bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Microalterations Detected at High Frequency in Oral Cancer
Authors: Baldwin Corisande , Garnis Cathie , Zhang Lewei , Rosin Miriam P. , Lam Wan L. 
Published: July 2017

Abstract
The development of array comparative genomic hybridization (array CGH) at tiling-path resolution has enabled the detection of gene-sized segmental DNA copy number gains and losses. Here, we present the first application of whole genome tiling-path array CGH to archival clinical specimens for the detailed analysis of oral squamous cell carcinomas (OSCC). We describe the genomes of 20 OSCCs as well as a selection of matched normal DNA in unprecedented detail. Examination of their whole genome profiles enabled the identification of alterations ranging in size from whole-arm, segmental, to gene size alterations. Tiling-path resolution enabled the detection of many more alterations within each tumor than previously reported, many of which include narrow alterations found to be frequent events among the 20 OSCCs. We report the presence of several novel frequent submegabase alterations, such as the 0.58 Mb gain at 5p15.2 containing triple functional domain (TRIO), detected in 45% of cases. We also report the first coamplification of two gene clusters, by fine-mapping the precise base pair boundaries of the high-level amplification at 11q22.2-22.3 containing both matrix metalloproteinase and baculoviral IAP repeat-containing protein 2 (BIRC) gene clusters. These results show the large improvement in detection sensitivity and resolution compared with genome interval marker arrays and the utility of tiling resolution array CGH for the detection of both submegabase and single copy gains and losses in cancer gene discovery.
EGFR Tyrosine Kinase Domain Mutations Are Detected in Histologically Normal Respiratory Epithelium in Lung Cancer Patients
Authors: Tang Ximing , Shigematsu Hisayuki , Bekele B. Nebiyou , Roth Jack A. , Minna John D. , Hong Waun Ki , Gazdar Adi F. , Wistuba Ignacio I. 
Published: July 2017

Abstract
To determine whether EGFR tyrosine kinase domain mutations are early events in the pathogenesis of lung adenocarcinomas, we tested for the presence of EGFR mutations in histologically normal bronchial and bronchiolar epithelia from lung adenocarcinomas bearing the common EGFR mutations. DNA was extracted from microdissected tissue obtained from 21 tumors with known EGFR mutations, 16 tumors without mutation, and 90 sites of normal bronchial and bronchiolar epithelium from the same surgical specimens. With the use of PCR and direct DNA sequencing, EGFR mutations identical to the tumors were detected in the normal respiratory epithelium in 9 of 21 (43%) patients with EGFR mutant adenocarcinomas but none in patients without mutation in the tumors. The finding of mutations being more frequent in normal epithelium within tumor (43%) than in adjacent sites (24%) suggests a localized field effect phenomenon. Our findings indicate that mutation of the tyrosine kinase domain of EGFR is an early event in the pathogenesis of lung adenocarcinomas, and suggest EGFR mutations as an early detection marker and chemoprevention target.
Methods of Academic Course Planning for Cancer Biology PhD Students to Enhance Knowledge of Clinical Oncology
Authors: Mattes Malcolm D. , Swart Elizabeth , Markwell Steven M. , Wen Sijin , Vona-Davis Linda C. 
Published: July 2017

Abstract
Little is known about how clinical oncology concepts are taught to PhD students or the most effective methods of doing so. In this study, electronic surveys were sent to faculty and students at PhD training programs, assessing their institution's methods of clinical oncology education and their perspective on optimal approaches to clinical oncology education. Only 40.0% of students reported any clinical oncology component to their institution's training, and only 26.5% had a clinician on their graduate advisory committee. Forty-three percent of students believed that they had a good understanding for translating basic science research into clinical practice, and 77.2% of all participants believed dual degree MD/PhD students were superior to PhD students in this regard. Lectures on clinical oncology research topics were the most valuable type of experience for all participants and were also the most common type of experience utilized. Working with a clinician to develop a clinical trial with correlative endpoints was also highly valued, but was only utilized by approximately 10% of programs. Faculty rated the value of nearly all types of clinical oncology exposure significantly lower than did students. Inclusion of the approaches identified in this study is likely to enhance PhD training in oncology-related disciplines. Cancer Res; 77(18); 4741–4. ©2017 AACR.
Tamoxifen Inhibition of Estrogen Receptor-α–Negative Mouse Mammary Tumorigenesis
Authors: Medina Daniel , Kittrell Frances S. , Hill Jamal , Shepard Anne , Thordarson Gudmundur , Brown Powel 
Published: July 2017

Abstract
Tamoxifen reduces the relative risk of breast cancer developing from specific premalignant lesions. Many breast cancers that arise after tamoxifen treatment are estrogen receptor-α (ER-α)–negative, although premalignant lesions such as atypical ductal hyperplasia are highly ER-α–positive. The p53 null mouse mammary epithelial transplant model is characterized by ER-α–positive premalignant lesions that give rise to both ER-α–positive and ER-α–negative tumors. Given this progression from ER-α–positive to ER-α–negative lesions, we tested the ability of tamoxifen to block or delay mammary tumorigenesis in several versions of this model. In groups 1 and 2, p53 null normal mammary epithelial transplants were maintained in virgin mice. In groups 3 to 5, the p53 null and mammary transplants were maintained in mice continuously exposed to high levels of progesterone. In groups 6 and 7, transplants of the premalignant outgrowth line PN8a were maintained in virgin mice. Tamoxifen blocked estrogen signaling in these mice as evidenced by decreases in progesterone-induced lateral branching and epithelial proliferation in the mammary epithelium. Tamoxifen did not alter the elevated levels of progesterone in the blood while significantly reducing the circulating level of prolactin. Tamoxifen reduced tumor incidence in p53 null normal mammary epithelial transplants maintained in virgin mice from 55% to 5% and in progesterone-stimulated mice from 81% to 21%. The majority of the resultant tumors were ER-α–negative. Tamoxifen also significantly delayed tumorigenesis in the ER-α–positive high premalignant line PN8a from 100% to 75%. These results show that tamoxifen delays the emergence of ER-α–negative tumors if given early in premalignant progression.
Wilms Tumor NCAM-Expressing Cancer Stem Cells as Potential Therapeutic Target for Polymeric Nanomedicine
Authors: Markovsky Ela , Vax Einav , Ben-Shushan Dikla , Eldar-Boock Anat , Shukrun Rachel , Yeini Eilam , Barshack Iris , Caspi Revital , Harari-Steinberg Orit , Pode-Shakked Naomi , Dekel Benjamin , Satchi-Fainaro Ronit 
Published: July 2017

Abstract
Cancer stem cells (CSC) form a specific population within the tumor that has been shown to have self-renewal and differentiation properties, increased ability to migrate and form metastases, and increased resistance to chemotherapy. Consequently, even a small number of cells remaining after therapy can repopulate the tumor and cause recurrence of the disease. CSCs in Wilms tumor, a pediatric renal cancer, were previously shown to be characterized by neural cell adhesion molecule (NCAM) expression. Therefore, NCAM provides a specific biomarker through which the CSC population in this tumor can be targeted. We have recently developed an NCAM-targeted nanosized conjugate of paclitaxel bound to a biodegradable polyglutamic acid polymer. In this work, we examined the ability of the conjugate to inhibit Wilms tumor by targeting the NCAM-expressing CSCs. Results show that the conjugate selectively depleted the CSC population of the tumors and effectively inhibited tumor growth without causing toxicity. We propose that the NCAM-targeted conjugate could be an effective therapeutic for Wilms tumor. Mol Cancer Ther; 16(11); 2462–72. ©2017 AACR.
Sema3F (Semaphorin 3F) Selectively Drives an Extraembryonic Proangiogenic Program
Authors: Regano Donatella , Visintin Alessia , Clapero Fabiana , Bussolino Federico , Valdembri Donatella , Maione Federica , Serini Guido , Giraudo Enrico 
Published: July 2017

Objective—
Molecular pathways governing blood vessel patterning are vital to vertebrate development. Because of their ability to counteract proangiogenic factors, antiangiogenic secreted Sema3 (class 3 semaphorins) control embryonic vascular morphogenesis. However, if and how Sema3 may play a role in the control of extraembryonic vascular development is presently unknown.

Approach and Results—

By characterizing genetically modified mice, here, we show that surprisingly Sema3F acts instead as a selective extraembryonic, but not intraembryonic proangiogenic cue. Both in vivo and in vitro, in visceral yolk sac epithelial cells, Sema3F signals to inhibit the phosphorylation-dependent degradation of Myc, a transcription factor that drives the expression of proangiogenic genes, such as the microRNA cluster 17/92. In
Sema3f
-null yolk sacs, the transcription of Myc-regulated microRNA 17/92 cluster members is impaired, and the synthesis of Myc and microRNA 17/92 foremost antiangiogenic target Thbs1 (thrombospondin 1) is increased, whereas Vegf (vascular endothelial growth factor) signaling is inhibited in yolk sac endothelial cells. Consistently, exogenous recombinant Sema3F inhibits the phosphorylation-dependent degradation of Myc and the synthesis of Thbs1 in mouse F9 teratocarcinoma stem cells that were in vitro differentiated in visceral yolk sac epithelial cells.
Sema3f
−/−
mice placentas are also highly anemic and abnormally vascularized.

Conclusions—
Sema3F functions as an unconventional Sema3 that promotes extraembryonic angiogenesis by inhibiting the Myc-regulated synthesis of Thbs1 in visceral yolk sac epithelial cells.
TGF-β (Transforming Growth Factor-β) Signaling Protects the Thoracic and Abdominal Aorta From Angiotensin II-Induced Pathology by Distinct Mechanisms
Authors: Angelov Stoyan N. , Hu Jie Hong , Wei Hao , Airhart Nathan , Shi Minghui , Dichek David A. 
Published: July 2017

Objective—
The role of TGF-β (transforming growth factor-β) signaling in abdominal aortic aneurysm (AAA) formation is controversial. Others reported that systemic blockade of TGF-β by neutralizing antibodies accelerated AAA development in angiotensin II-infused mice. This result is consistent with other studies suggesting that TGF-β signaling prevents AAA. Development of a therapy for AAA that exploits the protective actions of TGF-β would be facilitated by identification of the mechanisms through which TGF-β prevents AAA. We hypothesized that TGF-β signaling prevents AAA by its actions on aortic medial smooth muscle cells.

Approach and Results—

We compared the prevalence, severity, and histopathology of angiotensin II-induced AAA among control mice (no TGF-β blockade), mice with antibody-mediated systemic neutralization of TGF-β, and mice with genetically based smooth muscle–specific loss of TGF-β signaling. Surprisingly, we found that systemic—but not smooth muscle–specific—TGF-β blockade significantly increased the prevalence of AAA and tended to increase AAA severity, adventitial thickening, and aortic wall macrophage accumulation. In contrast, abdominal aortas of mice with smooth muscle–specific loss of TGF-β signaling differed from controls only in having a thinner media. We examined thoracic aortas of the same mice. Here we found that smooth muscle–specific loss of
Tgfbr2
—but not systemic TGF-β neutralization—significantly accelerated development of aortic pathology, including increased prevalence of intramural hematomas, medial thinning, and adventitial thickening.

Conclusion—
Our results suggest that TGF-β signaling prevents both abdominal and thoracic aneurysmal disease but does so by distinct mechanisms. Smooth muscle extrinsic signaling protects the abdominal aorta and smooth muscle intrinsic signaling protects the thoracic aorta.
Long‐Term Stroke Risk Prediction in Patients With Atrial Fibrillation: Comparison of the ABC‐Stroke and CHA
2
DS
2
‐VASc Scores
Authors: Rivera‐Caravaca José Miguel , Roldán Vanessa , Esteve‐Pastor María Asunción , Valdés Mariano , Vicente Vicente , Lip Gregory Y. H. , Marín Francisco 
Published: July 2017

Background

The
ABC
‐stroke score (age, biomarkers [N‐terminal fragment B‐type natriuretic peptide, high‐sensitivity troponin], and clinical history [prior stroke/transient ischemic attack]) was proposed to predict stroke in atrial fibrillation (
AF
). This score was derived/validated in 2 clinical trial cohorts in which patients with AF were highly selected and carefully followed‐up. However, the median follow‐up was 1.9 years in the trial cohort; therefore, its long‐term predictive performance remains uncertain. This study aimed to compare the long‐term predictive performances of the
ABC
‐stroke and
CHA
2
DS
2
‐
VAS
c (cardiac failure or dysfunction, hypertension, age ≥75 [doubled], diabetes mellitus, stroke [doubled]—vascular disease, age 65 to 74 years and sex category [female]) scores in a cohort of anticoagulated patients with AF.

Methods and Results

We recruited 1125 consecutive patients with AF who were stable on vitamin K antagonists and followed‐up for a median of 6.5 years.
ABC
‐stroke and
CHA
2
DS
2
‐
VAS
c (cardiac failure or dysfunction, hypertension, age ≥75 [doubled], diabetes mellitus, stroke [doubled]—vascular disease, age 65 to 74 years and sex category [female]) scores were calculated and compared. Median
CHA
2
DS
2
‐
VAS
c and
ABC
‐stroke scores were 4 (interquartile range 3–5) and 9.1 (interquartile range 7.3–11.3), respectively. There were 114 ischemic strokes (1.55% per year) at 6.5 years. The C‐index of
ABC
‐stroke at 3.5 years was significantly higher than
CHA
2
DS
2
‐
VAS
c (0.663 versus 0.600,
P
=0.046), but both C‐indexes were nonsignificantly different at 6.5 years. Integrated discrimination improvement showed a small improvement (<2%) in sensitivity at 3.5 and 6.5 years with
ABC
‐stroke. For
ABC
‐stroke, net reclassification improvement was nonsignificantly different at 3.5 years, and showed a negative reclassification at 6.5 years compared with
CHA
2
DS
2
‐
VAS
c. Decision curve analyses did not show a marked improvement in clinical usefulness of the
ABC
‐stroke score over the
CHA
2
DS
2
‐
VAS
c score.

Conclusions

In anticoagulated patients with AF followed‐up over a long‐term period, the novel
ABC
‐stroke score does not offer significantly better predictive performance compared with the
CHA
2
DS
2
‐
VAS
c score.
The Traffic in Knowledge in the Winter Nights of Antonio de Eslava, Matthäus Drummer von Pabenpach, and Johann Beer
Authors: Tatlock Lynne 
Published: July 2017

This essay examines the ways in which three related works set and thematize knowledge in motion: Antonio de Eslava’s Spanish original, Noches de Invierno (1609); Matthäus Drummer von Pabenpach’s German translation thereof (1649); and Johann Beer’s Teutsche Winternächte (1682). It interrogates the material book as a vehicle of knowledge transfer and text – in the form of storytelling, conversation, and autobiography – as a means of producing, circulating, and cementing received and new knowledge. Finally, it reveals the role of gender in knowledge creation and sharing.
From the Harz Mountains to the Atlantic and Back Again
Authors: Meyer Matthias 
Published: July 2017

Abtract
This essay concerns the newspaper Stolbergische Sammlung neuer und merckwürdiger Weltgeschichte (1735, 1736, 1738), as published by Schnabel, as well as the novel Insel Felsenburg. It focuses on the relation between the production of knowledge and narration. Schnabel’s methods as a newspaper editor are compared with contemporary usage as well as with his narrative technique as a novelist. It is significant how Schnabel makes use of narrative strategies not only in the small news items in the category “Sonderbare [Weltgeschichte]” but also in order to create a coherent narrative in the political sections of his newspaper, spanning longer periods of time.
A Transbasin Mode of Interannual Variability of the Central American Gap Winds: Seasonality and Large-Scale Forcing
Authors: Yang Jun-Chao , Lin Xiaopei , Xie Shang-Ping 
Published: July 2017

Abstract
A transbasin mode (TBM) is identified as the leading mode of interannual surface wind variability over the Intra-Americas Seas across Central America based on empirical orthogonal function analysis. The TBM is associated with variability in Central American gap winds, most closely with the Papagayo jet but with considerable signals over the Gulfs of Tehuantepec and Panama. Although El Niño–Southern Oscillation (ENSO) is the main large-scale forcing, the TBM features a distinct seasonality due to sea level pressure (SLP) adjustments across the Pacific and Atlantic. During July–September, ENSO causes meridional SLP gradient anomalies across Central America, intensifying anomalous geostrophic winds funneling through Papagayo to form the TBM. During wintertime, ENSO peaks but imparts little anomalous SLP gradient across Central America with a weak projection on the TBM because of the competing effects of the Pacific–North American teleconnection and tropospheric Kelvin waves. Besides ENSO, tropical Atlantic sea surface temperature anomalies make a weak contribution to the TBM in boreal summer by strengthening the cross-basin gradient. ENSO and the Atlantic forcing constitute a cross-basin seesaw pattern in SLP, manifested as an anomalous Walker circulation across the tropical Americas. The TBM appears to be part of the low-level branch of the anomalous Walker circulation, which modulates Central American wind jets by orographic effect. This study highlights the seasonality of gap wind variability, and calls for further research into its influence on regional climate.
Intervention and management of developmental coordination disorder: Are we providing evidence-based services?
Authors: Withers Renée , Tsang Yoyo , Zwicker Jill G. 
Published: July 2017

Background. Occupational therapists are well positioned to provide intervention to improve outcomes for children with developmental coordination disorder. However, little is known about what occupational therapy services are provided for these children. Purpose. As part of a larger study exploring service provision for children with developmental coordination disorder, the purpose of this study was to examine intervention and referral practices of occupational therapists in British Columbia, Canada. Method. An online survey was e-mailed to a convenience and snowball sample of paediatric occupational therapists, with 165 therapists responding. Descriptive statistics were used for the data analysis. Findings. Results show that the type and duration of intervention varied greatly throughout the province, as well as within health regions. Although 70% (87/124) of therapists reported being at least moderately familiar with current evidence, only 47% to 59% selected task-based methods as their primary intervention approach. Implications. Findings provide a baseline for current intervention and an opportunity for targeted knowledge translation initiatives.
Gabapentin in the Management of Pain following Tonsillectomy: A Randomized Double‐Blind Placebo‐Controlled Trial
Authors: Sanders James G. , Cameron Claire , Dawes Patrick J. D. 
Published: July 2017

ObjectiveTo determine if a single dose of oral gabapentin given prior to tonsillectomy decreases postoperative morbidity.Study DesignProspective randomized double‐blind placebo‐controlled trial.SettingSouthern District Health Board University Hospitals, New Zealand, over a 10‐month period.Subjects and MethodsSeventy‐three adults undergoing tonsillectomy were randomized to receive either a single preoperative dose of oral gabapentin (600 mg) or placebo. A standard analgesic protocol was prescribed for 14 postoperative days. The primary outcome was a patient‐assigned visual analog scale pain score during rest and swallow; secondary outcomes were analgesic consumption, nausea, vomiting, and return to normal diet and activities. Complications and adverse effects were also recorded.ResultsThirty‐seven participants were allocated to the placebo group and 36 to the gabapentin group. After withdrawals, data were analyzed from 31 in the placebo group and 27 in the gabapentin group. Pain scores between groups were not significantly different within the first 6 hours. The gabapentin group recorded significantly higher pain scores between days 5 and 10 (maximal difference, day 8: 17.6 mm; effect size, –8.87; P =. 03; 95% CI, −16.883 to −0.865). There was no significant difference in swallow pain scores or early postoperative fentanyl consumption. Consumption of paracetamol (P =. 01 at day 13 and P =. 004 at day 14) and codeine (P <. 05 at days 3‐5, 7, 8, 10, 14) was higher in the gabapentin group. No significant difference between groups was found for the other outcomes.ConclusionsPreemptive gabapentin (600 mg) was associated with greater postoperative pain scores and analgesic consumption following adult tonsillectomy when compared with placebo.
Treadmill training to improve mobility for people with sub-acute stroke: a phase II feasibility randomized controlled trial
Authors: Baer Gillian D , Salisbury Lisa G , Smith Mark T , Pitman Jane , Dennis Martin 
Published: July 2017

Objective: This phase II study investigated the feasibility and potential effectiveness of treadmill training versus normal gait re-education for ambulant and non-ambulant people with sub-acute stroke delivered as part of normal clinical practice. Design: A single-blind, feasibility randomized controlled trial. Setting: Four hospital-based stroke units. Subjects: Participants within three months of stroke onset. Interventions: Participants were randomized to treadmill training (minimum twice weekly) plus normal gait re-education or normal gait re-education only (control) for up to eight weeks. Main Measures: Measures were taken at baseline, after eight weeks of intervention and at six-month follow-up. The primary outcome was the Rivermead Mobility Index. Other measures included the Functional Ambulation Category, 10-metre walk, 6-minute walk, Barthel Index, Motor Assessment Scale, Stroke Impact Scale and a measure of confidence in walking. Results: In all, 77 patients were randomized, 39 to treadmill and 38 to control. It was feasible to deliver treadmill training to people with sub-acute stroke. Only two adverse events occurred. No statistically significant differences were found between groups. For example, Rivermead Mobility Index, median (interquartile range (IQR)): after eight weeks treadmill 5 (4–9), control 6 (4–11) p = 0.33; or six-month follow-up treadmill 8.5 (3–12), control 8 (6–12.5) p = 0.42. The frequency and intensity of intervention was low. Conclusion: Treadmill training in sub-acute stroke patients was feasible but showed no significant difference in outcomes when compared to normal gait re-education. A large definitive randomized trial is now required to explore treadmill training in normal clinical practice.