bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situimmunization of a TLR9 agonist virus-like particle enhances anti-PD1 therapy
Authors: Cheng Yinwen , Lemke-Miltner Caitlin D , Wongpattaraworakul Wattawan , Wang Zhaoming , Chan Carlos H F , Salem Aliasger K , Weiner George J , Simons Andrean L 
Published: October 2020

BackgroundCMP-001 is a novel Toll-like receptor-9 agonist that consists of an unmethylated CpG-A motif-rich G10 oligodeoxynucleotide (ODN) encapsulated in virus-like particles.In situvaccination of CMP-001 is believed to activate local tumor-associated plasmacytoid dendritic cells (pDCs) leading to type I interferon secretion and tumor antigen presentation to T cells and systemic antitumor T cell responses. This study is designed to investigate if CMP-001 would enhance head and neck squamous cell carcinoma (HNSCC) tumor response to anti-programmed cell death protein-1 (anti-PD-1) therapy in a human papilloma virus-positive (HPV+) tumor mouse model.MethodsImmune cell activation in response to CMP-001±anti-Qβ was performed using co-cultures of peripheral blood mononuclear cells and HPV+/HPV- HNSCC cells and then analyzed by flow cytometry.In situvaccination with CMP-001 alone and in combination with anti-PD-1 was investigated in C57BL/6 mice-bearing mEERL HNSCC tumors and analyzed for anti-Qβ development, antitumor response, survival and immune cell recruitment. The role of antitumor immune response due to CMP-001+anti-PD-1 treatment was investigated by the depletion of natural killer (NK), CD4+T, and CD8+T cells.ResultsResults showed that the activity of CMP-001 on immune cell (pDCs, monocytes, CD4+/CD8+ T cells and NK cells) activation depends on the presence of anti-Qβ. A 2-week ‘priming’ period after subcutaneous administration of CMP-001 was required for robust anti-Qβ development in mice.In situvaccination of CMP-001 was superior to unencapsulated G10 CpG-A ODN at suppressing both injected and uninjected (distant) tumors.In situvaccination of CMP-001 in combination with anti-PD-1 therapy induced durable tumor regression at injected and distant tumors and significantly prolonged mouse survival compared with anti-PD-1 therapy alone. The antitumor effect of CMP-001+anti-PD-1 was accompanied by increased interferon gamma (IFNγ)+CD4+/CD8+T cells compared with control-treated mice. The therapeutic and abscopal effect of CMP-001+ anti-PD-1 therapy was completely abrogated by CD8+T cell depletion.ConclusionsThese results demonstrate thatin situvaccination with CMP-001 can induce both local and abscopal antitumor immune responses. Additionally, the antitumor efficacy of CMP-001 combined with α-PD-1 therapy warrants further study as a novel immunotherapeutic strategy for the treatment of HNSCC.
CRISPR–Cas9/long-read sequencing approach to identify cryptic mutations in BRCA1 and other tumour suppressor genes
Authors: Walsh Tom , Casadei Silvia , Munson Katherine M , Eng Mary , Mandell Jessica B , Gulsuner Suleyman , King Mary-Claire 
Published: October 2020

AbstractCurrent clinical approaches for mutation discovery are based on short sequence reads (100–300 bp) of exons and flanking splice sites targeted by multigene panels or whole exomes. Short-read sequencing is highly accurate for detection of single nucleotide variants, small indels and simple copy number differences but is of limited use for identifying complex insertions and deletions and other structural rearrangements. We used CRISPR-Cas9 to excise complete BRCA1 and BRCA2 genomic regions from lymphoblast cells of patients with breast cancer, then sequenced these regions with long reads (>10 000 bp) to fully characterise all non-coding regions for structural variation. In a family severely affected with early-onset bilateral breast cancer and with negative (normal) results by gene panel and exome sequencing, we identified an intronic SINE-VNTR-Alu retrotransposon insertion that led to the creation of a pseudoexon in the BRCA1 message and introduced a premature truncation. This combination of CRISPR–Cas9 excision and long-read sequencing reveals a class of complex, damaging and otherwise cryptic mutations that may be particularly frequent in tumour suppressor genes replete with intronic repeats.
Determining factors related to impaired spinal and hip mobility in patients with axial spondyloarthritis: longitudinal results from the DESIR cohort
Authors: Carvalho Pedro D , Ruyssen-Witrand Adeline , Fonseca Joao , Marreiros Ana , Machado Pedro M 
Published: October 2020

ObjectiveTo investigate the determinants of impaired spinal and hip mobility in patients with early axial spondyloarthritis (axSpA).MethodsFive-year longitudinal data from the DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR) cohort were analysed. Associations were investigated using generalised estimating equations, using Bath Ankylosing Spondylitis Metrology Index (BASMI) linear or each of the five components of BASMI as dependent variables, and clinical and demographic variables as independent variables in univariable models. Multivariable analyses were performed, adjusting for potential confounders.ResultsData from 644 patients and 5152 visits were analysed. Higher BASMI values were independently and positively associated with Ankylosing Spondylitis Disease Activity Score C reactive protein (ASDAS-CRP) (adjusted B (adjB)=0.21; 95% CI=0.15 to 0.28), MRI spinal inflammation score (adjB=0.11; 95% CI=0.04 to 0.19), enthesitis score (adjB=0.02; 95% CI=0.01 to 0.04) and age (adjB=0.02; 95% CI=0.01 to 0.03). All BASMI components were independently associated with ASDAS-CRP and MRI spinal inflammation, except for maximal intermalleolar distance (reflecting hip mobility), which was not associated with MRI spinal inflammation.ConclusionIn early axSpA, spinal mobility impairment is independently determined by clinical disease activity, MRI spinal inflammation, enthesitis and age. The influence of spinal inflammation prevails in early axSpA, as opposed to spinal structural damage, which may become more relevant in later disease stages.
Adenocarcinoma as a novel complication following incisional colopexy in a dog
Authors: Taylor Oliver , Knight Rebekah , Owen Laura 
Published: October 2020

This report describes the development of an adenocarcinoma at a pexy site in an eight‐year‐old, male neutered Old English sheepdog 12 months post colopexy. Laparoscopic‐assisted incisional colopexy was performed as an adjunctive surgical treatment alongside unilateral perineal herniorrhaphy for management of a right‐sided perineal hernia. The adenocarcinoma initially developed as a subcutaneous mass at the colopexy site, with the colon and transversus abdominis muscle appearing macroscopically normal. Surgical resection of the mass was incomplete based on histopathological examination. Recurrence of the tumour was noted within the rectum and caudal colon 12 months postoperatively, although not at the flank site, and due to the severity of the associated clinical signs the decision was made to euthanase the dog. It is recommended that neoplastic transformation at organ pexy sites should be considered as a rare but possible complication which can carry a grave prognosis.
A New Semantic-based Multi-Level Classification Approach for Activity Recognition Using Smartphones
Authors: Brahim Ghassen Ben , El-Hajj Wassim , El-Hayek Cynthia , Hajj Hazem 
Published: October 2020

In this paper, we address the problem of recognizing the semantic human activities through the analysis of large dataset collected from users’ sensor-based smartphones. Our approach is unique in terms of covering a large number of activities that users could possibly engage in, and considering the multi-level-based classification model. Our model has three properties that never seemed to be addressed by existing approaches dealing with the same problem. These are: (1) comprehensiveness — in terms of the activity set, (2) accuracy — in terms of the activity classification, and (3) applicability — in terms of flexibility in being applied in real-life settings. Current approaches do not tackle all these properties. When tested on realistic dataset, our multi-level-based model achieved promising results despite the large number of activities being considered. When compared to similar approaches, our approach achieved comparable results in terms of accuracy and outperformed them in terms of the activity types, environment and settings covered, comprehensiveness, and applicability.
FRACTAL INTERPOLATION FUNCTIONS ON AFFINE FRACTAL INTERPOLATION CURVES
Authors: RI SONGIL , NAM SONGMIN , KIM HYONCHOL 
Published: October 2020

In this paper, we give fractal interpolation functions generated on some special affine fractal interpolation curve by harmonic functions of fractal analysis. In the case of Koch Curve, same statement is regarded as a corollary, that is, we show that it is possible to ensure that graphs of fractal interpolation functions on the Koch Curve are attractors of iterated function systems. In the case of fractal interpolation functions generated on general affine fractal interpolation curves by harmonic functions of fractal analysis, all the discussions are similar to those performed in some special affine fractal interpolation curve if their harmonic structures are given.
Aggressive PDACs Show Hypomethylation of Repetitive Elements and the Execution of an Intrinsic IFN Program Linked to a Ductal Cell of Origin
Authors: Espinet Elisa , Gu Zuguang , Imbusch Charles D. , Giese Nathalia A. , Büscher Magdalena , Safavi Mariam , Weisenburger Silke , Klein Corinna , Vogel Vanessa , Falcone Mattia , Insua-Rodríguez Jacob , Reitberger Manuel , Thiel Vera , Kossi Steffi O. , Muckenhuber Alexander , Sarai Karnjit , Lee Alex Y.L. , Backx Elyne , Zarei Soheila , Gaida Matthias M. , Rodríguez-Paredes Manuel , Donato Elisa , Yen Hsi-Yu , Eils Roland , Schlesner Matthias , Pfarr Nicole , Hackert Thilo , Plass Christoph , Brors Benedikt , Steiger Katja , Weichenhan Dieter , Arda H. Efsun , Rooman Ilse , Kopp Janel L. , Strobel Oliver , Weichert Wilko , Sprick Martin R. , Trumpp Andreas 
Published: October 2020

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylationlow tumors are characterized by higher expression of endogenous retroviral transcripts and double-stranded RNA sensors, which lead to a cell-intrinsic activation of an interferon signature (IFNsign). This results in a protumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived KrasG12D/Trp53−/− mouse PDACs show higher expression of IFNsign compared with acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylationlow/IFNsignhigh subtype potentially targetable by agents blocking intrinsic IFN signaling.

Significance:
The mutational landscapes of PDAC alone cannot explain the observed interpatient heterogeneity. We identified two PDAC subtypes characterized by differential DNA methylation, preserving traits from normal ductal/acinar cells associated with IFN signaling. Our work suggests that epigenetic traits and the cell of origin contribute to PDAC heterogeneity.
This article is highlighted in the In This Issue feature, p. 521
Epac1 (Exchange Protein Directly Activated by cAMP 1) Upregulates LOX-1 (Oxidized Low-Density Lipoprotein Receptor 1) to Promote Foam Cell Formation and Atherosclerosis Development
Authors: Robichaux William G. , Mei Fang C. , Yang Wenli , Wang Hui , Sun Hua , Zhou Zhen , Milewicz Dianna M. , Teng Ba-Bie , Cheng Xiaodong 
Published: October 2020

Objective:
The cAMP second messenger system, a major stress-response pathway, plays essential roles in normal cardiovascular functions and in pathogenesis of heart diseases. Here, we test the hypothesis that the Epac1 (exchange protein directly activated by cAMP 1) acts as a major downstream effector of cAMP signaling to promote atherogenesis and represents a novel therapeutic target.

Approach and Results:

To ascertain Epac1’s function in atherosclerosis development, a triple knockout mouse model (
LTe
) was generated by crossing
Epac1
−/−
mice with atherosclerosis-prone
LDb
mice lacking both
Ldlr
and
Apobec1
. Deletion of Epac1 led to a significant reduction of atherosclerotic lesion formation as measured by postmortem staining, accompanied by attenuated macrophage/foam cell infiltrations within atherosclerotic plaques as determined by immunofluorescence staining in
LTe
animals compared with
LDb
littermates. Primary bone marrow–derived macrophages were isolated from Epac1-null and wild-type mice to investigate the role of Epac1 in lipid uptake and foam cell formation. ox-LDLs (oxidized low-density lipoproteins) stimulation of bone marrow–derived macrophages led to elevated intracellular cAMP and Epac1 levels, whereas an Epac-specific agonist, increased lipid accumulation in wild-type, but not Epac1-null, bone marrow–derived macrophages. Mechanistically, Epac1 acts through PKC (protein kinase C) to upregulate LOX-1 (ox-LDL receptor 1), a major scavenger receptor for ox-LDL uptake, exerting a feedforward mechanism with ox-LDL to increase lipid uptake and propel foam cell formation and atherogenesis.

Conclusions:
Our study demonstrates a fundamental role of cAMP/Epac1 signaling in vascular remodeling by promoting ox-LDL uptake and foam cell formation during atherosclerosis lesion development. Therefore, Epac1 represents a promising, unexplored therapeutic target for atherosclerosis.
Association of Visceral Adipose Tissue and Subclinical Atherosclerosis in US‐Born Mexican Americans but not First Generation Immigrants
Authors: Gill Clarence , Lee Miryoung , Vatcheva Kristina P. , Rianon Nahid , Smulevitz Beverly , McPherson David D. , McCormick Joseph B. , Fisher‐Hoch Susan P. , Laing Susan T. 
Published: October 2020

Background
Excess visceral adipose tissue (VAT) is a primary driver for the cardiometabolic complications of obesity; VAT‐associated cardiovascular disease risk varies by race, but most studies have been done on Non‐Hispanics. This study aimed to evaluate the clinical and metabolic correlates of VAT, its association with subclinical atherosclerosis, and the factors affecting this association in Mexican Americans.

Methods and Results

Participants (n=527) were drawn from the Cameron County Hispanic Cohort (CCHC), on whom a carotid ultrasound to assess carotid intima media thickness and a dual‐energy X‐ray absorptiometry scan to assess for VAT were obtained. Those in the highest quartiles of VAT were more likely to have hypertension, hypertriglyceridemia, low high‐density lipoprotein, diabetes mellitus, and metabolic syndrome. Increased carotid intima media thickness was more prevalent in those in the highest quartile for VAT (57.4% versus 15.4% for the lowest quartile;
P
<0.001). There was a graded increase in mean carotid intima media thickness with increasing VAT, after adjusting for covariates; for every 10 cm
2
increase in VAT, there was an increase of 0.004 mm (SE=0.002;
P
=0.0299) in mean carotid intima media thickness. However, this association was only seen among second or higher generation US‐born Mexican Americans but not among first generation immigrants (
P
=0.024).

Conclusions
Excess VAT is associated with indicators of metabolic disorders and subclinical atherosclerosis in Mexican Americans regardless of body mass index. However, acculturation appears to be an important modulator of this association. Longitudinal follow‐up with targeted interventions among second or higher generation Hispanics to lower VAT and improve cardiometabolic risk may help prevent premature cardiovascular disease in this cohort.
College Students’ Experiences of Nonhuman Animal Harm in the United States and The Bahamas
Authors: Fielding William J. , Cronin Travis W. , Risley-Curtiss Christina 
Published: October 2020

Abstract
This study compares and contrasts experiences of harm to nonhuman animals in the lives of 830 college students in The Bahamas and the United States. Overall, students in The Bahamas were more likely to have been exposed to seeing animals harmed (65%) than those in the United States (16%), and they were more likely to have seen an animal killed (22% in The Bahamas and 12% in the United States). Bahamian students reported a higher rate of participation in harming animals than United States students. Stray animals were at greater risk of harm than animals designated as companion animals. The occurrence of coerced harm to animals including zoophilia was low. Participants were indirect victims of animal harm at older ages than the ages at which they had first witnessed or participated in harming animals. Cross-societal implications of harming animals are discussed in the context of teaching animal welfare.
Anthropomorphized Nonhuman Animals in Mass Media and Their Influence on Human Attitudes Toward Wildlife
Authors: Grasso Chiara , Lenzi Christian , Speiran Siobhan , Pirrone Federica 
Published: October 2020

Abstract
Anthropomorphic figures of nonhuman animals are omnipresent in various forms of mass media (e.g., movies, books, and advertising). The depiction of companion and wild animals, including nonhuman primates (e.g., chimpanzees), as possessing human characteristics or behaviors can influence these animals’ desirability as companions. Ultimately, this can distort general public perception of what constitutes “normal” wild behavior, as well as the conservation status of these animals. Therefore, anthropomorphic animal representations can contribute to the spread of misleading messages that may have highly unpredictable effects. In the present review, we have highlighted various articles from the academic literature which focus on anthropomorphised animals, noting the main thematic issues. We suggest that further studies on this topic are needed to deepen such a complex and not yet clarified topic.
Hydrometeorological Characteristics of Ice Jams on the Pemigewasset River in Central New Hampshire
Authors: Sanders Matthew C. , Cordeira Jason M. , Metz Nicholas D. 
Published: October 2020

AbstractIce jams that occurred on the Pemigewasset River in central New Hampshire resulted in significant localized flooding on 26 February 2017 and 13 January 2018. Analyses of these two case studies shows that both ice jam events occurred in association with enhanced moisture transport characteristic of atmospheric rivers (ARs) that resulted in rain-on-snow, snowpack ablation, and rapid increases in streamflow across central New Hampshire. However, while the ice jams and ARs that preceded them were similar, the antecedent hydrometeorological characteristics of the region were different. The February 2017 event featured a “long melting period with low precipitation” scenario, with several days of warm (~5°–20°C) maximum surface temperatures that resulted in extensive snowmelt followed by short-duration, weak AR that produced ~10–15 mm of precipitation during a 6-h period prior to the formation of the ice jam. Alternatively, the January 2018 event featured a “short melting period with high precipitation” scenario with snowmelt that occurred primarily during a more intense and long-duration AR that produced >50 mm of rainfall during a 30-h period prior to the formation of the ice jam. Composite analysis of 20 ice jam events during 1981–2019 illustrates that 19 of 20 events were preceded by environments characterized by ARs along the U.S. East Coast and occur in association with a composite corridor of enhanced integrated water vapor > 25 mm collocated with integrated water vapor transport magnitudes > 600 kg m−1 s−1. Additional analyses suggest that most ice jams on the Pemigewasset River share many common synoptic-scale antecedent meteorological characteristics that may provide situational awareness for future events.
Assessment of Sampling Sufficiency for Low-Cost Satellite Missions: Application to PREFIRE
Authors: Kahn Brian H. , Drouin Brian J. , L’Ecuyer Tristan S. 
Published: October 2020

AbstractThe Polar Radiant Energy in the Far Infrared Experiment (PREFIRE) mission will, for the first time, systematically document the far-infrared (15–54 µm) spectral region from space. The environmental sampling characteristics of the PREFIRE CubeSats, defined in terms of surface temperature (Tsfc) and column water vapor (CWV) are evaluated for a range of possible orbit scenarios for both clear-sky and all-sky conditions over a variety of surface types (land, ocean, sea ice, snow, glacier ice) at both poles. Using NASA Aqua’s Atmospheric Infrared Sounder (AIRS) and Advanced Microwave Sounding Unit (AMSU) retrievals to define the climatological ranges of Tsfc and CWV, the fraction of environmental regimes observed by distinct PREFIRE configurations are evaluated. The sampling rates within any single year for two-orbit CubeSat launches spanning both polar regions are ~75% for clear-sky and ~85% for all-sky compared to the AIRS/AMSU climatology. Decreasing mission duration from 12 to 3 months decreases sampling much more (10%–20%) than decreasing the swath width from 15 to 8 footprints (6%–9%). For a single CubeSat launch, a 98° orbital inclination provides slightly better sampling than either 93° or 103°. For a two-orbit CubeSat launch, a combination of 93° + 98° is somewhat preferable to 103° + 98°. Finally, a 50% data loss rate simulated by dropping out every other orbit leads to only a modest 7%–8% reduction in sampling from full data coverage. This statistical analysis demonstrates that low-cost platforms could offer similar coverage as present-day flagship missions for sampling wide-ranging Tsfc and CWV states over polar regions.
Characteristics of General Surgery Social Media Influencers on Twitter
Authors: Elson Nora C. , Le Diana T. , Johnson Mark D. , Reyna Chantal , Shaughnessy Elizabeth A. , Goodman Michael D. , Lewis Jaime D. 
Published: October 2020

Background The influence of social media and Twitter in general surgery research, mentorship, networking, and education is growing. Limited data exist regarding individuals who control the dialogue. Our goal was to characterize influencers leading the discussion in general surgery. Methods Right Relevance Insight API was searched for “general surgery,” and individual influencers were ranked by a comprehensive assessment of connections (followers/following) and engagement (likes, retweets, and comments). Profession, specialty, gender, and location were collected utilizing Twitter, Doximity, LinkedIn, ResearchGate, and institutional websites. American Board of Surgery and Royal College of Physicians and Surgeons of Canada were queried for board certification and academic h-index scores were acquired from Scopus. Results Eighty-eight individual influencers in general surgery were identified, with 73 holding positions in general surgery. Attending level general surgeons comprised 50%, of which 91% are board certified, and 94% completed a fellowship (surgical oncology, laparoscopic surgery, critical care/trauma, and colorectal surgery). Residents comprised 31%; 11% were nonsurgeons and 3% were not physicians. The majority of residents and fellow influencers were female (72%). Many general surgery influencers were international (51%), particularly Canadian (28% overall). The academic h-indices for these influencers (n = 73) ranged from 0 to 73 (mean 14.5 ± 8.2; median 9.5). Discussion Our data describe the positions, backgrounds, and research contributions of the top Twitter influencers in general surgery. Those engaged in social media should consider the background, expertise, and motivation of these influencers as the utilization and impact of this platform grows.