bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yield of the Fricke dosimeter irradiated with the recoil α and Li ions of the 10B(n,α)7Li nuclear reaction: effects of multiple ionization and temperature
Authors: Zakaria Abdullah Muhammad , Lertnaisat Phantira , Islam Muhammad Mainul , Meesungnoen Jintana , Katsumura Yosuke , Jay-Gerin Jean-Paul 
Published: November 2020

Monte Carlo track chemistry simulations were used to investigate the effects of multiple ionization (MI) of water on the yields (G values) of the ferrous sulfate (Fricke) dosimeter, which was irradiated with low-energy α and lithium ion recoils from the 10B(n,α)7Li nuclear reaction as a function of temperature from 25 to 350 °C. Calculations were performed individually for 1.47 MeV α-particles and 0.84 MeV lithium nuclei with dose-average linear energy transfer (LET) values of ∼196 and 225 keV/µm at 25 °C, respectively. The total yields were obtained by summing the G values for each recoil α and Li ion weighted with its fraction of the total energy absorbed. At room temperature, our G(Fe3+) values calculated under aerated and deaerated conditions only agreed well with the experimental results, provided the MI of water was incorporated in the simulations. This strongly supports the importance of the role of MI of water in the high-LET radiolysis of water. We also simulated the effects of MI of water on G-values for the primary species of the radiolysis of deaerated 0.4 M H2SO4 aqueous solutions by 10B(n,α)7Li recoils. As with the Fricke dosimeter, the best agreement between experiment and simulation was found at 25 °C when the MI of water was included in the simulations. It was also shown that G(Fe3+) decreases slightly as a function of temperature over the range of 25–350 °C. However, at elevated temperatures, no experimental data were available with which to compare our results.
The Kodaira dimension and singularities of moduli of stable sheaves on some elliptic surfaces
Authors: Yamada Kimiko 
Published: November 2020

Let [Formula: see text] be an elliptic surface over [Formula: see text] with [Formula: see text], and [Formula: see text] be the moduli scheme of rank-two stable sheaves [Formula: see text] on [Formula: see text] with [Formula: see text] in [Formula: see text]. We look into defining equations of [Formula: see text] at its singularity [Formula: see text], partly because if [Formula: see text] admits only canonical singularities, then the Kodaira dimension [Formula: see text] can be calculated. We show the following:(A)[Formula: see text] is at worst canonical singularity of [Formula: see text] if the restriction of [Formula: see text] to the generic fiber of [Formula: see text] has no rank-one subsheaf, and if the number of multiple fibers of [Formula: see text] is a few.(B)We obtain that [Formula: see text] and the Iitaka program of [Formula: see text] can be described in purely moduli-theoretic way for [Formula: see text], when [Formula: see text], [Formula: see text] has just two multiple fibers, and one of its multiplicities equals [Formula: see text].(C)On the other hand, when [Formula: see text] has a rank-one subsheaf, it may be insufficient to look at only the degree-two part of defining equations to judge whether [Formula: see text] is at worst canonical singularity or not.
GSK3β-Mediated Expression of CUG-Translated WT1 Is Critical for Tumor Progression
Authors: Yoshitomi Hisae , Lee Kun Y. , Yao Ke , Shin Seung Ho , Zhang Tianshun , Wang Qiushi , Paul Souren , Roh Eunmiri , Ryu Joohyun , Chen Hanyong , Aziz Faisal , Chakraborty Abhijit , Bode Ann M. , Dong Zigang 
Published: November 2020

Abstract

The Wilms' tumor 1 (WT1) gene is well known as a chameleon gene. It plays a role as a tumor suppressor in Wilms' tumor but also acts as an oncogene in other cancers. Previously, our group reported that a canonical AUG starting site for the WT1 protein (augWT1) acts as a tumor suppressor, whereas a CUG starting site for the WT1 protein (cugWT1) functions as an oncogene. In this study, we report an oncogenic role of cugWT1 in the AOM/DSS-induced colon cancer mouse model and in a urethane-induced lung cancer model in mice lacking cugWT1. Development of chemically-induced tumors was significantly depressed in cugWT1-deficient mice. Moreover, glycogen synthase kinase 3β promoted phosphorylation of cugWT1 at S64, resulting in ubiquitination and degradation of the cugWT1 associated with the F-box−/− WD repeat-containing protein 8. Overall, our findings suggest that inhibition of cugWT1 expression provides a potential candidate target for therapy.

Significance:
These findings demonstrate that CUG-translated WT1 plays an oncogenic role in vivo, and GSK3β-mediated phosphorylation of cugWT1 induces its ubiquitination and degradation in concert with FBXW8.
Calcium Ion Chelation Preserves Platelet Function During Cold Storage
Authors: Xiang Binggang , Zhang Guoying , Zhang Yan , Wu Congqing , Joshi Smita , Morris Andrew J. , Ware Jerry , Smyth Susan S. , Whiteheart Sidney W. , Li Zhenyu 
Published: November 2020

Objective:
Platelet transfusion is a life-saving therapy to prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. However, for >6 decades, safe and effective strategies for platelet storage have been an impediment to widespread use of platelet transfusion. Refrigerated platelets are cleared rapidly from circulation, precluding cold storage of platelets for transfusion. Consequently, platelets are stored at room temperature with an upper limit of 5 days due to risks of bacterial contamination and loss of platelet function. This practice severely limits platelet availability for transfusion. This study is to identify the mechanism of platelet clearance after cold storage and develop a method for platelet cold storage.

Approach and Results:
We found that rapid clearance of cold-stored platelets was largely due to integrin activation and apoptosis. Deficiency of integrin β3 or caspase-3 prolonged cold-stored platelets in circulation. Pretreatment of platelets with EGTA, a cell impermeable calcium ion chelator, reversely inhibited cold storage-induced platelet activation and consequently prolonged circulation of cold-stored platelets. Moreover, transfusion of EGTA-treated, cold-stored platelets, but not room temperature-stored platelets, into the mice deficient in glycoprotein Ibα significantly shortened tail-bleeding times and diminished blood loss.

Conclusions:
Integrin activation and apoptosis is the underlying mechanism of rapid clearance of platelets after cold storage. Addition of a cell impermeable calcium ion chelator to platelet products is potentially a simple and effective method to enable cold storage of platelets for transfusion.
Sex-Specific Platelet Activation Through Protease-Activated Receptors Reverses in Myocardial Infarction
Authors: Soo Kim Beom , Auerbach David S. , Sadhra Hamza , Godwin Matthew , Bhandari Rohan , Ling Frederick S. , Mohan Amy , Yule David I. , Wagner Larry , Rich David Q. , Ture Sara , Morrell Craig N. , Timpanaro-Perrotta Livia , Younis Arwa , Goldenberg Ilan , Cameron Scott J. 
Published: November 2020

Objective:
The platelet phenotype in certain patients and clinical contexts may differ from healthy conditions. We evaluated platelet activation through specific receptors in healthy men and women, comparing this to patients presenting with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction.

Approach and Results:
We identified independent predictors of platelet activation through certain receptors and a murine MI model further explored these findings. Platelets from healthy women and female mice are more reactive through PARs (protease-activated receptors) compared with platelets from men and male mice. Multivariate regression analyses revealed male sex and non-ST-segment-elevation myocardial infarction as independent predictors of enhanced PAR1 activation in human platelets. Platelet PAR1 signaling decreased in women and increased in men during MI which was the opposite of what was observed during healthy conditions. Similarly, in mice, thrombin-mediated platelet activation was greater in healthy females compared with males, and lesser in females compared with males at the time of MI.

Conclusions:
Sex-specific signaling in platelets seems to be a cross-species phenomenon. The divergent platelet phenotype in males and females at the time of MI suggests a sex-specific antiplatelet drug regimen should be prospectively evaluated.
Abstract 14913: The Impact of the Wearable Cardioverter-defibrillators on Quality of Life: Insights From the Vest Trial
Authors: Cheung Chris C , Olgin Jeffrey , Pletcher Mark J , Hue Trisha , Vittinghoff Eric , Lin Feng , Lai Mason , Lee Byron K 
Published: November 2020

Background:
There is scant research on the effect of wearable cardioverter-defibrillators (WCDs) on quality of life (QOL). One retrospective observational study concluded that WCDs have a negative impact. The VEST Trial was a randomized controlled trial of the WCD allowing a more definitive and complete analysis of QOL among WCD users.

Hypothesis:
We sought to determine if the WCD impacts patient-reported QOL, including depression, anxiety, and physical activity levels.

Methods:
In the VEST trial, participants with severe left ventricular dysfunction (EF≤35%) after MI were randomized in a 2:1 ratio to receive a WCD plus guideline directed therapy (GDMT) versus GDMT alone. During the 3-month follow-up period, participants were asked to complete QOL assessments and health questionnaires.

Results:
1524 participants were randomized to WCD plus GDMT versus 778 participants to GDMT alone. The mean age was 60.9±12.6 years and 61.4±12.3 years in the two groups, respectively. Participants were 73.5% male, had an average body-mass index of 28.4±5.5 kg/m2, and a mean EF of 28%.

During a mean follow-up of 84.3±15.6 days, health questionnaires and QOL assessments were completed by 1340 participants, including 898 receiving WCD plus GDMT, and 442 receiving GDMT alone.
See Table 1 for the results of QOL assessments and health questionnaires. There were no differences in QOL according to the SF-36 physical and mental component scores, and EQ-5D scores between WCD plus GDMT versus GDMT alone. There were also no differences in depression (CES-D 10), anxiety (State-Trait Anxiety Inventory), physical activity (International Physical Activity Questionnaire), or self-reported health scale between groups (all p>0.05).

Conclusions:
In post-MI patients with low EF, the WCD does not affect QOL, depression, anxiety, physical activity, or self-reported health. Prescribers can be reassured that the WCD has no detrimental impact on patient-reported health measures.
Mitochondrial Reversible Changes Determine Diastolic Function Adaptations During Myocardial (Reverse) Remodeling
Authors: Miranda-Silva Daniela , G. Rodrigues Patrícia , Alves Estela , Rizo David , Fonseca Ana Catarina R.G. , Lima Tânia , Baganha Fabiana , Conceição Gloria , Sousa Cláudia , Gonçalves Alexandre , Miranda Isabel , Vasques-Nóvoa Francisco , Magalhães José , Leite-Moreira Adelino , Falcão-Pires Inês 
Published: November 2020

Background:
Often, pressure overload–induced myocardial remodeling does not undergo complete reverse remodeling after decreasing afterload. Recently, mitochondrial abnormalities and oxidative stress have been successively implicated in the pathogenesis of several chronic pressure overload cardiac diseases. Therefore, we aim to clarify the myocardial energetic dysregulation in (reverse) remodeling, mainly focusing on the mitochondria.

Methods:

Thirty-five Wistar Han male rats randomly underwent sham or ascending (supravalvular) aortic banding procedure. Echocardiography revealed that banding induced concentric hypertrophy and diastolic dysfunction (early diastolic transmitral flow velocity to peak early-diastolic annular velocity ratio, E/E′: sham, 13.6±2.1, banding, 18.5±4.1,
P
=0.014) accompanied by increased oxidative stress (dihydroethidium fluorescence: sham, 1.6×10
8
±6.1×10
7
, banding, 2.6×10
8
±4.5×10
7
,
P
<0.001) and augmented mitochondrial function. After 8 to 9 weeks, half of the banding animals underwent overload relief by an aortic debanding surgery (n=10).

Results:

Two weeks later, hypertrophy decreased with the decline of oxidative stress (dihydroethidium fluorescence: banding, 2.6×10
8
±4.5×10
7
, debanding, 1.96×10
8
±6.8×10
7
,
P
<0.001) and diastolic dysfunction improved simultaneously (E/E′: banding, 18.5±4.1, debanding, 15.1±1.8,
P
=0.029). The reduction of energetic demands imposed by overload relief allowed the mitochondria to reduce its activity and myocardial levels of phosphocreatine, phosphocreatine/ATP, and ATP/ADP to normalize in debanding towards sham values (phosphocreatine: sham, 38.4±7.4, debanding, 35.6±8.7,
P
=0.71; phosphocreatine/ATP: sham, 1.22±0.23 debanding, 1.11±0.24,
P
=0.59; ATP/ADP: sham, 6.2±0.9, debanding, 5.6±1.6,
P
=0.66). Despite the decreased mitochondrial area, complex III and V expression increased in debanding compared with sham or banding. Autophagy and mitophagy-related markers increased in banding and remained higher in debanding rats.

Conclusions:
During compensatory and maladaptive hypertrophy, mitochondria become more active. However, as the disease progresses, the myocardial energetic demands increase and the myocardium becomes energy deficient. During reverse remodeling, the concomitant attenuation of cardiac hypertrophy and oxidative stress allowed myocardial energetics, left ventricle hypertrophy, and diastolic dysfunction to recover. Autophagy and mitophagy are probably involved in the myocardial adaptation to overload and to unload. We conclude that these mitochondrial reversible changes underlie diastolic function adaptations during myocardial (reverse) remodeling.
Heart Failure and Shared Decision-Making: Patients Open to Medication-Related Cost Discussions
Authors: Rao Birju R. , Dickert Neal W. , Morris Alanna A. , Speight Candace D. , Smith Graham H. , Shore Supriya , Moore Miranda A. 
Published: November 2020

Background:
Discussions of medication costs between patients and clinicians are infrequent and often suboptimal. In the context of recently introduced drugs that are effective but expensive, patients with heart failure with reduced ejection fraction provide an ideal population to understand the perspectives of patients with chronic illness on medication cost and cost discussions.

Methods:
To explore patients’ perspectives on discussing out-of-pocket medication costs with clinicians, 49 adults, aged 44 to 70 years, with heart failure with reduced ejection fraction were recruited from outpatient heart failure clinics. Descriptive qualitative analysis was performed on open-ended text data.

Results:
Participants who had prior medication-related cost discussions described their experience as generally positive, but about half of the participants had never had a cost discussion with their clinician. Most participants were open to cost discussions with clinicians and preferred that the clinician initiate discussions regarding medication cost. Importantly, these preferences held constant across reported levels of financial burden.

Conclusions:
These data suggest a substantial willingness on the part of patients with heart failure with reduced ejection fraction to incorporate cost discussions into their care and identify important aspects of these discussions for clinicians to consider when engaging in conversations where cost is relevant. Improving understanding about how to integrate patient preferences regarding cost discussions into clinical encounters is an important priority for advancing patient-centered care.
Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure
Authors: Felker G. Michael , Solomon Scott D. , McMurray John J.V. , Cleland John G.F. , Abbasi Siddique A. , Malik Fady I. , Zhang Hanze , Globe Gary , Teerlink John R. ,   for the COSMIC-HF Investigators
Published: November 2020

Background:
Chronic heart failure with reduced ejection fraction impairs health-related quality of life (HRQL). Omecamtiv mecarbil (OM)—a novel activator of cardiac myosin—improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of OM on symptoms and HRQL in patients with chronic heart failure with reduced ejection fraction and elevated natriuretic peptides enrolled in the COSMIC-HF trial (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure).

Methods:
Patients (n=448) were randomized 1:1:1 to placebo, 25 mg of OM BID, or to pharmacokinetically guided dose titration (OM-PK) for 20 weeks. The Kansas City Cardiomyopathy Questionnaire was administered to assess HRQL at baseline, 16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom Score, Physical Limitation Scale, and Clinical Summary Score.

Results:

Mean change in score from baseline to 20 weeks for the Total Symptom Score was 5.0 (95% CI, 1.8–8.1) for placebo, 6.6 (95% CI, 3.4–9.8) for OM 25 mg (
P
=0.32 versus placebo), and 9.9 (95% CI, 6.7–13.0) for OM-PK (
P
=0.03 versus placebo); for the Physical Limitation Scale, it was 3.1 for placebo (95% CI, −0.3 to 6.6), 6.0 (95% CI, 3.1–8.9) for OM 25 mg (
P
=0.12), and 4.3 (95% CI, 0.7–7.9) for OM-PK (
P
=0.42); for the Clinical Summary Score, it was 4.1 (95% CI, 1.4–6.9) for placebo, 6.3 (95% CI, 3.6–9.0) for OM 25 mg (
P
=0.19), and 7.0 (95% CI, 4.1–10.0) for OM-PK (
P
=0.14). Differences between OM and placebo were greater in patients who were more symptomatic at baseline.

Conclusions:
HRQL as measured by the Total Symptom Score improved in patients with heart failure with reduced ejection fraction assigned to the OM-PK group relative to placebo. Ongoing trials are prospectively testing whether OM improves symptoms and HRQL in heart failure with reduced ejection fraction.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01786512.
Determinants of Value in Coronary Artery Bypass Grafting
Authors: Brescia Alexander A. , Vu Joceline V. , He Chang , Li Jun , Harrington Steven D. , Thompson Michael P. , Norton Edward C. , Regenbogen Scott E. , Syrjamaki John D. , Prager Richard L. , Likosky Donald S. ,   on behalf of the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative (MSTCVS-QC) and the Michigan Value Collaborative (MVC)
Published: November 2020

Background
Over 180 000 coronary artery bypass grafting (CABG) procedures are performed annually, accounting for $7 to $10 billion in episode expenditures. Assessing tradeoffs between spending and quality contributing to value during 90-day episodes has not been conducted but is essential for success in bundled reimbursement models. We, therefore, identified determinants of variability in hospital 90-day episode value for CABG.

Methods
Medicare and private payor admissions for isolated CABG from 2014 to 2016 were retrospectively linked to clinical registry data for 33 nonfederal hospitals in Michigan. Hospital composite risk-adjusted complication rates (≥1 National Quality Forum-endorsed, Society of Thoracic Surgeons measure: deep sternal wound infection, renal failure, prolonged ventilation >24 hours, stroke, re-exploration, and operative mortality) and 90-day risk-adjusted, price-standardized episode payments were used to categorize hospitals by value by defining the intersection between complications and spending.

Results

Among 2573 total patients, those at low- versus high-value hospitals had a higher percentage of prolonged length of stay >14 days (9.3% versus 2.4%,
P
=0.006), prolonged ventilation (17.6% versus 4.8%,
P
<0.001), and operative mortality (4.8% versus 0.6%,
P
=0.001). Mean total episode payments were $51 509 at low-compared with $45 526 at high-value hospitals (
P
<0.001), driven by higher readmission ($3675 versus $2177,
P
=0.005), professional ($7462 versus $6090,
P
<0.001), postacute care ($7315 versus $5947,
P
=0.031), and index hospitalization payments ($33 474 versus $30 800,
P
<0.001). Among patients not experiencing a complication or 30-day readmission (1923/2573, 74.7%), low-value hospitals had higher inpatient evaluation and management payments ($1405 versus $752,
P
<0.001) and higher utilization of inpatient rehabilitation (7% versus 2%,
P
<0.001), but lower utilization of home health (66% versus 73%,
P
=0.016) and emergency department services (13% versus 17%,
P
=0.034).

Conclusions
To succeed in emerging bundled reimbursement programs for CABG, hospitals and physicians should identify strategies to minimize complications while optimizing inpatient evaluation and management spending and use of inpatient rehabilitation, home health, and emergency department services.
What God Does Not Possess: Moses Mendelssohn’s Philosophy of Imperfection
Authors: Atlas Dustin Noah 
Published: November 2020

Abstract
This paper proposes that Moses Mendelssohn’s Morning Hours be viewed as the final chapter in a philosophy of imperfection that Mendelssohn had been developing over the course of his life. It is further argued that this philosophy of imperfection is still of philosophical interest. After demonstrating that the concept of imperfection animates Mendelssohn’s early work, this paper turns towards the specific arguments about imperfection Mendelssohn made in the midst of the pantheism controversy—in particular, the claim that human imperfection attests to an independent existence. Simply put: God knows human imperfection, but does not possess it. Therefore, there is a sense in which humans, because of our imperfections, are distinct from God. It is shown that, at least in part, Mendelssohn’s entry into the pantheism controversy, and his willingness to engage even his recently departed friend Lessing in argument, is part of his strategy to preserve his philosophy of imperfection.
On the Legitimacy of National Interests of Sponsoring States: A Deep Sea Mining Conundrum
Authors: Willaert Klaas 
Published: November 2020

Abstract
Beyond national jurisdiction, the deep seabed and its mineral resources are designated as the ‘common heritage of mankind’. Nevertheless, the governing legal framework does not only consist of international instruments, as domestic legislation issued by sponsoring States also plays a decisive role. The legitimacy of certain national provisions can be questioned though, taking into account the duty to carry out activities in the Area for the benefit of mankind as a whole. For instance, can a sponsoring state demand that the proposed mining activities are in the public interest of the State? Are they allowed to generate revenue by introducing a recovery fee or other taxes? Should developing States enjoy more leeway, given the particular consideration for their interests and needs in the Law of the Sea Convention? This article analyses to what extent creeping national interests in domestic legislation on deep sea mining are in accordance with international law.