bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring Aggregate Market Expectations from the Cross Section of Stock Prices
Authors: Bali Turan G. , Nichols D. Craig , Weinbaum David
Published: April 2023

We introduce a new approach to estimating long-term aggregate discount rates using the cross section of earnings and book values to explain current stock prices and extract expected market returns. The proposed discount rate measure is countercyclical. Shocks to it account for nearly half of historical market return variation; in contrast, shocks to other discount rate measures account for no more than 2%. It dominates other measures in explaining time-series variation in returns on duration-sorted portfolios and delivers out-of-sample predictability that exceeds that afforded by other expected return measures and predictive variables. It also performs well in international equity markets.
Particle-in-cell simulations of Alfvén wave parametric decay in a low-beta plasma
Authors: González C.A. , Innocenti Maria Elena , Tenerani Anna
Published: April 2023

We study the parametric decay instability of parallel-propagating Alfvén waves in a low-beta plasma using one-dimensional fully kinetic simulations. We focus for the first time on the conversion of the energy stored in the initial Alfvén wave into particle internal energy, and on its partition between particle species. We show that compressible fluctuations generated by the decay of the pump wave into a secondary ion-acoustic mode and a reflected Alfvén wave contribute to the gain of internal energy via two distinct mechanisms. First, the ion-acoustic mode leads nonlinearly to proton trapping and proton phase-space mixing, in agreement with previous work based on hybrid simulations. Second, during the nonlinear stage, a compressible front of the fast type develops at the steepened edge of the backward Alfvén wave leading to a field-aligned proton beam propagating backwards at the Alfvén speed. We find that parametric decay heats preferentially protons, which gain approximately 50 % of the pump wave energy in the form of internal energy. However, we find that electrons are also energized and that they contribute to the total energy balance by gaining 10 % of the pump wave energy. By investigating energy partition and particle heating during parametric decay, our results contribute to the determination of the role of compressible and kinetic effects in wave-driven models of the solar wind.
Generation of terahertz radiation by a Hermite–Gaussian laser beam inside magnetoplasma with a density ramp
Authors: Kad Proxy , Rana Vidisha , Singh Arvinder
Published: April 2023

In the present scheme of work, the Hermite–Gaussian (HG) laser beam dynamics has been investigated under the influence of an upward density ramp inside magnetized plasma, where both relativistic and ponderomotive nonlinearities are operative. One can achieve self-focusing of laser beam due to the change in the medium's dielectric function, which comes into operation due to the expulsion of plasma electrons from the high intensity to the low-intensity region by ponderomotive force and their motion at relativistic speeds. The dynamics of the laser beam and terahertz generation have been investigated by using the moment theory approach. It has been observed from the present analysis that the dynamics of the laser beam and the production of terahertz radiations strongly depends upon the HG laser beam and plasma parameters. In addition to this, the effect of density ramp and magnetic field has also been investigated on the efficiency of terahertz generation. It has been observed that higher-order modes of the HG laser beam play a dominant role in the production of terahertz radiations.
Divine Representation in Documentary Style: Gods on the Columns of Trajan and Marcus Aurelius
Authors: Runeckles Thomas
Published: April 2023

This article examines the important roles played by gods in the friezes of the Columns of Trajan and Marcus Aurelius and argues that they are treated in a distinctive ‘documentary’ style, comparable in certain ways to accounts of divine action in Roman historiography and designed to produce a compelling narrative effect. First, the Columns and the deities they depict are discussed. The article then looks at cognate descriptions of gods in historiographical texts. Finally, other contemporary monuments that portray the gods are briefly examined to bring out further the distinctive character of the gods on the Columns. This analysis will be seen to have wider implications for our understanding of ‘historical narrative reliefs’ and imperial representation.
Bidirectional cross-linguistic influence with different-script languages: Evidence from eye tracking
Authors: Taylor Jamie , Mukai Yoichi
Published: April 2023

This study compared patterns of nonselective cross-language activation in L1 and L2 visual word recognition with different-script bilinguals. The aim was to determine (1) whether lexical processing is nonselective in the L1 (as in L2), and (2) if the same cross-linguistic factors affected processing similarly in each language. To examine the time course of activation, eye movements were tracked during lexical decision. Thirty-two Japanese–English bilinguals responded to 250 target words in Japanese and in English. The same participants and items (i.e., cognate translation equivalents) were used to directly compare L1 and L2 processing. Response latencies as well as eye movements representing early and late processing were analyzed using mixed-effects regression modeling. Similar cross-linguistic effects, namely cognate word frequency, phonological similarity, and semantic similarity, were found in both languages. These factors affected processing to different degrees in each language, however. While cognate frequency was significant as early as the first fixation, effects of cross-linguistic phonological and semantic similarity arose later in time. Increased phonological similarity slowed responses in L2 but speeded them in L1, while greater semantic overlap was facilitatory in both languages. Results are discussed from the perspective of the BIA+ model of visual word recognition.
Oh help! Oh no! The international politics of The Gruffalo: Children’s picturebooks and world politics
Authors: Jarvis Lee , Robinson Nick
Published: April 2023

The article explores the complicity of children’s picturebooks in the construction and critique of world politics. Focusing on The Gruffalo, it argues that this spectacularly successful book: (1) stories the international as a pessimistic, anarchical world populated by self-interested, survival-seekers; (2) disrupts this reading and its assumptions through evocation of the social production of threat; and, (3) provides a more fundamental decolonial critique of the international through parochial privileging of its protagonist’s journey through a ‘deep dark wood’. In doing this, we argue, the book vividly demonstrates the world’s susceptibility to multiple incompatible readings, while rendering visible the assumptions, framing, and occlusions of competing understandings of the international. As such, it theorises both world politics and knowledge thereof as contingent and unstable. In making this argument, three contributions are made. First, empirically, we expand research on popular culture and world politics through investigating a surprisingly neglected example of the former. Second, theoretically, we demonstrate the work such texts perform in (re)creating and (de)stabilising (knowledge of) global politics. Third, we offer a composite methodological framework for future research into the context, content, and framing of complex texts like The Gruffalo.
Regulatory, health technology assessment and company interactions: the current landscape and future ecosystem for drug development, review and reimbursement
Authors: Wang Ting , McAuslane Neil , Goettsch Wim G. , Leufkens Hubert G.M. , De Bruin Marie L.
Published: April 2023

Background

Multi-stakeholder interactions have evolved at product and policy levels. There is a need to assess the current and future landscape of interactions between companies, and regulatory and HTA agencies to address challenges and identify areas for improvement.

Objectives

The aims of this study were to review the current interactions within and across regulatory and HTA agencies, and companies’ experiences in engaging in these activities; to assess the added value of interactions as well as limitations; to explore the future ecosystem for stakeholder interactions.

Method

Three separate questionnaires were developed for companies, regulators and HTA agencies, respectively, to assess their experiences and perceptions. The responses were analyzed using descriptive statistics and discussed at a multi-stakeholder workshop. Key outcomes from the surveys and workshop discussion were reported.

Results

All seven regulators and seven HTA agencies in the survey indicated that they had stakeholder interactions. More formal collaboration occurred with regulators compared with HTA agencies. All nine companies have taken early advice but indicated the need for future prioritization. Success indicators can be built at the product and therapy levels, with the added value of faster patient access. Four principles were proposed for the future ecosystem: separate remit and functions between regulators and HTA; align processes; converge evidence requirements where possible; increase transparency.

Conclusions

This research brought together regulators, HTA agencies, companies to examine how they interact with one another. We propose measures of value and make recommendations on future evolution to enable better evidence generation and improve regulatory and HTA decision-making.
Intermediate-scale statistics for real-valued lacunary sequences
Authors: YESHA NADAV
Published: April 2023

We study intermediate-scale statistics for the fractional parts of the sequence
$\left(\alpha a_{n}\right)_{n=1}^{\infty}$
, where
$\left(a_{n}\right)_{n=1}^{\infty}$
is a positive, real-valued lacunary sequence, and
$\alpha\in\mathbb{R}$
. In particular, we consider the number of elements
$S_{N}\!\left(L,\alpha\right)$
in a random interval of length
$L/N$
, where
$L=O\!\left(N^{1-\epsilon}\right)$
, and show that its variance (the number variance) is asymptotic to L with high probability w.r.t.
$\alpha$
, which is in agreement with the statistics of uniform i.i.d. random points in the unit interval. In addition, we show that the same asymptotic holds almost surely in
$\alpha\in\mathbb{R}$
when
$L=O\!\left(N^{1/2-\epsilon}\right)$
. For slowly growing L, we further prove a central limit theorem for
$S_{N}\!\left(L,\alpha\right)$
which holds for almost all
$\alpha\in\mathbb{R}$
.
Stable finiteness does not imply linear soficity
Authors: GREENFELD BE’ERI
Published: April 2023

We prove that there exist finitely generated, stably finite algebras which are not linear sofic. This was left open by Arzhantseva and Păunescu in 2017.
Current trends and future directions in the rural history of later medieval England (c. 1200–c. 1500)
Authors: Briggs Chris
Published: April 2023

This article surveys a range of work on the later medieval English countryside published since 2000, and offers some predictions and suggestions about future research. It shows that the field of ‘rural history’ has rarely been closely defined, and indeed has tended to be treated as a broad church that can accommodate many different kinds of approach, themselves drawing on a variety of disciplinary traditions. The article identifies and discusses recent and current innovation and creativity in research within two such broad approaches, one mainly ‘economic’, the other ‘cultural’. It concludes by arguing for the gains that can be enjoyed through the combination of elements of the two approaches, and especially through a renewed emphasis on the illumination of the general through an intensive focus on the local.
The prevalence and nature of COLAs in public sector retirement plans
Authors: Fitzpatrick Maria D. , Goda Gopi Shah
Published: April 2023

State and local employees comprise a significant proportion of the workforce and are largely covered by defined benefit pensions. Many of these retirement plans have been facing funding gaps, but legal restrictions often prevent them from reducing benefits for current employees. However, retirement plans can reduce liabilities by changing cost-of-living adjustments, or COLAs, which are commonly applied to benefits each year to allow retirees to maintain purchasing power in retirement. In this study, we examine the prevalence of COLAs in public sector retirement plans through original data collection for 49 plans in 30 states, which cover approximately 52% of public sector workers overall. Among these samples, on average 45% of workers each year experienced some change in COLAs between 2005 and 2018, with more than half of these workers experiencing negative changes. We consider stylized examples of public sector workers subject to reductions in COLAs to understand how COLAs may affect workers’ retirement decisions. Our analysis suggests that eliminating a 3% COLA could delay retirement of affected workers by approximately 4.5 months.
Associations between Latino ethnicity and the use of emotional support and completion of advance directives
Authors: Shen Megan Johnson , Prigerson Holly G. , Maciejewski Paul K.
Published: April 2023

Objectives

Latino patients have been shown to engage in advance care planning (ACP) at much lower rates than non-Latino White patients. Coping strategies, such as the use of emotional support, may differentially relate to engagement in ACP among Latino and non-Latino patients. The present study sought to examine the moderating effect of ethnicity on the relationship between the use of emotional support as a coping strategy and completion of advance directives.

Methods

The present study employed a weighted sample (Nw = 185) of Latino and non-Latino White patient participants in Coping with Cancer III, an National Institutes of Health–sponsored, multisite, longitudinal, observational cohort study of patients with advanced cancer and their informal caregivers and oncology providers designed to evaluate Latino/non-Latino disparities in ACP and end-of-life cancer care. Main and interaction effects of Latino ethnicity and use of emotional support on patient use of advance directives were estimated as odds ratios.

Results

Use of emotional support was associated with dramatically lower do-not-resuscitate (DNR) order completion to a greater extent among Latino as compared to non-Latino patients (interaction AOR = 0.33, p = 0.005). Interaction effects were not statistically significant for living will or health-care proxy form completion.

Significance of results

Use of emotional support is associated with lower odds of completing DNRs among Latino than among non-Latino patients. Seeking and/or receiving emotional support may deter Latino patients from completing DNR orders. Research is needed to address both emotional needs and practicalities to ensure high quality end-of-life care among Latino patients with cancer.
Prevalence and management of chronic nonmalignant pain in palliative care populations: A systematic review
Authors: Kernick Lucy , Glare Paul , Hosie Annmarie , Chiu Annie , Kissane David W.
Published: April 2023

Objectives

To investigate the prevalence and current approaches to clinical management of chronic nonmalignant pain in patients referred to palliative care services.

Methods

A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD42021205432). Six databases were searched on 25 August 2020 and again on 11 July 2022: PubMed and Ovid MEDLINE, Elsevier Scopus, PsychINFO, the Cochrane Library, and CINAHL. Search included prevalence or intervention studies with patients who had chronic nonmalignant pain and were referred to palliative care services. Screening was undertaken independently by 2 reviewers.

Results

The searches returned 417 titles; subsequent screening identified 5 eligible studies, 4 from the USA and 1 from Hong Kong, including 2 cohort and 3 cross-sectional studies. Sample sizes ranged from 137 to 323, with a total of 1,056 patients. The prevalence of chronic nonmalignant pain ranged from 14% to 34% across different palliative care settings. There was significant crossover of pain types; 54% of patients with chronic no-malignant pain had additional cancer-related pain or cancer treatment–related pain. Opioids were used to manage stand-alone chronic nonmalignant pain for 39% of patients compared to 58% with mixed chronic nonmalignant pain and other pain diagnoses.

Significance of results

Five studies have documented the prevalence of chronic nonmalignant pain of 14–34% in palliative care. Further research including prevalence and treatment studies would provide clearer evidence for best practice management of chronic nonmalignant pain in the palliative care setting.
Estimation of short- and long-term floor and ceiling prices for manure in a crop and livestock farms exchange
Authors: Thiery Eglantine , Brunschwig Gilles , Veysset Patrick , Mosnier Claire
Published: April 2023

Organic matter is a key element of soil fertility. However, in-soil stocks of organic matter are in decline in specialized crop farms. Reintroducing organic fertilizers could be a way to increase or at least maintain organic matter stocks in these soils. Straw/manure exchanges between crop farms and livestock farms could improve overall land fertility and thus the long-term income of farmers. Here we used a bioeconomic model to estimate the agronomic and economic benefits of straw/manure exchanges as part of a strategy to improve soil fertility. Iterative simulations were run with prices of farmyard manure varying from €0 to €20 ton−1 to identify the price at which a crop farm can buy manure and sell straw without degrading its net income (manure ceiling price) compared to purchasing mineral fertilizer only and ploughing back straw. Parallel simulations were run to identify the price at which a livestock farmer can sell manure and buy straw without degrading its net income (manure floor price) compared to keeping all manure on the farm and buying straw on the market. The key new contributions of this study are that it (i) considers the characteristics of manure beyond its short-term fertilizing value, i.e., better mineralization of humus and a 10% increase in crop yields, (ii) estimates both the economic and agronomic benefits of manure and (iii) assesses the impacts of uncertainties on manure effects and prices. The results show that it is profitable for a French farmer in a conventional field crop system to buy manure at a price between €10 ton−1 in the short term and €18 ton−1 in the long term. The results also show that it is still economically advantageous for a livestock farmer to sell part of their manure, even at a very low price. This study shows that it is possible to better distribute manure resources over a territory in a way that enriches the soils of crop farms without degrading the soils of livestock farms.
Exploring the Future of Rainfall Extremes Over CONUS: The Effects of High Emission Climate Change Trajectories on the Intensity and Frequency of Rare Precipitation Events
Authors: Emmanouil Stergios , Langousis Andreas , Nikolopoulos Efthymios I. , Anagnostou Emmanouil N.
Published: April 2023

The impacts of climate change on extreme rainfall characteristics at fine spatiotemporal scales are governed by substantial uncertainty, primarily due to the systematic error components inherited from conventional numerical prediction systems, and/or the intrinsic assumptions of the selected modeling schemes. Here, we attempt to robustly evaluate the effects of future climate scenarios on intensity‐duration‐frequency (IDF) curves over the entire Contiguous United States, while accounting for the nonstationary nature of the rainfall process across adequately fine spatiotemporal resolutions. To do so, we apply a parametric approach to statistically downscaled climate model outputs that reflect the Representative Concentration Pathway 8.5, which are offered by the North American Coordinated Regional Downscaling Experiment. Compared to traditional IDF estimation techniques, the employed framework is based on multifractal (MF) scaling arguments and assumes that the statistical structure of rainfall at interannual scales can be approximated by sequential realizations of a stationary MF process with parameters that vary slowly across (not within) realizations. The obtained results show that return period estimates exhibit significant downward trends over most of the domain, which slowly dampen with time, as the effects of climate change are more pronounced at lower exceedance probability levels. Given the observed rate of changes in the frequency and intensity of extreme rainfall for the remainder of the century, we argue that future infrastructure design should be strategically tailored to account for a wide range of potential outcomes.
Role of Topography in Triggering Elevated Thunderstorms Associated With Winter Cold Fronts Over the Eastern Yunnan‐Guizhou Plateau
Authors: Luo Xinyue , Huang Xiaogang , Fei Jianfang , Wang Ju , Li Chao , Cheng Xiaoping
Published: April 2023

Using observations and reanalysis data, the circulation characteristics of elevated thunderstorms behind winter cold fronts (ETCFs) over the eastern Yunnan‐Guizhou Plateau are summarized, and a new triggering mechanism in the cold season related to topography is proposed. ETCFs always occur on the ridge and eastern side of the Dalou Mountain and are triggered at night. Pattern classifications using obliquely rotated T‐mode principal component analysis show that low‐level large‐scale circulation patterns have the following two characteristics: a southwestern airflow at 850 hPa, changing from southwest wind to east wind; and a northeast airflow at 900 hPa, changing from northeast wind to east wind. ETCFs occur in the area of this low easterly wind. A case study of 21 January 2020, shows that it is the intersection of the topography and cold front that provides unique geographical and circulation conditions for triggering elevated thunderstorms. Lateral friction along the mountains causes horizontal wind shear to flow parallel to them, forming positive and negative vortices above and below the front, respectively. This pair of vortices is strengthened by inertial oscillation at night, producing a stronger easterly wind. In the combined effects of frontal lift and topographical lift of the easterly flow, the elevated convection is triggered in the convergence zone above the front. These results provide a new insight into how topography helps to trigger convection in the cold season.
VprBP/DCAF1 regulates p53 function and stability through site-specific phosphorylation
Authors: Ghate Nikhil Baban , Kim Sungmin , Mehmood Roasa , Shin Yonghwan , Kim Kyunghwan , An Woojin
Published: April 2023

VprBP (also known as DCAF1) is a recently identified kinase that is overexpressed in cancer cells and serves as a major determinant for epigenetic gene silencing and tumorigenesis. The role of VprBP in driving target gene inactivation has been largely attributed to its ability to mediate histone H2A phosphorylation. However, whether VprBP also phosphorylates non-histone proteins and whether these phosphorylation events drive oncogenic signaling pathways have not been explored. Here we report that serine 367 phosphorylation (S367p) of p53 by VprBP is a key player in attenuating p53 transcriptional and growth suppressive activities. VprBP catalyzes p53S367p through a direct interaction with the C-terminal domain of p53. Mechanistically, VprBP-mediated S367p inhibits p53 function in the wake of promoting p53 proteasomal degradation, because blocking p53S367p increases p53 protein levels, thereby enhancing p53 transactivation. Furthermore, abrogation of VprBP-p53 interaction by p53 acetylation is critical for preventing p53S367p and potentiating p53 function in response to DNA damage. Together, our findings establish VprBP-mediated S367p as a negative regulator of p53 function and identify a previously uncharacterized mechanism by which S367p modulates p53 stability.
Within- and between-twin comparisons of risk for childhood behavioral difficulties after preterm birth
Authors: Fitzallen Grace C. , Taylor H. Gerry , Liley Helen G. , Bora Samudragupta
Published: April 2023

Background

Preterm birth and multiple gestation are independently associated with adverse neurodevelopmental outcomes. The objective of this study was to describe risks of screening positive for attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and anxiety in preterm-born twin children by zygosity (monozygotic, dizygotic) and birth order (first-born, second-born).

Methods

Caregivers of 349 preterm-born twin pairs (42% monozygotic) aged 3–18 years reported child behavioral outcomes on Strengths and Weaknesses of ADHD Symptoms and Normal Behavior; Social Responsiveness Scale, Second Edition; and Preschool Anxiety Scale or Screen for Child Anxiety and Related Emotional Disorders.

Results

Concordance for behavioral outcomes in twin pairs ranged from 80.06 to 89.31% for ADHD, 61.01 to 84.23% for ASD, and 64.76 to 73.35% for anxiety. Monozygotic twins had a greater risk than dizygotic of screening positive for inattention (risk ratio = 2.91, 95% CI = 1.48–5.72) and social anxiety (1.79, 1.23–2.61). Relative to first-born, second-born twins had a greater risk of screening positive for hyperactivity/impulsivity (1.51, 1.06–2.16); overall ASD (2.38, 1.62–3.49); difficulties with social awareness (2.68, 1.94–3.71), social cognition (4.45, 3.06–6.46), and social communication (2.36, 1.56–3.57); restricted/repetitive behavior (1.91, 1.30–2.81); overall anxiety (1.34, 1.10–1.64); generalized anxiety (1.34, 1.11–1.60); and social anxiety (1.32, 1.06–1.64).

Conclusion

The current findings emphasize considering zygosity and birth order in preterm and multiple birth outcomes research, and highlight clinical implications for discharge planning, neurodevelopmental surveillance, and facilitating parenting and family support.

Impact

Zygosity and birth order are important determinants of behavioral and socioemotional outcomes in preterm-born twins.

Among 349 preterm-born twin pairs aged 3–18 years (42% monozygotic), 61–89% demonstrated concordance for behavioral and socioemotional outcomes.

Monozygosity had greater risks than dizygosity for positive screening of inattention and social anxiety.

Second-born twins had greater risks than first-born for hyperactivity/impulsivity, social difficulties (awareness, cognition, communication), restricted/repetitive behavior, and anxiety (generalized, social).

These findings have implications for discharge planning, neurodevelopmental surveillance, and facilitating parenting and family support.
Long non-coding RNA HIF1A-As2 and MYC form a double-positive feedback loop to promote cell proliferation and metastasis in KRAS-driven non-small cell lung cancer
Authors: Yang Kaixin , Zhang Wenyang , Zhong Linghui , Xiao Yinan , Sahoo Sudhakar , Fassan Matteo , Zeng Kang , Magee Peter , Garofalo Michela , Shi Lei
Published: April 2023

Lung cancer is the leading cause of cancer-related deaths worldwide. KRAS is the main oncogenic driver in lung cancer that can be activated by gene mutation or amplification, but whether long non-coding RNAs (lncRNAs) regulate its activation remains unknown. Through gain and loss of function approaches, we identified that lncRNA HIF1A-As2, a KRAS-induced lncRNA, is required for cell proliferation, epithelial-mesenchymal transition (EMT) and tumor propagation in non-small cell lung cancer (NSCLC) in vitro and in vivo. Integrative analysis of HIF1A-As2 transcriptomic profiling reveals that HIF1A-As2 modulates gene expression in trans, particularly regulating transcriptional factor genes including MYC. Mechanistically, HIF1A-As2 epigenetically activates MYC by recruiting DHX9 on MYC promoter, consequently stimulating the transcription of MYC and its target genes. In addition, KRAS promotes HIF1A-As2 expression via the induction of MYC, suggesting HIF1A-As2 and MYC form a double-regulatory loop to strengthen cell proliferation and tumor metastasis in lung cancer. Inhibition of HIF1A-As2 by LNA GapmeR antisense oligonucleotides (ASO) significantly improves sensitization to 10058-F4 (a MYC-specific inhibitor) and cisplatin treatment in PDX and KRASLSLG12D-driven lung tumors, respectively.
RNF2 inhibits E-Cadherin transcription to promote hepatocellular carcinoma metastasis via inducing histone mono-ubiquitination
Authors: Yao Lei , Li Jun , Jiang Bo , Zhang Zeyu , Li Xinying , Ouyang Xiwu , Xiao Yao , Liu Guodong , Wang Zhiming , Zhang Gewen
Published: April 2023

RNF2 is a RING domain-containing E3 ubiquitin ligase that mediate histone H2A mono-ubiquitination to repress gene transcription, but its expression patterns and molecular function in hepatocellular carcinoma (HCC) remain unclear. Herein, we extracted data from TGCA database and validated RNF2 expression in our own cohort, which revealed that RNF2 was highly expressed in HCC and was associated with malignant characteristics and poor prognosis of HCC. Moreover, RNF2 was demonstrated to promote HCC metastasis via enhancing epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, RNF2 repressed E-Cadherin transcription by increasing the deposition of H2K119ub at the E-Cadherin promoter region. In addition, RNF2-regulated crosstalk between H2AK119ub, H3K27me3 and H3K4me3 synergistically reduced E-Cadherin transcription, which promoted EMT and HCC metastasis. These results indicate that RNF2 played an oncogenic role in HCC progression via inducing EMT, and RNF2 could be a potential therapeutic target for HCC.
XIAP deletion sensitizes mice to TNF-induced and RIP1-mediated death
Authors: Witt Axel , Goncharov Tatiana , Lee Yujung Michelle , Kist Matthias , Dohse Monika , Eastham Jeff , Dugger Debra , Newton Kim , Webster Joshua D. , Vucic Domagoj
Published: April 2023

XIAP is a caspase-inhibitory protein that blocks several cell death pathways, and mediates proper activation of inflammatory NOD2-RIP2 signaling. XIAP deficiency in patients with inflammatory diseases such as Crohn’s disease, or those needing allogeneic hematopoietic cell transplantation, is associated with a worse prognosis. In this study, we show that XIAP absence sensitizes cells and mice to LPS- and TNF-mediated cell death without affecting LPS- or TNF-induced NF-κB and MAPK signaling. In XIAP deficient mice, RIP1 inhibition effectively blocks TNF-stimulated cell death, hypothermia, lethality, cytokine/chemokine release, intestinal tissue damage and granulocyte migration. By contrast, inhibition of the related kinase RIP2 does not affect TNF-stimulated events, suggesting a lack of involvement for the RIP2-NOD2 signaling pathway. Overall, our data indicate that in XIAP’s absence RIP1 is a critical component of TNF-mediated inflammation, suggesting that RIP1 inhibition could be an attractive option for patients with XIAP deficiency.
Sex-specific risk factors associated with graves’ orbitopathy in Korean patients with newly diagnosed graves’ disease
Authors: Lee Jooyoung , Kang Jinmo , Ahn Hwa Young , Lee Jeong Kyu
Published: April 2023

Objective

To assess sex-specific risk factors for Graves’ orbitopathy (GO) in newly diagnosed Graves’ disease (GD) patients.

Methods

A retrospective cohort study was conducted using the National Health Insurance Service’s sample database, which consisted of 1,137,861 subjects from 2002 to 2019. The international classification of disease-10 codes was used to identify those who developed GD (E05) and GO (H062). A multivariable Cox proportional hazards model was used to estimate the effect of risk factors on GO development.

Results

Among 2145 male and 5047 female GD patients, GO occurred in 134 men (6.2%) and 293 women (5.8%). A multivariable Cox regression model revealed that GO development was significantly associated with younger age (HR = 0.84, 95% CI = 0.73–0.98), low income (HR = 0.55, 95% CI = 0.35–0.86), and heavy drinking (HR = 1.79, 95% CI = 1.10–2.90) in men, and with younger age (HR = 0.89, 95% CI = 0.81–0.98), lower body mass index (HR = 0.55, 95% CI = 0.33–0.90), high total cholesterol (HR = 1.04, 95% CI = 1.01–1.06), hyperlipidaemia (HR = 1.37, 95% CI = 1.02–1.85), and lower statin dose (HR = 0.37, 95% CI = 0.22–0.62) in women. There was no association between smoking and GO development in both men and women.

Conclusions

The risk factors for GO development were sex-dependent. These results show the need for more sophisticated attention and support considering sex characteristics in GO surveillance.
Ex vivo demonstration of canine corneal pre-Descemet’s anatomy using pneumodissection as for the big bubble technique for deep anterior lamellar keratoplasty
Authors: Kafarnik Christiane , Faraj Lana A. , Ting Darren S. J. , Goh Jia Ni , Said Dalia G. , Dua Harminder S.
Published: April 2023

The recent discovery and characterization of pre-Descemet’s layer (PDL; also termed the Dua’s layer or the Dua-Fine layer) has advanced the understanding of various posterior corneal pathologies and surgeries in human. This study aimed to characterize the ultrastructure of the posterior stroma and interfacial zone of Descemet’s membrane (DM) in canine eyes. Eighteen canine corneo-scleral discs were included. Intrastromal air injection resulted in the formation of type 1 big bubble (BB) in 73% (n = 11/15) of corneas, with a mean diameter of 11.0 ± 1.3 mm. No type 2 BB was created. Anterior segment optical coherence tomography, histology and transmission electron microscopy confirmed that the wall of BB was composed of DM, in contact with remaining stroma (canine PDL; cPDL). The cPDL was populated with keratocytes, of varying thickness of 16.2 ± 4.2 µm in close apposition to the DM, and composed of collagen bundles arranged in transverse, longitudinal and oblique directions. The interfacial zone, between DM and cPDL, showed fibril extension in all three directions, predominantly longitudinal. Irregular extensions of DM material into cPDL stroma were observed. No long-spaced collagen was detected. In conclusion, there exists a well-defined cleavage plane between the posterior stroma and cPDL, with similar but not identical characteristics as in humans, that is revealed by pneumodissection. This adds to our understanding of the anatomy of the posterior most canine cornea, which will have significant clinical impact on posterior corneal surgery and understanding of corneal pathology in dogs.
Association of feed efficiency with organ characteristics and fatty liver haemorrhagic syndrome in laying hens
Authors: Anene Doreen Onyinye , Akter Yeasmin , Groves Peter John , Horadagoda Neil , Liu Sonia Yun , Moss Amy , Hutchison Christine , O’Shea Cormac John
Published: April 2023

Poor feed efficiency (FE) in hens impacts body weight (BW) and may reflect suboptimal health. Fatty Liver Haemorrhagic Syndrome (FLHS) is mostly observed in laying hens and affects egg production and hen performance. The aim of this study was to investigate the relationships of FE and BW with organ characteristics, liver composition and incidence of FLHS of 150 individually housed ISA Brown hens ranked on the basis of feed conversion ratio (FCR) attained from early lay. At 45 weeks, 10 birds per FE group (HFE—High feed efficient; MFE—medium feed efficient; LFE—low feed efficient) were randomly selected and euthanized. Hen BW was positively associated with feed intake and FCR. The HFE hens had a lower abdominal fat pad and liver weight compared to LFE hens. FLHS lesion score was higher (worse) in the LFE than HFE hen group and was moderately positively associated with BW and abdominal fat pad, but strongly positively associated with liver weight. Liver pathology of LFE hens showed hepatocytes with abnormal retention of lipids causing distended cytoplasmic vacuoles compared to the HFE hens. Hens which exhibited poorer FE in early lay had heavier abdominal fat pads, heavier, fatter livers and were more prone to FLHS.
CannaCount: an improved metric for quantifying estimates of maximum possible cannabinoid exposure
Authors: Lambros Ashley M. , Sagar Kelly A. , Dahlgren M. Kathryn , Kosereisoglu Deniz , El-Abboud Celine , Smith Rosemary T. , Gruber Staci A.
Published: April 2023

Increasing numbers of individuals have access to cannabinoid-based products containing various amounts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and other cannabinoids. Exposure to specific cannabinoids likely influences outcomes; however, current methods for quantifying cannabis exposure do not account for the cannabinoid concentrations of the products used. We developed CannaCount, an examiner-driven metric that quantifies estimated maximum possible cannabinoid exposure by accounting for variables related to cannabinoid concentration, duration, frequency, and quantity of use. To demonstrate feasibility and applicability, CannaCount was used to quantify estimated maximum THC and CBD exposure in 60 medical cannabis patients enrolled in a two-year, longitudinal, observational study. Medical cannabis patients reported using a variety of product types and routes of administration. Calculating estimated exposure to THC and CBD was possible for the majority of study visits, and the ability to generate estimated cannabinoid exposure improved over time, likely a function of improved product labeling, laboratory testing, and more informed consumers. CannaCount is the first metric to provide estimated maximum possible exposure to individual cannabinoids based on actual cannabinoid concentrations. This metric will ultimately facilitate cross-study comparisons and can provide researchers and clinicians with detailed information regarding exposure to specific cannabinoids, which will likely have significant clinical impact.
CryoFIB milling large tissue samples for cryo-electron tomography
Authors: Wang Sihan , Zhou Heng , Chen Wei , Jiang Yifeng , Yan Xuzhen , You Hong , Li Xueming
Published: April 2023

Cryo-electron tomography (cryoET) is a powerful tool for exploring the molecular structure of large organisms. However, technical challenges still limit cryoET applications on large samples. In particular, localization and cutting out objects of interest from a large tissue sample are still difficult steps. In this study, we report a sample thinning strategy and workflow for tissue samples based on cryo-focused ion beam (cryoFIB) milling. This workflow provides a full solution for isolating objects of interest by starting from a millimeter-sized tissue sample and ending with hundred-nanometer-thin lamellae. The workflow involves sample fixation, pre-sectioning, a two-step milling strategy, and localization of the object of interest using cellular secondary electron imaging (CSEI). The milling strategy consists of two steps, a coarse milling step to improve the milling efficiency, followed by a fine milling step. The two-step milling creates a furrow–ridge structure with an additional conductive Pt layer to reduce the beam-induced charging issue. CSEI is highlighted in the workflow, which provides on-the-fly localization during cryoFIB milling. Tests of the complete workflow were conducted to demonstrate the high efficiency and high feasibility of the proposed method.
Prediction of Fishman’s skeletal maturity indicators using artificial intelligence
Authors: Kim Harim , Kim Cheol-Soon , Lee Ji-Min , Lee Jae Joon , Lee Jiyeon , Kim Jung-Suk , Choi Sung-Hwan
Published: April 2023

The present study aimed to evaluate the performance of automated skeletal maturation assessment system for Fishman’s skeletal maturity indicators (SMI) for the use in dental fields. Skeletal maturity is particularly important in orthodontics for the determination of treatment timing and method. SMI is widely used for this purpose, as it is less time-consuming and practical in clinical use compared to other methods. Thus, the existing automated skeletal age assessment system based on Greulich and Pyle and Tanner-Whitehouse3 methods was further developed to include SMI using artificial intelligence. This hybrid SMI-modified system consists of three major steps: (1) automated detection of region of interest; (2) automated evaluation of skeletal maturity of each region; and (3) SMI stage mapping. The primary validation was carried out using a dataset of 2593 hand-wrist radiographs, and the SMI mapping algorithm was adjusted accordingly. The performance of the final system was evaluated on a test dataset of 711 hand-wrist radiographs from a different institution. The system achieved a prediction accuracy of 0.772 and mean absolute error and root mean square error of 0.27 and 0.604, respectively, indicating a clinically reliable performance. Thus, it can be used to improve clinical efficiency and reproducibility of SMI prediction.
Validating the APACHE IV score in predicting length of stay in the intensive care unit among patients with sepsis
Authors: Zangmo Kinley , Khwannimit Bodin
Published: April 2023

The Acute Physiology and Chronic Health Evaluation (APACHE) IV model can predict the intensive care unit (ICU) length of stay (LOS) in critically ill patients. Thus, this study aimed to validate the performance of the APACHE IV score in predicting ICU LOS among patients with sepsis. This retrospective study was conducted in the medical ICU of a tertiary university between 2017 and 2020. A total of 1,039 sepsis patients were enrolled. Patients with an ICU stay of 1 and > 3 days accounted for 20.1% and 43.9%. The overall observed and APACHE IV predicted ICU LOS were 6.3 ± 6.5 and 6.8 ± 6.5, respectively. The APACHE IV slightly over-predicted ICU LOS with standardized length of stay ratio 0.95 (95% CI 0.89–1.02). The predicted ICU LOS based on the APACHE IV score was statistically longer than the observed ICU LOS (p < 0.001) and were poorly correlated (R2 = 0.02, p < 0.001), especially in patients with a lower severity of illness. In conclusions the APACHE IV model poorly predicted ICU LOS in patients with sepsis. The APACHE IV score needs to be modified or we need to make a new specific model to predict ICU stays in patients with sepsis.
Photocontrolled RAFT polymerization: past, present, and future
Authors: Lee Yungyeong , Boyer Cyrille , Kwon Min Sang
Published: April 2023

This review summarizes the development, progress, applications, and future challenges of photocontrolled reversible addition–fragmentation chain transfer (RAFT) polymerization, which has attracted considerable attention in the past several years.
Rapid exocytosis kinetics measured by amperometry within volcano microelectrodes
Authors: Maïno Nicolas , Bertsch Arnaud , Renaud Philippe
Published: April 2023

Exocytosis from PC12 cells measured within volcano microelectrodes proceeds with faster kinetic than reported with other amperometric methods. We investigated this finding and propose an explanation relying on the topography of the sensor.
Distinguishing the mechanism of electrochemical carboxylation in CO2eXpanded Electrolytes
Authors: Stalcup Matthew A. , Nilles Christian K. , Subramaniam Bala , Blakemore James D. , Leonard Kevin C.
Published: April 2023

We shed light on the mechanism and rate-determining steps of the electrochemical carboxylation of acetophenone as a function of CO2concentration by using a robust finite element analysis model that incorporates each reaction step.
Impact of the core on the inter-branch exciton exchange in dendrimers
Authors: Bonilla Valeria , Freixas Victor M. , Fernandez-Alberti Sebastian , Galindo Johan Fabian
Published: April 2023

Multichromophore dendrimers are light-harvesting materials. Their application in photovoltaic processes depends on the energy transfer mechanism, where a small core promotes higher delocalization of the exciton.
Metalloporphyrins: their multitalented nature as observed in multi-metal complex systems
Authors: Kuramochi Yusuke , Satake Akiharu
Published: April 2023

Combination produces new findings in multi-metal complexes of metalloporphyrins.
In situLu–Hf geochronology with LA-ICP-MS/MS analysis
Authors: Wu Shitou , Wang Hao , Yang Yueheng , Niu Junlong , Lan Zhongwu , Zhang Liangliang , Huang Chao , Xie Liewen , Xu Lei , Yang Jinhui , Wu Fuyuan
Published: April 2023

In situLu–Hf geochronology is useful for constraining the evolution of geological systems.
Mn–Zr composite oxides as efficient catalysts for catalytic oxidation of vinyl chloride
Authors: Deng Zhiyong , Wang Mingju , Zhang Hongliang , Zhang Chuanhui
Published: April 2023

Mn–Zr composite oxides with variable molar ratios of Mn/Zr were prepared by a citrate sol–gel method for catalytic oxidation of vinyl chloride. The structure–activity relationship was studied by numerous characterization and experimental approaches.
Mechanism of pH influence on aptamer binding with Cd2+ revealed by molecular dynamics simulation
Authors: Yuan Hongen , Wu Xiuxiu , Ren Xingfa , Xue Bin , Qiu Wenjie , Nong Dinghui , Yang Tao , Xu Fei
Published: April 2023

pH decrease changes the interbase hydrogen bonds and negative charge of the aptamer, destroying its affinity for Cd2+.
Rapid and scalable synthesis of sulfur quantum dots through ozone etching: photoluminescence and FRET-mediated Co2+ sensing
Authors: Reji R. V. , Biju V.
Published: April 2023

A novel ozone-assisted strategy for the rapid synthesis of luminescent sulfur quantum dots (SQDs). First report on utilizing SQDs as a fluorescent probe for the sensing of Co2+ based on the FRET mechanism.
Phases of surface-confined trivalent colloidal particles
Authors: Swinkels Piet J. M. , Gong Zhe , Sacanna Stefano , Noya Eva G. , Schall Peter
Published: April 2023

We assemble pseudo-trivalent patchy particles confined to a plane into honeycomb, triangular and amorphous phases, and elucidate the phase diagram by combining the experiments with simulations.
The construction of CRISPR/Cas9-mediated FRET 16S rDNA sensor for detection of Mycobacterium tuberculosis
Authors: Zhou Ming , Li Xin , Wen Herui , Huang Bin , Ren Jiali , Zhang Jialin
Published: April 2023

The construction of the CRISPR/Cas9-mediated FRET sensor for the highly sensitive detection of M. tuberculosis.
VITAS, a sensitivein vivoselection assay to discover enzymes producing antiviral natural products
Authors: Alharbi Aws Fahd , Kim Hayun , Chumroo Dhirish , Ji Yuxuan , Hakil Mohammed , Ebrahimi Kourosh H.
Published: April 2023

We demonstrate the VITAS (Viral polymerase-Inhibition Toxin-Associated Selection) assay for thein vivoselection and discovery of enzymes producing one of the largest groups of antivirals, namely antiviral nucleotide analogues (ANAs).
Combining ligand-enhanced backdonation and steric shielding to stabilize a mono-substituted Au(i) carbene
Authors: Vesseur David , Miqueu Karinne , Bourissou Didier
Published: April 2023

A P^P-ligated Au(i) aryl carbene stable up to −10 °C.
Syntheses of heterotriptycenes and their Pt complexes that emit circularly polarised fluorescence and phosphorescence
Authors: Inoue Ryo , Furumoto Kyosuke , Morisaki Yasuhiro
Published: April 2023

Optically active 2-azatriptycenes and their platinum(ii) complexes were synthesized. The molecules could be employed as efficient emitters exhibiting circularly polarized fluorescence and phosphorescence.
Applying Na/Co(ii) bimetallic partnerships to promote multiple Co–H exchanges in polyfluoroarenes
Authors: Logallo Alessandra , Hevia Eva
Published: April 2023

Using a bimetallic base combining Na and Co(ii) enables the regioselective sodium-mediated di-cobaltation of fluoroarenes as well as transforming the three C–F bonds of trifluorobenzene into C–N bonds via a cascade activation process.
Electrochemical deoxygenative arylation of aldehydes and ketones
Authors: Li Meng , Tian Yue , Sun Kunhui , Xu Zhimin , Tian Lifang , Wang Yahui
Published: April 2023

The construction of diaryl alkanes from aromatic aldehydes or ketones with electron-deficient arenes is achieved in the presence of trivalent phosphine under electrochemical conditions.