bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endovascular treatment in the acute and non-acute phases of carotid dissection: a therapeutic approach
Authors: Delgado Fernando , Bravo Isabel , Jiménez Elvira , Murías Eduardo , Saiz Antonio , Vega Pedro , López-Rueda Antonio , Blasco Jordi , Macho Juan , González Alejandro 
Published: July 2016

BackgroundCarotid dissection (CD) may, in certain cases, lead to significant stenosis, occlusion, or pseudoaneurysm formation, causing embolic stroke or hemodynamic failure, despite medical therapy.ObjectiveTo evaluate the results of endovascular treatment and clinical outcomes of patients with CD.MethodsA four-hospital retrospective study of endovascular treatment of extracranial CD in which medical treatment had failed or patients presented with a National Institute of Health Stroke Scale (NIHSS) score ≥8.ResultsThirty-eight patients (mean age 46.6±13.5 years, 78.9% male, 84.2% spontaneous CD, 44.7% left CD and 26.3% bilateral CD) were analyzed. In 24 patients (63.2%) treatment was undertaken in the acute-phase CD (APCD). IV recombinant tissue plasminogen activator was administered in 7 (29.2%) APCD cases. The patients with APCD exhibited a high rate of successful revascularization (Thrombolysis In Cerebral Infarction ≥2b; 19 patients (79.2%)), a low risk of symptomatic intracranial hemorrhage (n=2 (8.3%)), and good global functional outcomes (modified Rankin Scale (mRS) ≤2; n=17 (70.8%)). Good recanalization correlated (p=0.001) with good clinical evolution (mRS ≤2) in the patients with APCD. Of the 14 patients with non-acute phase CD (NAPCD), seven were treated for pseudoaneurysm with multiple stents (six patients) or covered prostheses, with stenosis being treated in the remaining seven patients.ConclusionsEndovascular treatment of selected cases of patients with CD associated with thromboembolic events and hemodynamic failure after unsuccessful medical therapy is a safe and effective method of restoring vessel lumen integrity, with good short-term clinical evolution.
Geographical and geological explorations of the La Plata Museum 1884–1905
Authors: Riccardi Alberto C. 
Published: July 2016

Abstract

The contributions of the La Plata Museum to the geology of Argentina began following the exploratory trips of its founder, F.P. Moreno, in the 1870s. The geological expeditions of the La Plata Museum started in the 1880s and covered the Andean region, although they were focused in the Patagonian Andes. They became more important from 1893 when they were related to explorations aimed at fixing the boundary between Argentina and Chile. Within 10 years the geographical and geological bases of large and almost unknown regions were established. R. Hauthal studied the area between the Last Hope Inlet and Lake Belgrano, defining its stratigraphy and publishing the first geological map of the Cordilleran region between
c.
49° 30′ and 52° S. The geology between Lake Buenos Aires and the Rio Negro (41–47° S) was established by Santiago Roth. The stratigraphic succession, facies and structural changes through the Argentine–Chilean Cordillera at the latitude of Lake Nahuel Huapi and Lake Lacar were studied by L. Wehrli, while studies at the latitude of Neuquén and Mendoza (36–39° S) were carried out by C. Burckhardt. Mesozoic and Cenozoic fossils were studied either in the Museum or abroad.

Supplementary material:
Map of southern South America (Argentina and Chile) showing the distribution of towns in 1870 is available at
https://doi.org/10.6084/m9.figshare.c.3283385.v1
Review of the history of higher education in geology during the past 100 years in China
Authors: Zhou Yufeng 
Published: July 2016

Abstract
Higher education in geology has been available for more than 100 years in China and many scholars have researched the history of geological education. This paper considers the development of geological education in China, reviews the research and summarizes the characteristics of various studies.

H.T. Chang (1877–1951), one of the founders of Chinese geology, once said:

Education is the foundation for the development of all the fields. The reason for past failures is due to the fact that the government has not placed enough emphasis on education. The achievements of geological work after 1912, the year the Republic of China was founded, are the result of education. If we want to achieve more, we need to place more emphasis on education. (
Chang 1937, pp. 41–42)

Over much of this time, scholars have reviewed its history. This period can be broadly divided into three stages: from the 1920s to 1949; from 1949 to 1976; and from the 1980s to the present day.
INHIGEO in recent times
Authors: Bork Kennard B. , Cooper Barry J. 
Published: July 2016

Abstract

David Oldroyd served a double term (1996–2004) as Secretary-General of INHIGEO, working with Hugh Torrens (1996–2000) and Manuel Pinto (2000–04) as Presidents. Meeting sites during this time included Beijing (1996), Liège (1997), Neuchâtel (1998), Freiberg (1999), Rio de Janeiro (2000), Lisbon and Aveiro (2001), Paris (2002), Dublin (2003) and Florence (2004). Minor changes in the Terms of Reference and By-Laws aided the mission of INHIGEO. Continuity was a key aspect of Kennard Bork's term (2004–08). President Philippe Taquet (2004–08) and the INHIGEO Board were responsive to resolving operational issues. Annual meetings were held in Italy (2004), the Czech Republic (2005), the Baltic States (2006), Germany (2007) and Norway (2008). In the period since 2008, INHIGEO has continued its success while undergoing constructive changes. The
INHIGEO Newsletter
has been transformed into the
INHIGEO Annual Record
, which is publicly available on the internet. The longstanding limit on membership numbers per country has been abandoned, a category of Associate Membership has been introduced and a quarterly
INHIGEO Circular
was introduced in 2012. An Affiliated Association category was created in 2014. This contribution focuses on the progress of INHIGEO in the years 1996 to the present day. It has been prepared by Kennard B. Bork, INHIGEO Secretary-General (2004–08) and Barry J. Cooper Secretary-General (2008–16). Tragically, David Oldroyd passed away on 7 November 2014 and could not contribute to this paper. In his place, one of us (KBB) discusses David's major contributions.
MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.
Authors: Joshi Sachindra Raj , Dhagia Vidhi , Gairhe Salina , Edwards John G. , McMurtry Ivan F. , Gupte Sachin A. 
Published: July 2016

Heart failure, a major cause of morbidity and mortality in patients with pulmonary arterial hypertension (PAH), is an outcome of complex biochemical processes. In this study, we determined changes in microRNAs (miRs) in the right and left ventricles of normal and PAH rats. Using an unbiased quantitative miR microarray analysis, we found 1) miR-21-5p, miR-31-5 and 3p, miR-140-5 and 3p, miR-208b-3p, miR-221-3p, miR-222-3p, miR-702-3p, and miR-1298 were upregulated (>2-fold; P < 0.05) in the right ventricle (RV) of PAH compared with normal rats; 2) miR-31-5 and 3p, and miR-208b-3p were upregulated (>2-fold; P < 0.05) in the left ventricle plus septum (LV+S) of PAH compared with normal rats; 3) miR-187-5p, miR-208a-3p, and miR-877 were downregulated (>2-fold; P < 0.05) in the RV of PAH compared with normal rats; and 4) no miRs were up- or downregulated with >2-fold in LV+S compared with RV of PAH and normal. Upregulation of miR-140 and miR-31 in the hypertrophic RV was further confirmed by quantitative PCR. Interestingly, compared with control rats, expression of mitofusin-1 (MFN1), a mitochondrial fusion protein that regulates apoptosis, and which is a direct target of miR-140, was reduced in the RV relative to LV+S of PAH rats. We found a correlation between increased miR-140 and decreased MFN1 expression in the hypertrophic RV. Our results also demonstrated that upregulation of miR-140 and downregulation of MFN1 correlated with increased RV systolic pressure and hypertrophy. These results suggest that miR-140 and MFN1 play a role in the pathogenesis of PAH-associated RV dysfunction. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/mir140-and-right-heart-hypertrophy/ .
αVβ3 Integrin-Targeted Radionuclide Therapy with 64Cu-cyclam-RAFT-c(-RGDfK-)4
Authors: Jin Zhao-Hui , Furukawa Takako , Degardin Mélissa , Sugyo Aya , Tsuji Atsushi B. , Yamasaki Tomoteru , Kawamura Kazunori , Fujibayashi Yasuhisa , Zhang Ming-Rong , Boturyn Didier , Dumy Pascal , Saga Tsuneo 
Published: July 2016

AbstractThe transmembrane cell adhesion receptor αVβ3 integrin (αVβ3) has been identified as an important molecular target for cancer imaging and therapy. We have developed a tetrameric cyclic RGD (Arg-Gly-Asp) peptide–based radiotracer 64Cu-cyclam-RAFT-c(-RGDfK-)4, which successfully captured αVβ3-positive tumors and angiogenesis by PET. Here, we subsequently evaluated its therapeutic potential and side effects using an established αVβ3-positive tumor mouse model. Mice with subcutaneous U87MG glioblastoma xenografts received single administrations of 37 and 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4 (37 MBq/nmol), peptide control, or vehicle solution and underwent tumor growth evaluation. Side effects were assessed in tumor-bearing and tumor-free mice in terms of body weight, routine hematology, and hepatorenal functions. Biodistribution of 64Cu-cyclam-RAFT-c(-RGDfK-)4 with ascending peptide doses (0.25–10 nmol) and with the therapeutic dose of 2 nmol were determined at 3 hours and at various time points (2 minutes–24 hours) postinjection, respectively, based on which radiation-absorbed doses were estimated. The results revealed that 64Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently slowed down the tumor growth. The mean tumor doses were 1.28 and 1.81 Gy from 37 and 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4, respectively. Peptide dose study showed that the tumor uptake of 64Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently decreased at doses ≥1 nmol, indicating a saturation of αVβ3 with the administered therapeutic doses (1 and 2 nmol). Combined analysis of the data from tumor-bearing and tumor-free mice revealed no significant toxicity caused by 37–74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4. Our study demonstrates the therapeutic efficacy and safety of 64Cu-cyclam-RAFT-c(-RGDfK-)4 for αVβ3-targeted radionuclide therapy. 64Cu-cyclam-RAFT-c(-RGDfK-)4 would be a promising theranostic drug for cancer imaging and therapy. Mol Cancer Ther; 15(9); 2076–85. ©2016 AACR.
Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS-Mutant Lung Cancer
Authors: Kim Jae-Young , Welsh Eric A. , Fang Bin , Bai Yun , Kinose Fumi , Eschrich Steven A. , Koomen John M. , Haura Eric B. 
Published: July 2016

Abstract
Pathway inhibition of the RAS-driven MAPK pathway using small-molecule kinase inhibitors has been a key focus for treating cancers driven by oncogenic RAS, yet significant clinical responses are lacking. Feedback reactivation of ERK driven by drug-induced RAF activity has been suggested as one of the major drug resistance mechanisms, especially in the context of oncogenic RAS. To determine whether additional adaptive resistance mechanisms may coexist, we characterized global phosphoproteomic changes after MEK inhibitor selumetinib (AZD6244) treatment in KRAS-mutant A427 and A549 lung adenocarcinoma cell lines employing mass spectrometry–based phosphoproteomics. We identified 9,075 quantifiable unique phosphosites (corresponding to 3,346 unique phosphoproteins), of which 567 phosphosites were more abundant and 512 phosphosites were less abundant after MEK inhibition. Selumetinib increased phosphorylation of KSR-1, a scaffolding protein required for assembly of MAPK signaling complex, as well as altered phosphorylation of GEF-H1, a novel regulator of KSR-1 and implicated in RAS-driven MAPK activation. Moreover, selumetinib reduced inhibitory serine phosphorylation of MET at Ser985 and potentiated HGF- and EGF-induced AKT phosphorylation. These results were recapitulated by pan-RAF (LY3009120), MEK (GDC0623), and ERK (SCH772984) inhibitors, which are currently under early-phase clinical development against RAS-mutant cancers. Our results highlight the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K–AKT signaling when the MAPK pathway is inhibited.
Implications: This study highlights the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K/AKT signaling when the MAPK pathway is inhibited. Mol Cancer Res; 14(10); 1019–29. ©2016 AACR.
Cell-free DNA (cfDNA): Clinical Significance and Utility in Cancer Shaped By Emerging Technologies
Authors: Volik Stanislav , Alcaide Miguel , Morin Ryan D. , Collins Colin 
Published: July 2016

Abstract
Precision oncology is predicated upon the ability to detect specific actionable genomic alterations and to monitor their adaptive evolution during treatment to counter resistance. Because of spatial and temporal heterogeneity and comorbidities associated with obtaining tumor tissues, especially in the case of metastatic disease, traditional methods for tumor sampling are impractical for this application. Known to be present in the blood of cancer patients for decades, cell-free DNA (cfDNA) is beginning to inform on tumor genetics, tumor burden, and mechanisms of progression and drug resistance. This substrate is amenable for inexpensive noninvasive testing and thus presents a viable approach to serial sampling for screening and monitoring tumor progression. The fragmentation, low yield, and variable admixture of normal DNA present formidable technical challenges for realization of this potential. This review summarizes the history of cfDNA discovery, its biological properties, and explores emerging technologies for clinically relevant sequence-based analysis of cfDNA in cancer patients. Molecular barcoding (or Unique Molecular Identifier, UMI)-based methods currently appear to offer an optimal balance between sensitivity, flexibility, and cost and constitute a promising approach for clinically relevant assays for near real-time monitoring of treatment-induced mutational adaptations to guide evidence-based precision oncology. Mol Cancer Res; 14(10); 898–908. ©2016 AACR.
Genomic Integration of High-Risk HPV Alters Gene Expression in Oropharyngeal Squamous Cell Carcinoma
Authors: Walline Heather M. , Komarck Christine M. , McHugh Jonathan B. , Bellile Emily L. , Brenner J. Chad , Prince Mark E. , McKean Erin L. , Chepeha Douglas B. , Wolf Gregory T. , Worden Francis P. , Bradford Carol R. , Carey Thomas E. 
Published: July 2016

Abstract
High-risk HPV (hrHPV) is the leading etiologic factor in oropharyngeal cancer. HPV-positive oropharyngeal tumors generally respond well to therapy, with complete recovery in approximately 80% of patients. However, it remains unclear why some patients are nonresponsive to treatment, with 20% of patients recurring within 5 years. In this study, viral factors were examined for possible clues to differences in tumor behavior. Oropharynx tumors that responded well to therapy were compared with those that persisted and recurred. Viral oncogene alternate transcripts were assessed, and cellular sites of viral integration were mapped and sequenced. Effects of integration on gene expression were assessed by transcript analysis at the integration sites. All of the tumors demonstrated active viral oncogenesis, indicated by expression of HPV E6 and E7 oncogenes and alternate E6 splicing. In the responsive tumors, HPV integration occurred exclusively in intergenic chromosome regions, except for one tumor with viral integration into TP63. Each recurrent tumor exhibited complex HPV integration patterns into cancer-associated genes, including TNFRSF13B, SCN2A, SH2B1, UBE2V2, SMOC1, NFIA, and SEMA6D. Disrupted cellular transcripts were identified in the region of integration in four of the seven affected genes.
Implications: Integration of transcriptionally active hrHPV into cellular intergenic regions associates with tumor behavior by altering gene expression. Mol Cancer Res; 14(10); 941–52. ©2016 AACR.
Mechanism, Consequences, and Therapeutic Targeting of Abnormal IL15 Signaling in Cutaneous T-cell Lymphoma
Authors: Mishra Anjali , La Perle Krista , Kwiatkowski Sonya , Sullivan Laura A. , Sams Gregory H. , Johns Jessica , Curphey Douglas P. , Wen Jing , McConnell Kathleen , Qi Jun , Wong Henry , Russo Giandomenico , Zhang Jianying , Marcucci Guido , Bradner James E. , Porcu Pierluigi , Caligiuri Michael A. 
Published: July 2016

Abstract
Cutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. Here, we report that patients with CTCL show increased IL15 in a clinical stage–dependent manner. Mechanistically, we show that ZEB1 is a transcriptional repressor of IL15 in T cells and that hypermethylation of the ZEB1 binding region within the IL15 promoter, as seen in patients with CTCL, prevents ZEB1 binding and causes increased transcription of IL15. Using a transgenic mouse model of IL15, we provide evidence that overexpression of IL15 induces a spontaneous CTCL that mimics the human neoplasm. Excessive autocrine production of IL15 in T cells inhibits an HDAC1-mediated negative autoregulatory loop, resulting in the upregulation of HDAC1 and HDAC6 and transcriptional induction of the onco-miR-21. Interruption of IL15 downstream signaling with isotype-specific HDAC inhibitors halts (HDAC1) or significantly delays (HDAC6) the progression of CTCL in vivo and provides preclinical evidence supporting a hierarchical model of oncogenic signaling in CTCL.
Significance: To date, CTCL pathogenesis remains unknown, and there are no curative therapies. Our findings not only demonstrate a critical role for IL15-mediated inflammation in cutaneous T-cell lymphomagenesis, but also uncover a new oncogenic regulatory loop in CTCL involving IL15, HDAC1, HDAC6, and miR-21 that shows differential sensitivity to isotype-specific HDAC inhibitors. Cancer Discov; 6(9); 986–1005. ©2016 AACR.
This article is highlighted in the In This Issue feature, p. 932
Association of Exome Sequences With Cardiovascular Traits Among Blacks in the Jackson Heart Study
Authors: Peloso Gina M. , Lange Leslie A. , Varga Tibor V. , Nickerson Deborah A. , Smith Joshua D. , Griswold Michael E. , Musani Solomon , Polfus Linda M. , Mei Hao , Gabriel Stacey , Quarells Rakale Collins , Altshuler David , Boerwinkle Eric , Daly Mark J. , Neale Benjamin , Correa Adolfo , Reiner Alex P. , Wilson James G. , Kathiresan Sekar 
Published: July 2016

Background—
The correlation of null alleles with human phenotypes can provide insight into gene function in humans. In individuals of African ancestry, we set out to identify null and damaging missense variants, and test these variants for association with a range of cardiovascular phenotypes.

Methods and Results—

We performed whole-exome sequencing in 3223 black individuals from the Jackson Heart Study and found a total of 729 666 variant sites with minor allele frequency <5%, including 17 263 null variants and 49 929 missense variants predicted to be damaging by in silico algorithms. We tested null and damaging missense variants within each gene for association with 36 cardiovascular traits. We found 3 associations that met our prespecified level of significance (α=1.1×10
−7
). Null and damaging missense variants in
PCSK9
were associated with 36 mg/dL lower low-density lipoprotein cholesterol (
P
=3×10
−21
). Three individuals in their 50s with complete PCSK9 deficiency (each compound heterozygote for
PCSK9
p.Y142X and p.C679X) were identified, with one having a coronary artery calcification score in the 83rd percentile despite a low-density lipoprotein cholesterol of 32 mg/dL. A damaging missense variant in
HBQ1
(p.G52A) was associated with a 2 pg/cell lower mean corpuscular hemoglobin (
P
=9×10
−13
) and rare damaging missense variants in
VPS13A
with higher red blood cell distribution width (
P
=9.9×10
–8
).

Conclusions—
A limited number of null/damaging alleles with a large effect on cardiovascular traits were detectable in ≈3000 black individuals.
Effect of collection tube type and freeze–thaw cycles on myeloperoxidase concentrations in blood samples of acute coronary syndrome patients
Authors: Naz Saima , Ghafoor Farkhanda , Iqbal Imran Akhtar 
Published: July 2016

BackgroundMyeloperoxidase has shown potential as a marker for prognosis of coronary artery disease, but presently little is known about preanalytical handling of samples for quantifying myeloperoxidase. The present study was conducted to evaluate the effect of collection tube and freeze–thaw cycles on myeloperoxidase concentrations.MethodsAcute coronary syndrome patients ( n = 88) were enrolled after obtaining written informed consent from coronary care unit of a tertiary care hospital (January 2012–June 2014). About 5 mL venous blood was collected from patients and divided into serum, lithium heparin, ethylenediaminetetraacetic acid and sodium citrate tubes. Except serum, all tubes were kept on ice immediately after collection. Samples were centrifuged at −4℃, separated immediately after centrifugation and stored at −40℃ until analysis. Myeloperoxidase was quantified by in-house and commercial assays and re-quantified after five freeze–thaw cycles.ResultsMyeloperoxidase concentrations, (serum samples) determined by commercial and in-house assays correlated well (r = 0.946) ( P < 0.001) and were higher in serum samples. Within plasma, myeloperoxidase concentrations were slightly higher in ethylenediaminetetraacetic acid (307.7 ± 52.1) and lower in lithium heparin (290.3 ± 49.2) and sodium citrate (221.4 ± 40.3) but not statistically significant. Correlation between myeloperoxidase concentrations (in-house enzyme-linked immunosorbent assay) after first cycle and fifth freeze–thaw cycle dropped to r = 0.448 ( P < 0.001).ConclusionMyeloperoxidase concentrations are comparable in three types of plasma tubes when samples are placed on ice immediately, centrifuged at low temperatures and separated immediately after centrifugation. Multiple freeze–thaw cycles have an effect on myeloperoxidase and should be avoided for quantifying myeloperoxidase.
Measurement of titanium in hip-replacement patients by inductively coupled plasma optical emission spectroscopy
Authors: Harrington Chris F , McKibbin Craig , Rahanu Monika , Langton David , Taylor Andrew 
Published: July 2016

Background Patients with metal-on-metal hip replacements require testing for cobalt and chromium. There may also be a need to test for titanium, which is used in the construction of the femoral stem in total hip replacements. It is not possible to use quadrupole inductively coupled plasma mass spectrometry due to interferences. Methods Titanium was measured using inductively coupled plasma optical emission spectroscopy using the emission line at 336.1 nm and Y (internal standard) at 371.0 nm. Internal quality control materials were prepared for blood and serum and concentrations assigned using a sector field-inductively coupled plasma mass spectrometer. A candidate whole blood certified reference material was also evaluated. Results The method had detection and quantitation limits of 0.6 and 1.9 µg/L, respectively. The respective bias (%) and measurement uncertainty ( U) (k = 2) were 3.3% and 2.0 µg/L (serum) and − 1.0% and 1.4 µg/L (whole blood). The respective repeatability and intermediate precision (%) were 5.1% and 10.9% (serum) and 2.4% and 8.6% (whole blood). The concentration of titanium was determined in patients’ samples, serum (median = 2.4 µg/L, n = 897) and whole blood (median = 2.4 µg/L, n = 189). Serum is recommended for monitoring titanium in patients, since the concentration is higher than in whole blood and the matrix less problematic. In hip fluid samples, the concentrations were much higher (mean 58.5 µg/L, median 5.1 µg/L, n = 83). Conclusions A method based on inductively coupled plasma optical emission spectroscopy was developed and validated for measuring titanium in clinical samples.