bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the predisposing factor of pemphigus and its clinical subtype through a genome‐wide association and next generation sequence analysis
Authors: Sun Y. , Liu H. , Yang B. , Wang C. , Foo J.N. , Bao F. , Irwanto A. , Yu G. , Fu X. , Wang Z. , You J. , Liu J. , Zhou G. , Liu J. , Zhang F. 
Published: August 2018

AbstractBackgroundPemphigus is an autoimmune blistering disease with pemphigus vulgaris (PV) and foliaceus (PF) as the two major histological subtypes. Associations with HLA molecules have been suggested, but specific HLA risk variants as well as non‐HLA risk variants remain to be discovered.MethodsWe performed a two‐stage genome‐wide association study in the Chinese Han population through a genome‐wide discovery analysis and follow‐up validation analysis in a total number of 210 PV, 159 PF and 2493 healthy controls. HLA imputation as well as high coverage next generation sequencing based HLA genotyping was employed to investigate the association of classical HLA alleles and amino acid change.ResultsWe have discovered independent novel associations with PF at rs2178077 on 12q24.33, located next to RAN (PPF = 1.57 × 10−9) and rs3888722 within the MHC region (P = 6.73 × 10−9). For the HLA variants, we confirmed independent genome‐wide level risk associations in HLA‐DQB1 and HLA‐DRB1, with DQB1*05:03 to be the strongest association with PV (P = 8.59 × 10−68, OR = 31.16) and PF (P = 4.84 × 10−17, OR = 5.64). In addition, DRB1*14 was demonstrated to be a second independent variants (P = 4.2 × 10−63, OR = 35.47) for PV, while DRB1*04:06 was demonstrated to be the second independent signal (P = 7.44 × 10−13, OR = 5.58) for PF.ConclusionsThese findings advance our understanding of the genetic basis of pemphigus susceptibility and may offer opportunities for risk prediction and preventive treatment for pemphigus, in particular for PV.
Evaluation of a non‐ablative, fractional 1565 nm laser for the improvement of striae distensae albae
Authors: Guertler A. , Reinholz M. , Steckmeier S. , Gauglitz G.G. 
Published: August 2018

AbstractBackground and objectiveStriae distensae (SD) represent therapeutically challenging forms of dermal atrophic scarring. In addition to topical ointments, medical needling and various energy‐based devices, non‐ablative fractional lasers have been suggested for their improvement. However, objective evaluations of their efficacy are widely missing. In this study, we aimed to assess the clinical improvement of SD albae after three treatments with a non‐ablative fractional 1565 nm Er: glass laser by employing three‐dimensional analysis and several questionnaires.MethodsA total of 16 Caucasians suffering from SD albae were included in this prospective study. Every patient received three treatments – one every 4 weeks – using a non‐ablative, fractional 1565 nm laser (two passes: 300 μbeams/cm2, 40 mJ inside the SD; 150 μbeams/cm2, 50 mJ inside the SD and within the surrounding area). Questionnaires (DLQI, POSAS), digital photography and three‐dimensional analysis employing PRIMOS® software and VECTRA® camera system were taken at baseline, 1 and 6 months after the last treatment.ResultsEvaluation of objective measurements at 6‐month follow‐up (FU) showed a significant reduction in depth of atrophic lesions by 31.7% and less skin irregularities with Smax at baseline of 621.2 μm decreasing to 411.6 μm (P < 0.01, respectively).Improvement in objective measurements was supported by significant changes in patients’ rating of skin appearance. POSAS patient total score declined from 33.5 points to 17.5 points throughout the study (P < 0.001). From baseline to 6‐month FU, patients’ life quality improved by 68.0% (DLQI score). Procedures showed no lasting negative side‐effects and little to no down time.ConclusionThe use of a fractional non‐ablative 1565 nm laser represents a safe approach for the treatment of SD albae. Clinically observed improvements were supported by significant data from objective measurements. The results achieved at 1‐month FU represented at 6‐month FU, showing stable clinical improvements.
Continuous invasive hemodynamic monitoring using steerable guide catheter to optimize mitraclip transcatheter mitral valve repair: A multicenter, proof‐of‐concept study
Authors: Tang Gilbert H. L. , Ong Lawrence Y. , Kaple Ryan , Ramlawi Basel , Dutta Tanya , Zaid Syed , Ahmad Hasan , Kalimi Robert , Undemir Cenap , Khan Asaad , Yudi Matias B. , Nadir M. Adnan , Majeed Farhan , Ali Omar , Skiles Jeffrey , Bhim Chandra , Cohen Martin , Lansman Steven L. , Sharma Samin K. , Kini Annapoorna 
Published: August 2018

ObjectivesWe report our multicenter experience on continuous hemodynamic monitoring using exclusively the steerable guide catheter (SGC) during MitraClip repair.BackgroundLeft atrial pressure (LAP) and V‐wave are useful to evaluate MitraClip repair but no simple method of continuous monitoring exists.MethodsFrom 11/2016 to 8/2017, 74 patients from four centers with symptomatic moderate‐severe to severe mitral regurgitation (MR), underwent MitraClip NT repair with continuous hemodynamic monitoring via the SGC. Real‐time LAP/V‐wave changes were compared with transesophageal echocardiography (TEE). When mitral stenosis was suspected, transmitral gradients were verified by invasive hemodynamics. Clinical and echocardiographic outcomes were determined.ResultsMean age was 78 ± 10 years and STS score 9.1 ± 11.0%. Pathology included leaflet prolapse/flail (45%), restriction (35%), and mixed (20%). Number of clips averaged 1.7 ± 0.7 per case. There was a significant reduction in LAP (21 ± 10 to 15 ± 7 mmHg, P < 0.0001) and V‐wave(37 ± 19 to 24 ± 10 mmHg, P < 0.0001) post MitraClip, but the decrease was less in patients with atrial fibrillation (P < 0.05). Transmitral gradient significantly increased from 2.0 ± 1.2 to 4.0 ± 1.7 mmHg (P < 0.0001). Paradoxical increases in LAP and V‐wave despite MR reduction were observed in three cases requiring MitraClip repositioning or retrieval to avoid stenosis. Follow‐up averaged 5.0 ± 2.9 months and was 100% complete. KCCQ improvement was significant and MR reduction to <1+ was 67% and <2+ was 93% at 30 days.ConclusionsContinuous hemodynamic monitoring using the SGC complements TEE to assess and optimize MitraClip repair in real‐time. Further validation is necessary but this feature may be part of future MitraClip and other transcatheter mitral repair systems.
Association between type of health insurance and children's oral health, NHANES 2011–2014
Authors: Duffy Erin L. , Kranz Ashley M. , Dick Andrew W. , Sorbero Mark , Stein Bradley D. 
Published: August 2018

AbstractObjectivesTo examine the association between type of health insurance (public, uninsured, private, or other) and oral health outcomes for children in the United States using nationally representative surveillance data.MethodsUsing the National Health and Nutrition Examination Survey (2011/12–2013/14), logistic regression models were used to estimate the odds of any dental caries and any untreated caries by type of health insurance (public, uninsured, private, and other) for children aged 2–19 years, with adjustment for relevant individual and socioeconomic characteristics.ResultsAmong 6,057 children, the odds of having any dental caries or untreated caries was not significantly different for publicly insured and uninsured children compared to privately insured children, when adjusting for family income and education. Children in families with income to poverty ratios <200 percent had greater odds of caries and untreated caries relative to children in families with income to poverty ratios ≥400 percent. Children with less educated parents also experienced greater odds of caries and untreated caries.ConclusionsOral health outcomes, after adjusting for covariates, were similar for children with public and private health insurance. However, children in low‐income families and with less educated parents had greater odds of untreated caries and dental caries, suggesting that initiatives focused on publicly insured populations may miss other vulnerable children of low socioeconomic status.
Towards a new “folkloric turn” in the literature of early modernIreland
Authors: Covington Sarah 
Published: August 2018

AbstractThis essay offers new suggestions in the study of sixteenth‐ and seventeenth‐century English and Irish literature through a specifically folkloric lens. While scholars of medieval and modern texts in Ireland have made much progress in uncovering and debating the presence of popular oral traditions (and orality in general) in their respective sources, those who focus on the sixteenth and seventeenth centuries have yet to fully explore the same attributes in their own rich body of literature. This essay will therefore survey the sources, methods, and directions which a “folkloric turn” can take, especially as it incorporates a range of models that can be used to analyze orality, residues of popular traditions, and the utilization of particular motifs to open a new prism onto the period. While there are certainly challenges in utilizing this approach, folklore has the potential to contextualize and deepen our understanding of sources that include antiquarian records, travel accounts, ballads, legal depositions, English and Irish poetry, and even the modern folkloric tales to which they relate.
Monetary policy, inequality and political instability
Authors: Duarte Pablo , Schnabl Gunther 
Published: August 2018

AbstractVoters in the industrialised countries are increasingly expressing dissatisfaction by dissenting from the established political parties and candidates. Based on the concepts of justice by Hayek, Rawls and Buchanan, we argue that the growing dissatisfaction is rooted in the asymmetric pattern of monetary policies since the mid‐1980s for two reasons. First, the structurally declining interest rates and the unconventional monetary policy measures have granted privileges to specific groups. Second, the increasingly expansionary monetary policies have negative growth effects, which have reduced the scope for compensation of the ones excluded from the privileges. As a result, the acceptance of the prevailing economic and political order is undermined and political instability increases.
Evaluating veterinary student skill acquisition on a laparoscopic suturing exercise after simulation training
Authors: Kilkenny Jessica J. , White Kadi , Singh Ameet 
Published: August 2018

AbstractObjectiveTo determine whether veterinary students could train to a predefined proficiency level on a simulated intracorporeal laparoscopic suturing task.Study designSingle group preinterventional and postinterventional study.Sample populationTen veterinary students.MethodsTen veterinary students completed a questionnaire about prior experiences and watched a 7‐minute demonstration video prior to performing a laparoscopic intracorporeal suture task on a simulator. Participants were tested at pretraining and for a period of 8 weeks. Overall group improvement in scores and time to completion (seconds) from pretraining to final testing was analyzed by using a Wilcoxon matched‐pairs signed‐rank test. The same variables were compared among individuals with different background experiences (eg, video game experience) by using a Mann‐Whitney U test. The average number of repetitions to reach proficiency was recorded.ResultsAll participants reached the predefined proficiency level on the Fundamentals of Laparoscopic Surgery intracorporeal suture task. The average number of repetitions required to reach proficiency was 18 ± 7, and there was significant improvement in both time to completion (seconds) and scores from pretraining to final testing (P = .005). The number of repetitions required to reach proficiency, pretraining times, final times, pretraining scores, and final scores did not differ among veterinary students with different background experiences.ConclusionVeterinary students naïve to laparoscopic surgery can learn the technical skills required to perform a simulated intracorporeal suture through repetitive, self‐directed practice on a laparoscopic box trainer regardless of prior experiences (eg, videogame experience, craft experience, chopstick use, etc).Clinical significanceSimulation offers an adequate platform for the standardized training of laparoscopic skills in veterinary students and likely novice laparoscopic surgeons.
Prognostication in urgent intensive care unit referrals: a cohort study
Authors: Ramos Joao Gabriel Rosa , Dias Roger Daglius , Passos Rogerio da Hora , Batista Paulo Benigno Pena , Forte Daniel Neves 
Published: August 2018

ObjectivesPrognostication is an essential ability to clinicians. Nevertheless, it has been shown to be quite variable in acutely ill patients, potentially leading to inappropriate care. We aimed to assess the accuracy of physician’s prediction of hospital mortality in acutely deteriorating patients referred for urgent intensive care unit (ICU) admission.MethodsProspective cohort of acutely ill patients referred for urgent ICU admission in an academic, tertiary hospital. Physicians’ prognosis assessments were recorded at ICU referral. Prognosis was assessed as survival without severe disabilities, survival with severe disabilities or no survival. Prognosis was further dichotomised in good prognosis (survival without severe disabilities) or poor prognosis (survival with severe disabilities or no survival) for prediction of hospital mortality.ResultsThere were 2374 analysed referrals, with 2103 (88.6%) patients with complete data on mortality and physicians’ prognosis. There were 593 (34.4%), 215 (66.4%) and 51 (94.4%) deaths in the groups ascribed a prognosis of survival without disabilities, survival with severe disabilities or no survival, respectively (p<0.001). Sensitivity was 31%, specificity was 91% and the area under the receiver operating characteristic curve was 0.61 for prediction of mortality. After multivariable analysis, severity of illness, performance status and ICU admission were associated with an increased likelihood of incorrect classification, while worse predicted prognosis was associated with a lower chance of incorrect classification.ConclusionsPhysician’s prediction was associated with hospital mortality, but overall accuracy was poor, mainly due to low sensitivity to detect risk of poor prognosis.
The radion as a dark matter candidate
Authors: Abu-Ajamieh Fayez 
Published: August 2018

I study a class of Randall–Sundrum (RS) models with Spontaneous Breaking of Scale Invariance (SBSI). This class of models implements the Contino–Pomarol–Rattazzi (CPR) mechanism to achieve SBSI through the small running of an external close-to-marginal scale-breaking operator that leads to a light dilaton/radion with couplings to matter suppressed by the small running. I show that for radion masses [Formula: see text] KeV, it can serve as a dark matter (DM) candidate, with a lifetime longer than the age of the universe, and show that the experimental bounds from LHC, non-Newtonian gravity and Axion-Like Particle (ALP) searches allow for the existence of such a radion. In spite of the small relic abundance of the light radion produced in this model, we show that it could be possible to obtain the required abundance through additional assumptions, an issue we postpone to the future.
HER2/EGFR–AKT Signaling Switches TGFβ from Inhibiting Cell Proliferation to Promoting Cell Migration in Breast Cancer
Authors: Huang Fei , Shi Qiaoni , Li Yuzhen , Xu Linlin , Xu Chi , Chen Fenfang , Wang Hai , Liao Hongwei , Chang Zai , Liu Fang , Zhang Xiang H.-F. , Feng Xin-Hua , Han Jing-Dong J. , Luo Shiwen , Chen Ye-Guang 
Published: August 2018

Abstract
TGFβ signaling inhibits cell proliferation to block cancer initiation, yet it also enhances metastasis to promote malignancy during breast cancer development. The mechanisms underlying these differential effects are still unclear. Here, we report that HER2/EGFR signaling switches TGFβ function in breast cancer cells from antiproliferation to cancer promotion. Inhibition of HER2/EGFR activity attenuated TGFβ–induced epithelial–mesenchymal transition and migration but enhanced the antiproliferative activity of TGFβ. Activation of HER2/EGFR induced phosphorylation of Smad3 at Ser208 of the linker region through AKT, which promoted the nuclear accumulation of Smad3 and subsequent expression of the genes related to EMT and cell migration. In contrast, HER2/EGFR signaling had no effects on the nuclear localization of Smad2. Knockdown of Smad3, but not Smad2, blocked TGFβ–induced breast cancer cell migration. We observed a positive correlation between the nuclear localization of Smad3 and HER2 activation in advanced human breast cancers. Our results demonstrate a key role for HER2/EGFR in differential regulation of Smad3 activity to shift TGFβ function from antitumorigenic to protumorigenic during breast cancer development.
Significance: TGFβ signaling can shift from inhibiting to promoting breast cancer development via HER2/EGFR AKT-mediated phosphorylation of Smad3 at S208, enhancing its nuclear accumulation and upregulation of EMT-related genes.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/21/6073/F1.large.jpg. Cancer Res; 78(21); 6073–85. ©2018 AACR.
Consecutive Day HSP90 Inhibitor Administration Improves Efficacy in Murine Models of KIT-Driven Malignancies and Canine Mast Cell Tumors
Authors: London Cheryl A. , Acquaviva Jaime , Smith Donald L. , Sequeira Manuel , Ogawa Luisa Shin , Gardner Heather L. , Bernabe Louis Feo , Bear Misty D. , Bechtel Sandra A. , Proia David A. 
Published: August 2018

Abstract

Purpose:
STA-1474, prodrug of the heat shock protein 90 inhibitor (HSP90i) ganetespib, previously demonstrated activity in canine preclinical models of cancer; interestingly, prolonged infusions were associated with improved biologic activity. The purpose of this study was to identify the ideal treatment schedule for HSP90i in preclinical models of KIT-driven malignancies and in dogs with spontaneous mast cell tumors (MCT), where KIT is a known driver.

Experimental Design:
In vitro and murine xenograft experiments and clinical studies in dogs with MCTs were used to define the effects of HSP90i-dosing regimen on client protein downregulation and antitumor activity.

Results:
Continuous HSP90 inhibition led to durable destabilization of client proteins in vitro; however, transient exposure required &gt;10× drug for comparable effects. In vivo, KIT was rapidly degraded following a single dose of HSP90i but returned to baseline levels within a day. HSP90 levels increased and stabilized 16 hours after HSP90i and were not elevated following a subsequent near-term exposure, providing a functional pool of chaperone to stabilize proteins and a means for greater therapeutic activity upon HSP90i reexposure. HSP90i administered on days 1 and 2 (D1/D2) demonstrated increased biologic activity compared with D1 treatment in KIT or EGFR-driven murine tumor models. In a trial of dogs with MCT, D1/D2 dosing of HSP90i was associated with sustained KIT downregulation, 50% objective response rate and 100% clinical benefit rate compared with D1 and D1/D4 schedules.

Conclusions:
These data provide further evidence that prolonged HSP90i exposure improves biologic activity through sustained downregulation of client proteins.
A Leukocyte Infiltration Score Defined by a Gene Signature Predicts Melanoma Patient Prognosis
Authors: Zhao Yanding , Schaafsma Evelien , Gorlov Ivan P. , Hernando Eva , Thomas Nancy E. , Shen Ronglai , Turk Mary Jo , Berwick Marianne , Amos Christopher I. , Cheng Chao 
Published: August 2018

Abstract

Melanoma is the most aggressive type of skin cancer in the United States with an increasing incidence. Melanoma lesions often exhibit high immunogenicity, with infiltrating immune cells playing important roles in regression of tumors occurring spontaneously or caused by therapeutic treatment. Computational and experimental methods have been used to estimate the abundance of immune cells in tumors, but their applications are limited by the requirement of large gene sets or multiple antibodies. Although the prognostic role of immune cells has been appreciated, a systematic investigation of their association with clinical factors, genomic features, prognosis and treatment response in melanoma is still lacking. This study, identifies a 25-gene signature based on RNA-seq data from The Cancer Genome Atlas (TCGA)—Skin Cutaneous Melanoma (TCGA-SKCM) dataset. This signature was used to calculate sample-specific Leukocyte Infiltration Scores (LIS) in six independent melanoma microarray datasets and scores were found to vary substantially between different melanoma lesion sites and molecular subtypes. For metastatic melanoma, LIS was prognostic in all datasets with high LIS being associated with good survival. The current approach provided additional prognostic information over established clinical factors, including age, tumor stage, and gender. In addition, LIS was predictive of patient survival in stage III melanoma, and treatment efficacy of tumor-specific antigen vaccine.

Implications:
This study identifies a 25-gene signature that effectively estimates the level of immune cell infiltration in melanoma, which provides a robust biomarker for predicting patient prognosis.
Safety and Potential Therapeutic Effect of Two Intracavernous Autologous Bone Marrow Derived Mesenchymal Stem Cells injections in Diabetic Patients with Erectile Dysfunction: An Open Label Phase I Clinical Trial
Authors: Al Demour Saddam , Jafar Hanan , Adwan Sofia , AlSharif Abedallatif , Alhawari Hussam , Alrabadi Adel , Zayed Ayman , Jaradat Ahmad , Awidi Abdalla 
Published: August 2018

<b><i>Objectives:</i></b> This open label, phase I clinical trial (NCT02945462) using 2 consecutive intracavernous autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) for the first time in the treatment of diabetic patients with erectile dysfunction (ED). The primary outcome is to assess the safety and tolerability of intracavernous autologous BM-MSCs, the secondary outcome is to assess efficacy of the procedure. <b><i>Patients and Methods:</i></b> Four diabetic patients with refractory ED were included. Two consecutive intracavernous autologous BM-MSC injections were performed. Tolerability was assessed immediately and at 24 h, safety was evaluated for 2 years. Efficacy was assessed using International Index of Erectile Function-15 (IIEF-15) and Erection Hardness Score (EHS) for 12 months. <b><i>Results:</i></b> procedure was well tolerated and no patients reported significant adverse effects. There was significant improvement of IIEF-15 and EHS; IIEF-15 (<i>p</i> = 0.04), Erectile Function (<i>p</i> = 0.03), Sexual Desire (<i>p</i> = 0.04), Intercourse Satisfaction (<i>p</i> = 0.04), and Overall Satisfaction (<i>p</i> = 0.04). <b><i>Conclusion:</i></b> This is the first human study with proven tolerability, safety and efficacy of intracavernous autologous BM-MSC injections for treatment of diabetic patients with ED.
A Report on the Difference Between the Precipitation Records as Taken on the Standard Canadian and United States Rain-gauges
Authors: Denison F. Napier 
Published: August 2018

Synopsis
This describes a comparison of rainfall observations as taken at the Victoria College on the Canadian standard rain gauge of 3.57 inch diameter, and the standard U. S. 8 inch gauge, and a similar comparison made at Seattle Weather Bureau. The results appear to show that the small gauge records more rainfall than the larger gauge, but the difference is less during windy weather. No cause for this difference is given at the present time. It is also pointed out that the cedar stick causes a displacement of .01 inch per inch in the 8 inch gauge.