bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of lockdown on physical activity and arrhythmia burden in patients with an implantable cardioverter-defibrillator: the COVID-19 Lockdown ICD-Carelink (CLIC) study
Authors: Ghossein M A , Linz D , Van Kraaij D J W , Van Stipdonk A M W , De Melis M , Vernooy K , Heijman J
Published: December 2022

Background

Both COVID-19 and the measures taken to control the pandemic may significantly affect cardiovascular health. The effects of a lockdown on physical activity and its potential consequences for arrhythmia burden remain largely unknown.

Purpose

In this study, we investigated the effect of the lockdown during the first COVID-19 wave on patients' physical activity and arrhythmia burden.

Methods

All patients with an ICD connected to a Carelink home-monitoring system from two Dutch hospitals were included. Anonymized data on physical activity, heart rate, and occurrence of ventricular tachycardia/fibrillation (VT/VF), and atrial fibrillation/tachycardia (AF/AT) were obtained and were compared between March-April 2020 (lockdown) and March-April 2019 (reference) within each patient. The study was approved by the local ethics committee.

Results

The ICDs of 531 patients registered significantly less activity during de lockdown period compared to the reference period (210±104 min vs 182±103 min, p<0.0001, Figure 1, panels A and B), while weather conditions improved (1A). Daytime and nighttime heart rates were significantly lower during lockdown compared to the reference period (71.3±9 bpm vs 72.6±9 bpm, p<0.0001 and 63.4±9 vs 63.8±9, p=0.02, respectively). AF/AT burden increased (Figure 2A) while number of VT/VF episodes decreased (2B). There was no significant difference in number of NSVT episodes.

Conclusion

During the lockdown in the first COVID-19 wave, the Carelink system revealed significantly less activity, increase in AF/AT burden and decrease in VT/VF episodes. Further investigation is needed to understand the relationship between physical activity and the occurrence of arrhythmias in ICD patients.

Funding Acknowledgement

Type of funding sources: None.
Performance metrics of AI-enhanced single lead EKG maintained after entry of organised clustered data
Authors: Mehta S , Vieira D , Zerpa D , Guillen V , Gonzalez A , Brena-Pastor L , Siyam T , Stoica S , Ozair S , Pinos D , Martinez F , Fleming M , Carrera K , Rossitto F , Whuking C
Published: December 2022

Background

Our experience in creating innovative Artificial Intelligence-guided single lead EKG methodologies for ST-Elevation Myocardial Infarction (STEMI) detection within complex EKG records has been previously validated.

Purpose

By expanding the intricate variables of our previously tested algorithm input, we seek to further improve our STEMI detecting tool.

Methods

11,567 12-lead EKG records (10-s length, 500 Hz sample frequency) derived from the Latin America Telemedicine Infarct Network database from April 2014 to December 2019. From these records, we included the following balanced classes: angiographically confirmed and unconfirmed STEMI (divided by wall affected), branch blocks, non-specific ST-T changes, normal, and abnormal (Remaining 200+ CPT codes). Cardiologist annotations ensured precision (Ground truth). Determined classes were “STEMI” and “Not-STEMI”. A 1-D Convolutional Neural Network model was trained and tested for each lead with dataset proportions of 90/10, respectively. The last dense layer outputs a probability for each record being STEMI/Not-STEMI. The analysis also included performance metrics and false-negative reports.

Results

Overall, the most promising Single lead for STEMI detection was V2 (91.2% Accuracy, 89.6% Sensitivity, and 92.9% Specificity). 55% of false negatives were inferior wall STEMI (Table 1).

Conclusion

Appreciable progress of our new methodology compared to our previous experiences in AI-guided Single Lead for STEMI detection, especially for lead V2. By performing a thorough analysis of false-negative reports, we aspire to identify potential areas of STEMI detection weakness which will become the focus of future ventures.

Funding Acknowledgement

Type of funding sources: None.
The effectiveness of a telemedical program for COVID-19 positive high-risk patients in domestic isolation
Authors: Brunelli L , Poelzl L , Hirsch J , Engler C , Naegele F , Egelseer-Bruendl T , Scheffauer T , Rassel C , Schmit C , Nawabi F , Luckner-Hornischer A , Bauer A , Poelzl G
Published: December 2022

Background

For almost two years, the Covid-19 pandemic has posed an enormous challenge to healthcare systems. Recurrent waves of disease brought the health systems to the limit of their resilience.

Purpose

The Tele-Covid telemedicine care program was installed in December 2020 to monitor high-risk patients in home isolation. Close monitoring allows early detection of disease deterioration and timely intensification of therapy, ideally avoiding intensive care. Conversely, if the course of the disease is stable, unnecessary hospitalisation can be avoided, thus reducing the burden on the healthcare system.

Methods

Patient acquisition was performed in collaboration with the local public health service and primary care physicians. Covid-19 positive high-risk patients (age >65 years and/or severe comorbidities) from the greater Innsbruck area were fitted with an ear sensor-based home monitoring system. The ear sensor measures SpO2, respiratory rate, body temperature and heart rate. The monitoring team (25 medical students supervised by 6 physicians) provided continuous monitoring of vital signs (24/7).

After validation of the measurements, the collected parameters were evaluated using a specially developed risk score. If a defined risk score was exceeded, the patient was contacted by telephone. The combination of the clinical condition and the risk score determined the further course of action: (a) wait and see, (b) notify the primary care physician, or (c) refer for inpatient admission.

The program was active from December 2020 to March 2022. In Summer 2021, the program was temporarily paused due to the epidemiological situation.

Results

A total of 132 patients (59.8% women) were monitored. The median age was 74 years (IQR: [67.3–80.8]). 91 patients (68.9%) had at least one relevant comorbidity. During the monitoring period, hospitalisation was required in 20 patients (15.2%), 3 of whom were transferred to the intensive care unit. Of the hospitalised patients, 3 (15%) patients died. During the same monitoring period, the Austrian Ministry of Health reported a mortality rate of 20.5% of all hospitalised patients in Austria aged 70–79 years. Subjectively, the patients felt safe due to close monitoring.

Conclusion

The Tele-Covid program is the successful implementation of a remote monitoring system in a pandemic situation. In the future, a broad application of the program is feasible.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Region of the Tyrol
Neuromodulation in patients with refractory angina pectoris: a review
Authors: Vervaat Fabienne Elvira , van der Gaag Antal , Teeuwen Koen , van Suijlekom Hans , Wijnbergen Inge
Published: December 2022

The number of patients with coronary artery disease (CAD) who have persisting angina pectoris despite optimal medical treatment known as refractory angina pectoris (RAP) is growing. Current estimates indicate that 5–10% of patients with stable CAD have RAP. In absolute numbers, there are 50 000–100 000 new cases of RAP each year in the USA and 30 000–50 000 new cases each year in Europe. The term RAP was formulated in 2002. RAP is defined as a chronic disease (more than 3 months) characterized by diffuse CAD in the presence of proven ischaemia which is not amendable to a combination of medical therapy, angioplasty, or coronary bypass surgery. There are currently few treatment options for patients with RAP. One such last-resort treatment option is spinal cord stimulation (SCS) with a Class of recommendation IIB, level of evidence B in the 2019 European Society of Cardiology guidelines for the diagnosis and management of chronic coronary syndromes. The aim of this review is to give an overview of neuromodulation as treatment modality for patients with RAP. A comprehensive overview is given on the history, proposed mechanism of action, safety, efficacy, and current use of SCS.
Treatment of acute type A aortic dissection with the Ascyrus Medical Dissection Stent in a consecutive series of 57 cases
Authors: Luehr Maximilian , Gaisendrees Christopher , Yilmaz Abdul Kadir , Winderl Leila , Schlachtenberger Georg , Van Linden Arnaud , Wahlers Thorsten , Walther Thomas , Holubec Tomas
Published: December 2022

OBJECTIVES

The Ascyrus Medical Dissection Stent (AMDS) has been recently introduced as an alternative for total arch replacement in acute aortic dissection type A (AADA). The aim of this study was to evaluate the postoperative outcomes after AMDS treatment in a large contemporary cohort of AADA patients.

METHODS

Data acquisition was performed retrospectively at 2 German aortic centres between 2020 and 2022 and comprised the perioperative parameters and postoperative results of all AADA patients. All patients treated with the AMDS for AADA were included in the study. The primary end point was in-hospital mortality. Secondary end points were defined as early postoperative and AMDS-related complications.

RESULTS

Fifty-seven AADA patients treated by AMDS were included in the study group. The mean age was 64.6 ± 10.8 years and 59.7% (n = 34) were males. The actual in-hospital mortality was considerably lower than the predicted mortality risk by the German registry for acute aortic dissection type A score (16% vs 22%). The median ICU and in-hospital stay were 5 (interquartile range: 3–13) and 12 (interquartile range: 10–22) days, respectively. Postoperative complications comprised acute renal insufficiency (37%) with need for temporary (16%) or permanent dialysis (5%), delirium (26%), re-exploration for bleeding (14%), tracheostomy (14%) and new stroke (4%). A new AMDS-related complication (central stent collapse) was observed in 9% (n = 5) by postoperative computed tomography and chest X-ray. The incidence of complete central AMDS collapse did not impact 30-day mortality.

CONCLUSIONS

The AMDS may be successfully used in AADA with acceptable 30-day mortality in accordance with the German registry for acute aortic dissection type A score. However, careful preoperative evaluation of the patient’s individual aortic anatomy regarding potential contraindications and proper device implantation are strongly recommended to avoid complete central AMDS collapse.
Preventing extrinsic mechanisms of bioprosthetic degeneration using polyphenols
Authors: Melder Robert J , Naso Filippo , Nicotra Francesco , Russo Laura , Vesely Ivan , Tuladhar Sugat R , Calafiore Antonio M , Zilla Peter , Gandaglia Alessandro , Korossis Sotiris
Published: December 2022

OBJECTIVES

The purpose of this study was to evaluate the impact of a polyphenols-based treatment on the extrinsic mechanisms responsible for early bioprosthetic heart valve (BHV) degeneration. Structural degeneration can be driven by both extrinsic and intrinsic mechanisms. While intrinsic mechanisms have been associated with inherent biocompatibility characteristics of the BHV, the extrinsic ones have been reported to involve external causes, such as chemical, mechanical and hydrodynamic, responsible to facilitate graft damage.

METHODS

The chemical interaction and the stability degree between polyphenols and pericardial tissue were carefully evaluated. The detoxification of glutaraldehyde in commercial BHVs models and the protective effect from in vivo calcification were taken into relevant consideration. Finally, the hydrodynamic and biomechanical features of the polyphenols-treated pericardial tissue were deeply investigated by pulse duplicator and stress-strain analysis.

RESULTS

The study demonstrated the durability of the polyphenols-based treatment on pericardial tissue and the stability of the bound polyphenols. The treatment improves glutaraldehyde stabilization's current degree, demonstrating a surprising in vivo anti-calcific effect. It is able to make the pericardial tissue more pliable while maintaining the correct hydrodynamic characteristics.

CONCLUSIONS

The polyphenols treatment has proved to be a promising approach capable of acting simultaneously on several factors related to the premature degeneration of cardiac valve substitutes by extrinsic mechanisms.
Prevalence, patterns and outcomes of cardiac involvement in Erdheim–Chester disease
Authors: Azoulay Lévi-Dan , Bravetti Marine , Cohen-Aubart Fleur , Emile Jean-François , Seilhean Danielle , Plu Isabelle , Charlotte Frédéric , Waintraub Xavier , Carrat Fabrice , Amoura Zahir , Cluzel Philippe , Haroche Julien
Published: December 2022

Aims

Cardiac involvement of Erdheim–Chester disease (ECD), a rare L group histiocytosis, has been reported to be associated with poor outcomes, but systematic studies are lacking. The present study aimed to investigate the prevalence, clinical features, imaging features, and prognosis of cardiac involvement in ECD in a large series.

Methods and results

All patients with ECD who underwent cardiac magnetic resonance (CMR) imaging between 2003 and 2019 at a French tertiary center were retrospectively included. Primary outcome was all-cause mortality. Secondary outcomes were pericarditis, cardiac tamponade, conduction disorders, device implantation and coronary artery disease (CAD). A total of 200 patients were included [63 (54–71) years, 30% female, 58% BRAFV600E mutated]. Median follow-up was 5.5 years (3.3–9 years). On CMR, right atrioventricular sulcus infiltration was observed in 37% of patients, and pericardial effusion was seen in 24% of patients. In total, 8 patients (4%) had pericarditis (7 acute, 1 constrictive), 10 patients (5%) had cardiac tamponade, 5 patients (2.5%) had ECD-related high-degree conduction disorders, and 45 patients (23%) had CAD. Overall, cardiac involvement was present in 96 patients (48%) and was associated with BRAFV600E mutation [Odds ratio (OR) = 7.4, 95% confidence interval (CI) (3.5–16.8), P < 0.001] and ECD-related clinical events [OR = 5, 95%CI (1.5–21.2), P = 0.004] but not with lower survival in multivariate analysis [adjusted hazard ratio (HR) = 1.4, 95% CI (0.8–2.5), P = 0.2].

Conclusion

Cardiac involvement is present in nearly half of ECD patients and is associated with BRAFV600E mutation and complications (pericarditis, cardiac tamponade, and conduction disorders) but not with lower survival.
Very high-power short-duration ablation for pulmonary vein isolation utilizing a very-close protocol—the FAST AND FURIOUS PVI study
Authors: Heeger Christian-H , Sano Makoto , Popescu Sorin Ștefan , Subin Behnam , Feher Marcel , Phan Huong-Lan , Kirstein Bettina , Vogler Julia , Eitel Charlotte , Hatahet Sascha , Kuck Karl-Heinz , Tilz Roland R
Published: December 2022

Aims

The very high-power short-duration (vHP-SD) radiofrequency (RF) ablation concept of atrial fibrillation (AF) treatment by pulmonary vein isolation (PVI) aims for safer, more effective, and faster procedures. Utilizing conventional ablation, the ‘close protocol’ has been verified. Since lesion formation of vHP-SD ablation creates wider but shallower lesions we adapted the close protocol to an individualized and tighter ‘very-close protocol’ of 3–4 mm of inter-lesion distance (ILD) at the anterior and 5–6 mm at the posterior aspect of the left atrium using vHP-SD only. Here, we evaluated the safety and efficacy of vHP-SD ablation for PVI utilizing a very-close protocol in comparison with standard ablation.

Methods and results

A total of 50 consecutive patients with symptomatic AF were treated with a very-close protocol utilizing vHP-SD (vHP-SD group). The data were compared with 50 consecutive patients treated by the ablation-index-guided strategy (control group). The mean RF time was 352 ± 81 s (vHP-SD) and 1657 ± 570 s (control, P < 0.0001), and the mean procedure duration was 59 ± 13 (vHP-SD) and 101 ± 38 (control, P < 0.0001). The first-pass isolation rate was 74% (vHP-SD) and 76% (control, P = 0.817). Severe adverse events were reported in 1 (2%, vHP-SD) and 3 (6%, control) patients (P = 0.307). A 12-month recurrence-free survival was 78% (vHP-SD) and 64% (control, P = 0.142). PVI durability assessed during redo-procedures was 75% (vHP-SD) vs. 33% (control, P < 0.001).

Conclusions

PVI solely utilizing vHP-SD via a very-close protocol provides safe and effective procedures with a high rate of first-pass isolations. The procedure duration and ablation time were remarkably low. A 12-month follow-up and PVI durability are promising.
Autoimmune diseases and new-onset atrial fibrillation: a UK Biobank study
Authors: Tilly Martijn J , Geurts Sven , Zhu Fang , Bos Maxime M , Ikram M Arfan , de Maat Moniek P M , de Groot Natasja M S , Kavousi Maryam
Published: December 2022

Aims

The underlying mechanisms of atrial fibrillation (AF) are largely unknown. Inflammation may underlie atrial remodelling. Autoimmune diseases, related to increased systemic inflammation, may therefore be associated with new-onset AF.

Methods and results

Participants from the population-based UK Biobank were screened for rheumatic fever, gastrointestinal autoimmune diseases, autoimmune diseases targeting the musculoskeletal system and connective tissues, and neurological autoimmune diseases. Between 2006 and 2022, participants were followed for incident AF. Cox proportional hazards regression analyses were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations. 494 072 participants free from AF were included (median age 58.0 years, 54.8% women). After a median of 12.8 years, 27 194 (5.5%) participants were diagnosed with new-onset AF. Rheumatic fever without heart involvement (HR, 95% CI: 1.47, 1.26–1.72), Crohn’s disease (1.23, 1.05–1.45), ulcerative colitis (1.17, 1.06–1.31), rheumatoid arthritis (1.39, 1.28–1.51), polyarteritis nodosa (1.82, 1.04–3.09), systemic lupus erythematosus (1.82, 1.41–2.35), and systemic sclerosis (2.32, 1.57–3.44) were associated with a larger AF risk. In sex-stratified analyses, rheumatic fever without heart involvement, multiple sclerosis, Crohn’s disease, seropositive rheumatoid arthritis, psoriatic and enteropathic arthropathies, systemic sclerosis and ankylosing spondylitis were associated with larger AF risk in women, whereas only men showed a larger AF risk associated with ulcerative colitis.

Conclusions

Various autoimmune diseases are associated with new-onset AF, more distinct in women. Our findings elaborate on the pathophysiological differences in autoimmunity and AF risk between men and women.
The demographic history of house mice (Mus musculus domesticus) in eastern North America
Authors: Agwamba Kennedy D , Nachman Michael W
Published: December 2022

The Western European house mouse (Mus musculus domesticus) is a widespread human commensal that has recently been introduced to North America. Its introduction to the Americas is thought to have resulted from the transatlantic movements of Europeans that began in the early 16th century. To study the details of this colonization history, we examine population structure, explore relevant demographic models, and infer the timing of divergence among house mouse populations in the eastern United States using published exome sequences from five North American populations and two European populations. For North American populations of house mice, levels of nucleotide variation were lower, and low-frequency alleles were less common than for European populations. These patterns provide evidence of a mild bottleneck associated with the movement of house mice into North America. Several analyses revealed that one North American population is genetically admixed, which indicates at least two source populations from Europe were independently introduced to eastern North America. Estimated divergence times between North American and German populations ranged between ∼1,000 and 7,000 years ago and overlapped with the estimated divergence time between populations from Germany and France. Demographic models comparing different North American populations revealed that these populations diverged from each other mostly within the last 500 years, consistent with the timing of the arrival of Western European settlers to North America. Together, these results support a recent introduction of Western European house mice to eastern North America, highlighting the effects of human migration and colonization on the spread of an invasive human commensal.
Toward an Understanding of Healthy Cognitive Aging: The Importance of Lifestyle in Cognitive Reserve and the Scaffolding Theory of Aging and Cognition
Authors: Oosterhuis Elise J , Slade Kate , May Patrick J C , Nuttall Helen E
Published: December 2022

The World Health Organization (WHO) aims to improve our understanding of the factors that promote healthy cognitive aging and combat dementia. Aging theories that consider individual aging trajectories are of paramount importance to meet the WHO’s aim. Both the revised Scaffolding Theory of Aging and Cognition (STAC-r) and Cognitive Reserve theory (CR) offer theoretical frameworks for the mechanisms of cognitive aging and the positive influence of an engaged lifestyle. STAC-r additionally considers adverse factors, such as depression. The two theories explain different though partly overlapping aspects of cognitive aging. Currently, it is unclear where the theories agree and differ and what compensation mechanism of age-related cognitive decline might be better explained by either STAC-r, CR, or by both. This review provides an essential discussion of the similarities and differences between these prominent cognitive aging theories, their implications for intervention methods and neurodegenerative disease, and significant shortcomings that have not yet been addressed. This review will direct researchers to common insights in the field and to intervention targets and testable hypotheses for future research. Future research should investigate the potential use of STAC-r in neurodegenerative diseases and provide clarity as to what combination of factors build CR, including their relative importance and when in life they are most effective.
Convenient consumption: a critical qualitative inquiry into the gambling practices of younger women in Australia
Authors: Thomas Samantha L , Pitt Hannah , Randle Melanie , Cowlishaw Sean , Rintoul Angela , Kairouz Sylvia , Daube Mike
Published: December 2022

There are a range of stereotypes and assumptions associated with women’s gambling behaviours. While researchers have demonstrated that the practices associated with women’s gambling are changing and becoming increasingly normalized, there is a limited understanding of how younger women ascribe meanings to these practices. This study explored the gambling practices of younger women. Forty-one women (20–40 years) participated in qualitative telephone interviews. Participants were asked open-ended questions about personal engagement in gambling, including experiences of gambling, gambling engagement, and experiences with different gambling products and environments. Data interpretation was guided by reflexive thematic analysis. Three themes were constructed from the data: (i) gambling infrastructures, including both products and the embedding of gambling in community environments, contributed to the convenient and regular consumption of gambling, with gambling easy to access and engage with; (ii) social networks and intergenerational gambling practices impacted the perceived social value and competencies related to gambling; and (iii) technology facilitated new gambling practices, routinizing gambling behaviours through automation and building perceived competencies with a range of gambling products. Gambling regulation and public health responses to gambling often focus on either individual behaviours or product characteristics. This study suggests that this focus is too narrow and excludes important influences on younger women’s gambling practices, which include the infrastructure that supports the provision and consumption of gambling products. Public health research, policy and practice must consider the full range of determinants that may contribute to the initiation and continuation of gambling in younger women.
Leading causes of deaths in the mortality transition in Papua New Guinea: evidence from the Comprehensive Health and Epidemiological Surveillance System
Authors: Pham Bang Nguyen , Jorry Ronny , Silas Vinson D , Okely Anthony D , Maraga Seri , Pomat William
Published: December 2022

Background

Changing causes of deaths in the mortality transition in Papua New Guinea (PNG) are poorly understood. This study analysed community-level data to identify leading causes of death in the population and variations across age groups and sexes, urban-rural sectors and provinces.

Method

Mortality surveillance data were collected from 2018–20 as part of the Comprehensive Health and Epidemiological Surveillance System (CHESS), using the World Health Organization 2016 verbal autopsy (VA) instrument. Data from 926 VA interviews were analysed, using the InterVA-5 cause of death analytical tool to assign specific causes of death among children (0–14 years), those of working age (15–64 years) and the elderly (65+ years).

Result

Nearly 50% of the total deaths were attributed to non-communicable diseases (NCDs), followed by infectious and parasitic diseases (35%), injuries and external causes (11%) and maternal and neonatal deaths (4%). Leading causes of death among children were acute respiratory tract infections (ARTIs) and diarrhoeal diseases, each contributing to 13% of total deaths. Among the working population, tuberculosis (TB) contributed to 12% of total deaths, followed by HIV/AIDS (11%). TB- and HIV/AIDS-attributed deaths were highest in the age group 25–34 years, at 20% and 18%, respectively. These diseases killed more females of working age (n = 79, 15%) than males (n = 52, 8%). Among the elderly, the leading causes of death were ARTIs (13%) followed by digestive neoplasms (10%) and acute cardiac diseases (9%).

Conclusion

The variations in leading causes of death across the populations in PNG suggest diversity in mortality transition. This requires different strategies to address specific causes of death in particular populations.
The Free Factor Complex and the Dualizing Module for the Automorphism Group of a Free Group
Authors: Himes Zachary , Miller Jeremy , Nariman Sam , Putman Andrew
Published: December 2022

Answering a question of Hatcher and Vogtmann, we prove that the top homology group of the free factor complex is not the dualizing module for $\operatorname {Aut}(F_{n})$, at least for $n = 5$.
Chemical Profiles and Lethal Toxicities of Native Botanical Insecticides for the Control of Musca domestica Linnaeus and Stomoxys indicus Picard (Diptera: Muscidae) in Songkhla Province, Thailand
Authors: Klakankhai Warin , Sathantriphop Sunaiyana , Ngoenklan Ratchadawan , Dada Nsa , Muenworn Vithee , Khawniam Tassanee , Tainchum Krajana
Published: December 2022

Livestock farming is currently reducing the use of synthetic insecticides because of the development of resistance in insect pests. Plant-based bioinsecticides are considered alternatives to synthetic pesticides. Therefore, the present study investigated the chemical composition and discriminating concentrations (DCs) of essential oils from Syzygium aromaticum (L.) Merr. and L. M. Perry (SA), Cinnamomum porrectum (Roxb.) Kosterm (CP), and Litsea cubeba (Loureiro) Persoon (LC) against laboratory-reared Musca domestica (larvae and adults) and field-derived Stomoxys indicus (adults) using larval dip and adult contact bioassays. All essential oils were analyzed using gas chromatography/mass spectroscopy. The most common components in the SA, CP, and LC oils were eugenol, safrole, and terpenoids, respectively. The results of a larval test indicated that CP was most effective against M. domestica with a DC of 6.134% v/v. In adult bioassays, CP was also the most toxic oil against M. domestica (DC = 30.644% v/v), whereas SA displayed the greatest toxicity against S. indicus (DC = 1.434% v/v). Moreover, in the larval bioassay results of oils tested at 1, 5, and 10% v/v in M. domestica, 1% and 5% v/v CP had the shortest median lethal times values of 68.88 and 19.44 min, respectively, whereas, at 10% v/v, SA displayed the shortest median lethal time (0.03 min), followed by CP (1.74 min) and LC (19.02 min). However, additional data are needed to further evaluate the semi-field and field effects of CP and SA on M. domestica and S. indicus under realistic operational conditions.
The draft genome of the Tibetan partridge (Perdix hodgsoniae) provides insights into its phylogenetic position and high-altitude adaptation
Authors: Zhou Chuang , Zheng Xiaofeng , Feng Kaize , Peng Kexin , Zhang Yanni , Zhao Guangqing , Meng Yang , Zhang Li , Yue Bisong , Wu Yongjie
Published: December 2022

The Tibetan partridge (Perdix hodgsoniae) is a widely distributed endemic species in high-altitude areas across the Tibetan Plateau where the hypoxia, lower temperature and high ultraviolet radiation are pivotal factors influencing survival. However, the underlying genetic adaptation of the Tibetan partridge to extreme environments remains uncertain due to limited genomic resources. Similarly, the phylogenetic position of Perdix within Phasianidae remains controversial due to lacking information. Consequently, we de novo assembled and annotated the whole genome of the Tibetan partridge. The genome size was 1.15 Gb with contig N50 of 3.70 Mb. A total of 202.30 Mb (17.61%) repetitive elements and 445,876 perfect microsatellites were identified. A total of 16,845 functionally annotated protein-coding genes were identified in the Tibetan partridge. Genomic phylogenetic analysis across 30 Galliformes species indicated a close relationship between Perdix and typical pheasants composed of Chrysolophus, Symaticus, Phasianus, Crossopilon, and Lophura. However, the phylogenetic relationship of (Perdix + (Chrysolophus + (Syrmaticus + other pheasants))) was different from those of (Perdix + (Syrmaticus + (Chrysolophus + other pheasants))) in previous studies. Comparative genomic results identified NFKB1 and CREBBP positively selected genes related to hypoxia with 3 and 2 Tibetan partridge-specific missense mutations, respectively. Expanded gene families were mainly associated with energy metabolism and steroid hydroxylase activity, meanwhile, contracted gene families were mainly related to immunity and olfactory perception. Our genomic data considerably contribute to the phylogeny of Perdix and the underlying adaptation strategies of the Tibetan partridge to a high-altitude environment.
A novel germlineSMAD4variant detected in a Japanese family with juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia
Authors: Kananazawa Yoshikazu , Yamada Takeshi , Yamaguchi Tatsuro , Saito Yoshinobu , Kakinuma Daisuke , Masuda Yuka , Ando Fumihiko , Ohashi Ryuji , Eguchi Hidetaka , Okazaki Yasushi , Ishida Hideyuki , Yoshida Hiroshi
Published: December 2022

Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder caused by pathogenic germline variants of mainly SMAD4 or BMPR1A genes. Some patients with JPS, especially with SMAD4 variants, also develop hereditary, hemorrhagic telangiectasia (HHT). HHT is also an autosomal dominant inherited disorder. Herein, we identified a novel germline pathogenic variant of the SMAD4 in a Japanese family with JPS and HHT. A six-base pair deletion in the SMAD4 gene (NM_005359.6:c.1495_1500delTGCATA) was identified in the patients. Two amino acids are deleted from SMAD4 protein (p.Cys499_Ile500del), which are located in MSH2 domain essential for the binding with SMAD3. This is a novel variant that has not been registered in any database surveyed. Amino acid structural analysis predicted significant changes in the secondary and three-dimensional structures in the vicinity of the two amino acids’ deletion. The variant is classified as ‘Likely Pathogenic’ according to the American College of Medical Genetics and Genomics guidelines.
Retroperitoneal dermoid cyst presenting with radiculopathy symptoms: a case report
Authors: Kelly-Hedrick Margot , Frerich Jason M , Peairs Emily M , Cardona Diana M , Arcot Rohith , Smith Brandon , Abern Michael , Miller Chad , Abd-El-Barr Muhammad M
Published: December 2022

Dermoid cysts rarely present in the retroperitoneal space or during adulthood. In this case report, we describe the clinical presentation, operative and post-operative course of a 31-year old with a retroperitoneal dermoid cyst. The patient presented with buttock and leg pain/paresthesia found to have a retroperitoneal mass between the psoas muscle and L5/S1 disk space. We describe the operative approach, including intra-operative images, of the resection by a team of urologists and neurosurgeons. The histology is also presented. Finally, we discuss the benefits of use of intra-operative ultrasound and neuromonitoring.
Thomas Betterton’s Book-Trade Apprenticeship and the Amazing Careers of His Two Masters, John Holden and John Rhodes, with Some Notes on the Actor’s Library
Authors: Ferdinand Christine
Published: December 2022

Thomas Betterton has been described as ‘the greatest English actor between Burbage and Garrick’ as well ‘the pre-eminent manager of his time’ (ODNB); yet he began his career in the book trade, with an informal apprenticeship split between entirely different masters. The first was the ambitious John Holden who might have succeeded Humphrey Moseley as the most important literary publisher of the day, had he not died young. His second master was John Rhodes, who took a more pragmatic view of bookselling. Rhodes’ heart was in the theatre—he briefly had his own company and purchased shares in a playhouse—but he understood that bookselling provided a more stable income. Rhodes would have kept the young Betterton busy in his bookshop, but he probably also gave Betterton his first stage experience. While Betterton went on to a brilliant acting and managing career, he continued his association with books, accumulating a large working library.
A social network approach to critical discourse studies
Authors: Chen Fu , Wang Guofeng
Published: December 2022

Viewing discourse as a social practice, one important task of critical discourse studies (CDS) is to unveil inequality, power, and ideologies through linguistic and discoursal analysis of social events, social identities, and social relations represented in oral or written texts. As such, it lends itself to social network analysis (SNA) which aims to discover relation patterns and structures among such social actors as people, organizations, and political entities. This article proposes an integration of SNA techniques into CDS and explores this possibility via an example in diachronic study on international relations represented in news reporting on China in The New York Times between 1980 and 2020 by examining subject–direct object pairs to approach the target relations between national actors. It is shown that the coupling of these two approaches effectively reveals international relation networks surrounding key national actors, based on which detailed linguistic and discoursal analysis further sheds light on the underlying ideological and socio-political factors in the news reports. Considering the fact that SNA consists of a great variety of network statistics, which can be broadly categorized into those related to the relative position of the actor in the network and those concerned with the structure of the network itself, there is vast space for the utility of SNA metrics in aiding CDS in further research.
X-ray emission of the radio-loud quasar SDSS J121426.52+140258.9: independent variations between optical/UV and X-ray emission
Authors: Zhou Minhua , Gu Minfeng , Liao Mai , Anjum Muhammad S
Published: December 2022

To understand the X-ray emission of active galactic nuclei (AGNs), we explored the optical-to-X-ray variation correlation of a radio-loud quasar (RLQ) SDSS J121426.52+140258.9 (hereafter J1214+1402) with multi-epoch observations by the Swift and XMM–Newton telescopes. With the historical multiband data, we found that the infrared-to-X-ray flux of RLQ J1214+1402 should not be dominated by the beamed-jet emission. The Swift optical/UV and X-ray light curves showed that J1214+1402 has two optical states, with low flux before 2014 April 8 and high flux after 2014 June 11, but has no significant X-ray variations during the time range between 2007 March 9 and 2014 August 4. This result was supported by the XMM–Newton observations in the time overlapping with Swift. Interestingly, the early XMM–Newton data prior to the Swift time present two unusual emission epochs when J1214+1402 has relatively low optical fluxes but has the brightest X-ray fluxes. The overall independence of optical-to-X-ray variation seems hard to describe by the disc–corona model. With the X-ray spectral fitting, we find that the soft X-ray excess in J1214+1402 appears only during the high optical state when the X-ray emission is at a low state. The soft X-ray excess in J1214+1402 is difficult to explain by an ionized accretion disc; instead, it may be related to the warm corona.
Rimmed and rippled accretion disc models to explain AGN continuum lags
Authors: Starkey D A , Huang Jiamu , Horne Keith , Lin Douglas N C
Published: December 2022

We propose a solution to the problem of accretion disc sizes in active galactic nuclei being larger when measured by reverberation mapping than predicted by theory. Considering the disc’s exposed-surface thickness profile H(r), our solution invokes a steep rim or rippled structures irradiated by the central lamp-post. We model the continuum lags and the faint and bright disc spectral energy distribution (SED) in the best-studied case NGC 5548 (black hole mass $M_\bullet =7\times 10^7\, \mathrm{M}_\odot$, disc inclination i = 45°). With the lamp-post off, the faint-disc SED fixes a low accretion rate $\dot{M}\simeq 0.0014~\mathrm{M}_\odot \, {\rm yr}^{-1}$ and high prograde black hole spin a• ≃ 0.93, for which $r_{\rm in}=2\, G\, M_\bullet /c^2$ and $L_{\rm disc}=0.25\, \dot{M}\, c^2$. The bright-disc SED then requires a lamp-post luminosity ${L_{\rm LP}}\simeq 5\, \dot{M}\, c^2/(1-A)$ for disc albedo A. Reprocessing on the thin disc with T ∝ r−3/4 gives time lags τ ∝ λ4/3 but three times smaller than observed. Introducing a steep H(r) rim, or multiple crests, near r ∼ 5 light days, reprocessing on the steep centre-facing slope increases temperatures from ∼1500 to ∼6000 K, and this increases optical lags to match the lag data. Most of the disc surface maintains the cooler T ∝ r−3/4 profile that matches the SED. The bright lamp-post may be powered by magnetic links tapping the black hole spin. The steep rim occurs near the disc’s dust sublimation radius as in the ‘failed disc wind model for broad-line clouds’. Lens–Thirring torques aligning the disc and black hole spin may also raise a warp and associated waves. In both scenarios, the small density scale height implied by the inferred value of H(r) suggests possible marginal gravitational instability in the disc.
Galaxy image classification using hierarchical data learning with weighted sampling and label smoothing
Authors: Ma Xiaohua , Li Xiangru , Luo Ali , Zhang Jinqu , Li Hui
Published: December 2022

With the development of a series of Galaxy sky surveys in recent years, the observations increased rapidly, which makes the research of machine learning methods for galaxy image recognition a hot topic. Available automatic galaxy image recognition researches are plagued by the large differences in similarity between categories, the imbalance of data between different classes, and the discrepancy between the discrete representation of Galaxy classes (DDRGC) and the essentially gradual changes from one morphological class to the adjacent class. These limitations have motivated several astronomers and machine learning experts to design projects with improved galaxy image recognition capabilities. Therefore, this paper proposes a novel learning method, ‘Hierarchical Imbalanced data learning with Weighted sampling and Label smoothing’ (HIWL). The HIWL consists of three key techniques respectively dealing with the above-mentioned three problems: (1) designed a hierarchical galaxy classification model based on an efficient backbone network; (2) utilized a weighted sampling scheme to deal with the imbalance problem; and (3) adopted a label smoothing technique to alleviate the DDRGC problem. We applied this method to galaxy photometric images from the Galaxy Zoo-The Galaxy Challenge, exploring the recognition of completely round smooth, in between smooth, cigar-shaped, edge-on, and spiral. The overall classification accuracy is 96.32 per cent, and some superiorities of the HIWL are shown based on recall, precision, and F1-Score in comparing with some related works. In addition, we also explored the visualization of the galaxy image features and model attention to understand the foundations of the proposed scheme.
Quenching in cosmic sheets: tracing the impact of large-scale structure collapse on the evolution of dwarf galaxies
Authors: Pasha Imad , Mandelker Nir , van den Bosch Frank C , Springel Volker , van de Voort Freeke
Published: December 2022

Dwarf galaxies are thought to quench primarily due to environmental processes most typically occurring in galaxy groups and clusters or around single, massive galaxies. However, at earlier epochs, (5 < z < 2), the collapse of large-scale structure (forming Zel’dovich sheets and subsequently filaments of the cosmic web) can produce volume-filling accretion shocks which elevate large swaths of the intergalactic medium (IGM) in these structures to a hot (T > 106 K) phase. We study the impact of such an event on the evolution of central dwarf galaxies (5.5 < log M* < 8.5) in the field using a spatially large, high resolution cosmological zoom simulation which covers the cosmic web environment between two protoclusters. We find that the shock-heated sheet acts as an environmental quencher much like clusters and filaments at lower redshift, creating a population of quenched, central dwarf galaxies. Even massive dwarfs that do not quench are affected by the shock, with reductions to their sSFR and gas accretion. This process can potentially explain the presence of isolated quenched dwarf galaxies, and represents an avenue of pre-processing, via which quenched satellites of bound systems quench before infall.
SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression
Authors: Cioetto-Mazzabò Laura , Boldrin Francesca , Beauvineau Claire , Speth Martin , Marina Alberto , Namouchi Amine , Segafreddo Greta , Cimino Mena , Favre-Rochex Sandrine , Balasingham Seetha , Trastoy Beatriz , Munier-Lehmann Hélène , Griffiths Gareth , Gicquel Brigitte , Guerin Marcelo E , Manganelli Riccardo , Alonso-Rodríguez Noelia
Published: December 2022

The emergence of drug-resistant Mycobacterium tuberculosis strains highlights the need to discover anti-tuberculosis drugs with novel mechanisms of action. Here we discovered a mycobactericidal strategy based on the prodrug activation of selected chemical derivatives classified as nitronaphthofurans (nNFs) mediated by the coordinated action of the sigH and mrx2 genes. The transcription factor SigH is a key regulator of an extensive transcriptional network that responds to oxidative, nitrosative, and heat stresses in M. tuberculosis. The nNF action induced the SigH stress response which in turn induced the mrx2 overexpression. The nitroreductase Mrx2 was found to activate nNF prodrugs, killing replicating, non-replicating and intracellular forms of M. tuberculosis. Analysis of SigH DNA sequences obtained from spontaneous nNF-resistant M. tuberculosis mutants suggests disruption of SigH binding to the mrx2 promoter site and/or RNA polymerase core, likely promoting the observed loss of transcriptional control over Mrx2. Mutations found in mrx2 lead to structural defects in the thioredoxin fold of the Mrx2 protein, significantly impairing the activity of the Mrx2 enzyme against nNFs. Altogether, our work brings out the SigH/Mrx2 stress response pathway as a promising target for future drug discovery programs.
Crystal structures and fragment screening of SARS-CoV-2 NSP14 reveal details of exoribonuclease activation and mRNA capping and provide starting points for antiviral drug development
Authors: Imprachim Nergis , Yosaatmadja Yuliana , Newman Joseph A
Published: December 2022

NSP14 is a dual function enzyme containing an N-terminal exonuclease domain (ExoN) and C-terminal Guanine-N7-methyltransferase (N7-MTase) domain. Both activities are essential for the viral life cycle and may be targeted for anti-viral therapeutics. NSP14 forms a complex with NSP10, and this interaction enhances the nuclease but not the methyltransferase activity. We have determined the structure of SARS-CoV-2 NSP14 in the absence of NSP10 to 1.7 Å resolution. Comparisons with NSP14/NSP10 complexes reveal significant conformational changes that occur within the NSP14 ExoN domain upon binding of NSP10, including helix to coil transitions that facilitate the formation of the ExoN active site and provide an explanation of the stimulation of nuclease activity by NSP10. We have determined the structure of NSP14 in complex with cap analogue 7MeGpppG, and observe conformational changes within a SAM/SAH interacting loop that plays a key role in viral mRNA capping offering new insights into MTase activity. We perform an X-ray fragment screen on NSP14, revealing 72 hits bound to sites of inhibition in the ExoN and MTase domains. These fragments serve as excellent starting point tools for structure guided development of NSP14 inhibitors that may be used to treat COVID-19 and potentially other future viral threats.
Legal Positivism’s Internal Morality
Authors: Gallego Javier
Published: December 2022

This article examines the jurisprudential arguments elaborated in David Dyzenhaus’s The Long Arc of Legality. In particular, it looks into the main claim of the book: that the fact of ‘very unjust laws’ is central to illuminating the idea of law’s authority, the elaboration of which Dyzenhaus takes to be the purpose of legal theory. The article analyses Dyzenhaus’s own normative proposal in this matter, which consists of a version of legal positivism committed to Lon Fuller’s principles of the internal morality of law, with the corollary of a conception of the judicial role as bound to a duty to apply these internal principles of legality when exercising their main function. While I cast some doubts on the feasibility of constructing the judge’s function that way, in the end I celebrate Dyzenhaus’s attempt at refining legal positivism’s identity, especially in light of the ongoing debate with contemporary anti-positivism.