bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bilaterality, not multifocality, is an independent risk factor for recurrence in low-risk papillary thyroid cancer
Authors: Rodriguez Schaap Pedro Manuel , Lin Jia Feng , Metman Madelon J H , Dreijerink Koen M A , Links Thera P , Bonjer H Jaap , Nieveen van Dijkum Els J M , Dickhoff Chris , Kruijff Schelto , Engelsman Anton F 
Published: June 2023

Abstract

Background
The impact of multifocality and bilaterality on recurrence in patients with low-risk papillary thyroid cancer (PTC) is relevant when considering patients for a de-escalated treatment strategy: hemithyroidectomy instead of total thyroidectomy followed with or without radioactive iodine. This study aims to analyze contralateral tumor probability in patients treated for low-risk PTC and assess multifocality and bilaterality as possible predictors for recurrence.

Methods
Patients with low-risk PTC treated with total thyroidectomy followed with or without radioactive iodine in the Netherlands between 2005 and 2015 were included in this study. Patients were identified from the Netherlands Comprehensive Cancer Organization (IKNL) and linked with the nationwide network and registry of Pathology in the Netherlands (PALGA). Contralateral tumor probability and recurrence were assessed.

Results
Of 791 included patients, 41.8% (331 of 791) had multifocal disease, with 68.9% (228 of 331) of those patients having bilateral disease. The contralateral tumor probability after hemithyroidectomy was 24.6% (150 of 610) for patients with unifocal disease and 43.1% (78 of 181) for patients with multifocal disease. We found a higher trend of recurrence in patients with bilateral disease, regardless of multifocality: in patients with contralateral disease after precompletion diagnosed unifocal disease 7.3% (11 of 150) had recurrent disease, and patients without contralateral disease after precompletion diagnosed multifocal disease 1.9% (2 per 103) had recurrence. Cox regression analysis showed that bilaterality (hazard ratio = 3.621, 95% confidence interval = 1.548 to 8.471) was the sole statistically significant risk factor for recurrence.

Conclusion
Low recurrence rates are found in patients with either multifocal or bilateral disease with low-risk PTC. Bilaterality should be taken into account when considering these patients for de-escalated treatment strategy.
Sacubitril/valsartan cardioprotective effect against cisplatin-induced cardiotoxicity via modulation of VEGF/eNOS and TLR4/TNFα/IL6 signalling pathways
Authors: Mahmoud Refaie Marwa Monier , Ahmed Rifaai Rehab , Bayoumi Asmaa M A , Shehata Sayed 
Published: June 2023

Abstract

Objectives
Drug-induced cardiac injury is a potentially preventable cause of heart failure. Cisplatin (CIS) is a widely used chemotherapeutic agent complicated with cardiotoxicity that limits its clinical application so we aimed to evaluate the suspected cardioprotective effect of sacubitril/valsartan (Sac/Val) against CIS cardiotoxic injury.

Methods
Forty male rats of Wistar albino species were divided into four groups. group I received the vehicle; group II was given the vehicle plus CIS (10 mg/kg) single i.p. on fifth day; group III was given Sac/Val (30 mg/kg/d) orally for 7 days plus CIS (10 mg/kg) single i.p. on fif5th day; group IV was given the same as group III plus nitro-ω-L-arginine (L-NNA) (25 mg/kg/d) orally for 7 days.

Key findings
CIS-induced cardiotoxicity and L-NNA co-administered group showed significant increases in cardiac enzymes, toxic histopathological features, elevated heart weights, angiotensin II (Ang II), neprilysin, malondialdehyde (MDA), inflammatory mediators, blood pressure (BP) and caspase 3 expressions, but there are significant decreases in the antioxidant parameters, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). However, the co-administration of Sac/Val could ameliorate these changes of CIS.

Conclusion
Sac/Val has an important cardioprotective effect against CIS cardiotoxicity with the involvement of eNOS.
Improving Military Medical Retention Through Growth Counseling: A Cross-sectional Retention Survey of U.S. Army Physician Assistants
Authors: Greener Robert K , Love Ashley S , Niu Chunling , Downs Lynn T 
Published: June 2023

ABSTRACT

Introduction
Although compensation is often the only factor considered with military medical retention, retention has been shown to have many other important factors. Maximizing the retention of military medical personnel not only decreases the cost of recruiting them but also maintains the institutional knowledge of military medicine needed to conduct military medical operations. This study used a recent retention survey of U.S. Army physician assistants (PAs) to understand military medical retention needs.

Materials and Methods
The study analyzed a survey created, implemented, and collected by the Statistical Cell at the U.S. Army Center of Excellence. In September 2020, all 864 active duty PAs were sent a link to the survey and 290 completed the survey, with a participation rate of 34%. The study used cross-tabulation, Pearson’s chi-square, and multivariate logistical regression to analyze the results. Institutional review board approval was obtained through the Army Medical Center of Excellence and University of the Incarnate Word.

Results
Pearson’s chi-square found that 18 questions in the survey were answered significantly different (P &lt; .05) among those who intended to stay for 20 years in the Army. Binomial logistical regression found that each point higher on a 5-point Likert scale of the belief a PA could accomplish their career goals in Army medicine increased probability of likelihood to stay for 20 years by 74% (95% CI [0.57-0.98]). Each point higher on a 5-point Likert scale of perception Defense Health Agency control of Army medicine affected retention increased probability of likelihood to stay by 54% (95% CI [0.39-0.75]). Every decade older of age increased probability of increased likelihood to stay for 20 years by 63% (95% CI [0.40-0.98]).

Conclusions
The belief a service member can reach their career goals in the military is critical for retention. Using Army Techniques Publication 6-22.1 as a guide, leaders can help subordinates meet their career goals, and this may be the most important task a leader can accomplish to improve their unit’s retention. Strengths of this study include the high response rate of 33.6% and results demonstrating the importance of growth counseling which is already part of Army doctrine. Weaknesses include the use of secondary cross-sectional data which impair the ability to derive conclusions from the data. Future studies should explore how training programs for military leaders in growth counseling can help subordinates find their career goals in the military and the effect on military retention.
Outcome of patients with cystic fibrosis colonized byScedosporiumandLomentosporaspecies: A longitudinal cohort study
Authors: Parize Perrine , Fleury Maxime , Poupon-Bourdy Stéphanie , Persat Florence , Touzet Sandrine , Bienvenu Anne-Lise , Wallon Martine , Reix Philippe , Bouchara Jean-Philippe , Durieu Isabelle 
Published: June 2023

AbstractScedosporium and Lomentospora species rank second among the filamentous fungi colonizing the airways of cystic fibrosis (CF) patients. These fungi could be responsible for allergic bronchopulmonary mycosis (ABPM) and bronchitis before lung transplantation and invasive infections after. However, their role in CF lung disease is debated. This study aimed to identify clinical or environmental factors associated with an airway colonization by Scedosporium/Lomentospora species in patients with CF over a period of 7 years. A longitudinal cohort study was conducted from 2008 to 2014 in the CF reference centre in Lyon, France, to compare the characteristics of patients with Scedosporium/Lomentospora colonized and non-colonized patients. During the study period, 283 patients completed the clinical and microbiological follow-up. The analysis revealed that a higher number and duration of hospitalizations, an increased number of courses of parenteral antibiotic therapy, a history of ABPA, and treatment by itraconazole were significantly associated with an airway colonization by Scedosporium/Lomentospora species. The rate of decline of forced expiratory volume in the first second was not statistically different between colonized and non-colonized patients. This study provides evidence that patients colonized by Scedosporium/Lomentospora species require more medical care than non-colonized patients. Additional care could be in part explained by the management of Scedosporium/Lomentospora-related diseases such as ABPM or bronchitis. However, we did not demonstrate a faster rate of decline of respiratory function or body mass index in colonized patients, suggesting, as previously reported, that colonization of the airways by these fungi does not play a significant role in the progression of CF disease.
High-energy synchrotron flares powered by strongly radiative relativistic magnetic reconnection: 2D and 3D PIC simulations
Authors: Schoeffler K M , Grismayer T , Uzdensky D , Silva L O 
Published: June 2023

ABSTRACT
The time evolution of high-energy synchrotron radiation generated in a relativistic pair plasma energized by reconnection of strong magnetic fields is investigated with 2D and 3D particle-in-cell (PIC) simulations. The simulations in this 2D/3D comparison study are conducted with the radiative PIC code OSIRIS, which self-consistently accounts for the synchrotron radiation reaction on the emitting particles, and enables us to explore the effects of synchrotron cooling. Magnetic reconnection causes compression of the plasma and magnetic field deep inside magnetic islands (plasmoids), leading to an enhancement of the flaring emission, which may help explain some astrophysical gamma-ray flare observations. Although radiative cooling weakens the emission from plasmoid cores, it facilitates additional compression there, further amplifying the magnetic field B and plasma density n, and thus partially mitigating this effect. Novel simulation diagnostics utilizing 2D histograms in the n-B space are developed and used to visualize and quantify the effects of compression. The n-B histograms are observed to be bounded by relatively sharp power-law boundaries marking clear limits on compression. Theoretical explanations for some of these compression limits are developed, rooted in radiative resistivity or 3D kinking instabilities. Systematic parameter-space studies with respect to guide magnetic field, system size, and upstream magnetization are conducted and suggest that stronger compression, brighter high-energy radiation, and perhaps significant quantum electrodynamic effects such as pair production, may occur in environments with larger reconnection-region sizes and higher magnetization, particularly when magnetic field strengths approach the critical (Schwinger) field, as found in magnetar magnetospheres.
Spectroscopic survey of faint planetary-nebula nuclei – II. The subdwarf O central star of Fr 2-30
Authors: Bond Howard E , Werner Klaus , Zeimann Gregory R , Talbot Jonathan 
Published: June 2023

ABSTRACT
Fr 2-30 = PN? G126.8−15.5 is a faint emission nebula, hosting a 14th-mag central star that we identify here for the first time. Deep Hα and [O iii] images reveal a roughly elliptical nebula with dimensions of at least 22 arcmin × 14 arcmin, fading into a surrounding network of even fainter emission. Optical spectrograms of the central star show it to have a subdwarf O spectral type, with a Gaia parallax distance of 890 pc. A model-atmosphere analysis gives parameters of $T_{\rm eff}=60\, 000$ K, log g = 6.0, and a low helium content of nHe/nH = 0.0017. The location of the central star in the log g–Teff plane is inconsistent with a post-asymptotic-giant-branch evolutionary status. Two alternatives are that it is a helium-burning post-extreme-horizontal-branch object, or a hydrogen-burning post-red-giant-branch star. In either case, the evolutionary ages are so long that a detectable planetary nebula (PN) should not be present. We find evidence for a variable radial velocity (RV), suggesting that the star is a close binary. However, there are no photometric variations, and the spectral-energy distribution rules out a companion earlier than M2 V. The RVs of the star and surrounding nebula are discordant, and the nebula lacks typical PN morphology. We suggest that Fr 2-30 is a ‘PN mimic’ – the result of a chance encounter between the hot sdO star and an interstellar cloud. However, we note the puzzling fact that there are several nuclei of genuine PNe that are known to be in evolutionary states similar to that of the Fr 2-30 central star.
A thermal–kinetic subgrid model for supernova feedback in simulations of galaxy formation
Authors: Chaikin Evgenii , Schaye Joop , Schaller Matthieu , Benítez-Llambay Alejandro , Nobels Folkert S J , Ploeckinger Sylvia 
Published: June 2023

ABSTRACT
We present a subgrid model for supernova feedback designed for cosmological simulations of galaxy formation that may include a cold interstellar medium (ISM). The model uses thermal and kinetic channels of energy injection, which are built upon the stochastic kinetic and thermal models for stellar feedback used in the owls and eagle simulations, respectively. In the thermal channel, the energy is distributed statistically isotropically and injected stochastically in large amounts per event, which minimizes spurious radiative energy losses. In the kinetic channel, we inject the energy in small portions by kicking gas particles in pairs in opposite directions. The implementation of kinetic feedback is designed to conserve energy, linear and angular momentum, and is statistically isotropic. To test the model, we run simulations of isolated Milky Way-mass and dwarf galaxies, in which the gas is allowed to cool down to 10 K. Using the thermal and kinetic channels together, we obtain smooth star formation histories and powerful galactic winds with realistic mass loading factors. Furthermore, the model produces spatially resolved star formation rates (SFRs) and velocity dispersions that are in agreement with observations. We vary the numerical resolution by several orders of magnitude and find excellent convergence of the global SFRs and wind mass loading. We show that large thermal energy injections generate a hot phase of the ISM and modulate the star formation by ejecting gas from the disc, while the low-energy kicks increase the turbulent velocity dispersion in the neutral ISM, which in turn helps suppress star formation.
Growing black holes through successive mergers in galactic nuclei – I. Methods and first results
Authors: Atallah Dany , Trani Alessandro A , Kremer Kyle , Weatherford Newlin C , Fragione Giacomo , Spera Mario , Rasio Frederic A 
Published: June 2023

ABSTRACT
We present a novel, few-body computational framework designed to shed light on the likelihood of forming intermediate-mass (IM) and supermassive (SM) black holes (BHs) in nuclear star clusters (NSCs) through successive BH mergers, initiated with a single BH seed. Using observationally motivated NSC profiles, we find that the probability of an ${\sim }100\hbox{-}\mathrm{M}_\odot$ BH to grow beyond ${\sim }1000 \, \mathrm{M}_\odot$ through successive mergers ranges from ${\sim }0.1~{{\ \rm per\ cent}}$ in low-density, low-mass clusters to nearly 90 per cent in high-mass, high-density clusters. However, in the most massive NSCs, the growth time-scale can be very long ($\gtrsim 1\,$ Gyr); vice versa, while growth is least likely in less massive NSCs, it is faster there, requiring as little as ${\sim }0.1\,$Gyr. The increased gravitational focusing in systems with lower velocity dispersions is the primary contributor to this behaviour. We find that there is a simple ‘7-strikes-and-you’re-in’ rule governing the growth of BHs: Our results suggest that if the seed survives 7–10 successive mergers without being ejected (primarily through gravitational wave recoil kicks), the growing BH will most likely remain in the cluster and will then undergo runaway, continuous growth all the way to the formation of an SMBH (under the simplifying assumption adopted here of a fixed background NSC). Furthermore, we find that rapid mergers enforce a dynamically mediated ‘mass gap’ between about ${50\!-\!300 \, \mathrm{M}_\odot }$ in an NSC.
The evolution of radial gradients of MaNGA quiescent elliptical galaxies: inside-out quenching or outer mass growth?
Authors: Avila-Reese V , Ibarra-Medel H , Lacerna I , Rodríguez-Puebla A , Vázquez-Mata J A , Sánchez S F , Hernández-Toledo H M , Cannarozzo C 
Published: June 2023

ABSTRACT
Using spatially resolved fossil record analysis on a large sample of ‘red and dead’ elliptical galaxies (classical ellipticals, CLEs) from the MaNGA/SDSS-IV DR15 survey, we reconstruct the archaeological evolution of their radial gradients in mass-to-luminosity ratio (M/L), g − r colour, and specific star formation (SF) rate. We also calculate other metrics that quantify the inside-out SF quenching and external mass growth processes. The M/L gradients, ∇Υ⋆, are approximately flat at high look-back times (tlb), but then they become negative and steeper until an epoch, when this trend reverses. These trends are shifted to later epochs the less massive the galaxies are. Colour gradients follow qualitatively similar trends. We find that these trends are mainly driven by strong inside-out quenching, without significant outer growth or structural changes overall. Our results suggest a scenario where the main progenitors of local CLE galaxies evolved quasi-passively after an early dissipative phase, but underwent radial photometric changes due to the inside-out quenching that led to the systematic decrease of ∇Υ⋆ and to an increase of the light-weighted radius. The late reversing of ∇Υ⋆, tlb≈2 − 4 Gyr, roughly coincides with the global quenching of the CLE galaxies. We have pushed archaeological inferences to the limit, but thanks to the large number of objects and an understanding of how the caveats and assumptions affect our results, we conclude that they offer an average description of evolutionary behaviours of CLE progenitors that is valid at least qualitatively.
Decoding the Fundamental Drivers of Phylodynamic Inference
Authors: Featherstone Leo A , Duchene Sebastian , Vaughan Timothy G 
Published: June 2023

Abstract
Despite its increasing role in the understanding of infectious disease transmission at the applied and theoretical levels, phylodynamics lacks a well-defined notion of ideal data and optimal sampling. We introduce a method to visualize and quantify the relative impact of pathogen genome sequence and sampling times—two fundamental sources of data for phylodynamics under birth–death-sampling models—to understand how each drives phylodynamic inference. Applying our method to simulated data and real-world SARS-CoV-2 and H1N1 Influenza data, we use this insight to elucidate fundamental trade-offs and guidelines for phylodynamic analyses to draw the most from sequence data. Phylodynamics promises to be a staple of future responses to infectious disease threats globally. Continuing research into the inherent requirements and trade-offs of phylodynamic data and inference will help ensure phylodynamic tools are wielded in ever more targeted and efficient ways.
Cell type deconvolution of methylated cell-free DNA at the resolution of individual reads
Authors: Keukeleire Pia , Makrodimitris Stavros , Reinders Marcel 
Published: June 2023

Abstract
Cell-free DNA (cfDNA) are DNA fragments originating from dying cells that are detectable in bodily fluids, such as the plasma. Accelerated cell death, for example caused by disease, induces an elevated concentration of cfDNA. As a result, determining the cell type origins of cfDNA molecules can provide information about an individual’s health. In this work, we aim to increase the sensitivity of methylation-based cell type deconvolution by adapting an existing method, CelFiE, which uses the methylation beta values of individual CpG sites to estimate cell type proportions. Our new method, CelFEER, instead differentiates cell types by the average methylation values within individual reads. We additionally improved the originally reported performance of CelFiE by using a new approach for finding marker regions that are differentially methylated between cell types. We show that CelFEER estimates cell type proportions with a higher correlation (r = 0.94 ± 0.04) than CelFiE (r = 0.86 ± 0.09) on simulated mixtures of cell types. Moreover, we show that the cell type proportion estimated by CelFEER can differentiate between ALS patients and healthy controls, between pregnant women in their first and third trimester, and between pregnant women with and without gestational diabetes.
Correction of transposase sequence bias in ATAC-seq data with rule ensemble modeling
Authors: Wolpe Jacob B , Martins André L , Guertin Michael J 
Published: June 2023

Abstract
Chromatin accessibility assays have revolutionized the field of transcription regulation by providing single-nucleotide resolution measurements of regulatory features such as promoters and transcription factor binding sites. ATAC-seq directly measures how well the Tn5 transposase accesses chromatinized DNA. Tn5 has a complex sequence bias that is not effectively scaled with traditional bias-correction methods. We model this complex bias using a rule ensemble machine learning approach that integrates information from many input k-mers proximal to the ATAC sequence reads. We effectively characterize and correct single-nucleotide sequence biases and regional sequence biases of the Tn5 enzyme. Correction of enzymatic sequence bias is an important step in interpreting chromatin accessibility assays that aim to infer transcription factor binding and regulatory activity of elements in the genome.
When do parts form wholes? Integrated information as the restriction on mereological composition
Authors: McQueen Kelvin J , Tsuchiya Naotsugu 
Published: June 2023

AbstractUnder what conditions are material objects, such as particles, parts of a whole object? This is the composition question and is a longstanding open question in philosophy. Existing attempts to specify a non-trivial restriction on composition tend to be vague and face serious counterexamples. Consequently, two extreme answers have become mainstream: composition (the forming of a whole by its parts) happens under no or all conditions. In this paper, we provide a self-contained introduction to the integrated information theory (IIT) of consciousness. We show that IIT specifies a non-trivial restriction on composition: composition happens when integrated information is maximized. We compare the IIT restriction to existing proposals and argue that the IIT restriction has significant advantages, especially in response to the problems of vagueness and counterexamples. An appendix provides an introduction to calculating parts and wholes with a simple system.