bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro
Authors: Gray M. E. , Lee S. , McDowell A. L. , Erskine M. , Loh Q. T. M. , Grice O. , Argyle D. J. , Bergkvist G. T. 
Published: May 2016

AbstractMembers of the epidermal growth factor receptor (EGFR/ERBB) gene family are frequently dysregulated in a range of human cancers, and therapeutics targeting these proteins are in clinical use. We hypothesized that similar pathways are involved in feline and canine tumours and that the same drugs may be of clinical use in veterinary patients. We investigated EGFR and ERBB2 targeting using a panel of feline and canine cell lines. EGFR and ERBB2 were targeted with siRNAs or tyrosine kinase inhibitors (TKIs) and their effect on cellular proliferation, colony formation and migration was investigated in vitro. Here we report that EGFR and ERBB2 combined siRNA targeting produced synergistic effects in feline and canine cell lines similar to that reported in human cell lines. We conclude that dual EGFR and ERBB2 targeting using TKIs should be further evaluated as a potential new therapeutic strategy in feline head and neck and mammary tumours and canine mammary tumours.
Feasibility of improving identification of familial hypercholesterolaemia in general practice: intervention development study
Authors: Qureshi Nadeem , Weng Stephen , Tranter Jennifer , El-Kadiki Alia , Kai Joe 
Published: May 2016

ObjectivesTo assess the feasibility of improving identification of familial hypercholesterolaemia (FH) in primary care, and of collecting outcome measures to inform a future trial.DesignFeasibility intervention study.Setting6 general practices (GPs) in central England.Participants831 eligible patients with elevated cholesterol >7.5 mmol/L were identified, by search of electronic health records, for recruitment to the intervention.InterventionEducational session in practice; use of opportunistic computer reminders in consultations or universal postal invitation over 6 months to eligible patients invited to complete a family history questionnaire. Those fulfilling the Simon-Broome criteria for possible FH were invited for GP assessment and referred for specialist definitive diagnosis.Outcome measuresRates of recruitment of eligible patients, identification of patients with possible FH, referral to specialist care, diagnosis of confirmed FH in specialist care; and feasibility of collecting relevant outcome measures for a future trial.ResultsOf 173 general practices, 18 were interested in participating and 6 were recruited. From 831 eligible patients, 127 (15.3%) were recruited and completed family history questionnaires: 86 (10.7%) through postal invitation and 41 (4.9%) opportunistically. Among the 127 patients, 32 (25.6%) had a possible diagnosis of FH in primary care. Within 6 months of completing recruitment, 7 patients had had specialist assessment confirming 2 patients with definite FH (28.6%), and 5 patients with possible FH (71.4%). Potential trial outcome measures for lipid tests, statin prescribing and secondary causes of hypercholesterolaemia were extracted using automated data extraction from electronic records alone without recourse to other methods.ConclusionsThe intervention is feasible to implement in GP, and facilitates recruitment of patients with raised cholesterol for targeted assessment and identification of FH. Extracting data directly from electronic records could be used to evaluate relevant outcome measures in a future trial.
Private Class Action Litigation Risk of Chinese Firms Listed in the US
Authors: Jindra Jan , Voetmann Torben , Walkling Ralph A. 
Published: May 2016

We analyze the litigation risk of Chinese firms listed in the US. We find that firm-specific characteristics from prior literature studying US firms are not correlated with the litigation risk of US-listed Chinese firms. However, our findings indicate that the method of listing is the only reliable predictor of litigation risk — firms listing via reverse merger are significantly more likely to face lawsuits compared to firms listing via initial public offering (IPO). We find that Chinese reverse merger (CRMs) firms, relative to Chinese IPOs, have lower analyst following, similar post-listing stock performance, higher operating cash flows, smaller size, and lower cash holdings. We conclude that the litigation risk differential is consistent with the bonding hypothesis of [Stulz 1999, Globalization of Equity Markets and the Cost of Capital, Journal of Applied Corporate Finance 12, 8–25], wherein the higher litigation risk of CRMs is a reflection of increased but varying levels of monitoring, starting with the regulatory oversight at the pre-listing stage and a post-listing tradeoff between enforcement and monitoring by shareholders.
ОСОБЛИВОСТІ ПРОЯВІВ ТРИВОЖНОСТІ В ЕМІГРАНТІВ ТА РЕЕМІГРАНТІВ, ХВОРИХ НА ДЕПРЕСИВНІ РОЗЛАДИ
Authors: Венгер О. П. 
Published: May 2016

<p class="NoSpacing"><span>Проведене дослідження особливостей тривоги у 196 емігрантів, 191 реемігрантів порівняно з 198 неемігрантами із різними формами депресивних розладів за допомогою шкали тривоги М. Hamilton (HARS) виявило високе ураження цього контингенту тривожними розладами. Загальною тенденцією є більше вираження тривожних розладів у емігрантів (середній показник (23,3±8,5) бала у групі психогенної депресії, (25,5±9,6) бала – ендогенної, (27,8±3,8) бала – органічної), високим є також показник у групі реемігрантів – відповідно (18,8±5,2) бала, (21,3±6,0) бала та (25,6±2,6) бала. Найнижчими рівні тривоги є у неемігрантів: відповідно (16,9±6,2) бала, (20,5±9,1) бала та (23,8±7,2) бала. Значущі розбіжності виявлено при порівнянні усіх груп хворих із психогенними депресіями (р&lt;0,05 і більше), серед хворих із ендогенними депресіями – між групами неемігрантів та емігрантів, неемігрантів та реемігрантів (р&lt;0,01 та р&lt;0,05 відповідно), серед пацієнтів із органічними депресивними розладами – між усіма групами (р&lt;0,01). Ці закономірності тісно пов’язані з соціально-психологічними умовами – необхідністю для емігрантів повернутися за кордон і побоюваннями у зв’язку з цим щодо можливості продовження роботи через психічний розлад і фрустраційні тенденції серед реемігрантів. </span></p>
ОСОБЛИВОСТІ КОРЕКЦІЇ МЕТАБОЛІЧНИХ ПОРУШЕНЬ У ХВОРИХ НА СТАБІЛЬНУ СТЕНОКАРДІЮ ТА СУБКЛІНІЧНИЙ ГІПОТИРЕОЗ ЗАЛЕЖНО ВІД ТРИВАЛОСТІ ХВОРОБИ
Authors: Швед М. І. , Припхан І. Б. 
Published: May 2016

<p>У статті наведено особливості метаболічних порушень (ліпідного спектра крові та процесів вільнорадикального окиснення), а також методи їх корекції у хворих із субклінічним гіпотиреозом та стабільною стенокардією зі тривалістю до та понад 5 років. У пацієнтів із стабільною стенокардією понад 5 років та субклінічним гіпотиреозом встановлено достовірно вищі значення рівня тригліцеридів (ТГ), загального холестерину (ХС), ХС ліпопротеїнів низької щільності (ЛПНЩ), коефіцієнта атерогенності (КА) та малонового діальдегіду (МДА), а також суттєве зниження концентрації супероксиддисмутази (СОД), каталази (КТ) та церулоплазміну (ЦП), порівняно із хворими, в яких стабільна стенокардія тривала до 5 років. Комбінація стандартного антиішемічного лікування та L-тироксину позитивно впливала на покращення загального клінічного стану хворих та показників ліпідоргами і перекисного окиснення ліпідів (ПОЛ) лише у хворих із субклінічним гіпотиреозом та тривалістю стабільної стенокардії до 5 років. У пацієнтів із тривалістю хвороби понад 5 років для нормалізації клінічного стану і досягнення цільових рівнів основних показників ліпідограми, процесів вільнорадикального окиснення та антиоксидантного захисту доцільно застосовувати комплексну терапію із використанням стандартного антиішемічного лікування, L-тироксину та L-карнітину. Отримані результати дозволяють рекомендувати використання диференційної комплексної терапії у хворих зі стабільною стенокардією та субклінічним гіпотиреозом з метою адекватного відновлення клінічного стану та попередження метаболічних порушень у даної категорії хворих.</p>
ВПЛИВ МАГІСТРАЛІЗАЦІЇ ЗОВНІШНЬОЇ СОННОЇ АРТЕРІЇ НА НЕВРОЛОГІЧНУ СИМПТОМАТИКУ В ПАЦІЄНТІВ З ОКЛЮЗІЄЮ ВНУТРІШНЬОЇ СОННОЇ АРТЕРІЇ
Authors: Мелень А. П. 
Published: May 2016

<p>У пацієнтів із хронічною оклюзією внутрішньої сонної артерії іпсілатеральна зовнішня сонна артерія є шляхом важливого колатерального кровообігу, що багато в чому впливає на перебіг захворювання в цілому. Метою нашого дослідження було встановити вплив магістралізації зовнішньої сонної артерії на динаміку неврологічної симптоматики. Головну групу склали 74 пацієнти з оклюзією ВСА, які перенесли магістралізацію зовнішньої сонної атрерії. Для оцінки результатів хірургічного лікування у віддаленому періоді сформована контрольна група, що складалася з 30 хворих з оклюзією ВСА, які отримували тільки медикаментозну терапію. Оцінку неврологічної симптоматики проводили перед операційним втручанням та через 3 місяці після нього.<strong> </strong>При порівнянні динаміки неврологічної симптоматики в головній та контрольній групах встановлено таке: зникнення або зменшення частоти ретинальних ТІА виявлено в 100 % хворих головної групи проти 33,3 % контрольної (р=0,05; ВШ – 10,2; 95 %, ДІ – 0,3–336,9), класичні ТІА регресували в 100 % пацієнтів головної групи проти 25 % у контрольній (р=0,008; ВШ – 9,8; 95 %, ДІ – 0,32–300,4). Зникнення ТІА у пацієнтів головної групи, на нашу думку, зумовлено видаленням атеросклеротичної бляшки та ліквідацією сліпої кукси ВСА, які є джерелом емболії. Поліпшення мовлення відзначили 47,8 % пацієнтів головної групи проти 27,8 % у контрольній групі (р=0,34; ВШ – 2,25; 95 %, ДІ – 0,34–14,6). Регресування клінічної картини хронічної ішемії сітківки встановлено в 33,3 % пацієнтів головної групи проти 0 % контрольної (р=0,13; ВШ – 6,72; 95 %, ДІ – 0,33–136,2). Прояви парезів та паралічів регресували в 48,8 % пацієнтів головної групи та у 26,6 % контрольної (р=0,11; ВШ – 2,61; 95 %, ДІ – 0,71–9,6).</p>
Transcriptome-Wide Analysis Reveals Modulation of Human Macrophage Inflammatory Phenotype Through Alternative Splicing
Authors: Lin Jennie , Hu Yu , Nunez Sara , Foulkes Andrea S. , Cieply Benjamin , Xue Chenyi , Gerelus Mark , Li Wenjun , Zhang Hanrui , Rader Daniel J. , Musunuru Kiran , Li Mingyao , Reilly Muredach P. 
Published: May 2016

Objective—
Human macrophages can shift phenotype across the inflammatory M1 and reparative M2 spectrum in response to environmental challenges, but the mechanisms promoting inflammatory and cardiometabolic disease–associated M1 phenotypes remain incompletely understood. Alternative splicing (AS) is emerging as an important regulator of cellular function, yet its role in macrophage activation is largely unknown. We investigated the extent to which AS occurs in M1 activation within the cardiometabolic disease context and validated a functional genomic cell model for studying human macrophage-related AS events.

Approach and Results—
From deep RNA-sequencing of resting, M1, and M2 primary human monocyte–derived macrophages, we found 3860 differentially expressed genes in M1 activation and detected 233 M1-induced AS events; the majority of AS events were cell- and M1-specific with enrichment for pathways relevant to macrophage inflammation. Using genetic variant data for 10 cardiometabolic traits, we identified 28 trait-associated variants within the genomic loci of 21 alternatively spliced genes and 15 variants within 7 differentially expressed regulatory splicing factors in M1 activation. Knockdown of 1 such splicing factor, CELF1, in primary human macrophages led to increased inflammatory response to M1 stimulation, demonstrating CELF1’s potential modulation of the M1 phenotype. Finally, we demonstrated that an induced pluripotent stem cell–derived macrophage system recapitulates M1-associated AS events and provides a high-fidelity macrophage AS model.

Conclusions—
AS plays a role in defining macrophage phenotype in a cell- and stimulus-specific fashion. Alternatively spliced genes and splicing factors with trait-associated variants may reveal novel pathways and targets in cardiometabolic diseases.
Implantable Loop Recorder Monitoring for Refining Management of Children With Inherited Arrhythmia Syndromes
Authors: Avari Silva Jennifer N. , Bromberg Burt I. , Emge Fredrick K. , Bowman Tammy M. , Van Hare George F. 
Published: May 2016

Background
Implantable loop recorders (ILRs) are conventionally utilized to elucidate the mechanism of atypical syncope. The objective of this study was to assess the impact of these devices on management of pediatric patients with known or suspected inherited arrhythmia syndromes.

Methods and Results
A retrospective chart review was undertaken of all pediatric patients with known or suspected inherited arrhythmia syndromes in whom an ILR was implanted from 2008 to 2015. Captured data included categorization of diagnosis, treatment, transmitted tracings, and the impact of ILR tracings on management. Transmissions were categorized as symptomatic, autotriggered, or routine. Actionable transmissions were abnormal tracings that directly resulted in a change of medical or device therapy. A total of 20 patients met the stated inclusion criteria (long QT syndrome, n=8, catecholaminergic polymorphic ventricular tachycardia,n=9, Brugada syndrome, n=1, arrhythmogenic right ventricular cardiomyopathy, n=2), with 60% of patients being genotype positive. Primary indication for implantation of ILR included ongoing monitoring +/− symptoms (n=15, 75%), suspicion of noncompliance (n=1, 5%), and liberalization of recommended activity restrictions (n=4, 25%). A total of 172 transmissions were received in patients with inherited arrhythmia syndromes, with 7% yielding actionable data. The majority (52%) of symptom events were documented in the long QT syndrome population, with only 1 tracing (5%) yielding actionable data. Automatic transmissions were mostly seen in the catecholaminergic polymorphic ventricular tachycardia cohort (81%), with 21% yielding actionable data. There was no actionable data in routine transmissions.

Conclusions
ILRs in patients with suspected or confirmed inherited arrhythmia syndromes may be useful for guiding management. Findings escalated therapies in 30% of subjects. As importantly, in this high‐risk population, the majority of symptom events represented normal or benign rhythms, reassuring patients and physicians that no further intervention was required.
Simulations of the Tropical General Circulation with a Multiscale Global Model
Authors: Randall David , DeMott Charlotte , Stan Cristiana , Khairoutdinov Marat , Benedict James , McCrary Rachel , Thayer-Calder Katherine , Branson Mark 
Published: May 2016

Abstract
Cloud processes play a central role in the dynamics of the tropical atmosphere, but for many years the shortcomings of cloud parameterizations have limited our ability to simulate and understand important tropical weather systems such as the Madden–Julian oscillation. Since about 2001, “superparameterization” has emerged as a new path forward, complementing but not replacing studies based on conventional parameterizations. This chapter provides an overview of work with superparameterization, including a discussion of the method itself and a summary of key results.
Perceived Spaciousness and Preference in Sequential Experience
Authors: Bokharaei Saleheh , Nasar Jack L. 
Published: May 2016

Objective: We assessed the perceived spaciousness and preference for a destination space in relation to six attributes (size, lighting, window size, texture, wall mural, and amount of furniture) of it and of the space experienced before it. Background: Studies have examined effects of these attributes but not for dynamic experience or preference. Method: We created 24 virtual reality walks between each possible pair of two levels of each attribute. For each destination space, 31 students (13 men, 18 women) rated spaciousness and 30 students (16 men, 14 women) rated preference. We conducted separate 2 × 2 repeated-measure ANOVAs across each condition for perceived spaciousness and preference. Results: Participants judged the space that was larger, was more brightly lit, with a larger window, or with less furniture as the more spacious. These attributes also increased preference. Consonant with adaptation-level theory, participants judged offices as higher in spaciousness and preference if preceded by a space that was smaller, was more dimly lit, or had smaller windows. Conclusion: The findings suggest that perceived spaciousness varies with size, lightness, window size, and amount of furniture but that perception also depends on the size, lightness, and size of the space experienced before. Application: Designers could use the findings to manipulate features to make a space appear larger or more desirable.
Pulse volume recordings to identify falsely elevated ankle brachial index
Authors: Shirasu Takuro , Hoshina Katsuyuki , Akagi Daisuke , Miyahara Takuya , Yamamoto Kota , Watanabe Toshiaki 
Published: May 2016

Background Ankle brachial index can be falsely elevated in cases of medial arterial calcification, and its clinical use should be limited, especially in patients with diabetes. The aim of this study was to evaluate the potential role of pulse volume recording in detecting falsely elevated ankle brachial index. Methods Two parameters of the pulse waveform were automatically calculated: upstroke time and percentage mean artery pressure. Pulse volume recordings were retrospectively evaluated in 171 consecutive patients (342 limbs); 73 (43%) had a diagnosis of diabetes. Results On multivariate analysis, diabetes (hazard ratio = 1.7), ankle brachial index ≤ 0.90 (hazard ratio = 4.4), upstroke time ≥ 180 ms (hazard ratio = 2.1), and percentage mean artery pressure ≥ 45% (hazard ratio = 2.8) were significantly related to toe brachial index < 0.60. Further analysis for falsely elevated ankle brachial index was performed in 196 limbs (146 patients) with ankle brachial index > 0.90. The difference between ankle brachial index and toe brachial index differentiated the limbs of diabetic patients, with percentage mean artery pressure ≥ 45%, from controls (0.45 ± 0.17 vs. 0.35 ± 0.16, p = 0.03); upstroke time was not found to be a discriminating factor. Conclusions Although measurement of ankle brachial index remains the gold standard for diagnosing peripheral arterial disease, percentage mean artery pressure, automatically obtained in ankle brachial index measurement, may be useful to detect falsely elevated ankle brachial index, especially in patients with diabetes.
Nurse ethical sensitivity: An integrative review
Authors: Milliken Aimee 
Published: May 2016

Background: Ethical sensitivity has been identified as a foundational component of ethical action. Diminished or absent ethical sensitivity can result in ethically incongruent care, which is inconsistent with the professional obligations of nursing. As such, assessing ethical sensitivity is imperative in order to design interventions to facilitate ethical practice and to ensure nurses recognize the nature and extent of professional ethical obligations. Aim: To review and critique the state of the science of nurse ethical sensitivity and to synthesize findings across studies. Research design: Whittemore and Knafl’s revised framework for integrative reviews guided the analysis. Research context and data sources: A comprehensive, computer-assisted search of literature published in Cumulative Index of Nursing and Allied Health Literature and PubMed was performed. A systematic approach was used to extract, reduce, and synthesize the data. Findings: Four major conceptualizations of ethical sensitivity emerged from the literature. A sample of 25 reports met inclusion criteria, including 17 empirical reports and 8 theoretical reports. Discussion: Despite the existence of a concept analysis and a validated tool, ethical sensitivity remains a highly theoretical concept with multiple, and at times competing, conceptualizations. Ethical sensitivity has been assessed extensively in the context of ethical dilemmas; however, little attention has been paid to the way the concept operates in day-to-day practice. Conclusion: Future research should focus on better ways to operationalize and assess the concept, with particular attention to nurse awareness of the ethical content of everyday practice.
Natalizumab versus fingolimod in patients with relapsing-remitting multiple sclerosis non-responding to first-line injectable therapies
Authors: Baroncini Damiano , Ghezzi Angelo , Annovazzi Pietro O , Colombo Bruno , Martinelli Vittorio , Minonzio Giorgio , Moiola Lucia , Rodegher Mariaemma , Zaffaroni Mauro , Comi Giancarlo 
Published: May 2016

Background: Natalizumab and fingolimod have not been compared in controlled trials but only in observational studies, with inconclusive results. Objectives: The objective of this study is to compare the effect of natalizumab and fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Methods: We included all consecutive RRMS patients switched from first-line agents (glatiramer acetate/interferons) to natalizumab or fingolimod, with a follow-up of 24 months. Data of relapses, Expanded Disability Status Scale score and brain magnetic resonance imaging (MRI) scans were collected. We used propensity score (PS) matching and intention-to-treat analysis. Results: We retained 102 patients in each cohort after PS matching, with similar baseline characteristics. More patients discontinued natalizumab compared to fingolimod (33% vs 11%, p < 0.001), mainly for progressive multifocal leukoencephalopathy (PML) concern. No serious adverse events occurred in the two cohorts. Compared to fingolimod, the natalizumab group presented a higher percentage of relapse-free patients (66% vs 80%, p = 0.015), a higher percentage of disability-improved patients (6% vs 15%, p = 0.033), a lower percentage of MRI-active patients (38% vs 14%, p = 0.001) and a higher percentage of patients with no evidence of disease activity (NEDA-3; 44% vs 70%, p < 0.001) after 2 years of follow-up. Disability worsening was not statistically different in the two groups. Conclusion: Natalizumab is superior to fingolimod in RRMS patients non-responding to first-line agents.
Annual risk of tuberculosis infection in rural China: a population-based prospective study
Authors: Gao Lei , Bai Liqiong , Liu Jianmin , Lu Wei , Wang Xinhua , Li Xiangwei , Du Jiang , Chen Xinchun , Zhang Haoran , Xin Henan , Sui Hongtao , Li Hengjing , Su Haoxiang , He Jian , Pan Shouguo , Peng Hong , Xu Zuhui , Catanzaro Antonino , Evans Thomas G. , Zhang Zongde , Ma Yu , Li Mufei , Feng Boxuan , Li Zhen , Guan Ling , Shen Fei , Wang Zhijian , Zhu Tao , Yang Shumin , Si Hongyan , Wang Yi , Tan Yunhong , Chen Tianzhu , Chen Chen , Xia Yinyin , Cheng Shiming , Xu Weiguo , Jin Qi 
Published: May 2016

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.