bluuebunny/crossref_metadata_2025_split huggingface dataset:
The onset of the Early Toarcian flooding of the Pliensbachian carbonate platform of central Tunisia (north–south axis) as inferred from trace fossils and geochemistry
Authors: Reolid Matías , Soussi Mohamed , Reolid Jesús , Ruebsam Wolfgang , Taher Ilef Belhaj , Mattioli Emanuela , Saidi Moncef , Schwark Lorenz 
Published: July 2021

Abstract

The flooding of the Lower Jurassic shelf in the North Gondwana Palaeomargin during the early Toarcian occurred on a fragmented and irregular topography affected by differential subsidence – owing to the activity of listric faults along the North–South Axis of Tunisia – that favoured lateral changes in facies and thickness at a kilometric scale. The onset of Toarcian sedimentation (Polymorphum ammonite Zone, NJT5c nannofossil Subzone) in two adjacent sections was characterized by the deposition of limestones under high-energy conditions. The Châabet El Attaris section was located in a depressed sub-basin, and recorded restricted environmental conditions owing to water stagnation and an oxygen-depleted sea bottom. Therefore, dark mudstones developed, with increased total organic carbon contents and enhanced accumulation of redox-sensitive elements. The sedimentation of limestones bearing gutter cast structures is related to gravity flows probably linked to storm activities. These processes favoured the remobilization of sediments at the seafloor, as well as oxygen input to bottom waters, as shown by the record of trace fossils including
Zoophycos
,
Ophiomorpha
, and secondarily,
Chondrites
and
Diplocraterion
. The thinly interbedded dark mudstones are locally rich in thin-shelled bivalves that re-colonized the sea bottom after the sedimentation of these high-energy deposits, and subsequently underwent mass mortality related to the return of oxygen-depleted conditions. The Kef El Hassine section is located in the upper part of a tilted, less subsident block, as indicated by its reduced thickness compared with the Châabet El Attaris section; the absence of dark mudstones implies oxic conditions. The Polymorphum Zone consists of limestones showing evidence of sedimentation under high-energy conditions, along with hardgrounds. The occurrence of
Zoophycos
(deep-tiers) in the upper part of some limestone beds of the Polymorphum Zone is linked to minor erosive processes. The top of the high-energy sequence – below the deposits of a marly interval corresponding to the Levisoni Zone – is interpreted as a hardground given the high content of belemnites and
Arenicolites
, some of them boring on the eroded
Zoophycos
and
Thalassinoides
. This study shows that the sedimentary expression of the Jenkyns Event is not uniform across Tunisia, supporting the importance of local conditions in determining the development of anoxic conditions.
Posttreatment Downregulation of Type III Interferons in Patients with Acute Brucellosis
Authors: Shokri Mehran , Khonakdar Oreinab Ghaffari , Mohammadnia-Afrouzi Mousa , Sadeghi-Haddad-Zavareh Mahmoud , Hasanpour Amirhossein , Barary Mohammad , Ebrahimpour Soheil 
Published: July 2021

There is a limited number of clinical studies on interferon (IFN) levels in human brucellosis. The novel group of interferons, type III interferons, which consists of four IFN-λ (lambda) molecules called IFN-λ1 or interleukin-29 (IL-29), IFN-λ2 or IL-28A, IFN-λ3 or IL-28B, and IFN-λ4, is not fully known. This study is one of the first studies of IL-28A and IL-29 levels in brucellosis cases at the end of their treatment course. A total of 33 acute brucellosis patients were included in this study. We considered changes in the levels of IL-28A and IL-29 in cases with acute brucellosis before and after treatment with standard therapy that referred to the Ayatollah Rohani Hospital in Babol, northern Iran. Of 33 included patients, 22 (66.6%) were males, and 11 (33.4%) were females. The range of patients’ age was

49.21
±
17.70

years. Serum IL-29 and IL-28A (acute form:

56.4
±
30.32

pg/mL and

48.73
±
27.72

pg/mL, respectively, and posttreatment:

40.15
±
20.30

pg/mL and

38.79
±
22.66

pg/mL, respectively) levels were elevated significantly in acute brucellosis than after treatment (

p
<
0.05

). These findings indicate that considering biomarker levels in brucellosis patients may indicate the chronicity of infection. In conclusion, we suggest that IL-29 and IL-28A levels may be valuable biomarkers for follow-up patients with brucellosis.
A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kβ Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer
Authors: Sarker Debashis , Dawson Nancy A. , Aparicio Ana M. , Dorff Tanya B. , Pantuck Allan J. , Vaishampayan Ulka N. , Henson Lynn , Vasist Lakshmi , Roy-Ghanta Sumita , Gorczyca Michele , York Whitney , Ganji Gopinath , Tolson Jerry , de Bono Johann S. 
Published: July 2021

Abstract

Purpose:
In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR)-targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory PTEN activates PI3K/AKT signaling and contributes to resistance to androgen deprivation therapy and poor outcomes. Therefore, dual targeting of AR and PI3K/AKT pathways may limit tumor growth and reverse resistance.

Patients and Methods:
In this phase I study (NCT02215096), patients with PTEN-deficient mCRPC who progressed on prior enzalutamide received once-daily enzalutamide 160 mg plus PI3Kβ inhibitor GSK2636771 at 300 mg initial dose, with escalation or de-escalation in 100-mg increments, followed by dose expansion. Primary objectives were to evaluate safety/tolerability, determine the recommended phase II dose, and assess the 12-week non-progressive disease (PD) rate.

Results:
Overall, 37 patients were enrolled; 36 received ≥1 dose of GSK2636771 (200 mg: n = 22; 300 mg: n = 12; 400 mg: n = 2) plus 160 mg enzalutamide. Dose-limiting toxicities occurred in 5 patients (200 mg: n = 1; 300 mg: n = 2, 400 mg: n = 2). No new or unexpected adverse events or evidence of drug–drug interaction were observed. At the recommended dose of GSK2636771 (200 mg) plus enzalutamide, the 12-week non-PD rate was 50% (95% confidence interval: 28.2–71.8, n = 22); 1 (3%) patient achieved a radiographic partial response lasting 36 weeks. Four of 34 (12%) patients had prostate-specific antigen reduction of ≥50%.

Conclusions:
Although there was acceptable safety and tolerability with GSK2636771 plus enzalutamide in patients with PTEN-deficient mCRPC after failing enzalutamide, limited antitumor activity was observed.
Super and Nonresponders to Catheter Ablation for Atrial Fibrillation: A Quality-of-Life Assessment Using Patient Reported Outcomes
Authors: Farwati Medhat , Wazni Oussama M. , Tarakji Khaldoun G. , Diab Mohamed , Scandinaro Anna , Amin Mustapha , Zmaili Mohammad , Bazarbashi Najdat , Dikilitas Ozan , Nakagawa Hiroshi , Kuroda Shunsuke , Kanj Mohamed , Dresing Thomas J. , Callahan Thomas D. , Bhargava Mandeep , Baranowski Bryan , Rickard John , Cantillon Daniel J. , Tchou Patrick J. , Saliba Walid I. , Hussein Ayman A. 
Published: July 2021

Background:
Atrial fibrillation (AF) ablation targets improvement in quality of life (QoL). Data is scarce on predictors of QoL improvement following ablation. We aimed to investigate the clinical characteristics underlying differential response in QoL after AF ablation (with or without arrhythmia recurrence).

Methods:
All patients undergoing AF ablation (2013–2016) at our center were prospectively enrolled in a fully automated patient-reported outcomes registry. A large number of variables were collected including AF symptom severity scale and AF burden (as indicated by AF frequency and duration scores). Patients were divided into 3 groups based on self-report of QoL improvement: remarkable (super responders), mild/moderate, and unchanged or worse (nonresponders). Univariable and multivariable logistic regression models assessed clinical characteristics and QoL outcomes.

Results:

A total of 956 patients were included (25% females, mean age 63.9). Most patients (≈80%) were super responders (n=761), 138 (14.4%) had mild/moderate improvement, and 57 (5.9%) were nonresponders. The strongest predictors of remarkable QoL improvement were freedom of arrhythmia recurrence (OR, 2.42 [95% CI, 1.27–4.59],
P
=0.007) and lower AF burden at 12 months. Similarly, higher AF burden was significantly associated with clinical nonresponse. In patients with observed clinical recurrence-QoL mismatch, changes in AF burden at 12 months were the main predictors of QoL outcome, with lower burden predicting higher improvement in QoL and vice versa.

Conclusions:
Most patients derive significant QoL benefit from AF ablation. Freedom from arrhythmia recurrence and lower AF burden predict remarkable QoL improvement following ablation.
Propagation Vectors Facilitate Differentiation Between Conduction Block, Slow Conduction, and Wavefront Collision
Authors: Yavin Hagai D. , Bubar Zachary P. , Higuchi Koji , Sroubek Jakub , Yarnitsky Jonathan , Anter Elad 
Published: July 2021

Background:
Differentiation between conduction block, slow conduction, and wavefront collision can be difficult using activation mapping alone, often requiring differential pacing. Therefore, a real-time method for determination of complex patterns of conduction may be desired. We hereby report a novel algorithm for displaying propagation vectors, allowing differentiation between complex patterns of conduction and facilitating real-time detection of block during ablation.

Methods:
In 10 swine, a chronic transcaval ablation line with an intentional gap or complete block was created, simulating conduction block, slow conduction, and wavefront collision. The line was mapped during atrial pacing using Carto 3 and a novel high-resolution array that includes 48 minielectrodes (surface area, 0.9 mm2, spacing 2.4 mm) distributed over 6 splines (Optrell, Biosense Webster). Propagation vectors were created from unipolar waveforms of adjacent electrodes along and across splines that were acquired at single beats. To examine the utility of propagation vectors for detection conduction block during ablation, a cavotricuspid isthmus line was created during coronary sinus pacing with the array positioned lateral to the line.

Results:
Propagation vectors detected the gap in all 6 interrupted ablation lines, while activation maps only identified gap in 3/6 lines; in the remainder, activation maps alone could not differentiate between conduction block, slow conduction, or wavefront collision. Propagation vectors accurately determined block in all 4 contiguous ablation line, while activation maps suggested conduction block or were indeterminant due to wavefront collision in 2/4 lines. Cavotricuspid isthmus line block was detected during ablation by abrupt reversal of propagation vectors from a lateral-to-septal direction, and acute reconnection was detected by reversal of the propagating vectors back to a lateral direction.

Conclusions:
Real-time propagation vectors enhance the ability of standard activation maps to differentiate between complex patterns of conduction, including determination of conduction block during ablation.
Is Transposition of the Great Arteries Associated With Shortening of the Intrapericardial Portions of the Great Arterial Trunks? An Echocardiographic Analysis on Newborn Infants With Simple Transposition of the Great Arteries to Explore an Animal Model‐Based Hypothesis on Human Beings
Authors: Omer Seham O. , Alhabshan Fahad M. , Jijeh Abdulraouf M. Z. , Caimbon Natalia C. , Enriquez Carmelita C. , Männer Jörg , Yelbuz Talat Mesud 
Published: July 2021

Background
The pathogenesis of transposition of the great arteries (TGA) as a congenital heart defect of the outflow tract with discordant ventriculoarterial connections remains an enigma. TGA usually have parallel great arteries suggesting that deficient torsion of the embryonic arterial heart pole might cause discordant ventriculoarterial connections. It has been speculated that deficient elongation of the embryonic outflow tract might prevent its normal torsion resulting in TGA. The aim of our study was to clarify whether the intrapericardial portions of the great arteries in human patients with TGA might be indeed shorter than in normal hearts.

Methods and Results

Thirty‐four newborns with simple TGA and 35 newborns with normal hearts were analyzed by using images of the outflow tract in their echocardiograms and the following defined lengths of the great arteries were measured: aortic length 1, (AoL‐1) and aortic length 2 (AoL‐2) = distance between left and right aortic valve level and origin of the brachiocephalic artery, respectively. Pulmonary trunk length 1 (PTL‐1) and pulmonary trunk length 2 (PTL 2) = distance between left and right pulmonary valve level and origin of left and right pulmonary artery, respectively. All measurements of the AoL were significantly shorter in TGA compared to normal hearts (AoL‐1: 1.6±0.2 versus 2.05±0.1;
P
<0.0001; AoL‐2: 1.55±0.2 versus 2.13±0.1;
P
<0.0001). With regard to the pulmonary trunk (PT), PTL‐1 and PTL‐2 were found to be shorter and longer, respectively, in TGA compared with normal hearts, reflecting the differences in the spatial arrangement of the PT between the 2 groups as in TGA the PT is showing a mirror image of the normal anatomy. However, the overall length of the PT between the 2 groups did not differ.

Conclusions
Our data demonstrate that, compared with normal newborns, the ascending aorta is significantly shorter in newborns with TGA whereas the overall length of the PT does not differ between the 2 groups. This finding is in accord with the animal model‐based hypothesis that TGA may result from a growth deficit at the arterial pole of the embryonic heart.
Proteomic Signature of Dysfunctional Circulating Endothelial Colony‐Forming Cells of Young Adults
Authors: Tan Cheryl M. J. , Lewandowski Adam J. , Williamson Wilby , Huckstep Odaro J. , Yu Grace Z. , Fischer Roman , Simon Jillian N. , Alsharqi Maryam , Mohamed Afifah , Leeson Paul , Bertagnolli Mariane 
Published: July 2021

Background
A subpopulation of endothelial progenitor cells called endothelial colony‐forming cells (ECFCs) may offer a platform for cellular assessment in clinical studies because of their remarkable angiogenic and expansion potentials in vitro. Despite endothelial cell function being influenced by cardiovascular risk factors, no studies have yet provided a comprehensive proteomic profile to distinguish functional (ie, more angiogenic and expansive cells) versus dysfunctional circulating ECFCs of young adults. The aim of this study was to provide a detailed proteomic comparison between functional and dysfunctional ECFCs.

Methods and Results
Peripheral blood ECFCs were isolated from 11 subjects (45% men, aged 27±5 years) using Ficoll density gradient centrifugation. ECFCs expressed endothelial and progenitor surface markers and displayed cobblestone‐patterned morphology with clonal and angiogenic capacities in vitro. ECFCs were deemed dysfunctional if <1 closed tube formed during the in vitro tube formation assay and proliferation rate was <20%. Hierarchical functional clustering revealed distinct ECFC proteomic signatures between functional and dysfunctional ECFCs with changes in cellular mechanisms involved in exocytosis, vesicle transport, extracellular matrix organization, cell metabolism, and apoptosis. Targeted antiangiogenic proteins in dysfunctional ECFCs included SPARC (secreted protein acidic and rich in cysteine), CD36 (cluster of differentiation 36), LUM (lumican), and PTX3 (pentraxin‐related protein PYX3).

Conclusions
Circulating ECFCs with impaired angiogenesis and expansion capacities have a distinct proteomic profile and significant phenotype changes compared with highly angiogenic endothelial cells. Impaired angiogenesis in dysfunctional ECFCs may underlie the link between endothelial dysfunction and cardiovascular disease risks in young adults.
Coronary Circulatory Indexes Before and After Percutaneous Coronary Intervention in a Porcine Tandem Stenoses Model
Authors: Chang Haseong , Kim Hyun Kuk , Shin Doosup , Lim Kyung Seob , Kim Sun‐Uk , Jeon Chang‐Yeop , Lee Hwal‐Yong , Lee Youngjeon , Won Jinyoung , Lee Seung Hun , Kakuta Tsunekazu , Lee Joo Myung 
Published: July 2021

Background
In tandem stenoses, nonhyperemic pressure ratio pullback is the preferred method to fractional flow reserve (FFR), based on the assumption of stable resting coronary flow. This study aimed to evaluate temporal changes of coronary circulatory indexes in tandem stenoses before and after angioplasty for proximal stenosis.

Methods and Results

Coronary tandem stenoses were created by porcine restenosis model with 2 bare metal stents in the left anterior descending artery. Four weeks later, changes in distal coronary pressure (Pd), averaged peak velocity, microvascular resistance, transstenotic pressure gradient across distal stenosis, resting Pd/aortic pressure, and FFR were measured before and 1, 5, 10, 15, and 20 minutes after balloon angioplasty for proximal stenosis. After angioplasty, there were significant changes in both resting and hyperemic Pd, averaged peak velocity, microvascular resistance, and transstenotic pressure gradient across distal stenosis (all
P
values <0.01). After initial acute changes, hyperemic averaged peak velocity and microvascular resistance did not show significant difference from the baseline values (
P
=0.712 and 0.972, respectively). Conversely, resting averaged peak velocity remained increased (10.1±0.7 to 17.8±0.7;
P
<0.001) and resting microvascular resistance decreased (6.0±0.1 to 2.2±0.7;
P
<0.001). Transstenotic pressure gradient across distal stenosis was significantly increased in both resting (13.1±7.6 to 25.3±4.2;
P
=0.040) and hyperemic conditions (11.0±3.0 to 27.4±3.3 mm Hg;
P
<0.001). Actual post–percutaneous coronary intervention Pd/aortic pressure and FFR were significantly lower than predicted values (Pd/aortic pressure, 0.68±0.22 versus 0.85±0.14;
P
<0.001; FFR, 0.63±0.08 versus 0.81±0.08;
P
<0.001).

Conclusions
After angioplasty for proximal stenosis, transstenotic pressure gradient across distal stenosis showed similar changes between resting and hyperemic conditions. Both actual post–percutaneous coronary intervention resting Pd/aortic pressure and FFR were significantly lower than predicted values.
White Supremacy, Terrorism, and the Failure of Reconstruction in the
United States
Authors: Byman Daniel 
Published: July 2021

Abstract
Reconstruction failed in the United States because white Southerners who were opposed to it effectively used violence to undermine Black political power and force uncommitted white Southerners to their side. Although structural factors made it harder to suppress this violence, a series of policy failures proved most important. The Radical Republican-led U.S. government did not deploy enough troops or use them aggressively. Nor did it pursue alternative paths that might have made success more likely, such as arming the Black community. The violence caused Reconstruction to fail, and the victorious white supremacists embedded structural racism into the post-Reconstruction political and social system in the South. Reconstruction's failure illustrates the dangers of half measures. The United States sought to reshape the American South at low cost, in terms of both troop levels and time. In addition, the failure indicates the importance of ensuring that democratization includes the rule of law, not just elections. Most important, Reconstruction demonstrates that a common policy recommendation—compromise with the losers after a civil war—is often fraught, with the price of peace being generations of injustice.
When Do Ideological Enemies Ally?
Authors: Haas Mark L. 
Published: July 2021

Abstract
Why is it that international ideological enemies—states governed by leaders engaged in deep disputes about preferred domestic institutions and values—are sometimes able to overcome their ideological differences and ally to counter shared threats, and sometimes they are not? Alliances among ideological enemies confronting a common foe are unlike coalitions among ideologically similar states facing comparable threats. Members of these alliances are perpetually torn by two sets of powerful contending forces. Shared material threats push these states together, while the effects of ideological differences pull them apart. To predict when ideological enemies are and are not likely to ally in the pursuit of common interests, it is necessary to know which of these contending forces is likely to dominate at a particular time. The values of two ideological variables beyond that of ideological enmity play the key role in determining outcomes: (1) states’ susceptibility to major domestic ideological changes and (2) the nature of the ideological differences among countries. Similar levels of ideological enmity and material threats will have vastly different effects on leaders’ alliance policies as the values of these additional ideological variables alter.
Statistical Properties of Color Matching Functions
Authors: da Fonseca María , Samengo Inés 
Published: July 2021

AbstractIn trichromats, color vision entails the projection of an infinite-dimensional space (the one containing all possible electromagnetic power spectra) onto the three-dimensional space that modulates the activity of the three types of cones. This drastic reduction in dimensionality gives rise to metamerism, that is, the perceptual chromatic equivalence between two different light spectra. The classes of equivalence of metamerism are revealed by color-matching experiments in which observers adjust the intensity of three monochromatic light beams of three preset wavelengths (the primaries) to produce a mixture that is perceptually equal to a given monochromatic target stimulus. Here we use the linear relation between the color matching functions and the absorption probabilities of each type of cone to find particularly useful triplets of primaries. As a second goal, we also derive an analytical description of the trial-to-trial variability and the correlations of color matching functions stemming from Poissonian noise in photon capture. We analyze how the statistical properties of the responses to color-matching experiments vary with the retinal composition and the wavelengths of peak absorption probability, and compare them with experimental data on subject-to-subject variability obtained previously.