bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing chemical processes and kinetics of drug action within single living cells via plasmonic Raman probes
Authors: Li Shan-Shan , Guan Qi-Yuan , Meng Gang , Chang Xiao-Feng , Wei Ji-Wu , Wang Peng , Kang Bin , Xu Jing-Juan , Chen Hong-Yuan 
Published: May 2017

AbstractBetter understanding the drug action within cells may extend our knowledge on drug action mechanisms and promote new drugs discovery. Herein, we studied the processes of drug induced chemical changes on proteins and nucleic acids in human breast adenocarcinoma (MCF-7) cells via time-resolved plasmonic-enhanced Raman spectroscopy (PERS) in combination with principal component analysis (PCA). Using three popular chemotherapy drugs (fluorouracil, cisplatin and camptothecin) as models, chemical changes during drug action process were clearly discriminated. Reaction kinetics related to protein denaturation, conformational modification, DNA damage and their associated biomolecular events were calculated. Through rate constants and reaction delay times, the different action modes of these drugs could be distinguished. These results may provide vital insights into understanding the chemical reactions associated with drug-cell interactions.
Preparation, characterization and pharmacokinetics of cyadox nanosuspension
Authors: Sattar Adeel , Chen Dongmei , Jiang Lishun , Pan Yuanhu , Tao Yanfei , Huang Lingli , Liu Zhenli , Xie Shuyu , Yuan Zonghui 
Published: May 2017

AbstractAn increase in number of newly developed synthetic drugs displays bioavailability constraints because of poor water solubility. Nanosuspensions formulation may help to overwhelm these problems by increasing dissolution velocity and saturation solubility. In the present study, cyadox (Cyx) nanosuspension was successfully prepared by recrystallization based on acid–base neutralization combined with high pressure homogenization method using Polyvinylpyrrolidone K30 (PVP) as stabilizer. The nanosuspension had uniform particle distribution, excellent sedimentation rate and redispersibility. The nanosuspension significantly improved the solubility, dissolution and bioavailability. The saturation solubility of Cyx nanocrystal was higher than that of bulk Cyx and released the total drug in very short time. Further, pharmacokinetics of Cyx nanosuspension and normal suspension following oral administration was investigated in beagle dogs. Nanosuspension improved the bioavailability of Cyx which could be beneficial for intestinal bacterial infection in animals. Maximum concentration and area under concentration time curve were increased with particles size reduction which might give rise to pronounce fluctuations in plasma concentration and more intensified antibacterial effects. The terminal half-life and mean resident time of Cyx nanosuspension had also increased compared to normal Cyx suspension. In conclusion, nanosuspensions may be a suitable delivery approach to increase the bioavailability of poorly soluble drugs.
Surface PEGylation of Mesoporous Silica Nanorods (MSNR): Effect on loading, release, and delivery of mitoxantrone in hypoxic cancer cells
Authors: Wani Amit , Savithra Galbokka H. Layan , Abyad Ayat , Kanvinde Shrey , Li Jing , Brock Stephanie , Oupický David 
Published: May 2017

AbstractMesoporous silica nanomaterials show great potential to deliver chemotherapeutics for cancer treatment. The key challenges in the development of injectable mesoporous silica formulations are colloidal instability, hemolysis and inefficient drug loading and release. In this study, we evaluated the effect of PEGylation of mesoporous silica nanorods (MSNR) on hemolysis, colloidal stability, mitoxantrone (MTX) loading, in vitro MTX release, and cellular MTX delivery under hypoxic conditions. We found that PEGylation prevented dose-dependent hemolysis in the concentrations studied (0–10 mg/ml) and improved colloidal stability of MSNR. A negative effect of PEGylation on MTX loading was observed but PEGylated MSNR (PMSNR) demonstrated increased MTX release compared to non-PEGylated particles. Under hypoxic conditions, a decrease in the IC50 of MTX and MTX-loaded MSNR was observed when compared to normoxic conditions. These results showed that MSNR could deliver the chemotherapeutic agent, MTX to tumor cells and induce effective cell killing. However, the effect of PEGylation needs to be carefully studied due to the observed adverse effect on drug loading.
Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil
Authors: Ishida Kaoru , Ito Chie , Ohmori Yukimi , Kume Kohei , Sato Kei A. , Koizumi Yuka , Konta Akari , Iwaya Takeshi , Nukatsuka Mamoru , Kobunai Takashi , Takechi Teiji , Nishizuka Satoshi S. 
Published: May 2017

AbstractDrug-tolerant cancer cell subpopulations are responsible for relapse after chemotherapy. By continuously exposing the gastric cancer cell line MKN45 to 5-FU for >100 passages, we established a 5-fluorouracil (5-FU)-tolerant line, MKN45/5FU. Orthotopic xenografts of MKN45/5FU cells in the stomach of nude mice revealed that these cells had a high potential to metastasize to sites such as the liver. Levels of phosphorylated phosphatidylinositide 3-kinase (PI3K) increased both in 5-FU-tolerant subpopulations according to the 5-FU dose, and in gastric submucosal orthotopic xenografts of MKN45/5FU cells. Sequential administration of 5-FU and a PI3K inhibitor, GDC-0941, targeted the downstream ribosomal S6 kinase phosphorylation to significantly suppress 5-FU-tolerant subpopulations and tumor propagation of orthotopic MKN45/5FU xenografts. These results suggest that administration of 5-FU followed by GDC-0941 may suppress disease relapse after 5-FU-based gastric cancer chemotherapy.
Intravenous Thrombolysis in Chinese Patients with Different Subtype of Mild Stroke: Thrombolysis in Patients with Mild Stroke
Authors: Chen Weiqi , Pan Yuesong , Zhao Xingquan , Liu Liping , Li Hao , Liao Xiaoling , Wang Chunjuan , Wang Yilong , Wang Yongjun 
Published: May 2017

AbstractThrombolysis treatment for patients with mild stroke is controversial. The aim of our study was to investigate whether patients with mild stroke or its specific etiologic subtype might benefit from rt-PA therapy. Data were derived from two cohorts of patients with and without rt-PA treatment: (1) the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) and (2) the China National Stroke Registry (CNSR) database. Patients with mild stroke (defined as National Institutes of Health Stroke Scale ≤5) receiving the rt-PA therapy and without rt-PA therapy were matched in 1:2 for age, sex, stroke severity and etiologic subtype. A total of 134 rt-PA-treated patients were matched to 249 non-rt-PA-treated patients in the study. Among them, 104 (76%) rt-PA-treated patients with mild stroke had good outcome after 3 months compared with 173 (69.5%) non-rt-PA-treated matching cases (odds ratio [OR], 1.48; 95% confidence interval [CI], 0.91–2.43; P = 0.12). Compared with non-rt-PA-treated group, rt-PA-treated patients had good outcome after 3 months in those with stroke subtype of large-artery atherosclerosis (LAA) (80.5% vs 65.1%; OR, 2.19; 95%CI, 1.14–4.21; P = 0.02). For patients with mild stroke, intravenous rt-PA treatment may be effective. Patients with stroke subtype of LAA might benefit more from rt-PA treatment.
Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma
Authors: Ritter Cathrin , Fan Kaiji , Paschen Annette , Reker Hardrup Sine , Ferrone Soldano , Nghiem Paul , Ugurel Selma , Schrama David , Becker Jürgen C. 
Published: May 2017

AbstractMerkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host’s immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2. Notably, experimental provisions of HLA class-I binding peptides restored HLA class-I surface expression on MCC cells. Silencing of the HLA class-I APM is due to histone deacetylation as inhibition of histone deacetylases (HDACs) not only induced acetylation of histones in the respective promoter regions but also re-expression of APM components. Thus, HDAC inhibition restored HLA class-I surface expression in vitro and in a mouse xenotransplantation model. In contrast to re-induction of HLA class-I by interferons, HDAC inhibitors did not interfere with the expression of immuno-dominant viral proteins. In summary, restoration of HLA class-I expression on MCC cells by epigenetic priming is an attractive approach to enhance therapies boosting adaptive immune responses.
Fabrication of cerebral aneurysm simulator with a desktop 3D printer
Authors: Liu Yu , Gao Qing , Du Song , Chen ZiChen , Fu JianZhong , Chen Bing , Liu ZhenJie , He Yong 
Published: May 2017

AbstractNow, more and more patients are suffering cerebral aneurysm. However, long training time limits the rapid growth of cerebrovascular neurosurgeons. Here we developed a novel cerebral aneurysm simulator which can be better represented the dynamic bulging process of cerebral aneurysm The proposed simulator features the integration of a hollow elastic vascular model, a skull model and a brain model, which can be affordably fabricated at the clinic (Fab@Clinic), under $25.00 each with the help of a low-cost desktop 3D printer. Moreover, the clinical blood flow and pulsation pressure similar to the human can be well simulated, which can be used to train the neurosurgical residents how to clip aneurysms more effectively.
Mary's Case: An Illustration of Interprofessional Collaborative Practice for a Child With Severe Disabilities
Authors: Ogletree Billy T. , Brady Nancy , Bruce Susan , Dean Evan , Romski MaryAnn , Sylvester Lorraine , Westling David 
Published: May 2017

Purpose
The principles of interprofessional collaborative practice (IPCP) are illustrated through the case of Mary, a child with severe disabilities.

Method
Mary's experiences from early childhood to young adulthood are highlighted by both optimal and less-than-ideal examples of clinical services and collaborative practice. The range of collaboration illustrates potential variations in service delivery. Thematic comments and resources are provided by professionals experienced with and committed to IPCP who represent the following four disciplines: occupational therapy, physical therapy, special education, and speech-language pathology.

Conclusions
Although potentially challenging, IPCP is a dynamic practice methodology appropriate for speech-language pathologists and others serving persons with severe disabilities.
Comprehensive Literacy Instruction, Interprofessional Collaborative Practice, and Students With Severe Disabilities
Authors: Erickson Karen A. 
Published: May 2017

PurposeThe purpose of this clinical focus article is to briefly describe comprehensive emergent and conventional literacy instruction for students with severe disabilities. Specific attention is given to interprofessional collaborative practice and the roles of team members in planning and delivering instruction.MethodA rationale for the delivery of comprehensive instruction that balances skill and meaning emphases is provided with reference to new college and career readiness standards, the literature on literacy acquisition for students without disabilities, and, when possible, the literature on literacy acquisition for students with severe disabilities. Specific instructional approaches are presented to demonstrate how teams can actively engage students with severe disabilities in instruction that is collaborative, participatory, and interactive.Results/ConclusionsSuccessful provision of comprehensive literacy instruction that allows students with severe disabilities to achieve conventional literacy takes time and the efforts of a collaborative interprofessional team. Speech-language pathologists play a critical role on these teams as they ensure that students with severe disabilities have the language and communication supports they need to be successful.
Totally Minimally Invasive Esophagectomy and Gastric Pull-Up Reconstruction with an Intrathoracic Circular Stapled Anastomosis with a Team of Two (Surgeon and Assistant Only)
Authors: Lang Hauke , Grimminger Peter 
Published: May 2017

AbstractTotally minimally invasive esophagectomy (MIE) is nowadays en vogue.1
2
3
4
5 There are several reports showing that already partial minimally invasive esophagectomies (hybrid esophagectomies) with a laparoscopic approach and open transthoracic resection are beneficial for patients due to the reduced operative trauma. Also for total MIE several groups have reported benefits for patients in terms of morbidity and quality of life.1
5 However, different approaches and experiences of different esophageal surgery groups are hardly comparable and thus do not allow a simple answer in favor of a specific total MIE technique. To enlighten the field of total MIE, we present the technique as we perform this procedure nearly weekly in our department. The described MIE technique is safe and feasible. Changing to this demonstrating technique, we did not have any mortality so far, even in the first 30 cases. Especially for surgeons who plan to switch from the open surgical technique toward hybrid, MIE or robotic-assisted MIE.
Acute Treatment Patterns for Lower Extremity Trauma in the United States: Flaps versus Amputation
Authors: Mundy Lily , Truong Tracy , Shammas Ronnie , Gage Mark , Pomann Gina-Maria , Hollenbeck Scott 
Published: May 2017

Background Treatment algorithms for large soft tissue defects in lower extremity trauma are not clearly defined. The aim of this study is to determine if there are geographic or demographic differences in the management of open tibia fractures with soft tissue defects requiring either soft tissue reconstruction or amputation in the United States (US).
Methods A retrospective analysis was performed on the Nationwide Inpatient Sample (NIS), 2000 to 2011. We evaluated flap and amputation rates in the open tibia fractures with soft tissue defects based on geographic and socioeconomic factors.
Results From 2000 to 2011, there were 175,283 open tibia fractures in the US; 7.2% (n = 12,620) had a concomitant soft tissue defect requiring either flap or amputation. The overall flap rate was 73.2% (n = 9,235). When compared with the South at 68%, flap rates were highest in the West at 79% (adjusted odds ratio [AOR] = 2.06; 95% confidence interval [CI] = 1.49, 2.86; p < 0.0001), followed by the Northeast at 77% (AOR = 1.63; 95% CI = 1.22, 2.19; p = 0.001), and the Midwest at 74% (AOR = 1.76; 95% CI = 1.25, 2.47; p = 0.001). Flap rates were lower in the rural hospitals in the West (AOR = 0.24; 95% CI = 0.07, 0.84; p = 0.03) and Northeast (AOR = 0.55; 95% CI = 0.37, 0.82; p = 0.003) when compared with the urban hospitals. Flap rates were highest in the highest income quartile at 77% (AOR = 1.53; 95% CI = 1.05, 2.25; p = 0.03) compared with 72% in the lowest income quartile.
Conclusions Reconstruction rates were significantly higher in three major US regions when compared with the South, urban hospitals in the West and Northeast, and the highest income quartile.
Physiological Dynamic Apnea Responses in Relation to Apnea Capacity in Triathletes
Authors: Guimard Alexandre , Zorgati Houssem , Brulaire Sylvain , Amiot Virgile , Prieur Fabrice , Collomp Katia 
Published: May 2017

AbstractThe aim was to assess the cardiac, arterial oxygen saturation, lactate, hormonal and Borg rating of perceived exertion (RPE) responses to acute apnea in relation to apnea capacity in 18 middle-aged triathletes. Subjects were monitored while swimming two 50-m freestyle exercise trials with fins at maximal speed: with normal frequency breathing (NB) and with complete apnea (Ap); the latter was used to assess apnea capacity. The subjects with significant alteration in swimming performance inducing a time increase greater than 2.5% during Ap vs. NB were put in the group: bad apnea capacity (Bad Ap); the others, who showed no significant alteration in performance, were put in the group: Good Ap. Under apnea, both groups showed a decrease in arterial oxygen saturation (p<0.05). In Ap conditions, only Bad Ap had a significant lower maximal heart rate vs. NB (p<0.05), with lower blood lactate (p<0.05) and arm stroke frequency (p<0.01). No change in saliva hormonal concentrations was found during the experiment for both groups, whereas RPE responses were increased in the Good Ap group under Ap vs. NB conditions. In conclusion, a good apnea capacity seems to be associated with lower cardiovascular and metabolic apnea alterations in middle-aged recreationally-trained triathletes.
Möglichkeiten und Grenzen der OCT-Angiografie bei Patienten mit Chorioretinopathia centralis serosa
Authors: Cakir B. , Reich M. , Lang S. , Bühler A. , Stahl A. , Böhringer D. , Agostini H. , Lange C. 
Published: May 2017

Zusammenfassung
Hintergrund Die Chorioretinopathia centralis serosa (CCS) ist eine der häufigsten Ursachen für erworbene Makulopathien. Die neue OCT-Angiografie (OCTA) erlaubt als ein nicht invasives, kontaktloses Verfahren erstmals eine detaillierte Beurteilung und Charakterisierung der Aderhaut bei CCS-Patienten.
Methoden Es wurden 43 Augen von 29 CCS-Patienten in diese retrospektive Studie eingeschlossen. Als Kontrollkollektiv dienten 18 Augen von 9 gesunden Probanden. Die OCTA-Aufnahmen wurden beurteilt und mit konventionellen Aufnahmen der Fluoreszenz- (FAG) und Indocyaningrünangiografie (ICG) verglichen.
Ergebnisse Bei allen CCS-Patienten zeigten sich im Vergleich zur gesunden Kontrolle Veränderungen in Form von fokalen Hyper- und Hypoperfusionsarealen in der Choriokapillaris. Diese waren besonders bei Patienten mit chronischer, atropher CCS ausgeprägt. Die konventionelle FAG/ICG wies in 10 von 43 Augen einen Quellpunkt und in 3 von 43 Augen eine chorioidale Neovaskularisation (CNV) auf. Die OCTA konnte in 4 von 10 Fällen den Quellpunkt in Form eines Hyperperfusionsareals bestätigen und in 2 von 3 Fällen die chorioidale Neovaskularisation detektieren. In einem Fall zeigte die OCTA eine CNV, die in der FAG/ICG nicht nachweisbar war.
Schlussfolgerung Patienten mit CCS weisen in der OCTA deutliche Hyper- und Hypoperfusionsareale in der Choriokapillaris auf. Die Detektion von Quellpunkten ist aufgrund des fehlenden Nachweises von Leckagen in der OCTA nicht zuverlässig möglich. Die OCTA ist jedoch im Gegensatz zur FAG/ICG in der Lage, unabhängig von der exsudativen Aktivität CNV präzise darzustellen und stellt somit eine wichtige Ergänzung in der Diagnostik der CCS dar.
High Arctic Holocene temperature record from the Agassiz ice cap and Greenland ice sheet evolution
Authors: Lecavalier Benoit S. , Fisher David A. , Milne Glenn A. , Vinther Bo M. , Tarasov Lev , Huybrechts Philippe , Lacelle Denis , Main Brittany , Zheng James , Bourgeois Jocelyne , Dyke Arthur S. 
Published: May 2017

Significance
Reconstructions of past environmental changes are important for placing recent climate change in context and testing climate models. Periods of past climates warmer than today provide insight on how components of the climate system might respond in the future. Here, we report on an Arctic climate record from the Agassiz ice cap. Our results show that early Holocene air temperatures exceed present values by a few degrees Celsius, and that industrial era rates of temperature change are unprecedented over the Holocene period (∼12,000 y). We also demonstrate that the enhanced warming leads to a large response of the Greenland ice sheet; providing information on the ice sheet's sensitivity to elevated temperatures and thus helping to better estimate its future evolution.
Shear bands as manifestation of a criticality in yielding amorphous solids
Authors: Parisi Giorgio , Procaccia Itamar , Rainone Corrado , Singh Murari 
Published: May 2017

Significance
The art of making structural, polymeric, and metallic glasses is rapidly developing with many applications. A limitation is that, under increasing external strain, all amorphous solids have a yield stress, which when exceeded, results in a plastic response leading to mechanical failure. Understanding this is crucial for assessing the risk of failure of glassy materials under loads. The universality of the mechanical yield requires a theory that is general enough to transcend the microscopic details of different glasses, which all show similar stress–strain curves with a yield point. We provide a general theory that is thermodynamic in nature, showing that the mechanical yield is a spinodal criticality in an appropriately constructed free energy landscape.
Approach to the translation ofsoundin comic books
Authors: Igareda Paula 
Published: May 2017

AbstractThe relationship between texts and images in comics is essential from the graphic point of view and for the understanding of the story. Hence, the translation of comics has certain peculiarities that other literature genres do not have, partly due to its combination of iconic language and literary language.Among the wide array of interesting topics within this field, we are going to focus on a great challenge for translators: the graphic and phonetic values of the sounds in comics. Technical advances have improved comic books translation: nowadays modifying an element of the vignette no longer involves redrawing the whole animation. Thus, the translation of this literature genre can now focus on other problematic issues, such as the translation of sounds. Taking into account the lack of categorization of these sounds, this article deals with the translation of inarticulate sounds, interjections and onomatopoeias from English comic books into Spanish in order to observe the existing trends in these issues and to confirm if the new technologies have changed the translators’ task in the last 25 years.
Skype appearances, multiple greetings and ‘coucou’
Authors: Licoppe Christian 
Published: May 2017

Abstract
This paper analyses the organization of ‘openings’ in Skype video-mediated conversation. It uncovers order in their apparent complexity by showing the relevance of a particular sequential adjacent pair organization, the appearing/noticing sequence, and its particular instantiation as an appearance-for-the-first-time greeting. The paper shows how this is a crucial resource in establishing a joint video interactional frame for the parties involved. This accounts for the occurrence of some specific phenomena in Skype openings, such as multiple greetings, and for the use of greetings which reflexively index their being occasioned by an appearance and related greeting, such as the French ‘coucou’, even when these do not occur at the start of Skype calls. When analysed this way, Skype openings, though complex, can be seen as an accomplished ‘dance of appearances and multiple greetings’.