bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining statistics from two national complex surveys to estimate injury rates per hour exposed and variance by activity in the USA
Authors: Lin Tin-chi , Marucci-Wellman Helen R , Willetts Joanna L , Brennan Melanye J , Verma Santosh K 
Published: November 2016

BackgroundA common issue in descriptive injury epidemiology is that in order to calculate injury rates that account for the time spent in an activity, both injury cases and exposure time of specific activities need to be collected. In reality, few national surveys have this capacity. To address this issue, we combined statistics from two different national complex surveys as inputs for the numerator and denominator to estimate injury rate, accounting for the time spent in specific activities and included a procedure to estimate variance using the combined surveys.MethodsThe 2010 National Health Interview Survey (NHIS) was used to quantify injuries, and the 2010 American Time Use Survey (ATUS) was used to quantify time of exposure to specific activities. The injury rate was estimated by dividing the average number of injuries (from NHIS) by average exposure hours (from ATUS), both measured for specific activities. The variance was calculated using the ‘delta method’, a general method for variance estimation with complex surveys.ResultsAmong the five types of injuries examined, ‘sport and exercise’ had the highest rate (12.64 injuries per 100 000 h), followed by ‘working around house/yard’ (6.14), driving/riding a motor vehicle (2.98), working (1.45) and sleeping/resting/eating/drinking (0.23). The results show a ranking of injury rate by activity quite different from estimates using population as the denominator.ConclusionsOur approach produces an estimate of injury risk which includes activity exposure time and may more reliably reflect the underlying injury risks, offering an alternative method for injury surveillance and research.
Medical morbidity and mortality conferences: past, present and future
Authors: George J 
Published: November 2016

ABSTRACTMorbidity and mortality conferences (MMCs) have three potential aims—to improve patient safety by reducing adverse events and preventable deaths, to improve overall quality of care as part of the hospital governance structure and as educational learning events. At present, medical MMCs vary widely in format and attendance from hospital to hospital. The evidence for MMCs actually reducing adverse events and preventing avoidable deaths is disappointing. There is better evidence for their educational role. The majority of medical deaths in hospitals are frail older people with poor life expectancy in whom inadequate care is more likely to be due to errors of omission rather than commission. Medical MMCs should be multidisciplinary and led by a senior clinician to encourage discussion and reflection in a ‘blame-free’ environment. They should be learning events for both clinicians and the organisation as a whole with a structure to support this.
Conformational Change of Mutant form of Amyloid Precursor Protein by Carbon Nanotube Functionalized with Morin
Authors: Jafarinezhad Sa’ideh , Ashkezari Mahmood Dehghani , Jebali Ali 
Published: November 2016

The aim of this study was to find the effect of carbon nanotube functionalized with Morin molecule (CNTFM) on normal and mutant forms of amyloid precursor protein (APP), found in Alzheimer’s disease. In this study, one mutant and one normal APP were separately modeled in Hyperchem software. After minimization of system energy, molecular dynamic (MD) simulation was separately carried out for 30[Formula: see text]000[Formula: see text]ps in NVT ensemble at 310[Formula: see text]K. At the end of simulation, different parameters, such as free energy, intermolecular energy and root mean square displacement (RMSD) were separately monitored for each APP. Finally, the ratio of change was calculated for each parameter. To confirm simulation results, one mL of mutant APP (10 mM) was incubated with one mL of CNTFM (10[Formula: see text]mg/mL) for 1[Formula: see text]h. Finally, the percentages of the different secondary structures of both treated and untreated APP were separately estimated by FTIR analysis. Based on MD simulation, high ratio of change was seen for mutant APP. Experimental study showed that the proportion of [Formula: see text]-sheets (parallel [Formula: see text] anti-parallel) and random coil was decreased when incubated with CNTFM. Moreover, the proportion of [Formula: see text]-turns was increased. Interestingly, the proportion of [Formula: see text]-sheets (anti-parallel) was not changed.
Throw partitioning across normal fault zones in the Ptolemais Basin, Greece
Authors: Delogkos Efstratios , Manzocchi Tom , Childs Conrad , Sachanidis Christos , Barbas Tryfon , Schöpfer Martin P. J. , Chatzipetros Alexandros , Pavlides Spyros , Walsh John J. 
Published: November 2016

Abstract
The total throw across a fault zone may not occur entirely on a single fault strand but may be distributed onto several strands or may be accommodated by distributed deformation within or adjacent to the fault zone. Here we conduct a quantitative analysis of the partitioning of throw into three components, the throw accommodated by: (a) the largest fault strand; (b) subsidiary faults; and (c) continuous deformation in the form of bed rotation in sympathy with the fault downthrow direction. This analysis is applied to seven seismic-scale fault zones at outcrop resolution (maximum throw 50 m) that were mapped over a four-year period during open-cast lignite mining within the late Miocene–Pliocene Ptolemais Basin, West Macedonia, Greece. The analysis shows that the fault zones offsetting the lignite–marl sequence are more localized at higher throws with progressively more of the total throw accommodated by the largest fault strand. Normal drag, which can account for up to 12 m of the total throw, accommodates a lower proportion of the total throw on larger faults. It appears that initial fault segmentation is the main control on the degree of, and spatial variation in, fault throw partitioning.
Transcriptional Induction of Periostin by a Sulfatase 2–TGFβ1–SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma
Authors: Chen Gang , Nakamura Ikuo , Dhanasekaran Renumathy , Iguchi Eriko , Tolosa Ezequiel J. , Romecin Paola A. , Vera Renzo E. , Almada Luciana L. , Miamen Alexander G. , Chaiteerakij Roongruedee , Zhou Mengtao , Asiedu Michael K. , Moser Catherine D. , Han Shaoshan , Hu Chunling , Banini Bubu A. , Oseini Abdul M. , Chen Yichun , Fang Yong , Yang Dongye , Shaleh Hassan M. , Wang Shaoqing , Wu Dehai , Song Tao , Lee Ju-Seog , Thorgeirsson Snorri S. , Chevet Eric , Shah Vijay H. , Fernandez-Zapico Martin E. , Roberts Lewis R. 
Published: November 2016

Abstract
Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo. The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and upregulation of POSTN transcription. In clinical HCC specimens, elevated levels of SULF2 correlated with increased microvascular density, POSTN levels, and relatively poorer patient survival. Together, our findings define an important axis controlling angiogenesis in HCC and a mechanistic foundation for rational drug development. Cancer Res; 77(3); 632–45. ©2016 AACR.
Macrophage-Secreted TNFα and TGFβ1 Influence Migration Speed and Persistence of Cancer Cells in 3D Tissue Culture via Independent Pathways
Authors: Li Ran , Hebert Jess D. , Lee Tara A. , Xing Hao , Boussommier-Calleja Alexandra , Hynes Richard O. , Lauffenburger Douglas A. , Kamm Roger D. 
Published: November 2016

AbstractThe ability of a cancer cell to migrate through the dense extracellular matrix within and surrounding the solid tumor is a critical determinant of metastasis. Macrophages enhance invasion and metastasis in the tumor microenvironment, but the basis for their effects is not fully understood. Using a microfluidic 3D cell migration assay, we found that the presence of macrophages enhanced the speed and persistence of cancer cell migration through a 3D extracellular matrix in a matrix metalloproteinases (MMP)-dependent fashion. Mechanistic investigations revealed that macrophage-released TNFα and TGFβ1 mediated the observed behaviors by two distinct pathways. These factors synergistically enhanced migration persistence through a synergistic induction of NF-κB–dependent MMP1 expression in cancer cells. In contrast, macrophage-released TGFβ1 enhanced migration speed primarily by inducing MT1-MMP expression. Taken together, our results reveal new insights into how macrophages enhance cancer cell metastasis, and they identify TNFα and TGFβ1 dual blockade as an antimetastatic strategy in solid tumors. Cancer Res; 77(2); 279–90. ©2016 AACR.
Conflicting Signals for Cancer Treatment
Authors: Sujobert Pierre , Trautmann Alain 
Published: November 2016

Abstract
Next-generation sequencing technologies have provided us with a precise description of the mutational burden of cancers, making it possible to identify targetable oncogene addictions. However, the emergence of resistant clones is an inevitable limitation of therapies targeting these addictions. Alternative approaches to cancer treatment are therefore required. We propose here a novel approach, based on the notion of conflicting signals and on a phenotypic description of cancer cells. “Phenotype” is an inherently complex notion that we describe in the conceptual framework of the epigenetic landscape, with a view to bridging the gap between theory and practice at the patient's bedside. By passing from theory to the description of several examples, we will illustrate how this approach can facilitate data analysis and the design of new strategies for cancer treatment. Cancer Res; 76(23); 6768–73. ©2016 AACR.
Menin and Daxx Interact to Suppress Neuroendocrine Tumors through Epigenetic Control of the Membrane Metallo-Endopeptidase
Authors: Feng Zijie , Wang Lei , Sun Yanmei , Jiang Zongzhe , Domsic John , An Chiying , Xing Bowen , Tian Jingjing , Liu Xiuheng , Metz David C. , Yang Xiaolu , Marmorstein Ronen , Ma Xiaosong , Hua Xianxin 
Published: November 2016

Abstract
Neuroendocrine tumors (NET) often harbor loss-of-function mutations in the MEN1 and DAXX tumor suppressor genes. Here, we report that the products of these genes, menin and Daxx, interact directly with each other to suppress the proliferation of NET cells, to a large degree by inhibiting expression of the membrane metallo-endopeptidase (MME). Menin and Daxx were required to enhance histone H3 lysine9 trimethylation (H3K9me3) at the MME promoter, as mediated partly by the histone H3 methyltransferase SUV39H1. Notably, the menin T429K mutation associated with a NET syndrome reduced Daxx binding, MME repression, and proliferation of NET cells. Conversely, inhibition of MME in NET cells repressed proliferation and tumor growth in vivo. Our findings reveal a previously unappreciated cross-talk between two crucial tumor suppressor genes thought to work by independent pathways, focusing on MME as a common target of menin/Daxx to treat NET. Cancer Res; 77(2); 401–11. ©2016 AACR.
Rapid and Continued T-Cell Differentiation into Long-term Effector and Memory Stem Cells in Vaccinated Melanoma Patients
Authors: Gannon Philippe O. , Baumgaertner Petra , Huber Alexandre , Iancu Emanuela M. , Cagnon Laurène , Abed Maillard Samia , Maby-El Hajjami Hélène , Speiser Daniel E. , Rufer Nathalie 
Published: November 2016

AbstractPurpose: Patients with cancer benefit increasingly from T-cell–based therapies, such as adoptive T-cell transfer, checkpoint blockade, or vaccination. We have previously shown that serial vaccinations with Melan-AMART-126-35 peptide, CpG-B, and incomplete Freund adjuvant (IFA) generated robust tumor-specific CD8 T-cell responses in patients with melanoma. Here, we describe the detailed kinetics of early- and long-term establishment of T-cell frequency, differentiation (into memory and effector cells), polyfunctionality, and clonotype repertoire induced by vaccination.Experimental Design: Twenty-nine patients with melanoma were treated with multiple monthly subcutaneous vaccinations consisting of CpG-B, and either the native/EAA (n = 13) or the analogue/ELA (n = 16) Melan-AMART-126-35 peptide emulsified in IFA. Phenotypes and functionality of circulating Melan-A–specific CD8 T cells were assessed directly ex vivo by multiparameter flow cytometry, and TCR clonotypes were determined ex vivo by mRNA transcript analyses of individually sorted cells.Results: Our results highlight the determining impact of the initial vaccine injections on the rapid and strong induction of differentiated effector T cells in both patient cohorts. Moreover, long-term polyfunctional effector T-cell responses were associated with expansion of stem cell–like memory T cells over time along vaccination. Dominant TCR clonotypes emerged early and persisted throughout the entire period of observation. Interestingly, one highly dominant clonotype was found shared between memory and effector subsets.Conclusions: Peptide/CpG-B/IFA vaccination induced powerful long-term T-cell responses with robust effector cells and stem cell-like memory cells. These results support the further development of CpG-B–based cancer vaccines, either alone or as specific component of combination therapies. Clin Cancer Res; 23(13); 3285–96. ©2016 AACR.
НАУКОВО-МЕТОДИЧНІ ОСНОВИ ВИКЛАДАННЯ ФАРМАКОЛОГІЇ ЛІКАРСЬКИХ ЗАСОБІВ, ЩО ВПЛИВАЮТЬ НА ПРОЦЕСИ ЗГОРТАННЯ КРОВІ
Authors: Voloshchuk N. I. , Denysіuk O. M. , Danylchuk V. V. , Bihovshchyts S. V. 
Published: November 2016

Швидкий розвиток фармакологічної науки та поява нових лікарських засобів вимагають постійної зміни програмного матеріалу і вдосконалення методичних підходів до викладання цього матеріалу майбутнім лікарям. Метa роботи – виділити підходи до викладання одного з найбільш складних та важливих розділів фармакології – “Засоби, що впливають на згортання крові” студентам 3-го курсу медичного факультету й 2-го курсу стоматологічного факультету. Аналіз педагогічного досвіду викладачів кафедри фармакології Вінницького національного медичного університету та літературних даних показав, що оптимальним є комплексний підхід. Він включає надання інформації викладачем на лекційних і практичних заняттях (пояснювально-ілюстративний метод), активний самостійний пошук інформації студентом (репродуктивний, проблемний, евристичний методи), а також інноваційні та нетрадиційні методи навчання (наприклад, фармакологічна вікторина). Принцип “від простого до складного” при збереженні послідовності дидактичних підходів викладання, а також правильна організація аудиторної та позааудиторної самостійної роботи студентів дозволяють отримати стабільні і глибокі знання та вміння, навчити його працювати самостійно.
ДОСВІД ПІДГОТОВКИ СТУДЕНТІВ ДО УЧАСТІ У ВСЕУКРАЇНСЬКІЙ СТУДЕНТСЬКІЙ ОЛІМПІАДІ З КЛІНІЧНОЇ ІМУНОЛОГІЇ ТА АЛЕРГОЛОГІЇ (підсумки викладачів та погляд студентів)
Authors: Rodionova V. V. , Kovalenko O. M. , Nіkolayenko-Kamyshova T. P. , Sobko S. V. , Khmel O. S. 
Published: November 2016

У роботі представлено узагальнення досвіду з проведення І етапу студентської олімпіади з клінічної імунології та алергології в рамках підготовки студентів до участі в ІІ етапі Всеукраїнської студентської олімпіади. Метою проведеної роботи було показати можливі шляхи підвищення навчальної мотивації студентів та якості навчання на клінічному циклі. На кафедрі внутрішньої медицини № 2 та профпатології ДЗ “Дніпропетровська медична академія МОЗ України” протягом 3-х років проводиться І етап Всеукраїнської студентської олімпіади, в якій беруть участь студенти 5, 6 курсів. Описано етапи, які входять до програми внутрішньовузівської олімпіади. У висновках надаються рекомендації: проведення фахової олімпіади надає змогу підвести підсумки роботи з викладання дисципліни “Клінічна імунологія та алергологія”; змагання сприяють виконанню мети і головного завдання вузу і кожного викладача – підвищення якості підготовки кваліфікованих спеціалістів; проведення І етапу та підготовку до ІІ етапу Всеукраїнської студентської олімпіади бажано здійснювати із залученням провідних фахівців - практичних лікарів, що надає змогу студентам отримати не тільки глибокі теоретичні знання, але й практичний досвід, що загалом сприяє самоствердженню студентів та підвищенню науково-практичного потенціалу студентського корпусу.
Plasma Metabolomics Implicates Modified Transfer RNAs and Altered Bioenergetics in the Outcomes of Pulmonary Arterial Hypertension
Authors: Rhodes Christopher J. , Ghataorhe Pavandeep , Wharton John , Rue-Albrecht Kevin C. , Hadinnapola Charaka , Watson Geoffrey , Bleda Marta , Haimel Matthias , Coghlan Gerry , Corris Paul A. , Howard Luke S. , Kiely David G. , Peacock Andrew J. , Pepke-Zaba Joanna , Toshner Mark R. , Wort S. John , Gibbs J. Simon R. , Lawrie Allan , Gräf Stefan , Morrell Nicholas W. , Wilkins Martin R. 
Published: November 2016

Background:
Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality.

Methods:
We conducted a comprehensive study of plasma metabolites using ultraperformance liquid chromatography mass spectrometry to identify patients at high risk of early death, to identify patients who respond well to treatment, and to provide novel molecular insights into disease pathogenesis.

Results:

Fifty-three circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy control subjects (n=121) after correction for multiple testing (
P
<7.3e-5) and confounding factors, including drug therapy, and renal and hepatic impairment. A subset of 20 of 53 metabolites also discriminated patients with PAH from disease control subjects (symptomatic patients without pulmonary hypertension, n=139). Sixty-two metabolites were prognostic in PAH, with 36 of 62 independent of established prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2-dimethylguanosine, N1-methylinosine), tricarboxylic acid cycle intermediates (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan, and polyamine metabolites and decreased levels of steroids, sphingomyelins, and phosphatidylcholines distinguished patients from control subjects. The largest differences correlated with increased risk of death, and correction of several metabolites over time was associated with a better outcome. Patients who responded to calcium channel blocker therapy had metabolic profiles similar to those of healthy control subjects.

Conclusions:
Metabolic profiles in PAH are strongly related to survival and should be considered part of the deep phenotypic characterization of this disease. Our results support the investigation of targeted therapeutic strategies that seek to address the alterations in translational regulation and energy metabolism that characterize these patients.
A Contemporary Muslim Scholar’s Approach to Revelation: Moḥammad Moǧtahed Šabestarī’s Reform Project
Authors: Akbar Ali 
Published: November 2016

Over the late twentieth and early twenty-first centuries, rethinking the traditional understanding of revelation has been welcomed by a number of Muslim scholars. Moḥammad Moǧtahed Šabestarī, an influential Šīʿī reformer from contemporary Iran, certainly falls in the category of such scholars. The aim of this paper is to discuss his theory of revelation for the purpose of exploring the potential values it holds for flexible interpretation of Islam in the present context. The paper argues that Šabestarī’s method of interpretation of the Qurʾān has its roots in his account of revelation. In order to show in practice how Šabestarī’s understanding of the nature of revelation influences the way he approaches the Qurʾān, the paper focuses on three main themes that consistently appear throughout his writings, namely Qurʾānic socio-political provisions, religious pluralism and the relation between state and religion. The paper, in general, provides an insight of how rethinking the classical methods, ideas and approaches can take place within Islamic tradition in the modern period.À la fin du xxe et début du xxie siècles, le fait de repenser la compréhension traditionnelle de la Révélation fut bien accueilli par un certain nombre de savants musulmans. Moḥammad Moǧtahed Šabestarī, un influent réformateur chiite de l’Iran contemporain, appartient sans nul doute à cette catégorie de savants. Le propos de cet article est d’analyser sa théorie sur la Révélation dans le but d’explorer ses valeurs potentielles pour une interprétation souple de l’islam en fonction du contexte contemporain. L’article démontre que la méthode d’interprétation du Coran de Šabestarī trouve ses racines dans son récit de la Révélation. Afin de montrer concrètement comment la compréhension qu’avait Šabestanī de la nature de la Révélation influence la façon dont il aborde le Coran, l’article se concentre sur trois thèmes principaux qui apparaissent systématiquement dans ses écrits, à savoir les dispositions socio-politiques du Coran, le pluralisme religieux et la relation entre l’État et la religion. D’une manière générale, l’article donne un aperçu de la façon dont le fait de repenser les méthodes, idées et approches classiques peut avoir sa place dans la tradition islamique à l’époque contemporaine.
This article is in English.
The Court of the Grand Prince of Muscovy and the Court of France in the 14th–16th Centuries: Comparing the Incomparable? (Государев двор России и королевский двор Франции в XIV–XVI вв.
Authors: Korzinin A.L. , Shishkin V.V. 
Published: November 2016

This study compares the organization, function, and personnel of the royal courts in Muscovy and France in the fourteenth through sixteenth centuries, a period vital to the consolidation of monarchical power in both states. The article traces the rise and parallel development of the ruler’s court in Muscovy and France, and makes the case for significant similarities between the two. In both, membership in the court elite was rooted in similar social and political structures (in Muscovy, membership in the elite was rooted in birth and longtime service to the ruler, while in France it was rooted in birth and proximity to the king), and both courts were positioned in similar ways at the center of politics and religious culture. The similarities between Muscovy and France become especially apparent during the reigns of Ivan IV and Henry III, when both monarchs instituted reforms aimed at strengthening central monarchical power and institutions, and when the rulers were confronting significant centrifugal pressures among the nobility and regional elites. The article argues that the court of the Grand Prince of Muscovy in the second half of fifteenth and first half of the sixteenth centuries was in function, structure, and ritual form very close to that of many other Renaissance courts of Europe, particularly to that of France.