bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole Genome Sequencing Applications in Hospital Epidemiology and Infection Prevention
Authors: Doll Michelle , Bryson Alexandra L. , Palmore Tara N.
Published: January 2024

Purpose of Review

Whole genome sequencing is increasingly used in epidemiologic surveillance in healthcare centers, shedding new light on the transmission of healthcare-associated infections. As processing times for these technologies shorten, the ability to use sequencing data for targeted infection prevention is seemingly attainable and of great interest to infection prevention practitioners in an era of limited resources.

Recent Findings

Common healthcare-associated infections such as C. difficile and methicillin-resistant Staphylococcus aureus may be acquired in diverse settings including the community, rather than direct patient-to-patient transmission as previously thought. This along with the emergence of new organisms such as Candida auris may indicate that infection prevention interventions should be all-encompassing rather than organism-specific in focus.

Whole genome sequencing technologies are providing a level of detail in assessing organism relatedness that is changing our understanding of the transmission of infections in healthcare settings and may impact infection prevention strategies in the future.
The Emotional Burden of Loneliness and its Association with Mental Health Outcomes
Authors: Lazuras Lambros , Ypsilanti Antonia , Mullings Emma
Published: January 2024

Background

The present study examined, for the first time, the emotional burden of loneliness on dimensions of emotional valence and arousal, and its association with mental health outcomes.

Method

A cross-sectional design was used, and data were collected from 503 adults across the UK with an online survey. Measures included socio-demographic characteristics, self-reported measures of loneliness and social isolation, affective ratings (i.e., valence and arousal) of loneliness experiences, and symptoms of depression and anxiety as mental health outcomes.

Results

The emotional burden of loneliness differed significantly across groups with differing loneliness experiences, and females scored significantly higher in the emotional burden of loneliness than males. The emotional burden of loneliness was associated with both depression and anxiety symptoms, and respectively added 4.7% and 6.2% of the variance, on top of measures of loneliness frequency and social isolation.

Conclusions

Measuring the valence and arousal dimensions of loneliness experiences advances our understanding of loneliness experiences and its association with mental health outcomes. The theoretical, methodological, and practical implications of our study are discussed.
Using the Listening2Faces App with Three Young Adults with Autism: A Feasibility Study
Authors: Baron Alisa , Harwood Vanessa , Woodard Cooper , Anderson Kaitlyn , Fernandes Barbara , Sullivan Jessica , Irwin Julia
Published: January 2024

Objectives

Listening2Faces (L2F) is a therapeutic, application-based training program designed to improve audiovisual speech perception for persons with communication disorders. The purpose of this research was to investigate the feasibility of using the L2F application with young adults with autism and complex communication needs.

Methods

Three young adults with autism and complex communication needs completed baseline assessments and participated in training sessions within the L2F application. Behavioral supports, including the use of cognitive picture rehearsal, were used to support engagement with the L2F application. Descriptive statistics were used to provide (1) an overview of the level of participation in L2F application with the use of behavioral supports and (2) general performance on L2F application for each participant.

Results

All three participants completed the initial auditory noise assessment (ANA) as well as 8 or more levels of the L2F application with varying accuracy levels. One participant completed the entire L2F program successfully. Several behavioral supports were used to facilitate participation; however, each individual demonstrated varied levels of engagement with the application.

Conclusions

The L2F application may be a viable intervention tool to support audiovisual speech perception in persons with complex communication needs within a school-based setting. A review of behavioral supports and possible beneficial modifications to the L2F application for persons with complex communication needs are discussed.
EFESTO-2: European Flexible Heat Shields Advanced TPS Design and Tests for Future In-Orbit Demonstration-2
Authors: Guidotti Giuseppe , Princi Alessandro , Gutierrez-Briceno Jaime , Trovarelli Federico , Governale Giuseppe , Viola Nicole , Dietlein Ingrid , Callsen Steffen , Bergmann Kevin , Zhai Junnai , Gawehn Thomas , Gardi Roberto , Tiseo Barbara , Prevereaud Ysolde , Dauvois Yann , Gambacciani Giovanni , Dammacco Giada
Published: January 2024

EFESTO-2 is an EU-funded project under Horizon Europe that aims to enhance European expertise in Inflatable Heat Shields (IHS). Building on the achievements of the previous EFESTO project (H2020 funds No 821801), EFESTO-2 focuses on advancing key IHS technologies to increase their Technology Readiness Level (TRL). The project pillars include analysing the business case for IHS applications, exploring additional aspects of IHS, improving tools and models and establishing a development roadmap for IHS systems. This paper outlines the project objectives and plan, highlighting ongoing and future activities for the next 2 years, positioning it within the European re-entry technology roadmap. This project has received funding from the European Union's Horizon Europe program (grant agreement No 1010811041).
Colonialism, World Literature, and the Making of the Modern Culture of Letters
Authors: Bhattacharya Baidik
Published: January 2024

In a radical and ambitious reconceptualization of the field, this book argues that global literary culture since the eighteenth century was fundamentally shaped by colonial histories. It offers a comprehensive account of the colonial inception of the literary sovereign – how the realm of literature was thought to be separate from history and politics – and then follows that narrative through a wide array of different cultures, multilingual archives, and geographical locations. Providing close studies of colonial archives, German philosophy of aesthetics, French realist novels, and English literary history, this book shows how colonialism shaped and reshaped modern literary cultures in decisive ways. It breaks fresh ground across disciplines such as literary studies, anthropology, history, and philosophy, and invites one to rethink the history of literature in a new light.
Knowledge, Attitude and Awareness of Oman Emergency Physicians and Residents Regarding Radiation Emergencies
Authors: Al-Sulaimani Suad K. , Al-Balushi Hassan , AL-Balushi Aaisha , Panchatcharam Sathiya Murthi , AL-Shamsi Mohamed , Kazzi Ziad , Alhatali Badria
Published: January 2024

Objective:

Radiological emergency preparedness and response are increasingly acknowledged as vital components of both emergency readiness and public health. Previous studies have shown that medical providers feel unprepared to respond to radiation incidents. The existing level of knowledge, attitudes, and awareness held by emergency medicine residents and physicians in Oman, remain unexplored. This study aims to evaluate the knowledge, attitude, and awareness level of emergency residents and physicians in Oman regarding the management of radiation emergencies.

Methods:

An electronic survey was distributed to 44 emergency residents and 57 emergency physicians.

Results:

The response rate was 62.7% (N = 69/110). Notably, 62% reported no prior engagement in radiation emergency training. The majority of participants had neither employed nor received training in operating radiation detection devices. A significant gap in knowledge emerged, with the median self-reported knowledge score of 50/100. The majority of participants (59%) expressed a need for educational programs and materials.

Conclusion:

Our findings underscore the imperative for enhanced training in radiological incident preparedness for emergency medicine residents and physicians in Oman. The study reveals a clear necessity to bridge the existing gaps in knowledge and attitudes to bolster the readiness of health-care professionals to respond effectively to radiation emergencies.
Influence of small inertia on Jeffery orbits
Authors: Di Giusto Davide , Bergougnoux Laurence , Marchioli Cristian , Guazzelli Élisabeth
Published: January 2024

We experimentally investigate the rotational dynamics of neutrally buoyant axisymmetric particles in a simple shear flow. A custom-built shearing cell and a multi-view shape-reconstruction method are used to obtain direct measurements of the orientation and period of rotation of particles having oblate and prolate shapes (such as spheroids and cylinders) of varying aspect ratios. By systematically changing the viscosity of the fluid, we examine the effect of inertia (which may be originated from either phase) on the dynamical behaviour of these suspended particles up to a particle Reynolds number of approximately one. While no significant effect on the period of rotation is found in this small-inertia regime, a systematic drift among several rotations toward limiting stable orbits is observed. Prolate particles are seen to drift towards the tumbling orbit in the plane of shear, whereas oblate particles are driven either to the tumbling or to the vorticity-aligned spinning orbits, depending on their initial orientation. These results are compared with recent small-inertia asymptotic theories, assessing their range of validity, as well as to numerical simulations in the small-inertia regime for both prolate and oblate particles.
The “MH17” judgment and its legal implications for the International Court of Justice's ruling in Ukraine v. Russia: a critical appraisal
Authors: Musmeci Daniele
Published: January 2024

On November 17, 2022, the Dutch District Court of The Hague found three persons liable in connection with the downing of Malaysia Airlines Flight 17, which occurred in the breakaway oblast of Donetsk in July 2014. Drawing on this judgment, the present essay examines whether the Russian Federation can be regarded as a State actively involved in this incident with a view to investigating to what extent it exercised “overall control” over the Donetsk People's Republic's separatists. Afterwards, the analysis is framed in the context of the wider legal dispute between Ukraine and the Russian Federation before the International Court of Justice, where the former maintained, inter alia, that the latter failed to honour its obligation under the 1999 International Convention for the Suppression of the Financing of Terrorism—specifically, by providing the separatists with the “fund” (i.e., a BUK TELAR) that forced the aircraft to crash. Ultimately, the legal implications of the findings are assessed to foresee the outcome of the International Court of Justice's decision on the merits.
Structural bioinformatics studies of six human ABC transporters and their AlphaFold2-predicted water-soluble QTY variants
Authors: Pan Emily , Tao Fei , Smorodina Eva , Zhang Shuguang
Published: January 2024

Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants. In the native structures, there are hydrophobic amino acids such as leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in the transmembrane alpha helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Therefore, these QTY variants become water soluble. We also present the superposed structures of native ABC transporters and their water-soluble QTY variants. The superposed structures show remarkable similarity with root mean square deviations between 1.064 and 3.413 Å despite significant (41.90–54.33%) changes to the protein sequence of the transmembrane domains. We also show the differences in hydrophobicity patches between the native ABC transporters and their QTY variants. We explain the rationale behind why the QTY membrane protein variants become water soluble. Our structural bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices and will likely further stimulate designs of water-soluble multispan transmembrane proteins and other aggregated proteins. The water-soluble ABC transporters may be useful as soluble antigens to generate therapeutic monoclonal antibodies for combating multidrug resistance in clinics.
Association between glycaemic control and malnutrition in older adults with type 2 diabetes mellitus: a cross-sectional study
Authors: Thaenpramun Rattiyaphon , Komolsuradej Narucha , Buathong Napakkawat , Srikrajang Siwaluk
Published: January 2024

Malnutrition is a major problem among older adults with type 2 diabetes mellitus (T2DM). Some studies suggest that well glycaemic control increases the risk of frailty due to reduced intake. Therefore, it could be hypothesised that adequate glycaemic controlled patients may be at risk of malnutrition. This study aimed to examine, in older adults with T2DM, the association between adequate glycaemic control and malnutrition as well as identify the risk factors for malnutrition. Data including general characteristics, health status, depression, functional abilities, cognition and nutrition status were analysed. Poor nutritional status is defined as participants assessed with the Mini Nutritional Assessment as being at risk of malnutrition or malnourished. Adequate glycaemic control refers to an HbA1c level that meets the target base in the American Diabetes Association 2022 guidelines with individualised criteria. There were 287 participants with a median (interquartile range) age of 64 (61–70) years, a prevalence of poor nutrition, 15 %, and adequate glycaemic control, 83·6 %. This study found no association between adequate glycaemic control and poor nutrition (P = 0·67). The factors associated with poor nutritional status were low monthly income (adjusted OR (AOR) 4·66, 95 % CI 1·28, 16·98 for income < £118 and AOR 7·80, 95 % CI 1·74, 34·89 for income £118–355), unemployment (AOR 4·23, 95 % CI 1·51, 11·85) and cognitive impairment (AOR 5·28, 95 % CI 1·56, 17·93). These findings support the notion that older adults with T2DM should be encouraged to maintain adequate glycaemic control without concern for malnutrition, especially those who have low income, unemployment or decreased cognitive functions.
A theory of plural constituent power for federal systems
Authors: Aroney Nicholas , Duke George , Tierney Stephen
Published: January 2024

Federations present difficulties for prevailing theories of constituent power, which usually attribute ultimate constitution-making authority to a singular people. This article examines how a ‘pluralized’ constituent power functions in federal systems. It argues that the operation of plural constituent power in federations reflects a distinctive model of constitutional formation according to which a ‘polity of polities’ is established and sustained through the maintenance of a tension between plurality and unity.
Waria, Worship, and Welfare: Exploring Trans Women's Conditions of Precarity Amidst COVID-19 in Yogyakarta, Indonesia
Authors: Fadhlina Amirah
Published: January 2024

Due to the widescale impact of 212 Action's anti-blasphemy campaign in 2016, there has been a spike in Islamic moral panic discourse and religiously driven vigilante attacks targeting LGBTQ citizens in Indonesia. Simultaneously, gender nonconforming citizens who have gained social recognition, like a segment of transwomen communities called waria, have continued to carve out alternative spaces and subvert anti-LGBTQ discourse. Waria activists in Yogyakarta, for instance, created the world's first trans-led Islamic boarding school in 2008. Despite suffering attacks from Front Jihad Islam members in 2016, the school has managed to reopen and even to expand its services further for waria communities. In capturing the recent trajectory of activism at the waria Islamic boarding school, this article highlights the multifaceted conditions of precarity faced by Muslim waria in Yogyakarta in the wake of the COVID-19 pandemic. Presenting ethnographic data from the summer of 2022, this paper argues that since the pandemic, in addition to demanding the right to practice Islam, Muslim waria activists have increasingly focused on wellbeing (e.g., food sustainability and emergency shelter) in their rights advocacy in Yogyakarta. Merely perceiving the Islamic boarding school as a site of religious activism diminishes a fundamental aspect of its current grassroots efforts, which is to gain access to basic welfare — a key strategy for the survival of LGBTQ citizens in Yogyakarta and beyond. With greater socioeconomic and psychological uncertainties sparked by COVID-19, human rights for waria and what holistic security means for Indonesian LGBTQ citizens, must also be carefully understood through a lens of health, welfare, and wellbeing.
Infrared Radiative Effects of Increasing CO2 and CH4 on the Atmosphere in Antarctica Compared to the Arctic
Authors: Notholt Justus , Schmithüsen Holger , Buschmann Matthias , Kleidon Axel
Published: January 2024

We simulated the seasonal temperature evolution in the atmosphere of Antarctica and the Arctic focusing on infrared processes. Contributions by other processes were parametrized and kept fixed throughout the simulations. The model was run for current CO2 and CH4 and for doubled concentrations. For doubling CH4 the warming in Antarctica is restricted to the lowest few hundred meters above the surface while in the Arctic we find a warming in the whole troposphere. We find that the amount of water is the main driver for the differences between both polar regions. When increasing both, CO2 and CH4 from pre‐industrial values to current concentrations, and averaged over the whole troposphere, we find a warming of 0.42 K for the Arctic and a slight cooling of 0.01 K for Antarctica. Our results contribute to the understanding of the lack of warming seen in Antarctica throughout the last decades.
Co‐Occurring Extremes of Fine Particulate Matter (PM2.5) and Ground‐Level Ozone in the Summer of Southern China
Authors: Lyu Yan , Wu Haonan , Liu Xiaoran , Han Fuliang , Lv Fengmao , Pang Xiaobing , Chen Jianmin
Published: January 2024

Concurrent pollution of fine particulate matter (PM2.5) and ozone has been increasingly reported in China recently. Here, we further confirm widespread co‐occurring summertime PM2.5‐ozone extremes in southern China. Annual‐average frequency of co‐occurrence is above 50% from 2015 to 2022, especially in Pearl River Delta region (72 ± 12%). The spatial extent (city numbers) and temporal persistence (co‐occurrence days) for cities with co‐occurrence frequency >50% increase at a rate of two cities/year and 14 days/year, respectively. We further identify typical synoptic conditions (e.g., typhoon periphery circulation, West Pacific subtropical high) conducive to widespread co‐occurrence. Through combining multi‐source data, Random Forest model well predicts PM2.5‐ozone co‐occurrence and identifies common precursors (e.g., volatile organic compounds) as important variables. Finally, we postulate co‐occurrence is linked to synoptic conditions and secondary generation of PM2.5‐ozone from shared precursors. Our results suggest high potentials for co‐occurring PM2.5‐ozone extremes in southern China and control strategies on common precursors to mitigate concurrent pollution.
Apatite Textures, Elemental and Isotopic Compositions Unmask the Homogenizing Process in Silicic Magma Chambers
Authors: Xu Jian , Xia Xiao‐Ping , Wang Qiang , Spencer Christopher J. , Zhang Le , Zhu Xin
Published: January 2024

Silicic magmas are the most viscous of all magmas, however some granitic plutons display remarkably homogeneous compositions, which contradicts the hypothesis that mechanical mixing is the main homogenizing process in the magma chamber. Thus much remains controversial about the mechanisms responsible for the homogeneities of silicic plutons. Here, we present textural observations, elemental mapping, and in situ elemental and Nd‐O isotopic data of apatites from the compositionally homogeneous Late Permian Yuanyang A‐type granitic pluton (SW Yunnan, South China). Apatite grains display oscillatory chemical zonation and resorption‐precipitation texture, suggesting incremental growth dominated by co‐genetic magma batches injection. The intra‐/inter‐grain core to rim elemental and Nd‐O isotopic variations imply crystal transfer and crystallization from different melt domains within the crystal mush. We propose that rejuvenation events associated with hotter cogenetic intermediate magma batch injection has induced crystal mush reactivation and convective stirring in silicic magma chambers, thereby homogenizing the entire reservoir.
Under‐Ice Mixed Layers and the Regulation of Early Spring Phytoplankton Growth in the Southern Ocean
Authors: Smith Walker O. , Zhong Yisen
Published: January 2024

Under‐ice phytoplankton “blooms” have been observed in the Southern Ocean, although irradiance is extremely low and vertical mixing is assumed to be deep. Most under‐ice data have been collected using Argo floats, as research expeditions during austral fall and winter are limited. Hydrographic measurements under dense ice cover indicate that vertical mixing in weakly stratified systems may be less than previously suggested, and that the accepted determinations of mixed layer depths are inappropriate in regions with extremely weak stratification, such as those under ice. Vertical gradients in density suggest that mixed layers in the Ross Sea in early October are not extremely deep; furthermore, while phytoplankton biomass is low, it has begun to accumulate under ice. Growth rates indicate that phytoplankton growth in the Ross Sea begins in early September. Extending the period of growth may have substantial impacts on carbon biogeochemistry and food web energetics in ice‐covered waters.
Thermal Equation of State and Structural Evolution of Al‐Bearing Bridgmanite
Authors: Criniti Giacomo , Boffa Ballaran Tiziana , Kurnosov Alexander , Liu Zhaodong , Glazyrin Konstantin , Merlini Marco , Hanfland Michael , Frost Daniel J.
Published: January 2024

(Mg, Fe, Al)(Si, Al)O3 bridgmanite is the most abundant mineral of Earth′s lower mantle. Al is incorporated in the crystal structure of bridgmanite through the Fe3+AlO3 and AlAlO3 charge coupled (CC) mechanisms, and the MgAlO2.5 oxygen vacancy (OV) mechanism. Oxygen vacancies are believed to cause a substantial decrease of the bulk modulus of aluminous bridgmanite based on first‐principles calculations on the MgAlO2.5 end‐member. However, there is no conclusive experimental evidence supporting this hypothesis due to the uncertainties on the chemical composition, crystal chemistry, and/or high‐pressure behavior of samples analyzed in previous studies. Here, we synthesized high‐quality single crystals of bridgmanite in the MgO–AlO1.5–SiO2 system with different bulk Al contents and degrees of CC and OV substitutions. Suitable crystals with different compositions were loaded in resistively heated diamond anvil cells and analyzed by synchrotron X‐ray diffraction at pressures up to approximately 80 GPa at room temperature and 35 GPa at temperatures up to 1,000 K. Single‐crystal structural refinements at high pressure show that the compressibility of bridgmanite is mainly controlled by Al–Si substitution in the octahedral site and that oxygen vacancies in bridgmanite have no detectable effect on the bulk modulus in the compositional range investigated here, which is that relevant to a pyrolytic lower mantle. The proportion of oxygen vacancies in Al‐bearing bridgmanite has been calculated using a thermodynamic model constrained using experimental data at 27 GPa and 2,000 K for an Fe‐free system and extrapolated to pressures equivalent to 1,250 km depth using the thermoelastic parameters of Al‐bearing bridgmanite determined in this study.
Climate Response to Vegetation Removal on Different Continents
Authors: Guo Jiaqi , Liu Yonggang , Hu Yongyun
Published: January 2024

Understanding the climatic effect of vegetation in different regions is important for understanding the climate impact of vegetation change in both the past and future. Here we quantify the climate response to vegetation removal on each continent, except Antarctica, using CESM1.2.2 under pre‐industrial climate condition, and the associated mechanisms are analyzed. Results show that removing the global vegetation lowers the global mean surface temperature (GMST) by 3.65°C. Removing vegetation over Eurasia and North America lowers GMST by 1.83°C and 0.88°C, respectively. They also reduce the global precipitation, but at a much slower rate than that would be caused in the CO2 perturbation experiments. Removing vegetation on all other continents has negligible influence on global climate, but has significant local warming effect due to weakening of evapotranspiration. The removal of low‐latitude vegetation tends to reduce the local precipitation, but increase the precipitation over nearby oceans, especially to the west. The feedbacks of thermodynamic sea ice and oceans amplify the initial direct cooling due to vegetation removal by a factor of >5. The response of ocean circulation has a negligible impact on GMST, but has a significant influence on the pattern of temperature changes by redistributing heat. Without the ocean‐circulation feedback, the Northern Hemisphere would be 1.30°C colder while the Southern Hemisphere 1.17°C warmer when the global vegetation is removed.
Trends in Seasonal Mean Speciated Aerosol Composition in Remote Areas of the United States From 2000 Through 2021
Authors: Hand J. L. , Prenni A. J. , Schichtel B. A.
Published: January 2024

Large reductions in anthropogenic emissions of particulate matter and its precursor emissions have occurred since the enactment of the Clean Air Act Amendments of 1990. The Interagency Monitoring of Protected Visual Environments network has measured PM2.5 gravimetric mass (mass of particles with aerodynamic diameters less than 2.5 μm, also referred to here as fine mass, “FM”) and speciated PM2.5 aerosol composition at remote sites since 1988. Measured species include inorganic anions such as sulfate, nitrate, and chloride, carbonaceous aerosols such as organic (OC) and elemental carbon (EC), and elemental concentrations used to estimate fine dust (FD). Trends in seasonal and annual mean mass concentrations were calculated from 2000 through 2021, a period that includes the largest reductions in emissions. On average, annual mean FM at remote sites in the continental United States has decreased at a rate of −1.8% yr−1. This reduction is largely due to annual mean trends in sulfate (−6.1% yr−1), nitrate (−2.7% yr−1), EC (−2.2% yr−1), FD (−1.3% yr−1), and OC (−0.9% yr−1), although the OC annual mean trend was insignificant. Seasonal and regional mean FM trends varied significantly, with strong reductions in the East in all seasons due to sulfate reductions, and flat and insignificant trends in summer and fall in the West due to the influence of biomass burning emissions on OC trends. Evaluating regional and seasonal mean trends in aerosol composition helps identify sources that continue to adversely impact air quality and hinder progress in FM reductions due to successful regulatory activity.
A transcriptomic analysis in mice following a single dose of ibogaine identifies new potential therapeutic targets
Authors: Biosca-Brull Judit , Ona Genis , Alarcón-Franco Lineth , Colomina Maria Teresa
Published: January 2024

Ibogaine (IBO) is an atypical psychedelic with a complex mechanism of action. To date, the mechanisms that may underlie its anti-addictive effects are still not defined. This study aims to identify changes in gene expression induced by a single oral dose of IBO in the cortex of mice by means of a transcriptomic analysis for the first time. Our results showed significant alterations in gene expression in mouse frontal cortex samples 4 h after a single oral dose of IBO. Specifically, genes involved in hormonal pathways and synaptogenesis exhibited upregulation, while genes associated with apoptotic processes and endosomal transports showed downregulation. The findings were further corroborated through quantitative polymerase chain reaction (qPCR) analysis. However, the validation of gene expression related to hormonal pathways did not entirely align with the transcriptomic analysis results, possibly due to the brain region from which tissue was collected. Sex differences were observed, with female mice displaying more pronounced alterations in gene expression after IBO treatment. High variability was observed across individual animals. However, this study represents a significant advancement in comprehending IBO’s molecular actions. The findings highlight the influence of IBO on gene expression, particularly on hormonal pathways, synaptogenesis, apoptotic processes, and endosomal transports. The identification of sex differences underscores the importance of considering sex as a potential factor influencing IBO’s effects. Further research to assess different time points after IBO exposure is warranted.
DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts
Authors: Shumliakivska Mariana , Luxán Guillermo , Hemmerling Inga , Scheller Marina , Li Xue , Müller-Tidow Carsten , Schuhmacher Bianca , Sun Zhengwu , Dendorfer Andreas , Debes Alisa , Glaser Simone-Franziska , Muhly-Reinholz Marion , Kirschbaum Klara , Hoffmann Jedrzej , Nagel Eike , Puntmann Valentina O. , Cremer Sebastian , Leuschner Florian , Abplanalp Wesley Tyler , John David , Zeiher Andreas M. , Dimmeler Stefanie
Published: January 2024

Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A), play a pivotal role in driving clonal hematopoiesis of indeterminate potential (CHIP), and are associated with unfavorable outcomes in patients suffering from heart failure (HF). However, the precise interactions between CHIP-mutated cells and other cardiac cell types remain unknown. Here, we identify fibroblasts as potential partners in interactions with CHIP-mutated monocytes. We used combined transcriptomic data derived from peripheral blood mononuclear cells of HF patients, both with and without CHIP, and cardiac tissue. We demonstrate that inactivation of DNMT3A in macrophages intensifies interactions with cardiac fibroblasts and increases cardiac fibrosis. DNMT3A inactivation amplifies the release of heparin-binding epidermal growth factor-like growth factor, thereby facilitating activation of cardiac fibroblasts. These findings identify a potential pathway of DNMT3A CHIP-driver mutations to the initiation and progression of HF and may also provide a compelling basis for the development of innovative anti-fibrotic strategies.
Site-selective protonation enables efficient carbon monoxide electroreduction to acetate
Authors: Wang Xinyue , Chen Yuanjun , Li Feng , Miao Rui Kai , Huang Jianan Erick , Zhao Zilin , Li Xiao-Yan , Dorakhan Roham , Chu Senlin , Wu Jinhong , Zheng Sixing , Ni Weiyan , Kim Dongha , Park Sungjin , Liang Yongxiang , Ozden Adnan , Ou Pengfei , Hou Yang , Sinton David , Sargent Edward H.
Published: January 2024

Electrosynthesis of acetate from CO offers the prospect of a low-carbon-intensity route to this valuable chemical––but only once sufficient selectivity, reaction rate and stability are realized. It is a high priority to achieve the protonation of the relevant intermediates in a controlled fashion, and to achieve this while suppressing the competing hydrogen evolution reaction (HER) and while steering multicarbon (C2+) products to a single valuable product––an example of which is acetate. Here we report interface engineering to achieve solid/liquid/gas triple-phase interface regulation, and we find that it leads to site-selective protonation of intermediates and the preferential stabilization of the ketene intermediates: this, we find, leads to improved selectivity and energy efficiency toward acetate. Once we further tune the catalyst composition and also optimize for interfacial water management, we achieve a cadmium-copper catalyst that shows an acetate Faradaic efficiency (FE) of 75% with ultralow HER (<0.2% H2 FE) at 150 mA cm−2. We develop a high-pressure membrane electrode assembly system to increase CO coverage by controlling gas reactant distribution and achieve 86% acetate FE simultaneous with an acetate full-cell energy efficiency (EE) of 32%, the highest energy efficiency reported in direct acetate electrosynthesis.
The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells
Authors: Liao Xiaofeng , Li Wenxue , Zhou Hongyue , Rajendran Barani Kumar , Li Ao , Ren Jingjing , Luan Yi , Calderwood David A. , Turk Benjamin , Tang Wenwen , Liu Yansheng , Wu Dianqing
Published: January 2024

CD8+ T cells play an important role in anti-tumor immunity. Better understanding of their regulation could advance cancer immunotherapies. Here we identify, via stepwise CRISPR-based screening, that CUL5 is a negative regulator of the core signaling pathways of CD8+ T cells. Knocking out CUL5 in mouse CD8+ T cells significantly improves their tumor growth inhibiting ability, with significant proteomic alterations that broadly enhance TCR and cytokine signaling and their effector functions. Chemical inhibition of neddylation required by CUL5 activation, also enhances CD8 effector activities with CUL5 validated as a major target. Mechanistically, CUL5, which is upregulated by TCR stimulation, interacts with the SOCS-box-containing protein PCMTD2 and inhibits TCR and IL2 signaling. Additionally, CTLA4 is markedly upregulated by CUL5 knockout, and its inactivation further enhances the anti-tumor effect of CUL5 KO. These results together reveal a negative regulatory mechanism for CD8+ T cells and have strong translational implications in cancer immunotherapy.
Molecular understanding of the critical role of alkali metal cations in initiating CO2 electroreduction on Cu(100) surface
Authors: Zhang Zhichao , Li Hengyu , Shao Yangfan , Gan Lin , Kang Feiyu , Duan Wenhui , Hansen Heine Anton , Li Jia
Published: January 2024

Molecular understanding of the solid–liquid interface is challenging but essential to elucidate the role of the environment on the kinetics of electrochemical reactions. Alkali metal cations (M+), as a vital component at the interface, are found to be necessary for the initiation of carbon dioxide reduction reaction (CO2RR) on coinage metals, and the activity and selectivity of CO2RR could be further enhanced with the cation changing from Li+ to Cs+, while the underlying mechanisms are not well understood. Herein, using ab initio molecular dynamics simulations with explicit solvation and enhanced sampling methods, we systematically investigate the role of M+ in CO2RR on Cu surface. A monotonically decreasing CO2 activation barrier is obtained from Li+ to Cs+, which is attributed to the different coordination abilities of M+ with *CO2. Furthermore, we show that the competing hydrogen evolution reaction must be considered simultaneously to understand the crucial role of alkali metal cations in CO2RR on Cu surfaces, where H+ is repelled from the interface and constrained by M+. Our results provide significant insights into the design of electrochemical environments and highlight the importance of explicitly including the solvation and competing reactions in theoretical simulations of CO2RR.
HLA class I peptide polymorphisms contribute to class II DQβ0603:DQα0103 antibody specificity
Authors: Shih N. Remi , Nong Thoa , Murphey Cathi , Lopez-Cepero Mayra , Nickerson Peter W. , Taupin Jean-luc , Devriese Magali , Nilsson Jakob , Matignon Marie-Benedicte , Bray Robert A. , Lee Jar-How
Published: January 2024

Antibodies reactive to human leukocyte antigens (HLA) represent a barrier for patients awaiting transplantation. Based on reactivity patterns in single-antigen bead (SAB) assays, various epitope matching algorithms have been proposed to improve transplant outcomes. However, some antibody reactivities cannot be explained by amino acid motifs, leading to uncertainty about their clinical relevance. Antibodies against the HLA class II molecule, DQβ0603:DQα0103, present in some candidates, represent one such example. Here, we show that peptides derived from amino acids 119-148 of the HLA class I heavy chain are bound to DQβ0603:DQα0103 proteins and contribute to antibody reactivity through an HLA-DM-dependent process. Moreover, antibody reactivity is impacted by the specific amino acid sequence presented. In summary, we demonstrate that polymorphic HLA class I peptides, bound to HLA class II proteins, can directly or indirectly be part of the antibody binding epitope. Our findings have potential important implications for the field of transplant immunology and for our understanding of adaptive immunity.
Machine learning assisted discovery of high-efficiency self-healing epoxy coating for corrosion protection
Authors: Liu Tong , Chen Zhuoyao , Yang Jingzhi , Ma Lingwei , Mol Arjan , Zhang Dawei
Published: January 2024

Machine learning is a powerful means for the rapid development of high-performance functional materials. In this study, we presented a machine learning workflow for predicting the corrosion resistance of a self-healing epoxy coating containing ZIF-8@Ca microfillers. The orthogonal Latin square method was used to investigate the effects of the molecular weight of the polyetheramine curing agent, molar ratio of polyetheramine to epoxy, molar content of the hydrogen bond unit (UPy-D400), and mass content of the solid microfillers (ZIF-8@Ca microfillers) on the low impedance modulus (lg|Z|0.01Hz) values of the scratched coatings, generating 32 initial datasets. The machine learning workflow was divided into two stages: In stage I, five models were compared and the random forest (RF) model was selected for the active learning. After 5 cycles of active learning, the RF model achieved good prediction accuracy: coefficient of determination (R2) = 0.709, mean absolute percentage error (MAPE) = 0.081, root mean square error (RMSE) = 0.685 (lg(Ω·cm2)). In stage II, the best coating formulation was identified by Bayesian optimization. Finally, the electrochemical impedance spectroscopy (EIS) results showed that compared with the intact coating ((4.63 ± 2.08) × 1011 Ω·cm2), the |Z|0.01Hz value of the repaired coating was as high as (4.40 ± 2.04) × 1011 Ω·cm2. Besides, the repaired coating showed minimal corrosion and 3.3% of adhesion loss after 60 days of neutral salt spray testing.
AMPKα2 regulates fasting-induced hyperketonemia by suppressing SCOT ubiquitination and degradation
Authors: Zhang Lingxue , Lu Yanqiao , An Junqing , Wu Yin , Liu Zhixue , Zou Ming-Hui
Published: January 2024

Ketone bodies serve as an energy source, especially in the absence of carbohydrates or in the extended exercise. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a crucial energy sensor that regulates lipid and glucose metabolism. However, whether AMPK regulates ketone metabolism in whole body is unclear even though AMPK regulates ketogenesis in liver. Prolonged resulted in a significant increase in blood and urine levels of ketone bodies in wild-type (WT) mice. Interestingly, fasting AMPKα2–/– and AMPKα1–/– mice exhibited significantly higher levels of ketone bodies in both blood and urine compared to fasting WT mice. BHB tolerance assays revealed that both AMPKα2–/– and AMPKα1–/– mice exhibited slower ketone consumption compared to WT mice, as indicated by higher blood BHB or urine BHB levels in the AMPKα2–/– and AMPKα1–/– mice even after the peak. Interestingly, fasting AMPKα2–/– and AMPKα1–/– mice exhibited significantly higher levels of ketone bodies in both blood and urine compared to fasting WT mice. . Specifically, AMPKα2ΔMusc mice showed approximately a twofold increase in blood BHB levels, and AMPKα2ΔMyo mice exhibited a 1.5-fold increase compared to their WT littermates after a 48-h fasting. However, blood BHB levels in AMPKα1ΔMusc and AMPKα1ΔMyo mice were as same as in WT mice. Notably, AMPKα2ΔMusc mice demonstrated a slower rate of BHB consumption in the BHB tolerance assay, whereas AMPKα1ΔMusc mice did not show such an effect. Declining rates of body weights and blood glucoses were similar among all the mice. Protein levels of SCOT, the rate-limiting enzyme of ketolysis, decreased in skeletal muscle of AMPKα2–/– mice. Moreover, SCOT protein ubiquitination increased in C2C12 cells either transfected with kinase-dead AMPKα2 or subjected to AMPKα2 inhibition. AMPKα2 physiologically binds and stabilizes SCOT, which is dependent on AMPKα2 activity.
A hierarchical approach for evaluating athlete performance with an application in elite basketball
Authors: de Paula Oliveira Thiago , Newell John
Published: January 2024

In this paper, we present the ON score for evaluating the performance of athletes and teams that includes a season-long evaluation system, a single-game evaluation, and an evaluation of an athlete’s overall contribution to their team. The approach used to calculate the ON score is based on mixed-effects regression models that take into account the hierarchical structure of the data and a principal component analysis to calculate athlete rating. We apply our methodology to a large dataset of National Basketball Association (NBA) games spanning four seasons from 2015–2016 to 2018–2019. Our model is validated using two systematic approaches, and our results demonstrate the reliability of our approach to calculate an athlete’s performance. This provides coaches, General Managers and player agents with a powerful tool to gain deeper insights into their players’ performance, make more informed decisions and ultimately improve team performance. Our methodology has several key advantages. First, by incorporating the hierarchical structure of the data, we can obtain valuable information about an athlete’s contribution within their team. Second, the use of principal component analysis allows us to calculate a single score, the ON score, that captures the overall performance of an athlete. Third, our approach is based on classical restricted likelihood methods, which makes the calculation faster than Bayesian methods typically requiring 1000 posterior samples. With our approach, coaches and managers can evaluate athletes’ performance throughout the season, compare athletes and teams over a year, and assess an athlete’s performance during a single game. Our methodology can also complement other ratings and box score metrics to provide a more comprehensive assessment of an athlete’s performance as our method uses the hierarchical nature of performance data (i.e. player nested within team over season) which is typically ignored in player rating systems. In summary, our methodology represents a significant contribution to the field of sports analytics and provides the foundation for future developments.
Larvicidal potential, antimicrobial properties and molecular docking analysis of Egyptian Mint (Mentha rotundifolia) against Culex pipiens L. (Diptera: Culicidae) and Midgut-borne Staphylococcus aureus
Authors: Abu-Hussien Samah H. , Hemdan Bahaa , Abd-Elhalim Basma T. , Aboul Fotouh Mohamed M. , Soliman Ahmed G. , Ghallab Youssef K. , Adly Eslam , El-Sayed Salwa M.
Published: January 2024

Mosquitoes prefer stagnant areas near hospitals to live and easily spread pathogenic bacteria. Our current study aims to isolate multidrug-resistant (MDR) Staphylococcus aureus isolates from midguts of Mosquito Culex pipiens and study the potential of mint as a biocontrol strategy against C. pipiens larvae and their midgut-borne S. aureus. Samples of the third and fourth larval instars of C. pipiens were collected from water ponds around three Cairo hospitals. Ciprofloxacin, gentamycin and tetracycline, as well as various concentrations of mint leaf extract (MLE) were tested for antibiotic susceptibility. Sixty-five isolates were obtained and showed antibiotic resistance to tetracycline, gentamycin, ciprofloxacin, and undiluted MLE with resistant percentages (%) of 27.69, 30.76, 17.46, and 23.08%, respectively. Undiluted MLE inhibited 61.53% of the multidrug S. aureus isolates, whereas it couldn't inhibit any of these isolates at dilutions less than 50 μg/mL. The MIC of MLE was ≤ 700 µg/mL, while the MIC of the antibiotics ranged from 0.25 to 5.0 µg/mL for the three antibiotics. The most inhibited S. aureus isolate was identified by 16SrRNA sequencing approach and registered in GenBank as S. aureus MICBURN with gene accession number OQ766965. MLE killed all larval stages after 72 h of exposure, with mortality (%) reaching 93.33 and 100% causing external hair loss, breakage of the outer cuticle epithelial layer of the abdomen, and larvae shrinkage. Histopathology of treated larvae showed destruction of all midgut cells and organelles. Gas chromatography (GC) of MLE revealed that menthol extract (35.92%) was the largest active ingredient, followed by menthone (19.85%), D-Carvone (15.46%), Pulegone (5.0579%). Docking analysis confirmed that alpha guanine and cadinol had the highest binding affinity to both predicted active sites of Culex pipiens acetylcholinesterase. As a result, alpha-guanine and cadinol might have a role as acetylcholinesterase inhibitors.
The role of attitudes towards contradiction in psychological resilience: the cortical mechanism of conflicting resolution networks
Authors: Yao Zai-Fu , Yang Meng-Heng , Yang Cheng-Ta , Chang Yun-Hsuan , Hsieh Shulan
Published: January 2024

Managing contradictions and building resilience help us overcome life's challenges. Here, we explored the link between attitudes towards contradictions and psychological resilience, examining the role of cortical conflict resolution networks. We enlisted 173 healthy young adults and used questionnaires to evaluate their cognitive thinking styles and resilience. They underwent structural and functional magnetic resonance imaging scans. Our results revealed that contrasting attitudes toward contradictions, formal logic, and naïve dialecticism thinking styles corresponded with varying degrees of resilience. We noted structural and functional differences in brain networks related to conflict resolution, including the inferior frontal and parietal cortices. The volumetric variations within cortical networks indicated right-hemispheric lateralization in different thinking styles. These findings highlight the potential links between conflict resolution and resilience in the frontoparietal network. We underscore the importance of frontoparietal brain networks for executive control in resolving conflicting information and regulating the impact of contradictions on psychological resilience.