bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of PD-L1 Surface Expression on Leukemia Cells with the Ratio of PD-L1 mRNA Variants and with Electrophoretic Mobility
Authors: Brodská Barbora , Otevřelová Petra , Kuželová Kateřina 
Published: August 2016

Abstract
The expression on the surface of tumor cells of ligands for the PD-1 inhibitory receptor prevents the antitumor immune response and is considered to be a negative prognostic factor in a variety of solid tumors as well as in hematologic malignancies. To determine if it were possible to analyze PD-L1 with PCR-based methods, we assessed the expression of PD-L1 in primary samples from patients with acute myeloid leukemia, in healthy donors, and in a panel of cell lines, by means of flow cytometry, RT-PCR, and Western blotting. Although the surface density of the protein was not correlated with the amount of expressed full-length mRNA, we found a statistically significant positive correlation between PD-L1 surface density and the ratio of two transcript variants (variant 1/variant 2). Our PCR-based method allows for retrospective examination of PD-L1 surface expression from frozen cDNA samples, without the need for a reference gene. Our results also suggest that variant 2, which is produced by alternative splicing, negatively regulates PD-L1 protein expression on the cell surface. In addition, PD-L1 exposition on the cell surface is clearly associated with a shift of electrophoretic mobility, observed on Western blots. This finding can explain the relatively large variability in PD-L1 apparent molecular weight reported in the literature and offers an alternate means for the assessment of PD-L1 surface expression. Cancer Immunol Res; 4(10); 815–9. ©2016 AACR.
MicroRNA-21 Lowers Blood Pressure in Spontaneous Hypertensive Rats by Upregulating Mitochondrial Translation
Authors: Li Huaping , Zhang Xiaorong , Wang Feng , Zhou Ling , Yin Zhongwei , Fan Jiahui , Nie Xiang , Wang Peihua , Fu Xiang-Dong , Chen Chen , Wang Dao Wen 
Published: August 2016

BACKGROUND:
Excessive reactive oxygen species generated in mitochondria has been implicated as a causal event in hypertensive cardiomyopathy. Multiple recent studies suggest that microRNAs (miRNAs) are able to translocate to mitochondria to modulate mitochondrial activities, but the medical significance of such a new miRNA function has remained unclear. Here, we characterized spontaneous hypertensive rats (SHRs) in comparison with Wistar rats, finding that micro RNA-21 (miR-21) was dramatically induced in SHRs relative to Wistar rats. We designed a series of experiments to determine whether miR-21 is involved in regulating reactive oxygen species generation in mitochondria, and if so, how induced miR-21 may either contribute to hypertensive cardiomyopathy or represent a compensatory response.

METHODS:
Western blotting was used to compare the expression of key nuclear genome (nDNA)–encoded and mitochondrial genome (mtDNA)–encoded genes involved in reactive oxygen species production in SHRs and Wistar rats. Bioinformatics was used to predict miRNA targets followed by biochemical validation using quantitative real-time polymerase chain reaction and Ago2 immunoprecipitation. The direct role of miRNA in mitochondria was determined by GW182 dependence, which is required for miRNA to function in the cytoplasm, but not in mitochondria. Recombinant adeno-associated virus (type 9) was used to deliver miRNA mimic to rats via tail vein, and blood pressure was monitored with a photoelectric tail-cuff system. Cardiac structure and functions were assessed by echocardiography and catheter manometer system.

RESULTS:
We observed a marked reduction of mtDNA-encoded cytochrome b (mt-Cytb) in the heart of SHRs. Downregulation of mt-Cytb by small interfering RNA in mitochondria recapitulates some key disease features, including elevated reactive oxygen species production. Computational prediction coupled with biochemical analysis revealed that miR-21 directly targeted mt-Cytb to positively modulate mt-Cytb translation in mitochondria. Circulating miR-21 levels in hypertensive patients were significantly higher than those in controls, showing a positive correlation between miR-21 expression and blood pressure. Remarkably, recombinant adeno-associated virus–mediated delivery of miR-21 was sufficient to reduce blood pressure and attenuate cardiac hypertrophy in SHRs.

CONCLUSIONS:
Our findings reveal a positive function of miR-21 in mitochondrial translation, which is sufficient to reduce blood pressure and alleviate cardiac hypertrophy in SHRs. This observation indicates that induced miR-21 is part of the compensatory program and suggests a novel theoretical ground for developing miRNA-based therapeutics against hypertension.
2013 ACC/AHA Cholesterol Guideline Versus 2004 NCEP ATP III Guideline in the Prediction of Coronary Artery Calcification Progression in a Korean Population
Authors: Cho Yun Kyung , Jung Chang Hee , Kang Yu Mi , Hwang Jenie Yoonoo , Kim Eun Hee , Yang Dong Hyun , Kang Joon‐Won , Park Joong‐Yeol , Kim Hong‐Kyu , Lee Woo Je 
Published: August 2016

Background

Since the release of the 2013 American College of Cardiology/American Heart Association (
ACC
/
AHA)
guidelines, significant controversy has surrounded the applicability of the new cholesterol guidelines and the Pooled Cohort Equations. In this present study, we investigated whether eligibility for statin therapy determined by the 2013
ACC
/
AHA
guidelines on the management of blood cholesterol is better aligned with the progression of coronary artery calcification (
CAC
) detected by coronary computed tomography angiography (
CCTA
) than the previously recommended 2004 National Cholesterol Education Program (
NCEP
) Adult Treatment Panel (
ATP
)
III
guidelines.

Methods and Results

We enrolled 1246 asymptomatic participants who underwent repeated
CAC
score measurement during routine health examinations. The
CAC
score progression was defined as either incident
CAC
in a population free of
CAC
at baseline or increase ≥2.5 units between the baseline and final square root of
CAC
scores participants who had detectable
CAC
at baseline examination. Application of the
ACC
/
AHA
guidelines to the study population increased the proportion of statin‐eligible subjects from 20.5% (according to
ATP III
) to 54.7%. Statin‐eligible subjects, as defined by
ACC
/
AHA
guidelines, showed a higher odds ratio for
CAC
score progression than those considered statin eligible according to
ATP III
guidelines (2.73 [95% CI, 2.07–3.61] vs 2.00 [95% CI, 1.49–2.68]).

Conclusions

Compared with the
ATP III
guidelines, the new
ACC
/
AHA
guidelines result in better discrimination of subjects with cardiovascular risk detected by
CAC
score progression in an Asian population.
2013 ACC/AHA Cholesterol Guideline and Implications for Healthy People 2020 Cardiovascular Disease Prevention Goals
Authors: Egan Brent M. , Li Jiexiang , White Kellee , Fleming Douglas O. , Connell Kenneth , Hernandez German T. , Jones Daniel W. , Ferdinand Keith C. , Sinopoli Angelo 
Published: August 2016

Background

Healthy People 2020 aim to reduce fatal atherosclerotic cardiovascular disease (
ASCVD
) by 20%, which translates into 310 000 fewer events annually assuming proportional reduction in fatal and nonfatal
ASCVD
. We estimated preventable
ASCVD
events by implementing the American College of Cardiology/American Heart Association (
ACC
/
AHA
) 2013 Cholesterol Guideline in all statin‐eligible adults. Absolute risk reduction (
ARR
) and number needed‐to‐treat (
NNT
) were calculated.

Methods and Results

National Health and Nutrition Examination Survey data for 2007–2012 were analyzed for adults aged 21 to 79 years and extrapolated to the US population. Literature‐guided assumptions were used including (1) low‐density lipoprotein cholesterol falls 33% with moderate‐intensity statins and 51% with high‐intensity statins; (2) for each 39 mg/dL decline in low‐density lipoprotein cholesterol, 10‐year
ASCVD
10
risk would fall 21% when
ASCVD
10
risk was ≥20% and 33% when
ASCVD
10
risk was <20%; and (3) either all statin‐eligible untreated adults or all with
ASCVD
10
risk ≥7.5% would receive statins. Of 175.9 million adults aged 21 to 79 years not taking statins, 44.8 million (25.5%) were statin eligible. Treating all statin‐eligible adults would prevent an estimated 243 589
ASCVD
events annually (
ARR
5.4%, 10‐year
NNT
18). Treating all statin‐eligible adults with
ASCVD
10
risk ≥7.5% reduces the number treated to 32.2 million (28.2% fewer), whereas
ASCVD
events prevented annually fall only 10.5% to 217 974 (6.8%
ARR
,
NNT
15).

Conclusions

Implementing the
ACC
/
AHA
2013 Cholesterol Guideline in all untreated, statin‐eligible adults could achieve ≈78% of the Healthy People 2020
ASCVD
prevention goal. Most of the benefit is attained by individuals with 10‐year
ASCVD
risk ≥7.5%.
Obstructive Sleep Apnea and Circulating Potassium Channel Levels
Authors: Jiang Ning , Zhou Anyu , Prasad Bharati , Zhou Li , Doumit Jimmy , Shi Guangbin , Imran Hafiz , Kaseer Bahaa , Millman Richard , Dudley Samuel C. 
Published: August 2016

Background

Cardiac arrhythmias and sudden cardiac death are more frequent in patients with obstructive sleep apnea (
OSA
).
OSA
is associated with
QT
prolongation, and
QT
prolongation is an independent risk factor for sudden cardiac death. Because
QT
prolongation can be mediated by potassium channel loss of function, we tested whether
OSA
or continuous positive airway pressure therapy altered
mRNA
expression of circulating white blood cell potassium channels.

Methods and Results

In total, 28 patients with OSA newly diagnosed by polysomnogram and 6 participants without
OSA
were enrolled. Potassium channel levels in white blood cells at baseline and at a 4‐week follow‐up visit were compared. There was a significant inverse correlation between the severity of the
OSA
stratified by apnea–hypopnea index and
mRNA
expression of the main potassium channels assessed:
KCNQ
1 (
r
=−0.486,
P
=0.007),
KCNH
2 (
r
=−0.437,
P
=0.016),
KCNE
1 (
r
=−0.567,
P
=0.001),
KCNJ
2 (
r
=−0.442,
P
=0.015), and
KCNA
5 (
r
=−0.468,
P
=0.009). In addition,
KCNQ
1,
KCNH
2, and
KCNE
1 inversely correlated with the oxygen desaturation index 4. After 4 weeks of continuous positive airway pressure therapy, circulating
KCNQ
1 and
KCNJ
2 were increased 1.4±0.4‐fold (
P
=0.040) and 2.1±1.4‐fold (
P
=0.046) in the moderate
OSA
group. Compared with patients with mild or moderate
OSA
, patients with severe
OSA
had a persistently higher apnea–hypopnea index (mild 2.0±1.8, moderate 1.0±0.9, severe 5.8±5.6;
P
=0.015), perhaps explaining why the potassium channel changes were not seen in the severe
OSA
group.

Conclusions

The
mRNA
expression of most potassium channels inversely correlates with the severity of
OSA
and hypoxemia. Continuous positive airway pressure therapy improves circulating
KCNQ
1 and
KCNJ
2 in patients with moderate
OSA
.
Diagnostic Performance of Treadmill Exercise Cardiac Magnetic Resonance: The Prospective, Multicenter Exercise CMR's Accuracy for Cardiovascular Stress Testing (EXACT) Trial
Authors: Raman Subha V. , Dickerson Jennifer A. , Mazur Wojciech , Wong Timothy C. , Schelbert Erik B. , Min James K. , Scandling Debbie , Bartone Cheryl , Craft Jason T. , Thavendiranathan Paaladinesh , Mazzaferri Ernest L. , Arnold John W. , Gilkeson Robert , Simonetti Orlando P. 
Published: August 2016

Background

Stress cardiac magnetic resonance (
CMR
) has typically involved pharmacologic agents. Treadmill
CMR
has shown utility in single‐center studies but has not undergone multicenter evaluation.

Methods and Results

Patients referred for treadmill stress nuclear imaging (
SPECT
) were prospectively enrolled across 4 centers. After rest
99m
Tc
SPECT
, patients underwent resting cine
CMR
. In‐room stress was then performed using an
MR
‐compatible treadmill with continuous 12‐lead electrocardiogram monitoring. At peak stress,
99m
Tc was injected, and patients rapidly returned to the
MR
scanner isocenter for real‐time, free‐breathing stress cine and perfusion imaging. After recovery, cine and rest perfusion followed by late gadolinium enhancement acquisitions concluded
CMR
imaging. Stress
SPECT
was then acquired in adjacent nuclear laboratories. A subset of patients not referred for invasive coronary angiography within 2 weeks of stress underwent coronary computed tomography angiography. Angiographic data available in 94 patients showed sensitivity of 79%, specificity of 99% for exercise
CMR
with positive predictive value of 92% and negative predictive value of 96%. Agreement between treadmill stress
CMR
and angiography was strong (κ=0.82), and moderate between
SPECT
and angiography (κ=0.46) and
CMR
versus
SPECT
(κ=0.48).

Conclusions

The multicenter
EXACT
trial indicates excellent diagnostic value of treadmill stress
CMR
in typical patients referred for exercise
SPECT
.
Political, Interparty and Moral Crisis of the “War Communism” Policy in Kazakhstan 1920-1922
Authors: Medeubayev Erlan 
Published: August 2016

The article deals with the implementation of the complex of political and socio-economic measures of the Soviet state, called the policy of “war communism” in the cities of the Steppes and Turkestan in 1918-1921. Based on materials gleaned from various sources, the author endeavours to explore the processes of socialization and municipalization of private houses and dwellings, the nationalization of private property, which took place in the cities of the KazASSR and tassr; highlight some of the issues related to the subject policy of “war communism” in the cities of Kazakhstan. Various restrictive decrees and orders of the Soviet power in this period, aimed at limiting commodity-money relations and the prohibition of the right to private property put people into a rigid framework of survival. Approved in the sphere of public life, the ideology of “war communism” inevitably left its mark on the life of the city. This ideology was a special sociocultural phenomenon, strengthening other social psychology and ethics which propagandized the need to destroy the old “bourgeois” culture and create a new “proletarian culture”. “War Communism” as opposed to “bourgeois individualism” principles of the socialist community, broske vital foundations of society.
A characteristic feature of this period is the legitimization of violence and its use as a universal remedy of solving all problems. Under the pressure of revolutionary changes the sense of justice in society underwent considerable transformation. The right to inviolability of private property was completely ignored. The ruling regime no longer recognized the existing legal mechanisms, replacing them with the amorphous concept of “revolutionary legality.”
Imperial Statistical Research in the Kazakh Steppes (Late 19th-early 20th Centuries)
Authors: Jampeissova Zhanar 
Published: August 2016

The notion of a ‘commune’ has become a part of evolutionistic view on social development over the course of 19th-20th cc. and heavily influenced various fields of Social Sciences and Humanities. The Russian statisticians have also accepted the category of a commune while they were investigating the Russian peasants’ household budgets. This theoretical pattern was also applied to Kazakh land tenure during the carrying out the Russian colonial project on searching land ‘surpluses’ for Russian settlers in the Kazakh steppes. In particular, it was used in the statistical research “Materials on Kirgiz land tenure collected and developed by the expedition for research of the Steppe area” under Fedor Shcherbina’s leadership (1896-1903).
In fact, the statisticians could not identify the commune borders among the nomads as those borders were very conditional. As a result, the surveyors turned from investigating commune to their creation. Soon the maps on Kazakh land tenure were made and ‘communes’ were established on the juridical base. After finishing that statistical research those invented communes served for colonial authorities as the ground for ceasing land in favor of the Russian peasants.
South-Eastern Policy of Tsarizm
Authors: Izbassarova Gulbanu Bolatovna 
Published: August 2016

This article is devoted to the penetration of the Russian Empire to the territory of the Junior Horde of Kazakhs and the strengthening of Russian power in South Volga Region. Taking into consideration the ethnical origin and territorial contacts due to close proximity, cultural connections of Kazakhs and Bashkirs during the period under research, the article sheds light on the involvement of Kazakhs in Bashkir rebellions and looks into the changing character of the relations between these two Turkic ethnic groups. The nature of Orenburg expedition has been studied through the activities of the following rulers of the region: I.K. Kirillov, V.N. Tatishev, V.A. Urussov, I.I. Neplyuev. The construction of the city of Orenburg, the fortresses along the border with Bashkiriya and Western Kazakhstan, the colonization of the Orenburg region by Russians, and locating military units in a number of fortified cities was aimed at ensuring free and safe rear for further penetration into Central Asia.
The issue of the participation of Kazakhs in Bashkir rebellion in 1737-1740 and its causes are under study. The author dwells on the decision of Bashkir officers to surrender to the reign of Kazakhs and to invite one of the Kazakh sultans to become a sovereign Bashkir khan. The attitude of Kazakhs toward Bashkirs is studied through the activity of Abulkhair, the Kazakh Junior Horde khan, Semeke, the Kazakh Middle Horde аnd sultans Abulmambet, Ablay and others. The author estimates the number of casualties during the rebellion and the number of refugees seeking asylum in the Kazakh steppe. The marriage of Abulkhair Khan to a daughter of a Bashkir officer is considered as one of the methods of Bashkir influence on the Kazakh khan.
A unique case of acute embolus in a renal transplant with salvage by catheter-directed thrombolysis
Authors: McIlveen E , Jackson A , Bowie J , Stirling C , Downie A , Kingsmore D 
Published: August 2016

Introduction Acute renal transplant emboli can be disastrous and result in loss of the renal transplant. This case was successfully treated with thrombolysis. Case presentation A 66-year-old female underwent a right-sided deceased heart-beating donor renal transplant. She had excellent transplant function but presented acutely three years later with pain in the transplanted kidney, an acute rise in serum creatinine and new onset atrial fibrillation. Bedside ultrasound scan demonstrated absent transplant perfusion. Emergency angiogram confirmed acute emboli in the transplant renal artery with some kidney perfusion. Thrombolysis with alteplase and anticoagulation with heparin was commenced. Serial imaging at 24 and 36 h demonstrated significant improvement in transplant perfusion. Following a period of supportive therapy, her transplant function recovered, although not to pre-morbid baseline levels. Conclusion Consider acute embolus in a renal transplant patient with acute kidney injury, transplant tenderness and cardiac arrhythmia. Early thrombolysis may salvage renal transplants and good transplant function may be regained.
High-Stakes Systematic Reviews
Authors: Goesling Brian , Oberlander Sarah , Trivits Lisa 
Published: August 2016

Background: Systematic reviews help policy makers and practitioners make sense of research findings in a particular program, policy, or practice area by synthesizing evidence across multiple studies. However, the link between review findings and practical decision-making is rarely one-to-one. Policy makers and practitioners may use systematic review findings to help guide their decisions, but they may also rely on other information sources or personal judgment. Objectives: To describe a recent effort by the U.S. federal government to narrow the gap between review findings and practical decision-making. The Teen Pregnancy Prevention (TPP) Evidence Review was launched by the U.S. Department of Health and Human Services (HHS) in 2009 as a systematic review of the TPP literature. HHS has used the review findings to determine eligibility for federal funding for TPP programs, marking one of the first attempts to directly link systematic review findings with federal funding decisions. Conclusions: The high stakes attached to the review findings required special considerations in designing and conducting the review. To provide a sound basis for federal funding decisions, the review had to meet accepted methodological standards. However, the review team also had to account for practical constraints of the funding legislation and needs of the federal agencies responsible for administering the grant programs. The review team also had to develop a transparent process for both releasing the review findings and updating them over time. Prospective review authors and sponsors must recognize both the strengths and limitations of this approach before applying it in other areas.
A Structured Approach Using the Systematic Review Data Repository (SRDR)
Authors: Bonardi Alexandra , Clifford Christine J. , Hadar Nira 
Published: August 2016

Background: This review describes the methods used for a systematic review of oral health intervention literature in a target population (people with intellectual and developmental disability (I/DD)), which spans a broad range of interventions and study types, conducted with specialized software. Objective: The aim of this article is to demonstrate the review strategy, using the free, online systematic review data repository (SRDR) tool, for oral health interventions aimed at reducing disparities between people with I/DD and the general population. Research Design: Researchers used online title/abstract review (Abstrackr) and data extraction (SRDR) tools to structure the literature review and data extraction. A practicing clinician and an expert methodologist completed the quality review for each study. The data extraction team reported on the experience of using and customizing the SRDR. Results: Using the SRDR, the team developed four extraction templates for eight key questions and completed extraction on 125 articles. Conclusions: This report discusses the advantages and disadvantages of using an electronic tool, such as the SRDR, in completing a systematic review in an area of growing research. This review provides valuable insight for researchers who are considering the use of the SRDR.
Approaches to study across four year-levels of undergraduate occupational therapy students: Similar or different?
Authors: Brown Ted , Murdolo Yuki 
Published: August 2016

Introduction Past studies that have investigated approaches to study adopted by undergraduate students suggest that university learners enrolled in different year-levels in the same academic course may take up different approaches to study. No research to date has investigated how approaches to learning may differ among undergraduate occupational therapy students enrolled in their first, second, third or fourth year of tertiary level study. The aim of the current study was to examine the similarities and differences in approaches to study among four year-levels of occupational therapy students at one Australian university. Method First-, second-, third- and fourth-year undergraduate occupational therapy students ( N = 376; 92.8% response rate) completed the Approaches and Study Skills Inventory for Students. A one-way ANOVA and Tukey HSD were conducted to identify differences in approaches to study across the four year-level cohorts of students. Results Fourth-year students differed significantly from first-, second- and third-year students on the mean scores of the deep and strategic approaches to study ( F(3,372) = 6.958, p = .01 and F(3,372) = 8.366, p = .001 respectively) and on a number of the associated Approaches and Study Skills Inventory for Students subscales. There was no statistically significant difference across the four student cohorts on the mean score of the surface study approach. Conclusion Findings from the current study highlighted the difficulties in facilitating a deep approach to study and the prevalence of a surface study approach among undergraduate occupational therapy students.