bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microaneurysms visualisation using five different optical coherence tomography
angiography devices compared to fluorescein angiography
Authors: Parrulli Salvatore , Corvi Federico , Cozzi Mariano , Monteduro Davide , Zicarelli Federico , Staurenghi Giovanni 
Published: June 2020

Background
To compare fluorescein angiography (FA) and five different optical
coherence tomography angiography (OCTA) devices and to test their
reproducibility in the evaluation of retinal microaneurysms (MAs) secondary to
diabetic retinopathy (DR).

Methods
On the same day, patients with DR were imaged with FA and five OCTA
devices: prototype Spectralis OCTA, prototype PlexElite, RTVue XR Avanti,
AngioPlex and DRI OCT Triton. For all OCTA devices, a 3×3 volume scan pattern
was performed. MAs were evaluated for the superficial capillary plexus (SCP)
and deep capillary plexus (DCP).

Results
Twenty eyes of 15 patients with DR were included. FA counted a
significantly higher number of MAs compared to OCTA devices. Spectralis OCTA
obtained a significantly higher number of MAs compared to PlexElite, RTVue XR
Avanti, AngioPlex and DRI OCT Triton (p<0.0001). PlexElite and AngioPlex
showed a greater number of MAs in the SCP, Spectralis OCTA, RTVue XR Avanti and
DRI OCT Triton in the DCP. Higher sensitivity (43.3%) but lowest specificity
(54.4%) was observed for Spectralis OCTA compared to other devices. The higher
specificity (78.5%) and positive predictive value (83.3%) were observed for DRI
OCT Triton.

Conclusions
FA remains the best imaging modality to visualise retinal MAs. Spectralis
OCTA was able to detect more MAs compared to other devices, likely due to the
higher number of B-scans in the scanned area as well as due to the higher
number of repeated B-scans. The high variability between OCTA devices should be
taken into account for future clinical trials as in clinical practice.
Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) Study: design of lifestyle intervention
Authors: Dagogo-Jack Samuel , Brewer Amy A , Owei Ibiye , French Lindsey , Umekwe Nkiru , Rosenthal Renate , Wan Jim 
Published: June 2020

IntroductionIntensive lifestyle intervention (ILI) prevents progression from prediabetes to type 2 diabetes (T2D) but reversal of prediabetes is less well studied.Research design and methodsThe overall objectives of the Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) Study (ClinicalTrials.gov ID:NCT02027571) are to determine the natural history and reversibility of prediabetes. The study tests specific hypotheses on the patterns of progression to prediabetes among normoglycemic African-American (AA) and European-American (EA) offspring of parents with T2D; emergence of microvascular and macrovascular complications during transition from normal to impaired glucose regulation; significance of the ‘metabolically healthy’ obese phenotype; and effect of duration of the prediabetic state on its reversibility with lifestyle intervention. Participants who developed incident prediabetes were offered ILI and evaluated quarterly for 5 years. The primary outcome was restoration of normal glucose regulation (fasting plasma glucose <100 mg/dL and two-hour plasma glucose (2hrPG)<140 mg/dL).ResultsOf the 223 subjects enrolled in the PROP-ABC Study, 158 participants with incident prediabetes started ILI. The mean age was 53.3±9.28 years; body mass index 30.6±6.70 kg/m2; 70% were female, 52.4% AA and 47.6% EA. The ILI program used goal setting, weight-based calorie restriction, physical activity (180 min/week), self-monitoring, and meal replacement. Monthly face-to-face (F2F) counseling sessions during the initial 6 months, and quarterly visits thereafter, were supplemented with electronic and postal contacts. Attendance at F2F sessions was highly correlated with weight loss (r=0.98, p<0.0001). Meal replacement induced ~5 kg weight loss within 3 months in participants with recrudescent weight pattern. Self-reported exercise minutes correlated with pedometer step counts (r=0.47, p<0.0001).ConclusionThe PROP-ABC Study has demonstrated the feasibility of executing an ILI program designed to test reversibility of incident prediabetes in a biracial cohort.
Feasibility study of in vitro drug sensitivity assay of advanced non-small cell lung adenocarcinomas
Authors: Papp Emoke , Steib Anita , Abdelwahab Elhusseiny MM , Meggyes-Rapp Judit , Jakab Laszlo , Smuk Gabor , Schlegl Erzsebet , Moldvay Judit , Sárosi Veronika , Pongracz Judit E 
Published: June 2020

Background Despite improved screening techniques, diagnosis of lung cancer is often late and its prognosis is poor. In the present study, in vitro chemosensitivity of solid tumours and pleural effusions of lung adenocarcinomas were analysed and compared with clinical drug response.Methods Tumour cells were isolated from resected solid tumours or pleural effusions, and cryopreserved. Three-dimensional (3D) tissue aggregate cultures were set up when the oncoteam reached therapy decision for individual patients. The aggregates were then treated with the selected drug or drug combination and in vitro chemosensitivity was tested individually measuring ATP levels. The clinical response to therapy was assessed by standard clinical evaluation over an 18 months period.Results Based on the data, the in vitro chemosensitivity test results correlate well with clinical treatment response.Conclusions Such tests if implemented into the clinical decision making process might allow the selection of an even more individualised chemotherapy protocol which could lead to better therapy response.
Outpatient palliative medicine consultations: urgent or routine?
Authors: Alam Sorayya , Pope Ashley , Le Lisa , Al-Awamer Ahmed , Banerjee Subrata , Lau Jenny , Mak Ernie , Zimmermann Camilla , Hannon Breffni 
Published: June 2020

BackgroundAlthough outpatient palliative care clinics (OPCCs) provide a venue for early, pre-emptive referral to palliative care on a routine basis, some patients will continue to require urgent referrals. The purpose of this study was to characterise these urgent referrals to determine whether they reflect clinical need or convenience.MethodsWe retrospectively compared new patients in an OPCC who were seen urgently versus those seen at routine appointments. Descriptive statistics compared the two groups in terms of clinical characteristics, referring teams, symptoms, performance status and outcomes. Logistic regression was used to identify factors associated with urgent referral to the OPCC. Overall survival was compared using the log-rank test.ResultsBetween January 2016 and December 2017, a total of 113 urgent referrals were reviewed in the OPCC; these were compared with a random sample of 217 routine referrals. Patients seen urgently were more likely to be referred by surgical oncology, and to report worse symptom scores for pain (p=0.0007), tiredness (p=0.02), well-being (p=0.001), constipation (p=0.02) and sleep (p=0.01). More patients seen urgently required direct admission to hospital following the visit (17.7% vs 0.9%, p<0.001). Median survival was shorter for patients seen urgently (4.3 months, 95% CI 3.4 to 7.8) versus routinely (8.1 months, 95% CI 7.2 to 9.5).ConclusionsCompared with routine referrals, new patients seen urgently in the OPCC had higher symptom burden, shorter median survival and a greater chance of direct admission to hospital. Palliative care clinics should consider how best to accommodate urgent referrals.
Identification of PD1-mediated regulation of antitumor antigen response in patients with NSCLC using the trans vivo DTH assay
Authors: Lema Diego A , Jankowska-Gan Ewa , Sethakorn Nan , Burlingham William , Leal Ticiana 
Published: June 2020

ObjectivesEmerging evidence has shown a role for tumor antigen-specific regulation in cancer. Identifying individuals with pre-existing regulatory responses may be key to understand those who are more likely to respond to Programmed Death-1 (PD-1) or PD-1 Ligand 1 (PD-L1) checkpoint blockade. We hypothesized that a functional assay could identify the role of PD-1/PD-L1 interactions on tumor-specific immune cells in the peripheral blood in patients with advanced non-small-cell lung cancer (NSCLC).MethodsWe performed the trans vivo delayed-type hypersensitivity assay to identify the role of PD-1/PD-L1-mediated tumor-specific immune regulation in ten patients with advanced NSCLC.ResultsThe majority of patients had PD-1-mediated anergic immune responses towards their tumor antigens. Eight out of nine of these patients did not respond to their own tumor antigens but responded in the presence of anti-PD-1 antibody (‘PD-1 anergy’ phenotype). A minority (3/9) also had ‘active’ PD-1-mediated immune suppressive regulatory responses. Our results suggest that PD-1-anergy is a common feature of NSCLC immune responses, whereas PD-1-mediated immune suppression is present only in a minority of patients. The latter was associated with poor clinical outcomes in our sample.ConclusionsOverall, our results indicate that bystander suppression or the ‘anergy-only’ phenomenon may be novel biomarkers in NSCLC and suggest prediction value based on these phenotypes.
Nanopore sequencing as a scalable, cost-effective platform for analyzing polyclonal vector integration sites following clinical T cell therapy
Authors: Zhang Ping , Ganesamoorthy Devika , Nguyen Son Hoang , Au Raymond , Coin Lachlan J , Tey Siok-Keen 
Published: June 2020

BackgroundAnalysis of vector integration sites in gene-modified cells can provide critical information on clonality and potential biological impact on nearby genes. Current short-read next-generation sequencing methods require specialized instruments and large batch runs.MethodsWe used nanopore sequencing to analyze the vector integration sites of T cells transduced by the gammaretroviral vector, SFG.iCasp9.2A.ΔCD19. DNA from oligoclonal cell lines and polyclonal clinical samples were restriction enzyme digested with two 6-cutters,NcoIandBspHI; and the flanking genomic DNA amplified by inverse PCR or cassette ligation PCR. Following nested PCR and barcoding, the amplicons were sequenced on the Oxford Nanopore platform. Reads were filtered for quality, trimmed, and aligned. Custom tool was developed to cluster reads and merge overlapping clusters.ResultsBoth inverse PCR and cassette ligation PCR could successfully amplify flanking genomic DNA, with cassette ligation PCR showing less bias. The 4.8 million raw reads were grouped into 12,186 clusters and 6410 clones. The 3′long terminal repeat (LTR)-genome junction could be resolved within a 5-nucleotide span for a majority of clusters and within one nucleotide span for clusters with ≥5 reads. The chromosomal distributions of the insertional sites and their predilection for regions proximate to transcription start sites were consistent with previous reports for gammaretroviral vector integrants as analyzed by short-read next-generation sequencing.ConclusionOur study shows that it is feasible to use nanopore sequencing to map polyclonal vector integration sites. The assay is scalable and requires minimum capital, which together enable cost-effective and timely analysis. Further refinement is required to reduce amplification bias and improve single nucleotide resolution.
Impact of thrombus surface on first pass reperfusion in contact aspiration and stent retriever thrombectomy
Authors: Kaiser Daniel , Laske Katharina , Winzer Robert , Hädrich Kevin , Wahl Hannes , Krukowski Pawel , Daubner Dirk , Pallesen Lars-Peder , Linn Jennifer , Puetz Volker , Gerber Johannes C 
Published: June 2020

BackgroundTo assess whether thrombus surface morphology has an impact on first pass reperfusion in contact aspiration (CA) and stent retriever (SR) thrombectomy.MethodsFrom January 2016 to December 2018, consecutive stroke patients with an occlusion of the middle cerebral artery and thrombectomy (CA or SR) were examined in this retrospective study. We assessed patients’ characteristics, procedural data and clinical outcome. Thrombus surface on pretreatment digital subtraction angiography (DSA) was categorized into regular versus irregular phenotype by blinded three-reader-consensus. Primary outcome was successful reperfusion (modified treatment in cerebral ischemia (mTICI) 2b-3) after first pass. Data analysis was stratified according to thrombectomy technique and thrombus phenotype.ResultsAmong 203 patients (76 years (IQR 65.5–81.9), 47.3% male, National Institutes of Health Stroke Scale Score 16 (IQR 12–20)), 155 patients were treated primarily with CA and 48 with SR. 40% (n=62/155) CA and 41.7% (n=20/48) SR-treated patients had a regular thrombus phenotype. In the CA group, successful reperfusion after first pass was more frequently obtained in patients with regular compared with irregular phenotype (69.4% (n=43/62) vs 34.4% (n=32/93); P<0.0001). In contrast, in the SR group, reperfusion after first pass was achieved in 35% (n=7/20; P=0.01) of patients with regular phenotypes. In the CA group, median number of passes (1 (1–2) vs 2 (1–4); P<0.00001) and time from reaching the thrombus to reperfusion (19±27 vs 38±36 min; P=0.0001) were lower among patients with a regular phenotype.ConclusionDirect CA is associated with higher rates of successful first pass reperfusion in patients with a regular thrombus phenotype in pretreatment DSA.
Simulation of geodesic trajectory of charged BTZ black holes in massive gravity
Authors: Hendi S. H. , Tavakkoli A. M. , Panahiyan S. , Panah B. Eslam , Hackmann E. 
Published: June 2020

AbstractIn order to classify and understand structure of the spacetime, investigation of the geodesic motions of massive and massless particles is a key tool. So the geodesic equation is a central equation of gravitating systems and the subject of geodesics in the black hole dictionary attracted much attention. In this paper, we give a full description of geodesic motions in three-dimensional spacetime. We investigate the geodesics near charged BTZ black holes and then generalize our prescriptions to the case of massive gravity. We show that electric charge is a critical parameter for categorizing the geodesic motions of both lightlike and timelike particles. In addition, we classify the type of geodesics based on the particle properties and geometry of spacetime.
Neoproterozoic–paleozoic detrital sources in the Variscan foreland of northern Iberia: primary v. recycled sediments
Authors: Gutiérrez-Alonso G. , López-Carmona A. , Núñez-Guerrero E. , Martínez García A. , Fernández-Suárez J. , Pastor-Galán D. , Gutiérrez-Marco J. C. , Bernárdez E. , Colmenero J. R. , Hofmann M. , Linnemann U. 
Published: June 2020

Abstract
The Cantabrian Zone, in the Variscan belt of Western Europe, has one of the most continuous Ediacaran–Paleozoic stratigraphic successions in the world. This succession has been extensively studied, including several detrital zircon U–Pb geochronological studies on 30 samples spanning the aforementioned time slice. In this work, we present data from three new samples covering previously unsampled time-slices and perform multidimensional analysis on the 33 samples in order to quantify the similarity/dissimilarity among all of them with the aim of detecting potential changes in source areas through time and the role of recycling. The results indicate a continuous source of sediments from Ediacaran to late Devonian times punctuated by a sudden ephemeral change in the Early Cambrian that can be attributed to local causes during the inception of the Paleozoic passive margin.
Integrated geophysical and sedimentological datasets for assessment of offshore borrow areas: the CHIMERA project (western Portuguese Coast)
Authors: Mil-Homens Mário , Brito Pedro , Magalhães Vitor , Rosa Marcos , Neres Marta , Silva Marta , Salgueiro Emília , Drago Teresa , Rodrigues Ana Isabel , Guerra Miriam Tuaty , Gaudêncio Maria José , Almeida Eveline , Silva Mariana , Freitas Mafalda , Pinto Celso Aleixo , Bandarra Cidália , Terrinha Pedro 
Published: June 2020

Abstract

Coastal erosion impact on low-lying sandy shorelines represents a worldwide problem, which is particularly felt in various segments of the Portuguese coast where this geomorphological type represents 42% of its total length. Beach nourishment is a viable engineering alternative for shore protection and the assessment of offshore sources of beach-fill material is an essential aspect when implementing this mitigation strategy. The CHIMERA project carried out a multidisciplinary inspection on four segments of the west Portuguese coast to assess their potential as offshore borrow areas for beach nourishment. Altogether, these segments covered an area of
c
. 35 km
2
, at water depths between 20 and 42 m. They were surveyed using multibeam, sub-bottom profiler, ultra-high resolution multichannel seismics and a set of 126 surface samples and 72 vibrocores (with 3 m long each). To comply with the Portuguese legislation, sand types were assessed by granulometric and chemical analyses for evaluating the quality of sediments in terms of contamination. High-resolution magnetic surveys were conducted to find potential archaeological artefacts. The adopted methodology proved to be adequate to quantify and describe the spatial distribution of useful sediment volumes, supporting the ongoing Integrated Coastal Sediment Strategy for mainland Portugal.
Phosphodiesterase 3A and Arterial Hypertension
Authors: Ercu Maria , Markó Lajos , Schächterle Carolin , Tsvetkov Dmitry , Cui Yingqiu , Maghsodi Sara , Bartolomaeus Theda U.P. , Maass Philipp G. , Zühlke Kerstin , Gregersen Nerine , Hübner Norbert , Hodge Russell , Mühl Astrid , Pohl Bärbel , Illas Rosana Molé , Geelhaar Andrea , Walter Stephan , Napieczynska Hanna , Schelenz Stefanie , Taube Martin , Heuser Arnd , Anistan Yoland-Marie , Qadri Fatimunnisa , Todiras Mihail , Plehm Ralph , Popova Elena , Langanki Reika , Eichhorst Jenny , Lehmann Martin , Wiesner Burkhard , Russwurm Michael , Forslund Sofia K. , Kamer Ilona , Müller Dominik N. , Gollasch Maik , Aydin Atakan , Bähring Sylvia , Bader Michael , Luft Friedrich C. , Klussmann Enno 
Published: June 2020

Background:

High blood pressure is the primary risk factor for cardiovascular death worldwide. Autosomal dominant hypertension with brachydactyly clinically resembles salt-resistant essential hypertension and causes death by stroke before 50 years of age. We recently implicated the gene encoding phosphodiesterase 3A (
PDE3A
); however, in vivo modeling of the genetic defect and thus showing an involvement of mutant PDE3A is lacking.

Methods:
We used genetic mapping, sequencing, transgenic technology, CRISPR-Cas9 gene editing, immunoblotting, and fluorescence resonance energy transfer. We identified new patients, performed extensive animal phenotyping, and explored new signaling pathways.

Results:

We describe a novel mutation within a 15 base pair (bp) region of the
PDE3A
gene and define this segment as a mutational hotspot in hypertension with brachydactyly. The mutations cause an increase in enzyme activity. A CRISPR/Cas9-generated rat model, with a 9-bp deletion within the hotspot analogous to a human deletion, recapitulates hypertension with brachydactyly. In mice, mutant transgenic PDE3A overexpression in smooth muscle cells confirmed that mutant PDE3A causes hypertension. The mutant PDE3A enzymes display consistent changes in their phosphorylation and an increased interaction with the 14-3-3θ adaptor protein. This aberrant signaling is associated with an increase in vascular smooth muscle cell proliferation and changes in vessel morphology and function.

Conclusions:

The mutated
PDE3A
gene drives mechanisms that increase peripheral vascular resistance causing hypertension. We present 2 new animal models that will serve to elucidate the underlying mechanisms further. Our findings could facilitate the search for new antihypertensive treatments.
Higher Activation of the Rostromedial Prefrontal Cortex During Mental Stress Predicts Major Cardiovascular Disease Events in Individuals With Coronary Artery Disease
Authors: Moazzami Kasra , Wittbrodt Matthew T. , Lima Bruno B. , Nye Jonathon A. , Mehta Puja K. , Pearce Brad D. , Almuwaqqat Zakaria , Hammadah Muhammad , Levantsevych Oleksiy , Sun Yan V. , Raggi Paolo , Garcia Ernest V. , Goetz Margarethe , Quyyumi Arshed A. , Bremner J. Douglas , Vaccarino Viola , Shah Amit J. 
Published: June 2020

Background:
Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in individuals with coronary artery disease. Certain brain regions that control both emotional states and cardiac physiology may be involved in this relationship. The rostromedial prefrontal cortex (rmPFC) is an important brain region that processes stress and regulates immune and autonomic functions. Changes in rmPFC activity with emotional stress (reactivity) may be informative of future risk for MACE.

Methods:
Participants with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors and simultaneous brain imaging with high-resolution positron emission tomography brain imaging. We defined high rmPFC activation as a difference between stress and control scans greater than the median value for the entire cohort. Interleukin-6 levels 90 minutes after stress, and high-frequency heart rate variability during stress were also assessed. We defined MACE as a composite of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure hospitalization.

Results:

We studied 148 subjects (69% male) with mean±SD age of 62±8 years. After adjustment for baseline demographics, risk factors, and baseline levels of interleukin-6 and high-frequency heart rate variability, higher rmPFC stress reactivity was independently associated with higher interleukin-6 and lower high-frequency heart rate variability with stress. During a median follow-up of 3 years, 34 subjects (21.3%) experienced a MACE. Each increase of 1 SD in rmPFC activation with mental stress was associated with a 21% increase risk of MACE (hazard ratio, 1.21 [95% CI, 1.08–1.37]). Stress-induced interleukin-6 and high-frequency heart rate variability explained 15.5% and 32.5% of the relationship between rmPFC reactivity and MACE, respectively. Addition of rmPFC reactivity to conventional risk factors improved risk reclassification for MACE prediction, and C-statistic improved from 0.71 to 0.76 (
P
=0.03).

Conclusions:
Greater rmPFC stress reactivity is associated with incident MACE. Immune and autonomic responses to mental stress may play a contributory role.
The Two Forms of Modern Capitalism: Liberal and Illiberal States
Authors: Mihályi Péter , Szelenyi Ivan 
Published: June 2020

Abstract
What is the relationship between liberalism, illiberalism and despotic forms of dictatorship – this is the central question of this paper. From the 1970’s and especially after 1989-91 it appeared that the rise of global capitalism and liberal democracy was unstoppable. Since 2005 this trend seems to be reversed. The number of countries classified as “non-free,” “undemocratic” or “illiberal” has been increasing. The bottom line of this paper is that illiberal regimes (even if they tend to be dictatorial in some ways) as long as they offer a minimal legal guarantee to capitalist businesses, can accommodate a capitalist system. Under despotic-dictatorial systems this is unimaginable. In the second part of the paper the authors make an attempt to re-conceptualize capitalism with a new theory of rent.