bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood–brain barrier and laser technology for drug brain delivery
Authors: Semyachkina-Glushkovskaya Oxana V. , Abdurashitov Arkady S. , Saranceva Elena I. , Borisova Eketerina G. , Shirokov Alexander A. , Navolokin Nikita V. 
Published: September 2017

Here, we discuss an important problem in medicine as development of effective strategies for brain drug delivery. This problem is related to the blood–brain barrier (BBB), which is a “customs” controlling the entrance of different molecules from blood into the brain protecting the normal function of central nervous system (CNS). We show three interfaces of anatomical side of BBB and two functional types of BBB — physical and transporter barriers. Although this protective mechanism is essential for health of CNS, it also creates a hindrance to the entry of drugs into the brain. The BBB was discovered over 100 years ago but till now, there is no effective methods for brain drug delivery. There are more than 70 approaches for overcoming BBB including physical, chemical and biological techniques but all of these tools have limitation to be widely used in clinical practice due to invasiveness, challenge in performing, very costly or limitation of drug concentration.Photodynamic therapy (PDT) is usual clinical method of surgical navigation for the resection of brain tumor and anti-cancer therapy. Nowadays, the application of PDT is considered as a potential promising tool for brain drug delivery via opening of BBB. Here, we show the first successful experimental results in this field discussing the adventures and disadvantages of PDT-related BBB disruption as well as alternatives to overcome these limitations and possible mechanisms with new pathways for brain clearance via glymphatic and lymphatic systems.
Performance Implications of Extended Page Tables on Virtualized x86 Processors
Authors: Merrifield Timothy , Taheri H. Reza 
Published: September 2017

Managing virtual memory is an expensive operation, and becomes even more expensive on virtualized servers. Processing TLB misses on a virtualized x86 server requires a twodimensional page walk that can have 6x more page table lookups, hence 6x more memory references, than a native page table walk. Thus much of the recent research on the subject starts from the assumption that TLB miss processing in virtual environments is significantly more expensive than on native servers. However, we will show that with the latest software stack on modern x86 processors, most of these page table lookups are satisfied by internal paging structure caches and the L1/L2 data caches, and the actual virtualization overhead of TLB miss processing is a modest fraction of the overall time spent processing TLB misses.
We show that even for the heaviest workloads, a welltuned application that uses large pages on a recent OS release with a modern hypervisor running on the latest x86 processors sees only minimal degradation from the additional overhead of the two-dimensional page walks in a virtualized server.
Hybrid Cloud Storage
Authors: Gupta Abhishek , Spillane Rick , Wang Wenguang , Austruy Maxime , Fereydouny Vahid , Karamanolis Christos 
Published: September 2017

Thanks to the compelling economics of public cloud storage, the trend in the IT industry is to move the bulk of analytics and application data to services such as AWS S3 and Google Cloud Storage. At the same time, customers want to continue accessing and analyzing much of that data using applications that run on compute clusters that may reside either on public clouds or on-premise. For VMware customers, those clusters run vSphere (sometimes with vSAN) on-premise and in the future may utilize SDDCaaS. Cloud storage exhibits high latencies and it is not appropriate for direct use by applications. A key challenge for these use cases is determining the subset of the typically huge data sets that need to be moved into the primary storage tier of the compute clusters.
This paper introduces a novel approach for creating a hybrid cloud storage that allows customers to utilize the fast primary storage of their compute clusters as a caching tier in front of a slow secondary storage tier. This approach can be completely transparent requiring no changes to the application. To achieve this, we extended VDFS [16], a POSIX-compliant scale-out filesystem, with the concept of caching-tier volumes.
VDFS caching-tier volumes resemble regular file system volumes, but they fault-in data from a cloud storage back-end on first access. Cached data are persisted on fast primary storage, close to the compute cluster, like VMware's vSAN.
Caching-tier volumes use a write-back approach. The enterprise features of the primary storage ensure the persistence and fault tolerance of new or updated data. Write-back from the primary to cloud storage is managed using an efficient change-tracking mechanism built into VDFS called exo-clones [18].
This paper outlines the architecture and implementation of caching tier volumes on VDFS and reports on an initial evaluation of the current prototype.
VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma
Authors: Yao Xiaosai , Tan Jing , Lim Kevin Junliang , Koh Joanna , Ooi Wen Fong , Li Zhimei , Huang Dachuan , Xing Manjie , Chan Yang Sun , Qu James Zhengzhong , Tay Su Ting , Wijaya Giovani , Lam Yue Ning , Hong Jing Han , Lee-Lim Ai Ping , Guan Peiyong , Ng Michelle Shu Wen , He Cassandra Zhengxuan , Lin Joyce Suling , Nandi Tannistha , Qamra Aditi , Xu Chang , Myint Swe Swe , Davies James O. J. , Goh Jian Yuan , Loh Gary , Tan Bryan C. , Rozen Steven G. , Yu Qiang , Tan Iain Bee Huat , Cheng Christopher Wai Sam , Li Shang , Chang Kenneth Tou En , Tan Puay Hoon , Silver David Lawrence , Lezhava Alexander , Steger Gertrud , Hughes Jim R. , Teh Bin Tean , Tan Patrick 
Published: September 2017

Abstract
Protein-coding mutations in clear cell renal cell carcinoma (ccRCC) have been extensively characterized, frequently involving inactivation of the von Hippel–Lindau (VHL) tumor suppressor. Roles for noncoding cis-regulatory aberrations in ccRCC tumorigenesis, however, remain unclear. Analyzing 10 primary tumor/normal pairs and 9 cell lines across 79 chromatin profiles, we observed pervasive enhancer malfunction in ccRCC, with cognate enhancer-target genes associated with tissue-specific aspects of malignancy. Superenhancer profiling identified ZNF395 as a ccRCC-specific and VHL-regulated master regulator whose depletion causes near-complete tumor elimination in vitro and in vivo. VHL loss predominantly drives enhancer/superenhancer deregulation more so than promoters, with acquisition of active enhancer marks (H3K27ac, H3K4me1) near ccRCC hallmark genes. Mechanistically, VHL loss stabilizes HIF2α–HIF1β heterodimer binding at enhancers, subsequently recruiting histone acetyltransferase p300 without overtly affecting preexisting promoter–enhancer interactions. Subtype-specific driver mutations such as VHL may thus propagate unique pathogenic dependencies in ccRCC by modulating epigenomic landscapes and cancer gene expression.
Significance: Comprehensive epigenomic profiling of ccRCC establishes a compendium of somatically altered cis-regulatory elements, uncovering new potential targets including ZNF395, a ccRCC master regulator. Loss of VHL, a ccRCC signature event, causes pervasive enhancer malfunction, with binding of enhancer-centric HIF2α and recruitment of histone acetyltransferase p300 at preexisting lineage-specific promoter–enhancer complexes. Cancer Discov; 7(11); 1284–305. ©2017 AACR.
See related commentary by Ricketts and Linehan, p. 1221.
This article is highlighted in the In This Issue feature, p. 1201
Serial 3-Vessel Optical Coherence Tomography and Intravascular Ultrasound Analysis of Changing Morphologies Associated With Lesion Progression in Patients With Stable Angina Pectoris
Authors: Yamamoto Myong Hwa , Yamashita Kennosuke , Matsumura Mitsuaki , Fujino Akiko , Ishida Masaru , Ebara Seitarou , Okabe Toshitaka , Saito Shigeo , Hoshimoto Koichi , Amemiya Kisaki , Yakushiji Tadayuki , Isomura Naoei , Araki Hiroshi , Obara Chiaki , McAndrew Thomas , Ochiai Masahiko , Mintz Gary S. , Maehara Akiko 
Published: September 2017

Background—
Optical coherence tomographic (OCT) morphologies associated with lesion progression are not well studied. The aim of this study was to determine the morphological change for untreated lesion progression using both OCT and intravascular ultrasound (IVUS).

Methods and Results—

We used baseline and 8-month follow-up 3-vessel OCT and IVUS to assess 127 nonculprit lesions (IVUS plaque burden ≥40%) in 45 patients with stable angina after target lesion treatment. Lesion progression was defined as an IVUS lumen area decrease >0.5 mm
2
. A layered pattern was identified as a superficial layer that had a different optical intensity and a clear demarcation from underlying plaque. Lesion progression was observed in 19% (24/127) lesions, and its pattern was characterized into 3 types: type I, new superficial layered pattern at follow-up that was not present at baseline (n=9); type II, a layered pattern at baseline whose layer thickness increased at follow-up (n=7); or type III, no layered pattern at baseline or follow-up (n=8). The increase of IVUS plaque+media area was largest in type I and least in type III (1.9 mm
2
[1.6–2.1], 1.1 mm
2
[0.9–1.4], and 0.3 mm
2
[−0.2 to 0.8], respectively;
P
=0.002). Type III, but not types I or II, showed negative remodeling during follow-up (IVUS vessel area; from 14.3 mm
2
[11.4–17.2] to 13.5 mm
2
[10.4–16.7];
P
=0.02). OCT lipidic plaque was associated with lesion progression (odds ratio, 13.6; 95% confidence interval, 3.7–50.6;
P
<0.001).

Conclusions—
Lesion progression was categorized to distinct OCT morphologies that were related to changes in plaque mass or vessel remodeling.
Patient and Physician Perspectives on Public Reporting of Mortality Ratings for Percutaneous Coronary Intervention in New York State
Authors: Fernandez Genaro , Narins Craig R. , Bruckel Jeffrey , Ayers Brian , Ling Frederick S. 
Published: September 2017

Background—
Public reporting of physician-specific outcome data for procedures, such as percutaneous coronary intervention (PCI), can influence physicians to avoid high-risk patients who may benefit from treatment. Prior physician attitudes toward public scorecards in New York State (NYS) have been studied, but the exclusion criteria have evolved. Additionally, patient perceptions toward such reports remain poorly understood. This study evaluates (1) whether exclusion of certain high-risk patients from public reporting of PCI outcomes in NYS has influenced physician attitudes, (2) current patient awareness and use of publicly reported outcome data, and (3) differences in physician and patient attitudes toward public reporting.

Methods and Results—
A questionnaire was administered to interventional cardiologists in NYS with specific emphasis on how modifications in publicly reported outcome data have influenced their practice. The results were compared with a 2003 survey administered by our group. A separate questionnaire regarding the publicly available NYS PCI Report was administered to patients referred to our center for possible PCI. The majority of interventional cardiologists indicated that the exclusion of patients with anoxic brain injury and refractory cardiogenic shock from public reporting has made them more likely to perform PCI for these subgroups. While patient awareness of the NYS PCI Report was low, patients were significantly more likely than physicians to think that publication of physician-specific mortality data can provide an accurate measure of physician quality, serve to improve patient care, and provide useful information in terms of physician selection.

Conclusions—
The study provides further evidence that public reporting of physician-specific outcome data influences physician behavior and indicates that significant discrepancies exist in how scorecards are perceived by physicians versus patients.
Sleep‐Disordered Breathing in Acute Ischemic Stroke: A Mechanistic Link to Peripheral Endothelial Dysfunction
Authors: Scherbakov Nadja , Sandek Anja , Ebner Nicole , Valentova Miroslava , Nave Alexander Heinrich , Jankowska Ewa A. , Schefold Jörg C. , von Haehling Stephan , Anker Stefan D. , Fietze Ingo , Fiebach Jochen B. , Haeusler Karl Georg , Doehner Wolfram 
Published: September 2017

Background

Sleep‐disordered breathing (
SDB
) after acute ischemic stroke is frequent and may be linked to stroke‐induced autonomic imbalance. In the present study, the interaction between
SDB
and peripheral endothelial dysfunction (
ED
) was investigated in patients with acute ischemic stroke and at 1‐year follow‐up.

Methods and Results

SDB
was assessed by transthoracic impedance records in 101 patients with acute ischemic stroke (mean age, 69 years; 61% men; median National Institutes of Health Stroke Scale, 4) while being on the stroke unit.
SDB
was defined by apnea‐hypopnea index ≥5 episodes per hour. Peripheral endothelial function was assessed using peripheral arterial tonometry (Endo
PAT
‐2000).
ED
was defined by reactive hyperemia index ≤1.8. Forty‐one stroke patients underwent 1‐year follow‐up (390±24 days) after stroke.
SDB
was observed in 57% patients with acute ischemic stroke. Compared with patients without
SDB
,
ED
was more prevalent in patients with
SDB
(32% versus 64%;
P
<0.01). After adjustment for multiple confounders, presence of
SDB
remained independently associated with
ED
(odds ratio, 3.1; [95% confidence interval, 1.2–7.9];
P
<0.05). After 1 year, the prevalence of
SDB
decreased from 59% to 15% (
P
<0.001). Interestingly, peripheral endothelial function improved in stroke patients with normalized
SDB
, compared with patients with persisting
SDB
(
P
<0.05).

Conclusions

SDB
was present in more than half of all patients with acute ischemic stroke and was independently associated with peripheral
ED
. Normalized
ED
in patients with normalized breathing pattern 1 year after stroke suggests a mechanistic link between
SDB
and
ED
.

Clinical Trial Registration

URL
:
https://drks-neu.uniklinik-freiburg.de
. Unique identifier:
DRKS
00000514.
Marxism after Marx: Karl Kautsky’s Disputed Legacy
Authors: Lewis Ben 
Published: September 2017

AbstractToday, Karl Kautsky (1854–1938) is mainly remembered for his polemics against the young Bolshevik regime or as the ‘renegade’ in Lenin’sThe Proletarian Revolution and the Renegade Kautsky(1918), which pillories him for his wavering stance in opposing World War I and his (later) outright hostility to the Russian Revolution of October 1917. Kautsky’s authority as a Marxist theoretician was seriously called into question ever since Lenin’s polemic. During the Cold War in particular, a consensus emerged which suggested that Kautsky’s views of democracy, organisation and revolutionary change had little or nothing to do with the political practice of Russian Bolshevism and the Russian Revolution of 1917. Recently, however, several studies have challenged this consensus. They highlight the profound impact which Kautsky had on the development of Russian Bolshevism and make the case that – prior to his renegacy in 1914 – thinkers such as Lenin and Trotsky viewed Kautsky as the legitimate intellectual heir of Marx and Engels. This article introduces an autobiographical essay written by Kautsky in 1924 and calls for closer engagement with his œuvre as a whole.
How Capitalist Were the ‘Bourgeois Revolutions’?
Authors: Post Charles 
Published: September 2017

AbstractThe canonical version of the ‘bourgeois revolutions’ has been under attack from both pro-capitalist ‘Revisionist’ historians and ‘Political Marxists’. Neil Davidson’s bookHow Revolutionary Were the Bourgeois Revolutions?provides a thorough review of the intellectual history of the notion of the bourgeois revolution and attempts to rescue the concept from varied criticism. Despite distancing himself from problematic formulations of the bourgeois revolution inherited from Second-International Marxism, Davidson’s own framework reproduces many of the historical and conceptual problems of this tradition.
Reification and the Human Commodity: Theorizing Modern Slavery in Brazil
Authors: Issa Daniela 
Published: September 2017

Modern slavery in Brazil exemplifies the culmination of reification as theorized by György Lukács, characterized by the commodification and dehumanization of labor and the extreme objectification of workers, who become “human commodities” in the capitalist system—“commodities” that produce other commodities. The concept of reification was incorporated into the 2003 Brazilian law on slave labor, where equating a human being with a thing in the performance of labor is a crime regardless of whether a worker is confined. A escravidão moderna no Brasil exemplifica o ponto culminante da teoria da reificação descrita por György Lukács, a qual é caracterizada pela mercantilização e desumanização do trabalho, e a extrema coisificação dos trabalhadores, que tornam-se “mercadorias humanas” no sistema capitalista—“mercadorias” produtoras de outras mercadorias. O conceito de reificação sobre o trabalho escravo foi incorporado à legislação brasileira em 2003, na qual igualar um ser humano a uma coisa, no exercício do trabalho, é crime mesmo que o trabalhador não esteja confinado.
Environmental Protection, Work, and Social Inclusion: Formalizing the Recycling of Urban Solid Waste in Buenos Aires
Authors: Bonelli Johanna Maldovan 
Published: September 2017

The changes in the paradigms regarding urban solid waste management that have occurred in the past few decades have led to a reformulation of Argentine social, labor, and environmental policies. In the case of the city of Buenos Aires, the presence of thousands of “informal” recyclers dedicated to the recovery of recyclable materials for their subsistence has given a particular imprint to the design of these policies, the focus of which has been the social inclusion of these workers through the creation of cooperatives. An examination of the assumptions underlying the use of the concept of informality in the development of cooperatives for recycling from 2007 to 2013 shows that they are part of a complex process in which measures for increasing rights and protections are associated with various forms of labor instability. En las últimas décadas, los cambios en los paradigmas de manejo de residuos sólidos urbanos han dado lugar a una reformulación de las políticas sociales, laborales y ambientales argentinas. En el caso de la ciudad de Buenos Aires, la presencia de miles de recicladores “informales” dedicados a recuperar materiales reciclables para su subsistencia le ha dado un cariz particular al diseño de dichas políticas, las cuales buscan la inclusión social de estos trabajadores a través de la creación de cooperativas. Un análisis de los supuestos que subyacen el uso del concepto de informalidad en el desarrollo de las cooperativas para reciclaje de 2007 a 2013 muestra que son parte de un complejo proceso en el que las medidas para aumentar los derechos y grado de protección de los trabajadores se asocian a diversas formas de inestabilidad laboral.
Identifying Occupations at Risk for Laryngeal Disorders Requiring Specialty Voice Care
Authors: Mori Matthew C. , Francis David O. , Song Phillip C. 
Published: September 2017

ObjectiveTo identify occupational groups’ use of specialty voice clinic evaluation.Study DesignRetrospective cohort study.SettingTertiary subspecialty clinic.Subjects and MethodsWe analyzed data collected on patients presenting to the Massachusetts Eye and Ear Infirmary Voice and Speech Laboratory over a 20‐year period (1993‐2013). The relative risk (RR) and 99% confidence interval (CI) of presentation were calculated for each occupational category in the greater Boston population using year‐matched data from the Bureau of Labor Statistics (BLS).ResultsThe records of 12,120 new patients were reviewed. Using year‐ and occupation‐matched BLS data from 2005 to 2013, 2726 patients were included in the cohort analysis. Several occupations had significantly higher risk of presentation. These included arts and entertainment (RR 4.98, CI 4.18‐5.95), law (RR 3.24, CI 2.48‐4.23), education (RR 3.08, CI 2.70‐3.52), and social services (RR 2.07, CI 1.57‐2.73). In contrast, many occupations had significantly reduced risk of presentation for laryngological disorders, for example, maintenance (RR 0.25, CI 0.15‐0.42), food preparation (RR 0.35, CI 0.26‐0.48), and administrative support (RR 0.49, CI 0.41‐0.57).ConclusionCertain occupations are associated with higher use of laryngological services presumably because of their vocational voice needs. In addition to confirming findings from other studies, we identified several new occupation groups with increased or decreased risk for laryngologic disorders. Understanding what factors predispose to requiring specialty voice evaluation may help in targeting preventative efforts.
Polysomnography in Pediatric Otolaryngology: If Not Obstructive Sleep Apnea, What Is It?
Authors: Heubi Christine H. , Meinzen‐Derr Jareen , Shott Sally R. , Smith David F. , Ishman and Stacey L. 
Published: September 2017

ObjectiveTo determine common polysomnographic (PSG) diagnoses for children referred by otolaryngologists.Study DesignRetrospective case series with chart review.SettingSingle tertiary pediatric hospital (2010‐2015).Subjects and MethodsReview of the medical records of 1258 patients undergoing PSG by otolaryngology referral. Patients who underwent previous otolaryngologic surgery were excluded. Data distributions were evaluated using means with standard deviations for continuous variables and frequencies with percentages for categorical variables.ResultsA total of 1258 patients were included; 55.9% were male, 64.5% were Caucasian, 16.6% had Down syndrome, and 48% had public insurance. The median age at the time of PSG was 5.2 years (range = 0.2‐18.94). Indications for PSG were sleep‐disordered breathing (SDB; 69.4%), restless sleep (12.7%), airway anomalies (7.5%), and laryngomalacia (7.2%). SDB was seen in 73.4%, obstructive sleep apnea (OSA) in 53.2%, OSA + central sleep apnea (CSA) in 4.5%, CSA in 0.9%, and non‐OSA snoring in 15%. Other diagnoses included periodic limb movements of sleep (PLMS; 7.4%), hypoventilation (6.8%), and nonapneic hypoxemia (2.6%). SDB was more common in younger children and seen in 91.4% of children <12 months and in 69.2% of children ≥24 months, while non‐OSA snoring was more common with increasing age (3.7% in children <12 months, 17.7% of children ≥24 months). PLMS were seen in 8.9% of children ≥24 months and in no children <12 months.ConclusionWhile OSA and snoring were the most common diagnoses reported, PLMS, alveolar hypoventilation, and CSA occurred in 7.4%, 6.8%, and 5.4%, respectively. These findings indicate that additional diagnoses other than OSA should be considered for children seen in an otolaryngology clinic setting who undergo PSG for sleep disturbances.