bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and biological analysis of LncSPRY4‐IT1‐targeted functional proteins in photoaging skin
Authors: Hou Wenyi , Lin Yao , Xu Weichun , Chen Haiyan , Liu Yufang , Li Changxing , Zheng Yue 
Published: June 2021

AbstractBackground/purposeSkin photoaging, main causes of skin aging, is induced by chronic UV irradiation. LncSPRY4‐IT1, a broadly expressed lncRNA, takes part in various biological functions by combining with functional protein molecules. However, the role of LncSPRY4‐IT1 in skin photoaging process has not been characterized. This study is to investigate the interacting proteins of LncSPRY4‐IT1 by combining RNA pull‐down, high‐throughput, and bioinformatic analysis.MethodsHuman skin fibroblasts (HDFs) were exposed to 10 J/cm2 UVA irradiation, once a day for 14 days. LncSPRY4‐IT1 expression was qualified via RT‐PCR. In vitro RNA pull‐down assays and liquid chromatography‐mass spectrometry analysis were used to identify the LncSPRY4‐IT1‐related proteins. Functional annotation analysis and pathway enrichment were preformed via Gene Ontology and KEGG.ResultsLncSPRY4‐IT1 expression in photoaging fibroblasts was increased 1.66 ± 0.23 folds. 181 LncSPRY4‐IT1‐interacting proteins in UVA‐induced photoaging skin fibroblast irradiation were identified, of which 56 proteins with two or more unique peptides, 73 proteins related to RNA processing, and 5 proteins related to DNA processing. High‐throughput and bioinformatic analysis showed that LncSPRY4‐IT1‐targeting proteins were involved in cellular process, metabolic process, biological regulation, and cell part in skin photoaging process. The KEGG revealed that LncSPRY4‐IT1‐targeting proteins were mainly enriched in metabolic pathways.ConclusionThe results of our studies illuminate how LncSPRY4‐IT1 formed a LncRNA‐protein regulatory network in skin photoaging mechanisms and suggest that LncSPRY4‐IT1 may serve as a novel upstream intervention target for the prevention and treatment of photoaging and related skin diseases.
Biting one’s tongue: autoglossotomy and agency in The Spanish Tragedy
Authors: Skuse Alanna 
Published: June 2021

AbstractWhen the protagonist Hieronimo bites out his own tongue in Thomas Kyd's The Spanish Tragedy, his actions seem to make little sense. After all, he has already explained the very plot which he claims to be keeping a secret through his self‐injury. However this article argues that Hieronimo's tongue‐biting taps into rich discourses about self‐injury, personal agency, stoicism and madness. I argue that self‐injury was related to suicide in its assertion of control over the individual body, and could therefore operate as a type of protest. Moreover, stories of tongue‐biting from classical sources functioned as stoic exemplars of resistance to political tyranny. Revisions of The Spanish Tragedy shifted the meaning of this scene by placing increasing emphasis on Hieronimo's madness and the role of the supernatural forces in determining the play's events. overall, however, I argue that Hieronimo's tongue‐biting should be read as bringing together a number of cultural scripts, which interact and overlap to produce a morally ambiguous and richly allusive scene.
‘Regionalism’ and the global trade system
Authors: Pomfret Richard 
Published: June 2021

AbstractThe post‐1945 global trading system was designed around the principle of non‐discrimination. During the 1947–94 GATT era, regionalism and multilateralism were often viewed as antagonistic approaches to international trade, and preferential treatment within regional blocs was to be deterred. Since 1995, although regional trade agreements are monitored by the WTO Secretariat and presented as a threat to the system, regionalism poses little threat to the multilateral trading system. This paper argues that major twenty‐first century RTAs go beyond preferential tariff treatment to focus on deeper integration issues. Such issues are addressed outside the WTO because, despite new features of the international trade map since 1995 such as Internet use and global value chains, extension of WTO rules has proved difficult due to the requirement for consensus. The paper analyses the rise of megaregional agreements such as CPTPP and RCEP, the shift in EU policy from protecting domestic producers to facilitating imports from best global suppliers and the use of WTO plurilateral agreements within the context of providing rules fit for purpose in the modern global trading system.
Association of VEGFA polymorphisms with chronic obstructive pulmonary disease in Chinese Han and Mongolian populations
Authors: Gao Xiaoyu , Wang Xin , Jiao Na , Chen Jiyuan , Sun Dejun 
Published: June 2021

New Findings

What is the central question of this study?
Vascular endothelial growth factor A (VEGFA) is an important growth factor involved in changes in the bronchial microvascular and airway inflammation in chronic obstructive pulmonary disease (COPD) progression. What is the association of single nucleotide polymorphisms (SNPs) in VEGFA with the risk of COPD in the Chinese Han and Mongolian populations?

What is the main finding and its importance?
The effect of five SNPs in the VEGFA gene was analysed and compared between the Chinese Han and Mongolian populations. A contribution of risk alleles rs833068, rs833070 and rs3024997 to COPD was detected in the Chinese Mongolian population only. The study provided data from different populations to validate the role of VEGFA polymorphisms in COPD and provided reliable SNPs to predict the risk of COPD.

AbstractWe attempted to define the associations between single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGFA) gene and chronic obstructive pulmonary disease (COPD) in Chinese Han and Mongolian cohorts. Five SNPs were genotyped in cohorts of 684 COPD patients (350 Mongolian and 334 Han) and 784 healthy controls (350 Mongolian and 434 Han) using SNPscan multiplex PCR. SNP frequencies, genetic models and haplotypes were analysed using the chi‐square test. The associations of SNPs with COPD and linkage disequilibrium were analysed using logistic regression and HaploView, respectively. We found that only rs833068G>A, rs833070T>C and rs3024997G>A were significantly associated with the risk of COPD in the Mongolian population (rs833068: P < 0.001, rs833070: P < 0.001, rs3024997: P = 0.002). In the analysis of genotype distributions, the A/A and G/A genotypes in rs833068 (A/A: odds ratio (OR) = 0.313, P < 0.001; G/A: OR = 0.724, P < 0.001) and rs3024997 (A/A: OR = 0.513, P = 0.008; G/A: OR = 0.671, P = 0.008) and the C/C and T/C genotypes in rs833070 (C/C: OR = 0.435, P = 0.007; T/C: OR = 0.593, P = 0.007) were associated with protection against COPD in the Mongolian population. The haplotype frequencies of GCCAT and GTCGC were significantly different between the patients and controls (GCCAT: P = 0.001; GTCGC: P < 0.001) in the Mongolian population. Our findings indicate that five SNPs in the VEGFA gene play divergent roles in the Han and Mongolian populations. rs833068A, rs833070C and rs3024997A were observed to be associated with the risk of COPD in the Mongolian population.
On the Modeling of Anisotropic Fiber-Reinforced Polymer Flange Joints
Authors: Bouzid Abdel-Hakim , Vafadar Ali Khazraiyan , Ngô Anh Dung 
Published: June 2021

Abstract
Fiber-reinforced plastic composite flanges have recently experienced a spectacular development in the area of pressure vessels and piping. The current procedures used for the design of these flanges are a major concern because of their inappropriateness to address the anisotropic behavior of composite materials. The current ASME code section X related to the design procedure of composite flanges uses the same analytical method as that of section VIII division 2, which treats the flanges as isotropic materials such as metallic flanges. This study deals with Fiber-reinforced plastic (FRP) bolted flange joints integrity and bolt tightness. A new developed analytical FRP model that treats anisotropic flanges with and without a hub is presented. The model is based on the anisotropy and a flexibility analysis of all joint elements including the gasket, bolts, and flanges. It is supported experimentally with tests conducted on a real NPS 3 class 150 WN FRP bolted flange. Furthermore, three different numerical models based on three-dimensional anisotropic layered shell and solid element models were conducted to further compare and verify the results obtained from the new developed analytical approach. The results show that the new model has potential to be used as an alternative tool to FEM to analyze the stresses and deformation of problematic FRP bolted joints.
Advances in Computers and Information in Engineering Research, Volume 2
Authors: Michopoulos John G. , Paredis Christiaan J.J. , Rosen David W. , Vance Judy M. 
Published: June 2021

Book Series Editorial Board
John Michopoulos, Naval Research Laboratory
David Rosen, Georgia Institute of Technology
Chris Paredis, Georgia Institute of Technology
Judy Vance, Iowa State University
This is the second volume in this book series that aims to capture advances in computers and information in engineering research, especially by researchers and members of ASME’s Computers & Information in Engineering (CIE) Division.
The series is focusing on advances in computational methods, algorithms, tools, and processes on the cutting edge of research and development as they have evolved and/or have been reported during the last three to five annual CIE conferences. The series will provide a resource for enhancing engineering practice by enabling the understanding and the application of evolving and emerging technologies that impact critical engineering issues related to the topics and themes under CIE’s technical committees areas of interest, but not limited to:
Advanced Modeling and Simulation; Computer-Aided Product and Process Development; Systems Engineering, Information and Knowledge Management; Virtual Environments and Systems.
Highly localized upper mantle deformation during plate boundary initiation near the Alpine fault, New Zealand
Authors: Kidder Steven , Prior David J. , Scott James M. , Soleymani Hamid , Shao Yilun 
Published: June 2021

AbstractPeridotite xenoliths entrained in magmas near the Alpine fault (New Zealand) provide the first direct evidence of deformation associated with the propagation of the Australian-Pacific plate boundary through the region at ca. 25–20 Ma. Two of 11 sampled xenolith localities contain fine-grained (40–150 μm) rocks, indicating that deformation in the upper mantle was focused in highly sheared zones. To constrain the nature and conditions of deformation, we combine a flow law with a model linking recrystallized fraction to strain. Temperatures calculated from this new approach (625–970 °C) indicate that the observed deformation occurred at depths of 25–50 km. Calculated shear strains were between 1 and 100, which, given known plate offset rates (10–20 mm/yr) and an estimated interval during which deformation likely occurred (&lt;1.8 m.y.), translate to a total shear zone width in the range 0.2–32 km. This narrow width and the position of mylonite-bearing localities amid mylonite-free sites suggest that early plate boundary deformation was distributed across at least ∼60 km but localized in multiple fault strands. Such upper mantle deformation is best described by relatively rigid, plate-like domains separated by rapidly formed, narrow mylonite zones.
Surveillance of people with previously successfully treated diabetic macular oedema and proliferative diabetic retinopathy by trained ophthalmic graders: cost analysis from the EMERALD study
Authors: Maredza Mandy , Mistry Hema , Lois Noemi , Aldington Steve , Waugh Norman 
Published: June 2021

Background/aimsSurveillance of people with previously successfully treated diabetic macular oedema (DMO) and proliferative diabetic retinopathy (PDR) adds pressure on ophthalmology services. This study evaluated a new surveillance pathway entailing multimodal imaging reviewed by trained ophthalmic graders and compared it with the current standard care (face-to-face evaluation by an ophthalmologist).MethodsCost analysis of the new ophthalmic grader pathway, compared with the standard of care, from the perspective of the UK National Health Service, based on evidence from the Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy study. Resource use data were prospectively obtained including times to undertake each procedure. Effectiveness was assessed in terms of sensitivity and specificity of referral decisions in the grader pathway. Costs (SDs) were analysed per 100 patients separately for DMO and PDR at 2018/2019 costs.ResultsFor DMO, where sensitivity was very high (97%), the cost difference (savings) for the grader’s pathway would be £1390 per 100 patients. For PDR, the cost would be reduced by £461 for seven-field Early Treatment for Diabetic Retinopathy Study (ETDRS) images and by £1889 for ultrawide field images, per 100 patients. Ultrawide images required less time to be obtained and read than seven-field ETDRS. The real savings would be in ophthalmologist time, which could be then redirected to the evaluation of people at high risk of visual loss.ConclusionsSurveillance of people with previously successfully treated DMO and PDR by trained ophthalmic graders can achieve satisfactory results and release ophthalmologist time.Trial registration numbersNCT03490318,ISRCTN10856638.
Decoy bypass for appetite suppression in obese adults: role of synergistic nutrient sensing receptors GPR84 and FFAR4 on colonic endocrine cells
Authors: Peiris Madusha , Aktar Rubina , Reed David , Cibert-Goton Vincent , Zdanaviciene Ausra , Halder Writaja , Robinow Adam , Corke Simon , Dogra Harween , Knowles Charles H , Blackshaw Ashley 
Published: June 2021

ObjectiveColonic enteroendocrine cells (EECs) store and release potent anorectic hormones that are key regulators of satiety. EECs express multiple nutrient sensing receptors, particularly for medium-chain fatty acids (MCFAs): GPR84 and FFAR4. Here we show a non-surgical approach with targeted colonic delivery of MCFA, which induces EEC and neuronal activation leading to anorectic effects.DesignA randomised, double-blind, placebo-controlled, cross-over study was performed in obese adults given combined GPR84 and FFAR4 agonists in colonic release capsules before meals. We measured serum hormones, energy intake and appetite perception. Cell type, activation by agonists and hormone/serotonin release were determined in human colonic explants. Mouse colonic afferent nerve responses to nutrients/mediators were recorded electrophysiologically.ResultsSubjects receiving GPR84 and FFAR4 agonists had reduced overall calorific intake and increased postprandial levels of PYY versus placebo. Receptors including GPR84 and FFAR4 were coexpressed on human colonic EEC. Activation of GPR84 exclusively induced intracellular pERK, whereas FFAR4 selectively activated pCaMKII. Coactivation of GPR84 and FFAR4 induced both phosphoproteins, and superadditive release of GLP-1 and PYY. Nutrients and hormones convergently activated murine colonic afterent nerves via GLP-1, Y2 and 5-HT3 receptors.ConclusionsColonic GPR84 and FFAR4 agonists reduce energy intake and increase postprandial PYY in obese adults. Human colonic EECs coexpress these receptors, which activate cells via parallel intracellular pathways and synergistically evoke hormone release. Further synergism occurs in sensory nerve responses to MCFA and EEC mediators. Thus, synergistic activation of colonic endocrine cells via nutrient receptors is an important target for metabolic regulation.Trail registration numberNCT04292236.
Transradial cerebral angiography becomes more efficient than transfemoral angiography: lessons from 500 consecutive angiograms
Authors: Wilkinson D Andrew , Majmundar Neil , Catapano Joshua S , Fredrickson Vance L , Cavalcanti Daniel D , Baranoski Jacob F , Rutledge Caleb , Ducruet Andrew F , Albuquerque Felipe C 
Published: June 2021

BackgroundTransradial arterial access (TRA) for cerebral diagnostic angiography is associated with fewer access site complications than transfemoral access (TFA). However, concerns about increased procedure time and radiation exposure with TRA may slow its adoption. Our objective was to measure TRA rates of success and fluoroscopy time per vessel after ‘radial-first’ adoption and to compare these rates to those obtained with TFA.MethodsWe examined 500 consecutive cerebral angiograms on an intent-to-treat basis during the first full year of radial-first adoption, recording patient and procedural characteristics and outcomes.ResultsOver a 9-month period at a single center, 457 of 500 angiograms (91.4%) were performed with intent-to-treat via TRA, and 431 cases (86.2%) were ultimately performed via TRA. One patient (0.2%) experienced a temporary neurologic deficit in the TRA group, and none (0%) did in the TFA group (p=0.80). The mean±SD fluoroscopy time per vessel decreased significantly from the first half of the study to the second half for TRA (5.0±3.8 vs 3.4±3.5 min/vessel; p<0.001), while TFA time remained unchanged (3.7±1.8 vs 3.5±1.4 min/vessel; p=0.69). The median fluoroscopy time per vessel for TRA became faster than that for TFA after 150 angiograms.ConclusionOf 500 consecutive angiograms performed during the first full year of radial-first implementation, 86.2% were performed successfully using TRA. TRA efficiency exceeded that of TFA after 150 angiograms. Concerns about the length of procedure or radiation exposure should not be barriers to TRA adoption.
Omeprazole-clopidogrel interaction and neurovascular complications after flow-diverter device placement
Authors: Catapano Joshua S , Srinivasan Visish M , Wakim Andre A , Lundberg Jaclyn N , Rutledge Caleb , Cole Tyler S , Baranoski Jacob F , Fredrickson Vance L , Rahmani Redi , Albuquerque Felipe C , Ducruet Andrew F 
Published: June 2021

BackgroundOmeprazole is a common proton pump inhibitor that interferes with the hepatic activation of clopidogrel and potentially reduces its platelet-inhibitory effect. Omeprazole has been shown to increase P2Y12levels and adverse cardiovascular outcomes in patients treated with drug-eluting stents. However, omeprazole use among patients treated with flow-diverting stents for intracranial aneurysms has not been evaluated.MethodsAll patients with placement of a flow-diverting device for treatment of an intracranial aneurysm at a tertiary institution from January 1, 2014, to December 31, 2018, were retrospectively analyzed. Inclusion criteria included documented clopidogrel administration, available P2Y12levels, and thorough documentation of administration of other medications, including omeprazole.ResultsA total of 138 patients met the inclusion criteria. Sixteen patients (12%) were receiving omeprazole and clopidogrel at treatment. P2Y12reactivity was significantly greater in the omeprazole cohort (mean P2Y12level, 250 P2Y12reaction units (PRU)) than in the control cohort (mean P2Y12level, 112PRU) (P<0.001). Furthermore, a greater proportion of patients had a P2Y12level >180 PRU in the omeprazole cohort (14 of 16 [88%] vs 24 of 122 [20%]; P<0.001; OR [95% CI], 29 [6–134]).ConclusionOmeprazole was associated with a significant increase in the mean P2Y12reactivity level among patients with intracranial aneurysms treated with flow-diverting devices who received clopidogrel. However, receipt of omeprazole was not associated with an increased risk of ischemic events or stent stenosis. For neuroendovascular patients who are treated with a flow diverter while receiving clopidogrel, alternative gastrointestinal medication regimens should be considered.
Cadaveric study investigating the phrenic-sparing volume for anterior suprascapular nerve block
Authors: Maikong Naraporn , Kantakam Perada , Sinthubua Apichat , Mahakkanukrauh Pasuk , Tran De Q , Leurcharusmee Prangmalee 
Published: June 2021

Background
This cadaveric study investigated the maximum effective volume of dye in 90% of cases (MEV90), required to stain the suprascapular nerve while sparing the phrenic nerve during the performance of an anterior suprascapular nerve block.

Methods

In cadaveric neck specimens, using ultrasound guidance, the block needle was advanced until its tip was positioned underneath the omohyoid muscle next to the suprascapular nerve. The dye was injected in order to achieve circumferential spread around the latter. Successful phrenic-sparing suprascapular nerve block was defined as the non-staining of the phrenic nerve on dissection. Volume assignment was carried out using a Biased Coin Design, whereby the volume of dye administered to each cadaveric specimen depended on the response of the previous one. In case of failure (ie, stained phrenic nerve), the next one received a lower volume (defined as the previous volume with a decrement of 2 mL). If the previous cadaveric specimen had a successful block (ie, non-stained phrenic nerve), the next one was randomized to a higher volume (defined as the previous volume with an increment of 2 mL), with a probability of
b
=0.11, or the same volume, with a probability of 1 –
b
=0.89.

Results
Thirty-one cadavers (56 cadaveric neck specimens) were included in the study. Using isotonic regression and bootstrap CI, the MEV90 for phrenic-sparing anterior suprascapular nerve block was estimated to be 4.2 mL (95% CI 3.0 to 5.0 mL). The probability of a successful response was estimated to be 0.90 (95% CI 0.84 to 0.96).

Conclusion
For ultrasound-guided anterior suprascapular nerve block, the MEV90 of dye required to spare the phrenic nerve is 4.2 mL. Further studies are required to correlate this finding with the MEV90 of local anesthetic in live subjects.
First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody–Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors
Authors: Maitland Michael L. , Sachdev Jasgit C. , Sharma Manish R. , Moreno Victor , Boni Valentina , Kummar Shivaani , Stringer-Reasor Erica , Lakhani Nehal , Moreau Allison R. , Xuan Dawei , Li Ray , Powell Eric L. , Jackson-Fisher Amy , Bowers Michelle , Alekar Shilpa , Xin Xiaohua , Tolcher Anthony W. , Calvo Emiliano 
Published: June 2021

Abstract

Purpose:
We investigated safety, tolerability, pharmacokinetics, and antitumor activity of the protein tyrosine kinase 7 (PTK7)-targeted, auristatin-based antibody–drug conjugate (ADC) PF-06647020/cofetuzumab pelidotin (NCT02222922).

Patients and Methods:
Patients received PF-06647020 intravenously every 3 weeks at 0.2–3.7 mg/kg or every 2 weeks at 2.1–3.2 mg/kg, in sequential dose escalation, following a modified toxicity probability interval method. In dose expansion, pretreated patients with advanced, platinum-resistant ovarian cancer, non–small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC) received PF-06647020 2.8 mg/kg every 3 weeks.

Results:
The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia, fatigue, headache, neutropenia, and vomiting (45%–25%); 25% of patients had grade ≥ 3 neutropenia. Two patients experienced dose-limiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.8 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27% in ovarian cancer (n = 63), 19% in NSCLC (n = 31), and 21% in TNBC (n = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC.

Conclusions:
This PTK7-targeted ADC demonstrated therapeutic activity in previously treated patients with ovarian cancer, NSCLC, and TNBC at a dose range of 2.1–3.2 mg/kg, supporting further clinical evaluation to refine dose, schedule, and predictive tissue biomarker testing in patients with advanced malignancies.