bluuebunny/crossref_metadata_2025 huggingface dataset:
Plan quality assessment of modern radiosurgery technologies in the treatment of multiple brain metastases
Authors: Hiscoke K , Leong A , Hogan AM , Cowley I
Published: January 2024

Stereotactic radiosurgery (SRS) of multiple brain metastases has evolved over the last 40 years allowing centres to treat an increasing number of brain metastases in a single treatment fraction. HyperArcTM planning optimisation technique is one such development that streamlines the treatment of multiple metastases with a single isocentre. Several studies have investigated the plan quality of HyperArc compared to CyberKnife or Gamma Knife, however there are limited number of studies that include all three modalities. It is the aim of this study to provide an assessment of plan quality between the three SRS platforms across ten patients with multiple brain metastases ranging from three to eight metastases per patient. Strict planning workflows were established to avoid bias towards any particular treatment platform. Plan quality was assessed through dose to organs at risk, Paddick conformity index (PCI), gradient index (GI), global efficiency index (Gη) and dose to normal brain tissue. Results from this study found mean PCI observed across Gamma Knife plans was significantly lower than HyperArc and CyberKnife. HyperArc plans observed significantly shorter beam-on times which were 10 to 20 times faster than CyberKnife and Gamma Knife plans. Gamma Knife and CyberKnife were found to produce plans with significantly superior GI, global efficiency index and the volume of healthy brain receiving greater than 12 Gy (V12Gy) when compared to HyperArc plans. Lesion volume was seen to influence the relative difference in dose metrics between systems. The study revealed that all three treatment modalities produced high quality plans for the SRS treatment of multiple brain metastases, each with respective benefits and limitations.
From wide to ultrawide-bandgap semiconductors for high power and high frequency electronic devices
Authors: Woo Kelly , Bian Zhengliang , Noshin Maliha , Perez Martinez Rafael , Malakoutian Mohamadali , Shankar Bhawani , Chowdhury Srabanti
Published: January 2024

Wide and ultrawide-bandgap (U/WBG) materials have garnered significant attention within the semiconductor device community due to their potential to enhance device performance through their substantial bandgap properties. These exceptional material characteristics can enable more robust and efficient devices, particularly in scenarios involving high power, high frequency, and extreme environmental conditions. Despite the promising outlook, the physics of UWBG materials remains inadequately understood, leading to a notable gap between theoretical predictions and experimental device behavior. To address this knowledge gap and pinpoint areas where further research can have the most significant impact, this review provides an overview of the progress and limitations in U/WBG materials. The review commences by discussing Gallium Nitride, a more mature WBG material that serves as a foundation for establishing fundamental concepts and addressing associated challenges. Subsequently, the focus shifts to the examination of various UWBG materials, including AlGaN/AlN, Diamond, and Ga2O3. For each of these materials, the review delves into their unique properties, growth methods, and current state-of-the-art devices, with a primary emphasis on their applications in power and radio-frequency electronics.
Mechanical properties and hydration behavior of dehydrated cement paste-slag based composite cementitious material
Authors: Zhang Ruofei , Tang Ning , Du Wenjie , Nie Nan
Published: January 2024

Mechanical properties are critical in engineering applications involving cementitious materials. While dehydrated cement paste-based materials are considered environmentally friendly, they suffer from poor mechanical properties, limiting their engineering applications. Therefore, enhancing the mechanical properties of these materials is crucial to overcoming their limitations in engineering and supporting the development of sustainable building engineering. Based on the pozzolanic reaction mechanism and alkali activation theory, a composite cementitious material was created by combining dehydrated cement paste with slag. Na2SiO3 and NaAlO2 were used as alkali activators. The study investigated the effects of the ratio of dehydrated cement paste to slag, alkali activator dosage, water-binder ratio, and calcination temperature on the material’s mechanical properties through an orthogonal test. The optimized ratio, determined through the orthogonal test and mathematical model, resulted in a compressive strength of 37.33 MPa (7d) and 46.89 MPa (28d), surpassing the compressive strength of the original Portland cement paste. Hydration products of the composite cementitious material primarily comprised C-(A)-S-H, C-A-H, and CaCO3, with no observed presence of AFt, AFm, and Ca(OH)2. Notably, the hydration products of the composite material exhibited clear distinctions from those of Portland cement.
Inductor based I-V curve measurement method for photovoltaic panels
Authors: Borekci S , Acar N C
Published: January 2024

The output power of a photovoltaic panel (PV) depends on temperature and irradiance. Aging, partial shading and electrical load can also affect the operating current and voltage of PV systems. I-V curve tracers are used to determine the performance of PV panels in any environmental condition and are widely used in both the design and operation of PV systems. In this study, a simple, effective, and rapid I-V curve tracer method is described for photovoltaic (PV) panels. The method is developed based on transient analyses of the current and voltage of an inductor load that is connected to a 175 W standalone PV panel via a semiconductor switch. The I-V and P-V characteristics curves of the PV panel are obtained in a few microseconds rapidly.
Amortized simulation-based frequentist inference for tractable and intractable likelihoods
Authors: Al Kadhim Ali , Prosper Harrison B , Prosper Olivia F
Published: January 2024

High-fidelity simulators that connect theoretical models with observations are indispensable tools in many sciences. If the likelihood is known, inference can proceed using standard techniques. However, when the likelihood is intractable or unknown, a simulator makes it possible to infer the parameters of a theoretical model directly from real and simulated observations when coupled with machine learning. We introduce an extension of the recently proposed likelihood-free frequentist inference (LF2I) approach that makes it possible to construct confidence sets with the p-value function and to use the same function to check the coverage explicitly at any given parameter point. Like LF2I, this extension yields provably valid confidence sets in parameter inference problems for which a high-fidelity simulator is available. The utility of our algorithm is illustrated by applying it to three pedagogically interesting examples: the first is from cosmology, the second from high-energy physics and astronomy, both with tractable likelihoods, while the third, with an intractable likelihood, is from epidemiology
3

3

Code to reproduce all of our results is available on https://github.com/AliAlkadhim/ALFFI.

.
BCFtools/liftover: an accurate and comprehensive tool to convert genetic variants across genome assemblies
Authors: Genovese Giulio , Rockweiler Nicole B , Gorman Bryan R , Bigdeli Tim B , Pato Michelle T , Pato Carlos N , Ichihara Kiku , McCarroll Steven A
Published: January 2024

Motivation

Many genetics studies report results tied to genomic coordinates of a legacy genome assembly. However, as assemblies are updated and improved, researchers are faced with either realigning raw sequence data using the updated coordinate system or converting legacy datasets to the updated coordinate system to be able to combine results with newer datasets. Currently available tools to perform the conversion of genetic variants have numerous shortcomings, including poor support for indels and multi-allelic variants, that lead to a higher rate of variants being dropped or incorrectly converted. As a result, many researchers continue to work with and publish using legacy genomic coordinates.

Results

Here we present BCFtools/liftover, a tool to convert genomic coordinates across genome assemblies for variants encoded in the variant call format with improved support for indels represented by different reference alleles across genome assemblies and full support for multi-allelic variants. It further supports variant annotation fields updates whenever the reference allele changes across genome assemblies. The tool has the lowest rate of variants being dropped with an order of magnitude less indels dropped or incorrectly converted and is an order of magnitude faster than other tools typically used for the same task. It is particularly suited for converting variant callsets from large cohorts to novel telomere-to-telomere assemblies as well as summary statistics from genome-wide association studies tied to legacy genome assemblies.

Availability and implementation

The tool is written in C and freely available under the MIT open source license as a BCFtools plugin available at http://github.com/freeseek/score.
Baricitinib statistically significantly reduced COVID-19-related mortality: a systematic review and meta-analysis of five phase III randomized, blinded and placebo-controlled clinical trials
Authors: Manoharan Sivananthan , Ying Ying Lee
Published: January 2024

Due to high heterogeneity and risk of bias (RoB) found in previously published meta-analysis (MA), a concrete conclusion on the efficacy of baricitinib in reducing mortality in coronavirus disease 2019 (COVID-19) patients was unable to form. Hence, this systematic review and MA were conducted to analyse whether RoB, heterogeneity, and optimal sample size from placebo-controlled randomized controlled trials (RCTs) are still the problems to derive a concrete conclusion.

Search engines PubMed/MEDLINE, ScienceDirect, and other sources like preprints and reference lists were searched with appropriate keywords. The RoB and MA were conducted using RevMan 5.4. The grading of the articles was conducted using the GRADEPro Guideline Development Tool.

Ten RCTs were included in the current systematic review. Only five low RoB articles are Phase III placebo-controlled RCTs with a high certainty level based on the GRADE grading system. For the MA, based on five low RoB articles, baricitinib statistically significantly reduced mortality where the risk ratio (RR) = 0.68 [95% confidence interval (95% CI) 0.56–0.82; P < 0.0001; I2 = 0%; P = 0.85]. The absolute mortality effect (95% CI) based on the grading system was 35 fewer mortalities per 1000 COVID-19 patients, whereas in the baricitinib and control groups, the mortality was 7.4% and 10.9%, respectively.

With the presence of an optimal sample size of 3944 from five low RoB–placebo-controlled RCTs, which represent a minimum of 300 million population of people and with the presence of 0% heterogeneity from MA, the effectiveness of baricitinib in reducing the mortality in COVID-19 patients is concretely proven.
The construct validity, responsiveness, reliability and interpretability of the Recap of atopic eczema questionnaire (RECAP) in children
Authors: Ragamin Aviël , Zhang Junfen , Pasmans Suzanne G M A , Schappin Renske , Romeijn Geertruida L E , van Reusel Maroos A , Oosterhaven Jart A F , Schuttelaar Marie L A
Published: January 2024

Background

The Recap of atopic eczema questionnaire (RECAP) was developed to measure eczema control in patients with atopic dermatitis (AD). The measurement properties of RECAP have not yet been validated in caregivers of children with AD.

Objectives

To assess the construct validity, responsiveness, reliability and interpretability of the Dutch proxy version of RECAP.

Methods

A prospective validation study was conducted in children (aged < 12 years) with AD and their caregivers (in a Dutch tertiary hospital). At three timepoints (T0 = baseline; T1 = after 1–7 days; T2 = after 4–8 weeks) RECAP and multiple reference instruments were completed by caregivers of child patients. Single- and change-score validity (responsiveness) were tested with a priori hypotheses on correlations with reference instruments. Intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were reported. Bands for perceived eczema control were proposed. The smallest detectable change (SDC) and minimally important change (MIC) were determined. Two anchor-based methods based on receiver operating characteristic curve (ROC) and predictive modelling were used to determine the MIC.

Results

A total of 231 children with AD and their caregivers participated. Of our a priori hypotheses for single-score and change-score validity, 77% and 80% were confirmed, respectively. A stronger correlation than hypothesized was found for all rejected hypotheses.

Excellent reliability was found (ICCagreement = 0.94, 95% confidence interval 0.90–0.96). The SEMagreement was 1.9 points. The final banding was 0–1 (completely controlled), 2–7 (mostly controlled), 8–12 (moderately controlled), 13–18 (a little controlled) and 19–28 (not at all controlled). A cutoff point of ≥ 8 was selected to identify children whose AD is not under control. The SDC was 5.3 and the MIC values were 1.5 and 3.6 for the ROC and predictive modelling approaches, respectively. No floor or ceiling effects were observed.

Conclusions

The proxy version of RECAP is a valid, reliable and responsive measurement instrument for measuring eczema control in children with AD. An improvement of ≥ 6 points can be regarded as a real and important change in children with AD.
The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of short QT syndrome type 3
Authors: Moreno-Manuel Ana I , Macías Álvaro , Cruz Francisco M , Gutiérrez Lilian K , Martínez Fernando , González-Guerra Andrés , Martínez Carrascoso Isabel , Bermúdez-Jimenez Francisco José , Sánchez-Pérez Patricia , Vera-Pedrosa María Linarejos , Ruiz-Robles Juan Manuel , Bernal Juan A , Jalife José
Published: January 2024

Aims

Short QT syndrome type 3 (SQTS3) is a rare arrhythmogenic disease caused by gain-of-function mutations in KCNJ2, the gene coding the inward rectifier potassium channel Kir2.1. We used a multidisciplinary approach and investigated arrhythmogenic mechanisms in an in-vivo model of de-novo mutation Kir2.1E299V identified in a patient presenting an extremely abbreviated QT interval and paroxysmal atrial fibrillation.

Methods and results

We used intravenous adeno-associated virus-mediated gene transfer to generate mouse models, and confirmed cardiac-specific expression of Kir2.1WT or Kir2.1E299V. On ECG, the Kir2.1E299V mouse recapitulated the QT interval shortening and the atrial-specific arrhythmia of the patient. The PR interval was also significantly shorter in Kir2.1E299V mice. Patch-clamping showed extremely abbreviated action potentials in both atrial and ventricular Kir2.1E299V cardiomyocytes due to a lack of inward-going rectification and increased IK1 at voltages positive to −80 mV. Relative to Kir2.1WT, atrial Kir2.1E299V cardiomyocytes had a significantly reduced slope conductance at voltages negative to −80 mV. After confirming a higher proportion of heterotetrameric Kir2.x channels containing Kir2.2 subunits in the atria, in-silico 3D simulations predicted an atrial-specific impairment of polyamine block and reduced pore diameter in the Kir2.1E299V-Kir2.2WT channel. In ventricular cardiomyocytes, the mutation increased excitability by shifting INa activation and inactivation in the hyperpolarizing direction, which protected the ventricle against arrhythmia. Moreover, Purkinje myocytes from Kir2.1E299V mice manifested substantially higher INa density than Kir2.1WT, explaining the abbreviation in the PR interval.

Conclusion

The first in-vivo mouse model of cardiac-specific SQTS3 recapitulates the electrophysiological phenotype of a patient with the Kir2.1E299V mutation. Kir2.1E299V eliminates rectification in both cardiac chambers but protects against ventricular arrhythmias by increasing excitability in both Purkinje-fiber network and ventricles. Consequently, the predominant arrhythmias are supraventricular likely due to the lack of inward rectification and atrial-specific reduced pore diameter of the Kir2.1E299V-Kir2.2WT heterotetramer.
Lipoprotein(a) and cardiovascular disease: sifting the evidence to guide future research
Authors: Kamstrup Pia R , Neely R Dermot G , Nissen Steven , Landmesser Ulf , Haghikia Arash , Costa-Scharplatz Madlaina , Abbas Cheryl , Nordestgaard Børge G
Published: January 2024

Lipoprotein(a) (Lp(a)) is a genetically determined causal risk factor for cardiovascular disease including coronary heart disease, peripheral arterial disease, ischaemic stroke, and calcific aortic valve stenosis. Clinical trials of specific and potent Lp(a)-lowering drugs are currently underway. However, in clinical practice, widespread assessment of Lp(a) is still lacking despite several guideline recommendations to measure Lp(a) at least once in a lifetime in all adults to identify those at high or very high risk due to elevated levels. The present review provides an overview of key findings from observational and genetic Lp(a) studies, highlights the main challenges in observational Lp(a) studies, and proposes a minimum set of requirements to enhance the quality and harmonize the collection of Lp(a)-related data. Adherence to the recommendations set forth in the present manuscript is intended to enhance the quality of future observational Lp(a) studies, to better define thresholds for increased risk, and to better inform clinical trial design. The recommendations can also potentially assist in the interpretation and generalization of clinical trial findings, to improve care of patients with elevated Lp(a) and optimize treatment and prevention of cardiovascular disease.
P2X7 receptor inhibition prevents atrial fibrillation in rodent models of depression
Authors: Ye Tianxin , Zhou Yunping , Yang Jinxiu , Yu Fangcong , Song Zhuonan , Shi Jiaran , Wang Longbo , Huang Zhouqing , Yang Bo , Wang Xingxiang
Published: January 2024

Aims

Depression, the most prevalent psychiatric disorder, is associated with the occurrence and development of atrial fibrillation (AF). P2X7 receptor (P2X7R) activation participates in the development of depression, but little attention has been given to its role in AF. This study was to investigate the effects of P2X7R on AF in depression models.

Methods and results

Lipopolysaccharide (LPS) and chronic unpredictable stress (CUS) were carried out to induce depression in rodents. Behavioural assessments, atrial electrophysiological parameters, electrocardiogram (ECG) parameters, western blot, and histology were performed. Atrial fibrillation inducibility was increased in both LPS- and CUS-induced depression, along with the up-regulation of P2X7R in atria. CUS facilitated atrial fibrosis. CUS reduced heart rate variability (HRV) and increased the expression of TH and GAP43, representing autonomic dysfunction. Down-regulation of Nav1.5, Cav1.2, Kv1.5, Kv4.3, Cx40, and Cx43 in CUS indicated the abnormalities in ion channels. In addition, the expression levels of TLR4, P65, P-P65, NLRP3, ASC, caspase-1, and IL-1β were elevated in depression models. Pharmacological inhibitor (Brilliant Blue G, BBG) or genetic deficiency of P2X7R significantly mitigated depressive-like behaviours; ameliorated electrophysiological deterioration and autonomic dysfunction; improved ion channel expression and atrial fibrosis; and prevented atrial NLRP3 inflammasome activation in the pathophysiological process of AF in depression models.

Conclusion

LPS or CUS induces AF and promotes P2X7R-dependent activation of NLRP3 inflammasome, whereas pharmacological P2X7R inhibition or P2X7R genetic deficiency prevents atrial remodelling without interrupting normal atrial physiological functions. Our results point to P2X7R as an important factor in the pathology of AF in depression.
Effect of a case-capped, fee-for-service payment mechanism on accessibility and affordability of health care
Authors: Cielo Bernardo , Santillan Melanie , de Claro Vergil
Published: January 2024

In response to a government audit report in 2021, the Philippine health insurance system transitioned its case-based payment system back into a fee-for-service model capped at individual case rates. This commentary discusses the adverse effects of this policy on health care accessibility and affordability in the country. A rapid review of data shows that it may have resulted in delayed insurance payments, increased denial rates, and reduced coverage, and weakened the strategic purchasing capacity of public health insurance, hugely affecting vulnerable populations and public health care facilities. The commentary calls for a reconsideration of the policy and emphasizes the importance of aligning financial auditing procedures with the needs of health-financing institutions. It advocates for a transformation of audits, moving beyond their traditional role as compliance checks, to become valuable tools supporting a nation's health care purchasing strategies, ultimately benefiting both health care providers and the broader public.
Quantitative criticalism for social justice and equity-oriented communication research
Authors: Kim Youllee
Published: January 2024

An increasing number of communication researchers have noted the potential of quantitative criticalism (QuantCrit) or the use of quantitative approaches to pursue social justice and equity agenda. Nonetheless, how to achieve the goals and ideals of QuantCrit in communication studies still largely remains uncharted terrain. This article offers five concrete suggestions for how researchers can bring critical consciousness to quantitative communication research: (a) broadening and diversifying the scope of communication research, (b) (re)framing research questions with a social justice orientation, (c) critiquing dominant narratives and centering the counternarratives, (d) incorporating intersectionality to address marginalization, and (e) employing statistical methods that illuminate interdependence, systems, and power dynamics. This article seeks to enrich the discussion on ways to embrace QuantCrit in communication research to revitalize perspectives and means for identifying and addressing inequalities, and eventually to advance transformative scholarship.
Adapting national data systems for donor transition: comparative analysis of experience from Georgia and China
Authors: Chikovani Ivdity , Soselia Giorgi , Huang Aidan , Uchaneishvili Maia , Zhao Yingxi , Cao Chunkai , Lyu Mohan , Tang Kun , Gotsadze George
Published: January 2024

Health management information systems (HMISs) are essential in programme planning, budgeting, monitoring and evidence-informed decision-making. This paper focuses on donor transitions in two upper-middle-income countries, China and Georgia, and explores how national HMIS adaptations were made and what facilitated or limited successful and sustainable transitions. This comparative analytical case study uses a policy triangle framework and a mixed-methods approach to explore how and why adaptations in the HMIS occurred under the Gavi Alliance and the Global Fund–supported programmes in China and Georgia. A review of published and grey literature, key informant interviews and administrative data analysis informed the study findings. Contextual factors such as the global and country context, and health system and programme needs drove HMIS developments. Other factors included accountability on a national and international level; improvements in HMIS governance by establishing national regulations for clear mandates of data collection and reporting rules and creating institutional spaces for data use; investing in hardware, software and human resources to ensure regular and reliable data generation; and capacitating national players to use data in evidence-based decision-making for programme and transition planning, budgeting and outcome monitoring. Not all the HMIS initiatives supported by donors were sustained and transitioned. For the successful adaptation and sustainable transition, five interlinked and closely coordinated support areas need to be considered: (1) coupling programme design with a good understanding of the country context while considering domestic and external demands for information, (2) regulating appropriate governance and management arrangements enhancing country ownership, (3) avoiding silo HMIS solutions and taking integrative approach, (4) ensuring the transition of funding onto domestic budget and enforcing fulfilment of the government’s financial commitments and finally (5) investing in technologies and skilled human resources for the HMIS throughout all levels of the health system. Neglecting any of these elements risks not delivering sustainable outcomes.
Sample Size and Geometric Morphometrics Methodology Impact the Evaluation of Morphological Variation
Authors: Rummel A D , Sheehy E T , Schachner E R , Hedrick B P
Published: January 2024

Synopsis

Geometric morphometrics has had a profound impact on our understanding of morphological evolution. However, factors such as sample size and the views and elements selected for two-dimensional geometric morphometric (2DGM) analyses, which are often dictated by specimen availability and time rather than study design, may affect the outcomes of those analyses. Leveraging large intraspecific sample sizes (n > 70) for two bat species, Lasiurus borealis and Nycticeius humeralis, we evaluate the impact of sample size on calculations of mean shape, shape variance, and centroid size. Additionally, we assessed the concordance of multiple skull 2D views with one another and characterized morphological variation in skull shape in L. borealis and N. humeralis, as well as a closely related species, Lasiurus seminolus. Given that L. seminolus is a morphologically cryptic species with L. borealis, we assessed whether differences in skull shape and in 2DGM approach would allow species discrimination. We found that reducing sample size impacted mean shape and increased shape variance, that shape differences were not consistent across views or skull elements, and that trends shown by the views and elements were not all strongly associated with one another. Further, we found that L. borealis and L. seminolus were statistically different in shape using 2DGM in all views and elements. These results underscore the importance of selecting appropriate sample sizes, 2D views, and elements based on the hypothesis being tested. While there is likely not a generalizable sample size or 2D view that can be employed given the wide variety of research questions and systems evaluated using 2DGM, a generalizable solution to issues with 2DGM presented here is to run preliminary analyses using multiple views, elements, and sample sizes, thus ensuring robust conclusions.
Pledge and Forget? Testing the Effects of NATO’s Wales Pledge on Defense Investment
Authors: Becker Jordan
Published: January 2024

Do informal international agreements without coercive mechanisms affect states’ behavior? While scholars have long been interested in this question, answering it often poses empirical challenges, particularly in the arena of international security. By asking and answering a narrower question—Is NATO’s Wales Pledge on defense spending working?—I can empirically test the extent to which states have adhered to a public agreement without formal or coercive enforcement mechanisms. I argue that the Wales Pledge has led to higher spending because NATO the organization uniquely enables allies to influence one another’s defense planning, publicly and privately. I find support for this argument by interrogating disaggregated defense expenditures of NATO and EU members, and by comparing NATO allies Denmark and Norway with non-allies Finland and Sweden. Although the Wales Pledge has been maligned, it served its purpose by encouraging allies to spend more on defense, particularly on equipment modernization.
Grace periods in comparative effectiveness studies of sustained treatments
Authors: Wanis Kerollos Nashat , Sarvet Aaron L , Wen Lan , Block Jason P , Rifas-Shiman Sheryl L , Robins James M , Young Jessica G
Published: January 2024

Researchers are often interested in estimating the effect of sustained use of a treatment on a health outcome. However, adherence to strict treatment protocols can be challenging for individuals in practice and, when non-adherence is expected, estimates of the effect of sustained use may not be useful for decision making. As an alternative, more relaxed treatment protocols which allow for periods of time off treatment (i.e. grace periods) have been considered in pragmatic randomized trials and observational studies. In this article, we consider the interpretation, identification, and estimation of treatment strategies which include grace periods. We contrast natural grace period strategies which allow individuals the flexibility to take treatment as they would naturally do, with stochastic grace period strategies in which the investigator specifies the distribution of treatment utilization. We estimate the effect of initiation of a thiazide diuretic or an angiotensin-converting enzyme inhibitor in hypertensive individuals under various strategies which include grace periods.
Exploring the radio loudness of SDSS quasars with spectral stacking
Authors: Arnaudova M I , Smith D J B , Hardcastle M J , Das S , Drake A , Duncan K , Gürkan G , Magliocchetti M , Morabito L K , Petley J W , Shenoy S , Tasse C
Published: January 2024

We use new 144 MHz observations over 5634 deg2 from the LOFAR (Low Frequency Array) Two-metre Sky Survey (LoTSS) to compile the largest sample of uniformly selected, spectroscopically confirmed quasars from the 14th data release of the Sloan Digital Sky Survey (SDSS-DR14). Using the classical definition of radio loudness, R = log (L1.4GHz/Li), we identify 3697 radio-loud (RL) and 111 132 radio-quiet (RQ) sources at 0.6 < z < 3.4. To study their properties, we develop a new rest-frame spectral stacking algorithm, designed with forthcoming massively multiplexed spectroscopic surveys in mind, and use it to create high signal-to-noise composite spectra of each class, matched in redshift and absolute i-band magnitude. We show that RL quasars have redder continuum and enhanced [O ii] emission than their RQ counterparts. These results persist when additionally matching in black hole mass, suggesting that this parameter is not the defining factor in making a quasi-stellar object (QSO) RL. We find that these features are not gradually varying as a function of radio loudness, but are maintained even when probing deeper into the RQ population, indicating that a clear-cut division in radio loudness is not apparent. Upon examining the star formation rates (SFRs) inferred from the [O ii] emission line, with the contribution from active galactic nucleus removed using the [Ne v] line, we find that RL quasars have a significant excess of star formation relative to RQ quasars out to z = 1.9 at least. Given our findings, we suggest that RL sources either preferably reside in gas-rich systems with rapidly spinning black holes, or represent an earlier obscured phase of QSO evolution.
Virialized equation of state for warm and dense stellar plasmas in proto-neutron stars and supernova matter
Authors: Barba-González D , Albertus C , Pérez-García M A
Published: January 2024

We present microscopic molecular dynamics simulations including the efficient Ewald sum procedure to study warm and dense stellar plasmas consisting of finite-size ion charges immerse in a relativistic neutralizing electron gas. For densities typical of Supernova matter and crust in a proto-neutron star, we select a representative single ion composition and obtain the virialized equation of state (vEoS). We scrutinize the finite-size and screening corrections to the Coulomb potential appearing in the virial coefficients B2, B3, and B4 as a function of temperature. In addition, we study the thermal heat capacity at constant volume, CV, and the generalized Mayer’s relation i.e. the difference CP − CV with CP being the heat capacity at constant pressure, obtaining clear features signalling the onset of the liquid–gas phase transition. Our findings show that microscopic simulations reproduce the discontinuity in CV, whose value lies between that of idealized gas and crystallized configurations. We study the pressure isotherms marking the boundary of the metastable region before the gaseous transition takes place. The resulting vEoS displays a behaviour where effective virial coefficients include extra density dependence showing a generalized density–temperature form. As an application we parametrize pressure as a function of density and temperature under the form of an artificial neural network showing the potential of machine learning for future regression analysis in more refined multicomponent approaches. This is of interest to size the importance of these corrections in the liquid–gas phase transition in warm and dense plasma phases contributing to the cooling behaviour of early Supernova phases and proto-neutron stars.
Genomic profiling of six human somatic histone H1 variants denotes that H1X accumulates at recently incorporated transposable elements
Authors: Salinas-Pena Mónica , Serna-Pujol Núria , Jordan Albert
Published: January 2024

Histone H1, a vital component in chromatin structure, binds to linker DNA and regulates nuclear processes. We have investigated the distribution of histone H1 variants in a breast cancer cell line using ChIP-Seq. Two major groups of variants are identified: H1.2, H1.3, H1.5 and H1.0 are abundant in low GC regions (B compartment), while H1.4 and H1X preferentially localize in high GC regions (A compartment). Examining their abundance within transposable elements (TEs) reveals that H1X and H1.4 are enriched in recently-incorporated TEs (SVA and SINE-Alu), while H1.0/H1.2/H1.3/H1.5 are more abundant in older elements. Notably, H1X is particularly enriched in SVA families, while H1.4 shows the highest abundance in young AluY elements. Although low GC variants are generally enriched in LINE, LTR and DNA repeats, H1X and H1.4 are also abundant in a subset of recent LINE-L1 and LTR repeats. H1X enrichment at SVA and Alu is consistent across multiple cell lines. Further, H1X depletion leads to TE derepression, suggesting its role in maintaining TE repression. Overall, this study provides novel insights into the differential distribution of histone H1 variants among repetitive elements, highlighting the potential involvement of H1X in repressing TEs recently incorporated within the human genome.
Coordinated evolution of the SNORD115 and SNORD116 tandem repeats at the imprinted Prader–Willi/Angelman locus
Authors: Guibert Mathilde , Marty-Capelle Hélène , Robert Anne , Charpentier Bruno , Labialle Stéphane
Published: January 2024

The Prader–Willi/Angelman syndrome (PWS/AS) locus is regulated by the epigenetic mechanism of parental genomic imprinting. This region holds two eutherian-specific, large tandem repeats of box C/D small nucleolar RNA (Snord) genes called SNORD115 and SNORD116, whose loss of paternal expression is key in the development of the PWS. Snords represent an ancient class of noncoding RNAs that typically direct the 2′-O-methylation of specific nucleotides of ribosomal RNAs. However, Snord115 and Snord116 belong to the large class of orphan Snords whose functions remain unclear. The constraints that generated and maintained their unusual genetic organization for mammalian genomes have been poorly addressed to date. Here, a comparative analysis of the evolutionary history of both tandem repeats reveals that several genetic events affected them concomitantly, including copy gains and losses between species, emergence of gene subfamilies in catarrhines or partial tandem duplication in rats. Several indications suggest that parental genomic imprinting orchestrated this coordination of events, adding a new effect on mammalian genome structure and evolution to its roles in gene dosage, meiotic recombination and replication timing. Finally, our work provides a functional rationale for the existence of closely located tandem repeats of small RNA genes in mammalian genomes.
Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer
Authors: Hou Da-Yong , Zhang Ni-Yuan , Wang Lu , Lv Mei-Yu , Li Xiang-Peng , Zhang Peng , Wang Yue-Ze , Shen Lei , Wu Xiu-Hai , Fu Bo , Guo Peng-Yu , Wang Zi-Qi , Cheng Dong-Bing , Wang Hao , Xu Wanhai
Published: January 2024

Mitochondriopathy inspired adenosine triphosphate (ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration (IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites, leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like damages. Briefly, the reported transformable nucleopeptide (NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei, which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines (T24, EJ and RT-112) revealed that the half-maximal inhibitory concentration (IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.
Ginger intervention on body weight and body composition in adults: a GRADE-assessed systematic review and dose-response meta-analysis of 27 randomized controlled trials
Authors: Rafieipour Nastaran , Gharbi Negin , Rahimi Homan , Kohansal Atefeh , Sadeghi-Dehsahraei Hamed , Fadaei Marjan , Tahmasebi Marzieh , Momeni Seyed Aref , Ostovar Navid , Ahmadi Mohammad , Majd Sara Sadeghi , Mohammadi-Sartang Mohsen
Published: January 2024

Context

Ginger consumption may have an inverse relationship with obesity and metabolic syndrome parameters; however, clinical trials have reported contradictory results.

Objective

To systematically review and analyze randomized controlled trials (RCTs) assessing the effects of ginger on body weight and body composition parameters.

Methods

Databases were searched for appropriate articles up to August 20, 2022. All selected RCTs investigated the impact of ginger on glycemic indices in adults. A random effects model was used to conduct a meta-analysis, and heterogeneity was assessed using the I2 statistic. Net changes in body weight, body mass index (BMI), waist circumference (WC), and percent body fat were used to calculate the effect size, which was reported as a weighted mean difference (WMD) and 95% confidence intervals (CIs). The risk of bias was assessed.

Results

A total of 27 RCTs involving 1309 participants were included. The certainty in the evidence was very low for WC and BMI, and low for body weight and percent body fat as assessed by the GRADE evidence profiles. The meta-analysis showed a significant association between ginger supplementation and a reduction in body weight (WMD, –1.52 kg; 95%CI, –2.37, –0.66; P < 0.001), BMI (WMD, –0.58 kg/m2; 95%CI, –0.87, –0.30; P < 0.001), WC (WMD, –1.04 cm; 95%CI: –1.93, –0.15; P = 0.021), and percent body fat consumption (WMD, –0.87%; 95%CI, –1.71, –0.03; P = 0.042). The results of the nonlinear dose-response analysis showed a significant association between the ginger dose with body weight (Pnonlinearity = 0.019) and WC (Pnonlinearity = 0.042). The effective dose of ginger intervention for body mass reduction was determined to be 2 g/d in dose-response analysis. The duration of ginger intervention had a significant nonlinear relationship with body weight (Pnonlinearity = 0.028) with an effective duration of longer than 8 weeks.

Conclusions

Our findings provide evidence that ginger consumption may significantly affect body composition parameters nonlinearly. More, well-constructed RCTs are needed.
Sediment trap samples reveal regional differences in the population structure of Calanus hyperboreus from the Arctic Ocean
Authors: Tokuhiro Koki , Matsuno Kohei , Onodera Jonaotaro , Sampei Makoto , Fujiwara Amane , Harada Naomi , Niehoff Barbara , Nöthig Eva-Maria , Yamaguchi Atsushi
Published: January 2024

Calanus hyperboreus is one of the dominant copepod species in the Arctic zooplankton communities. The impact of climate change varies among regions within the Arctic, implying that C. hyperboreus populations may be differently affected at different locations, but knowledge on seasonal population dynamics in relation to biogeography is scarce. To fill this gap, we counted C. hyperboreus in samples from sediment traps that were moored from 2009 to 2014 in three regions of the Arctic Ocean (eastern Fram Strait, northern Chukchi Sea and MacKenzie Trough). The C. hyperboreus flux increased between April and May in all regions, likely associated with the ascent from overwintering depth to the surface. In the descent period, high fluxes were observed between July and September in the Fram Strait, between September and November in the northern Chukchi Sea, and between August and October in the MacKenzie Trough, suggesting that the timing of descent varied among the regions characterized by differences in light regime, phytoplankton development and water temperature. The copepodite stage composition in the eastern Fram Strait and the MacKenzie Trough varied with season, suggesting successful local reproduction while it was uniform in the northern Chukchi Sea, possibly because the population is fueled by advection.
Relationship between insomnia and pain in patients with chronic orofacial pain
Authors: Alessandri-Bonetti Anna , Sangalli Linda , Boggero Ian A
Published: January 2024

Objective

Few studies have investigated specific associations between insomnia and orofacial pain (OFP). The aim of this cross-sectional study was to examine relationships of insomnia with pain, mental health, and physical health variables among treatment-seeking patients with chronic OFP.

Methods

OFP diagnosis, demographics, insomnia symptoms, pain intensity, interference, and duration, mental health measures, and number of medical comorbidities were extracted from the medical records of 450 patients receiving an initial appointment at a university-affiliated tertiary OFP clinic. T-tests compared differences between patients with and without insomnia symptomatology, and between patients with different insomnia subtypes (delayed onset/early wakening).

Results

Compared to patients without insomnia, those with elevated insomnia symptomatology (45.1%) reported higher pain intensity (60.70 ± 20.61 vs 44.15 ± 21.69; P < .001) and interference (43.81 ± 29.84 vs 18.40 ± 23.43; P < 0.001), depression/anxiety symptomatology (5.53 ± 3.32 vs 2.72 ± 2.66; P < 0.001), dissatisfaction with life (21.63 ± 6.95 vs 26.50 ± 6.21; P < .001), and number of medical comorbidities (6.72 ± 5.37 vs 4.37 ± 4.60; P < .001). Patients with Sleep Onset Latency insomnia (SOL-insomnia) (N = 76) reported higher pain intensity (t = 3.57; P < 0.001), and pain interference (t = 4.46; P < .001) compared to those without SOL-insomnia. Those with Early Morning Awakening insomnia (EMA-insomnia) (N = 71) did not significantly differ from those without EMA-insomnia on any of the variables. Differences remained significant after adjusting for age, sex, primary OFP diagnosis, and pain intensity.

Conclusions

Insomnia is associated with pain outcomes and should be appropriately managed when treating patients with chronic OFP.
Monitoring drug metabolic pathways through extracellular vesicles in mouse plasma
Authors: Wu Xiaofeng , Quan Menchus , Hadisurya Marco , Hu Jianzhong , Liu Yi-Kai , Zhuang Yuxin , Li Li , Iliuk Anton B , Yang Jun J , Kuang Shihuan , Tao W Andy
Published: January 2024

The ability to monitor the response of metabolic enzymes to drug exposure in individuals is highly appealing and critical to personalized medicine. Although pharmacogenomics assesses genotypic differences, it does not report changes in metabolic enzyme activities due to environmental factors such as drug interactions. Here, we report a quantitative proteomics strategy to monitor drug metabolic pathways by profiling metabolic enzymes in circulating extracellular vesicles (EVs) upon drug exposure. Mass spectrometry (MS)-based measurement revealed that changes in metabolic enzyme abundance in EVs paralleled those in hepatic cells isolated from liver tissue. Coupling with multiplexed isotopic labeling, we temporally quantified 34 proteins involved in drug absorption, distribution, metabolism, and excretion (ADME) pathways. Out of 44 known ADME proteins in plasma EVs, previously annotated mouse cytochrome P450 3A11 (Cyp3a11), homolog to human CYP3A4, and uridine 5'-diphospho (UDP) glucuronosyltransferase 2A3 (Ugt2a3), increased upon daily rifampicin dosage. Dasatinib, a tyrosine kinase inhibitor to treat leukemia, also elevated Cyp3a11 levels in plasma EVs, but to a lesser extent. Altogether, this study demonstrates that measuring drug enzymes in circulating EVs as an effective surrogate is highly feasible and may transform today's drug discovery and development for personalized medicine.
The role of advanced nuclear reactors and fuel cycles in a future energy system
Authors: Kornecki Kasia , Wise Catherine F
Published: January 2024

Nuclear power has been an important part of the US electricity system since the 1950s and continues to be a major source of low-carbon electricity today. Despite having low emissions, high grid reliability, and an excellent track record of safety, nuclear power also demands significant time and upfront capital to deploy, can struggle to compete economically with other generation sources, has intrinsic proliferation risk by relying on fissile material for fuel, and generates radioactive waste for which there are currently no disposal sites. Given the emissions and energy security benefits of having nuclear as part of the energy mix, advanced nuclear technologies have garnered significant interest and investment in recent years. Advanced reactor designs differ from the current operating fleet and have several potential advantages, including lower cost, faster construction, smaller size, inherent safety features, and lower waste yields. Yet, many challenges related to their deployment remain, and overcoming them will dictate whether or not new nuclear technologies become a material element of the future energy infrastructure. This article synthesizes the opportunities and barriers to deploying advanced nuclear reactors and their associated fuel cycles as described in two National Academies consensus reports. It highlights the consensus recommendations that could allow these new technologies to reach commercial success as part of a long-term decarbonization strategy.