bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of coronary artery calcium on the prognosis of heterozygous familial hypercholesterolemia
Authors: Tada H , Nomura A , Usui S , Sakata K , Takamura M , Kawashiri M
Published: November 2023

Aims

This study was designed to examine the association between coronary artery calcium (CAC) and major adverse cardiac events (MACEs) and to estimate CAC progression in patients with familial hypercholesterolemia (FH) in primary prevention settings.

Methods and results

Data of patients with FH admitted to our university hospital between 2000 and 2020, who underwent CAC measurement and were followed up (N = 622, male = 306), were retrospectively reviewed. Risk factors for MACEs were determined using the Cox proportional hazard model. The median follow-up duration was 13.2 years (interquartile range: 9.8–18.4 years). We observed 132 MACEs during the follow-up period. The event rate per 1,000 person-years for CAC scores of 0 (N = 283 [45.5%]), 1–100 (N = 260 [41.8%]), and >100 (N = 79 [12.7%]) was 1.2, 17.0, and 78.8, respectively. Log (CAC score+1) was a significant predictor of the occurrence of MACEs (hazard ratio: 3.24; 95% confidence interval: 1.68–4.80; p = 5.6×10−5) in the multivariate Cox regression analysis, independent of other factors. The risk discrimination of MACEs was enhanced by adding CAC information to other conventional risk factors (C-statistics: 0.833–0.934; p = 1.4×10−15). The regression equations between age and the CAC score in male and female were Y = 0.074X–1.52 and Y = 0. 087X–3.21, respectively.

Conclusion

CAC score helps in further risk stratification in patients with FH. Furthermore, the average age of CAC onset was 21 years in male and 37 years in females.
The distribution of lipoprotein(a) in Norway: a nationwide population-based study
Authors: Jeevanathan J , Blom S M , Retterstol K , Christensen J J
Published: November 2023

Background

Lipoprotein(a)[Lp(a)] is shown to be a common and important risk factor for atherosclerotic cardiovascular disease (ASCVD) because of its proatherogenic and prothrombotic properties. The concentrations of Lp(a) are mainly determined by genetics, and the median value can differ by up to fourfold between ethnic groups. Nevertheless, the distribution of Lp(a) in the Norwegian population remains unknown.

Aim of study: To investigate the distribution of Lp(a) levels in the Norwegian population in individuals <50 years. To investigate awareness and test frequency of Lp(a) among Norwegian doctors.

Methods

The study material is nationwide clinical laboratory data with ̴ 275 000 Lp(a) measurements from 185 000 unique individuals <50 years of age, measured between 2000 and 2019. The data material is restricted to individuals <50 years because we assume a low use of medication among young adults.

Results

Analyses based on samples from 20 597 individuals measured between 2018-2019, show that 72.3% of the individuals have Lp(a)-levels < 30 mg/dL, 8.7% have Lp(a)-levels 30-50 mg/dL and 18.9% have Lp(a)-levels > 50 mg/dL. The distribution of Lp(a)-levels are similar for men and women < 50 years. There is high consciousness of Lp(a) among cardiologists, but low test frequency among cardiologists in other workplaces than lipid clinics.

Conclusion

This is the first study that shows the distribution of Lp(a) in the Norwegian population, which is similar to other European distributions of Lp(a).
Variability of Vaccine Responsiveness in Young Children
Authors: Pichichero Michael E , Xu Lei , Gonzalez Eduardo , Pham Minh , Kaur Ravinder
Published: November 2023

Background

Variability in vaccine responsiveness among young children is poorly understood.

Methods

Nasopharyngeal secretions were collected in the first weeks of life for measurement of cytokines/chemokines seeking a biomarker, and blood samples were collected at age 1 year to identify vaccine responsiveness status, defined as low vaccine responder (LVR), normal vaccine responder (NVR), and high vaccine responder (HVR), to test for vaccine antigen–induced immune memory and for antigen-presenting cell (APC) function.

Results

Significantly lower specific cytokine/chemokine levels as biosignatures, measurable in nasopharyngeal secretions at infant age 1–3 weeks, predicted LVR status compared to NVR and HVR children. Antibiotic exposures were correlated with increased occurrence of LVR. At age 1 year, LVRs had fewer CD4+ T-helper 1 and T-helper 2 memory cells responsive to specific vaccine antigens. APC responses observed among LVRs, both at rest and in response to Toll-like receptor 7/8 stimulation by R848, were suboptimal, suggesting that altered innate immunity may contribute to immune deficiency in LVRs.

Conclusions

Cytokine biosignatures in the first weeks of life may predict vaccine responsiveness in children during the first year of life. Antibiotic exposure is associated with LVR in children. CD4+ T-cell memory induction and APC deficiencies occur in LVR children.
Dancing on a Flaming World: Du Bois’s Religiously Inflected Poetry and Creative Fiction
Authors: Cladis Mark
Published: November 2023

In religious studies, W. E. B Du Bois is familiar as a sociologist of religion and as a Black intellectual and activist. He is less known as a poet and speculative fiction author and certainly not at all as a Romantic author. I present Du Bois as a radical Romantic poet and speculative fiction author who employs religious forms and motifs to reveal and combat anti-Black racism among other forms of oppression. This portrait of Du Bois will no doubt surprise many. Romanticism is usually understood as a specific, delimited period of artistic and intellectual history—a period that Du Bois does not belong to chronologically nor (as most would assume) ideologically. But by bringing attention to Du Bois the radical Romantic, we see religious thought employed as a vehicle to depict the pain, humiliation, and cruelty of racist oppression in North America as well as the possibilities of social change.
Emergence of multiple fluconazole-resistant Candida parapsilosis sensu stricto clones with persistence and transmission in China
Authors: Ning Ya-Ting , Sun Tian-Shu , Dai Rong-Chen , Luo Zheng-Yu , Yu Shu-Ying , Zhang Ge , Mei Ya-Ning , Lin Yu-Lan , Hasi Chao-Lu , Chen Sharon C A , Kong Fan-Rong , Xiao Meng , Xu Ying-Chun , Zhang Li
Published: November 2023

Objectives

We explored the epidemiological and molecular characteristics of Candida parapsilosis sensu stricto isolates in China, and their mechanisms of azole resistance.

Methods

Azole susceptibilities of 2318 non-duplicate isolates were determined using CLSI broth microdilution. Isolates were genotyped by a microsatellite typing method. Molecular resistance mechanisms were also studied and functionally validated by CRISPR/Cas9-based genetic alterations.

Results

Fluconazole resistance occurred in 2.4% (n = 56) of isolates, and these isolates showed a higher frequency of distribution in ICU inpatients compared with susceptible isolates (48.2%, n = 27/56 versus 27.8%, 613/2208; P = 0.019). Microsatellite-genotyping analysis yielded 29 genotypes among 56 fluconazole-resistant isolates, of which 10 genotypes, including 37 isolates, belonged to clusters, persisting and transmitting in Chinese hospitals for 1–29 months. Clusters harbouring Erg11Y132F (5/10; 50%) were predominant in China. Among these, the second most dominant cluster MT07, including seven isolates, characteristically harbouring Erg11Y132F and Mrr1Q625K, lent its carriage to being one of the strongest associations with cross-resistance and high MICs of fluconazole (>256 mg/L) and voriconazole (2–8 mg/L), causing transmission across two hospitals. Among mutations tested, Mrr1Q625K led to the highest-level increase of fluconazole MIC (32-fold), while mutations located within or near the predicted transcription factor domain of Tac1 (D440Y, T492M and L518F) conferred cross-resistance to azoles.

Conclusions

This study is the first Chinese report of persistence and transmissions of multiple fluconazole-resistant C. parapsilosis sensu stricto clones harbouring Erg11Y132F, and the first demonstration of the mutations Erg11G307A, Mrr1Q625K, Tac1L263S, Tac1D440Y and Tac1T492M as conferring resistance to azoles.
Rapamycin and caspofungin show synergistic antifungal effects in caspofungin-susceptible and caspofungin-resistant Candida strains in vitro
Authors: Lefranc Maxime , Accoceberry Isabelle , Fitton-Ouhabi Valérie , Biteau Nicolas , Noël Thierry
Published: November 2023

Objectives

Caspofungin is an echinocandin antifungal agent that inhibits synthesis of glucan required for the fungal cell wall. Resistance is mediated by mutation of Fks1 glucan synthase, among which S645P is the most common resistance-associated polymorphism. Rapamycin is a macrolide that inhibits the mechanistic target of rapamycin (mTOR) protein kinase activity. This study investigated the interaction between rapamycin and caspofungin in inhibiting the growth of WT Candida albicans and Fks1 S645P mutant clinical isolate, and WT Candida lusitaniae and genetically engineered isogenic strain with Fks1 S645P mutation at equivalent position.

Methods

Interactions between caspofungin and rapamycin were evaluated using the microdilution chequerboard method in liquid medium. The results were analysed using the Loewe additivity model (FIC index, FICI) and the Bliss independence model (response surface, RS, analysis).

Results

Synergy between rapamycin and caspofungin was shown for C. albicans and C. lusitaniae strains by RS analysis of the chequerboard tests. Synergy was observed in strains susceptible and resistant to caspofungin. Weak subinhibitory concentrations of rapamycin were sufficient to restore caspofungin susceptibility.

Conclusions

We report here, for the first time, synergy between caspofungin and rapamycin in Candida species. Synergy was shown for strains susceptible and resistant to caspofungin. This study highlights the possible implication of the TOR pathway in sensing antifungal-mediated cell wall stress and in modulating the cellular response to echinocandins in Candida yeasts.
High survival simultaneous occurrence of papillary thyroid carcinoma and ectopic thyroid with medullary thyroid carcinoma; case report and literature review
Authors: Alshehri Saad , Alsarrani Faisal , Almanea Leenah , Alharbi Alanood
Published: November 2023

Thyroid cancer is usually treated with surgical intervention followed by ablative radiotherapy if indicated to eliminate any metastases. Five-year survival rates are 99% for papillary thyroid carcinoma (PTC) and 82% for medullary thyroid carcinoma (MTC). The chances of survival decrease significantly with two simultaneous types of cancers and with male gender. PTC and MTC present as different entities. The coexistence of different types of thyroid carcinoma in a patient is a rare event. We report the case of a 45-year-old Saudi male with a rare synchronous occurrence of PTC in the thyroid gland, along with ectopic MTC with a unique prognosis over the years. Our case adds data to the literature supporting the coincidental coexistence of PTC and MTC.
Novel application of Roux-en-Y for diversion of a cutaneous fistula from an irresectable mesenteric root mature teratoma: a case report
Authors: Field Xavier , Welsh Fraser
Published: November 2023

Reconfiguration of the alimentary tract with the Roux-en-Y has been utilized in a wide variety of contexts since its first description by Swiss physician César Roux. We present a novel and unique application of the Roux-en-Y whereby a chronically discharging cutaneous fistula originating at a retroperitoneal mature teratoma within the root of the mesentery was diverted enterically via a cystojejunostomy and the fistula tract excised, providing a resolution of symptoms. The location of the tumour in the root of the mesentery and the involvement of major mesenteric vessels made a radical resection of the tumour technically impossible but due to the distressing symptoms caused by the fistula made diversion of the fistula an excellent treatment option.
Mucinous non neoplastic cyst of the pancreas: a case report
Authors: Elahabadi Ismail , Rahnama Amir , Bazmandegan Gholamreza , Kamiab Zahra
Published: November 2023

The aim of this study was to introduce a patient with mucinous nonneoplastic cyst (MNNC) at an unusual age. MNNCs of the pancreas are uncommon primary tumors, which affect middle-aged women in their fifth decade of life and have significant malignant potential. Therefore, it is important to accurately diagnose and remove them. This case is a 28-year-old woman patient who presented with a pain in the right and upper abdomen from 3 months ago and worsened at night. A cystic lesion was observed near the upper bridge of the left kidney in abdominal ultrasonography. Contrast-enhanced abdominal computed tomography (CT) scan showed a cystic lesion in the trunk and umbilical cord of the pancreas. The patient underwent surgery and the mass was removed and the MNNC was diagnosed.
War, Women, and Sex Work in Occupied Istanbul, 1918–1923
Authors: MacArthur-Seal Daniel-Joseph
Published: November 2023

The occupation of Istanbul by British, French, and Italian forces and the broader political upheavals between 1918 and 1923 radically altered the lives of women selling sex in the Ottoman capital. Increased demand brought by Allied soldiers and increases in supply as waves of migration brought new and financially precarious women to the city led to an expansion in the scale of the sex trade, which soon became a major concern of Allied and Ottoman authorities, servicemen, and the wider public. British, French, and Italian soldiers not only visited brothels as paying customers, but also enforced new regulations on prostitution, making women sex workers particularly vulnerable to violence perpetrated by them. The end of occupation in 1923 posed further challenges, as shifts in the political and judicial framework and reductions in clientele instigated new outward flows of sex workers from the city, emigrations that were complicated by financial and legal restrictions. The article uses French, British, Turkish, and League of Nations sources to uncover the challenges that women faced while working in Istanbul’s brothels in this period and the ways in which they navigated occupation. In doing so, it hopes to contribute to the investigation of the occupation’s impact on subaltern Istanbulites, something that has been hitherto neglected in research centered on the political contest between imperialist, Ottoman, and Turkish nationalist cadres during these years.
A CRISPR/Cas9-based vector system enables the fast breeding of selection-marker-free canola with Rcr1-rendered clubroot resistance
Authors: Hu Hao , Zhang Yan , Yu Fengqun
Published: November 2023

Breeding for disease resistance in major crops is of crucial importance for global food security and sustainability. However, common biotechnologies such as traditional transgenesis or genome editing do not provide an ideal solution, whereas transgenic crops free of selection markers such as cisgenic/intragenic crops might be suitable. In this study, after cloning and functional verification of the Rcr1 gene for resistance to clubroot (Plasmodiophora brassicae), we confirmed that the genes Rcr1, Rcr2, Rcr4, and CRa from Brassica rapa crops and the resistance gene from B. napus oilseed rape cv. ‘Mendel’ on chromosome A03 were identical in their coding regions. We also determined that Rcr1 has a wide distribution in Brassica breeding materials and renders potent resistance against multiple representative clubroot strains in Canada. We then modified a CRISPR/Cas9-based cisgenic vector system and found that it enabled the fast breeding of selection-marker-free transgenic crops with add-on traits, with selection-marker-free canola (B. napus) germplasms with Rcr1-rendered stable resistance to clubroot disease being successfully developed within 2 years. In the B. napus background, the intragenic vector system was able to remove unwanted residue sequences from the final product with high editing efficiency, and off-target mutations were not detected. Our study demonstrates the potential of applying this breeding strategy to other crops that can be transformed by Agrobacterium. Following the streamlined working procedure, intragenic germplasms can be developed within two generations, which could significantly reduce the breeding time and labor compared to traditional introgression whilst still achieving comparable or even better breeding results.
Renovation sets and their applications in higher-order argumentation frameworks
Authors: Wu Jiachao , Li Hengfei
Published: November 2023

The acceptability of attacks plays a key role in defining semantics of higher-order argumentation frameworks (HO-AF). Several approaches have been put forward to describe the recursive acceptability of attacks. The diversity, on the one hand, leads to the variety of HO-AF semantics. However, on the other hand, it also brings difficulties in the formal examination of the relationship among these distinct semantics and the exploration of new semantics. This work aims at exploring the underlying commons in existing HO-AF semantics and examining the role of such commons in the study of HO-AF semantics. To this end, we introduce novel notion of renovation sets to represent the acceptability of attacks, and identify several types of renovation sets for different kinds of acceptability. We then use renovation sets to represent and compare HO-AF semantics built in four different approaches. The proposal of renovation sets provides a general tool for the study of HO-AFs. The representation demonstrates a method of using renovation sets to establish HO-AF semantics. The comparison shows the feasibility of investigating the relationship between different HO-AF semantics with the help of renovation sets.
Gamma-ray burst precursors from tidally resonant neutron star oceans: potential implications for GRB 211211A
Authors: Sullivan Andrew G , Alves Lucas M B , Márka Zsuzsa , Bartos Imre , Márka Szabolcs
Published: November 2023

Precursors have been observed seconds to minutes before some short gamma-ray bursts. While the precursor origins remain unknown, one explanation relies on the resonance of neutron star pulsational modes with the tidal forces during the inspiral phase of a compact binary merger. In this paper, we present a model for short gamma-ray burst precursors that relies on tidally resonant neutron star oceans. In this scenario, the onset of tidal resonance in the crust–ocean interface mode ignites the precursor flare, possibly through the interaction between the excited neutron star ocean and the surface magnetic fields. From just the precursor total energy, the time before the main event, and a detected quasi-periodic oscillation frequency, we may constrain the binary parameters and neutron star ocean properties. Our model can immediately distinguish neutron star–black hole mergers from binary neutron star mergers without gravitational wave detection. We apply our model to GRB 211211A, the recently detected long duration short gamma-ray burst with a quasi-periodic precursor, and explore the parameters of this system. The precursor of GRB 211211A is consistent with a tidally resonant neutron star ocean explanation that requires an extreme mass ratio neutron star–black hole merger and a high-mass neutron star. While difficult to reconcile with the main gamma-ray burst and associated kilonova, our results constrain the possible precursor mechanisms in this system. A systematic study of short gamma-ray burst precursors with the model presented here can test precursor origin and probe the possible connection between gamma-ray bursts and neutron star–black hole mergers.
Hunting down white dwarf–main sequence binaries using multiwavelength observations
Authors: Nayak Prasanta K , Ganguly Anindya , Chatterjee Sourav
Published: November 2023

Identification of white dwarfs (WD) with main-sequence (MS) companions and characterization of their properties can put important constraints on our understanding of binary stellar evolution and guide the theoretical predictions for a wide range of interesting transient events relevant for, e.g. Rubin Observatory (LSST), ZTF, and LISA. In this study, we combine ultraviolet (UV) and optical colour–magnitude diagrams (CMDs) to identify unresolved WD–MS binaries. In particular, we combine high-precision astrometric and photometric data in the optical from Gaia-DR3 and UV data from GALEX GR6/7 to identify 93 WD–MS candidates within 100 pc. Of these, 80 are newly identified. Using the Virtual Observatory SED Analyzer (VOSA), we fit the spectral energy distributions (SEDs) of all our candidates and derive stellar parameters, such as effective temperature, bolometric luminosity, and radius for both companions. We find that our identification method helps identify hotter and smaller WD companions (majority with ≥10 000 K and ≤0.02 R⊙) relative to the WDs identified by past surveys. We infer that these WDs are relatively more massive (median ∼ $0.76\, \mathrm{M}_\odot$). We find that most of the MS companions in our binaries are of the K and M spectral types.
The dynamical tides of spinning Newtonian stars
Authors: Pnigouras P , Gittins F , Nanda A , Andersson N , Jones D I
Published: November 2023

We carefully develop the framework required to model the dynamical tidal response of a spinning neutron star in an inspiralling binary system, in the context of Newtonian gravity, making sure to include all relevant details and connections to the existing literature. The tidal perturbation is decomposed in terms of the normal oscillation modes, used to derive an expression for the effective Love number which is valid for any rotation rate. In contrast to previous work on the problem, our analysis highlights subtle issues relating to the orthogonality condition required for the mode-sum representation of the dynamical tide and shows how the prograde and retrograde modes combine to provide the overall tidal response. Utilizing a slow-rotation expansion, we show that the dynamical tide (the effective Love number) is corrected at first order in rotation, whereas in the case of the static tide (the static Love number) the rotational corrections do not enter until second order.
First Light And Reionisation Epoch Simulations (FLARES) – XII: The consequences of star–dust geometry on galaxies in the EoR
Authors: Vijayan Aswin P , Thomas Peter A , Lovell Christopher C , Wilkins Stephen M , Greve Thomas R , Irodotou Dimitrios , Roper William J , Seeyave Louise T C
Published: November 2023

Using the First Light And Reionisation Epoch Simulations, a suite of hydrodynamical simulations, we explore the consequences of a realistic model for star–dust geometry on the observed properties of galaxies. We find that the ultraviolet (UV) attenuation declines rapidly from the central regions of galaxies, and bright galaxies have spatially extended star formation that suffers less obscuration than their fainter counterparts, demonstrating a non-linear relationship between the UV luminosity and the UV attenuation, giving a double power-law shape to the UVLF. Spatially distinct stellar populations within galaxies experience a wide range of dust attenuation due to variations in the dust optical depth along their line of sight, which can range from completely dust obscured to being fully unobscured. The overall attenuation curve of a galaxy is then a complex combination of various lines of sight within the galaxy. We explore the manifestation of this effect to study the reliability of line ratios to infer galaxy properties, in particular, the Balmer decrement and the Baldwin, Phillips, and Terlevich (BPT) diagram. We find the Balmer decrement predicted Balmer-line attenuation to be higher (factor of 1 to ≳ 10) than expected from commonly used attenuation curves. The observed BPT line ratios deviate from their intrinsic values [median difference of 0.08 (0.02) and standard deviation of 0.2 (0.05) for log10([N${\small II}]\lambda 6585/$Hα) (log10([O iii]λ5008/Hβ)]. Finally, we explore the variation in observed properties (UV attenuation, UV slope, and Balmer decrement) with viewing angle, finding average differences of ∼0.3 mag in the UV attenuation.
Spectrally resolved cosmic rays - III. Dynamical impact and properties of the circumgalactic medium
Authors: Girichidis Philipp , Werhahn Maria , Pfrommer Christoph , Pakmor Rüdiger , Springel Volker
Published: November 2023

Cosmic rays (CRs) are dynamically important in the evolution of galaxies by regulating star formation and powering galactic outflows. However, to what extent CRs regulate galaxy formation depends on the coupling strength of CRs with the ambient plasma and the effective CR transport speed. Moreover, both properties sensitively depend on the CR momentum, which is largely unexplored in three-dimensional hydrodynamical simulations. We perform magnetohydrodynamical simulations of entire galaxies with masses ranging from 1010 to $10^{12}\, \mathrm{M}_\odot$ and compare dynamically coupled CRs in the grey approximation with a spectrally resolved model that includes CR momenta from $0.1\, \mathrm{GeV} c^{-1}$ to $100\, \mathrm{TeV} c^{-1}$. We find that hadronic cooling of CRs dominates over Alfvén cooling, with the latter emulating CR losses as a result of streaming of CRs down their pressure gradient. While star formation rates and galaxy morphologies are only mildly affected by the spectral CR modelling, mass loading factors of galactic outflows can differ by up to a factor of 4 in dwarf galaxies. All simulated low-mass haloes (M = 1010, 1011, and $3\times 10^{11}\, \mathrm{M}_\odot$) drive strong outflows, where CR transport is temporally dominated by advection. In contrast, the Milky Way-mass galaxy with $M=10^{12}\, \mathrm{M}_\odot$ does not drive sustained outflows, so that CR transport is entirely dominated by diffusion. The effective energy weighted diffusion coefficients vary by two orders of magnitude from the canonical energy-weighted values of $\langle {D}\rangle _{e_\mathrm{cr}}\sim 10^{28}\, \mathrm{cm^2\, s^{-1}}$ in the disc up to $3\times 10^{29}\, \mathrm{cm^2\, s^{-1}}$ in the circumgalactic medium, where we observe substantial temperature and CR pressure differences between our grey and spectral CR models.
IPOP: An Integrative Plant Multi-omics Platform for Cross-species Comparison and Evolutionary Study
Authors: Huang Wenyue , Hu Xiaona , Ren Yanlin , Song Minggui , Ma Chuang , Miao Zhenyan
Published: November 2023

The advent of high-throughput sequencing technologies has led to the production of a significant amount of omics data in plants, which serves as valuable assets for conducting cross-species multi-omics comparative analysis. Nevertheless, the current dearth of comprehensive platforms providing evolutionary annotation information and multi-species multi-omics data impedes users from systematically and efficiently performing evolutionary and functional analysis on specific genes. In order to establish an advanced plant multi-omics platform that provides timely, accurate, and high-caliber omics information, we collected 7 distinct types of omics data from 6 monocots, 6 dicots, and 1 moss, and reanalyzed these data using standardized pipelines. Additionally, we furnished homology information, duplication events, and phylostratigraphic stages of 13 species to facilitate evolutionary examination. Furthermore, the integrative plant omics platform (IPOP) is bundled with a variety of online analysis tools that aid users in conducting evolutionary and functional analysis. Specifically, the Multi-omics Integration Analysis tool is available to consolidate information from diverse omics sources, while the Transcriptome-wide Association Analysis tool facilitates the linkage of functional analysis with phenotype. To illustrate the application of IPOP, we conducted a case study on the YTH domain gene family, wherein we observed shared functionalities within orthologous groups and discerned variations in evolutionary patterns across these groups. To summarize, the IPOP platform offers valuable evolutionary insights and multi-omics data to the plant sciences community, effectively addressing the need for cross-species comparison and evolutionary research platforms. All data and modules within IPOP are freely accessible for academic purposes (http://omicstudio.cloud:4012/ipod/).
Temporal Variation in Introgressed Segments’ Length Statistics Computed from a Limited Number of Ancient Genomes Sheds Light on Past Admixture Pulses
Authors: Di Santo Lionel N , Quilodrán Claudio S , Currat Mathias
Published: November 2023

Hybridization is recognized as an important evolutionary force, but identifying and timing admixture events between divergent lineages remain a major aim of evolutionary biology. While this has traditionally been done using inferential tools on contemporary genomes, the latest advances in paleogenomics have provided a growing wealth of temporally distributed genomic data. Here, we used individual-based simulations to generate chromosome-level genomic data for a 2-population system and described temporal neutral introgression patterns under a single- and 2-pulse admixture model. We computed 6 summary statistics aiming to inform the timing and number of admixture pulses between interbreeding entities: lengths of introgressed sequences and their variance within genomes, as well as genome-wide introgression proportions and related measures. The first 2 statistics could confidently be used to infer interlineage hybridization history, peaking at the beginning and shortly after an admixture pulse. Temporal variation in introgression proportions and related statistics provided more limited insights, particularly when considering their application to ancient genomes still scant in number. Lastly, we computed these statistics on Homo sapiens paleogenomes and successfully inferred the hybridization pulse from Neanderthal that occurred approximately 40 to 60 kya. The scarce number of genomes dating from this period prevented more precise inferences, but the accumulation of paleogenomic data opens promising perspectives as our approach only requires a limited number of ancient genomes.
Associations Between Self-Reported Sleep Quality, Fatigue Severity, Factors Associated With Successful Cessation, and Cessation Beliefs Among Regular Smokers
Authors: Matthews Joe A , Sallis Hannah M , Dyer Maddy L , McConville Ryan , Isotalus Hanna , Attwood Angela S
Published: November 2023

Background

Smokers report poorer sleep than nonsmokers and sleep quality deteriorates further during cessation, increasing risk of smoking relapse. Better understanding of the relationship between sleep and relapse-related outcomes could inform novel approaches to smoking cessation support. The aim of this study was to investigate same-day associations of self-reported sleep quality and fatigue severity with factors associated with successful cessation and cessation beliefs, among regular smokers.

Methods

This cross-sectional observational study (n = 412) collected self-reported sleep quality, fatigue severity, and factors associated with successful cessation and cessation beliefs among regular smokers via an online survey (60% male).

Results

There was evidence of an association between sleep quality (SQ) and reduced 24-hour (β = −0.12, p = .05) and lifetime (β = −0.09, p = .04) abstinence self-efficacy. In addition, poorer SQ and higher fatigue severity (FS) were associated with increased smoking urges (SQ: β = 0.27, p < .001; FS: β = 0.32, p < .001), increased barriers to cessation (SQ: β = 0.19, p < .001; FS: β = 0.32, p < .001), and increased perceived risks to cessation (SQ: β = 0.18, p < .001; FS: β = 0.26, p < .001). Fatigue severity was weakly associated with increased perceived benefits to cessation (β = 0.12, p = .017).

Conclusions

Self-reported sleep quality and fatigue severity were associated with multiple factors associated with successful cessation and cessation beliefs. Further research is needed to extend these findings by using different methods to identify the temporal direction of associations and causality.

Implications

This study is the first to examine associations between sleep quality, fatigue severity, and factors associated with successful cessation and cessation beliefs. Findings show that both sleep quality and fatigue severity are associated with multiple factors associated with successful cessation and could be modifiable targets for future smoking cessation interventions. Furthermore, our data suggest that fatigue severity has an independent effect on multiple factors associated with successful cessation when accounting for sleep quality. This indicates that fatigue, independent of sleep quality, could be an important factor in a quit attempt.
Five myths about carbon pricing
Authors: Metcalf Gilbert E
Published: November 2023

While carbon pricing, in general, and carbon taxes, in particular, are popular with economists, they are subject to considerable misunderstanding among policy-makers and the public. In this paper I consider and refute five myths about carnbon taxes: (i) that a carbon price will hurt economic growth; (ii) that carbon pricing will kill jobs; (iii) that a carbon tax and cap-and-trade programme have the same economic impacts; (iv) that we can’t achieve carbon reduction targets with a carbon tax; and (v) that carbon pricing is regressive. I then discuss implications for policy-making.
Double dividend? Transnational initiatives and governance innovation for climate change and biodiversity
Authors: Bulkeley Harriet , Betsill Michele , Fransen Anouk , VanDeveer Stacy
Published: November 2023

Growing recognition of the need to tackle climate change and biodiversity loss together is leading to shifts in the global environmental governance landscape such that these two traditionally separate domains are increasingly interlinked. This process is taking place not at the level of the international policy regimes but rather through the work of transnational governance initiatives (TGIs) that connect state and non-state actors and which form an increasingly formalized part of the hybrid regime complexes through which global environmental governance is conducted. Central to these dynamics are ‘nature-based solutions’, interventions designed to work with nature to achieve multiple sustainability goals. In this paper, we demonstrate the ways in which TGIs frame and implement nature-based solutions. We show how this is leading to an evolution in market and asset-based responses to addressing these twin challenges and consider the wider consequences for how we understand what effective responses to the interlinked problems of climate and biodiversity entail.
Competing Roles of Evolving P–T Conditions, Equilibration Volume and Chemical Potential Landscape in the Formation of Corona Texture: a Case Study from the Southern Granulite Terrane, India
Authors: Dey Anindita , Roy Choudhury Sirina , Sengupta Pulak
Published: November 2023

Corona texture is defined by the development of partial or complete rim of one or more minerals around a central reactant mineral depicting limited mass transport (local equilibration) in the length scale of the coronitic layers. The mineral assemblages forming corona texture in a metamorphic rock are commonly used to trace the P-T-X conditions through which the rock evolved during various tectonic processes. However, without a proper assessment of the changes in the equilibration volume (EV) and its effect on the mineralogy, any petrological interpretation deduced from the coronitic texture may be incorrect. In this study, we demonstrate that the double corona texture, observed in a suite of Mg-Al rich ortho-amphibole cordierite-bearing rock from the Cauvery Shear System (Southern Granulite Terrane, India), developed in response to the continuously evolving EV. The studied rock contains aluminosilicate porphyroblasts that are set in a matrix of ortho-amphibole ± quartz. The aluminosilicate porphyroblasts are rimmed successively by an inner symplectic corona of sapphirine + cordierite and an outer mono-mineralic corona of cordierite. Locally, patches of corundum with a rind of cordierite grow preferentially along the interface of aluminosilicate and the inner symplectic corona. Based on detailed petrography and mineral composition analyses, the corona textures are interpreted to have formed through a sequence of different chemical reactions that occurred in local micro-domains. We calculated quantitative P-T pseudosection in a NCFMASHT (Na2O-CaO-FeO-MgO-Al2O3-SiO2-H2O-TiO2) system and activity-adjusted P-T petrogenetic grid in a MASH (MgO-Al2O3-SiO2-H2O) system which, together, suggest that the coronitic assemblages were formed in response to a steeply decompressive retrograde P-T path from >8.8 kbar to <6 kbar, at a nearly constant temperature of ~700°C. Changes in EV in response to the limited transport of chemical components during the formation of corona texture were investigated through isothermal P-μMgO, P-μSiO2 and P-μMgO-μSiO2 MASH diagrams. Our results quantitatively model the continuously changing chemical potential landscape (P-μMgO- μSiO2 evolution path) around the central aluminosilicate porphyroblast within the corona-bearing micro-domain. The path demonstrates that a gradually shrinking EV around the central aluminosilicate during retrogression led to the sequential change of mineral reactions and equilibrium mineral assemblages and resulted in the formation of multiple coronae. Unavailability of fluids and/or rapid exhumation is considered as the most dominant factors responsible for the decreasing elemental mobility and the consequent shrinking in EV in the studied rock.
ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader
Authors: Wang Chuanle , Huang Yan , Yang Yue , Li Ruofei , Li Yingying , Qiu Hongxin , Wu Jiali , Shi Guang , Ma Wenbin , Songyang Zhou
Published: November 2023

Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability. The telomeric repeat-containing RNA (TERRA) that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop. In tumor cells, R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres (ALT) pathway. Dysregulated R-loops can cause stalled replication forks and telomere instability. However, how R-loops are recognized and regulated, particularly at telomeres, is not well understood. We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination. Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses. In addition, ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway. Using the proximity-dependent biotin identification (BioID) technology, we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases, including DHX9. Importantly, ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9. Our findings suggest that ILF3 may function as a reader of telomeric R-loops, helping to prevent abnormal homologous recombination and maintain telomere homeostasis.
Owner Incentives and Performance in Healthcare: Private Equity Investment in Nursing Homes
Authors: Gupta Atul , Howell Sabrina T , Yannelis Constantine , Gupta Abhinav
Published: November 2023

Amid an aging population and a growing role for private equity (PE) in the care of older adults, this paper studies how PE ownership affects U.S. nursing homes using patient-level Medicare data. We show that PE ownership leads to a patient cohort with lower health risk. However, after instrumenting for the patient-nursing home match, we find that PE ownership increases mortality by 11%. Declines in measures of patient well-being, nurse staffing, and compliance with care standards help to explain the mortality effect. Overall, we conclude that PE has nuanced effects with adverse outcomes for a subset of patients.
Validation of the PEDiatric Behçet’s Disease classification criteria: an evidence-based approach
Authors: Matucci-Cerinic Caterina , Palluy Helene , Al-Mayouf Sulaiman M , Brogan Paul A , Cantarini Luca , Gul Ahmet , Kasapcopur Ozgur , Kuemmerle-Deschner Jasmin , Ozen Seza , Saadoun David , Shahram Farhad , Bovis Francesca , Mosci Eugenia , Ruperto Nicolino , Gattorno Marco , Kone-Paut Isabelle
Published: November 2023

Objectives

To validate the PEDiatric Behçet’s Disease classification criteria (PEDBD) with an evidence-based approach.

Methods

A total of 210 pediatric patients [70 Behçet’s disease (BD), 40 periodic fever, aphthous stomatitis, pharyngitis, adenitis, 35 familial Mediterranean fever, 26 hyper-IgD syndrome, 22 TNF-receptor associated periodic fever syndrome, 17 undefined recurrent fevers] were randomly selected from the Eurofever Registry. A set of 11 experienced clinicians/researchers blinded to the original diagnosis evaluated the patients. Using the table consensus as gold standard (agreement ≥ 80%), the PEDBD, ISG and ICBD criteria were applied to BD patients and to confounding diseases with other autoinflammatory conditions in order to define their sensitivity, specificity and accuracy.

Results

At the end of the third round, a consensus was reached in 139/210 patients (66.2%). The patients with a consensus ≥80% were classified as confirmed BD (n = 24), and those with an agreement of 60–79% as probable BD (n = 10). When comparing these patients with the confounding diseases group, an older age at disease onset, the presence of oral and genital ulcers, skin papulo-pustular lesions, a positive pathergy test and posterior uveitis were BD distinctive elements. The ISG, ICBD and PEDBD criteria were applied to confirmed BD and to the confounding disease group, showing a sensitivity of 0.50, 0.79 and 0.58, a specificity of 1.00, 0.97 and 0.99, and an accuracy of 0.91, 0.94 and 0.92, respectively.

Conclusions

The PEDBD criteria were very specific, while the ICBD were more sensitive. The complexity of childhood BD suggests larger prospective international cohorts to further evaluate the performance of the criteria.
Effectiveness of biological targeted therapies may discriminate seronegative from seropositive rheumatoid arthritis
Authors: Iannone Florenzo , Lopalco Giuseppe , Cacciapaglia Fabio , Venerito Vincenzo , Perniola Simone , Fornaro Marco
Published: November 2023

Objective

To assess the real-world effectiveness of targeting biologic DMARDs (bDMARDs) in rheumatoid arthritis (RA) patients negative for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA).

Methods

We retrospectively selected 81 seronegative and 404 seropositive RA patients receiving treatment with abatacept, anti-TNF alpha or tocilizumab. Effectiveness was evaluated by analysing drug survival using Kaplan–Meyer analysis over 10-year follow-up. Survival rates were compared by log rank test, and hazard ratios (HRs) of therapy discontinuation were estimated through multivariate Cox regression.

Results

Clinical characteristics were similar between the two groups, except for a significantly higher percentage of inadequate responders to prior bDMARDs in the seronegative RA patients (P = 0.02). Among seronegative RA, tocilizumab demonstrated a survival rate of 73.9% with a mean survival time (MST) of 76.8 months (95% CI 61–92), which was significantly higher than abatacept [37.5%, MST 37.1 months (95% CI 22–51; P = 0.01)]. Anti-TNF alpha therapy fell in the middle [50.0%, MST 63.5 months (95% CI 47–79)] but the difference was not significant. Nevertheless, seropositive RA patients did not show significantly different drug survival rates. Negative predictors of drug discontinuation were RF/ACPA positivity (HR 0.56) and sex male (HR 0.58), but treatment with abatacept (HR 1.88) or anti-TNF alpha (HR 1.79), no co-therapy with conventional DMARDs (HR 1.74), absence of bone erosions (HR 1.41) and higher HAQ (HR 1.58) were positive predictors.

Conclusions

To confirm these preliminary findings and to explore the hypothesis of a distinctive therapeutic algorithm in seronegative RA, prospective studies on larger cohorts are needed.
Antenatal corticosteroid therapy, delivery intervals and perinatal mortality in low-resource settings
Authors: Mwita Stanley , Kamala Benjamin , Konje Eveline , Katabalo Deogratias , Msanga Delfina R , Marwa Karol J , Basinda Namanya , Kongola Gilbert , Jande Mary , Dewey Deborah
Published: November 2023

Background

Uncertainty exists regarding the ideal interval between the administration of antenatal corticosteroids (ACS) and delivery. The study’s objective was to assess the risks of perinatal mortality and respiratory distress syndrome (RDS) among preterm neonates whose mothers gave birth within 48 h of the administration of ACS and those whose mothers gave birth between 48 h and 7 days.

Methods

The study design was a secondary analysis of data from an observational prospective chart review study that was carried out in Tanzania in 2020. Preterm infants born to mothers who got at least one dose of ACS between 28 and 34 weeks of pregnancy were included.

Results

A total of 346 preterm neonates (294 singletons and 52 twins) were exposed to ACS. Compared to infants born 48 h following the first dose of ACS, those exposed to the drug between 48 h and 7 days had significantly decreased rates of perinatal mortality and RDS. Multivariable analysis revealed that infants exposed ACS between 48 h and 7 days prior to delivery had lower risk of perinatal mortality (aRR 0.30, 95% CI 0.14–0.66) and RDS (aRR 0.27, 95% CI 0.14–0.52).

Conclusion

The first dose of ACS given between 48 h and 7 days before delivery was associated with a lower risk of perinatal mortality and RDS than when the first dose was given <48 h before delivery. To improve neonatal outcomes, healthcare providers should consider administering ACS to mothers at the appropriate time.
EU financial market regulation a decade from the financial-crisis-era reforms: crisis, uncertainty, and capacity
Authors: Moloney Niamh
Published: November 2023

This article reflects on the effectiveness of European Union (EU) financial market regulation, a decade or so after the closure of the EU’s massive financial-crisis-era reform programme. To do so, it considers the first significant test of the financial-crisis-era reforms: the March 2020 period of acutely elevated financial stability risk as the COVID-19 pandemic intensified, global markets roiled, and the investment fund sector experienced large-scale disruption. It relates the EU’s broadly successful management of this period to, first, the resilience of the legislative choices made and refined over the financial crisis era as regards investment fund regulation and, secondly, to technocratic action, by the European Securities and Markets Authority (ESMA) and the European Systemic Risk Board (ESRB), that facilitated rule amplification, risk monitoring, supervisory coordination, and supervisory convergence and thereby supported the earlier legislative choices. Drawing on the March 2020 experience, the article goes on to consider the capacity of EU financial market regulation more generally to manage what are increasingly dynamic risks to financial market stability. It identifies a strengthening of the EU’s capacity in this regard, but also persistent and intractable risks to this capacity, including as regards legitimation.