bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crk Tyrosine Phosphorylation Regulates PDGF-BB–inducible Src Activation and Breast Tumorigenicity and Metastasis
Authors: Kumar Sushil , Lu Bin , Davra Viralkumar , Hornbeck Peter , Machida Kazuya , Birge Raymond B. 
Published: October 2017

AbstractThe activity of Src family kinases (Src being the prototypical member) is tightly regulated by differential phosphorylation on Tyr416 (positive) and Tyr527 (negative), a duet that reciprocally regulates kinase activity. The latter negative regulation of Src on Tyr527 is mediated by C-terminal Src kinase (CSK) that phosphorylates Tyr527 and maintains Src in a clamped negative regulated state by promoting an intramolecular association. Here it is demonstrated that the SH2- and SH3-domain containing adaptor protein CrkII, by virtue of its phosphorylation on Tyr239, regulates the Csk/Src signaling axis to control Src activation. Once phosphorylated, the motif (PIpYARVIQ) forms a consensus sequence for the SH2 domain of CSK to form a pTyr239-CSK complex. Functionally, when expressed in Crk−/− MEFs or in Crk+/+ HS683 cells, Crk Y239F delayed PDGF-BB–inducible Src Tyr416 phosphorylation. Moreover, expression of Crk Y239F in HS683 cells delayed Src kinase activation and suppressed the cell-invasive and -transforming phenotypes. Finally, through loss-of-function and epistasis experiments using CRISPR-Cas9–engineered 4T1 murine breast cancer cells, Crk Tyr239 is implicated in breast cancer tumor growth and metastasis in orthotopic immunocompetent 4T1 mice model of breast adenocarcinoma. These findings delineate a novel role for Crk Tyr239 phosphorylation in the regulation of Src kinases, as well as a potential molecular explanation for a long-standing question as to how Crk regulates the activation of Src kinases.Implications: These findings provide new perspectives on the versatility of Crk in cancer by demonstrating how Crk mechanistically drives, through a tyrosine phosphorylation–dependent manner, tumor growth, and metastasis. Mol Cancer Res; 16(1); 173–83. ©2017 AACR.
Vitamin K Antagonists Compared to Low-Molecular-Weight Heparins for Treatment of Cancer-Associated Venous Thromboembolism: An Observational Study in Routine Clinical Practice
Authors: den Exter Paul , Hooijer José , van der Hulle Tom , van Oosten Julien , Dekkers Olaf , Klok Frederikus , Huisman Menno 
Published: October 2017

AbstractSince several trials have demonstrated that low-molecular-weight-heparin (LMWH) is superior to vitamin K antagonist (VKA) in preventing recurrent venous thromboembolism (VTE) in patients with cancer-associated VTE, guidelines now recommend LMWH monotherapy in this setting. We evaluated whether this shift resulted in improved outcomes in routine clinical practice. We performed a cohort study of consecutive patients with cancer-associated VTE during 2001 and 2010. We compared the risks for recurrent VTE, major bleeding and mortality between patients diagnosed before and after 2008 during a 6-month routine follow-up. A total of 381 patients were included, of which 234 (61.4%) were diagnosed before 2008. Before 2008, 23% of the patients were treated with LMWH; thereafter, this percentage was higher: 67%. The 6-month incidence for recurrent VTE was 8.6% in patients diagnosed before 2008 versus 7.5% for patients diagnosed after 2008 (risk difference [RD]: −1.1%; 95% confidence interval [CI]: −6.3, 5.3). The respective risks for major bleeding were 6.4 versus 4.8% (RD: −1.6%; 95% CI: −3.8 to 5.8), and 39.7 versus 41.5% (RD: 1.8%; 95% CI: −8.8, 12) for overall mortality. The mean time in therapeutic range (TTR) of patients treated with VKA was 61%. Despite a clear shift toward LMWH as agent of choice for cancer-associated VTE, we did not observe a clear improvement in terms of recurrent VTE and bleeding complications.
СИНТЕЗ ОКТЕНІДИНУ ГЕКСАФТОРОСИЛІКАТУ – НОВОГО ПОТЕНЦІЙНОГО КАРІЄСПРОФІЛАКТИЧНОГО І АНТИБАКТЕРІАЛЬНОГО АГЕНТА
Authors: Gelmboldt V. O. , Anisimov V. Yu. , Shyshkin I. O. 
Published: October 2017

Мета роботи. Здійснити синтез октенідину гексафторосилікату як потенційного карієспрофілактичного і антибактеріального препарату.Матеріали і методи. Вихідні реагенти, октенідину дигідрохлорид і кремнефтороводнева кислота є комерційно доступними реактивами. ІЧ-спектри поглинання реєстрували на спектрофотометрі Spectrum BX II FT-IR System (Perkіn-Elmer), мас-спектри FAB – спектрометрі VG 7070 (VG Analytіcal), спектри ЯМР 1H, 19F – на спектрометрі Varіan Gemini-400. Термогравіметричний аналіз проводили на дериватографі Q-1500 D системи F. Paulik – J. Paulik – L. Erdey.Результати й обговорення. Одержано октенідину гексафторосилікату моногідрат на основі реакції іонного обміну між метанольним розчином октенідину дигідрохлориду і кремнефтороводневою кислотою. Склад і іонна будова синтезованої сполуки підтверджено методами ІЧ-, ЯМР 1H, 19F-спектроскопії, мас-спектрометрії. Термоліз комплексу супроводжується процесами дегідратації і деструкції з подальшим окисленням фрагментів катіону.Висновки. Синтезовано октенідину гексафторосилікату моногідрат, нове похідне октенідину, що становить інтерес як потенційний карієспрофілактичний і антибактеріальний засіб.
АСОРТИМЕНТНА ХАРАКТЕРИСТИКА ПРОСТАТОПРОТЕКТОРІВ, ЗАРЕЄСТРОВАНИХ В УКРАЇНІ, РЕСПУБЛІЦІ ПОЛЬЩА ТА РЕСПУБЛІЦІ БІЛОРУСЬ
Authors: Gadyak I. V. , Hromovyk B. P. 
Published: October 2017

Мета роботи. Вивчення особливостей формування aсортимeнту лікарських засобів (ЛЗ) для лікувaння прoстатиту в Україні, Республіці Польща (РП) та Республіці Білорусь (РБ).Матеріали і методи. Матеріали дослідження – дані офіційних джерел щодо реєстрації ЛЗ в Україні, РП та РБ станом на 01.08.2017 р. Методи дослідження – системний, статистичний, аналізу порівняння, ранжування, узагальнення.Результати і обговорення. Встановлено, що в Україні набагато більше (в 1,3 раза) торгових назв (ТН) простатопротекторів (ПП), ніж у РБ, проте удвічі менше, ніж у РП. Лідерами серед зарубіжних країн -виробників в Україні є Німеччина, Індія, Італія, Нідерланди, в РП – Німеччина, Велика Британія, Нідерланди, Франція, в РБ – Україна і Росія. У кожній з досліджуваних країн зареєстровані ПП виробництва лише 9 із сукупності 30 держав, а саме Німеччини, Італії, Нідерландів, Угорщини, РП, Іспанії, Румунії, Словенії та Чехії. Найбільшу частку усього асортименту зареєстрованих ТН ПП в Україні та РП займають aнтагоністи альфа-адренорецепторів, в РБ – інші препарати, що застосовують при доброякісній гіпертрофії передміхурової залози. Показано, що має місце використання контрактних форм виходу на досліджувані ринки. Виявлено, що на цих ринках існує висока залежність ПП від імпорту. Встановлено, що дев’ять з десяти ТН ПП на українському ринку зареєстровано у вигляді лікарських форм (ЛФ) для перорального застосування, решта – супозиторії і парентеральні ЛФ. На ринку РП присутні тільки ЛФ для перорального застосування. На ринку РБ понад чотири п’ятих ТН ПП представлені пероральними ЛФ, десята частина – супозиторіями, решта – парентеральними ЛФ.Висновки. На підставі аналізу даних офіційних реєстрів ЛЗ України, РП і РБ станом на 01.08.2017 р. визначено особливі та схожі характеристики ринків цих держав за асортиментом ПП, структурою їх виробників і заявників, форм виходу на ринки, асортиментною залежністю від імпорту та видом ЛФ. Отримані результати є важливими для подальшого формування aсортимeнтної політики щодо ПП в Україні.
СТАН БІОЦЕНОЗУ ПІХВИ ВАГІТНИХ З АНТЕНАТАЛЬНОЮ ЗАГИБЕЛЛЮ ПЛОДА
Authors: Gromova A. M. , Anwar. D. M. , Lyachovskaya T. Y. , Ketova E. N. 
Published: October 2017

Мета дослідження. Метою нашого дослідження було вивчення мікробного біоценозу піхви вагітних з антенатальною загибеллМатеріал і методи дослідження. Обстежено 55 жінок, з них 30 жінок з антенатальною загибеллю плода (АЗП, основна група) та 25 жінок з народженням живих дітей (контрольна група), порівняних за віком, паритетом, соматичною патологією. Дослідження інфекційного статусу включало: мікроскопічне дослідження вагінальних мазків; бактеріологічний посів на флору вмісту цервікального каналу; ПЛР-діагностику вмісту цервікального каналу. Результати дослідження та їх обговорення. Проведений аналіз показав, що серед жінок з АЗП коефіцієнт захворюваності (число захворювань на одну людину) становив 0,77 або 76,7 ± 4,3%, це в 2,4 рази більше, ніж у вагітних контрольної групи (коефіцієнт захворюваності 0, 32 або 32 ± 3,1%, р <0,05). Достовірно частіше у пацієнток основної групи вагітність супроводжувалася ранніми та пізніми гестозами, загрозливим абортом, анемією (р <0,05). Рівень інфікування піхви при взятті на облік в основній групі був у2,6 рази вищим, ніж у контрольній (р <0,05). Всім жінкам з інфікуванням піхви була проведена санація. При надходженні в стаціонар при порівнянні мікробіоценозу цервікального каналу у жінок з АЗП і нормальним перебігом вагітності виявлені значні відмінності в кількісному і якісному складі мікрофлори.Висновки. У вагітних з АЗП основними факторами ризику внутрішньоутробного інфікування плода є урогенітальні інфекції у матері, хронічні вогнища інфекції в організмі жінки, їх загострення під час вагітності, інфекційні захворювання в період гестації, наявність обтяженого акушерсько-гінекологічного анамнезу. Активація умовно-патогенної флори і тривалий вплив інфекційного агента сприяють розвитку імунних порушень, які, в свою чергу, ще більше посилюють дисбіотичний стан, підтримуючи тим самим запальний процес і значно підвищуючи ризик внутрішньоутробного інфікування плода аж до його антенатальної загибелі.
Outcomes of Reoperation After Acute Type A Aortic Dissection: Implications for Index Repair Strategy
Authors: Wang Hanghang , Wagner Matthew , Benrashid Ehsan , Keenan Jeffrey , Wang Alice , Ranney David , Yerokun Babatunde , Gaca Jeffrey G. , McCann Richard L. , Hughes G. Chad 
Published: October 2017

Background
The optimal surgical approach for management of acute type A aortic dissection remains controversial. This study aimed to assess outcomes of reoperation after acute type A dissection repair to help guide decision making around index operative strategy.

Methods and Results
All aortic reoperations (n=129) at a single referral institution from August 2005 to April 2016 after prior acute type A dissection repair were reviewed. The primary outcome was 30‐day or in‐hospital mortality. Secondary outcomes included organ‐specific morbidity and 1‐ and 5‐year outcomes as estimated using the Kaplan–Meier method. The majority of initial reoperations were proximal aortic (aortic valve, aortic root, or ascending) or aortic arch procedures (62.5%, n=55); most initial reoperations were performed in the elective setting (83.1%, n=74). Additional nonstaged second or more reoperations were required in 21 patients (23.6%) after the initial reoperation, during a median follow‐up of 2.5 years after the initial reoperation. Thirty‐day or in‐hospital mortality for all reoperations was 7.0% (elective: 6.3%; nonelective: 11.1%) with acceptable rates of organ‐specific morbidity, given the procedural complexity. One‐ and 5‐year overall survival after initial reoperation was 85.9% and 64.9%, respectively, with aorta‐specific survival of 88% at 5 years.

Conclusions
Reoperation after acute type A aortic dissection repair is associated with low rates of mortality and morbidity. These data support more limited index repair for acute type A dissection, especially for patients undergoing index repair in lower volume centers without expertise in extensive repair, because reoperations, if needed, can be performed safely in referral aortic centers.
Association Between Circulating Ketone Bodies and Worse Outcomes in Hemodialysis Patients
Authors: Obokata Masaru , Negishi Kazuaki , Sunaga Hiroaki , Ishida Hideki , Ito Kyoko , Ogawa Tetsuya , Iso Tatsuya , Ando Yoshitaka , Kurabayashi Masahiko 
Published: October 2017

Background
Cardiovascular disease is the leading cause of morbidity and mortality in patients receiving hemodialysis. Systemic metabolic perturbation is one of the hallmark abnormalities in patients at high cardiovascular risk. We sought to determine the relationship between circulating ketone body and clinical outcomes in patients with prevalent hemodialysis.

Methods and Results

We retrospectively assessed the relationship between serum β‐hydroxybutyrate (β
OHB
), the most abundant ketone body in the circulation, and prognosis in 405 stable hemodialysis patients. During a mean follow‐up of 3.2±0.9 years, there were 54 major adverse cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization attributed to heart failure) and 67 all‐cause deaths. Major adverse cardiovascular events rates increased from 11.1 per 1000 person‐years in the lowest β
OHB
quintile (<89 μmol/L) to 80.1 per 1000 person‐years in the highest quintile (>409 μmol/L). After adjusting for demographic characteristics, coronary artery disease, and atrial fibrillation, the highest β
OHB
quintile was associated with increased risk of major adverse cardiovascular events compared with the lowest quintile (hazard ratio, 10.2; 95% confidence interval [3.35–44.0];
P
<0.001). Increased quintiles of β
OHB
were independently and incrementally associated with major adverse cardiovascular events over the model based on an established risk score (the second Analyzing Data, Recognizing Excellence and Optimizing Outcomes cohort score) and N‐terminal pro‐B‐type natriuretic peptide (chi square 39.9 versus 21.7;
P
<0.001; c‐statistics, 0.713). Sensitivity analyses also confirmed the robustness of association between β
OHB
and all‐cause death.

Conclusions

Increased serum β
OHB
levels were independently associated with cardiovascular events and all‐cause death in patients receiving hemodialysis. These results highlight the need for future studies to understand the mechanisms underlying these observations.
Neither Fish nor Fowl. How eu Delegations Challenge the Institution of Diplomacy: The Cases of Moscow and Washington
Authors: Maurer Heidi , Raik Kristi 
Published: October 2017

Summary
This article explores European diplomatic cooperation abroad since 2009 by studying diplomatic structures and practices in two key locations: Moscow and Washington, dc. It analyses the functions of European Union (eu) delegations as part of the hybrid eu foreign policy system and their way of engaging with the changing global patterns of diplomatic practice. The empirical analysis draws on extensive semi-structured interviews conducted in Moscow and Washington during 2013-2014. Our cases confirm the deeper institutionalization and intensification of European diplomatic cooperation abroad. The eu delegations increasingly assumed traditional diplomatic tasks and coordinated member states on the ground. The eu delegations’ ability to establish good working relationships with member states as well as the leadership of key individuals (notably eu ambassadors) were key factors in shaping how this new system fell into place, which shows the continued prevalence of hybridity in eu foreign policy-making.
AGAMBEN. NAKED LIFE AND NUDITY
Authors: Östman Lars 
Published: October 2017

The Italian thinker Giorgio Agamben has achieved large international recognition since his first book in the homo sacer-project, Homo sacer. Il potere sovrano e la nuda vita, was published in 1995. The project’s basic aim is to try and understand the fundamental relation between man and power, politics and theology, which Agamben gives the name biopolitics. Such a politics, Agamben writes in the introduction, is the very fundamental element of Western metaphysics, “because it occupies the threshold in which the articulation between the living and logos is accomplished.” With relentless stringency scholars and researchers have analysed Agamben’s perhaps most famous concept, naked life, and related it to the history of religion, philosophy of law etc. The philosopher himself never thought that his term naked life would achieve such fame, as he said at a small conference at Iuav. However, what has been given less attention, if any, is the most obvious part in that concept: nudity. This holds the key, nonetheless, to understand Agamben’s thinking, because nudity is that very threshold holding together, as well as separating, life and logos, man and animal. Perhaps this is one of the reasons, if not needs, for Agamben writing a book with the telling title: Nudità.
Centre in the present article is to discuss Agamben’s concept of nudity alongside that of naked life in thematizing the term shame which is central in this regard. Furthermore, the attempt to argue in favour of a conceptual use of the metaphor-naked life-shall also be unfolded.
Rejection evaluation after renal transplantation using MR diffusion tensor imaging
Authors: Deger Emin , Celik Azim , Dheir Hamad , Turunc Volkan , Yardimci Ahmet , Torun Mert , Cihangiroglu Mutlu 
Published: October 2017

Background Renal allograft dysfunction monitoring is mainly performed using the serum creatinine (SC) level, Doppler ultrasound (US), or renal biopsy. Recently proposed diffusion-based magnetic resonance imaging (MRI) methods have been explored as new, non-invasive tools for assessing renal function after transplantation. Purpose To investigate the value of fractional anisotropy (FA) measurements in the evaluation of acute rejection cases after renal transplant. Material and Methods Doppler US and MRI diffusion tensor imaging (DTI) were performed in 21 patients with graft dysfunction requiring graft biopsy after renal transplantation and in 21 patients with normal graft function. The MR examinations were performed on a 1.5-T MRI using two b-values (0 and 800 s/mm2). FA values were measured from the cortex and medulla of the transplanted kidney at the upper, middle, and lower poles. Results Twenty-one transplant patients diagnosed with acute rejection (Group 1) were compared to the control group of 21 transplant patients with normal graft function (Group 2). The measured FA values of the medulla were 0.19 ± 0.02 and 0.22 ± 0.05 ( P = 0.017) for Groups 1 and 2, respectively. On the other hand, the measured FA values of the renal cortex were 0.18 ± 0.04 and 0.18 ± 0.04 ( P = 0.97) for Groups 1 and 2, respectively. Conclusion The good correlation between the renal medulla FA values and allograft function shows that MR DTI has potential for non-invasive functional assessment of transplanted kidneys. On the other hand, the renal cortex FA values had no correlation with the allograft function.
Understanding the Characteristics of Mass Spectrometry Data through the use of Simulation
Authors: Coombes Kevin R. , Koomen John M. , Baggerly Keith A. , Morris Jeffrey S. , Kobayashi Ryuji 
Published: October 2017

BackgroundMass spectrometry is actively being used to discover disease-related proteomic patterns in complex mixtures of proteins derived from tissue samples or from easily obtained biological fluids. The potential importance of these clinical applications has made the development of better methods for processing and analyzing the data an active area of research. It is, however, difficult to determine which methods are better without knowing the true biochemical composition of the samples used in the experiments.MethodsWe developed a mathematical model based on the physics of a simple MALDI-TOF mass spectrometer with time-lag focusing. Using this model, we implemented a statistical simulation of mass spectra. We used the simulation to explore some of the basic operating characteristics of MALDI or SELDI instruments.ResultsThe simulation reproduced several characteristics of actual instruments. We found that the relative mass error is affected by the time discretization of the detector (about 0.01%) and the spread of initial velocities (about 0.1%). The accuracy of calibration based on external standards decays rapidly outside the range spanned by the calibrants. Natural isotope distributions play a major role in broadening peaks associated with individual proteins. The area of a peak is a more accurate measure of its size than the height.ConclusionsThe model described here is capable of simulating realistic mass spectra. The simulation should become a useful tool for generating spectra where the true inputs are known, allowing researchers to evaluate the performance of new methods for processing and analyzing mass spectra.Availabilityhttp://bioinformatics.mdanderson.org/cromwell.html
Construction and Clarification of Dynamic Gene Regulatory Network of Cancer Cell Cycle via Microarray Data
Authors: Li Cheng-Wei , Chu Yung-Hsiang , Chen Bor-Sen 
Published: October 2017

BackgroundCell cycle is an important clue to unravel the mechanism of cancer cells. Recently, expression profiles of cDNA microarray data of Cancer cell cycle are available for the information of dynamic interactions among Cancer cell cycle related genes. Therefore, it is more appealing to construct a dynamic model for gene regulatory network of Cancer cell cycle to gain more insight into the infrastructure of gene regulatory mechanism of cancer cell via microarray data.ResultsBased on the gene regulatory dynamic model and microarray data, we construct the whole dynamic gene regulatory network of Cancer cell cycle. In this study, we trace back upstream regulatory genes of a target gene to infer the regulatory pathways of the gene network by maximum likelihood estimation method. Finally, based on the dynamic regulatory network, we analyze the regulatory abilities and sensitivities of regulatory genes to clarify their roles in the mechanism of Cancer cell cycle.ConclusionsOur study presents a systematically iterative approach to discern and characterize the transcriptional regulatory network in Hela cell cycle from the raw expression profiles. The transcription regulatory network in Hela cell cycle can also be confirmed by some experimental reviews. Based on our study and some literature reviews, we can predict and clarify the E2F target genes in G1/S phase, which are crucial for regulating cell cycle progression and tumorigenesis. From the results of the network construction and literature confirmation, we infer that MCM4, MCM5, CDC6, CDC25A, UNG and E2F2 are E2F target genes in Hela cell cycle.
Development of Query Strategies to Identify a Histologic Lymphoma Subtype in a Large Linked Database System
Authors: Graiser Michael , Moore Susan G. , Victor Rochelle , Hilliard Ashley , Hill Leroy , Keehan Michael S. , Flowers Christopher R. 
Published: October 2017

Background Large linked databases (LLDB) represent a novel resource for cancer outcomes research. However, accurate means of identifying a patient population of interest within these LLDBs can be challenging. Our research group developed a fully integrated platform that provides a means of combining independent legacy databases into a single cancer-focused LLDB system. We compared the sensitivity and specificity of several SQL-based query strategies for identifying a histologic lymphoma subtype in this LLDB to determine the most accurate legacy data source for identifying a specific cancer patient population. Methods Query strategies were developed to identify patients with follicular lymphoma from a LLDB of cancer registry data, electronic medical records (EMR), laboratory, administrative, pharmacy, and other clinical data. Queries were performed using common diagnostic codes (ICD-9), cancer registry histology codes (ICD-O), and text searches of EMRs. We reviewed medical records and pathology reports to confirm each diagnosis and calculated the sensitivity and specificity for each query strategy. Results Together the queries identified 1538 potential cases of follicular lymphoma. Review of pathology and other medical reports confirmed 415 cases of follicular lymphoma, 300 pathology-verified and 115 verified from other medical reports. The query using ICD-O codes was highly specific (96%). Queries using text strings varied in sensitivity (range 7–92%) and specificity (range 86–99%). Queries using ICD-9 codes were both less sensitive (34–44%) and specific (35–87%). Conclusions Queries of linked-cancer databases that include cancer registry data should utilize ICD-O codes or employ structured free-text searches to identify patient populations with a precise histologic diagnosis.