bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment and prevention of lipoprotein(a)-mediated cardiovascular disease: the emerging potential of RNA interference therapeutics
Authors: Swerdlow Daniel I , Rider David A , Yavari Arash , Wikström Lindholm Marie , Campion Giles V , Nissen Steven E 
Published: March 2021

Abstract
Lipid- and lipoprotein-modifying therapies have expanded substantially in the last 25 years, resulting in reduction in the incidence of major adverse cardiovascular events. However, no specific lipoprotein(a) [Lp(a)]-targeting therapy has yet been shown to reduce cardiovascular disease risk. Many epidemiological and genetic studies have demonstrated that Lp(a) is an important genetically determined causal risk factor for coronary heart disease, aortic valve disease, stroke, heart failure, and peripheral vascular disease. Accordingly, the need for specific Lp(a)-lowering therapy has become a major public health priority. Approximately 20% of the global population (1.4 billion people) have elevated levels of Lp(a) associated with higher cardiovascular risk, though the threshold for determining ‘high risk’ is debated. Traditional lifestyle approaches to cardiovascular risk reduction are ineffective at lowering Lp(a). To address a lifelong risk factor unmodifiable by non-pharmacological means, Lp(a)-lowering therapy needs to be safe, highly effective, and tolerable for a patient population who will likely require several decades of treatment. N-acetylgalactosamine-conjugated gene silencing therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotide targeting LPA, are ideally suited for this application, offering a highly tissue- and target transcript-specific approach with the potential for safe and durable Lp(a) lowering with as few as three or four doses per year. In this review, we evaluate the causal role of Lp(a) across the cardiovascular disease spectrum, examine the role of established lipid-modifying therapies in lowering Lp(a), and focus on the anticipated role for siRNA therapeutics in treating and preventing Lp(a)-related disease.
Mitral and tricuspid annuloplasty ring dehiscence: a systematic review with pooled analysis
Authors: Arjomandi Rad Arian , Naruka Vinci , Vardanyan Robert , Viviano Alessandro , Salmasi Mohammad Yousuf , Magouliotis Dimitris , Kendall Simon , Casula Roberto , Athanasiou Thanos 
Published: March 2021

Summary

OBJECTIVES
Mitral and tricuspid ring annuloplasty dehiscence with consequent recurrent valve regurgitation is a rare but challenging procedural failure. The incidence and predisposing risk factors for annuloplasty ring dehiscence include technical and pathological ones.

METHODS
A systematic database search with pooled analysis was conducted of original articles that only included dehiscence rate of mitral and tricuspid ring in EMBASE, MEDLINE, Cochrane database and Google Scholar, from inception to November 2020. The outcomes included were dehiscence rate in mitral and tricuspid, type of ring implanted, dehiscence rate by pathology and by ring size and shape.

RESULTS
Our search yielded 821 relevant studies. Thirty-three studies met the inclusion criteria with a total of 10 340 patients (6543 mitral, 1414 tricuspid) of which 87 (mitral) and 30 (tricuspid) had dehiscence. Overall, dehiscence rate was 1.43%, diagnosed at a median of 4.5 ± 1.0 months postoperatively. A significant difference in mitral dehiscence rate was found by ring type (semi-rigid 1.86%, rigid 2.32%; flexible 0.43%; P &lt; 0.001). There was no significant difference in rate of dehiscence by ring size (P = 0.067) and shape in mitral (P = 0.281) but there was higher dehiscence rate in ischaemic compared to non-ischaemic mitral regurgitation (3.91% vs 1.63%; P = 0.022). Among tricuspid studies, 9 of 10 studies did not report any dehiscence.

CONCLUSIONS
Although rigid, semi-rigid and flexible annuloplasty rings provide acceptable valve repair outcomes, mitral annuloplasty ring dehiscence is clinically more common among rigid rings. Understanding the multifactorial nature of ring dehiscence will help in identifying the patients at high risk and improve their clinical outcomes.
The Ship of Democracy
Authors: Whitehall Deborah 
Published: March 2021

Abstract
War, exile and democratic crisis organized the world-mind in the early 1940s around the transitive exigences of states. Political in origin, those trials also magnified the pressure points of international legal personality due to the disaggregation of territory, people and legitimate, being democratic, government. France presents the paradigm case worthy of attention for the unexpected recoding of the normative lines of state identity by the cultural internationalism of French scholars in exile. L’École Libre Hautes Etudes (l’ÉLHE) in New York stands out as the representative of a civic and cultural code of state identity framed by the cultural activism of esteemed intellectuals and contingent on ideas or rather, on the ideal of the free state. Their symbolic ship of democracy alerts internationalists to the aleatory meetings between different codes of statehood which disrupt, and might easily progress, the normative rules of state identity during crisis. Three such encounters matter now, anchoring this study about what happens to international law when democracy fails, for the recoding of legal standards by cultural agents of state: of rules of state recognition, of territorial sovereignty and of the meaning of legal internationalism after war.
Provenance and Family Variation in Biomass Potential of Loblolly Pine in the Piedmont of North Carolina
Authors: Maynor Jessica A , Isik Fikret , Walker Trevor D , Whetten Ross W , Heine Austin J , Payn Kitt G , McKeand Steven E 
Published: March 2021

Abstract
Considerable genetic differences in loblolly pine (Pinus taeda L.) exist for growth, stem form, and wood quality traits that influence biomass/biofuel production. By planting genetically superior trees with desirable biomass/biofuel traits, it is possible to substantially increase the amount of biomass and potential sawtimber trees produced from plantations. Ten of the fastest growing loblolly pine families from two provenances, Atlantic Coastal Plain and Piedmont, were tested for their biomass potential in North Carolina on a Piedmont site. At this northern Piedmont site at age six years, there were no provenance differences for biomass production or for trees with sawtimber potential. Variation in volume and sawtimber potential was significant at the family level. For biomass plantations, risks can be mitigated because of shorter rotation length, allowing for a higher-risk seed lot to capture greater gains in terms of volume. For a longer-rotation sawtimber stand, a more conservative family deployment strategy should be considered to maintain stem quality at the end of the rotation. Understanding the different seed source families and harvest regimes is essential to ensure profitable returns from pine plantations.
Reaction Time Intraindividual Variability Reveals Inhibitory Deficits in Single- and Multiple-Domain Amnestic Mild Cognitive Impairment
Authors: Chow Ricky , Rabi Rahel , Paracha Shahier , Vasquez Brandon P , Hasher Lynn , Alain Claude , Anderson Nicole D 
Published: March 2021

AbstractObjectivesAmnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer’s disease and other dementias, is characterized by episodic memory impairment. Recent evidence has shown inhibitory control deficits in aMCI, but the extent of these deficits across inhibitory domains (i.e., response inhibition and interference control) and aMCI subtypes (i.e., single vs multiple domain) remains unclear. Few studies have included reaction time intraindividual variability (RT IIV) in these efforts. The aim of this study was to compare response inhibition and interference control between aMCI subtypes using measures of accuracy, mean RT, and RT IIV.MethodsWe report data from 34 individuals with single-domain aMCI (sdaMCI, 66–86 years), 20 individuals with multiple-domain aMCI (mdaMCI, 68–88 years), and 52 healthy controls (HC, 64–88 years) who completed tasks of response inhibition (Go–NoGo) and interference control (Flanker). Group differences in accuracy, mean RT, and RT IIV were examined for both tasks.ResultsIndividuals with mdaMCI had higher RT IIV than the other groups on both tasks. In RT IIV, we observed an interference control deficit in mdaMCI and sdaMCI relative to healthy controls, a finding not observed through accuracy or mean RT.DiscussionRT IIV may detect subtle differences in inhibition deficits between aMCI subtypes that may not be evident with conventional behavioral measures. Findings support the supplementary use of RT IIV when assessing early executive function deficits.
Partner Contributions to Goal Pursuit: Findings From Repeated Daily Life Assessments With Older Couples
Authors: Zambrano Elizabeth , Pauly Theresa , Gerstorf Denis , Ashe Maureen C , Madden Kenneth M , Hoppmann Christiane A 
Published: March 2021

Abstract

Objectives
This study focuses on the role of spouses for facilitating goal progress during a phase in life when individual resources for goal pursuit are particularly limited. Specifically, we examined the moderating role of relationship characteristics in old age for time-varying partner involvement–goal progress associations as couples engaged in their everyday lives. We also assessed time-varying associations between everyday goal progress, effectiveness of partner contributions, and spousal satisfaction with this contribution.

Methods
We used multilevel modeling to analyze data from 118 couples (Mage = 70 years, SD = 5.9; 60–87 years, 50% women; 57% White). Both partners reported their personal goals and provided information on relationship satisfaction, conflict, and support. They also provided simultaneous ratings of everyday goal progress, effort, partner involvement as well as effectiveness of and satisfaction with partner contribution up to three times daily over 7 days.

Results
In line with expectations, higher relationship satisfaction and support and lower conflict were associated with higher goal progress when the partner was involved in goal pursuit. Both effectiveness of and satisfaction with partner contributions were positively associated with everyday goal progress.

Discussion
Whether partner involvement is beneficial for goal progress depends on characteristics of the relationship as well as what partners actually do in everyday life. This highlights the importance of considering both stable person characteristics as well as time-varying processes to capture the complexity of goal pursuit in older couples.
Bayesian inversion using nested trans-dimensional Gaussian processes
Authors: Ray Anandaroop 
Published: March 2021

SUMMARYTo understand earth processes, geoscientists infer subsurface earth properties such as electromagnetic resistivity or seismic velocity from surface observations of electromagnetic or seismic data. These properties are used to populate an earth model vector, and the spatial variation of properties across this vector sheds light on the underlying earth structure or physical phenomenon of interest, from groundwater aquifers to plate tectonics. However, to infer these properties the spatial characteristics of these properties need to be known in advance. Typically, assumptions are made about the length scales of earth properties, which are encoded a priori in a Bayesian probabilistic setting. In an optimization setting, appeals are made to promote model simplicity together with constraints which keep models close to a preferred model. All of these approaches are valid, though they can lead to unintended features in the resulting inferred geophysical models owing to inappropriate prior assumptions, constraints or even the nature of the solution basis functions. In this work it will be shown that in order to make accurate inferences about earth properties, inferences can first be made about the underlying length scales of these properties in a very general solution basis. From a mathematical point of view, these spatial characteristics of earth properties can be conveniently thought of as ‘properties’ of the earth properties. Thus, the same machinery used to infer earth properties can be used to infer their length scales. This can be thought of as an ‘infer to infer’ paradigm analogous to the ‘learning to learn’ paradigm which is now commonplace in the machine learning literature. However, it must be noted that (geophysical) inference is not the same as (machine) learning, though there are many common elements which allow for cross-pollination of useful ideas from one field to the other, as is shown here. A non-stationary trans-dimensional Gaussian Process (TDGP) is used to parametrize earth properties, and a multichannel stationary TDGP is used to parametrize the length scales associated with the earth property in question. Using non-stationary kernels, that is kernels with spatially variable length scales, models with sharp discontinuities can be represented within this framework. As GPs are multidimensional interpolators, the same theory and computer code can be used to solve geophysical problems in 1-D, 2-D and 3-D. This is demonstrated through a combination of 1-D and 2-D non-linear regression examples and a controlled source electromagnetic field example. The key difference between this and previous work using TDGP is generalized nested inference and the marginalization of prior length scales for better posterior subsurface property characterization.
Crustal seismic structure and anisotropy of Madagascar and southeastern Africa using receiver function harmonics: interplay of inherited local heterogeneities and current regional stress
Authors: Tsang-Hin-Sun E , Evain M , Julia J , Lamarque G , Schnurle P 
Published: March 2021

SummaryThis study investigates the seismic structure and anisotropy in the crust beneath Madagascar and southeastern Africa, using receiver functions. The understanding of seismic anisotropy is essential for imaging past and present deformation in the lithosphere–asthenosphere system. In the upper mantle, seismic anisotropy mainly results from the orientation of olivine, which deforms under tectonic (fossil anisotropy) or flow processes (in the asthenosphere). In the crust, the crystallographic alignment of amphiboles, feldspars (plagioclase) or micas or the alignment of heterogeneities such as fractures, add to a complex geometry, which results in challenges to understanding the Earth's shallow structure. The decomposition of receiver functions into backazimuth harmonics allows to characterize orientations of lithospheric structure responsible for azimuthally varying seismic signals, such as a dipping isotropic velocity contrasts or layers of azimuthal seismic anisotropy. By analysing receiver function harmonics from records of 48 permanent or temporary stations this study reveals significant azimuthally varying signals within the upper crust of Madagascar and southeastern Africa. At 30 stations crustal anisotropy dominates the harmonics while the signature of a dipping isotropic contrast is dominant at the remaining 18 stations. However, all stations’ backazimuth harmonics show complex signals involving both dipping isotropic and shallow anisotropic contrasts or more than one source of anisotropy at shallow depth. Our calculated orientations for the crust are therefore interpreted as reflecting either the average or the interplay of several sources of azimuthally varying signals depending of their strength. However, comparing information between stations allows us to draw the same conclusions regionally: in both southern Africa and Madagascar our measurements reflect the interplay between local, inherited structural heterogeneities and crustal seismic anisotropy generated by the current extensional stress field imposed by the southward propagation of the East-African Rift System. A final comparison of our crustal orientations with SKS orientations attributed to mantle deformation further probes the interplay of crustal and mantle anisotropy on SKS measurements.
The Holocaust and the Shadow Text of Anna and the Swallow Man
Authors: Smith Philip 
Published: March 2021

Abstract
This contribution addresses the challenges that face any attempt to render the Holocaust knowable through fiction, for children in particular: namely the need to balance truth with propriety, while giving form to an event that eludes depiction. Analyzing Gavriel Savit’s novel Anna and the Swallow Man, it argues that the text contains deliberate gaps and ambiguities. All of these gaps, to borrow Perry Nodelman’s term, suggest a “shadow text”—a version of the story unavailable to a younger reader, but hinted at throughout. This shadow text should prompt the child reader to approach an adult to learn more about the Second World War. Yet as Anna approaches her own more adult understanding, Savit reveals that the reality beyond the text remains essentially beyond articulation.
Modern Relics: The Sanctification of A-Bomb Objects in the Hiroshima Museum
Authors: Zwigenberg Ran 
Published: March 2021

Abstract
In April 2017, a group of mannequins was removed during renovation of the Hiroshima Peace Memorial Museum. The new exhibit instead focuses on objects left by the dead (ihin) as well as survivor testimonies, representing the latest change in a seventy-year controversy regarding museal representations of the devastation wrought by the atomic bomb. Controversies paralleled debates over Holocaust memorialization and the treatment of objects left by victims. The following examines the history of A-bomb objects in the Hiroshima museum, most importantly, the way relics have been discussed, exhibited, and debated. This evolution has elevated relics to the status of sacred objects, central to commemoration and memorialization.
Fredy Hirsch: Changing Perspectives on his Memory
Authors: Aharony Michal 
Published: March 2021

Abstract
At the Theresienstadt family camp in Auschwitz thousands of Jews were kept alive in “favorable” living conditions, only to be gassed after six months. Few scholars have examined one of the most influential figures there, Fredy Hirsch, a gay German-Jewish refugee to Czechoslovakia who initiated and managed the “children’s block.” Hundreds under his care received better food and were spared the brutality prevailing elsewhere in Auschwitz, brightening their final months. How he sacrificed his life for the children offers a particular window into the annihilation of Czech Jewry. The following analyzes changing images of Hirsch in literature and commemoration, the uncertainty surrounding his death, and the meaning survivors ascribed to Hirsch’s homosexuality.
Evaluation of Antimicrobial Susceptibility Profile inSalmonellaTyphi andSalmonellaParatyphi A: Presenting the Current Scenario in India and Strategy for Future Management
Authors: Veeraraghavan Balaji , Pragasam Agila K , Ray Pallab , Kapil Arti , Nagaraj Savitha , Perumal Sulochana Putli Bai , Saigal Karnika , Thomas Maria , Gupta Madhu , Rongsen-Chandola Temsunaro , Jinka Dasaratha Ramaiah , Shastri Jayanthi , Alexander Anna P , Koshy Roshine Mary , De Anuradha , Singh Ashita , Evelyn Ebenezer Sheena , Dutta Shanta , Bavdekar Ashish , More Deepak , Sanghavi Sonali , Nayakanti Raghuprakash Reddy , Jacob Jobin J , Amladi Anushree , Anandan Shalini , Abirami Baby S , Bakthavatchalam Yamuna D , Sethuvel Dhiviya P M , John Jacob , Kang Gagandeep 
Published: March 2021

AbstractBackgroundSystematic studies to estimate the disease burden of typhoid and paratyphoid in India are limited. Therefore, a multicenter study on the Surveillance of Enteric Fever in India was carried out to estimate the incidence, clinical presentation, and antimicrobial resistance (AMR) trend. The data presented here represent the national burden of AMR in Salmonella Typhi and Salmonella Paratyphi A.MethodsAntimicrobial susceptibility testing was performed for S. Typhi and S. Paratyphi A (n = 2373) isolates collected prospectively during a 2-year period from November 2017 to January 2020.ResultsOf 2373 Salmonella isolates, 2032 (85.6%) were identified as S. Typhi and 341 (14.4%) were S. Paratyphi A. Approximately 2% of S. Typhi were multidrug-resistant (MDR), whereas all 341 (100%) of S. Paratyphi A isolates were sensitive to the first-line antimicrobials. Among 98% of ciprofloxacin nonsusceptible isolates, resistance (minimum inhibitory concentration [MIC] &gt;0.5 µg/mL) was higher in S. Typhi (37%) compared with S. Paratyphi A (20%). Azithromycin susceptibility was 99.9% and 100% with a mean MIC of 4.98 μg/mL for S. Typhi and 7.39 μg/mL for S. Paratyphi A respectively. Ceftriaxone was the only agent that retained 100% susceptibility. Moreover, beta-lactam/beta-lactamase inhibitors showed potent in vitro activity against the study isolates.ConclusionsData obtained from this systematic surveillance study confirms the declining trend of MDR Salmonella isolates from India. The higher prevalence of ciprofloxacin nonsusceptibility enforces to limit its use and adhere to the judicious usage of azithromycin and ceftriaxone for enteric fever management.
Severe Acute Respiratory Syndrome Coronavirus 2 ACE2 and TMPRSS2 Receptor Protein Expression Patterns Throughout Gestation
Authors: Roberts Drucilla J , Bebell Lisa M , Edlow Andrea G 
Published: March 2021

Abstract
We previously demonstrated that the late gestation placental expression pattern of ACE2 (the primary severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] receptor) is localized to the villous syncytiotrophoblast (ST), usually in a polarized membranous pattern at the ST base sparing the apical surface (that directly exposed to maternal blood). We found that the late gestation placental expression pattern of TMPRSS2 (the spike proteinase required for SARS-CoV-2 cellular infection), is usually absent in the trophoblast but is rarely, weakly expressed in the placental endothelium. We now show the developmental protein expression patterns of ACE2 and TMPRSS2 by immunohistochemistry throughout gestation, from the first through third trimester. We found that TMPRSS2 expression was rarely detectable in villous endothelium and very rarely detectable in the ST across gestation. We found that ACE2 expression varied during gestation with circumferential ST expression more common in early gestations and polarized expression more common in later gestation. Although this study is small, these preliminary results suggest that earlier gestation pregnancies may be more vulnerable to infection than later gestation pregnancies.
Excessive Matrix Metalloproteinase-1 and Hyperactivation of Endothelial Cells Occurred in COVID-19 Patients and Were Associated With the Severity of COVID-19
Authors: Syed Fahim , Li Wei , Relich Ryan F , Russell Patrick M , Zhang Shanxiang , Zimmerman Michelle K , Yu Qigui 
Published: March 2021

Abstract

Background
Systemic vascular injury occurs in coronavirus disease 2019 (COVID-19) patients; however, the underlying mechanisms remain unknown.

Methods
To clarify the role of inflammatory factors in COVID-19 vascular injury, we used a multiplex immunoassay to profile 65 inflammatory cytokines/chemokines/growth factors in plasma samples from 24 hospitalized (severe/critical) COVID-19 patients, 14 mild/moderate cases, and 13 healthy controls (HCs).

Results
COVID-19 patients had significantly higher plasma levels of 20 analytes than HCs. Surprisingly, only 1 cytokine, macrophage migration inhibitory factor (MIF), was among these altered analytes, while the rest were chemokines/growth factors. Additionally, only matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in hospitalized COVID-19 patients when compared to mild/moderate cases. We further studied MMP-1 enzymatic activity and multiple endothelial cell (EC) activation markers (soluble forms of CD146, intercellular adhesion molecule 1 [ICAM-1], and vascular cell adhesion molecule 1 [VCAM-1]) and found that they were highly dysregulated in COVID-19 patients.

Conclusions
COVID-19 patients have a unique inflammatory profile, and excessive MMP-1 and hyperactivation of ECs are associated with the severity of COVID-19.