bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transthyretin amyloidosis in aortic stenosis: clinical and therapeutic implications
Authors: Fabbri Gioele , Serenelli Matteo , Cantone Anna , Sanguettoli Federico , Rapezzi Claudio 
Published: October 2021

Abstract
About one in seven elderly patients with severe calcific aortic stenosis (AS) also have ATTR amyloid cardiomyopathy (AC-TTR). The reasons for this close association are not fully known, but the two entities are not only related by common epidemiology. For example, it is possible to hypothesize that an amyloidotic infiltration of the aortic valve, even partial, can act as a trigger for the development of endothelial damage and subsequent calcification. Another hypothesis is the increased myocardial strain induced by AS may locally favour the process of amyloidogenesis and tissue infiltration. In a patient with AS, the coexistence of AC-TTR can be suspected by careful analysis of the echocardiogram and the ECG, especially if a clinical history of carpal tunnel syndrome coexists. Bone tracer scintigraphy allows a diagnosis of certainty. Recently, several studies have evaluated the prognostic implications of the coexistence of the two entities in candidates for percutaneous aortic valve replacement, showing how amyloidosis would not significantly impact the results of the procedure, but would only be associated with a greater risk of distant heart failure. In patients with AS associated with AC-TTR, valve replacement should not be ruled out in the presence of the usual clinical-haemodynamic indications.
Atrial fibrillation in advanced renal failure: are there alternative solutions to warfarin-dicumarol?
Authors: Rossini Roberta , Casula Matteo , Ferlini Marco 
Published: October 2021

Abstract
Patients with atrial fibrillation (AF) and chronic renal failure (CRF) represent a growing population in epidemiological terms since both conditions increase with advancing age. The association of AF and CRF is burdened with a poor prognosis and with a high risk of adverse events, both ischaemic and haemorrhagic. Oral anticoagulant therapy, in these patients, is more problematic, especially due to the concomitant increased risk of bleeding. The use of direct oral anticoagulants (DOACs) in patients with non-severe renal insufficiency appears to be safe and effective. Since all currently available DOACs are at least partially eliminated by the kidney (dabigatran is the direct anticoagulant with the highest rate of renal elimination, approximately 80%), periodic monitoring of renal function is recommended to evaluate possible need for dosage adjustment. In patients with advanced renal insufficiency, the use of DOAC appears controversial, given the small number of clinical studies that have tested its efficacy and safety. It is known, however, that oral anticoagulation therapy with vitamin K antagonists (VKAs) is associated with an increase in nephropathy and renal-vascular calcification. From this point of view, therapy with DOAC could be more advantageous than VKAs. Data from clinical studies would seem to show that the use of dabigatran and rivaroxaban in these patients may lead to a reduction in the inevitable deterioration of renal function.
Clinical impact of myocardial fibrosis in severe aortic stenosis
Authors: Castrichini Matteo , Vitrella Giancarlo , De Luca Antonio , Altinier Alessandro , Korcova Renata , Pagura Linda , Radesich Cinzia , Sinagra Gianfranco 
Published: October 2021

Abstract
The pressure overload due to the progressive narrowing of the valve area determines the development of the left ventricular hypertrophy which characterizes aortic stenosis (AS). The onset of myocardial fibrosis marks the inexorable decline of an initially compensatory response towards heart failure. However, myocardial fibrosis does not yet represent a key element in the prognostic and therapeutic framework of AS. In this context, cardiac magnetic resonance imaging plays a major role by highlighting both the focal irreversible fibrotic replacement, using the late gadolinium enhancement (LGE) technique, and the earlier diffuse reversible interstitial fibrosis, using the T1 mapping techniques. For this reason, the presence of myocardial fibrosis would be useful to identify a subgroup of patients at greater risk of events among the subjects with severe AS. Actually, more and more evidences seem to identify the presence of LGE as a powerful prognostic factor to be used to optimize the timing of prosthetic valve replacement. Randomized clinical trials, such as the EVoLVeD trial currently underway, will be needed to better define the importance of myocardial fibrosis assessment in the management of patients with AS.
What we have learned: is pulmonary vein isolation still the cornerstone of atrial fibrillation ablation?
Authors: Metzner Andreas , Kuck Karl-Heinz , Chun Julian K R 
Published: October 2021

Abstract
Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. The cornerstone of all ablation strategies is electrical isolation of the pulmonary veins (PVs). Ablation strategies going beyond PV isolation (PVI) might be considered in the setting of recurrent AF despite durably isolated PVs. The lack of persistent PVI, however, limits the opportunities to perceive the real impact of this endpoint on AF suppression and to fully understand the benefit of extended ablation strategies going beyond. To overcome this limitation, novel and innovative ablation systems have been developed to facilitate acute PVI and to increase its durability. These systems include balloon-based ablation devices incorporating different energy sources such as cryo energy, laser, or radiofrequency current, but also new energy sources such as pulsed field ablation as a non-thermal energy source. These technologies could advance catheter ablation of AF to an early stage of the disease and to the primary treatment tool. The current manuscript focuses on the past, the present, and the future value of PVI as the cornerstone for interventional treatment of AF and on how to achieve durable PVI during the first procedure and to further improve the clinical success rates of AF ablation. It also analyses extended ablation strategies going beyond PVI and their impact.
Antibiotic dispensing during the COVID-19 pandemic: analysis of Welsh primary care dispensing data
Authors: Wasag Diana R , Cannings-John Rebecca , Hughes Kathryn , Ahmed Haroon 
Published: October 2021

Abstract

Background
The COVID-19 pandemic led to rapid changes in demand and delivery of primary care services that could have led to increases in antibiotic prescribing.

Objective
We investigated the impact of the COVID-19 pandemic on oral antibiotic dispensing rates in primary care in Wales using longitudinal analysis of monthly oral antibiotic dispensing data from 1 April 2018 to 30 April 2021.

Methods
We used All-Wales primary care dispensing data. We examined trends in oral antibiotic dispensing per 1,000 people for Wales and for individual Health Boards. We used interrupted time series analysis to estimate changes in trends pre- and post-April 2020 to assess the impact of the first and subsequent lockdowns.

Results
Between April 2020 and April 2021, antibiotic dispensing in Wales was lower compared with the same period in 2018 and 2019, with an average monthly decrease of 14.00 dispensed items per 1,000 registered patients (95% confidence interval 19.89–8.11). The overall prepandemic monthly antibiotic dispensing rate ranged from 48.5 to 67.4 antibiotic items per 1,000 registered patients. From the onset of the pandemic, it ranged from 40.3 to 49.07 antibiotic items per 1,000 registered patients. This reduction was primarily driven by narrow-spectrum antibiotics. Statistically significant reductions were also observed for antibiotics commonly dispensed for the treatment of respiratory tract infections. Dispensing of antibiotics primarily used for urinary and skin infections remained stable.

Conclusions
Despite complexities of consulting during the COVID-19 pandemic in primary care we found no evidence of an increase in antibiotic dispensing during this time.
Age-Related Differences in T-Cell Subsets in a Nationally Representative Sample of People Older Than Age 55: Findings From the Health and Retirement Study
Authors: Thyagarajan Bharat , Faul Jessica , Vivek Sithara , Kim Jung K , Nikolich-Žugich Janko , Weir David , Crimmins Eileen M 
Published: October 2021

Abstract
Though T-cell immunosenescence is a major risk factor for age-related diseases, susceptibility to infections, and responses to vaccines, differences in T-cell subset counts and representation by age and sex have not been determined for a large sample representative of the national population of the United States. We evaluated the counts of T-cell subsets including total, CD4+, and CD8+ T cells and their naïve (Tn), effector memory (Tem), and effector subsets, in the context of age, sex, and exposure to cytomegalovirus (CMV) infection among 8 848 Health and Retirement Study participants, a nationally representative study of adults older than 55 years. Total T cells (CD3+) and CD4+ cells declined markedly with age; CD8+ T cells declined somewhat less. While CD4+ T cell declines with age occurred for both CMV-seropositive and CMV-seronegative groups, total T cells and CD8+ cells were both substantially higher among the CMV-seropositive group. Numbers of Tn CD4+ and CD8+ cells were strongly and inversely related to age, were better conserved among women, and were independent of CMV seropositivity. By contrast, accumulation of the CD8+ and CD4+ Tem and effector subsets was CMV-associated. This is the first study to provide counts of T-cell subsets by age and sex in a national sample of US adults older than the age of 55 years. Understanding T-cell changes with age and sex is an important first step in determining strategies to reduce its impact on age-related diseases and susceptibility to infection.
Clinical Features and Risk Factors for Mortality Among Long-term Care Facility Residents Hospitalized Due to COVID-19 in Spain
Authors: Ramos-Rincón José-Manuel , Bernabeu-Wittel Máximo , Fiteni-Mera Isabel , López-Sampalo Almudena , López-Ríos Carmen , García-Andreu María-del-Mar , Mancebo-Sevilla Juan-José , Jiménez-Juan Carlos , Matía-Sanz Marta , López-Quirantes Pablo , Rubio-Rivas Manuel , Paredes-Ruiz Diana , González-San-Narciso Candela , González-Vega Rocío , Sanz-Espinosa Pablo , Hernández-Milián Almudena , Gonzalez-Noya Amara , Gil-Sánchez Ricardo , Boixeda Ramon , Alcalá-Pedrajas José-Nicolás , Palop-Cervera Marta , Cortés-Rodríguez Begoña , Guisado-Espartero María-Esther , Mella-Pérez Carmen , Gómez-Huelgas Ricardo ,   SEMI-COVID-19 Network
Published: October 2021

Abstract

Background
COVID-19 severely impacted older adults and long-term care facility (LTCF) residents. Our primary aim was to describe differences in clinical and epidemiological variables, in-hospital management, and outcomes between LTCF residents and community-dwelling older adults hospitalized with COVID-19. The secondary aim was to identify risk factors for mortality due to COVID-19 in hospitalized LTCF residents.

Methods
This is a cross-sectional analysis within a retrospective cohort of hospitalized patients ≥75 years with confirmed COVID-19 admitted to 160 Spanish hospitals. Differences between groups and factors associated with mortality among LTCF residents were assessed through comparisons and logistic regression analysis.

Results
Of 6 189 patients ≥75 years, 1 185 (19.1%) were LTCF residents and 4 548 (73.5%) were community-dwelling. LTCF residents were older (median: 87.4 vs 82.1 years), mostly female (61.6% vs 43.2%), had more severe functional dependence (47.0% vs 7.8%), more comorbidities (Charlson Comorbidity Index: 6 vs 5), had dementia more often (59.1% vs 14.4%), and had shorter duration of symptoms (median: 3 vs 6 days) than community-dwelling patients (all, p &lt; .001). Mortality risk factors in LTCF residents were severe functional dependence (adjusted odds ratios [aOR]: 1.79; 95% confidence interval [CI]: 1.13–2.83; p = .012), dyspnea (1.66; 1.16–2.39; p = .004), SatO2 &lt; 94% (1.73; 1.27–2.37; p = .001), temperature ≥ 37.8°C (1.62; 1.11–2.38; p = .013); qSOFA index ≥ 2 (1.62; 1.11–2.38; p = .013), bilateral infiltrates (1.98; 1.24–2.98; p &lt; .001), and high C-reactive protein (1.005; 1.003–1.007; p &lt; .001). In-hospital mortality was initially higher among LTCF residents (43.3% vs 39.7%), but lower after adjusting for sex, age, functional dependence, and comorbidities (aOR: 0.74, 95%CI: 0.62–0.87; p &lt; .001).

Conclusion
Basal functional status and COVID-19 severity are risk factors of mortality in LTCF residents. The lower adjusted mortality rate in LTCF residents may be explained by earlier identification, treatment, and hospitalization for COVID-19.
Prediction–variance relation in a state-space fish stock assessment model
Authors: Breivik Olav Nikolai , Nielsen Anders , Berg Casper W 
Published: October 2021

AbstractThe state-space assessment model (SAM) is extended by allowing a functional relationship between observation variance and the corresponding prediction. An estimated relationship between observation variance and predicted value for each individual observation allows the model to assign smaller (or larger) variance to predicted larger log-observations. This relation is different from the usual assumption of constant variance of log-observations within age groups. The prediction–variance link is implemented and compared to the usual constant variance assumption for the official assessments of North East Arctic cod and haddock. For both of these stocks, the prediction–variance link is found to give a significant improvement.
Is it time to incorporate hands-on simulation into the cardiothoracic surgery curriculum?
Authors: Hussein Nabil , Zientara Alicja , Gollmann-Tepeköylü Can , Loubani Mahmoud 
Published: October 2021

Abstract
The COVID pandemic has had huge implications for training in cardiothoracic surgery. The reduction in training opportunities has led to concerns from trainees globally regarding the impact on their learning and their training progression. Surgical simulation is effective in the development of technical skills in cardiothoracic surgery with numerous examples of low and high-fidelity simulators. Despite this the incorporation of such methods into training curricula worldwide is seldom. Core fundamentals are required to successfully implement surgical simulation into training programmes, which includes; commitment from trainers, regular sessions and structured feedback. Few programmes have demonstrated the successful incorporation of surgical simulation and there is a growing acceptance of its place in the speciality. As we recover from this challenging period it may be the right opportunity to evolve how we train our current and future trainees by incorporating hands-on simulation as a fundamental part of the cardiothoracic curriculum.
The Choice of Either Quetiapine or Aripiprazole as Augmentation Treatment in a European Naturalistic Sample of Patients With Major Depressive Disorder
Authors: Bartova Lucie , Fugger Gernot , Dold Markus , Kautzky Alexander , Swoboda Marleen Margret Mignon , Rujescu Dan , Zohar Joseph , Souery Daniel , Mendlewicz Julien , Montgomery Stuart , Fabbri Chiara , Serretti Alessandro , Kasper Siegfried 
Published: October 2021

Abstract

Background
Augmentation with second-generation antipsychotics (SGAs) represents an evidence-based psychopharmacotherapeutic strategy recommended in case of insufficient response to the first-line antidepressant (AD) treatment in major depressive disorder (MDD). Comparative evidence regarding efficacy and prescription preferences of the individual SGAs is scarce.

Methods
In the scope of this European, multi-site, naturalistic cross-sectional investigation with retrospective assessment of treatment outcome, we compared sociodemographic and clinical characteristics of 187 MDD patients receiving either quetiapine (n = 150) or aripiprazole (n = 37) as augmentation of their first-line AD psychopharmacotherapy.

Results
Comorbid posttraumatic stress disorder and diabetes were significantly associated with aripiprazole augmentation in our primary and post-hoc binary logistic regression analyses. Furthermore, we identified an association between aripiprazole co-administration and the presence of additional psychotic features, higher rates of AD combination treatment, and a longer duration of psychiatric hospitalizations during the lifetime, which, however, lost significance after correcting for multiple comparisons. Regarding treatment outcome, we found a trend of higher response rates and greater reductions in severity of depressive symptoms in MDD patients dispensed quetiapine.

Conclusions
Factors associated with a more chronic and severe profile of MDD seem to encourage clinicians to choose aripiprazole over quetiapine, that was, however, administered in the majority of our MDD patients, which might reflect the current approval situation allowing to prescribe exclusively quetiapine as on-label augmentation in MDD in Europe. Given the retrospective assessment of treatment response, the markedly smaller proportion of patients receiving aripiprazole augmentation generally showing an unfavorable disease profile, and the partially heterogeneous statistical robustness of our findings, further studies are required to elaborate on our observation and to generate unambiguous recommendations regarding the choice of first-line SGA augmentation in MDD.
Creation of a synthesis-friendly inflammation-inducible promoter suitable for cell therapy
Authors: Jadav Anish , Truong Kevin 
Published: October 2021

AbstractThe development of ‘smart’ cell-based therapeutics requires cells that first recognize conditions consistent with disease (e.g. inflammation) and then subsequently release therapeutic proteins, thereby reducing potential toxicity from otherwise continuous expression. Promoters containing NF-κB response elements are often used as reporters of inflammation; however, endogenous promoters have crosstalk with other pathways, and current synthetic promoters have many exact sequence repeats of NF-κB response elements which make them both difficult to synthesize and inherently genetically unstable. Herein, a synthesis-friendly inflammation-inducible promoter (named SFNp) was created by the packing of 14 NF-κB response elements, which have no repeats &gt;9 bp, followed by a minimal cytomegalovirus promoter. In stably expressing human embryonic kidney 293 cells, we assessed the ability of SFNp to inducibly transcribe genes for reporting expression, changing cell morphology, and performing cell fusion. These experiments represent simple milestones for potentially using SFNp in the development of cell-based therapeutics. As strongly repeated DNA can compromise the long-term stability of genetic circuits, new designs used in ‘smart’ cell therapy will become more reliant on synthesis-friendly components like SFNp.
Reporting Security: Postcolonial Governmentality in the United Nations’ Trusteeship System
Authors: Bonacker Thorsten 
Published: October 2021

AbstractThis article examines the political rationality and governance practices that emerged in the course of the international politics of decolonization. It focuses primarily on the UN trusteeship system, within which the former League of Nations mandates were continued by the trusteeship powers. In this process, the trustees' policies were placed under international scrutiny. The article ties in with International Political Sociology's increased interest in historical perspectives. In particular, it asks how the political rationality of the trusteeship system differs from colonial governmentality. Two arguments are put forward: first, international governing, as can be seen from the trusteeship system, is characterized by a postcolonial governmentality that continues central elements of colonial governmentality, but transfers them to the international level. Second, following Latour, it is argued that trusteeship governance is constituted by forms of knowledge production and the bureaucratic circulation of information that continue to shape the governance of international organizations today. To this end, the article takes up in particular the reporting system of the trusteeship system as well as its central instruments of knowledge production: the visiting missions, the petition system, and the collection of data through questionnaires.
The International Responsibility to Protect in a Post-Liberal Order
Authors: Pattison James 
Published: October 2021

AbstractThis article considers the implications of a post-liberal order for the international responsibility to protect. It focuses on two questions. First, what challenges will the international responsibility to protect face in a post-liberal order? Second, in light of these challenges, how would the requirements of the international responsibility to protect differ in the post-liberal order? In response to the first question, the article argues that in a post-liberal order the international responsibility to protect is likely to be subject to the “Influence Challenge,” whereby its ability to constrain and influence states decreases. In response to the second question, it argues that the requirements of the international responsibility to protect would be affected in several ways, including necessitating greater consideration of questions of prioritization and requiring a re-evaluation, and potential abandonment, of the currently predominant approach to the responsibility to protect.
Indirect Genetic Effects: A Cross-disciplinary Perspective on Empirical Studies
Authors: Baud Amelie , McPeek Sarah , Chen Nancy , Hughes Kimberly A 
Published: October 2021

AbstractIndirect genetic effects (IGE) occur when an individual’s phenotype is influenced by genetic variation in conspecifics. Opportunities for IGE are ubiquitous, and, when present, IGE have profound implications for behavioral, evolutionary, agricultural, and biomedical genetics. Despite their importance, the empirical study of IGE lags behind the development of theory. In large part, this lag can be attributed to the fact that measuring IGE, and deconvoluting them from the direct genetic effects of an individual’s own genotype, is subject to many potential pitfalls. In this Perspective, we describe current challenges that empiricists across all disciplines will encounter in measuring and understanding IGE. Using ideas and examples spanning evolutionary, agricultural, and biomedical genetics, we also describe potential solutions to these challenges, focusing on opportunities provided by recent advances in genomic, monitoring, and phenotyping technologies. We hope that this cross-disciplinary assessment will advance the goal of understanding the pervasive effects of conspecific interactions in biology.