bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results
Authors: Nordström Maria , Schiller Maria , Fredriksson Anneli , Behndig Anders 
Published: November 2016

PurposeTo assess the refractive improvements and the corneal endothelial safety of an individualised topography-guided regimen for corneal crosslinking in progressive keratoconus.MethodsAn open-label prospective randomised clinical trial was performed at the Department of Clinical Sciences, Ophthalmology, Umeå University Hospital, Umeå, Sweden. Thirty-seven patients (50 eyes) with progressive keratoconus planned for corneal crosslinking were included. The patients were randomised to topography-guided crosslinking (photorefractive intrastromal crosslinking (PiXL); n=25) or uniform 9 mm crosslinking (corneal collagen crosslinking (CXL); n=25). Visual acuity, refraction, keratometry (K1, K2 and Kmax) and corneal endothelial morphometry were assessed preoperatively and at 1, 3, 6 and 12 months postoperatively. The PiXL treatment involved an asymmetrical treatment zone centred on the area of maximum corneal steepness with treatment energies ranging from 7.2 to 15.0 J/cm2; the CXL treatment was a uniform 9 mm 5.4 J/cm2pulsed crosslinking. The main outcome measures were changes in refractive errors and corneal endothelial cell density.ResultsThe spherical refractive errors decreased (p<0.05) and the visual acuity improved (p<0.01) at 3, 6 and 12 months after PiXL, but not after CXL. The between-groups differences, however, were not significant. K2 and Kmaxdecreased at 3, 6 and 12 months after PiXL (p<0.01), but not after CXL (p<0.01 when comparing the two treatments). No corneal endothelial cell loss was seen after either treatment.ConclusionsIndividualised topography-based crosslinking treatment centred on the ectatic cone has the potential to improve the corneal shape in keratoconus with decreased spherical refractive errors and improved visual acuity, without damage to the corneal endothelium.Trial registration numberNCT02514200, Results.
Topography of the supraorbital nerve with reference to the lacrimal caruncle: danger zone for direct browplasty
Authors: Gil Young-Chun , Shin Kang-Jae , Lee Shin-Hyo , Song Wu-Chul , Koh Ki-Seok , Shin Hyun Jin 
Published: November 2016

PurposeTo elucidate the course of the supraorbital nerve (SON) with reference to the lacrimal caruncle in order to facilitate safer direct browplasty by preventing nerve injury.MethodsThirty-four hemifaces from 18 embalmed Korean cadavers were dissected. A vertical line through the upmost point of the lacrimal caruncle and a horizontal line through the supraorbital margin were used as the horizontal and vertical reference positions, respectively. The course of the SON in the frontal view and the point at which it pierced the overlaying musculature were examined.ResultsThe SON divides into a superficial branch and a deep branch just after exiting the orbit. In all cases, the deep SON remains in the subgaleal plane deep to the corrugator and frontalis muscles. The superficial SON travels under the corrugator muscle dividing into three branches (medial, intermediate and lateral) and pierced the frontalis muscle at 19–32 mm above the supraorbital margin. However, in 11 cases (32%) the medial branch of the superficial SON pierced the lower portion of the corrugator muscle at 3.6 mm above the supraorbital margin and ran in front of the muscle along with the vertical line through the upmost point of the lacrimal caruncle.ConclusionsOne-third of the medial branch of the superficial SON without corrugator muscle protection is vulnerable to iatrogenic injury during direct browplasty. Therefore, the oculofacial surgeon must bring the dissection plane of the forehead tissue more superficially around the vertical line through the upmost point of the lacrimal caruncle in order to avoid nerve injury.
Insulin resistance of protein anabolism accompanies that of glucose metabolism in lean, glucose-tolerant offspring of persons with type 2 diabetes
Authors: Burgos Sergio A , Chandurkar Vikram , Tsoukas Michael A , Chevalier Stéphanie , Morais José A , Lamarche Marie , Marliss Errol B 
Published: November 2016

ObjectiveTo test whether protein anabolic resistance is an early defect in type 2 diabetes (T2D).Research design and methodsSeven lean, normoglycemic T2D offspring (T2D-O) and eight matched participants without family history (controls; C) underwent a 3-hour hyperinsulinemic (40 mU/m2/min), euglycemic (5.5 mmol/L) and isoaminoacidemic clamp. Whole-body glucose and protein kinetics were measured withd-[3–3H]glucose andl-[l-13C]leucine, respectively. Plasma amino acids were measured by liquid chromatography-tandem mass spectrometry.ResultsFasting glycemia and glucose kinetic variables did not differ between groups. Clamp decreases in glucose rate of appearance were not different, but rate of disappearance increased 29% less in T2D-O, to a significantly lower rate. Fasting leucine was higher in T2D-O, but kinetics did not differ. Clamp increases in leucine oxidation and decreases in endogenous rate of appearance (protein breakdown) were equal, but in T2D-O, non-oxidative rate of disappearance (protein synthesis) did not increase and net balance (synthesis—breakdown) did not become positive as in C.ConclusionsResistance of whole-body protein anabolism (synthesis and net balance) accompanies resistance of glucose uptake in T2D-O. Mechanisms responsible, possible roles in the increased risk of developing diabetes, and its potential impact on long-term protein balance require definition.
Ideal cardiovascular health score and incident end-stage renal disease in a community-based longitudinal cohort study: the Kailuan Study
Authors: Han Quan Le , Wu Shou Ling , Liu Xiao Xue , An Sha Sha , Wu Yun Tao , Gao Jing Sheng , Chen Shuo Hua , Liu Xiao Kun , Zhang Qi , Mao Rui Ying , Shang Xiao Ming , Jonas Jost B 
Published: November 2016

ObjectivesTo investigate an association between ideal cardiovascular health metrics (CVH) and the risk of developing end-stage renal disease (ESRD).SettingCommunity of Kailuan in Tangshan/China.ParticipantsWe examined in a community-based longitudinal cohort study 91 443 participants without history of stroke or myocardial infarction at baseline in 2006–2007, with a glomerular filtration rate (GFR) ≥15 mL/min at baseline, and who participated in at least 1 of 3 follow-up examinations in 2008–2009, 2010–2011 and 2012–2013.InterventionsCVH was measured by 7 key health factors (smoking, body mass index, physical activity, healthy dietary score, total cholesterol blood concentration, blood pressure, fasting blood glucose) each of which ranged between ‘ideal’ (2) and ‘poor’ (0). With a maximal CVH score of 14, the study participants were divided into categories of <5, 5–9 and 10–14 points.Primary and secondary outcome measuresCHV, incidence of ESRD.ResultsIncidence of ESRD ranged from 7.06‰ in the lowest CVH category to 2.34‰ in the highest CVH category. After adjusting for age, sex, educational level, income, alcohol consumption and GFR, the lowest CVH category as compared with the highest CVH category had a significantly higher risk of incident ESRD (adjusted HR 2.87; 95% CI 1.53 to 5.39). For every decrease in group number of the cum-CVH score, the risk of ESRD increased by 20% (HR 1.20; 95% CI 1.13 to 1.28). The effect was consistent across sex and all age groups.ConclusionsA low CVH score significantly increased the risk of incident ESRD. Risk factors for cardiovascular events may also be associated with an increased risk for kidney failure.
Initial clinical experience using the two-stage aspiration technique (TSAT) with proximal flow arrest by a balloon guiding catheter for acute ischemic stroke of the anterior circulation
Authors: Matsumoto Hiroyuki , Nishiyama Hirokazu , Tetsuo Yoshiaki , Takemoto Hideki , Nakao Naoyuki 
Published: November 2016

BackgroundOur initial experience using the two-stage aspiration technique (TSAT) with proximal flow arrest by a balloon guiding catheter is presented. In TSAT, aspiration is applied with the 5MAX ACE and also with the 3MAX catheter with a Penumbra aspiration pump, while arresting proximal flow by balloon inflation.MethodsIn patients treated with TSAT, clinical data including National Institutes of Health Stroke Scale (NIHSS) score at admission and the modiﬁed Rankin Scale (mRS) score at discharge, as well as procedural data including the Thrombolysis in Cerebral Infarction (TICI) score, procedural time, and complications were analyzed.ResultsThirty-four consecutive patients (19 men (56%); mean age 73 years) were treated with TSAT using a balloon guiding catheter. The patients presented with a mean NIHSS score of 17.4 and 23 (68%) patients received IV tissue plasminogen activator. Median time from groin puncture to successful recanalization was 41 min (range 15–160 min). All patients were successfully revascularized; TICI 2b or better recanalization was achieved in 30 (88%) patients. No patient required an additional procedure such as use of a stent retriever. Procedure-related complications occurred in two (5.9%) patients (vessel injury and guidewire perforation). Symptomatic intracranial hemorrhage occurred in one patient and asymptomatic hemorrhagic infarction occurred in two patients. There were no cases of embolization to new territory (ENT). The mean NIHSS score at discharge improved to 6.1. Sixteen patients (47%) achieved a good outcome with an mRS score of 0–2 at discharge (mean hospitalization period 20 days).ConclusionsTSAT with proximal flow arrest by a balloon guiding catheter is an effective and safe method to achieve good clinical and angiographic outcomes. This method may reduce ENT in the direct aspiration first-pass thrombectomy (ADAPT) technique.
How to build a lower-body differential pressure chamber integrated on a tilt-table: A pedagogy tool to demonstrate the cardiovagal baroreflex
Authors: Tymko Michael M. 
Published: November 2016

The cardiovagal baroreflex is an important physiological reflex that is commonly taught in health-related university physiology courses. This reflex is responsible for the rapid maintenance of blood pressure through dynamic changes in heart rate (HR) and vascular resistance. The use of lower-body negative pressure (LBNP) and lower-body positive pressure (LBPP) can manipulate these stretch sensitive baroreceptors. High performance and relatively inexpensive homemade LBNP and LBPP chambers can be easily constructed providing a valuable tool for both research and teaching purposes. There has been previous documentation of how to build a LBNP chamber; however, the information available usually lacks appropriate construction details, and there is currently no literature on how to build a chamber that can accommodate both LBNP and LBPP. In addition, a recently developed novel LBNP/LBPP chamber positioned on a 360° tilt-table provided the unique utility of superimposing both LBNP/LBPP and body position as independent or combined stressors to alter central blood volume. The primary purposes of this manuscript are to (1) provide step-by-step instructions on how to build a tilt-table LBNP/LBPP chamber, and (2) demonstrate the effectiveness of a tilt-table LBNP/LBPP chamber to facilitate undergraduate and graduate learning in the laboratory by effectively demonstrating the cardiovagal baroreflex.
The fundamental class of smooth Kuranishi atlases with trivial isotropy
Authors: McDuff Dusa , Wehrheim Katrin 
Published: November 2016

Kuranishi structures were introduced in the 1990s by Fukaya and Ono for the purpose of assigning a virtual cycle to moduli spaces of pseudoholomorphic curves that cannot be regularized by geometric methods. Their core idea was to build such a cycle by patching local finite dimensional reductions. The first sections of this paper discuss topological, algebraic and analytic challenges that arise in this program.We then develop a theory of Kuranishi atlases and cobordisms that transparently resolves these challenges, for simplicity concentrating on the case of trivial isotropy. In this case, we assign to a cobordism class of additive weak Kuranishi atlases both a virtual moduli cycle (VMC — a cobordism class of smooth manifolds) and a virtual fundamental class (VFC — a Cech homology class). We, moreover, show that such Kuranishi atlases exist on simple Gromov–Witten moduli spaces and develop the technical results in a manner that easily transfers to more general settings.
Body sway adaptation to addition but not withdrawal of stabilizing visual information is delayed by a concurrent cognitive task
Authors: Honeine Jean-Louis , Crisafulli Oscar , Schieppati Marco 
Published: November 2016

The aim of this study was to test the effects of a concurrent cognitive task on the promptness of the sensorimotor integration and reweighting processes following addition and withdrawal of vision. Fourteen subjects stood in tandem while vision was passively added and removed. Subjects performed a cognitive task, consisting of counting backward in steps of three, or were “mentally idle.” We estimated the time intervals following addition and withdrawal of vision at which body sway began to change. We also estimated the time constant of the exponential change in body oscillation until the new level of sway was reached, consistent with the current visual state. Under the mentally idle condition, mean latency was 0.67 and 0.46 s and the mean time constant was 1.27 and 0.59 s for vision addition and withdrawal, respectively. Following addition of vision, counting backward delayed the latency by about 300 ms, without affecting the time constant. Following withdrawal, counting backward had no significant effect on either latency or time constant. The extension by counting backward of the time interval to stabilization onset on addition of vision suggests a competition for allocation of cortical resources. Conversely, the absence of cognitive task effect on the rapid onset of destabilization on vision withdrawal, and on the relevant reweighting time course, advocates the intervention of a subcortical process. Diverting attention from a challenging standing task discloses a cortical supervision on the process of sensorimotor integration of new balance-stabilizing information. A subcortical process would instead organize the response to removal of the stabilizing sensory input. NEW & NOTEWORTHY This study is the first to test the effect of an arithmetic task on the time course of balance readjustment following visual withdrawal or addition. Performing such a cognitive task increases the time delay following addition of vision but has no effect on withdrawal dynamics. This suggests that sensorimotor integration following addition of a stabilizing signal is performed at a cortical level, whereas the response to its withdrawal is “automatic” and accomplished at a subcortical level.
Castration Resistance in Prostate Cancer Is Mediated by the Kinase NEK6
Authors: Choudhury Atish D. , Schinzel Anna C. , Cotter Maura B. , Lis Rosina T. , Labella Katherine , Lock Ying Jie , Izzo Francesca , Guney Isil , Bowden Michaela , Li Yvonne Y. , Patel Jinal , Hartman Emily , Carr Steven A. , Schenone Monica , Jaffe Jacob D. , Kantoff Philip W. , Hammerman Peter S. , Hahn William C. 
Published: November 2016

Abstract
In prostate cancer, the development of castration resistance is pivotal in progression to aggressive disease. However, understanding of the pathways involved remains incomplete. In this study, we performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial (LHSR-AR) cells under androgen-deprived conditions. In addition to the identification of known mediators of castration resistance, which served to validate the screen, we identified a mitotic-related serine/threonine kinase, NEK6, as a mediator of androgen-independent tumor growth. NEK6 was overexpressed in a subset of human prostate cancers. Silencing NEK6 in castration-resistant cancer cells was sufficient to restore sensitivity to castration in a mouse xenograft model system. Tumors in which castration resistance was conferred by NEK6 were predominantly squamous in histology with no evidence of AR signaling. Gene expression profiling suggested that NEK6 overexpression stimulated cytoskeletal, differentiation, and immune signaling pathways and maintained gene expression patterns normally decreased by castration. Phosphoproteome profiling revealed the transcription factor FOXJ2 as a novel NEK6 substrate, with FOXJ2 phosphorylation associated with increased expression of newly identified NEK6 transcriptional targets. Overall, our studies establish NEK6 signaling as a central mechanism mediating castration-resistant prostate cancer. Cancer Res; 77(3); 753–65. ©2016 AACR.
MYC Mediates mRNA Cap Methylation of Canonical Wnt/β-Catenin Signaling Transcripts By Recruiting CDK7 and RNA Methyltransferase
Authors: Posternak Valeriya , Ung Matthew H. , Cheng Chao , Cole Michael D. 
Published: November 2016

Abstract
MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here, it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/β-catenin signaling. Elevated mRNA cap methylation of Wnt signaling transcripts in response to MYC leads to augmented translational capacity, elevated protein levels, and enhanced Wnt signaling activity. Mechanistic evidence indicates that MYC promotes recruitment of RNA methyltransferase (RNMT) to Wnt signaling gene promoters by enhancing phosphorylation of serine 5 on the RNA polymerase II carboxy-terminal domain, mediated in part through an interaction between the TIP60 acetyltransferase complex and TFIIH.
Implications: MYC enhances mRNA cap methylation above and beyond transcriptional induction. Mol Cancer Res; 15(2); 213–24. ©2016 AACR.
Functional Definition of Progenitors Versus Mature Endothelial Cells Reveals Key SoxF-Dependent Differentiation Process
Authors: Patel Jatin , Seppanen Elke J. , Rodero Mathieu P. , Wong Ho Yi , Donovan Prudence , Neufeld Zoltan , Fisk Nicholas M. , Francois Mathias , Khosrotehrani Kiarash 
Published: November 2016

Background:
During adult life, blood vessel formation is thought to occur via angiogenic processes involving branching from existing vessels. An alternate proposal suggests that neovessels form from endothelial progenitors able to assemble the intimal layers. We here aimed to define vessel-resident endothelial progenitors in vivo in a variety of tissues in physiological and pathological situations such as normal aorta, lungs, and wound healing, tumors, and placenta, as well.

Methods:
Based on protein expression levels of common endothelial markers using flow cytometry, 3 subpopulations of endothelial cells could be identified among VE-Cadherin+ and CD45– cells.

Results:

Lineage tracing by using
Cdh5cre

ERt2

/Rosa-YFP
reporter strategy demonstrated that the CD31–/loVEGFR2lo/intracellular endothelial population was indeed an endovascular progenitor (EVP) of an intermediate CD31intVEGFR2lo/intracellular transit amplifying (TA) and a definitive differentiated (D) CD31hiVEGFR2hi/extracellular population. EVP cells arose from vascular-resident beds that could not be transferred by bone marrow transplantation. Furthermore, EVP displayed progenitor-like status with a high proportion of cells in a quiescent cell cycle phase as assessed in wounds, tumors, and aorta. Only EVP cells and not TA and D cells had self-renewal capacity as demonstrated by colony-forming capacity in limiting dilution and by transplantation in Matrigel plugs in recipient mice. RNA sequencing revealed prominent gene expression differences between EVP and D cells. In particular, EVP cells highly expressed genes related to progenitor function including
Sox9
,
Il33
,
Egfr
, and
Pdfgrα.
Conversely, D cells highly expressed genes related to differentiated endothelium including
Ets1&2
,
Gata2
,
Cd31
,
Vwf
, and
Notch
. The RNA sequencing also pointed to an essential role of the
Sox18
transcription factor. The role of SOX18 in the differentiation process was validated by using lineage-tracing experiments based on S
ox18Cre

ERt2

/Rosa-YFP
mice. Besides, in the absence of functional SOX18/SOXF, EVP progenitors were still present, but TA and D populations were significantly reduced.

Conclusions:
Our findings support an entirely novel endothelial hierarchy, from EVP to TA to D, as defined by self-renewal, differentiation, and molecular profiling of an endothelial progenitor. This paradigm shift in our understanding of vascular-resident endothelial progenitors in tissue regeneration opens new avenues for better understanding of cardiovascular biology.
Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients
Authors: Wang Yongjun , Minematsu Kazuo , Wong Ka Sing Lawrence , Amarenco Pierre , Albers Gregory W. , Denison Hans , Easton J. Donald , Evans Scott R. , Held Peter , Jonasson Jenny , Molina Carlos A. , Johnston S. Claiborne 
Published: November 2016

Background and Purpose—
In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis.

Methods—
Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model.

Results—

A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67–0.99). The exploratory
P
value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal
P
<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36–1.61).

Conclusions—
The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01994720.