bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical Methods for Estimating the Cumulative Risk of Screening Mammography Outcomes
Authors: Hubbard Rebecca A. , Ripping Theodora M. , Chubak Jessica , Broeders Mireille J.M. , Miglioretti Diana L. 
Published: January 2016

AbstractBackground: This study illustrates alternative statistical methods for estimating cumulative risk of screening mammography outcomes in longitudinal studies.Methods: Data from the US Breast Cancer Surveillance Consortium (BCSC) and the Nijmegen Breast Cancer Screening Program in the Netherlands were used to compare four statistical approaches to estimating cumulative risk. We estimated cumulative risk of false-positive recall and screen-detected cancer after 10 screening rounds using data from 242,835 women ages 40 to 74 years screened at the BCSC facilities in 1993–2012 and from 17,297 women ages 50 to 74 years screened in Nijmegen in 1990–2012.Results: In the BCSC cohort, a censoring bias model estimated bounds of 53.8% to 59.3% for false-positive recall and 2.4% to 7.6% for screen-detected cancer, assuming 10% increased or decreased risk among women screened for one additional round. In the Nijmegen cohort, false-positive recall appeared to be associated with subsequent discontinuation of screening leading to overestimation of risk of a false-positive recall based on adjusted discrete-time survival models. Bounds estimated by the censoring bias model were 11.0% to 19.9% for false-positive recall and 4.2% to 9.7% for screen-detected cancer.Conclusion: Choice of statistical methodology can substantially affect cumulative risk estimates. The censoring bias model is appropriate under a variety of censoring mechanisms and provides bounds for cumulative risk estimates under varying degrees of dependent censoring.Impact: This article illustrates statistical methods for estimating cumulative risks of cancer screening outcomes, which will be increasingly important as screening test recommendations proliferate. Cancer Epidemiol Biomarkers Prev; 25(3); 513–20. ©2015 AACR.
Association between Metformin Use and Mortality after Cervical Cancer in Older Women with Diabetes
Authors: Han Kathy , Pintilie Melania , Lipscombe Lorraine L. , Lega Iliana C. , Milosevic Michael F. , Fyles Anthony W. 
Published: January 2016

Abstract
Background: To examine the association between metformin use and mortality in patients with diabetes and cervical cancer.
Methods: Using Ontario health databases, a retrospective, population-based cohort study was conducted in women with diabetes ≥ age 66 years diagnosed with cervical cancer between 1997 and 2010. The association between metformin exposure and cervical cancer–specific mortality was examined using Fine–Gray regression models, with noncancer death as a competing risk and cumulative metformin use as a time-varying exposure. The association with overall mortality was examined using Cox regression models.
Results: Among the 181 women with diabetes and cervical cancer, there were 129 deaths, including 61 cervical cancer–specific deaths. The median follow-up was 5.8 years (interquartile range 4.2–9.6 years) for surviving patients. Cumulative dose of metformin after cervical cancer diagnosis was independently associated with a decreased risk of cervical cancer–specific mortality and overall mortality in a dose-dependent fashion [HR 0.79; 95% confidence interval (CI), 0.63–0.98; and HR 0.95; 95% CI, 0.90–0.996 per each additional 365 g of metformin use, respectively]. There was no significant association between cumulative use of other antidiabetic drugs and cervical cancer–specific mortality.
Conclusion: This study suggests an association between cumulative metformin use after cervical cancer diagnosis and lower cervical cancer–specific and overall mortality among older women with diabetes.
Impact: Cumulative dose of metformin use after cervical cancer diagnosis among older women with diabetes may be associated with a significant decrease in mortality. This finding has important implications if validated prospectively, as metformin is inexpensive and can be easily combined with standard treatment for cervical cancer. Cancer Epidemiol Biomarkers Prev; 25(3); 507–12. ©2015 AACR.
Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women
Authors: Bethea Traci N. , Rosenberg Lynn , Castro-Webb Nelsy , Lunetta Kathryn L. , Sucheston-Campbell Lara E. , Ruiz-Narváez Edward A. , Charlot Marjory , Park Song-Yi , Bandera Elisa V. , Troester Melissa A. , Ambrosone Christine B. , Palmer Julie R. 
Published: January 2016

Abstract
Background: The evidence on the relation of family history of cancers other than breast cancer to breast cancer risk is conflicting, and most studies have not assessed specific breast cancer subtypes.
Methods: We assessed the relation of first-degree family history of breast, prostate, lung, colorectal, ovarian, and cervical cancer and lymphoma or leukemia, to the risk of estrogen receptor–positive (ER+), ER−, and triple-negative breast cancer in data from the African American Breast Cancer Epidemiology and Risk Consortium. Multivariable logistic regression models were used to calculate ORs and 95% confidence intervals (CI).
Results: There were 3,023 ER+ and 1,497 ER− breast cancer cases (including 696 triple-negative cases) and 17,420 controls. First-degree family history of breast cancer was associated with increased risk of each subtype: OR = 1.76 (95% CI, 1.57–1.97) for ER+, 1.67 (1.42–1.95) for ER−, and 1.72 (1.38–2.13) for triple-negative breast cancer. Family history of cervical cancer was associated with increased risk of ER− (OR = 2.39; 95% CI, 1.36–4.20), but not ER+ cancer. Family history of both breast and prostate cancer was associated with increased risk of ER+ (3.40; 2.42–4.79) and ER− (2.09; 1.21–3.63) cancer, but family history of both breast and lung cancer was associated only with ER− cancer (2.11; 1.29–3.46).
Conclusions: A family history of cancers other than breast may influence the risk of breast cancer, and associations may differ by subtype.
Impact: Greater surveillance and counseling for additional screening may be warranted for women with a family history of cancer. Cancer Epidemiol Biomarkers Prev; 25(2); 366–73. ©2015 AACR.
New Strategies in Prostate Cancer: Prostate-Specific Membrane Antigen (PSMA) Ligands for Diagnosis and Therapy
Authors: Haberkorn Uwe , Eder Matthias , Kopka Klaus , Babich John W. , Eisenhut Michael 
Published: January 2016

Abstract
Key issues for prostate cancer patients are the detection of recurrent disease and the treatment of metastasized cancer. Early detection is a major challenge for all conventional imaging modalities. Furthermore, therapy of patients with hormone-resistant tumor lesions presents a major clinical challenge. Because the prostate-specific membrane antigen (PSMA) is frequently overexpressed in prostate cancer, several PSMA-targeting molecules are under development to detect and treat metastatic castration-resistant prostate cancer (mCRPC). mCRPC represents a situation where cure is no longer achievable and novel therapeutic approaches for palliation and increase of survival are needed. In this article, we discuss the recent development for noninvasive detection of recurrent disease and therapy of mCRPC with corresponding PSMA-targeted radioligands. Clin Cancer Res; 22(1); 9–15. ©2016 AACR.
Preclinical Evaluation of a Novel Orally Available SRC/Raf/VEGFR2 Inhibitor, SKLB646, in the Treatment of Triple-Negative Breast Cancer
Authors: Zheng Ming-Wu , Zhang Chun-Hui , Chen Kai , Huang Mei , Li Ya-Ping , Lin Wan-Ting , Zhang Rong-Jie , Zhong Lei , Xiang Rong , Li Lin-Li , Liu Xin-Yu , Wei Yu-Quan , Yang Sheng-Yong 
Published: January 2016

AbstractTriple-negative breast cancer (TNBC) is the most aggressive and deadly breast cancer subtype. To date, chemotherapy is the only systemic therapy and prognosis remains poor. Herein, we report the preclinical evaluation of SKLB646 in the treatment of TNBC; SKLB646 is a novel multiple kinase inhibitor developed by us recently. This compound potently inhibited SRC and VEGFR2 with IC50 values of 0.002 μmol/L and 0.012 μmol/L, respectively. It also considerably inhibited B-Raf and C-Raf with IC50 values of 0.022 and 0.019 μmol/L, respectively. It exhibited significant antiproliferation and antiviability activities against TNBC cell lines. Studies of mechanism of action indicated that SKLB646 inhibited the activation of SRC signaling and blocked the MAPK signaling through inhibiting the Raf kinases. Interestingly, SKLB646 dose dependently downregulated the expression of Fra1, a transcriptional factor that plays a critical role in the epithelial-to-mesenchymal transition. In addition, SKLB646 could inhibit HUVEC proliferation, migration, and invasion. It effectively blocked the formation of intersegmental vessels in zebrafish embryos and displayed considerable antiangiogenic effects in the tumor-induced neovascularization zebrafish model. In TNBC xenograft models, SKLB646 suppressed the tumor growth in a dose-dependent manner. Moreover, SKLB646 could remarkably inhibit TNBC cell migration and invasion in vitro. Furthermore, in an experimental lung metastasis model, the overall survival time of groups treated with SKLB646 was much longer compared with the control-, dasatinib-, and paclitaxel-treated groups. In a preliminary pharmacokinetic study, SKLB646 showed good pharmacokinetic properties. Taken together, the preclinical data show that SKLB646 could be a promising lead compound for the treatment of TNBC. Mol Cancer Ther; 15(3); 366–78. ©2015 AACR.
Structure-Based Screen Identification of a Mammalian Ste20-like Kinase 4 (MST4) Inhibitor with Therapeutic Potential for Pituitary Tumors
Authors: Xiong Weipeng , Matheson Christopher J. , Xu Mei , Backos Donald S. , Mills Taylor S. , Salian-Mehta Smita , Kiseljak-Vassiliades Katja , Reigan Philip , Wierman Margaret E. 
Published: January 2016

Abstract
Pituitary tumors of the gonadotrope lineage are often large and invasive, resulting in hypopituitarism. No medical treatments are currently available. Using a combined genetic and genomic screen of individual human gonadotrope pituitary tumor samples, we recently identified the mammalian sterile-20 like kinase 4 (MST4) as a protumorigenic effector, driving increased pituitary cell proliferation and survival in response to a hypoxic microenvironment. To identify novel inhibitors of the MST4 kinase for potential future clinical use, computational-based virtual library screening was used to dock the SelleckChem kinase inhibitor library into the ATP-binding site of the MST4 crystal structure. Several inhibitor candidates were identified with the potential to bind with high affinity. Using a TR-FRET in vitro recombinant kinase assay, hesperadin, initially described as an Aurora kinase inhibitor, exhibited potent inhibition of the MST4 kinase at nanomolar concentrations. The LβT2 gonadotrope pituitary cell hypoxic model was used to test the ability of this inhibitor to antagonize MST4 actions. Under short-term severe hypoxia (1% O2), MST4 protection from hypoxia-induced apoptosis was abrogated in the presence of hesperadin. Similarly, under chronic hypoxia (5%), hesperadin blocked the proliferative and colony-forming actions of MST4 as well as the ability to activate specific downstream signaling and hypoxia-inducible factor-1 effectors. Together, these data identify hesperadin as the first potent, selective inhibitor of the MST4 kinase with the capacity to block pituitary tumor cell growth in a hypoxic microenvironment. Mol Cancer Ther; 15(3); 412–20. ©2015 AACR.
ПРИНЦИПИ ОРГАНІЗАЦІЇ ПРОБЛЕМНО-ОРІЄНТОВАНОГО НАВЧАННЯ НА КАФЕДРІ ГІСТОЛОГІЇ, ЦИТОЛОГІЇ ТА ЕМБРІОЛОГІЇ В УМОВАХ ВПРОВАДЖЕННЯ СУЧАСНИХ ІНФОРМАЦІЙНИХ ТЕХНОЛОГІЙ
Authors: Klyuchko S. S. 
Published: January 2016

<p>The article by questioning senior researchers and students of the Department of Histology, Cytology and Embryology<br />Authority identified the main approaches to the formation of the principles of problem-based learning students and objective </p><p>control in the conditions of modern information technologies. Implementation at the Department of Histology, Cytology and<br />Embryology test control for control of knowledge and case studies for the evaluation of clinical thinking allows us to give an<br />objective assessment of how students understand the connection between the theoretical material and practical actions, are<br />able to analyze, synthesize the material and to predict development of the situation. To innovate the educational diagnosis can<br />be attributed to the successful use of the Department of Histology, Cytology and Embryology principles of modularity and rating<br />control training using computer programs. The undoubted advantages of the rating control are: evaluation of the individual<br />units of work ensures the reliability of the control (test control and situational problems, diagnostics 2 micropreparations and<br />electron diffraction); so its form satisfies the requirements of content and construct validity (compliance with the forms and<br />purposes); Extended Monitoring integrates and implements motivational and educational functions; detailed and phased<br />control procedure to develop students' skills of self-work, forms the experience of self-control in professional activities.</p>
ПОРІВНЯЛЬНИЙ АНАЛІЗ КІРЛІАНОГРАФІЧНОГО СВІТІННЯ БІОЛОГІЧНОЇ ТКАНИНИ З БІОХІМІЧНИМИ ПРОЦЕСАМИ
Authors: Pesotskaya L. A. , Glukhovа N. V. , Povstyanoy V. A. , Evdokimenko N. M. , Chernenko G. P. 
Published: January 2016

Kirlian diagram samples Conducted. Achilles tendon dead people with various postmorbidnym period (from 5:0 until 22 days) and optoelectronics is part of the standard terms of the x-ray film developer. The results obtained were compared with biochemical indicators of the level of enzymes and content of degradation products of proteins, trace elements, derived from <p>the investigated samples. For kirlianograficeskih studies used an experimental device, RIVERS 1, developed by Ukrainian Scientific Research Institute of mechanical engineering technologies (Dnepropetrovsk). For mathematical processing of results using Matlab program.</p><p>The growing shortage of ATP causes the breach and termination of ion exchange, increases reactive oxygen generation, lipid peroxidation destroys cell membranes. The process of self digestion (autoliza) tissue tendons, as shown by the results of the experiments, had cyclical changes metabolism enzyme activity (ALT), carbohydrate (LDH), nucleotides, of total protein and micronutrients.</p>
ДОСВІД ФАНТОМНО-СИМУЛЯЦІЙНОГО НАВЧАННЯ СТУДЕНТІВ ІЗ ДИСЦИПЛІНИ «АКУШЕРСТВО ТА ГІНЕКОЛОГІЯ»
Authors: Potapov V. A. , Donskaya Yu. V. , Medvediev M. V. , Petulko А. Р. 
Published: January 2016

<p>The article presents the results of simulation trainings at the Department of Obstetrics and Gynecology of State Establishment «Dnipropetrovsk Medical Academy of Health Ministry of Ukraine». In order to improve the quality of knowledge of students a lot of time to the development of practical skills of modern high-tech simulation equipment was given. During the 2013-<br />2015 academic years the department staff has conducted more than 7 thousands practical trainings for students of IV, V and VI years using modern simulation equipment. Analysis of the data showed that significant proportion of students has<br />improved the results of the basic skills after undergoing training. The introduction in the educational process of simulation training promotes quality practical skills and more efficient formation of students' motivation to learn.</p>
ЗАСТОСУВАННЯ ІНФОРМАЦІЙНИХ ТЕХНОЛОГІЙ ДЛЯ ОЦІНКИ ОСОБЛИВОСТЕЙ РЕАКТИВНОСТІ ОРГАНІЗМУ МОЛОДИХ ЩУРІВ ПРИ ЕКСПЕРИМЕНТАЛЬНІЙ ГІПОКСІЇ
Authors: Volkova N. M. 
Published: January 2016

<p>Research of adaptation mechanisms in young body to factors such as hypoxic effect is an actual scientific problem. The aim of the experiment was to determine the functional consequences of changes in ion permeability of cell membranes in the associative cortex in young rats ufter incubation at hypoxic environment under conditions of low atmospheric pressure.<br />Incubation of rats in the hypoxic environment under conditions of moderately low atmospheric pressure leads to increased permeability of cell membranes for Na + and Cl- ions at the associative cortex. This is a functional feature of hypoxic damage to membrane structures of nerve tissue that causes compensatory limit the activity of the central contour regulation of heart rate and decrease activity of the sympathetic regulation. Peculiarities in reactivity of young rats exist due to the immaturity of fronto-thalamic brain system.</p>
ЗАСТОСУВАННЯ ВІДКРИТОГО ПРОГРАМНОГО КОМПЛЕКСУ ДЛЯ ОБРОБКИ МЕДИЧНИХ ЗОБРАЖЕНЬ MEVISLAB ПРИ ВИВЧЕННІ КУРCУ «МЕДИЧНА ІНФОРМАТИКА»
Authors: Kravets N. O. , Semenets A. V. , Sverstyuk A. S. 
Published: January 2016

<p>The main capabilities of the MeVisLab image analysis suite to the medical images processing are shown. The application software package structure and the user interface are described. The methodology of the MeVisLab software package usage<br />to the studying of the corresponded topics of the Medical Informatics course is presented. An approach of the implementation of the image elements recognition algorithm is demonstrated.</p>
APPLICATION OF UKRAINIAN GRID INFRASTRUCTURE FOR ELECTROENCEPHALOGRAM AND ULTRASONIK DIAGNOSTIC IMAGES ANALYSIS
Authors: Byvalkevych R. V. , Gaidar V. O. , Radchenko S. P. , Sudakov O. О. 
Published: January 2016

<p>Ultrasonic introscopic imaging (USI) and electroencephalography (EEG) are powerful tools for diagnostics of different pathologies. In the same time USI and EEG equipment is available in almost all clinical and even in many educational institutions. Development of ultrasonic images and EEG data processing algorithms providing physicians with additional specific clinical parameters is a popular current research subject. Successful operation of these<br />algorithms needs fast procession of large information volumes. These algorithms are based on an analysis of large databases with information about the patients. Grid infrastructures can provide distributed data<br />archiving, procession and access facilities for such<br />databases.</p>
MOLECULAR SIGNATURES OF LUNG CANCER BASED ON GENE EXPRESSION RANKING OF RNA-SEQ DATA
Authors: Bondarenko V. , Emmert-Streib Frank 
Published: January 2016

<p>Whole Transcriptome Shotgun Sequencing or RNA-Seq is an experimental methodology which allows quantification of all transcripts expressed in a population of cells. In biomedicine, it is gradually gaining popularity to become a prevalent method<br />for transcriptome analysis. Sequencing of individual human transcriptomes has become a powerful tool in disease biomarkers discovery and setting up individual<br />treatment therapy of cancer and other disorders.</p>
THE EXPERIENCE OF THE INTRODUCTION OF «DOCTOR ELEKS»
Authors: Ventskivska N. I. , Korobchinska N. V. , Tumanina S. V. 
Published: January 2016

<p>The need for a single medical information space in Vinnitsa there was a long time, however, the actual implementation of the automated medical information system was made possible with<br />the debugging of the program «Doctor Eleks.» The «Doctor Eleks» provides automation and linking all the main processes of the medical institutions. The goal of creating a unified information space of urban health by implementing the program «Doctor Eleks» improve the quality of medical services in Vinnitsya.</p>
INFORMATIONAL TECHNOLOGIES IN THE DOCTOR'S WORK IN MUNICIPAL CHILDREN'S CLINICAL HOSPITAL
Authors: Semenyuk O. O. 
Published: January 2016

<p>The implementation of IT in combination with organizational changes in our hospital has contributed to: increase of<br />efficiency in the organization of work of the institution; speed up of diagnostics and treatment according to modern criteria of quality of medical care to the patient in compliance with clinical protocols and routes of the patient according to nosologies diseases; speed up and simplification of the documents circulation, conducting of the analytical data processing, formation of statements necessary for making decision by the administration of the hospital; protection of personal data of the patient in accordance with current legislation; information that contains electronic patient's card, can be transmitted electronically for consultation with the specialists of leading clinics, as well as to conduct telemedicine consultation online; implementation of the electronic patient's card puts our clinic along with the most advanced European clinics.</p>
APPLICATION OF UKRAINIAN GRID INFRASTRUCTURE FOR INVESTIGATION OF NONLINEAR DYNAMICS IN LARGE NEURONAL NETWORKS
Authors: Sudakov O. О. , Maistrenko V. L. 
Published: January 2016

<p>In present work the Ukrainian National Grid (UNG) infrastructure was applied for investigation of synchronization in large networks of interacting neurons. This application is important for solving of modern neuroscience problems related to mechanisms of nervous system activities (memory, cognition etc.) and nervous pathologies (epilepsy, Parkinsonism, etc.). Modern non-linear dynamics theories and applications provides powerful basis for computer simulations<br />of biological neuronal networks and investigation of phenomena which mechanisms hardly could be clarified by other approaches. Cubic millimeter of brain tissue contains about 105 neurons, so realistic (Hodgkin-Huxley model) and phenomenological (Kuramoto-Sakaguchi, FitzHugh-Nagumo, etc. models) simulations require consideration of large<br />neurons numbers.</p>
Dipeptidyl Peptidase 4 Inhibition Alleviates Shortage of Circulating Glucagon-Like Peptide-1 in Heart Failure and Mitigates Myocardial Remodeling and Apoptosis via the Exchange Protein Directly Activated by Cyclic AMP 1/Ras-Related Protein 1 Axis
Authors: Aoyama Morihiko , Kawase Haruya , Bando Yasuko K. , Monji Akio , Murohara Toyoaki 
Published: January 2016

Background—
Ample evidence demonstrates cardiovascular protection by incretin-based therapy using dipeptidyl peptidase 4 inhibitor (DPP4i) and glucagon-like peptide-1 (GLP-1) under either diabetic or nondiabetic condition. Their action on myocardium is mediated by the cyclic AMP (cAMP) signal; however, the pathway remains uncertain. This study was conducted to address the effect of DPP4i/GLP-1/cAMP axis on cardiac dysfunction and remodeling induced by pressure overload (thoracic aortic constriction [TAC]) independently of diabetes mellitus.

Methods and Results—
DPP4i (alogliptin, 10 mg/kg per day for 4 weeks) prevented TAC-induced contractile dysfunction, remodeling, and apoptosis of myocardium in a GLP-1 receptor antagonist (exendin [9-39])–sensitive fashion. In TAC, circulating level of GLP-1 (in pmol/L; 0.86±0.10 for TAC versus 2.13±0.54 for sham control) unexpectedly declined and so did the myocardial cAMP concentration (in pmol/mg protein; 33.0±1.4 for TAC versus 42.2±1.5 for sham). Alogliptin restored the decline in the GLP-1/cAMP levels observed in TAC, thereby augmented cAMP signaling effectors (protein kinase A [PKA] and exchange protein directly activated by cAMP 1 [EPAC1]). In vitro assay revealed distinct roles of PKA and EPAC1 in cardiac apoptosis. EPAC1 promoted cardiomyocyte survival via concomitant increase in B cell lymphoma-2 (Bcl-2) expression and activation of small G protein Ras-related protein 1 (Rap1) in a cAMP dose–dependent and PKA–independent fashion.

Conclusions—
DPP4i restores cardiac remodeling and apoptosis caused by the pathological decline in circulating GLP-1 in response to pressure overload. EPAC1 is essential for cardiomyocyte survival via the cAMP/Rap1 activation independently of PKA.