bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound imaging to tailor the treatment of acute shoulder pain: a randomised controlled trial in general practice
Authors: Ottenheijm Ramon P G , Cals Jochen W L , Winkens Bjorn , Weijers René E , de Bie Rob A , Dinant Geert-Jan 
Published: November 2016

ObjectiveTo determine the clinical effectiveness of ultrasound tailored treatment in patients with acute subacromial disorders.DesignPragmatic randomised controlled trial.SettingDutch general practice.ParticipantsPatients aged 18–65 years with acute (duration <3 months) unilateral shoulder pain and no previous treatment, in whom the general practitioner suspected a subacromial disorder was enrolled.InterventionsAll patients underwent ultrasound imaging of the affected shoulder. Patients who were still symptomatic after a qualification period of 2 weeks with standard treatment were randomised to treatment tailored to ultrasound diagnosis (disclosure of the ultrasound diagnosis) or usual care (non-disclosure of the ultrasound diagnosis).Primary outcome measurePatient-perceived recovery using the Global Perceived Effect questionnaire at 1 year.Results129 patients were included. 18 patients recovered during the 2-week qualification period, resulting in 111 randomised patients; 56 were allocated to ultrasound tailored treatment and 55 to usual care. After 1 year, no statistically significant differences in recovery were found between the ultrasound tailored treatment group (72.5% (37/51)) and the usual care group (60% (30/50), OR 2.24 (95% CI 0.72 to 6.89; p=0.16)). Also, healthcare use was similar.ConclusionsThis study has shown no clinically significant difference in the primary outcome measure between the ultrasound tailored treatment and usual care groups. Furthermore, there was no overall difference in healthcare resources used between groups. Although no formal cost data are included, one can only assume that the ultrasound examinations are additional costs for the intervention group, which cannot be justified in routine practice based on this trial. Based on this study, no change in current pragmatic guidelines to incorporate early ultrasound imaging can be recommended.Trial registration numberNTR2403; Results.
Reporting quality of abstracts of trials published in top five pain journals: a protocol for a systematic survey
Authors: Sriganesh Kamath , Bharadwaj Suparna , Wang Mei , Abbade Luciana P F , Couban Rachel , Mbuagbaw Lawrence , Thabane Lehana 
Published: November 2016

IntroductionAbstracts of randomised controlled trials (RCTs) are often the first and the only source read in a journal by busy healthcare providers. This necessitates good reporting of abstracts. The quality of reporting of abstracts, though gradually improving over time, is still not uniform across medical journals. Improvement in completeness of reporting of abstracts has been documented in general medical journals after the publication of the consolidated standards of reporting trials (CONSORT) extension for abstracts in 2008. Currently, this aspect has not been assessed with regards to pain journals. This study aims to compare the completeness of reporting of abstracts before and after the publication of CONSORT statement for abstracts in five pain journals.Methods and analysesThe abstracts of RCTs published from 1 January 2005 to 31 December 2007 (pre-CONSORT) and from 1 January 2013 to 31 December 2015 (post-CONSORT) will be assessed for the quality of reporting. Studies without abstracts, non-English abstracts, abstracts not reporting on RCTs or on humans and conference abstracts will be excluded. A thorough search of MEDLINE will be carried out in April 2016. All identified studies will be screened for inclusion based on titles and abstracts. Data will be extracted by two sets of independent reviewers for each abstract in duplicate regarding compliance with CONSORT statement for abstracts. Full-text review will be performed to obtain additional characteristics which are likely to affect reporting quality. The unadjusted and adjusted differences in the mean number of items reported will be analysed using a two sample t-test and generalised estimation equation in SPSS.Ethics and disseminationAs far as we know, this is the first study to evaluate reporting quality of abstracts of pain journals based on CONSORT extension for abstracts. The findings of this study will be disseminated by a presentation at a conference and through publication in a peer-reviewed journal. Ethics committee approval was not sought for this survey.
Tim-3 Expression on Tumor-Infiltrating PD-1+CD8+ T Cells Correlates with Poor Clinical Outcome in Renal Cell Carcinoma
Authors: Granier Clémence , Dariane Charles , Combe Pierre , Verkarre Virginie , Urien Saïk , Badoual Cécile , Roussel Hélène , Mandavit Marion , Ravel Patrice , Sibony Mathilde , Biard Lucie , Radulescu Camélia , Vinatier Emeline , Benhamouda Nadine , Peyromaure Michael , Oudard Stéphane , Méjean Arnaud , Timsit Marc-Olivier , Gey Alain , Tartour Eric 
Published: November 2016

Abstract
Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens, with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8+ T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry. The percentage of tumor-infiltrating CD8+ T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis. Coexpression of PD-1 and Tim-3 above the median conferred a higher risk of relapse and a poorer 36-month overall survival. Notably, other CD8+T-cell subsets did not exert a similar effect on overall survival. Moreover, only the PD-1+Tim-3+ subset of CD8+ T cells exhibited impaired function after stimulation. Our findings establish intratumoral Tim-3+PD1+CD8+ T cells as critical mediators of an aggressive phenotype in RCC. Use of the Vectra tool may be useful to identify similarly critical prognostic and predictive biomarkers in other tumor types and their response to immunotherapy. Cancer Res; 77(5); 1075–82. ©2016 AACR.
Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia
Authors: Ding Ling-Wen , Sun Qiao-Yang , Tan Kar-Tong , Chien Wenwen , Thippeswamy Anand Mayakonda , Eng Juh Yeoh Allen , Kawamata Norihiko , Nagata Yasunobu , Xiao Jin-Fen , Loh Xin-Yi , Lin De-Chen , Garg Manoj , Jiang Yan-Yi , Xu Liang , Lim Su-Lin , Liu Li-Zhen , Madan Vikas , Sanada Masashi , Fernández Lucia Torres , Preethi Hema , Lill Michael , Kantarjian Hagop M. , Kornblau Steven M. , Miyano Satoru , Liang Der-Cherng , Ogawa Seishi , Shih Lee-Yung , Yang Henry , Koeffler H. Phillip 
Published: November 2016

Abstract
Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targeted therapies. Here, we report the use of next-generation sequencing to interrogate the genetic and pathogenic mechanisms of 240 pediatric ALL cases with their matched remission samples. Commonly mutated genes fell into several categories, including RAS/receptor tyrosine kinases, epigenetic regulators, transcription factors involved in lineage commitment, and the p53/cell-cycle pathway. Unique recurrent mutational hotspots were observed in epigenetic regulators CREBBP (R1446C/H), WHSC1 (E1099K), and the tyrosine kinase FLT3 (K663R, N676K). The mutant WHSC1 was established as a gain-of-function oncogene, while the epigenetic regulator ARID1A and transcription factor CTCF were functionally identified as potential tumor suppressors. Analysis of 28 diagnosis/relapse trio patients plus 10 relapse cases revealed four evolutionary paths and uncovered the ordering of acquisition of mutations in these patients. This study provides a detailed mutational portrait of pediatric ALL and gives insights into the molecular pathogenesis of this disease. Cancer Res; 77(2); 390–400. ©2016 AACR.
PolyI:C and CpG Synergize with Anti-ErbB2 mAb for Treatment of Breast Tumors Resistant to Immune Checkpoint Inhibitors
Authors: Charlebois Roxanne , Allard Bertrand , Allard David , Buisseret Laurence , Turcotte Martin , Pommey Sandra , Chrobak Pavel , Stagg John 
Published: November 2016

Abstract
Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs, such as trastuzumab. In the clinic, breast tumors poorly infiltrated with immune cells are more resistant to trastuzumab, and patients have a worse prognosis. Because type I and II IFNs are critical to the immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse models of ErbB2+ breast cancer. We demonstrated that in situ delivery of polyI:C and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory response in breast tumors able to induce long-lasting CD8+ T cell–dependent antitumor immunity. Remarkably, polyI:C and CpG was superior to combined PD-1/CTLA-4 blockade in sensitizing tumors to anti-ErbB2 mAb therapy. Local injection of CpG and polyI:C in a primary tumor significantly enhanced the activity of systemic anti-ErbB2 mAb against a distant untreated tumor. Type I and II IFNs, as well as natural killer cells and CD8+ T cells, were indispensible to the synergistic activity of the combination treatment. Because synthetic RNA analogues and CpG oligodeoxynucleotides have been safely used in clinical trials, our study supports combination treatments with anti-ErbB2 mAbs. Cancer Res; 77(2); 312–9. ©2016 AACR.
Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton
Authors: Kazazian Karineh , Go Christopher , Wu Hannah , Brashavitskaya Olga , Xu Roland , Dennis James W. , Gingras Anne-Claude , Swallow Carol J. 
Published: November 2016

Abstract
The polo family serine threonine kinase Plk4 has been proposed as a therapeutic target in advanced cancers based on increased expression in primary human cancers, facilitation of tumor growth in murine xenograft models, and centrosomal amplification induced by its overexpression. However, both the causal link between these phenomena and the feasibility of selective Plk4 inhibition remain unclear. Here we characterize Plk4-dependent cancer cell migration and invasion as well as local invasion and metastasis of cancer xenografts. Plk4 depletion suppressed cancer invasion and induced an epithelial phenotype in poorly differentiated breast cancer cells. In an unbiased BioID screen for Plk4 interactors, we identified members of the Arp2/3 complex and confirmed a physical and functional interaction between Plk4 and Arp2 in mediating Plk4-driven cancer cell movement. This interaction is mediated through the Plk4 Polo-box 1-Polo-box 2 domain and results in phosphorylation of Arp2 at the T237/T238 activation site, which is required for Plk4-driven cell movement. Our results validate Plk4 as a therapeutic target in cancer patients and reveal a new role for Plk4 in regulating Arp2/3-mediated actin cytoskeletal rearrangement. Cancer Res; 77(2); 434–47. ©2016 AACR.
Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions
Authors: Vernieri Claudio , Casola Stefano , Foiani Marco , Pietrantonio Filippo , de Braud Filippo , Longo Valter 
Published: November 2016

AbstractMost tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacologic approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs, and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be highly specific and effective, but must be matched with a responsive tumor, which might rapidly adapt. In this review, we illustrate how dietary and pharmacologic therapies differ in their effect on tumor growth, proliferation, and metabolism and discuss the available preclinical and clinical evidence in favor of or against each of them. We also indicate, when appropriate, how to optimize future investigations on metabolic therapies on the basis of tumor- and patient-related characteristics.Significance: To our knowledge, this is the first review article that comprehensively analyzes the preclinical and preliminary clinical experimental foundations of both dietary and pharmacologic metabolic interventions in cancer therapy. Among several promising therapies, we propose treatment personalization on the basis of tumor genetics, tumor metabolism, and patient systemic metabolism.Cancer Discov; 6(12); 1315–33. ©2016 AACR.
РЕФОРМУВАННЯ ВИЩОЇ ОСВІТИ В УКРАЇНІ
Authors: Shukhtin V. V. , Коtiuzhynska S. H. , Lіebіedіevа T. L. , Shukhtina I. M. 
Published: November 2016

У статті розглянуті основні правові, організаційні, фінансові засади функціонування системи вищої освіти, які створюють умови для поєднання освіти з наукою та виробництвом з метою підготовки конкурентоспроможного людського капіталу для високотехнологічного та інноваційного розвитку країни, самореалізації особистості, забезпечення потреб суспільства, ринку праці та держави у кваліфікованих фахівцях. Автори статті аналізують ключові проблеми розвитку системи освіти, підвищення якості професійної підготовки фахівців, законодавчого регулювання розвитку системи вищої освіти в Україні в контексті Болонського процесу. Висвітлено стан і перспективи змін освітньої системи України в аспектах використання та вдосконалення різних засобів забезпечення якості навчального процесу і заключних освітніх кваліфікацій. Розглянуто проблемні фактори функціонування вищої освіти України під кутом зору нагальних потреб модернізації вітчизняного освітнього середовища, тобто приведення його у відповідність до імперативних вимог сучасності. Особлива увага приділяється міжнародному співробітництву в галузі освіти, інтеграції національної освіти до міжнародного освітянського простору.
МЕЖІ СЕРЦЕВОЇ ТУПОСТІ: ПРОТИРІЧЧЯ МІЖ ІСТИНОЮ І КАНОНІЧНИМИ ПРАВИЛАМИ ПЕРКУСІЇ В ПРОПЕДЕВТИЦІ ВНУТРІШНІХ ХВОРОБ
Authors: Buhai B. H. , Andreichyn S. M. , Chernets T. Yu. , Chlek M. V. , Bilkevych N. A. , Ruda M. M. , Vereshchahina N. Ya. , Yarema N. Z. , Kavetska N. A. , Hanberger I. I. , Kucher S. V. 
Published: November 2016

У статті викладена необхідність зміни стереотипів щодо канонічних методик перкуторного визначення меж відносної та абсолютної тупостей серця. Корективи, запропоновані авторами, дозволяють клініцистам біля ліжка хворого уникнути похибки в понад один сантиметр при визначенні верхньої межі серця за стандартами його відносної та абсолютної тупостей, і внести елементи примирення при інтерпретації різних варіантів його перкусії, що має особливе значення для викладачів кафедр пропедевтики внутрішньої медицини та майбутніх лікарів.
ОРГАНІЗАЦІЯ ПРАКТИЧНОЇ ПІДГОТОВКИ СТУДЕНТІВ-ПРОВІЗОРІВ ПРИ ВИВЧЕННІ ОРГАНІЧНОЇ ХІМІЇ
Authors: Zahrychuk H. Ya. , Demyd A. Ye. 
Published: November 2016

У статті розглянуто організацію практичної підготовки студентів фармацевтичного факультету в ДВНЗ “Тернопільський державний медичний університет імені І. Я. Горбачевського МОЗ України” при вивченні органічної хімії. Звернуто увагу на формування загальних компетентностей, зокрема: здатності застосовувати практичні знання у критичних ситуаціях, здатності до адаптації та дій у новій ситуації і здатності до абстрактного мислення, здатності проводити дослідження на сучасному науковому рівні, аналізу та синтезу, вчитися й бути сучасно навченим.
Methylenetetrahydrofolate Dehydrogenase 1 Polymorphisms Modify the Associations of Plasma Glycine and Serine With Risk of Acute Myocardial Infarction in Patients With Stable Angina Pectoris in WENBIT (Western Norway B Vitamin Intervention Trial)
Authors: Ding Yunpeng , Pedersen Eva R. , Svingen Gard F.T. , Helgeland Øyvind , Gregory Jesse F. , Løland Kjetil H. , Meyer Klaus , Tell Grethe S. , Ueland Per M. , Nygård Ottar K. 
Published: November 2016

Background—
Serine and glycine interconversion and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)–mediated 1-carbon transfer are the major sources of methyl groups for 1-carbon metabolism. Recently, plasma glycine and a common polymorphism in MTHFD1 have been associated with risk of acute myocardial infarction (AMI). It is, therefore, of interest to explore if these 2 pathways interact in relation to AMI.

Methods and Results—

A total of 2571 participants in the WENBIT (Western Norway B Vitamin Intervention Trial) undergoing coronary angiography for stable angina pectoris were studied. Associations of plasma serine and glycine concentrations with risk of AMI across 2 common and functional MTHFD1 polymorphisms (
rs2236225
and
rs1076991
) were explored in Cox regression models. During a median follow-up of 4.7 years, 212 patients (8.2%) experienced an AMI. In age- and sex-adjusted analyses, plasma glycine (
P
<0.01), but not serine (
P
=0.52), showed an overall association with AMI. However, interactions of MTHFD1
rs2236225
polymorphism with both plasma serine and glycine were observed (
P
interaction
=0.03 for both). Low plasma serine and glycine were associated with an increased risk of AMI among patients carrying the
rs2236225
minor A allele. Similarly, low plasma glycine showed stronger risk relationship with AMI in the
rs1076991
CC genotype carriers but weaker associations in patients carrying the minor T allele (
P
interaction
=0.02).

Conclusions—

Our results showed that 2 common and functional polymorphisms in the
MTHFD1
gene modulate the risk associations of plasma serine and glycine with AMI. These findings emphasize the possible role of the MTHFD1 in regulating serine and glycine metabolism in relation to atherosclerotic complications.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique Identifier: NCT00354081.
Incident Type 2 Myocardial Infarction in a Cohort of Patients Undergoing Coronary or Peripheral Arterial Angiography
Authors: Gaggin Hanna K. , Liu Yuyin , Lyass Asya , van Kimmenade Roland R. J. , Motiwala Shweta R. , Kelly Noreen P. , Mallick Aditi , Gandhi Parul U. , Ibrahim Nasrien E. , Simon Mandy L. , Bhardwaj Anju , Belcher Arianna M. , Harisiades Jamie E. , Massaro Joseph M. , D’Agostino Ralph B. , Januzzi James L. 
Published: November 2016

Background:
Despite growing recognition of type 2 myocardial infarction (T2MI; related to supply/demand mismatch), little is known about its risk factors or its association with outcome.

Methods:
A single-center cohort of patients undergoing coronary or peripheral angiography with or without intervention was prospectively enrolled and followed for incident type 1 and T2MI, and major adverse cardiovascular events (MACE, a composite of all-cause death, nonfatal myocardial infarction [MI], heart failure, stroke, transient ischemic attack, peripheral arterial complication, and cardiac arrhythmia), as well. T2MI was adjudicated using criteria from the Third Universal Definition of MI. Baseline characteristics, blood samples, and angiography information were obtained. Major end points subsequent to first MI were assessed using landmark analyses to compare the rates of first events only where everyone with a prior history of any MACE before MI were censored and adjusted for follow-up times. Cox proportional hazard models were used for time-to-event analyses with age and sex forced into all models and additional covariates evaluated by using the stepwise option for the selection.

Results:

One thousand two hundred fifty-one patients were enrolled and followed for a median of 3.4 years. Of these patients, 152 (12.2%) had T2MI during follow-up; T2MI was frequently recurrent. Multivariable predictors of T2MI were older age, lower systolic blood pressure, history of coronary artery disease, heart failure, chronic obstructive pulmonary disease, diabetes mellitus, nitrate use, and elevated concentrations of glucose, N-terminal pro-B type natriuretic peptide, and cystatin C. Patients with T2MI had higher rates of subsequent adverse events than those without T2MI (per 100 person-years: MACE, 53.7 versus 21.1,
P
<0.001; all-cause death, 23.3 versus 3.3,
P
<0.001; cardiovascular death, 17.5 versus 2.6,
P
<0.001; heart failure events, 22.4 versus 7.4,
P
<0.001); these rates are similar to those seen in patients with type 1 MI. Incident diagnosis of T2MI strongly predicted risk for subsequent MACE (adjusted hazard ratio, 1.90; 95% confidence interval, 1.46–2.48;
P
<0.001), all-cause death (adjusted hazard ratio, 2.96; 95% confidence interval, 2.01–4.36;
P
<0.001), and cardiovascular death (adjusted hazard ratio, 2.16; 95% confidence interval, 1.36–3.43;
P
=0.001).

Conclusions:
T2MI is common and associated with poor prognosis. Studies evaluating treatment strategies for management of T2MI are needed.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00842868.
Au sujet d’un mot prétendûment introuvable dans les dictionnaires
Authors: Rāġib Yūsuf 
Published: November 2016

The existence of the word ǧaytar which nominates small-sized persons has been formally refuted by Werner Diem simply because he did not find it in any dictionary. Yet this term is attested in some medieval Arabic lexicography works.
L’existence du mot ǧaytar qui désigne les personnes de petite taille a été formellement réfutée par Werner Diem simplement parce qu’il ne l’a trouvé dans aucun dictionnaire. Le terme est pourtant bien attesté dans des ouvrages de lexicographie arabes médiévaux.
This article is in French.
Typhoon Nina and the August 1975 Flood over Central China
Authors: Yang Long , Liu Maofeng , Smith James A. , Tian Fuqiang 
Published: November 2016

Abstract
The August 1975 flood in central China was one of the most destructive floods in history. Catastrophic flooding was the product of extreme rainfall from Typhoon Nina over a 3-day period from 5 to 7 August 1975. Despite the prominence of the August 1975 flood, relatively little is known about the evolution of rainfall responsible for the flood. Details of extreme rainfall and flooding for the August 1975 event in central China are examined based on empirical analyses of rainfall and streamflow measurements and based on downscaling simulations using the Weather Research and Forecasting (WRF) Model, driven by Twentieth Century Reanalysis (20CR) fields. Key hydrometeorological features of the flood event are placed in a climatological context through hydroclimatological analyses of 20CR fields. Results point to the complex evolution of rainfall over the 3-day period with distinctive periods of storm structure controlling rainfall distribution in the flood region. Blocking plays a central role in controlling anomalous storm motion of Typhoon Nina and extreme duration of heavy rainfall. Interaction of Typhoon Nina with a second tropical depression played a central role in creating a zone of anomalously large water vapor transport, a central feature of heavy rainfall during the critical storm period on 7 August. Analyses based on the quasigeostrophic omega equation identified the predominant role of warm air advection for synoptic-scale vertical motion. Back-trajectory analyses using a Lagrangian parcel tracking algorithm are used to assess and quantify water vapor transport for the flood. The analytical framework developed in this study is designed to improve hydrometeorological approaches for flood-control design.