bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum-memory-assisted entropic uncertainty and quantum correlation in structured reservoir
Authors: Li Bingbing , Feng Li , Shi Jiadong , Wu Tao
Published: January 2023

In this work, we investigate the dynamics of quantum-memory-assisted entropic uncertainty relation (EUR) and quantum correlation quantified by entropic discord and geometric discord within the Markovian reservoir and non-Markovian reservoir. Particularly, when the initial state is a pure sate or mixed state the EUR gradually increases during the evolution at first, but subsequently tends to stable in the long-time limit. On other hand, for the separable state the EUR almost keeps constant. In contrast, quantum discord decay asymptotically to zero for all types of initial states. As an application, we prove that both two quantum discords witnessed by the EUR are determined by the version of discord chosen, which regardless of the reservoir.
The scalings of the thermal energy confinement time in EAST H-mode plasmas
Authors: Jia T.Q. , Qian J.P. , Chen D.L. , Moreau D. , Shen B. , Zhang B. , Gong X.Z. , Huang J. , Zhang J.Y. , Yang X.D. , Liang R.R. , Hu Y.C. , Chen L.X. , He Y.F. , Tao Y. , Wang Z.H. , Zeng L. , Sun Y.W.
Published: January 2023

This paper describes scalings of the H-mode confinement database of neutral beam injection (NBI)-lower hybrid wave (LHW) and electron cyclotron resonant heating-LHW plasmas in the EAST tokamak. Fundamental information of the EAST H-mode database and the details of calculation of the thermal energy confinement time in EAST are presented. The result of the scaling model

τ

E,EASTS,H,NBI - LHW

of the thermal energy confinement time in NBI-LHW plasmas with root-mean-square-error

RMSE

=
5.5
%

, compared with the multi-machine scaling model

τ

th,98

y

2

derived from the multi-machine database (mainly NBI heating) with

RMSE

=
12.9
%

, is obtained. The scaling

τ

E,EAST,H,NBI - LHW

presents a similar dependency on plasma current and power loss and a lower dependency on plasma density and elongation, but stronger dependency on toroidal field than in

τ

th,98

y

2

. The scaling

τ

E,EAST,H,ECRH - LHW

demonstrates a similar dependency on plasma current and power loss and lower dependency on plasma density, but a negative dependency with large error bars on elongation compared with

τ

E,EAST,H,NBI - LHW

in NBI-LHW plasmas. The comparison of EAST models with the more recent multi-tokamak scaling ITPA20-IL shows a similar engineering dependency on plasma current, power loss and plasma density, but opposite dependency on toroidal field.
Tribological, mechanical and thermal response of diamond micro-particles reinforced copper matrix composites fabricated by powder metallurgy
Authors: Poulose Nixon , Selvakumar P , Philip Jibin T , George Jees
Published: January 2023

Copper/Diamond composites have gained a lot of attention in recent years due to their excellent thermal conductivity and their potential for use in high-power electronic devices. The current work targets on an experimental investigation of the tribological,mechanical, and thermal behaviour of copper diamond composite by using reinforced micro-diamond particles. Copper matrix composites with varying weight percentages of diamond particles were produced with the aid of the powder metallurgy. The wear tests were carried out on Pin-on-Disc wear test machine as per ASTM G99. The doping of an optimum amount of diamond particles (1% wt.) improved the overall wear performance by 51% under a normal load of 80 N. The doping had also showed a significant improvement in hardness by 26% and thermal conductivity by 1%. The primary wear mechanisms of Cu-Diamond composites appear to be a combination of brittle fracture, fragmentation of diamond-reinforced particles and ploughing in the Cu-alloy matrix.
Deformation behavior of a new Ni-Co base superalloy GH4251 during hot compression
Authors: Yu Hongyao , Wang Jue , Qin Hailong , Huang Canjin , Cheng Tijuan , Wang Chen , Bi Zhongnan
Published: January 2023

The deformation behavior of a new Ni-Co base superalloy GH4251 under hot compression tests within the deformation strain window of 0.36 to 1.2 was investigated in the temperature range of 1050 ∼ 1170 °C and strain rate range of 0.001 ∼ 1 s−1. Based on the analysis of true stress-strain curves, constitutive equations were established to describe the rheological behavior during hot compression. Microstructure evolution was investigated by transmission electron microscope (TEM), scanning electron microscope (SEM) and optical metallography (OM). The results show that flow behavior of GH4251 alloy is combinedly determined by the effect of work hardening and dynamic recrystallization (DRX). The deformation activation energies at strain of 0.36 to 1.2 are calculated to be 311 ∼ 536 kJ mol−1 in the super-solvus temperature region, and 796 ∼ 1064 kJ mol−1 in the sub-solvus temperature region. The recrystallization nucleation mechanism of GH4251 alloy is strain induced grain boundary migration (SIBGM). The occurrence and expansion of recrystallization are strongly promoted by high deformation temperatures and high strain rates, while the DRX grain size increases with elevated deformation temperature. When the deformation temperature is below 1090°C, the recrystallized grain can be extremely small (<17μm), which is rather independent on strain and strain rate. However, above 1110 °C the grain size at strain rate of 0.001s−1 is significantly larger than that of higher strain rates. The difference can be ascribed to the presence of γ′ phase, with which the development of dynamic recrystallization is postponed, while the growth of recrystallized grains is inhibited as well.
X-ray energy spectrum estimation based on a virtual computed tomography system
Authors: Higuchi Takayuki , Haga Akihiro
Published: January 2023

This paper presents a method for estimating the x-ray energy spectrum for computed tomography (CT) in the diagnostic energy range from the reconstructed CT image itself. To this end, a virtual CT system was developed, and datasets, including CT images for the Gammex phantom labeled by the corresponding energy spectra, were generated. Using these datasets, an artificial neural network (ANN) model was trained to reproduce the energy spectrum from the CT values in the Gammex inserts. In the actual application, an aluminum-based bow-tie filter was used in the virtual CT system, and an ANN model with a bow-tie filter was also developed. Both ANN models without/with a bow-tie filter can estimate the x-ray spectrum within the agreement, which is defined as one minus the absolute error, of more than 80% on average. The agreement increases as the tube voltage increases. The estimation was occasionally inaccurate when the amount of noise on the CT image was considerable. Image quality with a signal-to-noise ratio of more than 10 for the basis material of the Gammex phantom was required to predict the spectrum accurately. Based on the experimental data acquired from Activion16 (Canon Medical System, Japan), the ANN model with a bow-tie filter produced a reasonable energy spectrum by simultaneous optimization of the shape of the bow-tie filter. The present method requires a CT image for the Gammex phantom only, and no special setup, thus it is expected to be readily applied in clinical applications, such as beam hardening reduction, CT dose management, and material decomposition, all of which require exact information on the x-ray energy spectrum.
A synthesis and review of exacerbated inequities from the February 2021 winter storm (Uri) in Texas and the risks moving forward
Authors: Castellanos Sergio , Potts Jerry , Tiedmann Helena , Alverson Sarah , Glazer Yael R , Robison Andrew , Russo Suzanne , Harmon Dana , Ken-Opurum Bobuchi , Weisz Margo , Acuna Frances , Stephens Keri K , Faust Kasey , Webber Michael E
Published: January 2023

A severe winter storm in February 2021 impacted multiple infrastructure systems in Texas, leaving over 13 million people without electricity and/or water, potentially $100 billion in economic damages, and almost 250 lives lost. While the entire state was impacted by temperatures up to 10 °C colder than expected for this time of year, as well as levels of snow and ice accumulation not observed in decades, the responses and outcomes from communities were inconsistent and exacerbated prevailing social and infrastructure inequities that are still impacting those communities. In this contribution, we synthesize a subset of multiple documented inequities stemming from the interdependence of the water, housing, transportation, and communication sectors with the energy sector, and present a summary of actions to address the interdependency of infrastructure system inequities.
Prospects and problems in the development of biochar-filled plastic composites: a review
Authors: Adeniyi Adewale George , Iwuozor Kingsley O , Emenike Ebuka Chizitere , Amoloye Mubarak A , Aransiola Emmanuel S , Motolani Fawaz O , Kayode Sodiq H
Published: January 2023

This study is a review of published literature that discusses the utilization of biochar (BC) and plastics as filler and matrix, respectively, in a composite material. These composites, referred to as Biochar-filled plastic composites (BFPCs), play a significant role in the production of environmentally friendly materials. This paper provides an overview of BFPCs, their properties (mechanical, rheological, morphological, electrical, and thermal properties), fabrication techniques, and prospects and challenges associated with their development. Even though there have been previous studies on BFPCs, none of these studies have discussed the drawbacks and potential associated with the development of BFPCs. BCs’ small weight makes them a more appealing option than traditional mineral fillers when it comes to reducing vehicle weight. Due to their superior mechanical and thermal qualities, as well as their low carbon footprint, BC-filled plastic composites (BFPCs) play a significant role in the production of environmentally friendly materials. It was observed that either melt extrusion or injection molding are usually used to fabricate BFPC. It was observed that the properties of BFPCs are influenced by several factors such as the type and concentration of plastic, method of fabrication, the BC content, mixing uniformity of the mixture, wetting, and particle dispersion. Challenges of BFPCs were also discussed, such as the issue of particle agglomeration and poor interfacial bonding at high BC concentrations in the composite. Composites made from recycled polymers or biodegradable polymers can be developed to improve the composites’ overall sustainability.
Immoralism is Obviously True: Towards Progress on the Ethical Question
Authors: Stear Nils-Hennes
Published: January 2023

The Ethical Question asks whether ethical values in artworks determine their aesthetic value and, if so, how. I argue that the question is ambiguous between a direct and an indirect reading. I show how the indirect reading is philosophically uninteresting because it has an obvious answer: a view called ‘immoralism’. I also show how most of the significant figures in the relevant literature address the indirect form of the question anyway—needlessly, if I am right. Finally, I consider whether some version of the indirect question is more philosophically interesting, connecting it to the so-called ‘qua problem’. I attempt to give clarity to the discussion by applying work on the virtues and vices of explanations.
Development and validation of a minimally invasive and image-guided tape stripping method to sample atopic skin in children
Authors: Yélamos O , Andersen D , Pont M , Iglesias P , Potrony M , Domínguez M , Herrero A , Alejo B , Mateu J , Røpke M , Danneskiold-Samsøe N B , Malvehy J , Guy R H , Brix S , Puig S
Published: January 2023

Background

Molecular skin profiling techniques, typically performed on skin samples taken by punch biopsy, have enhanced the understanding of the pathophysiology of atopic dermatitis (AD), thereby enabling the development of novel targeted therapeutics. However, punch biopsies are not always feasible or desirable, and novel minimally invasive methods such as skin tape stripping have been developed.

Aim

To develop, optimize and validate a novel tape stripping method guided by noninvasive in vivo skin imaging to sample atopic skin in children.

Methods

Skin tape stripping-based procedures were compared and optimized using data from 30 healthy controls (HCs: 5 adults, 25 children) and 39 atopic children. Evaluations were guided by high-resolution photography, reflectance confocal microscopy, optical coherence tomography and transepidermal water loss measurements. We assessed and compared adverse events (AEs), the time needed to perform the sampling and the cDNA levels obtained from the tapes.

Results

Tape stripping methods based on previously described protocols resulted in erosions in all participants and required a median time of 65 min to perform (range 60–70 min), but provided good cDNA yield. Shorter durations appeared less invasive but provided lower cDNA yield. The final optimized tape stripping protocol, using 11 tapes of 22 mm in diameter, each applied twice for 5 s with 90° rotation, did not produce significant AEs, was completed within a median time of 7 min (range 5–15 min) and provided good cDNA yield both in HCs and atopic children.

Conclusion

Our minimally invasive method is safe and reliable, and provides reproducible acquisition of cDNA in atopic children. In addition, it enables rapid sample collection, a crucial factor in clinical practice.
CTLA4,SH2B3, andCLEC16Adiversely affect the progression of early islet autoimmunity in relatives of Type 1 diabetes patients
Authors: Vandewalle Julie , Desouter Aster K , Van der Auwera Bart J , Tenoutasse Sylvie , Gillard Pieter , De Block Christophe , Keymeulen Bart , Gorus Frans K , Van de Casteele Mark ,   the Belgian Diabetes Registry
Published: January 2023

The HLA region is the major genetic risk determinant of Type 1 diabetes. How non-HLA loci contribute to the genetic risk is incompletely understood, but there are indications that at least some impact progression of asymptomatic autoimmunity. We examined whether SNPs in 7 susceptibility loci (INS, SH2B3, PTPN2, PTPN22, CTLA4, CLEC16A, and IL2RA) could improve prediction of the progression from single to multiple autoantibody positivity, and from there on to diagnosis. SNPs were genotyped in persistently autoantibody positive relatives by allelic discrimination qPCR and disease progression was studied by multivariate Cox regression analysis. In our cohort, only the CTLA4 GA genotype (rs3087243, P = 0.002) and the CLEC16A AA genotype (rs12708716, P = 0.021) were associated with accelerated progression from single to multiple autoantibody positivity, but their effects were restricted to presence of HLA-DQ2/DQ8, and IAA as first autoantibody, respectively. The interaction of CTLA4 and HLA-DQ2/DQ8 overruled the effect of DQ2/DQ8 alone. The HLA-DQ2/DQ8-mediated risk of progression to multiple autoantibodies nearly entirely depended on heterozygosity for CTLA4. The SH2B3 TT genotype (rs3184504) was protective for HLA-DQ8 positive subjects (P = 0.003). At the stage of multiple autoantibodies, only the CTLA4 GA genotype was a minor independent risk factor for progression towards clinical diabetes (P = 0.034). Our study shows that non-HLA polymorphisms impact progression of islet autoimmunity in a subgroup-, stage- and SNP-specific way, suggesting distinct mechanisms. If confirmed, these findings may help refine risk assessment, follow-up, and prevention trials in risk groups.
A Novel HPLC Method for Quality Inspection of NRK Biosynthesized β-Nicotinamide Mononucleotide
Authors: Zhou Haoxuan , Liu Ai , Hu Mingxing , Zheng Xinyue , Kuang Weihong , Xie Yongmei
Published: January 2023

β-nicotinamide mononucleotide (NMN) has a good effect on delaying aging, repairing DNA and ameliorating metabolic disease. Biosynthesis with nicotinamide riboside kinase (NRK) takes a large part in NMN manufacture, but there is no available NMN quality standard and analytical method at present. In this study, we developed a specific high-performance liquid chromatography method for the assessment of NMN-related substances, including NMN and its potential impurities from NRK biological production and storage. Forced degradation study was performed under acid, base, oxidative, photolytic and thermal conditions. The separation of related substances was achieved on an Elite Hypersil ODS column using phosphate buffer–methanol gradient at a flow rate of 1.0 mL/min. The detection wavelength was maintained at 260 nm. The resolutions among all related substances were better than 1.5. Significant degradation was observed in basic and thermal conditions. All related substances showed good linearity with a coefficient of determination (R2) higher than 0.999. The accuracy values of all related substances were between 91.2% and 108.6%. Therefore, the validated analytical method is appropriate for inspecting the quality of NMN in its NRK biosynthetic manufacture and storage, thus further helping to unify NMN quality standards and facilitate related studies on NMN.
Magnetic sphincter augmentation for gastroesophageal reflux in overweight and obese patients
Authors: Vivek Anjali , Latorre-Rodríguez Andrés R , Mittal Sumeet K
Published: January 2023

Magnetic sphincter augmentation (MSA) is a successful treatment option for chronic gastroesophageal reflux disease; however, there is a paucity of data on the efficacy of MSA in obese and morbidly obese patients. To assess the relationship between obesity and outcomes after MSA, we conducted a literature search using MeSH and free-text terms in MEDLINE, EMBASE, Cochrane and Google Scholar. The included articles reported conflicting results regarding the effect of obesity on outcomes after MSA. Prospective observational studies with larger sample sizes and less statistical bias are necessary to understand the effectiveness of MSA in overweight and obese patients.
Effect of food safety recalls on consumer meat purchase: evidence from meat recalls 2007–2017
Authors: Yim Hyejin , Katare Bhagyashree
Published: January 2023

Food safety is a global public health concern, and food recalls cause several foodborne illnesses and significant costs to human health. We estimate the impact of meat recalls on consumer meat purchase in the USA using household-level scanner data. Meat recalls have a statistically significant but short-lived and small reduction in consumer meat purchase, suggesting an economically small impact on the intensive (how much to decrease) and extensive (whether to purchase) margins. There is heterogeneity in consumer recall response across household demographic and recall characteristics. The results provide an insight into domestic and international policymakers and industry stakeholders about food safety.
Determining Support for Humanitarian Interventions: Prospect Theory versus Cues
Authors: Mitkov Zlatin
Published: January 2023

To what extent can prospect theory’s framing effects and elite and social group cues moderate public support for humanitarian interventions? This study extends the research on public support for humanitarian interventions by capturing the interaction between prospect theory’s framing effects and elite and social group cues on individuals’ willingness to support risky foreign policies. The study incorporates four novel prospect theory decision problems while framing the expected costs as nonequivalent intervals across interventions and US–China trade war scenarios. The results provide evidence that prospect theory framing effects outperform the elite and social group cues in their ability to induce preference shifts among respondents’ willingness to support risk-acceptant or risk-averse humanitarian intervention plans. It also suggests that humanitarian interventions, with US troops on the ground, in a region noncentral for America's national security, retain substantial levels of support among Americans despite their country's changing role in international security.
Taiwan and the WHO: negotiating the deconstruction of racialized discourse during the COVID-19 pandemic
Authors: Li Yao-Tai
Published: January 2023

Racialized and politicized discourses on individuals and countries have accompanied the emergence and spread of COVID-19. Adopting critical discourse analysis (CDA) and investigating the WHO's news releases, press conferences and the Taiwanese government's formal responses, this article examines three discursive events involving the deconstruction of racialized discourses during the pandemic by the WHO, the WHO's Director-General and Taiwan. Specifically, I focus on the following: the WHO's calls on the international community to cease using the term ‘China virus’; Dr Ghebreyesus' calls on Taiwan to cease leveling racist insults against the Black community; and the Taiwanese government's refutation of racist allegations by deconstructing racialized meanings and highlighting its marginal status in the global health system due to international politics. The findings demonstrate the different ways each subject framed moral and immoral practice, highlighted or downplayed racialized discourse, and applied moral vs immoral distinction to manipulate and reinforce the audience's thoughts. This article contributes to the field of international relations and its connection with racism by showing how racial injustices ‘travel’ between places and are negotiated and re-politicized in the global health sphere.
Supposing the moral state: Japan and historical justice under liberal internationalism
Authors: Koyama Hitomi
Published: January 2023

Diplomatic spats over history between two of the United States' allies, Japan and the Republic of Korea, continue to simmer under the post-1945 liberal international order. The antagonism between the former colonizer and its colony has become a detriment not only for US security interests in the region, but also a challenge to the US claims to stand for human rights, as the issue of military sexual slavery has become tethered to the global human rights discourse by Korean American diaspora activists. Yet, when the US attempts to mediate between the two, it is rebuffed by its two allies because the US often acts as a neutral third party, rather than the major actor responsible for the making of post-1945 order in east Asia and the current impasse over history. This article asks how the entangled relation between order and justice in the making of the hub-and-spokes system in east Asia, mainly engineered by the United States, casts a long shadow over how to deal with history in Japan. This matters because questions of moral possibility in world politics always suppose a sovereign agentic state, and for Japan this creates a gap between the ideal moral state and the reality of being a semi-sovereign state. Thus, the persistence of Japan's ‘history problem’ must be understood not solely in terms of whether the empirical facts are accepted or not, but also in the sense of how being a sovereign matters when it comes to moral possibility in global politics.
Refractory diffuse coronary artery spasm post aortic valve replacement
Authors: Nagasawa Ayako , Okonogi Shuichi , Ohki Satoshi , Ohbayashi Tamiyuki
Published: January 2023

Postoperative coronary artery spasm occurs rarely after valve replacement surgery. We report the case of a 64-year-old man with normal coronary arteries who underwent aortic valve replacement. Nineteen hours postoperatively, his blood pressure plummeted with an elevated ST-segment. Coronary angiography demonstrated a 3-vessel diffuse coronary artery spasm, and direct intracoronary infusion therapy was performed with isosorbide nitrate, nicorandil and sodium nitroprusside hydrate within 1 h of onset. Nonetheless, there was no improvement, and the patient was resistant to treatment. The patient died due to prolonged low cardiac function and pneumonia complications. Prompt intracoronary vasodilator infusion is considered effective. However, this case was refractory to multi-drug intracoronary infusion therapy and was not salvageable.
Overall and abdominal obesity and risks of all-cause and cause-specific mortality in Korean adults: a pooled analysis of three population-based prospective cohorts
Authors: Jang Hajin , Kim Rockli , Lee Jong-Tae , Lee Dong Hoon , Giovannucci Edward L , Oh Hannah
Published: January 2023

Background

Studies found a J-shaped association between body mass index (BMI) and mortality. However, it is unclear whether the association is driven by biases, particularly confounding by fat-free mass.

Methods

We conducted an individual-level pooled analysis of three cohorts of Korean adults (aged ≥ 40 years; n = 153 248). Mortality was followed up through December 2019. Anthropometric data were directly measured at baseline. Fat and fat-free mass were predicted using validated prediction models. Using Cox proportional hazards models, we estimated the associations of BMI and waist circumference (WC) with all-cause and cause-specific mortality. To account for biases, we excluded participants aged ≥ 70 years, deaths that occurred within 5 years of follow-up and ever smokers, and adjusted for fat-free mass index (FFMI).

Results

During the follow-up of up to 18 years, 6061 deaths were identified. We observed J-shaped association of BMI (nadir at 22–26) and monotonically positive association of WC with all-cause, cardiovascular, and cancer mortality among Korean adults without a history of cancer or cardiovascular disease. In the BMI analysis, excluding ever smokers and adjusting for FFMI attenuated the excess mortality in underweight participants and transformed the J-shaped association into a monotonically positive shape, suggesting an increased mortality at BMI > 22.0. Excluding participants aged ≥ 70 years and deaths that occurred within 5 years of follow-up did not change the results. In the WC analysis, the monotonic positive associations did not change after the control. Similar results were observed among participants with a history of cancer or cardiovascular disease.

Conclusions

Our data suggest that both overall and abdominal body fat are associated with increased mortality in Korean adults.
Local Mixing of One-Parameter Diagonal Flows on Anosov Homogeneous Spaces
Authors: Chow Michael , Sarkar Pratyush
Published: January 2023

Let $G$ be a connected semisimple real algebraic group and $\Gamma < G$ be a Zariski dense Anosov subgroup with respect to a minimal parabolic subgroup. We prove local mixing of the one-parameter diagonal flow $\{\exp (t\mathsf {v}): t \in {\mathbb {R}}\}$ on $\Gamma \backslash G$ for any interior direction $\mathsf {v}$ of the limit cone of $\Gamma $ with respect to the Bowen–Margulis–Sullivan measure associated to $\mathsf {v}$. More generally, we allow a class of deviations to this flow along a direction $\mathsf {u}$ in some fixed subspace transverse to $\mathsf {v}$. We also obtain a uniform bound for the correlation function, which decays exponentially in $\|\mathsf {u}\|^2$. The precise form of the result is required for several applications such as the asymptotic formula for the decay of matrix coefficients in $L^2(\Gamma \backslash G)$ proved by Edwards–Lee–Oh.
Nonexistence of Negative Curves
Authors: González Anaya Javier , González José Luis , Karu Kalle
Published: January 2023

Let $X$ be the blowup of a weighted projective plane ${\mathbb {P}}(a,b,c)$ at a general point. The Kleiman–Mori cone of $X$ is two-dimensional with one ray generated by the class of the exceptional curve $E$. It is not known if the second extremal ray is always generated by the class of a curve. We construct an infinite family of projective toric surfaces of Picard number one such that their blowups $X$ at a general point have half-open Kleiman–Mori cones: there is no negative curve generating the other boundary ray of the cone.
Macroecology and Potential Drivers of Diversity in Webspinner Maternal Care (Order Embioptera)
Authors: Morinaga Gen , Soghigian John , Edgerly Janice S
Published: January 2023

Embioptera display variability in egg-handling as part of their defense against natural enemies. Because species living in tropical regions experience potentially higher risks of predation than those in temperate climes, we hypothesized that variable risk might explain this variability. We used actual evapotranspiration (AET) rates as a stand-in for climate, region, and potential interactions with natural enemies. We predicted that more complex investments, such as coating individual eggs, organizing them, and topping the cluster with thick silk would co-occur with greater predation threats in tropical regions, scored as higher AET. We predicted that simpler organization of eggs would occur where predator risk would be lower, as in temperate regions (lower AET). We used phylogenetic comparative methods to assess whether more complex egg handling behavior correlated with high AET scores. We quantified five traits of egg handling from field and laboratory evidence for 29 species from habitats ranging from low to high AET. Initial pGLS and pGLM analyses showed a weak effect of AET on parental care index. Upon exclusion of three exotic species spread artificially by trade and collected outside their native ranges, we found strong effects of predation threat in both pGLS and pGLM analyses. These analyses revealed that species that experience potentially greater predation threats exhibited behaviors that corresponded to more complex handling and organization of eggs by the mother. These results align nicely with analyses that also detected that additional lines of defense of eggs typify the behavior of tropical species of other primitively social arthropods.
Bronchopulmonary disposition of IV cefepime/taniborbactam (2–0.5 g) administered over 2 h in healthy adult subjects
Authors: Asempa Tomefa E , Kuti Joseph L , Nascimento Jeffrey C , Pope Samuel J , Salerno Edward L , Troy Patrick J , Nicolau David P
Published: January 2023

Introduction

Taniborbactam (formerly VNRX-5133) is an investigational β-lactamase inhibitor in clinical development in combination with cefepime for the treatment of MDR Gram-negative pathogens.

Objectives

To assess the safety profile and pulmonary disposition of 2–0.5 g cefepime/taniborbactam administered as a 2 h IV infusion every 8 h following three doses in healthy adult subjects.

Methods

In this Phase 1 trial, open-label study, plasma samples were collected over the last dosing interval, and subjects (n = 20) were randomized to undergo bronchoalveolar lavage (BAL) at four timepoints after the last dose. Drug concentrations in plasma (total and free as determined by protein binding), BAL fluid and alveolar macrophages (AM) were determined by LC-MS/MS, and the urea correction method was used to calculate epithelial lining fluid (ELF) drug concentrations. Pharmacokinetic parameters were estimated by non-compartmental analysis.

Results

Mean (±SD) taniborbactam Cmax and AUC0–8 in plasma were 24.1 ± 4.1 mg/L and 81.9 ± 13.9 mg·h/L, respectively. Corresponding values for cefepime were 118.4 ± 29.7 mg/L and 346.7 ± 71.3 mg·h/L. Protein binding was 0% for taniborbactam and 22.4% for cefepime. Mean taniborbactam concentrations (mg/L) at 2, 4, 6 and 8 h were 3.9, 1.9, 1.0 and 0.3 in ELF and 12.4, 11.5, 14.3 and 14.9 in AM, with corresponding AUC0–8 ELF of 13.8 and AUC0–8 AM of 106.0 mg·h/L. Cefepime AUC0–8 ELF was 77.9 mg·h/L. No serious adverse events were observed.

Conclusion

The observed bronchopulmonary exposures of taniborbactam and cefepime can be employed to design optimal dosing regimens for clinical trials in patients with pneumonia.
Effect of an Educational Intervention on Women’s Health Care Provider Knowledge Gaps About Breast Cancer Risk Model Use and High-risk Screening Recommendations
Authors: Seitzman Robin L , Pushkin JoAnn , Berg Wendie A
Published: January 2023

Objective

To assess effectiveness of a web-based educational intervention on women’s health care provider knowledge of breast cancer risk models and high-risk screening recommendations.

Methods

A web-based pre- and post-test study including 177 U.S.-based women’s health care providers was conducted in 2019. Knowledge gaps were defined as fewer than 75% of respondents answering correctly. Pre- and post-test knowledge differences (McNemar test) and associations of baseline characteristics with pre-test knowledge gaps (logistic regression) were evaluated.

Results

Respondents included 131/177 (74.0%) physicians; 127/177 (71.8%) practiced obstetrics/gynecology. Pre-test, 118/177 (66.7%) knew the Gail model predicts lifetime invasive breast cancer risk; this knowledge gap persisted post-test [(121/177, 68.4%); P = 0.77]. Just 39.0% (69/177) knew the Gail model identifies women eligible for risk-reducing medications; this knowledge gap resolved. Only 48.6% (86/177) knew the Gail model should not be used to identify women meeting high-risk MRI screening guidelines; this deficiency decreased to 66.1% (117/177) post-test (P = 0.001). Pre-test, 47.5% (84/177) knew the Tyrer-Cuzick model is used to identify women meeting high-risk screening MRI criteria, 42.9% (76/177) to predict BRCA1/2 pathogenic mutation risk, and 26.0% (46/177) to predict lifetime invasive breast cancer risk. These knowledge gaps persisted but improved. For a high-risk 30-year-old, 67.8% (120/177) and 54.2% (96/177) pre-test knew screening MRI and mammography/tomosynthesis are recommended, respectively; 19.2% (34/177) knew both are recommended; and 53% (94/177) knew US is not recommended. These knowledge gaps resolved or reduced.

Conclusion

Web-based education can reduce important provider knowledge gaps about breast cancer risk models and high-risk screening recommendations.
State of Communication Training During the Breast Imaging Fellowship Year
Authors: Dodelzon Katerina , Katzen Janine
Published: January 2023

Objective

The purpose of this study was to survey breast imaging fellowship programs nationally on the state of communication skills training during fellowship training.

Methods

In this IRB-exempt study, fellowship program director members of the Society of Breast Imaging (SBI) were anonymously surveyed on current provision and types of communication skills training in their fellowship curricula.

Results

A six-question survey was sent to all 95 SBI member fellowship program directors with a response rate of 56% (53/95). Although direct fellow patient-centered communication interactions are practiced across all respondent training programs, formal communication skills training was offered in a minority of programs with 32% (17/53) providing formal communication in the form of a didactic lecture and 17% (9/53) engaging fellows in a simulation communication skills workshop. Of the 53 programs, 12 (22%) reported no formal communication skills training of any kind, while a majority (44/53, 83%) of programs provide regular feedback based on observed fellow–patient communication interactions.

Conclusion

Despite nearly uniform practice of engaging breast imaging fellows in direct patient-centered interaction at the onset of the fellowship training year, the majority of fellowship programs do not provide any formal communication skills training curricula at any point during fellowship training. To equip future breast radiologists with the skills to provide value in an increasingly patient-centered field, dedicated formal communication curricula ought to be incorporated consistently into breast imaging fellowship training programs.
Ethics of Artificial Intelligence in Breast Imaging
Authors: Morgan Matthew B , Mates Jonathan L
Published: January 2023

There is great interest in the development of artificial intelligence (AI) applications for medical imaging in general and specifically in breast imaging. Because of the scale of application and the potential for harm, there has been a parallel interest in assuring that these new technologies are scrutinized and applied in ethical ways. The four principles of autonomy, beneficence, non-maleficence, and justice are widely accepted as a framework for bioethical analysis. We incorporate a fifth principle of explicability (adapted from Floridi and Cowls) because of the unique considerations of AI. We review definitions of each of these principles and provide examples of their practical application to breast imaging.
Disparities in cancer incidence by rurality in California
Authors: Oh Debora L , Schumacher Karen , Yang Juan , Wang Katarina , Lin Katherine , Gomez Scarlett Lin , Shariff-Marco Salma
Published: January 2023

Background

Cancer rates in rural areas across the United States have different patterns than in urban areas. This study examines associations between rurality and incidence for the top 5 cancers in California and evaluates whether these associations vary jointly by sex, race, and ethnicity.

Methods

We used 2015-2019 California Cancer Registry data to compare incidence rate ratios (IRRs) and trends for breast, prostate, lung, colorectal, and skin (melanoma) cancers. We leveraged census tract aggregation zones and 7 levels of percentage rural population (0%, >0% to <10%, 10% to <20%, 20% to <30%, 30% to <40%, 40% to <50%, and 50+%).

Results

Zones with higher proportions of rural population were significantly associated with lower incidence of female breast cancer and prostate cancer, though the trends were not statistically significant overall. Zones with higher proportions of rural population were significantly associated with higher incidence of lung cancer and melanoma. There were no statistically significant trends for colorectal cancer overall. Comparing areas with 50% and over rural population with areas with 0% rural population, the IRR for lung cancer in Hispanic females was higher (IRR = 1.43, 95% confidence interval [CI] = 1.17 to 1.74) than in Hispanic males (IRR = 0.90, 95% CI = 0.72 to 1.11). Also, in areas with 50% or more rural population, the IRR for melanoma was higher in Hispanic females (IRR = 1.75, 95% CI = 1.23 to 2.45) than non-Hispanic White females (IRR = 0.87, 95% CI = 0.80 to 0.95).

Conclusions

Our findings show that rurality is associated with cancer incidence and underscore the importance of jointly examining rural disparities with sex, race, and ethnicity by cancer site.
Transmicron: accurate prediction of insertion probabilities improves detection of cancer driver genes from transposon mutagenesis screens
Authors: Bredthauer Carl , Fischer Anja , Ahari Ata Jadid , Cao Xueqi , Weber Julia , Rad Lena , Rad Roland , Wachutka Leonhard , Gagneur Julien
Published: January 2023

Transposon screens are powerful in vivo assays used to identify loci driving carcinogenesis. These loci are identified as Common Insertion Sites (CISs), i.e. regions with more transposon insertions than expected by chance. However, the identification of CISs is affected by biases in the insertion behaviour of transposon systems. Here, we introduce Transmicron, a novel method that differs from previous methods by (i) modelling neutral insertion rates based on chromatin accessibility, transcriptional activity and sequence context and (ii) estimating oncogenic selection for each genomic region using Poisson regression to model insertion counts while controlling for neutral insertion rates. To assess the benefits of our approach, we generated a dataset applying two different transposon systems under comparable conditions. Benchmarking for enrichment of known cancer genes showed improved performance of Transmicron against state-of-the-art methods. Modelling neutral insertion rates allowed for better control of false positives and stronger agreement of the results between transposon systems. Moreover, using Poisson regression to consider intra-sample and inter-sample information proved beneficial in small and moderately-sized datasets. Transmicron is open-source and freely available. Overall, this study contributes to the understanding of transposon biology and introduces a novel approach to use this knowledge for discovering cancer driver genes.
Exploiting natural riboswitches for aptamer engineering and validation
Authors: Mohsen Michael G , Midy Matthew K , Balaji Aparaajita , Breaker Ronald R
Published: January 2023

Over the past three decades, researchers have found that some engineered aptamers can be made to work well in test tubes but that these same aptamers might fail to function in cells. To help address this problem, we developed the ‘Graftamer’ approach, an experimental platform that exploits the architecture of a natural riboswitch to enhance in vitro aptamer selection and accelerate in vivo testing. Starting with combinatorial RNA pools that contain structural features of a guanine riboswitch aptamer interspersed with regions of random sequence, we performed multiplexed in vitro selection with a collection of small molecules. This effort yielded aptamers for quinine, guanine, and caffeine that appear to maintain structural features of the natural guanine riboswitch aptamer. Quinine and caffeine aptamers were each grafted onto a natural guanine riboswitch expression platform and reporter gene expression was monitored to determine that these aptamers function in cells. Additionally, we determined the secondary structure features and survival mechanism of a class of RNA sequences that evade the intended selection strategy, providing insight into improving this approach for future efforts. These results demonstrate that the Graftamer strategy described herein represents a convenient and straightforward approach to develop aptamers and validate their in vivo function.
Alternative splicing mediates the compensatory upregulation of MBNL2 upon MBNL1 loss-of-function
Authors: Nitschke Larissa , Hu Rong-Chi , Miller Andrew N , Lucas Lathan , Cooper Thomas A
Published: January 2023

Loss of gene function can be compensated by paralogs with redundant functions. An example of such compensation are the paralogs of the Muscleblind-Like (MBNL) family of RNA-binding proteins that are sequestered and lose their function in Myotonic Dystrophy Type 1 (DM1). Loss of MBNL1 increases the levels of its paralog MBNL2 in tissues where Mbnl2 expression is low, allowing MBNL2 to functionally compensate for MBNL1 loss. Here, we show that loss of MBNL1 increases the inclusion of Mbnl2 exon 6 and exon 9. We find that inclusion of Mbnl2 exon 6 increases the translocation of MBNL2 to the nucleus, while the inclusion of Mbnl2 exon 9 shifts the reading frame to an alternative C-terminus. We show that the C-terminus lacking exon 9 contains a PEST domain which causes proteasomal degradation. Loss of MBNL1 increases the inclusion of exon 9, resulting in an alternative C-terminus lacking the PEST domain and the increase of MBNL2. We further find that the compensatory mechanism is active in a mouse DM1 model. Together, this study uncovers the compensatory mechanism by which loss of MBNL1 upregulates its paralog MBNL2 and highlights a potential role of the compensatory mechanism in DM1.
The recognition mode between hsRBFA and mitoribosome 12S rRNA during mitoribosomal biogenesis
Authors: Zhou Wanwan , Liu Xiaodan , Lv Mengqi , Shi Yunyu , Zhang Liang
Published: January 2023

Eukaryotes contain two sets of genomes: the nuclear genome and the mitochondrial genome. The mitochondrial genome transcripts 13 mRNAs that encode 13 essential proteins for the oxidative phosphorylation complex, 2 rRNAs (12s rRNA and 16s rRNA), and 22 tRNAs. The proper assembly and maturation of the mitochondrial ribosome (mitoribosome) are critical for the translation of the 13 key proteins and the function of the mitochondrion. Human ribosome-binding factor A (hsRBFA) is a mitoribosome assembly factor that binds with helix 28, helix 44 and helix 45 of 12S rRNA and facilitates the transcriptional modification of 12S rRNA during the mitoribosomal biogenesis. Previous research mentioned that the malfunction of hsRBFA will induce the instability of mitoribosomes and affect the function of mitochondria, but the mechanisms underlying the interaction between hsRBFA and 12S rRNA and its influence on mitochondrial function are still unknown. In this study, we found that hsRBFA binds with double strain RNA (dsRNA) through its whole N-terminus (Nt) instead of the KH-like domain alone, which is different from the other homologous. Furthermore, we mapped the key residues that affected the RNA binding and maturation of mitoribosomes in vitro. Finally, we investigated how these residues affect mitochondrial functions in detail and systematically.
Resolution of sequence divergence for repeat-mediated deletions shows a polarity that is mediated by MLH1
Authors: Trost Hannah , Merkell Arianna , Lopezcolorado Felicia Wednesday , Stark Jeremy M
Published: January 2023

Repeat-mediated deletions (RMDs) are a type of chromosomal rearrangement between two homologous sequences that causes loss of the sequence between the repeats, along with one of the repeats. Sequence divergence between repeats suppresses RMDs; the mechanisms of such suppression and of resolution of the sequence divergence remains poorly understood. We identified RMD regulators using a set of reporter assays in mouse cells that test two key parameters: repeat sequence divergence and the distances between one repeat and the initiating chromosomal break. We found that the mismatch repair factor MLH1 suppresses RMDs with sequence divergence in the same pathway as MSH2 and MSH6, and which is dependent on residues in MLH1 and its binding partner PMS2 that are important for nuclease activity. Additionally, we found that the resolution of sequence divergence in the RMD product has a specific polarity, where divergent bases that are proximal to the chromosomal break end are preferentially removed. Moreover, we found that the domain of MLH1 that forms part of the MLH1-PMS2 endonuclease is important for polarity of resolution of sequence divergence. We also identified distinctions between MLH1 versus TOP3α in regulation of RMDs. We suggest that MLH1 suppresses RMDs with sequence divergence, while also promoting directional resolution of sequence divergence in the RMD product.
The hnRNP C tetramer binds to CBC on mRNA and impedes PHAX recruitment for the classification of RNA polymerase II transcripts
Authors: Dantsuji Sayaka , Ohno Mutsuhito , Taniguchi Ichiro
Published: January 2023

In eukaryotic cells, various classes of RNAs are exported to the cytoplasm by class-specific factors. Accumulating evidence has shown that export factors affect the fate of RNA, demonstrating the importance of proper RNA classification upon export. We previously reported that RNA polymerase II transcripts were classified after synthesis depending on their length, and identified heterogeneous nuclear ribonucleoprotein (hnRNP) C as the key classification factor. HnRNP C inhibits the recruitment of PHAX, an adapter protein for spliceosomal U snRNA export, to long transcripts, navigating these RNAs to the mRNA export pathway. However, the mechanisms by which hnRNP C inhibits PHAX recruitment to mRNA remain unknown. We showed that the cap-binding complex, a bridging factor between m7G-capped RNA and PHAX, directly interacted with hnRNP C on mRNA. Additionally, we revealed that the tetramer-forming activity of hnRNP C and its strong RNA-binding activity were crucial for the inhibition of PHAX binding to longer RNAs. These results suggest that mRNA is wrapped around the hnRNP C tetramer without a gap from the cap, thereby impeding the recruitment of PHAX. The results obtained on the mode of length-specific RNA classification by the hnRNP C tetramer will provide mechanistic insights into hnRNP C-mediated RNA biogenesis.