bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pralsetinib: Treatment of metastatic RET fusion–positive non–small cell lung cancer
Authors: Nguyen Ly , Monestime Shanada 
Published: December 2021

Abstract

Purpose
To review the pharmacology, efficacy, safety, dosing and administration, and place in therapy of pralsetinib, a tyrosine kinase inhibitor, for the treatment of metastatic RET fusion–positive non–small-cell lung cancer (NSCLC).

Summary
RET fusion–positive NSCLC is a rare cancer caused by chromosomal rearrangements that lead to fusions of the RET gene with other genes, such as KIF5B and CCDC6. Until recently, patients were treated with platinum-based chemotherapy or multitargeted tyrosine kinase inhibitors. However, because of their nonspecific mechanism of action, these drugs did not have high response rates. In September 2020, the Food and Drug Administration approved pralsetinib, the first once-daily oral tyrosine kinase inhibitor, for patients with metastatic RET fusion–positive NSCLC. Pralsetinib has been demonstrated to have response rates of 57% and 70% in patients who were previously treated with platinum chemotherapy and patients who were treatment naive, respectively. Clinicians using pralsetinib should monitor for fatigue, hepatotoxicity, hemorrhagic events, hypertension, myelosuppression, pyrexia, and respiratory infections, as these may require treatment interruption, dose reduction, or treatment discontinuation.

Conclusion
Pralsetinib is a unique targeted tyrosine kinase inhibitor approved for the treatment of patients with RET fusion–positive metastatic NSCLC who may desire a once-daily regimen.
A multifaceted stewardship intervention helps curb steroid overprescribing in hospitalized patients with acute exacerbations of COPD
Authors: Cole Jennifer L , Smith Sarah E 
Published: December 2021

Abstract

Purpose
Corticosteroid overprescribing is well documented in real-world practice. There is currently no evidence to guide best practices for steroid stewardship. The aim of this study was to assess the effects of a 3-part stewardship intervention strategy on inpatient steroid prescribing in patients with acute exacerbations of COPD (AECOPD).

Summary
Investigators implemented a 3-part stewardship initiative consisting of (1) an anonymous survey for providers on steroid prescribing in a simplified case of AECOPD, (2) face-to-face education and review of survey results, and (3) prospective audit and feedback from a clinical pharmacist. This was a quasi-experimental before-and-after study evaluating hospitalized adults diagnosed with AECOPD in two 12-month study periods before (April 2019-March 2020) and after (May 2020-April 2021) implementation. The primary outcome was mean inpatient steroid dosing. Secondary outcomes were duration of therapy, length of stay (LOS), 30-day readmissions, 30-day mortality, and incidence of hyperglycemia. Per power analysis, there were 27 patients per cohort. The interventions resulted in a significant reduction in prednisone equivalents during hospitalization: 118 mg vs 53 mg (P = 0.0003). This decrease was similar in ICU (160 mg vs 61 mg, P = 0.008) and non-ICU (102 mg vs 49 mg, P = 0.004) locations. There was no significant difference in duration of therapy (8 days vs 7 days, P = 0.44), length of stay (3.3 days vs 3.9 days, P = 0.21), 30-day mortality (4% vs 7%, P = 0.55), 30-day readmissions (15% vs 7%, P = 0.39), or rate of hyperglycemia (48% vs 44%, P = 0.78).

Conclusion
A multifaceted stewardship intervention significantly reduced steroid dosing in hospitalized AECOPD patients. This reduction was not associated with known deleterious effects.
HolistIC: leveraging Hi–C and whole genome shotgun sequencing for double minute chromosome discovery
Authors: Hayes Matthew , Nguyen Angela , Islam Rahib , Butler Caryn , Tran Ethan , Mullins Derrick , Hicks Chindo 
Published: December 2021

AbstractMotivationDouble minute (DM) chromosomes are acentric extrachromosomal DNA artifacts that are frequently observed in the cells of numerous cancers. They are highly amplified and contain oncogenes and drug-resistance genes, making their presence a challenge for effective cancer treatment. Algorithmic discovery of DM can potentially improve bench-derived therapies for cancer treatment. A hindrance to this task is that DMs evolve, yielding circular chromatin that shares segments from progenitor DMs. This creates DMs with overlapping amplicon coordinates. Existing DM discovery algorithms use whole genome shotgun sequencing (WGS) in isolation, which can potentially incorrectly classify DMs that share overlapping coordinates.ResultsIn this study, we describe an algorithm called ‘HolistIC’ that can predict DMs in tumor genomes by integrating WGS and Hi–C sequencing data. The consolidation of these sources of information resolves ambiguity in DM amplicon prediction that exists in DM prediction with WGS data used in isolation. We implemented and tested our algorithm on the tandem Hi–C and WGS datasets of three cancer datasets and a simulated dataset. Results on the cancer datasets demonstrated HolistIC’s ability to predict DMs from Hi–C and WGS data in tandem. The results on the simulated data showed the HolistIC can accurately distinguish DMs that have overlapping amplicon coordinates, an advance over methods that predict extrachromosomal amplification using WGS data in isolation.Availability and implementationOur software, named ‘HolistIC’, is available at http://www.github.com/mhayes20/HolistIC.Supplementary informationSupplementary data are available at Bioinformatics online.
Gender and (Fictive) Family in a Women’s Post-Incarceration Mentoring Program
Authors: Garcia-Hallett Janet , Christian Johnna 
Published: December 2021

AbstractMentoring programs have become a popular tool of social support to facilitate post-incarceration re-entry. Still, we have a limited understanding of the fundamental aspects within mentor–mentee relationships that create a support network, particularly for women with troubled relationships with biological family. Through interviews with mentors and mentees, we examined key domains of women’s relationships with mentors to identify the potential and limitations of voluntary organizations in supporting the transition from prison to the community. We found that mentoring relationships, constructed as fictive kinships, helped formerly incarcerated women build a support network. Yet, navigating mentor–mentee relationships was complex given the dyadic familial-like nature and the hierarchical power dynamic.
European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1—epidemiology, pathophysiology, and diagnosis
Authors:   The Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent Colin , Windecker Stephan , Andreini Daniele , Arbelo Elena , Barbato Emanuele , Bartorelli Antonio L , Baumbach Andreas , Behr Elijah R , Berti Sergio , Bueno Héctor , Capodanno Davide , Cappato Riccardo , Chieffo Alaide , Collet Jean-Philippe , Cuisset Thomas , de Simone Giovanni , Delgado Victoria , Dendale Paul , Dudek Dariusz , Edvardsen Thor , Elvan Arif , González-Juanatey José R , Gori Mauro , Grobbee Diederick , Guzik Tomasz J , Halvorsen Sigrun , Haude Michael , Heidbuchel Hein , Hindricks Gerhard , Ibanez Borja , Karam Nicole , Katus Hugo , Klok Fredrikus A , Konstantinides Stavros V , Landmesser Ulf , Leclercq Christophe , Leonardi Sergio , Lettino Maddalena , Marenzi Giancarlo , Mauri Josepa , Metra Marco , Morici Nuccia , Mueller Christian , Petronio Anna Sonia , Polovina Marija M , Potpara Tatjana , Praz Fabien , Prendergast Bernard , Prescott Eva , Price Susanna , Pruszczyk Piotr , Rodríguez-Leor Oriol , Roffi Marco , Romaguera Rafael , Rosenkranz Stephan , Sarkozy Andrea , Scherrenberg Martijn , Seferovic Petar , Senni Michele , Spera Francesco R , Stefanini Giulio , Thiele Holger , Tomasoni Daniela , Torracca Luccia , Touyz Rhian M , Wilde Arthur A , Williams Bryan 
Published: December 2021

AbstractAimsSince its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19.Methods and resultsA narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19.ConclusionThis comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.
EACVI survey on hypertrophic cardiomyopathy
Authors: Podlesnikar Tomaz , Cardim Nuno , Ajmone Marsan Nina , D’Andrea Antonello , Cameli Matteo , Popescu Bogdan A , Schulz-Menger Jeanette , Stankovic Ivan , Toplisek Janez , Maurer Gerald , Haugaa Kristina H , Dweck Marc R 
Published: December 2021

Abstract

Aims
The European Association of Cardiovascular Imaging (EACVI) Scientific Initiatives Committee performed a global survey to evaluate current practice for the assessment and management of patients with hypertrophic cardiomyopathy (HCM).

Methods and results
A total of 213 centres from 38 different countries (87% European) responded to the survey. One hundred twenty-one (57%) centres followed HCM patients in a general cardiology outpatient clinic and 85 (40%) centres in a specialized HCM/cardiomyopathy clinic. While echocardiography was the primary imaging modality, cardiovascular magnetic resonance (CMR) has become an important complementary tool. Cardiac anatomy, left ventricular (LV) systolic, and diastolic function were assessed according to current European guidelines and recommendations. To evaluate LV obstruction, 49% of the centres performed bedside provocation manoeuvres in every patient and 55% of the centres used exercise stress echocardiography. The majority of centres used the 5-year risk assessment of sudden cardiac death (SCD) calculated with the HCM Risk-SCD score. However, 34% of the centres also used extensive non-infarct late gadolinium enhancement on CMR and 27% the presence of LV apical aneurysm to help select patients for primary prevention implantable cardioverter-defibrillator therapy. Ninety-nine percent of the responding centres performed regular imaging follow-up of HCM patients.

Conclusion
Most centres followed European guidelines and recommendations for the diagnosis and management of patients with HCM. The importance of bedside provocation manoeuvres and exercise stress echocardiography to diagnose LV outflow obstruction requires emphasis. Additional risk markers for SCD are used in many centres and might indicate the need for an update of current European recommendations.
Combined transcatheter treatment of severe mitral regurgitation and secundum atrial septal defect in an inoperable patient: a case report
Authors: Barbieri Fabian , Landmesser Ulf , Kasner Mario , Reinthaler Markus 
Published: December 2021

Abstract

Background
Chronic mitral regurgitation (MR) is one of the most common valvular heart diseases and is associated with poor outcomes. Although other structural diseases are regularly seen in such patients, concomitant atrial septal defects (ASDs) remain a rarity in the elderly.

Case summary
We report a case of an 82-year-old woman with progressive right-sided heart failure (HF) due to MR and an ASD of secundum type, despite optimal medical therapy. Combined transcatheter mitral valve repair (MVR) by utilizing a separate transseptal puncture and ASD closure was performed resulting in amelioration of symptoms.

Discussion
Procedural planning for simultaneous transcatheter therapies of coupled structural heart disease entities remains complex. Our case illustrates feasibility of percutaneous edge-to-edge MVR and consecutive closure of a large secundum ASD. Different options of accessing the left atrium should be discussed on an individual basis, while additional ASD closure may be beneficial in terms of right ventricular function and symptoms of right HF.
Association of coronary artery calcification and thoracic aortic calcification with incident peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Bakhshi Hooman , Bagchi Pramita , Meyghani Zahra , Tehrani Behnam , Qian Xiaoxiao , Garg Parveen K , Ambale-Venkatesh Bharath , Bhatia Harpreet S , Ohyama Yoshiaki , Wu Colin O , Budoff Matthew , Allison Matthew , Criqui Michael H , Bluemke David A , Lima Joao A C , deFilippi Christopher R 
Published: December 2021

AbstractAimsThe association of subclinical atherosclerotic disease in the coronary arteries and thoracic aorta with incident peripheral arterial disease (PAD) is unknown. We investigated the association between coronary artery calcium score (CACs) and thoracic aortic calcium score (TACs) with incident clinical and subclinical PAD.Methods and resultsThe Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 men and women aged 45–84 from four ethnic groups who were free of clinical cardiovascular disease at enrolment. Coronary artery calcium score and thoracic aortic calcium score were measured from computed tomography scans. Participants with a baseline ankle-brachial index (ABI) ≤0.90 or &gt;1.4 were excluded. Abnormal ABI was defined as ABI ≤0.9 or &gt;1.4 at follow-up exam. Multivariable logistic regression and Cox proportional hazards models were used to test the associations between baseline CACs and TACs with incident abnormal ABI and clinical PAD, respectively. A total of 6409 participants (female: 52.8%) with a mean age of 61 years were analysed. Over a median follow-up of 16.7 years, 91 participants developed clinical PAD. In multivariable analysis, each unit increase in log (CACS + 1) and log (TACs + 1) were associated with 23% and 13% (P &lt; 0.01for both) higher risk of incident clinical PAD, respectively. In 5725 (female: 52.6%) participants with an available follow-up ABI over median 9.2 years, each 1-unit increase in log (CACs + 1) and log (TACs + 1) were independently associated with 1.15-fold and 1.07-fold (P &lt; 0.01for both) higher odds of incident abnormal ABI, respectively.ConclusionHigher baseline CACs and TACs predict abnormal ABI and clinical PAD independent of traditional cardiovascular risk factors and baseline ABI.
Impact of the coronavirus disease 2019 pandemic on volume of thoracic aortic surgery on a national level
Authors: de Beaufort Hector W L , Roefs Maaike M , Daeter Edgar J , Heijmen Robin H ,   the Cardiothoracic Surgery Registration Committee of the Netherlands Heart Registration, Bramer S , van Boven W J P , Vonk A B A , Koene B M J A , Bekkers J A , Hoohenkerk G J F , Markou A L P , de Weger A , Segers P , Porta F , Speekenbrink R G H , Stooker W , Li W W L , Daeter E J , van der Kaaij N P , Douglas Y L 
Published: December 2021

Abstract

OBJECTIVES
The aim of this study was to evaluate the effects of the coronavirus 2019 pandemic on elective and acute thoracic aortic surgery in the Netherlands.

METHODS
The Netherlands Heart Registration database was used to compare the volume of elective and acute surgery on the thoracic aorta in 2019 and 2020, starting from week 11 in both years. A sub-analysis was done to assess the impact of the pandemic on high-volume and low-volume aortic centres.

RESULTS
During the pandemic, the number of elective thoracic aortic operations declined by 18% [incidence rate ratio (IRR) 0.82 [0.73–0.91]; P &lt; 0.01]. The decline in volume of elective surgery was significant in both high-volume (IRR 0.82 [0.71–0.94]; P &lt; 0.01) and low-volume aortic centres (IRR 0.81 [0.68–0.98]; P = 0.03). The overall number of acute aortic operations during the pandemic remained similar to that in 2019 (505 vs 499; P = 0.85), but an increased share of these operations occurred at high-volume centres. The number of acute operations performed in high-volume centres increased by 20% (IRR 1.20 [1.01–1.42]; P = 0.04), while the number of acute operations performed in low-volume centres decreased by 17% (IRR 0.83 [0.69–1.00]; P = 0.04).

CONCLUSIONS
The coronavirus 2019 pandemic led to a significant decrease in elective thoracic aortic surgery but did not cause a change in the volume of acute thoracic aortic surgery in the Netherlands. Moreover, the pandemic led to a centralization of care for acute thoracic aortic surgery.
The Influx of Refugees and Temporal Change in Attitudes towards Asylum Seekers: A Cross-National Perspective
Authors: Gorodzeisky Anastasia 
Published: December 2021

Abstract
The article studies over-time changes in public attitudes towards asylum seekers, from a cross-national comparative perspective. The article applies the ‘hierarchical age-period-cohort’ model to data from the European Social Survey collected in 17 European countries. The findings demonstrate that cross-cohort variations play a negligible role in the over-time changes in attitudes towards asylum seekers in Europe; and that most of these over-time changes can be attributed to period-related effect. The main findings reveal that not only exposure to an actual high inflow of asylum seekers (i.e. living in a country with an especially high inflow of asylum seekers) is associated with exclusionary attitudes towards asylum seekers, but also exposure to the potential of such an inflow (i.e. living in a country bordering countries with a high inflow of asylum seekers).
The auxin-inducible degron 2 (AID2) system enables controlled protein knockdown during embryogenesis and development in Caenorhabditis elegans
Authors: Negishi Takefumi , Kitagawa Saho , Horii Natsumi , Tanaka Yuka , Haruta Nami , Sugimoto Asako , Sawa Hitoshi , Hayashi Ken-ichiro , Harata Masahiko , Kanemaki Masato T 
Published: December 2021

Abstract
Targeted protein degradation using the auxin-inducible degron (AID) system is garnering attention in the research field of Caenorhabditis elegans, because of the rapid and efficient target depletion it affords, which can be controlled by treating the animals with the phytohormone auxin. However, the current AID system has drawbacks, i.e., leaky degradation in the absence of auxin and the requirement for high auxin doses. Furthermore, it is challenging to deplete degron-fused proteins in embryos because of their eggshell, which blocks auxin permeability. Here, we apply an improved AID2 system utilizing AtTIR1(F79G) and 5-phenyl-indole-3-acetic acid (5-Ph-IAA) to C. elegans and demonstrated that it confers better degradation control vs the previous system by suppressing leaky degradation and inducing sharp degradation using 1,300-fold lower 5-Ph-IAA doses. We successfully degraded the endogenous histone H2A.Z protein fused to an mAID degron and disclosed its requirement in larval growth and reproduction, regardless of the presence of maternally inherited H2A.Z molecules. Moreover, we developed an eggshell-permeable 5-Ph-IAA analog, 5-Ph-IAA-AM, that affords an enhanced degradation in laid embryos. Our improved system will contribute to the disclosure of the roles of proteins in C. elegans, in particular those that are involved in embryogenesis and development, through temporally controlled protein degradation.
Observer-based global output feedback controller design for an unstable wave PDE with nonlinear boundary condition
Authors: Ghaderi Najmeh , Keyanpour Mohammad 
Published: December 2021

Abstract
In this work, an observer-based output feedback controller for a one-dimensional wave equation with van der Pol type nonlinear boundary conditions is considered. The uncontrolled system with the energy injection and the cubic velocity nonlinearity reveals different kinds of dynamical behaviours, for example, chaotic acoustic vibration, period-doubling bifurcation, square wave and some other dynamical patterns. Firstly, an observer is designed, and next, we propose an observer-based output feedback controller using the backstepping approach. We prove well-posedness and globally asymptotic stability of the observer error and corresponding closed-loop system. To this purpose, pre-compactness of the trajectories is shown for the large-time analysis. The validity of the theoretical results is illustrated by some numerical simulations.
Exploring complementarities between modelling approaches that enable upscaling from plant community functioning to ecosystem services as a way to support agroecological transition
Authors: Gaudio Noémie , Louarn Gaëtan , Barillot Romain , Meunier Clémentine , Vezy Rémi , Launay Marie 
Published: December 2021

Abstract
Promoting plant diversity through crop mixtures is a mainstay of the agroecological transition. Modelling this transition requires considering both plant–plant interactions and plants’ interactions with abiotic and biotic environments. Modelling crop mixtures enables designing ways to use plant diversity to provide ecosystem services, as long as they include crop management as input. A single modelling approach is not sufficient, however, and complementarities between models may be critical to consider the multiple processes and system components involved at different and relevant spatial and temporal scales. In this article, we present different modelling solutions implemented in a variety of examples to upscale models from local interactions to ecosystem services. We highlight that modelling solutions (i.e. coupling, metamodelling, inverse or hybrid modelling) are built according to modelling objectives (e.g. understand the relative contributions of primary ecological processes to crop mixtures, quantify impacts of the environment and agricultural practices, assess the resulting ecosystem services) rather than to the scales of integration. Many outcomes of multispecies agroecosystems remain to be explored, both experimentally and through the heuristic use of modelling. Combining models to address plant diversity and predict ecosystem services at different scales remains rare but is critical to support the spatial and temporal prediction of the many systems that could be designed.