bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial-T cell crosstalk contributes to vascular injury in fatty liver disease
Authors: Cheung C , Ng C Y , Lee K L , Wu K X , Chioh F W J , Tan K , Siau A , Muthiah M D , Chen Q F , Tan N S , Ng H H , Dan Y Y 
Published: October 2021

Abstract

Cardiovascular complications are often the fundamental causes of death in non-alcoholic fatty liver disease (NAFLD) patients. While there are known systemic mediators in NAFLD that may induce vascular inflammation, the mechanism of endothelial dysfunction remain understudied. In this work, we harnessed the replicative potential of blood outgrowth endothelial cells (BOECs) to develop personalized cell lines from NAFLD patients and healthy controls. Our transcriptomic analysis showed that the top interactome network enriched in NAFLD BOECs comprised of several C-C and C-X-C chemokine ligands involved in immune cell chemotaxis. We previously reported T cell infiltration in mouse model of non-alcoholic steatohepatitis, and here, we confirmed enhanced endothelial chemokine signatures in arterial histological sections. To elucidate endothelial-immune crosstalk, we performed single-cell analysis on human peripheral blood mononuclear cells and found T cell intensification in NAFLD patients compared to healthy controls. Our immunoprofiling by flow cytometry further revealed that NAFLD patients possessed higher levels CD8+ memory cells. Functionally, T cells, instead of monocytes, adhered more pronouncedly to NAFLD BOECs. In evaluating the CXCL12-CXCR4 axis in chemotaxis, CXCR4 antagonist (AMD3100) substantially modulated the migration of patient-derived CD8+ T cells towards NAFLD BOECs, which was not observed in healthy endothelial-T cell chemotaxis coculture. Finally, we validated NAFLD-associated endothelial dysfunction by enumerating two folds more circulating endothelial cells, a biomarker of vascular injury, in the blood samples of NAFLD patients than healthy controls. Our work provides insights for translation to restore blood vessel health and potentially mitigate adverse vascular events in NAFLD.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Industrial Alignment Fund Pre-Positioning grant from the Agency for Science, Technology and Research, Singapore Endothelial-T cell crosstalk in NAFLD
Proprotein convertase subtilisin/kexin type 9 links inflammation to vascular endothelial cell dysfunction
Authors: Leucker T , Amat-Codina N , Chelko S , Gerstenblith G 
Published: October 2021

Abstract

Vascular endothelial cell (EC) dysfunction is a pathological mediator of the development, progression, and clinical manifestations of atherosclerotic disease. Inflammation is associated with EC dysfunction, but the responsible mechanisms are not well characterized. There is substantial evidence that serum proprotein convertase subtilisin/kexin type 9 (PCSK9) is increased in pro-inflammatory states and that elevated PCSK9 levels are associated with adverse cardiovascular outcomes after controlling for traditional risk factors, including low-density lipoprotein (LDL) cholesterol.
Here we investigate PCSK9 as a novel link between inflammation and vascular EC dysfunction, as assessed by nitric oxide (NO) bioavailability. Tumor necrosis factor alpha (TNF-α), a pro-inflammatory cytokine, increased PCSK9 mRNA expression (1.98 [0.7, 3.4]-fold increase, p=0.02 vs. control) and PCSK9 protein levels (1.52±0.1-fold increase, p&lt;0.01 vs. control) in isolated human aortic ECs. This was accompanied by reduced phosphorylated endothelial nitric oxide synthase (eNOS) protein which was 56% ± 5.6% of that in the controls (p&lt;0.01) and NO bioavailability, which was reduced by 29% ± 22.1% compared to that in the controls (p&lt;0.01). Finally, genetic PCSK9 reduction utilizing a PCSK9 specific siRNA in human aortic ECs resulted in the rescue of eNOS phosphorylation and NO bioavailability.
Our results demonstrate that PCSK9 is increased in human aortic ECs exposed to a pro-inflammatory stimulus and that this increase is associated with EC dysfunction. Silencing of TNFα-mediated augmentation of PCSK9 protein expression utilizing a small interfering RNA against PCSK9 rescued the inflammation-induced EC dysfunction. These results indicate that PCSK9 is a causal link between inflammation and EC dysfunction, a potent driver of atherosclerotic cardiovascular disease.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Career Development Award from the American Heart Association, OAIC pilot Award
Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DΔNΔC gene therapy: eight-year follow-up of phase 1 KAT301 study
Authors: Leikas A J , Hassinen I , Hedman A , Kivela A , Yla-Herttuala S , Hartikainen J E K 
Published: October 2021

Abstract

Backgound/Introduction
In phase I KAT301 trial, adenovirus-mediated intramyocardial vascular endothelial growth factor-DΔNΔC (VEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved angina at 1-year follow-up without major safety concerns.

Purpose
Our objective was to investigate the long-term safety and efficacy of AdVEGF-D GT. A total of 30 patients (24 VEGF-D and 6 randomized and blinded controls) participated in KAT301 trial.

Methods
The mean follow-up time was 8.2 years (range 6.3–10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse events (MACEs) and other predefined endpoints including cancer.

Results
MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.90; 95% confidence interval 0.09–9.32; P=0.95). Mortality and comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P=0.006) but not in control group (2.2 vs. 2.6; P=0.414).

Conclusion(s)
Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Kuopio University Hospital Heart Center Figure 1. The incidence of MACEFigure 2. CCS class
Building the mega single-cell transcriptome ocular meta-atlas
Authors: Swamy Vinay S , Fufa Temesgen D , Hufnagel Robert B , McGaughey David M 
Published: October 2021

AbstractBackground: The development of highly scalable single-cell transcriptome technology has resulted in the creation of thousands of datasets, &gt;30 in the retina alone. Analyzing the transcriptomes between different projects is highly desirable because this would allow for better assessment of which biological effects are consistent across independent studies. However it is difficult to compare and contrast data across different projects because there are substantial batch effects from computational processing, single-cell technology utilized, and the natural biological variation. While many single-cell transcriptome-specific batch correction methods purport to remove the technical noise, it is difficult to ascertain which method functions best. Results: We developed a lightweight R package (scPOP, single-cell Pick Optimal Parameters) that brings in batch integration methods and uses a simple heuristic to balance batch merging and cell type/cluster purity. We use this package along with a Snakefile-based workflow system to demonstrate how to optimally merge 766,615 cells from 33 retina datsets and 3 species to create a massive ocular single-cell transcriptome meta-atlas. Conclusions: This provides a model for how to efficiently create meta-atlases for tissues and cells of interest.
Cormatrix® for vessel reconstruction in paediatric cardiac surgery—a word of caution
Authors: Weis Johanna , Geiger Ralf , Kilo Juliane , Zimpfer Daniel 
Published: October 2021

Abstract

OBJECTIVES
The aim of this retrospective study was to determine if Cormatrix® (CM) represents a safe alternative to conventional patch materials used in congenital heart surgery.

METHODS
A total of 57 paediatric patients who underwent cardiac surgery using an Extracellular Matrix Bioscaffold (CM) were categorized into 4 groups according to the patch implant location. Patch-related complications and reintervention rates were analysed. A subgroup of 18 patients was subsequently compared to a matched group of 36 patients who underwent similar surgical procedures with autologous pericardium as patch material.

RESULTS
No patient died during hospitalization. There were 2 late deaths, not related to the implanted CM patch. Fourteen (66.7%) out of 21 patients with arterial patch plasty developed progressive vessel/right ventricular outflow tract stenosis or aneurysm. All 3 patients with a valved CM conduit developed haemodynamically relevant valve stenosis or regurgitation. A total of 18 (31.5%) patients needed reintervention and 12 (21.1%) related to CM. Four (7%) patients needed surgical treatment with operative removal of the stenosis. Redo valve replacement was performed on 2 (3.5%) patients. Six (10.5%) patients required an interventional cardiology procedure at a median interval of 5 months from surgery. The subgroup analysis revealed a significantly lower patch-related reintervention rate in patients treated with autologous pericardium when compared to CM (P = 0.006).

CONCLUSIONS
CM is safe for atrial and ventricular defect closure. The use of CM for arterial vessel reconstruction is associated with higher reintervention rates when compared to autologous pericardium.
Rethinking Proxy War Theory in IR: A Critical Analysis of Principal–Agent Theory
Authors: Farasoo Abbas 
Published: October 2021

AbstractThis paper explores the question of what drives proxy alignment in war and argues that current proxy war scholarship needs further thinking to go beyond focusing on the principal–agent theory and individual actors’ motivation analysis. Rather, there is a need to look at the generative mechanisms of proxy alignment as a process that constitutes patterns of friend–enemy relations. The paper argues securitization patterns from domestic to regional and international levels drive actors to re-evaluate their positions and define their enemies and friends. This is a process of securitization alignment and confluence, which serves as a generative mechanism for proxy alignment in a conflict. Securitization alignment is based on a convergence of securitizations by different actors that create a friend–enemy dynamic and convergence of security interests between actors. The confluence of securitizations from the domestic level to regional and beyond also connects actors across different levels to be in alignment and impact the conflict.
Predelli on Fictional Discourse
Authors: García-Carpintero Manuel 
Published: October 2021

AbstractJohn Searle argues that (literary) fictions are constituted by mere pretense—by the simulation of representational activities like assertions, without any further representational aim. They are not the result of sui generis, dedicated speech acts of a specific kind, on a par with assertion. The view had earlier many defenders, and still has some. Stefano Predelli enlists considerations derived from Searle in support of his radical fictionalism. This is the view that a sentence of fictional discourse including a prima facie empty fictional name like “Emma Woodhouse” in fact “is not a sentence, and it encodes no proposition whatsoever.” His argument is broadly abductive; he claims that this view affords compelling explanations of features of fictions he finds well-established, among them that fictions without explicit narrators nonetheless have covert ones. Here I take up his arguments, in defense of the dedicated speech act view. I thus address pressing issues about the status of fictional names and the nature and ubiquity of narrators in fictions.
Surveillance and Molecular Identification ofBorreliaSpecies in Ticks Collected at U.S. Army Garrison Humphreys, Republic of Korea, 2018–2019
Authors: Lee Seung-Ho , Chong Sung-Tae , Kim Heung-Chul , Klein Terry A , Park Kyungmin , Lee Jingyeong , Kim Jeong-Ah , Kim Won-Keun , Song Jin-Won 
Published: October 2021

AbstractTick-borne pathogens are contributing factors for the increased incidence of vector-borne diseases throughout the world, including Lyme borreliosis, one of the most prevalent spirochetes belonging to the Borrelia burgdorferi sensu lato group. The present study focused on the detection of Borrelia species from hard ticks collected at U.S. Army Garrison Humphreys, Republic of Korea (ROK), using molecular and genotypic analyses. Tick-borne disease surveillance was conducted from January to December, 2018–2019. A total of 24,281 ticks (2 genera and 5 species) were collected from road-killed Korean Water deer (KWD) and by tick drag. Haemaphysalis longicornis (92.0%) was the most commonly collected species, followed by Haemaphysalis flava (4.9%), Ixodes nipponensis (3.1%), Haemaphysalis phasiana (0.07%), and Haemaphysalis japonica (&lt;0.01%). The ospA gene sequences of Borrelia afzelii were detected in 12/529 pools of I. nipponensis. Three and one pools were positive for B. afzelii and Borrelia miyamotoi, respectively, using the 16s rRNA gene. None of the pools of Haemaphysalis ticks collected from KWD or by tick drag were positive for Borrelia species. I. nipponensis was collected throughout the year from KWD and from February to November by tick drag, suggesting that they were active throughout the year, and expanding the risk period for acquiring Lyme borreliosis and Borrelia relapsing fever in the ROK. This study assessed disease risk factors associated with the prevalence of Lyme disease in ticks collected from KWD and by tick drag using molecular analysis. These results provide an understanding and awareness into the prevalence and molecular characteristics of Borrelia species in the ROK.
INDI—integrated nanobody database for immunoinformatics
Authors: Deszyński Piotr , Młokosiewicz Jakub , Volanakis Adam , Jaszczyszyn Igor , Castellana Natalie , Bonissone Stefano , Ganesan Rajkumar , Krawczyk Konrad 
Published: October 2021

AbstractNanobodies, a subclass of antibodies found in camelids, are versatile molecular binding scaffolds composed of a single polypeptide chain. The small size of nanobodies bestows multiple therapeutic advantages (stability, tumor penetration) with the first therapeutic approval in 2018 cementing the clinical viability of this format. Structured data and sequence information of nanobodies will enable the accelerated clinical development of nanobody-based therapeutics. Though the nanobody sequence and structure data are deposited in the public domain at an accelerating pace, the heterogeneity of sources and lack of standardization hampers reliable harvesting of nanobody information. We address this issue by creating the Integrated Database of Nanobodies for Immunoinformatics (INDI, http://naturalantibody.com/nanobodies). INDI collates nanobodies from all the major public outlets of biological sequences: patents, GenBank, next-generation sequencing repositories, structures and scientific publications. We equip INDI with powerful nanobody-specific sequence and text search facilitating access to &gt;11 million nanobody sequences. INDI should facilitate development of novel nanobody-specific computational protocols helping to deliver on the therapeutic promise of this drug format.
Establishment of a near-contiguous genome sequence of the citric acid producing yeast Yarrowia lipolytica DSM 3286 with resolution of rDNA clusters and telomeres
Authors: Luttermann Tobias , Rückert Christian , Wibberg Daniel , Busche Tobias , Schwarzhans Jan-Philipp , Friehs Karl , Kalinowski Jörn 
Published: October 2021

Abstract
Yarrowia lipolytica is an oleaginous yeast that is particularly suitable for the sustainable production of secondary metabolites. The genome of this yeast is characterized by its relatively large size and its high number of different rDNA clusters located in its telomeric regions. However, due to the presence of long repetitive elements in the sub-telomeric regions, rDNA clusters and telomeres are missing in current genome assemblies of Y. lipolytica. Here, we present the near-contiguous genome sequence of the biotechnologically relevant strain DSM 3286. We employed a hybrid assembly strategy combining Illumina and nanopore sequencing reads to integrate all six rDNA clusters as well as telomeric repeats into the genome sequence. By fine-tuning of DNA isolation and library preparation protocols, we were able to create ultra-long reads that not only contained multiples of mitochondrial genomes but also shed light on the inter- and intra-chromosomal diversity of rDNA cluster types. We show that there are ten different rDNA units present in this strain that additionally appear in a predefined order in a cluster. Based on single reads, we also demonstrate that the number of rDNA repeats in a specific cluster varies from cell to cell within a population.
Characterizing batch effects and binding site-specific variability in ChIP-seq data
Authors: Teng Mingxiang , Du Dongliang , Chen Danfeng , Irizarry Rafael A 
Published: October 2021

Abstract
Multiple sources of variability can bias ChIP-seq data toward inferring transcription factor (TF) binding profiles. As ChIP-seq datasets increase in public repositories, it is now possible and necessary to account for complex sources of variability in ChIP-seq data analysis. We find that two types of variability, the batch effects by sequencing laboratories and differences between biological replicates, not associated with changes in condition or state, vary across genomic sites. This implies that observed differences between samples from different conditions or states, such as cell-type, must be assessed statistically, with an understanding of the distribution of obscuring noise. We present a statistical approach that characterizes both differences of interests and these source of variability through the parameters of a mixed effects model. We demonstrate the utility of our approach on a CTCF binding dataset composed of 211 samples representing 90 different cell-types measured across three different laboratories. The results revealed that sites exhibiting large variability were associated with sequence characteristics such as GC-content and low complexity. Finally, we identified TFs associated with high-variance CTCF sites using TF motifs documented in public databases, pointing the possibility of these being false positives if the sources of variability are not properly accounted for.
The role of tender and swollen joints for the assessment of inflammation in PsA using ultrasound
Authors: Bosch Philipp , Lackner Angelika , Dreo Barbara , Husic Rusmir , Ficjan Anja , Gretler Judith , Graninger Winfried , Duftner Christina , Hermann Josef , Dejaco Christian 
Published: October 2021

Abstract

Objective
To evaluate tender joints (TJ) and swollen joints (SJ) for the assessment of ultrasound (US) defined inflammation in PsA.

Methods
Eighty-three PsA patients underwent clinical and US examinations at two scheduled study visits 12 months apart. Tenderness and swelling were assessed at 68 and 66 joints, respectively, and US examinations were conducted at all 68 joints. At patient level, associations with clinical composites and US scores were performed using correlations and by analysing patients with predominantly tender (pTender) or swollen joints (pSwollen). At joint level, a Power Doppler (PD) value ≥ 1 was defined as active synovitis. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months.

Results
SJC showed better correlations with GS/PD scores (r = 0.37/0.47) than with TJC (PD: r = 0.33), while TJC correlated better with patient reported outcomes (PROMs) like patient global assessment (TJC: r = 0.57; SJC r = 0.39). Patients with pTender showed poorer results for PROMs and disease activity scores than patients with pSwollen, but not for laboratory or US markers of inflammation. Swollen joints showed active synovitis in 35% of cases, while only 16% of tender joints were active according to US. Swelling at baseline better predicted active synovitis at the same joint after 12 months [odds ratio (OR) 6.33, P &lt;0.001] as compared with tenderness (OR 3.58, P &lt;0.001).

Conclusions
SJ are more closely linked with US signs of inflammation as compared with TJ in PsA. Joint swelling is a better predictor for signs of US inflammation than tenderness after one year of follow-up.
Structural Racism, Managerialism, and the Future of the Human Services: Rewriting the Rules
Authors: Abramovitz Mimi , Zelnick Jennifer R 
Published: October 2021

Abstract
Over the past several decades, the introduction of the business model, managerialism, into the human services has led to dramatic changes in conditions of work and service delivery. This metric-driven approach increased the emphasis on measured performance outcomes and undercut the mission-driven nature of human services organizations. In 2020, the COVID-19 pandemic and widespread protests against racial injustice exposed routinely ignored structural racism long embedded in our social institutions. This reckoning led social workers to re-examine professional practices, organizational structures, and public policies through a critical, antiracist lens. Applying a racial justice lens to their study of the impact of managerialism in the human services workplace, authors identified troubling evidence of systemic racism in leadership hierarchies, worker control/surveillance on the job, quality of the physical work environment, exposure to workplace violence, exclusion by microinequities, and agency commitment to social justice. Worker resistance, ethical dilemmas, and well-being also varied by race. To become an antiracist profession, social work must seek long-term change in the human services workplace. The following analysis of the combined negative impact of managerialism and structural racism on human services organizations names the problem and presses us to rewrite the rules so we become a racial justice profession.
Non-18F-FDG-Avid Intrahepatic Metastasis of Breast Cancer Revealed by 68Ga-FAPI PET/CT
Authors: Wang Qixin , Tang Wenxin , Cai Liang , Chen Yue 
Published: October 2021

Abstract
A patient with intrahepatic breast cancer metastasis underwent both 18F-FDG and 68Ga-FAPI PET/CT. However, the lesions are only 68Ga-FAPI avid. Our case illustrates that 68Ga-FAPI PET/CT can be more sensitive in detecting intrahepatic metastasis of breast cancer in some cases.
Incidental [18F]PSMA-1007 Appendiceal Uptake Mimicking Nodal Disease
Authors: Nawwar Ayah Adel , Searle Julie , Lyburn Iain Douglas 
Published: October 2021

Abstract
When interpreting an [18F]prostate specific membrane antigen (PSMA)–1007 PET/CT, it is important to understand the normal biodistribution of the tracer. A 73-year-old man with prostate cancer underwent [18F]PSMA-1007 PET/CT for biochemical recurrence. There was no abnormal uptake in the prostatectomy bed, but PSMA-avid pelvic nodal disease was found. Incidental intense focal uptake was also noted corresponding to the tip of the appendix, which was concluded to be physiological. This is an example of an uncommon site of physiological uptake of [18F]PSMA-1007 in the appendix.