4 +/- 0.4 day signal period differs only 1.4 sigma from the well-known 679.85 +/- 0.04 day orbital period of Algol C. We detect these same signals also from the first 226.2 yr of data, and they give an excellent prediction for the last 9.2 yr of our data. The orbital planes of Algol C and the new companion candidates are probably coplanar because no changes have been observed in Algol's eclipses. The 2.867 day orbital period has been constant since it was determined by Goodricke.
  • Almangush, Alhadi; Mäkitie, Antti A.; Mäkinen, Laura K.; Kauppila, Joonas H.; Pukkila, Matti; Hagström, Jaana; Laranne, Jussi; Soini, Ylermi; Kowalski, Luiz Paulo; Grenman, Reidar; Haglund, Caj; Coletta, Ricardo D.; Salo, Tuula; Leivo, Ilmo (2018)
    One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (ae4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12-4.99) and disease-free survival (HR 2.12, 95% CI 1.09-4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27-7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.