bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarker analysis from CheckMate 214: nivolumab plus ipilimumab versus sunitinib in renal cell carcinoma
Authors: Motzer Robert J , Choueiri Toni K , McDermott David F , Powles Thomas , Vano Yann-Alexandre , Gupta Saurabh , Yao Jin , Han Celine , Ammar Ron , Papillon-Cavanagh Simon , Saggi Shruti S , McHenry M Brent , Ross-Macdonald Petra , Wind-Rotolo Megan 
Published: March 2022

BackgroundThe phase 3 CheckMate 214 trial demonstrated higher response rates and improved overall survival with nivolumab plus ipilimumab versus sunitinib in first-line therapy for advanced clear-cell renal cell carcinoma (RCC). An unmet need exists to identify patients with RCC who are most likely to benefit from treatment with nivolumab plus ipilimumab.MethodsIn exploratory analyses, pretreatment levels of programmed death ligand 1 were assessed by immunohistochemistry. Genomic and transcriptomic biomarkers (including tumor mutational burden and gene expression signatures) were also investigated.ResultsBiomarkers previously associated with benefit from immune checkpoint inhibitor-containing regimens in RCC were not predictive for survival in patients with RCC treated with nivolumab plus ipilimumab. Analysis of gene expression identified an association between an inflammatory response and progression-free survival with nivolumab plus ipilimumab.ConclusionsThe exploratory analyses reveal relationships between molecular biomarkers and provide supportive data on how the inflammation status of the tumor microenvironment may be important for identifying predictive biomarkers of response and survival with combination immunotherapy in patients with RCC. Further validation may help to provide biomarker-driven precision treatment for patients with RCC.
Cardiovascular outcomes in obstructive sleep apnoea and implications of clinical phenotyping on effect of CPAP treatment
Authors: Xu Pei-Hang , Fong Daniel Y T , Lui Macy M S , Lam David C L , Ip Mary Sau Man 
Published: March 2022

BackgroundThere is a growing awareness of the heterogeneity of obstructive sleep apnoea (OSA). Clinical trials of CPAP treatment on cardiovascular protection have been mostly negative. We aimed to assess the association between polysomnographic parameters and incident major adverse cardiovascular events (MACEs), and to investigate if the CPAP effect could be better delineated among clinical subgroups.MethodsThis sleep cohort study was conducted using a clinical database and territory-wide electronic health administration data in Hong Kong. Cox regressions were used to calculate HRs. Latent class analysis was used to cluster patients with OSA according to clinical and polysomnographic features.ResultsOf 1860 eligible Chinese subjects who underwent polysomnography (2006–2013), 1544 (83%) had OSA. Over median follow-up of 8.3 years, 278 (14.9%) experienced MACEs. Apnoea–hypopnoea index (AHI) did not predict MACEs (HR: 0.95; 95% CI 0.76 to 1.17), whereas sleep time with oxygen saturation <90% (TST90) (HR: 1.41; 95% CI 1.10 to 1.81) was an independent predictor of MACEs, as were wake and nocturnal heart rate. In moderate–severe OSA (n=1108) who were indicated for CPAP treatment, regular CPAP was not associated with reduction of incident MACEs. Further cluster analysis identified a subgroup (n=333) who was younger, more obese, had more severe OSA (higher AHI and TST90) and more cardiovascular risks, in whom regular CPAP was associated with a lower risk of MACEs (HR:0.49, 95% CI 0.25 to 0.95).ConclusionsOSA-related TST90 and mean heart rate, but not AHI, were robust predictors of MACEs. A clinical phenotype subgroup who demonstrated beneficial effect of CPAP treatment was identified.
Acoustic regular black hole in fluid and its similarity and diversity to a conformally related black hole
Authors: Lan Chen , Miao Yan-Gang , Zang Yi-Xiong 
Published: March 2022

AbstractWe address an interesting question in the present paper that whether the acoustic gravity can be applied as a tool to the study of regular black holes. For this purpose, we construct a general acoustic regular black hole in the spherically symmetric fluid, where its regularity is verified from the perspective of finiteness of curvature invariants and completeness of geodesics. In particular, we find that the acoustic interval not only looks like a line element of a conformally related black hole in which the fluid density can be regarded as a conformal factor, but also gives rise to a non-vanishing partition function which coincides with that of a conformally related black hole. As an application, we provide a specific acoustic regular black hole model, investigate its energy conditions and compute its quasinormal modes. We note that the strong energy condition of our model is violated completely outside the horizon of the model but remains valid in some regions inside the horizon, which may give a new insight into the relation between the regularity and strong energy condition. Moreover, we analyze the oscillating and damping features of our model when it is perturbed.
CORAL: COde RepresentAtion learning with weakly-supervised transformers for analyzing data analysis
Authors: Zhang Ge , Merrill Mike A. , Liu Yang , Heer Jeffrey , Althoff Tim 
Published: March 2022

AbstractLarge scale analysis of source code, and in particular scientific source code, holds the promise of better understanding the data science process, identifying analytical best practices, and providing insights to the builders of scientific toolkits. However, large corpora have remained unanalyzed in depth, as descriptive labels are absent and require expert domain knowledge to generate. We propose a novel weakly supervised transformer-based architecture for computing joint representations of code from both abstract syntax trees and surrounding natural language comments. We then evaluate the model on a new classification task for labeling computational notebook cells as stages in the data analysis process from data import to wrangling, exploration, modeling, and evaluation. We show that our model, leveraging only easily-available weak supervision, achieves a 38% increase in accuracy over expert-supplied heuristics and outperforms a suite of baselines. Our model enables us to examine a set of 118,000 Jupyter Notebooks to uncover common data analysis patterns. Focusing on notebooks with relationships to academic articles, we conduct the largest study of scientific code to date and find that notebooks which devote an higher fraction of code to the typically labor-intensive process of wrangling data in expectation exhibit decreased citation counts for corresponding papers. We also show significant differences between academic and non-academic notebooks, including that academic notebooks devote substantially more code to wrangling and exploring data, and less on modeling.
Achieving CS for all could take decades
Authors: Guzdial Mark 
Published: March 2022

The
Communications
website, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Mark Guzdial assesses the outlook for students taking computer science classes at the high school level.
Design and Analysis of a Compact Superwideband Millimeter Wave Textile Antenna for Body Area Network
Authors: Khan Mohammad Monirujjaman , Islam Kaisarul , Shovon Md. Nakib Alam , Abbasi Muhammad Inam , Bourouis Sami , Hussein Hany S. , Alshazly Hammam 
Published: March 2022

The advancement of wireless technology has led to an exponential increase in the usage of smart wearable devices. Current wireless bands are getting more congested, and we are already seeing a shift towards millimeter wave bands. This paper proposes a design for a millimeter wave textile antenna for body-centric communications. The antenna has a quasi-self-complementary (QSC) structure. The radiating patch is a semicircular disc with a radius of 1.855 mm and is fed by a 5.07 mm long, 0.70 mm wide microstrip feedline. A complementary leaf-shaped slot is etched in the ground plane. The radiating disc and the ground plane are attached to a 1.5 mm thick nonconducting 100% polyester substrate. The antenna has an overall dimension of

10

mm
×
7.00

mm

. In free space, the antenna achieved a superwideband impedance bandwidth that covers the Ka, V, and W bands designated by IEEE. At 60 GHz, the antenna’s radiation efficiency was 89.06%, with a maximum gain of 5.7 dBi. Millimeter waves are easily blocked by obstacles and have low skin penetration depth. On-body investigations were carried out by placing the antenna on a human phantom at five different distances. No significant amount of back radiation was observed. The radiation efficiency decreased to 67.48% at 2 mm away from the phantom, while the maximum gain slightly increased. The efficiency and radiation patterns improved as the distance between the antenna and the phantom gradually increased. Ten different textile substrates were also used to test the antenna. With a few exceptions, the free space and on-body simulation results were very similar to polyester. The design and simulation of the antenna were carried out using the CST microwave studio.
Abstract 462: Dose Matters: Omega-3 Polyunsaturated Fatty Acid Supplementation at 3600 mg/d but Not 900 mg/d Reduces Inflammatory Response to Evoked Endotoxemia in Healthy Volunteers
Authors: Ferguson Jane F , Mulvey Claire K , Shah Rhia , Patel Parth , Kong Stephanie , Tabita-Martinez Jennifer , Terembula Karen , Mehta Nehal N , Shah Rachana , Reilly Muredach P 
Published: March 2022

Inflammation is a key component in the pathogenesis of cardiometabolic disease. Certain anti-inflammatory compounds may improve atherosclerotic disease risk by modulating systemic and vascular inflammation. Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may represent a dietary mechanism for improving cardiometabolic health through reduction of inflammation. We hypothesized that n-3 PUFA supplementation would reduce the inflammatory response to evoked endotoxemia in healthy humans.
In the Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia study (FFAME Study), we recruited healthy individuals (N=60; age 18-45; BMI 18-30; 43% Female; 65% Caucasian, 20% African, 15% Asian ancestry) randomized to one of three treatment groups; n-3 PUFA (Lovaza 465mg EPA/375mg DHA) supplemented at either 900mg per day or 3,600mg per day, or placebo. An additional arm of the study included a fenofibrate treatment group, not included here. Participants were treated for ∼8 weeks then admitted to the research center for an endotoxin challenge of lipopolysaccharide (LPS) 0.6ng/kg intravenously. Multiple clinical and biochemical variables were assessed throughout, and analyzed using RM-ANOVA with Bonferroni post-hoc tests for between group differences.
Compared to placebo, high-dose (P<0.01) but not low dose n-3 PUFA reduced peak temperature, but not heart rate or blood pressure, responses to endotoxin. Cytokines and inflammatory markers (IL-6, TNFα, IL-10, CRP, SAA) were decreased in high-dose n-3 PUFA vs. placebo . Interestingly, these inflammatory markers tended to be increased in low-dose n-3 PUFA vs. placebo, with a significant difference in the effect of low-dose vs. high-dose n-3 PUFA on peak IL-6 (P<0.001), TNFα (P<0.01) and IL-10 (P<0.05). Plasma lipids tended to decrease in both n-3 PUFA groups compared with placebo, with equal lipid-lowering effect of 900 or 3,600 mg/day on cholesterol, ApoA-I, and triglycerides.
The specific anti-inflammatory properties of n-3 PUFA appear to be dose-specific, with high doses (3,600mg/day) leading to attenuation of the inflammatory response to evoked endotoxemia, while lower doses (900mg/day) do not reduce the inflammatory response despite similar reductions in plasma lipids.
Abstract 532: Periadventitial Adenoviral Ang-1/2 Gene Transfer Interferes with Atherosclerotic Plaque Progression and Angiogenesis in the Carotid Artery of LDLr
-/-
ApoB100/100 Mice
Authors: Lappalainen Jari P , Theelen Thomas , Verheyen Fons , Biessen Erik A , Aavik Einari , Anisimov Andrey , Alitalo Kari , Daemen Mat J , Sluimer Judith C , Ylä-Herttuala Seppo 
Published: March 2022

Accumulation of macrophages, red blood cells and lipids in atherosclerotic plaques is associated with plaque rupture. It has been shown that macrophages and erythrocytes can enter the plaque also via plaque microvasculature originating from the adventitia. Furthermore, it has been reported that in advanced or ruptured human coronary lesions the microvessel density is increased and these microvessels are leaky. The leaky phenotype is characterized by poor pericyte coverage and dysfunctional inter-endothelial junctions.
As angiopoietins are involved in angiogenic growth and maturation, we hypothesized that periadventitial Ang-1 or Ang-2 gene transfer would reduce atherogenesis and affect microvasculature in mouse carotid artery.

To study this, atherosclerosis was induced by placing a perivascular silastic collar around the carotid artery of LDLr
-/-
ApoB100/100 mice fed a high cholesterol (0,15 %) diet for 3 weeks. Simultaneous to surgery adenoviral gene transfer (5μl, 5 x 107 pfu/ml) of either Ang-1, Ang-2 or LacZ as a control was applied to the carotid artery (20 mice per group). After 1 or 5 weeks follow-up on high cholesterol diet mice were sacrificed. Plaque size and microvessel density were analyzed with morphometry software (Leica Qwin) using cross-sections stained with hematoxylin and eosin or CD31 respectively. Microvessel ultrastructure was studied using electron microscopy.

Ang-2 gene transfer led to significantly smaller plaque area and plaque volume 5 weeks after collar placement compared to LacZ group (2,7 fold, p<0,001 and 3,9 fold, p<0,01 respectively). Also the microvessel density in intima, media and adventitia was lower in the Ang-2 group compared to LacZ (4,5 fold, p<0,05; 7,5 fold p<0,05 and 11,8 fold p<0,05 respectively). Ang-1 gene transfer led to a non-significant trend towards smaller lesions and lower microvessel density compared to LacZ gene transfer. Plaque phenotype was quite fibrous in all groups at 5 weeks, although lesions in Ang-2 group were most human atheroma-like. Electron microscopy showed intact pericyte coverage and endothelial junctions of microvessels in all groups. Endothelial cell morphology after Ang-1 gene transfer showed less filopodia and cytoplasmic vacuoles compared to Ang-2 and LacZ, suggestive of a quiescent phenotype.

In conclusion:
Ang-2 over expression in mouse carotid arteries led to smaller plaque size and lower microvessel density, suggesting the involvement of angiopoietin signaling in angiogenesis of the atherosclerotic vessel wall.
Abstract 110: Novel Apoc-II Mimetic Peptide Activates LPL and Decreases Serum Triglycerides in Mice.
Authors: Amar Marcelo J , Freeman Lita , Sviridov Denis , Ashan Lusana , Stonik John , Demosky Stephen , Remaley Alan 
Published: March 2022

BACKGROUND
Elevated triglycerides (TG) over 1000 mg/dL in patients with severe dyslipidemias can lead to pancreatitis. ApoA-I and its mimetic peptides, which are currently being explored as therapeutic agents for acute coronary syndrome, can also markedly increase serum TG.

OBJECTIVE
To examine the mechanism behind hypertriglyceridemia caused by apoA-I mimetic peptides and to develop novel peptides based on apoC-II for activating LPL and decreasing serum TG.

METHODS
The 18A-CII peptide was synthesized, using standard solid phase FMOC chemistry, and contains the 18A amphipathic helix (DWLKAFYDKVAEKLKEAF) linked to the last helix of apoC-II (AMSTYTGIFTDQVLSVLKGEE) with an intervening Pro residue.

RESULTS
High doses of the 5A apoA-I mimetic peptide (>120mg/kg) raised serum TG between 1000-1200mg/dL in non-fasting C57B/6 mice after a single bolus. By FPLC analysis, most of the TG were observed in VLDL. By in vitro lipolysis studies, 5A was found to be a direct inhibitor of LPL, whereas 18A-CII activated LPL. An inactive analogue of 18A-CII, containing 4 Ala substitutions for the residues (18A-P-AMSTATGAFTAAVLSVLKGEE) shown to bind to LPL, inhibited LPL activity. Intravenous injection of 30mg/kg of 18A-CII in C57BL/6 mice showed a 52% of reduction of LDL-C. In ApoE KO and LDLR KO mice, treatment with 18A-CII led to a marked TG reduction at 4 h of 85% and 53%, respectively, when compared to sham injected mice. Co-administration of 5A along with 18A-CII in mice still resulted in an increase in HDL-C observed with the 5A peptide but with no increase in serum TG. In order to test the effect of 18A-CII in humans, plasma from an ApoC-II deficient patient was treated with LPL. Addition of 18A-CII or apoC-II was similarly effective in restoring normal level of lipolysis after the addition of LPL.

CONCLUSION
In summary, 18A-CII is able to activate LPL both in vitro and in vivo and reduces serum TG levels and can overcome the inhibition of LPL observed with 5A. These results suggest that 18A-CII may be of value either in combination with an apoA-I mimetic peptide and or can be possibly be used to treat apoC-II deficiency.
Abstract 121: Role of Leukocyte Gpr120 in Atherosclerosis Development in Polyunsaturated Fatty Acid Diet Induced Atheroprotection in LDLrKO Mice
Authors: Shewale Swapnil V , Boudyguina Elena , Bi Xin , Zhu Xuewei , MIshra Nilamadhab , Oh Da Young , Olefsky Jorrold , Parks John 
Published: March 2022

Introduction
Diets enriched in polyunsaturated n-3 and n-6 fatty acids (PUFAs) are atheroprotective. FO, which is enriched in n-3 PUFAs, reduces plasma lipids and has anti-inflammatory effects. Recent studies have shown that GPR120 is the physiological n-3 PUFA receptor and its ligation by n-3 PUFAs blunts pro-inflammatory signaling pathways. However, the role of GRP120 in atherogenesis is unknown.

Hypothesis
We hypothesized that leukocyte GPR120 contributes to the atheroprotective effects of n-3, but not n-6, PUFUs by ligation of GRP120, resulting in decreased leukocyte inflammation.

Methods
Female LDLr-/- mice were transplanted with bone marrow from male wild type or GPR120 knockout mice. After recovery from transplantation, recipient LDLr-/- mice were fed atherogenic diets containing 0.2% cholesterol and enriched in saturated/monounsaturated fat (palm oil, PO), n-6 PUFA (borage, BO), a botanical n-3 PUFA (echium oil, EO) or FO for 16 weeks. Periodic blood samples were taken for lipid and lipoprotein measurements and aortas were harvested after 16 weeks of diet feeding to quantify atherosclerosis.

Results
Compared to the PO group, mice fed BO, EO and FO had significantly lower plasma total and very low density lipoprotein (VLDL) cholesterol concentrations. EO and FO groups also had lower plasma triglyceride concentrations compare to PO and BO fed mice. Compared to the PO group, mice fed BO and EO had significantly reduced aortic CE, comparable to the FO group. However, lack of leukocyte GPR120 did not significantly affect plasma lipids or atherosclerosis severity within any diet group.

Conclusion
Atherogenic diets enriched in n-6 and n-3 PUFAs derived from botanical oils (BO and EO) were as atheroprotective as FO compared to a diet containing saturated/monounsaturated fat (PO). Furthermore, lack of leukocyte GPR120 had minimal effect on plasma lipid/lipoprotein profile and atherosclerosis, suggesting that n-3 as well as n-6 PUFA associated atheroprotection is primarily due to reduction of VLDL-cholesterol in LDLr-/- mice.
Abstract 126: Identification of an Individual With Extremely High HDL-C Who is Homozygous for a Loss-of-function Mutation in Scavenger Receptor BI (SR-BI) and Functional Characterization of the Mutation
Authors: Zanoni Paolo , Larach Dan , Peloso Gina , Rodrigues Amrith , Tohyama Junichiro , Billheimer Jeffrey T , Kathiresan Sekar , Cuchel Marina , Rader Daniel J 
Published: March 2022

Background
The role of SR-BI in human HDL metabolism and physiology has yet to be fully clarified and no humans with homozygous SR-BI deficiency have been reported to date. We report the identification of an individual with HDL-C > 160 mg/dL who is homozygous for a Pro376Leu mutation in the SCARB1 gene.

Methods
In silico tests were performed to evaluate the effect of the variant on protein function (Polyphen 2 and Condel) and on protein secondary structure (Raptor X and NetSurfP). HDL binding, cholesteryl-ether (CE) uptake and the effect on cholesterol efflux were assessed in vitro in COS7 cells. Serum efflux was measured using J774 macrophages. Subcellular distribution of the mutant protein was assessed through biotinylation of cell surface proteins and trypsin sensitivity.

Results
HDL-C was 166mg/dl and apoA-I was and 275 mg/dl in the homozygous subject. HDL particles were much larger and enriched in cholesterol and triglycerides as compared with a control subject matched for HDL-C levels. In silico analysis predicted that the variant would cause secondary structure modifications and be deleterious for function. In vitro studies in COS7 cells transfected with the P376L mutation showed a strongly diminished HDL binding (-69%) and CE uptake (-79%) as compared to cells transfected with the WT form of SR-BI. Efflux was also impaired (-59%). The biotinylation and trypsin sensitivity assays showed a defect in the delivery of the mutant protein to the cell surface.

Conclusions
We report the first identification of a homozygote for a loss-of-function mutation in SR-BI; the phenotype includes extremely elevated HDL-C levels. The P376L mutation in SCARB1 gene results in marked loss of SR-BI function at least in part by impairing the transport of the protein to the cell surface.
Abstract 139: Post-Translational Modifications of Connexins in Neointimal Formation
Authors: Johnstone Scott R , Martin Patricia E , Lampe Paul D , Isakson Brant E 
Published: March 2022

Intro
Connexins are integrally involved in the process of cell division and atherosclerosis. Recently we identified that connexin 43 (Cx43) could significantly alter smooth muscle cell proliferation in vitro and in vivo. We now investigate the involvement of Cx43 in human neointimal formation and the mechanisms through which it controls cell cycle.

Methods
Protein interactions between Cx43 were identified in smooth muscle cells through co-immunoprecipitation, immuno-transmission electron microscopy and proximity ligation assays. Novel mice with alanine substitutions at MAPK phosphorylated serines (Cx43-MK4A) were investigated. Samples from diseased and non-diseased human coronary arteries were assessed for level of Cx43 phosphorylation and interactions. Ex vivo saphenous vein explant cultures were used to assess the contribution of Cx43 phosphorylation to human neointimal formation. In vitro studies were performed in human coronary artery smooth muscle cells and in mouse aortic smooth muscle cells from wild type and knockout mice.

Results
We demonstrate that levels of Cx43 are increased in human atherosclerotic plaques and that neointimal formation in human tissues corresponds to a significant increase in Cx43 phosphorylation and cyclin E interactions. In vitro, Cx43 facilitates trafficking of cyclin E to the nucleus in a manner that is dependent on its MAPK phosphorylation.

Discussion
Our studies suggest that in human vascular disease and neointimal formation Cx43 interactions with cyclin E are elevated. Further, Cx43 facilitates the transport of the cell cycle promoter cyclin E to the nucleus suggesting that this is a critical component of VSMC proliferation and therefore could be a novel target in the prevention of neointimal formation in human vascular disease.