bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative proteomics by SWATH-MS reveals sophisticated metabolic reprogramming in hepatocellular carcinoma tissues
Authors: Gao Yanyan , Wang Xinzheng , Sang Zhihong , Li Zongcheng , Liu Feng , Mao Jie , Yan Dan , Zhao Yongqiang , Wang Hongli , Li Ping , Ying Xiaomin , Zhang Xuemin , He Kun , Wang Hongxia 
Published: April 2017

AbstractHepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and understanding its molecular pathogenesis is pivotal to managing this disease. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) is an optimal proteomic strategy to seek crucial proteins involved in HCC development and progression. In this study, a quantitative proteomic study of tumour and adjacent non-tumour liver tissues was performed using a SWATH-MS strategy. In total, 4,216 proteins were reliably quantified, and 338 were differentially expressed, with 191 proteins up-regulated and 147 down-regulated in HCC tissues compared with adjacent non-tumourous tissues. Functional analysis revealed distinct pathway enrichment of up- and down-regulated proteins. The most significantly down-regulated proteins were involved in metabolic pathways. Notably, our study revealed sophisticated metabolic reprogramming in HCC, including alteration of the pentose phosphate pathway; serine, glycine and sarcosine biosynthesis/metabolism; glycolysis; gluconeogenesis; fatty acid biosynthesis; and fatty acid β-oxidation. Twenty-seven metabolic enzymes, including PCK2, PDH and G6PD, were significantly changed in this study. To our knowledge, this study presents the most complete view of tissue-specific metabolic reprogramming in HCC, identifying hundreds of differentially expressed proteins, which together form a rich resource for novel drug targets or diagnostic biomarker discovery.
Chiral nanoparticles in singular light fields
Authors: Vovk Ilia A. , Baimuratov Anvar S. , Zhu Weiren , Shalkovskiy Alexey G. , Baranov Alexander V. , Fedorov Anatoly V. , Rukhlenko Ivan D. 
Published: April 2017

AbstractThe studying of how twisted light interacts with chiral matter on the nanoscale is paramount for tackling the challenging task of optomechanical separation of nanoparticle enantiomers, whose solution can revolutionize the entire pharmaceutical industry. Here we calculate optical forces and torques exerted on chiral nanoparticles by Laguerre–Gaussian beams carrying a topological charge. We show that regardless of the beam polarization, the nanoparticles are exposed to both chiral and achiral forces with nonzero reactive and dissipative components. Longitudinally polarized beams are found to produce chirality densities that can be 109times higher than those of transversely polarized beams and that are comparable to the chirality densities of beams polarized circularly. Our results and analytical expressions prove useful in designing new strategies for mechanical separation of chiral nanoobjects with the help of highly focussed beams.
Relevance of deep learning to facilitate the diagnosis of HER2 status in breast cancer
Authors: Vandenberghe Michel E. , Scott Marietta L. J. , Scorer Paul W. , Söderberg Magnus , Balcerzak Denis , Barker Craig 
Published: April 2017

AbstractTissue biomarker scoring by pathologists is central to defining the appropriate therapy for patients with cancer. Yet, inter-pathologist variability in the interpretation of ambiguous cases can affect diagnostic accuracy. Modern artificial intelligence methods such as deep learning have the potential to supplement pathologist expertise to ensure constant diagnostic accuracy. We developed a computational approach based on deep learning that automatically scores HER2, a biomarker that defines patient eligibility for anti-HER2 targeted therapies in breast cancer. In a cohort of 71 breast tumour resection samples, automated scoring showed a concordance of 83% with a pathologist. The twelve discordant cases were then independently reviewed, leading to a modification of diagnosis from initial pathologist assessment for eight cases. Diagnostic discordance was found to be largely caused by perceptual differences in assessing HER2 expression due to high HER2 staining heterogeneity. This study provides evidence that deep learning aided diagnosis can facilitate clinical decision making in breast cancer by identifying cases at high risk of misdiagnosis.
A lignan induces lysosomal dependent degradation of FoxM1 protein to suppress β-catenin nuclear translocation
Authors: Dong Guang-zhi , Jeong Ji Hye , Lee Yu-ih , Han Yeong Eun , Shin Jung Sook , Kim Yoon-Jung , Jeon Raok , Kim Young Hwa , Park Tae Jun , Kim Keun Il , Ryu Jae-Ha 
Published: April 2017

AbstractColon cancer is one of the most common cancers. In this study, we isolated a lignan [(−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica (Betulaceae) and investigated its biological activity and mechanism of action on colon cancer. DFS reduced the viability of colon cancer cells and induced cell cycle arrest. DFS also suppressed β-catenin nuclear translocation and β-catenin target gene expression through a reduction in FoxM1 protein. To assess the mechanism of the action of DFS, we investigated the effect of DFS on endogenous and exogenous FoxM1 protein degradation in colon cancer cells. DFS-induced FoxM1 protein degradation was suppressed by lysosomal inhibitors, chloroquine and bafilomycin A1, but not by knock-down of proteasomal proteins. The mechanism of DFS for FoxM1 degradation is lysosomal dependent, which was not reported before. Furthermore, we found that FoxM1 degradation was partially lysosomal-dependent under normal conditions. These observations indicate that DFS from A. japonica suppresses colon cancer cell proliferation by reducing β-catenin nuclear translocation. DFS induces lysosomal-dependent FoxM1 protein degradation. This is the first report on the lysosomal degradation of FoxM1 by a small molecule. DFS may be useful in treating cancers that feature the elevated expression of FoxM1.
The need to compare: assessing the level of agreement of three high-throughput assays against Plasmodium falciparum mature gametocytes
Authors: Lucantoni Leonardo , Loganathan Sasdekumar , Avery Vicky M. 
Published: April 2017

AbstractWhole-cell High-Throughput Screening (HTS) is a key tool for the discovery of much needed malaria transmission blocking drugs. Discrepancies in the reported outcomes from various HTS Plasmodium falciparum gametocytocidal assays hinder the direct comparison of data and ultimately the interpretation of the transmission blocking potential of hits. To dissect the underlying determinants of such discrepancies and assess the impact that assay-specific factors have on transmission-blocking predictivity, a 39-compound subset from the Medicines for Malaria Venture Malaria Box was tested in parallel against three distinct mature stage gametocytocidal assays, under strictly controlled parasitological, chemical, temporal and analytical conditions resembling the standard membrane feeding assay (SMFA). Apart from a few assay-specific outliers, which highlighted the value of utilizing multiple complementary approaches, good agreement was observed (average ΔpIC50 of 0.12 ± 0.01). Longer compound incubation times improved the ability of the least sensitive assay to detect actives by 2-fold. Finally, combining the number of actives identified by any single assay with those obtained at longer incubation times yielded greatly improved outcomes and agreement with SMFA. Screening compounds using extended incubation times and using multiple in vitro assay technologies are valid approaches for the efficient identification of biologically relevant malaria transmission blocking hits.
Biallelic mutations in the gene encoding eEF1A2 cause seizures and sudden death in F0 mice
Authors: Davies Faith C. J. , Hope Jilly E. , McLachlan Fiona , Nunez Francis , Doig Jennifer , Bengani Hemant , Smith Colin , Abbott Catherine M. 
Published: April 2017

AbstractDe novo heterozygous missense mutations in the gene encoding translation elongation factor eEF1A2 have recently been found to give rise to neurodevelopmental disorders. Children with mutations in this gene have developmental delay, epilepsy, intellectual disability and often autism; the most frequently occurring mutation is G70S. It has been known for many years that complete loss of eEF1A2 in mice causes motor neuron degeneration and early death; on the other hand heterozygous null mice are apparently normal. We have used CRISPR/Cas9 gene editing in the mouse to mutate the gene encoding eEF1A2, obtaining a high frequency of biallelic mutations. Whilst many of the resulting founder (F0) mice developed motor neuron degeneration, others displayed phenotypes consistent with a severe neurodevelopmental disorder, including sudden unexplained deaths and audiogenic seizures. The presence of G70S protein was not sufficient to protect mice from neurodegeneration in G70S/− mice, showing that the mutant protein is essentially non-functional.
Evidence of an application of a variable MEMS capacitive sensor for detecting shunt occlusions
Authors: Apigo David J. , Bartholomew Philip L. , Russell Thomas , Kanwal Alokik , Farrow Reginald C. , Thomas Gordon A. 
Published: April 2017

AbstractA sensor was tested subdural and in vitro, simulating a supine infant with a ventricular-peritoneal shunt and controlled occlusions. The variable MEMS capacitive device is able to detect and forecast blockages, similar to early detection procedures in cancer patients. For example, with gradual occlusion development over a year, the method forecasts a danger over one month ahead of blockage. The method also distinguishes between ventricular and peritoneal occlusions. Because the sensor provides quantitative data on the dynamics of the cerebrospinal fluid, it can help test new therapies and work toward understanding hydrocephalus as well as idiopathic normal pressure hydrocephalus. The sensor appears to be a substantial advance in treating brain injuries treated with shunts and has the potential to bring significant impact in a clinical setting.
Locking Plate Alone versus in Combination with Two Crossed Kirschner Wires for Fifth Metacarpal Neck Fracture
Authors: Zhu Hongyi , Xu Zhengyu , Wei Haifeng , Zheng Xianyou 
Published: April 2017

AbstractFracture of fifth metacarpal neck commonly requires open reduction and internal fixation. However, the current methods of internal fixation in fifth metacarpal neck fractures remain unsatisfactory. Patients with fractures of fifth metacarpal neck received open reduction and internal fixation with either locking plate in combination with two crossed Kirschner wires (K-wires) or locking plate alone were evaluated for the clinical outcomes. Clinical outcomes included grip strength, Michigan hand outcomes questionnaire (MHQ), final angulation and range of motion (ROM) one year after treatment. The averages of MHQ scores, final angulation and ROM of fifth metacarpophalangeal joint of plate with K-wire group were more superior to those of plate group (MHQ 96.7 versus 86.6, final angulation 11.8 versus 23.6, ROM 83.3 versus 72.2). The grip strength had no significant difference between two groups. Locking plate in combination with two crossed K-wires is a more optimal method of fixation compared with locking plate alone.
Early Results of Surgical Simultaneous Therapy for Significant Carotid Artery Stenosis and Heart Disease
Authors: Irqsusi Marc , Vannucchi Alessandro , Beckers Julius , Kasseckert Stefan , Waldhans Stefan , Moosdorf Rainer , Vogt Sebastian 
Published: April 2017

Background The purpose of this single-center, retrospective study was to review the early outcome with defined endpoints of myocardial infarction, brain injury, and death after coronary bypass grafting and simultaneous carotid endarterectomy with or without combined valve replacement.
Methods During the preoperative investigation 52 (44 males, 8 females) patients were examined by cardiac catheterization within the scope of their coronary status. In addition, all patients underwent echocardiography, CT angiography of the supra-aortic vessels, and full description of their neurologic status. Included were all patients with the need of coronary revascularization, valve disease, and either symptomatic or asymptomatic carotid artery stenosis with a maximal narrowing of >70%.
Results There was one (2%) patient with a perioperative stroke and paresis of the upper limb. One (2%) patient experienced PRIND (2%). Eighteen (35%) patients suffered symptomatic transitory psychotic syndrome that fully recovered in all patients. One (2%) patient incurred a perioperative myocardial infarction that could be cured by percutaneous coronary stent implantation. Overall mortality was 4%.
Conclusion Simultaneous coronary bypass grafting as a single procedure or in combination with valve replacement and endarterectomy of severe carotid lesions with or without patients' history of previous stroke can be performed with a calculated low surgical risk. The complication rate for neurologic and myocardial events is low compared with the hazard of a single surgical repair. The in-hospital mortality is not significantly different to isolated procedures. The concomitant appearance of coronary stenosis and carotid artery disease is reasonable due to the nature of arteriosclerosis. In our opinion these patients benefit from a combined surgical approach.
Entwicklung eines neuen Zellisolationsverfahrens zur Erforschung der Mammakarzinompathogenese und -angiogenese für experimentelle in vitro und in vivo Assays
Authors: Weigand Annika , Tasbihi Kereshmeh , Strissel Pamela , Strick Reiner , Horch Raymund , Boos Anja 
Published: April 2017

Zusammenfassung
Hintergrund Brustkrebs gilt als die weltweit häufigste Krebserkrankung bei Frauen. Zunehmend wird autologer Lipotransfer zum Wiederaufbau der Brust nach Tumorresektion angewandt. Im zellunterstützenden Lipotransfer wird das Transplantat mit Stammzellen aus dem Fettgewebe (ADSC) angereichert. Trotz der positiven klinischen Ergebnisse gibt es aufgrund des Stammzellanteils Bedenken hinsichtlich der onkologischen Sicherheit. Bislang gibt es nur wenige Studien mit primären Zellen aus derselben Patientin, durch die es möglich werden könnte die Komplexität der Zell-Zell-Interaktionen im Mamma(karzinom)gewebe besser in experimentellen Settings darzustellen.
Material und Methoden Es wurde eine Literaturrecherche zum Thema autologer Lipotransfer durchgeführt. Aus Mamma(karzinom)gewebe, bzw. Blut wurden 5 unterschiedliche Zelltypen (epitheliale, mesenchymale Zellen, ADSC, Endothelzellen, endotheliale Progenitorzellen) isoliert und nachfolgend hinsichtlich ihrer Gen- und Proteinexpression sowie funktioneller Eigenschaften charakterisiert. Das arteriovenöse (AV) loop Modell in der Ratte wurde als mögliches in vivo Modell für die Mammakarzinompathogenese und -angiogenese im Rahmen dieser Studie evaluiert.
Ergebnisse In der Literatur konnten Hinweise auf eine in vitro Interaktion zwischen ADSC und Zellen des Mamma(karzinom)gewebes gefunden werden. In einigen klinischen Studien erschienen bestimmte Patientensubgruppen einem erhöhten Tumorrezidivrisiko nach Lipotransfer ausgesetzt zu sein, jedoch konnte in der Mehrzahl der Studien kein Zusammenhang zwischen Lipotransfer und Rezidivrate festgestellt werden. Aus Gewebe derselben Patientin konnten unterschiedliche Zellpopulationen isoliert werden, die sich hinsichtlich ihrer Oberflächenmarker, der Genexpression sowie funktioneller Eigenschaften deutlich voneinander differenzieren lassen. Im AV loop Modell konnte erfolgreich axial vaskularisiertes Gewebe gezüchtet werden.
Schlussfolgerung Anhand dieser Studie können wir erstmalig zeigen, dass aus derselben Gewebeprobe unterschiedliche Zellpopulationen isoliert werden können, die die Heterogenität im Tumorgewebe widerspiegeln. Dadurch werden exakte Analysen der Zell-Zell-Interaktionen und ihre Auswirkungen auf die Tumorangiogenese und -pathogenese im Mammakarzinom möglich. In Kombination mit dem AV loop Modell könnten neue Wege eröffnet werden vaskularisiertes Mammakarzinom- sowie gesundes Mammagewebe in vivo als optimales Modell für das klinische Setting zu generieren.
Stufenkonzept zur Therapie der konnatalen Dakryostenose
Authors: Heichel J. 
Published: April 2017

ZusammenfassungDie unklare Epiphora im Kindesalter gehört zu den häufigsten kinderophthalmologischen Fragestellungen. Eine konnatale Dakryostenose (KDS) stellt hierfür die wichtigste Differenzialdiagnose dar. In den meisten Fällen liegt eine persistierende Hasner-Membran ursächlich zugrunde. Da sich Komplikationen einstellen können, ist eine Therapie anzustreben. Therapeutisch können konservative von invasiven Vorgehensweisen unterschieden werden. Da gerade innerhalb des 1. Lebensjahrs mit einer hohen Spontanheilungsrate zu rechnen ist, muss die Indikation für chirurgische Interventionen in diesem Lebensabschnitt sorgfältig gestellt werden. Konservative Maßnahmen wie die digitale Kompression des Tränensacks sollten bei jeglichem Verdacht für eine KDS angewandt werden. Komplikationen wie akute Dakryozystitiden und rezidivierend aszendierende Infektionen rechtfertigen eine invasive Therapie. Ferner scheint die KDS einen amblyogenen Risikofaktor darzustellen. Neben der Sondierung und Überdruckspülung besteht die Möglichkeit, die ableitenden Tränenwege vorübergehend mit Silikonstützmaterialien zu schienen. Als weitere transkanalikuläre Zugänge eignen sich die Dakryoendoskopie und die Ballondakryoplastik. Die Dakryozystorhinostomie bleibt besonderen Indikationen vorbehalten. Sie zeichnet sich dennoch durch eine niedrige Komplikationsrate aus und führt in über 90 % zur Heilung. Die verfügbaren Therapieansätze lassen sich in einem Stufenkonzept integrieren. Dieses unterliegt zahlreichen Einflussfaktoren, weshalb es individuell ausgelegt werden muss.
Klinischer Vergleich einer trifokalen und einer trifokal-torischen Intraokularlinse auf gleicher diffraktiver Plattform
Authors: Gerl M. , Breyer D. , Hagen P. , Koss M. , Mueller M. , Al Saad M. , Gerl R. , Kaymak H. , Klabe K. , Kretz F. 
Published: April 2017

Zusammenfassung
Hintergrund Trifokale Linsen ergänzen seit wenigen Jahren die Möglichkeiten der chirurgischen Presbyopiekorrektur. In dieser Studie werden 2 Intraokularlinsen (IOL) auf Basis des gleichen trifokalen diffraktiven Designs verglichen, ein Modell ohne und eines mit torischer Komponente zur Astigmatismuskorrektur.
Patienten/Material und Methoden Prospektive nicht randomisierte Vergleichsstudie mit 142 Augen von 77 Patienten (Alter 40–73 Jahre) mit komplikationsloser Linsenchirurgie. Die Patienten wurden entsprechend dem implantierten Linsenmodell in 2 Gruppen aufgeteilt, die trifokale Gruppe (98 Augen von 50 Patienten) mit der trifokalen diffraktiven IOL AT LISA tri 839MP (Carl Zeiss Meditec) und die trifokal-torische Gruppe (44 Augen von 27 Patienten) mit Implantation der trifokal-torischen diffraktiven IOL AT LISA tri toric 939MP (Carl Zeiss Meditec). Sehschärfe und Refraktion wurden 3 Monate postoperativ ausgewertet.
Ergebnisse Es gab keine signifikanten Unterschiede zwischen den Gruppen in Bezug auf postoperative Refraktion (p ≥ 0,144), monokularen und binokularen unkorrigierten Intermediärvisus (UIVA; p = 0,519 bzw. 0,398) und binokularen unkorrigierten Nahvisus (UNVA; p = 0,073). Dagegen wurden in der trifokalen Gruppe ein signifikant besserer monokularer und binokularer unkorrigierter Fernvisus (UDVA; p ≤ 0,002) und monokularer UNVA (p = 0,005) beobachtet. Das sphärische Äquivalent lag bei 98 bzw. 100 % der Patienten innerhalb von ± 1,00 dpt bei der trifokalen Gruppe und der trifokal-torischen Gruppe. Ein postoperativer binokularer UDVA, UIVA und UNVA von 0,63 dezimal oder besser wurde bei 100, 95 bzw. 100 % der Augen in der trifokalen Gruppe und bei 96,3, 95,8 bzw. 90,9 % der Augen mit dem torischen Linsenmodell beobachtet.
Nanoparticle amount, and not size, determines chain alignment and nonlinear hardening in polymer nanocomposites
Authors: Varol H. Samet , Meng Fanlong , Hosseinkhani Babak , Malm Christian , Bonn Daniel , Bonn Mischa , Zaccone Alessio , Parekh Sapun H. 
Published: April 2017

SignificanceWhen straining materials (e.g., pulling a rubber band), they initially deform with a certain stiffness; if one pulls harder, some materials strengthen. This phenomenon, known as nonlinear strain hardening, is a critical feature of composite polymer materials—polymers with reinforcing filler particles—used in, e.g., car tires. Engineering properties such as modulus, toughness, and strength of nanocomposites have been traditionally optimized through trial and error by changing the size and amount of fillers. Our work elucidates the molecular origin of strain hardening in polymer nanocomposites, showing that filler amount, but not size, sets the strain-hardening properties based on interfiller chain elongation. The insensitivity to filler size provides a facile concept to independently tune linear and nonlinear mechanics in composites.
Ancient individuals from the North American Northwest Coast reveal 10,000 years of regional genetic continuity
Authors: Lindo John , Achilli Alessandro , Perego Ugo A. , Archer David , Valdiosera Cristina , Petzelt Barbara , Mitchell Joycelynn , Worl Rosita , Dixon E. James , Fifield Terence E. , Rasmussen Morten , Willerslev Eske , Cybulski Jerome S. , Kemp Brian M. , DeGiorgio Michael , Malhi Ripan S. 
Published: April 2017

Significance
The peopling of the Americas has been examined on the continental level with the aid of SNP arrays, next generation sequencing, and advancements in ancient DNA, all of which have helped elucidate evolutionary histories. Regional paleogenomic studies, however, have received less attention and may reveal a more nuanced demographic history. We present genome-wide sequences of individuals from the northern Northwest Coast covering a timespan of ∼10,000 years and show that continental patterns of demography do not necessarily apply on the regional level. Compared with existing paleogenomic data, we show that geographically linked population samples from the Northwest Coast exhibit an early ancestral lineage and find that population structure existed among Native North American groups as early as the late Pleistocene.
‘Believing is adapting’: Belief in a just world and emigrants’ identification and satisfaction with the host country / ‘Creer es adaptarse’: Creer en un mundo justo y la identificación y satisfacción de los emigrantes con el país de acogida
Authors: Leite Ana C. , Cardoso Sónia G. , Marques André G. , Morais Catarina 
Published: April 2017

In an era in which Europe is experiencing a new wave of emigration as a result of the economic crisis, it seems socially relevant to study the processes that underlie emigrants’ adjustment to their new place of living. Research has thoroughly supported the assumption that believing in a just world is an adaptive mechanism that helps people to deal with uncertainty and harsh realities in life. We propose that the endorsement of such beliefs might also contribute to a positive identification with the host country. Using a sample of Portuguese emigrants ( N = 144), we demonstrate in a cross-sectional design that belief in a just world predicts a positive identification with the host country. In addition, positive levels of identification with the host country predicted higher levels of satisfaction with emigrant life. Theoretical and applied implications are discussed.