bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term photometric monitoring and spectroscopy of the white dwarf pulsar AR Scorpii
Authors: Pelisoli Ingrid , Marsh T R , Parsons S G , Aungwerojwit A , Ashley R P , Breedt E , Brown A J , Dhillon V S , Dyer M J , Green M J , Kerry P , Littlefair S P , Sahman D I , Shahbaz T , Wild J F , Chakpor A , Lakhom R 
Published: August 2022

ABSTRACT
AR Scorpii (AR Sco) is the only radio-pulsing white dwarf known to date. It shows a broad-band spectrum extending from radio to X-rays whose luminosity cannot be explained by thermal emission from the system components alone, and is instead explained through synchrotron emission powered by the spin-down of the white dwarf. We analysed NTT/ULTRACAM, TNT/ULTRASPEC, and GTC/HiPERCAM high-speed photometric data for AR Sco spanning almost seven years and obtained a precise estimate of the spin frequency derivative, now confirmed with 50-σ significance. Using archival photometry, we show that the spin-down rate of $P/\dot{P} = 5.6 \times 10^6$ yr has remained constant since 2005. As well as employing the method of pulse-arrival time fitting used for previous estimates, we also found a consistent value via traditional Fourier analysis for the first time. In addition, we obtained optical time-resolved spectra with WHT/ISIS and VLT/X-shooter. We performed modulated Doppler tomography for the first time for the system finding evidence of emission modulated on the orbital period. We have also estimated the projected rotational velocity of the M-dwarf as a function of orbital period and found that it must be close to Roche lobe filling. Our findings provide further constraints for modelling this unique system.
MeerKAT radio observations of the neutron star low-mass X-ray binary Cen X–4 at low accretion rates
Authors: van den Eijnden J , Fender R , Miller-Jones J C A , Russell T D , Saikia P , Sivakoff G R , Carotenuto F 
Published: August 2022

ABSTRACT
Centaurus X–4 (Cen X–4) is a relatively nearby neutron star low-mass X-ray binary that showed outbursts in 1969 and 1979, but has not shown a full outburst since. Due to its proximity and sustained period of quiescence, it is a prime target to study the coupling between accretion and jet ejection in quiescent neutron star low-mass X-ray binaries. Here, we present four MeerKAT radio observations at 1.3 GHz of Cen X–4, combined with NICER and Swift X-ray monitoring. During the first and most sensitive observation, Cen X–4 was in a fully quiescent X-ray state. The three later and shorter observations targeted a brief period of faint X-ray activity in 2021 January, which has been referred to as a ‘mis-fired’ outburst. Cen X–4 is not detected in any of the four MeerKAT observations. We place these radio non-detections on the X-ray–radio luminosity diagram, improving the constraints on the correlation between the two luminosities from earlier quiescent radio studies. We confirm that Cen X–4 is radio fainter than the transitional millisecond pulsar PSR J1023+0038 at the same X-ray luminosity. We discuss the radio behaviour of accreting neutron stars at low X-ray luminosity more generally and finally comment on future observing campaigns.
Radiative hydrodynamical simulations of super-Eddington accretion flow in tidal disruption event: the origin of optical/UV emission
Authors: Bu De-Fu , Qiao Erlin , Yang Xiao-Hong , Liu Jifeng , Chen Zhiwei , Wu Yongxin 
Published: August 2022

ABSTRACT
One of the most prominent problems of optical/ultraviolet (UV) tidal disruption events (TDEs) is the origin of their optical/UV emission. It has been proposed that the soft X-rays produced by the stellar debris accretion disc can be reprocessed into optical/UV photons by a surrounding optically thick envelope or outflow. However, there is still no detailed models for this mechanism. In this paper, by performing hydrodynamic simulations with radiative transfer, we calculate the optical/UV emission of the circularized stellar debris accretion flow/outflow system. We find that the optical/UV photons can be generated by reprocessing the emission of the accretion flow in the optically thick outflows. The model can well interpret the observed emission properties of optical/UV TDEs, including the emission radius, the radiation temperature, and the blackbody luminosity, as well as the evolution of these quantities with time, providing a strong theoretical basis for understanding the origin of optical/UV TDEs.
Internally controlled RNA sequencing comparisons using nucleoside recoding chemistry
Authors: Courvan Meaghan C S , Niederer Rachel O , Vock Isaac W , Kiefer Lea , Gilbert Wendy V , Simon Matthew D 
Published: August 2022

AbstractQuantitative comparisons of RNA levels from different samples can lead to new biological understanding if they are able to distinguish biological variation from variable sample preparation. These challenges are pronounced in comparisons that require complex biochemical manipulations (e.g. isolating polysomes to study translation). Here, we present Transcript Regulation Identified by Labeling with Nucleoside Analogues in Cell Culture (TILAC), an internally controlled approach for quantitative comparisons of RNA content. TILAC uses two metabolic labels, 4-thiouridine (s4U) and 6-thioguanosine (s6G), to differentially label RNAs in cells, allowing experimental and control samples to be pooled prior to downstream biochemical manipulations. TILAC leverages nucleoside recoding chemistry to generate characteristic sequencing signatures for each label and uses statistical modeling to compare the abundance of RNA transcripts between samples. We verified the performance of TILAC in transcriptome-scale experiments involving RNA polymerase II inhibition and heat shock. We then applied TILAC to quantify changes in mRNA association with actively translating ribosomes during sodium arsenite stress and discovered a set of transcripts that are translationally upregulated, including MCM2 and DDX5. TILAC is broadly applicable to uncover differences between samples leading to improved biological insights.
Processing oxidatively damaged bases at DNA strand breaks by APE1
Authors: Whitaker Amy M , Stark Wesley J , Freudenthal Bret D 
Published: August 2022

Abstract
Reactive oxygen species attack the structure of DNA, thus altering its base-pairing properties. Consequently, oxidative stress-associated DNA lesions are a major source of the mutation load that gives rise to cancer and other diseases. Base excision repair (BER) is the pathway primarily tasked with repairing DNA base damage, with apurinic/apyrimidinic endonuclease (APE1) having both AP-endonuclease and 3′ to 5′ exonuclease (exo) DNA cleavage functions. The lesion 8-oxo-7,8-dihydroguanine (8-oxoG) can enter the genome as either a product of direct damage to the DNA, or through polymerase insertion at the 3′-end of a DNA strand during replication or repair. Importantly, 3′-8-oxoG impairs the ligation step of BER and therefore must be removed by the exo activity of a surrogate enzyme to prevent double stranded breaks and cell death. In the present study, we use X-ray crystallography to characterize the exo activity of APE1 on 3′-8-oxoG substrates. These structures support a unified APE1 exo mechanism that differs from its more canonical AP-endonuclease activity. In addition, through complementation of the structural data with enzyme kinetics and binding studies employing both wild-type and rationally designed APE1 mutants, we were able to identify and characterize unique protein: DNA contacts that specifically mediate 8-oxoG removal by APE1.
The toxin–antitoxin RNA guards of CRISPR-Cas evolved high specificity through repeat degeneration
Authors: Cheng Feiyue , Wu Aici , Liu Chao , Cao Xifeng , Wang Rui , Shu Xian , Wang Lingyun , Zhang Yihan , Xiang Hua , Li Ming 
Published: August 2022

Abstract
Recent discovery of ectopic repeats (outside CRISPR arrays) provided unprecedented insights into the nondefense roles of CRISPR-Cas. A striking example is the addiction module CreTA (CRISPR-regulated toxin–antitoxins), where one or two (in most cases) ectopic repeats produce CRISPR-resembling antitoxic (CreA) RNAs that direct the CRISPR effector Cascade to transcriptionally repress a toxic RNA (CreT). Here, we demonstrated that CreTA repeats are extensively degenerated in sequence, with the first repeat (ψR1) being more diverged than the second one (ψR2). As a result, such addiction modules become highly specific to their physically-linked CRISPR-Cas loci, and in most cases, CreA could not harness a heterologous CRISPR-Cas to suppress its cognate toxin. We further disclosed that this specificity primarily derives from the degeneration of ψR1, and could generally be altered by modifying this repeat element. We also showed that the degenerated repeats of CreTA were insusceptible to recombination and thus more stable compared to a typical CRISPR array, which could be exploited to develop highly stable CRISPR-based tools. These data illustrated that repeat degeneration (a common feature of ectopic repeats) improves the stability and specificity of CreTA in protecting CRISPR-Cas, which could have contributed to the widespread occurrence and deep diversification of CRISPR systems.
Rbp95 binds to 25S rRNA helix H95 and cooperates with the Npa1 complex during early pre-60S particle maturation
Authors: Bhutada Priya , Favre Sébastien , Jaafar Mariam , Hafner Jutta , Liesinger Laura , Unterweger Stefan , Bischof Karin , Darnhofer Barbara , Siva Sankar Devanarayanan , Rechberger Gerald , Abou Merhi Raghida , Lebaron Simon , Birner-Gruenberger Ruth , Kressler Dieter , Henras Anthony K , Pertschy Brigitte 
Published: August 2022

Abstract
Eukaryotic ribosome synthesis involves more than 200 assembly factors, which promote ribosomal RNA (rRNA) processing, modification and folding, and assembly of ribosomal proteins. The formation and maturation of the earliest pre-60S particles requires structural remodeling by the Npa1 complex, but is otherwise still poorly understood. Here, we introduce Rbp95 (Ycr016w), a constituent of early pre-60S particles, as a novel ribosome assembly factor. We show that Rbp95 is both genetically and physically linked to most Npa1 complex members and to ribosomal protein Rpl3. We demonstrate that Rbp95 is an RNA-binding protein containing two independent RNA-interacting domains. In vivo, Rbp95 associates with helix H95 in the 3′ region of the 25S rRNA, in close proximity to the binding sites of Npa1 and Rpl3. Additionally, Rbp95 interacts with several snoRNAs. The absence of Rbp95 results in alterations in the protein composition of early pre-60S particles. Moreover, combined mutation of Rbp95 and Npa1 complex members leads to a delay in the maturation of early pre-60S particles. We propose that Rbp95 acts together with the Npa1 complex during early pre-60S maturation, potentially by promoting pre-rRNA folding events within pre-60S particles.
Association of single and serial measures of serum phosphorus with adverse outcomes in patients on peritoneal dialysis: results from the international PDOPPS
Authors: Lopes Marcelo Barreto , Karaboyas Angelo , Zhao Junhui , Johnson David W , Kanjanabuch Talerngsak , Wilkie Martin , Nitta Kosaku , Kawanishi Hideki , Perl Jeffrey , Pisoni Ronald L ,   The PDOPPS Steering Committee, Johnson David , Perl Jeffrey , Sanabria Mauricio , Kawanishi Hideki , Kim Yong-Lim , Kanjanabuch Talerngsak , Davies Simon , Pisoni Ronald , Robinson Bruce , Shen Jenny 
Published: August 2022

ABSTRACT

Background
While high serum phosphorus levels have been related to adverse outcomes in hemodialysis patients, further investigation is warranted in persons receiving peritoneal dialysis (PD).

Methods
Longitudinal data (2014–17) from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), a prospective cohort study, were used to examine associations of serum phosphorus with all-cause mortality and major adverse cardiovascular events via Cox regression adjusted for confounders. Serum phosphorus levels were parameterized by four methods: (i) baseline serum phosphorus; (ii) mean 6-month serum phosphorus; (iii) number of months with serum phosphorus &gt;4.5 mg/dL; and (iv) mean area-under-the-curve of 6-month serum phosphorus control.

Results
The study included 5847 PD patients from seven countries; 9% of patients had baseline serum phosphorus &lt;3.5 mg/dL, 24% had serum phosphorus ≥3.5 to ≤4.5 mg/dL, 30% had serum phosphorus &gt;4.5 to &lt;5.5 mg/dL, 20% had serum phosphorus ≥5.5 to &lt;6.5 mg/dL, and 17% had serum phosphorus ≥6.5 mg/dL. Compared with patients with baseline serum phosphorus ≥3.5 to ≤4.5 mg/dL, the adjusted all-cause mortality hazard ratio (HR) was 1.19 (0.92,1.53) for patients with baseline serum phosphorus ≥5.5 to &lt;6.5 mg/dL and HR was 1.53 (1.14,2.05) for serum phosphorus ≥6.5 mg/dL. Associations between serum phosphorus measurements over 6 months and clinical outcomes were even stronger than for a single measurement.

Conclusions
Serum phosphorus &gt;5.5 mg/dL was highly prevalent (37%) in PD patients, and higher serum phosphorus levels were a strong predictor of morbidity and death, particularly when considering serial phosphorus measurements. This highlights the need for improved treatment strategies in this population. Serial serum phosphorus measurements should be considered when assessing patients’ risks of adverse outcomes.
Model-based orbital-scale precipitation δ18O variations and distinct mechanisms in Asian monsoon and arid regions
Authors: Liu Xiaodong , Xie Xiaoxun , Guo Zhengtang , Yin Zhi-Yong , Chen Guangshan 
Published: August 2022

Abstract
The past Asian precipitation δ18O (δ18Op) records from stalagmites and other deposits have shown significant orbital-scale variations, but their climatic implications and regional differences are still not fully understood. This study, as the first attempt of a 300-kyr transient stable isotope-enabled simulation, investigated the characteristics and mechanisms of the orbital-scale δ18Op variations in three representative regions of Asia: arid Central Asia (CA), monsoonal South Asia (SA) and monsoonal East Asia (EA). The modelling results showed that the variations in the CA, SA and EA annual δ18Op exhibited significant but asynchronous 23-kyr precession cycles. Further analyses revealed that although the precession-induced insolation variation was the ultimate cause of the δ18Op variation in all three regions, the dominant mechanisms and the involved physical processes were distinct among them. For the CA region, the rainy-season (November–March) temperature effect and water vapour transport by the westerly circulation were identified as the key precession-scale processes linking the October–February boreal mid-latitude insolation to the rainy-season or annual δ18Op. In the SA region, the rainy-season (June–September) precipitation amount effect and upstream depletion of the monsoonal water vapour δ18O served as the main mechanisms linking the rainy-season or annual δ18Op to the April–July insolation variation at the precession scale. For the EA region, however, the precession-scale annual δ18Op was mainly controlled by the late-monsoon (August–September) and pre-monsoon (April–May) water vapour transport patterns, which were driven by the July–August insolation and the global ice volume, respectively. These results suggest that the climatic implications of the orbital-scale Asia δ18Op variations are sensitive to their geographic locations as determined by the combined effects of insolation and regional circulation patterns associated with the respective rainy seasons. This study provides new insights into understanding the regional differences and formation mechanisms of the Asian orbital-scale δ18Op variations.
Nutritional importance of tryptophan for improving treatment in depression and diabetes
Authors: Haleem Darakhshan Jabeen 
Published: August 2022

Abstract
The importance of nutrients in our diet is becoming increasingly recognized. From the viewpoint of protein synthesis and other physiologic and metabolic functions, all amino acids are important, but some of these amino acids are not synthesized endogenously. This subset, called essential amino acids, comprise dietarily indispensable nutrients. Tryptophan, an essential amino acid, is the sole precursor of neuronal as well as peripheral serotonin (5-hydroxytryptamine). Its systemic or oral administration increases serotonin synthesis because tryptophan hydroxylase, the rate-limiting enzyme of 5-hydroxytryptamine biosynthesis, is physiologically unsaturated with its substrate. Central serotonin is implicated in a number of psychiatric illnesses, including depression, and in responses to stress. Acting peripherally, serotonin affects vasoconstriction, intestinal motility, control of T cell–mediated immunity, and liver and pancreatic functions. Depression and diabetes are 2 highly prevalent diseases that often coexist. There is evidence that occurrence of depression is 2–3 times higher in people with diabetes mellitus. A comorbid condition of diabetes and depression worsens the treatment and increases risk for death. Stress, known for its causal role in depression, can also enhance risk for diabetes. Stress-induced decreases in the circulating levels of tryptophan can impair brain and pancreatic serotonin-dependent functions to precipitate these diseases. The importance of tryptophan supplementation for improving therapeutic intervention in depression and diabetes is the focus of this article. A deficiency of this essential amino acid may enhance risk for depression as well as diabetes, and can also weaken treatment efficacy of medicinal compounds for treating these diseases. Guidelines for optimal levels of circulating tryptophan can help if supplements of this amino acid can improve treatment efficacy.
An overview of vitamins as epidrugs for colorectal cancer prevention
Authors: Boughanem Hatim , Kompella Pallavi , Tinahones Francisco J , Macias-Gonzalez Manuel 
Published: August 2022

AbstractGene expression altering epigenomic modifications such as DNA methylation, histone modification, and chromosome remodeling is crucial to regulating many biological processes. Several lifestyle factors, such as diet and natural, bioactive food compounds, such as vitamins, modify epigenetic patterns. However, epigenetic dysregulation can increase the risk of many diseases, including cancer. Various studies have provided supporting and contrasting evidence on the relationship between vitamins and cancer risk. Though there is a gap in knowledge about whether dietary vitamins can induce epigenetic modifications in the context of colorectal cancer (CRC), the possibility of using them as epidrugs for CRC treatment is being explored. This is promising because such studies might be informative about the most effective way to use vitamins in combination with DNA methyltransferase inhibitors and other approved therapies to prevent and treat CRC. This review summarizes the available epidemiological and observational studies involving dietary, circulating levels, and supplementation of vitamins and their relationship with CRC risk. Additionally, using available in vitro, in vivo, and human observational studies, the role of vitamins as potential epigenetic modifiers in CRC is discussed. This review is focused on the action of vitamins as modifiers of DNA methylation because aberrant DNA methylation, together with genetic alterations, can induce the initiation and progression of CRC. Although this review presents some studies with promising results, studies with better study designs are necessary. A thorough understanding of the underlying molecular mechanisms of vitamin-mediated epigenetic regulation of CRC genes can help identify effective therapeutic targets for CRC prevention and treatment.
Management and outcome of febrile neutropenia in admitted presumed immunocompetent patients with suspected viral illness
Authors: Morin Estelle M , Corriveau-Bourque Catherine , Foulds Jessica L 
Published: August 2022

Abstract

Objectives
Febrile neutropenia (FN) creates concern in paediatrics due to the risk of serious bacterial infections (SBI). Protocols with empiric antibiotics designed for hematology and oncology are often applied in healthy children with FN despite lower rates of SBI in this population. This study quantifies rates of infections in presumed immunocompetent children hospitalized with suspected viral illnesses and FN.

Methods
This was a retrospective chart review of healthy children admitted to the Stollery Children’s Hospital between 2007 and 2017 with fever, absolute neutrophil counts &lt; 0.5 × 109/L, and viral symptoms. Primary outcomes were the incidence of SBI and bacterial pneumonia.

Results
Of 383 encounters reviewed, 96 admissions for 82 patients met inclusion criteria. Eighty-eight encounters (91.7%) were managed with empiric antibiotics. Viruses were identified in 42% of encounters. Three blood cultures were positive for coagulase-negative Staphylococcus and one for Coryneforms, all considered contaminants. There were three urinary tract infections and two pneumonias. Eighty-three per cent of patients had normalization of neutrophil counts, with a median neutropenia duration of 3.2 months. Follow-up diagnoses included chronic benign neutropenia of childhood (N = 17) and three rheumatologic/autoimmune conditions (N = 3).

Conclusion
Our results support previous findings of low rates of invasive bacterial infections in healthy children with FN. With an SBI rate of 3.1% and few patients found to have any pathologic etiology for their neutropenia, prospective studies would be valuable to evaluate the need for a practice change regarding antibiotic use in low-risk patients with suspected viral-induced neutropenia.
DALYs and the Minimally Good Life
Authors: Campbell Tim 
Published: August 2022

Abstract
Nicole Hassoun’s book Global Health Impact: Extending Access to Essential Medicines has three parts. Part 1 is about the right to health, Part 2 offers a concrete proposal for how to promote the ability of people in the developing world to live minimally good lives and Part 3 is concerned with consumer responsibility as it relates to global health. I argue that there is a philosophical tension between the respective projects of Parts 1 and 2. The project of Part 1 reflects a sufficientarian ideal, namely ensuring that each person in our global community has the ability to live a minimally good life. But, the concrete proposal offered in Part 2 reflects a different ideal, namely maximizing global health benefit. While these two ideals may often converge on a set of feasible health outcomes that we should aim to bring about, they can also diverge. The extent to which they diverge depends on our specification of the minimally good life. It is therefore crucial that we have a criterion for distinguishing lives that are at least minimally good from those that are not. Unfortunately, Hassoun’s proposed criterion is problematic in that no life satisfies it.