bluuebunny/crossref_metadata_2025 huggingface dataset:
A grease for domain walls motion in HfO2-based ferroelectrics
Authors: Kashir Alireza , Farahani Mehrdad Ghiasabadi , Lančok Ján , Hwang Hyunsang , Kamba Stanislav
Published: December 2021

A large coercive field E
C of HfO2 based ferroelectric devices poses critical performance issues in their applications as ferroelectric memories and ferroelectric field effect transistors. A new design to reduce E
C by fabricating nanolaminate Hf0.5Zr0.5O2/ZrO2 (HZZ) thin films is used, followed by an ensuing annealing process at a comparatively high temperature 700 °C. High-resolution electron microscopy imaging detects tetragonal-like domain walls between orthorhombic polar regions. These walls decrease the potential barrier of polarization reversal in HfO2 based films compared to the conventional domain walls with a single non-polar spacer, causing about a 40% decrease in E
C. Capacitance versus electric field measurements on HZZ thin film uncovered a substantial increase of dielectric permittivity near the E
C compared to the conventional Hf0.5Zr0.5O2 thin film, justifying the higher mobility of domain walls in the developed HZZ film. The tetragonal-like regions served as grease easing the movement of the domain wall and reducing E
C.
Environmental impact evaluation of five circular concrete scenarios
Authors: van den Bogert R E J , Ritzen M J
Published: December 2021

In the Netherlands, the material concrete accounts for 40-60% of the total environmental impact of the Dutch construction industry. Cement accounts for 80-95% of this impact, while not being the main component expressed in mass.
Upscaling non-residential bio-based circular construction in the United Kingdom
Authors: Dams B , Maskell D , Shea A , Allen S , Cascione V , Walker P , Emmitt S
Published: December 2021

Non-residential circular construction projects using bio-based materials have been realised in the United Kingdom. Case studies include the Adnams Distribution Centre, the University of East Anglia’s Enterprise Centre and the British Science Museum’s hempcrete storage facility. The bio-based buildings utilise the natural properties of bio-based materials to insulate and regulate internal environments, particularly with reducing fluctuations in temperature and relative humidity, which can be harmful to sensitive stored products and artefacts. Projects have been successful on both on environmental and physical performance levels; however, they have not led to a subsequent proliferation of non-residential large-scale circular projects within the UK using emerging bio-based materials. This study examines why and uses analysis based upon exclusive interviews with key figures associated with bio-based case studies. Challenges faced include the ability to upscale production by manufacturers of bio-based materials, problems surrounding initial costs, gaining accreditation for materials, the vested interests present in the construction industry and levels of knowledge among clients and construction professionals. Potential upscaling solutions identified include long-term financial savings on running costs and high staff productivity, policies regarding grants, incentives and planning applications and local economic regeneration.
Design potentials between empirical data and architectural imagination: an exploration
Authors: Paans O
Published: December 2021

This article discusses ways in which we can connect empirical data and design skills to create more circular and sustainable urban areas. The case of Hellersdorf-Süd (Berlin, DE) is used to describe a design approach that is context-driven and combines data and design skills to formulate coherent and relevant design proposals. Based on this exposition, this article presents and exploration of the future urbanist practices in which sustainability and circularity on a conceptualized larger scale. As such, it provides a speculative account of a future course of action to achieve urban sustainability and systemic circularity.
Circularity in Selected EU Countries: The Case of Construction and Demolition Industry
Authors: Dytianquin N , Gregersen-Hermans J , Kalogeras N , van Oorschot J , Ritzen M
Published: December 2021

The construction and demolition industry (CDI) became a priority area for the EU circular economy as the industry has the largest waste stream by volume. Most of the CDI waste, however, ends up in incinerators for energy production or as downcycled content for road surfaces despite its enormous potential for recycling and reuse. This study focuses on the application of circularity in the CDI. We recognize that the construction industry provides a prominent decision context for studying circularity since many scrap materials resulting from demolished buildings and houses could be recycled, reused and refurbished in newly constructed edifices from foundation to rooftops. Adopting the fundamental circularity concepts, the study intends to compare how selected countries as early adopters of circularity in the EU apply distinct concepts of the circular economy in the CDI. The study investigates the manner circularity in CDI is achieved in the selected countries using determinants for project success in integrating the three dimensions of sustainability to identify and determine best practices. These determinants are: 1) stage of circularity as described in the waste hierarchy and circularity ladder, 2) building design principles, 3) life cycle stages specific to construction, and 4) availability and extent of policy or strategy on circularity in the EU countries where the selected projects are located. The EU countries covered are: the Netherlands, Belgium, Germany, France, and Denmark who are among the top 10 waste generators in Western Europe. The projects chosen are: (i) Superlocal project in the Netherlands; (ii) the Circular Retrofit Lab (CRL) project in Belgium; (iii) Open Air Library in Germany; (iv) Rehafutur Engineer’s House project in France; and (v) Upcycle Studios in Denmark.
A critical review on circular and regenerative urban areas
Authors: Gejer L , Gomes da Silva V
Published: December 2021

Circular economy (CE) has gained relevance as a new economic-environmental paradigm. Despite their key role in this model, managing cities towards CE has taken different meanings, approaches, concepts and methods. Therefore, this study aims to clarify circularity approaches to urban areas, by identifying main trends and exploring potential organization into a framework for policymakers and urban managers. We first conducted a systematic literature review (SLR) to understand limits and divergences when spatially expressing circularity. Four approaches covering different possibilities regarding circularity in urban areas stood out: (i) specific flows within a circular city; (ii) flows integration for resource looping; (iii) planning the transition from linear to circular cities; and (iv) concepts of circular or regenerative urban areas. We then hypothesized that one of these concepts, the Cradle to Cradle (C2C) approach, embraces the multiplicity of quantitative and qualitative requisites needed for developing circular urban areas. Our contribution, in the second part of the paper, organizes the requisites and indicators raised during the SLR according to the C2C principles into a draft framework to enable optimization and integration of different flows with human activities to various urban and socioeconomic contexts.
Leadership of EU member States in building carbon footprint regulations and their role in promoting circular building design
Authors: Attia S , Santos M C , Al-Obaidy M , Baskar M
Published: December 2021

European countries are working towards carbon neutrality of the building sector. Regulations and initiatives, including the European Green Deal, aim at promoting circular buildings and low carbon design. Therefore, this paper seeks to investigate the role of legislation in paving the way towards achieving the circularity of buildings design and construction. A systematic literature review is conducted to compare the current regulations in different EU member states that address carbon emissions and life cycle thinking to achieve circularity. The study aims to demonstrate how the low-carbon emissions regulations in leading countries can lead to making the construction sector’s circularity. The research is focused on five leading EU member states in low carbon buildings, including Denmark, Finland, France, the Netherlands, and Sweden. The study compares the performance indicators, metrics, and target thresholds found in the five selected states’ regulations and examines them across a circularity assessment framework developed earlier by the authors. This paper provides insights on low emission building regulations state-of-the-art. Moreover, it offers a better understanding of the relationship between low-carbon emissions regulations and building circularity. The article explains the role of the legislative landscape and its impact on circular building design practices. Key findings from the study will assist the European Commission to identify policy options to support the uptake of “Circular economy principles for buildings design” in European, national and local policies.
Assessment of the circularity and carbon neutrality of an office building: The case of’t Centrum in Westerlo, Belgium
Authors: Al-Obaidy M , Santos M C , Baskar M , Attia S
Published: December 2021

Circular building design is a concept that is gaining great interest from architects, construction professionals, and their clients but is still rarely adopted in practice. One of the earliest design decisions architects and developers should make to design a circular building is to determine the building’s construction system. The choice of constructive and structural systems, such as columns, beams, and slabs, is crucial to upgrade the reuse cycles in the future. Flexible construction systems can make it easier to dismantle the structures and recover, upgrade, modify, or transform building materials. Therefore, this paper assesses the carbon emission impacts of two construction systems for an office building in Belgium using life cycle assessment (LCA) and circularity criteria. One-Click LCA software was used for the calculations. Parametric analysis took place for two construction systems scenarios involving a steel structure and a timber structure. Life Cycle Assessment and comparisons of the various construction systems are made based on ISO 14040, 14044, and CEN/TC 350 standards with a focus on carbon neutrality. The results show that using local plant-based materials such as wood can drastically reduce office buildings’ carbon footprint. Based on the sensitivity analysis results, the overall global warming potential impact is mostly sensitive to the construction material’s weight and reuse and dismantling ability. This paper provides a better understanding of building structural systems; to inform architects about the circularity potential of different construction systems.
Kinetic study of key species and reactions of atmospheric pressure pulsed corona discharge in humid air
Authors: PENG Yongkang , CHEN Xiaoyue , DENG Yeqiang , LAN Lei , ZHAN Haoyu , PEI Xuekai , CHEN Jiahao , YUAN Yukuan , WEN Xishan
Published: December 2021

In this study, we examined the key particles and chemical reactions that substantially influence plasma characteristics. In summarizing the chemical reaction model for the discharge process of N2–O2–H2O(g) mixed gases, 65 particle types and 673 chemical reactions were investigated. On this basis, a global model of atmospheric pressure humid air discharge plasma was developed, with a focus on the variation of charged particles densities and chemical reaction rates with time under the excitation of a 0–200 Td pulsed electric field. Particles with a density greater than 1% of the electron density were classified as key particles. For such particles, the top ranking generation or consumption reactions (i.e. where the sum of their rates was greater than 95% of the total rate of the generation or consumption reactions) were classified as key chemical reactions. On the basis of the key particles and reactions identified, a simplified global model was derived. A comparison of the global model with the simplified global model in terms of the model parameters, particle densities, reaction rates (with time), and calculation efficiencies demonstrated that both models can adequately identify the key particles and chemical reactions reflecting the chemical process of atmospheric pressure discharge plasma in humid air. Thus, by analyzing the key particles and chemical reaction pathways, the charge and substance transfer mechanism of atmospheric pressure pulse discharge plasma in humid air was revealed, and the mechanism underlying water vapor molecules’ influence on atmospheric pressure air discharge was elucidated.
Determinants and Trends of COVID-19 Vaccine Hesitancy and Vaccine Uptake in a National Cohort of US Adults: A Longitudinal Study
Authors: Rane Madhura S , Kochhar Shivani , Poehlein Emily , You William , Robertson McKaylee M , Zimba Rebecca , Westmoreland Drew A , Romo Matthew L , Kulkarni Sarah G , Chang Mindy , Berry Amanda , Parcesepe Angela M , Maroko Andrew R , Grov Christian , Nash Denis ,   for the CHASING COVID Cohort Study Team
Published: December 2021

We estimated the trends and correlates of vaccine hesitancy and its association with subsequent vaccine uptake among 5,458 adults in the United States. Participants belonged to the Communities, Households, and SARS-CoV-2 Epidemiology COVID (CHASING COVID) Cohort, a national longitudinal study. Trends and correlates of vaccine hesitancy were examined longitudinally in 8 interview rounds from October 2020 to July 2021. We also estimated the association between willingness to vaccinate and subsequent vaccine uptake through July 2021. Vaccine delay and refusal decreased from 51% and 8% in October 2020 to 8% and 6% in July 2021, respectively. Compared with non-Hispanic (NH) White participants, NH Black and Hispanic participants had higher adjusted odds ratios (aOR) for both vaccine delay (for NH Black, aOR = 2.0 (95% confidence interval (CI): 1.5, 2.7), and for Hispanic, 1.3 (95% CI: 1.0, 1.7)) and vaccine refusal (for NH Black, aOR = 2.5 (95% CI: 1.8, 3.6), and for Hispanic, 1.4 (95% CI: 1.0, 2.0)) in June 2021. COVID-19 vaccine hesitancy, compared with vaccine-willingness, was associated with lower odds of subsequent vaccine uptake (for vaccine delayers, aOR = 0.15, 95% CI: 0.13, 0.18; for vaccine refusers, aOR = 0.02; 95% CI: 0.01, 0.03 ), adjusted for sociodemographic factors and COVID-19 history. Vaccination awareness and distribution efforts should focus on vaccine delayers.
Evaluation of high-dose insulin/euglycemia therapy for suspected β-blocker or calcium channel blocker overdose following guideline implementation
Authors: Schult Rachel F , Nacca Nicholas , Grannell Tori L , Jorgensen Rachel M , Acquisto Nicole M
Published: December 2021

Purpose

High-dose insulin/euglycemia (HDIE) is targeted therapy for β-blocker and calcium channel blocker overdose. A guideline using concentrated insulin infusions (20 units/mL), aggressive monitoring, and supportive recommendations was implemented. We sought to evaluate safety before and after HDIE guideline implementation and describe the patient population, insulin doses, supplemental dextrose, vasopressor use, hospital and intensive care unit (ICU) lengths of stay, and mortality.

Methods

Retrospective review was performed of patients receiving HDIE before and after guideline implementation at an academic medical center and community hospital from March 2011 through December 2019. Information on patient and overdose demographics, ingestion data, vital signs, interventions, adverse events, and disposition was collected. Data are presented descriptively with comparisons using Mann-Whitney U analysis and Fisher’s exact tests.

Results

During the study period, 27 patients were treated with HDIE, 10 before guideline implementation (37%; mean [SD] initial insulin dose, 0.49 [0.35] units/kg/h; mean [SD] maximum insulin dose, 2.25 [3.29] units/kg/h; median [interquartile range] duration, 10 [5.5-18.75] hours) and 17 after guideline implementation (63%; mean [SD] initial insulin dose, 1.01 [0.34] units/kg/h; mean [SD] maximum insulin dose, 2.99 [5.05] unit/kg/h; median [interquartile range] duration, 16 [11.5-37] hours). Hypoglycemia, hypokalemia, and volume overload occurred in 80% vs 29% (P = 0.018), 40% vs 53% (P = 0.69), and 50% vs 65% (P = 0.69) of patients in the preguideline vs postguideline group, respectively. Most patients received an initial insulin bolus (85%; mean [SD], 70.3 [21.8] units, 0.9 [0.26] units/kg) and vasopressor infusion (85%). More postguideline patients received a dextrose infusion with a concentration of 20% or higher (93% vs 50%, P = 0.015). There were no differences in cardiac arrest, in-hospital mortality, or hospital or ICU length of stay between the groups.

Conclusion

Hypoglycemia was reduced using an HDIE guideline and concentrated insulin.
Home Economics: Sitcom Capitalism, Conservative Comedy, and Media Conglomeration in Post-Network Television
Authors: Marx Nick
Published: December 2021

This article argues that conservative comedy has become a considerable cultural force in the service of not only achieving political outcomes, but also protecting the wealth and class privileges of America’s right-wing elite. It surveys the scholarly conversation on the politics of American sitcoms, noting how existing research has only provided a partial accounting of conservatism in television comedy. It expands the notion of conservative comedy by considering the sitcom Last Man Standing’s (LMS) place in post-network television, an industry increasingly driven by financialization, corporate consolidation, and the tendency to treat intellectual property—i.e., television shows themselves—as commodities. Finally, it examines several key episodes from LMS centered on property ownership, financial struggle, and precarious labor. The program works to normalize conservative ideologies about these subjects, seamlessly resolving their tensions by making the wisdom of the show’s patriarch and that of free market capitalism one and the same.
Optimization of synchronized frequency and voltage control for a distributed generation system using the Black Widow Optimization algorithm
Authors: Sadeghi Baran , Shafaghatian Nima , Alayi Reza , El Haj Assad Mamdouh , Zishan Farhad , Hosseinzadeh Hasan
Published: December 2021

A distributed generation network could be a hybrid power system that includes wind–diesel power generation based on induction generators (IGs) and synchronous generators (SGs). The main advantage of these systems is the possibility of using renewable energy in their structures. The most important challenge is to design the voltage-control loop with the frequency-control loop to obtain optimal responses for voltage and frequency deviations. In this work, the voltage-control loop is designed by an automatic voltage regulator. A linear model of the hybrid system has also been developed with coordinated voltage and frequency control. Dynamic frequency response and voltage deviations are compared for different load disturbances and different reactive loads. The gains of the SG and the static volt-ampere reactive compensator (SVC) controllers in the IG terminal are calculated using the Black Widow Optimization (BWO) algorithm to insure low frequency and voltage deviations. The BWO optimization algorithm is one of the newest and most powerful optimization methods to have been introduced so far. The results showed that the BWO algorithm has a good speed in solving the proposed objective function. A 22% improvement in time adjustment was observed in the use of an optimal SVC. Also, an 18% improvement was observed in the transitory values.
Multisystem inflammatory syndrome in adults in a young male following severe acute respiratory syndrome coronavirus-2 infection: a case report
Authors: Kaufmann Christoph C , Simon Alexander , Reinhart-Mikocki David , Publig Sabine , Huber Kurt , Freynhofer Matthias K
Published: December 2021

Background

Multisystem inflammatory syndrome in adults (MIS-A) is a rare but potentially life-threatening condition that may occur during or in the weeks following severe acute respiratory syndrome coronavirus-2 infection. To date, only case reports and small case series have described typical findings and management of patients with MIS-A. The prevalence of MIS-A is largely unknown due to the lack of data.

Case summary

A 30-year-old male patient presented to the emergency department with new-onset of fever, chest discomfort, macular exanthema, abdominal pain, mild dyspnoea, and coughing. The patient reported a mildly symptomatic recent coronavirus disease-19 (COVID-19). Significantly increased markers of inflammation and a modest increase of cardiac troponin were found upon laboratory work-up at admission. Despite broad-spectrum antibiotics, the patient’s clinical status deteriorated continuously. Cardiac work-up, including echocardiography, coronary angiography, and cardiac magnetic resonance imaging, was done and signs of acute myocarditis with mildly reduced left ventricular systolic function were found. The complex multi-organ symptom constellation facilitated the diagnosis of MIS-A following COVID-19 infection. Besides aspirin, intravenous, continuous hydrocortisone treatment was initiated, resulting in a prompt improvement of symptoms and clinical findings.

Discussion

We report a case of successfully treated MIS-A in the context of COVID-19, which further adds to the existing literature on this rare but clinically significant condition. Our case highlights the necessity of an interdisciplinary approach to correctly diagnose this complex, multi-organ disease and enable fast and appropriate management of these high-risk patients.
Regional pericarditis following uncomplicated catheter ablation procedure: a case report
Authors: Davtyan Karapet V , Topchyan Arpi H , Mershina Elena A , Sinitsyn Valentin E
Published: December 2021

Background

Acute post-ablation pericarditis is the most common complication of epicardial ablation of ventricular arrhythmias, while regional pericarditis following an initially uneventful endocardial catheter ablation (CA) procedure is a rare and elusive diagnosis.

Case summary

We report a case of a 66-year-old Russian female who developed chest pain accompanied by electrocardiogram (ECG) changes—biphasic T waves in V1–V4 leads after an initially uncomplicated premature ventricular complex CA procedure. After examination and investigations, including transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (CMR) and cardiac computed tomography (CCT), she was diagnosed with regional pericarditis, which occurred even though the ablation was uneventful with the limited number of radiofrequency applications. Furthermore, the diagnosis was difficult due to normal body temperature and the absence of pericardial effusion and myocardial abnormalities on TTE, findings that are not characteristic of pericarditis. The patient’s last office visit was in 6 months after the procedure. Neither patient had any complaintsnor there were any changes on ECG and TTE.

Discussion

Regional post-ablation pericarditis is a relatively rare type of post-cardiac injury syndrome (PCIS). The varying severity of the PCIS clinical course makes the diagnosis of post-ablation pericarditis initially difficult, especially in patients undergoing an uneventful CA procedure. Non-invasive imaging modalities as CMR and CCT should be considered initially in elusive cases of PCIS.
Ischaemic and bleeding risk in atrial fibrillation with and without peripheral artery disease and efficacy and safety of full- and half-dose edoxaban vs. warfarin: insights from ENGAGE AF-TIMI 48
Authors: Bonaca Marc P , Antman Elliott M , Cunningham Jonathan W , Wiviott Stephen D , Murphy Sabina A , Halperin Jonathan L , Weitz Jeffrey I , Grosso Michael A , Lanz Hans J , Braunwald Eugene , Giugliano Robert P , Ruff Christian T
Published: December 2021

Aims

In patients with atrial fibrillation (AF), peripheral artery disease (PAD) is associated with higher rates of stroke and bleeding. Both higher dose edoxaban (60/30 mg) and lower dose edoxaban (30/15 mg) were non-inferior to warfarin for stroke and systemic embolism (SSE) and significantly reduced major bleeding in AF patients in the global study to assess the safety and effectiveness of edoxaban vs standard practice of dosing with warfarin in patients with atrial fibrillation (ENGAGE AF-TIMI 48) trial. Whether the efficacy and safety of these dosing strategies vs. warfarin are consistent in patients with AF and PAD has not been described.

Methods and results

Of 21 105 patients with AF randomized to warfarin, edoxaban 60/30 mg, or edoxaban 30/15 mg, 841 were identified with PAD. Endpoints included major adverse cardiovascular events (MACEs), SSE, and major bleeding. Patients with PAD had higher risk of MACEs [adjusted hazard ratio (HRadj) 1.33, 95% confidence interval (CI) 1.12–1.57, P = 0.001] and cardiovascular (CV) death (HRadj 1.49, 95% CI 1.21–1.83, P < 0.001) than those without PAD, but not major bleeding. The efficacy of edoxaban 60/30 mg vs. warfarin was consistent regardless of PAD (SSE HR; PAD 1.16, 95% CI 0.42–3.20; no-PAD 0.86, 95% CI 0.74–1.02, P-interaction 0.57) as was major bleeding (PAD 0.96, 95% CI 0.54–1.70; no-PAD 0.80, 95% CI 0.70–0.91, P-interaction 0.54). Edoxaban 30/15 mg was inferior for SSE, with significant heterogeneity when stratified by PAD status (P-interaction 0.039).

Conclusion

Patients with AF and PAD are at heightened risk of MACEs and CV death vs. those without PAD. The efficacy and safety of edoxaban 60/30 mg vs. warfarin in AF are consistent regardless of PAD; however, edoxaban 30/15 mg is inferior for stroke prevention in AF patients with PAD.

Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00781391
Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study
Authors: D’Erasmo Laura , Steward Kim , Cefalù Angelo Baldassare , Di Costanzo Alessia , Boersma Eric , Bini Simone , Arca Marcello , van Lennep Jeanine Roeters ,   the Italian and European Working Group on Lomitapide in HoFH, D’Erasmo Laura , Cefalù Angelo Baldassare , Di Costanzo Alessia , Bini Simone , Giammanco Antonina , Averna Maurizio , Iannuzzo Gabriella , Fortunato Giuliana , Gentile Marco , Puja Arturo , Montalcini Tiziana , Pavanello Chiara , Calabresi Laura , Vigna Giovanni Battista , Bucci Marco , Bonomo Katia , Nota Fabio , Sampietro Tiziana , Sbrana Francesco , Suppressa Patrizia , Sabbà Carlo , Fimiani Fabio , Cesaro Arturo , Calabrò Paolo , Ventura Fulvio , D’Addato Sergio , Pisciotta Livia , Bertolini Stefano , Arca Marcello , Kolovou Genovefa , Liberopoulos Evangelos , Daphnis Eugene , van Lennep Jeanine Roeters , Rutten Joost , Boersma Eric , Steward Kim , Vogt Anja , Cegla Jaimini , Walji Shahenaz , Kayikcioglu Meral , Real José , Martínez-Hervás Sergio , Ellis Avishay , Littmann Karin
Published: December 2021

Aims

Lomitapide is a lipid-lowering agent indicated as an adjunct therapy for adult homozygous familial hypercholesterolaemia (HoFH). This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe.

Methods and results

In a multicentre retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, low-density lipoprotein cholesterol (LDL-C) changes, adverse events (AEs), and major adverse cardiovascular events (MACE) were assessed. After a median 19 months (interquartile range 11–41 months) of treatment with a mean dosage of 20 mg of lomitapide. Low-density lipoprotein cholesterol decreased by 60%, from baseline 280.5 mg/dL (191.8–405.0 mg/dL) to 121.6 mg/dL (61.0–190.5 mg/dL). At the last visit, 32.0% of patients achieved LDL-C <100 mg/dL and 18.7% <70 mg/dL. At baseline, 38 HoFH patients were receiving LDL apheresis (LA), but after initiation of lomitapide 36.8% of patients discontinued LA. During follow-up, lomitapide was permanently interrupted in 13% of patients. Gastrointestinal AEs occurred in 40% and liver transaminases increased (3–5 × upper limits of normal) in 13% of patients. Among patients with liver ultrasound evaluation (n = 45), a modest increase in hepatic steatosis was noted during treatment; however, liver stiffness measured by elastography in 30 of them remained within the normal range. Among HoFH patients exposed to lomitapide for at least 2 years, MACE incident rate was 7.4 per 1000 person-years in the 2 years after as compared to 21.2 per 1000 person-years before treatment with lomitapide.

Conclusion

In this medium-term real-world experience, lomitapide proved to be very effective in reducing LDL-C in HoFH. Gastrointestinal AEs were common, but liver safety was reassuring with no sign of increased risk of liver fibrosis. A signal of cardiovascular protection was also observed.
Contributions from lithospheric and upper-mantle heterogeneities to upper crustal seismicity in the Korean Peninsula
Authors: Lee Sungho , Saxena Arushi , Song Jung-Hun , Rhie Junkee , Choi Eunseo
Published: December 2021

The Korean Peninsula (KP), located along the eastern margin of the Eurasian and Amurian plates, has experienced continual earthquakes from small to moderate magnitudes. Various models to explain these earthquakes have been proposed, but the origins of the stress responsible for this region's seismicity remain unclear and debated. This study aims to understand the stress field of this region in terms of the contributions from crustal and upper-mantle heterogeneities imaged via seismic tomography using a series of numerical simulations. A crustal seismic velocity model can determine the crustal thickness and density. Upper-mantle seismic velocity anomalies from a regional tomography model were converted to a temperature field, which can determine the structures (e.g. lithospheric thickness, subducting slabs, their gaps, and stagnant features) and density. The heterogeneities in the crustal and upper mantle governed the buoyancy forces and rheology in our models. The modelled surface topography, mantle flow stress, and orientation of maximum horizontal stress, derived from the variations in the crustal thickness, suggest that model with the lithospheric and upper-mantle heterogeneities is required to improve these modelled quantities. The model with upper-mantle thermal anomalies and east–west compression of approximately 50 MPa developed a stress field consistent with the observed seismicity in the KP. However, the modelled and observed orientations of the maximum horizontal stress agree in the western KP but they are inconsistent in the eastern KP. Our analysis, based on the modelled quantities, suggested that compressional stress and mantle heterogeneities may mainly control the seismicity in the western area. In contrast, we found a clear correlation of the relatively thin lithosphere and strong upper-mantle upwelling with the observed seismicity in the Eastern KP, but it is unclear whether stress, driven by these heterogeneities, directly affects the seismicity of the upper crust.
Clonal Hematopoiesis–Associated Gene Mutations in a Clinical Cohort of 448 Patients With Ovarian Cancer
Authors: Weber-Lassalle Konstantin , Ernst Corinna , Reuss Alexander , Möllenhoff Kathrin , Baumann Klaus , Jackisch Christian , Hauke Jan , Dietrich Dimo , Borde Julika , Park-Simon Tjoung-Won , Hanker Lars , Prieske Katharina , Schmidt Sandra , Weber-Lassalle Nana , Pohl-Rescigno Esther , Kommoss Stefan , Marmé Frederik , Heitz Florian , Stingl Julia C , Schmutzler Rita K , Harter Philipp , Hahnen Eric
Published: December 2021

Background

Cancer patients are at risk of secondary therapy–related myeloid neoplasms (t-MNs). Acquired blood-specific mutations in clonal hematopoiesis (CH)–associated genes are t-MN risk factors, and their occurrence associated with cancer therapy and age. Patients with ovarian cancer (OC) showed a particularly high prevalence of CH–associated gene mutations, which may additionally be explained by the high proportion of a hereditary disease cause in this cancer entity.

Methods

We performed a retrospective analysis of 448 OC patients enrolled in the AGO-TR1 study; 249 were enrolled at primary diagnosis and 199 at platinum-sensitive recurrence. Analyses included the most frequently altered CH–associated genes (ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, TP53). Results were analyzed according to the BRCA1/2 germline (gBRCA1/2) mutation status. All statistical tests were 2-sided.

Results

Advanced age at blood draw and a high number of prior platinum-based chemotherapy lines were risk factors to acquire CH–associated gene mutations, with gene-specific effects observed. Binomial logistic regression suggested increased probabilities for gBRCA1/2 mutation carriers to acquire CH-associated PPM1D and TP53 gene mutations (PPM1D: odds ratio = 4.30, 95% confidence interval = 1.48 to 12.46, P = .007; TP53: odds ratio = 6.20, 95% confidence interval = 0.98 to 53.9, P = .06). This observation was due to a statistically significantly increased number of platinum-based chemotherapy lines in gBRCA1/2 mutation carriers vs noncarriers (PPM1D: mean [SD] = 2.04 [1.27] vs 1.04 [0.99], P < .001; TP53: mean [SD] = 2.83 [1.33] vs 1.07 [1.01], P < .001). No interaction between platinum-based chemotherapy and gBRCA1/2 mutation status with the occurrence of CH–associated gene mutations was observed.

Conclusions

A positive gBRCA1/2 mutation status is not a risk factor to acquire CH–associated gene mutations. OC patients may benefit from monitoring CH–associated gene mutations, especially following carboplatin exposure. Future clinical studies are required to assess whether treatment regimen should be adapted according to individual t-MN risks.
Modulated termination of non-coding transcription partakes in the regulation of gene expression
Authors: Haidara Nouhou , Giannini Marta , Porrua Odil
Published: December 2021

Pervasive transcription is a universal phenomenon leading to the production of a plethora of non-coding RNAs. If left uncontrolled, pervasive transcription can be harmful for genome expression and stability. However, non-coding transcription can also play important regulatory roles, for instance by promoting the repression of specific genes by a mechanism of transcriptional interference. The efficiency of transcription termination can strongly influence the regulatory capacity of non-coding transcription events, yet very little is known about the mechanisms modulating the termination of non-coding transcription in response to environmental cues. Here, we address this question by investigating the mechanisms that regulate the activity of the main actor in termination of non-coding transcription in budding yeast, the helicase Sen1. We identify a phosphorylation at a conserved threonine of the catalytic domain of Sen1 and we provide evidence that phosphorylation at this site reduces the efficiency of Sen1-mediated termination. Interestingly, we find that this phosphorylation impairs termination at an unannotated non-coding gene, thus repressing the expression of a downstream gene encoding the master regulator of Zn homeostasis, Zap1. Consequently, many additional genes exhibit an expression pattern mimicking conditions of Zn excess, where ZAP1 is naturally repressed. Our findings provide a novel paradigm of gene regulatory mechanism relying on the direct modulation of non-coding transcription termination.
L’exposition aux aliments et la prévention des allergies chez les nourrissons à haut risque
Authors: Abrams Elissa M , Orkin Julia , Cummings Carl , Blair Becky , Chan Edmond S
Published: December 2021

Un nourrisson est à haut risque d’allergie alimentaire si lui ou un membre de sa famille immédiate présente une affection atopique (comme l’eczéma). Il faut promouvoir et soutenir l’allaitement, quels que soient les enjeux reliés à la prévention des allergies alimentaires, mais chez les nourrissons dont la mère ne peut pas allaiter ou choisit de ne pas le faire, il n’est pas recommandé d’utiliser une préparation en particulier (p. ex., les préparations hydrolysées) pour prévenir les allergies alimentaires. Lorsque les préparations à base de lait de vache sont introduites dans l’alimentation d’un nourrisson, il faut s’assurer de maintenir une ingestion régulière (pas nécessairement plus de 10 mL par jour) pour éviter la perte de tolérance. Chez les nourrissons à haut risque, des données concluantes indiquent que l’introduction précoce d’aliments allergènes (vers l’âge de six mois, mais pas avant l’âge de quatre mois) peut prévenir les allergies alimentaires courantes, notamment les allergies aux arachides et aux œufs. Lorsqu’un aliment allergène a été introduit, il est important d’en maintenir une ingestion régulière (p. ex., quelques fois par semaine) pour maintenir la tolérance. Il est possible d’introduire les aliments allergènes courants sans faire de pause de quelques jours entre chaque nouvel aliment. Par ailleurs, le risque d’une grave réaction lors de la première exposition est très faible chez le nourrisson. Il n’est pas recommandé de procéder au dépistage préventif en cabinet avant d’introduire des aliments allergènes. Aucune recommandation ne peut être formulée pour l’instant sur le rôle des modifications à l’alimentation de la mère pendant la grossesse ou l’allaitement, ou sur les suppléments de vitamine D, d’oméga 3, de prébiotiques ou de probiotiques pour prévenir les allergies alimentaires.
Searching for high-temperature superconductivity: from Mendeleev to Seiberg–Witten via Madelung and beyond
Authors: Kholodenko Arkady L
Published: December 2021

Recently, noticeable progress has been achieved in the area of high-temperature superconductors. Maximum temperatures Tc of 250 K (−23○ C) for LaH10 and 288 K (+15○ C) for CSH8 have been reported at megabar pressures. The highest possible Tcs were achieved by employing hydrides of chemical elements. Empirically, many of these are made of Madelung-exceptional atoms. Here, the theoretical background is provided to explain this observation. The, thus far empirical, Madelung rule controls Mendeleev’s law of periodicity. Although the majority of elements do obey this rule, there are some exceptions. Thus, it is of interest to derive it and its exceptions theoretically in view of experimental findings. As a by-product, such a study yields a plausible explanation of the role of Madelung-exceptional atoms in the design of high-Tc superconductors. Thus far the atoms obeying the Madelung rule and its exceptions have been studied with help of relativistic Hartree–Fock calculations. In this work we reobtain both the rule and the exceptions analytically. The newly developed methods are expected to be of value in quantum many-body theory and, in particular, in the theory of high-Tc superconductivity. Ultimately, the new methods involve some uses of the Seiberg–Witten theory known as the extended Ginzburg–Landau theory of superconductivity. Using results of Sieberg–Witten theory, the difference between Madelung-regular and Madelung-exceptional atoms is explained in terms of the topological transition. The extension of this single-atom result to solids of the respective elements is also discussed.
Association of hidradenitis suppurativa with autoimmune disease and autoantibodies
Authors: Ross Yael , Ballou Stanley
Published: December 2021

Objective

There is thought to be an association between hidradenitis suppurativa (HS) and autoimmune diseases. This retrospective longitudinal cohort study looked to identify whether certain autoimmune diseases or autoantibody specificities are more closely associated with HS than others and whether such associations are related to the severity of HS.

Methods

Patients were identified using the SlicerDicer search tool in Epic from 1 January 2010 to 15 August 2020. Search criteria included HS diagnosis by ICD-10 code (L73.2) and at least one visit to the dermatology department. Charts were reviewed to determine HS disease severity, treatment modalities, presence of autoimmune disease and autoantibody positivity.

Results

Six hundred and twenty-seven patients were identified. Most patients were female (75.3%) and had obese BMIs (71.1%), but there were no significant demographic differences between HS patients with and without autoimmune diseases. One hundred and one (16.1%) patients in the total cohort had at least one autoimmune disease, most commonly thyroid disease, lupus, psoriasis and IBD. Two hundred and twelve patients were also tested for the presence of autoantibodies. The most common positive autoantibody, found in 54 patients (28.4%), was ANA. Fifty-four patients with more severe HS disease manifestations required biologic medications to treat their HS. Neither HS severity nor biologic treatment was associated with presence of autoimmune disease or positive autoantibodies.

Conclusion

In a large cohort of patients with HS followed longitudinally, autoimmune disorders (especially lupus, psoriasis and IBD) and presence of autoantibodies were more commonly observed than expected in the normal population.
Cognition and driving ability in isolated and symptomatic REM sleep behavior disorder
Authors: Sandness David J , McCarter Stuart J , Dueffert Lucas G , Shepard Paul W , Enke Ashley M , Fields Julie , Mielke Michelle M , Boeve Bradley F , Silber Michael H , St. Louis Erik K
Published: December 2021

Study Objectives

To analyze cognitive deficits leading to unsafe driving in patients with REM Sleep Behavior Disorder (RBD), strongly associated with cognitive impairment and synucleinopathy-related neurodegeneration.

Methods

Twenty isolated RBD (iRBD), 10 symptomatic RBD (sRBD), and 20 age- and education-matched controls participated in a prospective case-control driving simulation study. Group mean differences were compared with correlations between cognitive and driving safety measures.

Results

iRBD and sRBD patients were more cognitively impaired than controls in global neurocognitive functioning, processing speeds, visuospatial attention, and distractibility (p < .05). sRBD patients drove slower with more collisions than iRBD patients and controls (p < .05), required more warnings, and had greater difficulty following and matching speed of a lead car during simulated car-following tasks (p < .05). Driving safety measures were similar between iRBD patients and controls. Slower psychomotor speed correlated with more off-road accidents (r = 0.65) while processing speed (−0.88), executive function (−0.90), and visuospatial impairment (0.74) correlated with safety warnings in sRBD patients. Slower stimulus recognition was associated with more signal-light (0.64) and stop-sign (0.56) infractions in iRBD patients.

Conclusions

iRBD and sRBD patients have greater selective cognitive impairments than controls, particularly visuospatial abilities and processing speed. sRBD patients exhibited unsafe driving behaviors, associated with processing speed, visuospatial awareness, and attentional impairments. Our results suggest that iRBD patients have similar driving-simulator performance as healthy controls but that driving capabilities regress as RBD progresses to symptomatic RBD with overt signs of cognitive, autonomic, and motor impairment. Longitudinal studies with serial driving simulator evaluations and objective on-road driving performance are needed.
Eligibility for Cervical Cancer Screening Exit: Comparison of a National and Safety Net Cohort
Authors: Mills Jacqueline M. , Morgan Jake R. , Dhaliwal Amareen , Perkins Rebecca B.
Published: December 2021

(Abstracted from Gynecol Oncol 2021;162:308–314)

Implementation of widespread screening has led to a dramatic decrease in cervical cancer rate over the past 30 years. Current screening guidelines by the United States Preventive Services Task Force, American Cancer Society, and American College of Obstetricians and Gynecologists recommend discontinuation of screening at age 65 years for patients with average risk and prior negative screening or history of total hysterectomy.
Rates of Neuropsychiatric Disorders and Gestational Age at Birth in a Danish Population
Authors: Xia Yuntian , Xiao Jingyuan , Yu Yongfu , Tseng Wan-Ling , Lebowitz Eli , DeWan Andrew Thomas , Pedersen Lars Henning , Olsen Jorn , Li Jiong , Liew Zeyan
Published: December 2021

(Abstracted from JAMA Network Open 2021;4:e2114913)

Gestational age (GA) is associated with brain growth and development. When the duration of gestation is not optimal, a range of adverse health outcomes in the offspring including neuropsychiatric morbidities may occur.
Birth by Cesarean Section and Educational Achievement in Adolescents
Authors: Slykerman Rebecca F. , Li Eileen , Shackleton Nichola , Milne Barry J.
Published: December 2021

(Abstracted from Aust N Z J Obstet Gynaecol 2021;61:386–393)

Evidence suggests that the process for colonizing and stabilizing infant gut microbiota may affect cognitive outcomes later in life, through pathways that connect the gut with the central nervous system. As the fetus's gut undergoes rapid change, so does early brain pathway development.
Association of Chemotherapy Timing in Pregnancy With Congenital Malformation
Authors: van Gerwen Mathilde , Maggen Charlotte , Cardonick Elyce , Verwaaijen Emma J. , van den Heuvel-Eibrink Marry , Shmakov Roman G. , Boere Ingrid , Gziri Mina M. , Ottevanger Petronella B. , Lok Christianne A. R. , Halaska Michael , Shao Long Ting , Struys Ilana , van Dijk-Lokkart Elisabeth M. , Van Calsteren Kristel , Fruscio Robert , Zola Paolo , Scarfone Giovanna , Amant Frédéric
Published: December 2021

(Abstracted from JAMA Network Open 2021;4:e2113180)

Chemotherapy puts a developing fetus at risk of teratogenic effects. The standard recommendation is that chemotherapy be administered after organogenesis is complete, however, the exact gestational age that chemotherapy can be administered safely and avoid causing congenital malformations remains unknown.
Human Metapneumovirus Infection in a Children’s Hospital – It Should Get More Attention
Authors: Hani Nellie , Gornick Wendi , Huff Beth , Atienza Jamie , Singh Jasjit
Published: December 2021

Background:

Respiratory syncytial virus (RSV) and influenza infections are a major cause of hospitalization and intensive care unit (ICU) admission to children’s hospitals and are closely tracked. We compared data over 6 seasons of human metapneumovirus (hMPV), RSV and influenza infections.

Methods:

During the 2014–2019 winter viral seasons, hMPV, RSV and influenza infections were tracked. For hMPV admissions, rates of hospitalizations, ICU admissions, hospital-acquired infections (HAIs) and mortalities were assessed and compared with RSV and influenza admissions. Retrospective data was used to study patients infected with hMPV.

Results:

During the winter seasons of 2014–2019, the rates of hospitalization due to hMPV were significantly higher than both RSV and influenza. ICU admissions, deaths and HAIs for hMPV were similar to RSV and influenza.

Of the 471 total cases with hMPV, 58 (12.3%) had chronic lung disease (CLD) and 23 (4.9%) were tracheostomy dependent. Among 104 hMPV ICU admissions from 2013 to 2019, 86 (82%) had an underlying medical diagnosis, 30 (29%) had CLD, 21 (20%) had tracheostomies and 33 (32%) required mechanical ventilation. The average age of hMPV infected children in our ICU is 3 years and 10 months.

Conclusions:

Our large descriptive study of hMPV infected children over 6 seasons showed higher rates of hospitalization compared with RSV and influenza, similar ICU and HAI rates, and deaths. ICU admitted children often had associated co-morbidities, including CLD. Further studies for focused disease surveillance and potential vaccine development for high-risk children are needed.