bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exceptional response to lorlatinib and cabozantinib in ROS1-rearranged NSCLC with acquired F2004V and L2086F resistance
Authors: Sakamoto Mandy , Patil Tejas 
Published: June 2023

AbstractPatients with ROS1-rearranged NSCLC demonstrate excellent disease control with ROS1-targeted therapy, but acquired resistance is inevitable. Of particular interest is the ROS1 L2086F kinase domain mutation which is refractory to all currently available ROS1 TKIs apart from cabozantinib. We present a case of a patient with metastatic ROS1-rearranged NSCLC with dual ROS1 F2004V and L2086F resistance mutations who radiographically responded to the combination of lorlatinib and cabozantinib in a patient with metastatic NSCLC. Furthermore, the patient experienced exceptional clinical improvement and tolerance with the combined use of lorlatinib and cabozantinib. This case builds the case for cabozantinib as an agent to overcome ROS1 L2086F resistance. It also highlights the efficacy and safety of using combination of ROS1 TKIs to overcome complex resistance patterns.
Generating immunogenomic data-guided virtual patients using a QSP model to predict response of advanced NSCLC to PD-L1 inhibition
Authors: Wang Hanwen , Arulraj Theinmozhi , Kimko Holly , Popel Aleksander S. 
Published: June 2023

AbstractGenerating realistic virtual patients from a limited amount of patient data is one of the major challenges for quantitative systems pharmacology modeling in immuno-oncology. Quantitative systems pharmacology (QSP) is a mathematical modeling methodology that integrates mechanistic knowledge of biological systems to investigate dynamics in a whole system during disease progression and drug treatment. In the present analysis, we parameterized our previously published QSP model of the cancer-immunity cycle to non-small cell lung cancer (NSCLC) and generated a virtual patient cohort to predict clinical response to PD-L1 inhibition in NSCLC. The virtual patient generation was guided by immunogenomic data from iAtlas portal and population pharmacokinetic data of durvalumab, a PD-L1 inhibitor. With virtual patients generated following the immunogenomic data distribution, our model predicted a response rate of 18.6% (95% bootstrap confidence interval: 13.3-24.2%) and identified CD8/Treg ratio as a potential predictive biomarker in addition to PD-L1 expression and tumor mutational burden. We demonstrated that omics data served as a reliable resource for virtual patient generation techniques in immuno-oncology using QSP models.
Progress towards the Sustainable Development Goals has been slowed by indirect effects of the COVID-19 pandemic
Authors: Yuan Haixia , Wang Xiaoming , Gao Lei , Wang Tao , Liu Bingsheng , Fang Dongping , Gao Yi 
Published: June 2023

AbstractThe COVID-19 pandemic has undermined the ability of many countries to achieve the Sustainable Developments Goals (SDGs) by 2030. Here, we systematically assess the likely impacts of the pandemic on progress towards each SDG by 2030 at global, regional and national scales. In our analysis, we account for the social and economic shocks triggered by COVID-19 and their relative impacts on the SDGs. We also analyze the interconnections between SDG indicators during the pandemic to assess the indirect cascading effects of COVID-19 on the SDGs. We find that these indirect effects slowed progress much more than the direct initial disruptions. Globally, poverty eradication (SDG 1) is most affected by the pandemic. Regionally, SDG progress has been set back most in Latin America and the Caribbean, South Asia, the Middle East and North Africa and Sub-Saharan Africa. We suggest that for high and upper-middle-income countries a focus on reducing inequality (SDG 10) would be most beneficial, whereas for low-income and lower-middle-income countries industry, innovation, and infrastructure (SDG 9) are a priority in the post-COVID-19 phase.
Projected increases in emissions of high global warming potential fluorinated gases in China
Authors: Guo Liya , Yang Yang , Fraser Paul J. , Velders Guus J. M. , Liu Zhu , Cui Duo , Quan Jiayu , Cai Zhouxiang , Yao Bo , Hu Jianxin , Fang Xuekun 
Published: June 2023

AbstractChina is the largest greenhouse gas emitter in the world and has committed to mitigating global warming through achieving carbon neutrality by 2060. However, detailed information on China’s historical and projected emissions of fluorinated greenhouse gases, with high global warming potentials, is lacking. Here we establish a comprehensive and up-to-date inventory of China’s fluorinated greenhouse gas emissions and find that they show an accelerating growth rate, increasing from 5.5 to 221 million tons CO2-equivalent per year from 1990 to 2019. China has become the world’s largest emitter of fluorinated greenhouse gases and contributed 93% of the global emission increase during the period 1990−2019. We find that total emissions of fluorinated greenhouse gases from China are projected to increase to 506–1356 million tons CO2-equivalent per year in 2060 if there is no regulation, which is larger than the projected CO2 emissions under China’s carbon neutrality commitment for 2060.
Targeting lymphoid-derived IL-17 signaling to delay skin aging
Authors: Solá Paloma , Mereu Elisabetta , Bonjoch Júlia , Casado-Peláez Marta , Prats Neus , Aguilera Mònica , Reina Oscar , Blanco Enrique , Esteller Manel , Di Croce Luciano , Heyn Holger , Solanas Guiomar , Benitah Salvador Aznar 
Published: June 2023

AbstractSkin aging is characterized by structural and functional changes that contribute to age-associated frailty. This probably depends on synergy between alterations in the local niche and stem cell-intrinsic changes, underscored by proinflammatory microenvironments that drive pleotropic changes. The nature of these age-associated inflammatory cues, or how they affect tissue aging, is unknown. Based on single-cell RNA sequencing of the dermal compartment of mouse skin, we show a skew towards an IL-17-expressing phenotype of T helper cells, γδ T cells and innate lymphoid cells in aged skin. Importantly, in vivo blockade of IL-17 signaling during aging reduces the proinflammatory state of the skin, delaying the appearance of age-related traits. Mechanistically, aberrant IL-17 signals through NF-κB in epidermal cells to impair homeostatic functions while promoting an inflammatory state. Our results indicate that aged skin shows signs of chronic inflammation and that increased IL-17 signaling could be targeted to prevent age-associated skin ailments.
Supramolecular assembly guided by photolytic redox cycling
Authors: Roth Patrick , Meyer Raphael , Harley Iain , Landfester Katharina , Lieberwirth Ingo , Wagner Manfred , Ng David Y. W. , Weil Tanja 
Published: June 2023

AbstractIn living systems, the formation of structures relies on balancing kinetic and thermodynamic influences powered by reversible covalent bond chemistry. Although synthetic efforts have replicated these processes to some extent, elucidating their combination is necessary to identify mechanisms that confer nature’s structural precision and flexibility within a complex environment. Here we design a photolytic reaction cascade where competing redox pathways control the transience, interconversion and production rates of thiol/disulfide supramolecular monomers in situ. In contrast to direct assembly by dissolution, cascade generation of the same monomers formed hierarchical assemblies with different structural order. Redox-induced cycling between thiol–disulfide formation led to the emergence of new secondary structures and chirality within the final assemblies. These multiple structural states found within the same molecular system demonstrate the concept of assembly plasticity engaged frequently in biology. We demonstrate the importance of reaction complexity in controlling supramolecular propagation and in expanding the library of nanoarchitectures that can be created.
Effects of optimisation parameters on data-driven magnetofrictional modelling of active regions
Authors: Kumari A. , Price D. J. , Daei F. , Pomoell J. , Kilpua E. K. J. 
Published: June 2023

Context. The solar magnetic field plays an essential role in the formation, evolution, and dynamics of large-scale eruptive structures in the corona. The estimation of the coronal magnetic field, the ultimate driver of space weather, particularly in the ‘low’ and ‘middle’ corona, is presently limited due to practical difficulties. Data-driven time-dependent magnetofrictional modelling (TMFM) of active region magnetic fields has been proven to be a useful tool to study the corona. The input to the model is the photospheric electric field that is inverted from a time series of the photospheric magnetic field. Constraining the complete electric field, that is, including the non-inductive component, is critical for capturing the eruption dynamics. We present a detailed study of the effects of optimisation of the non-inductive electric field on the TMFM of AR 12473.
Aims. We aim to study the effects of varying the non-inductive electric field on the data-driven coronal simulations, for two alternative parametrisations. By varying parameters controlling the strength of the non-inductive electric field, we wish to explore the changes in flux rope formation and their early evolution and other parameters, for instance, axial flux and magnetic field magnitude.
Methods. We used the high temporal and spatial resolution cadence vector magnetograms from the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO). The non-inductive electric field component in the photosphere is critical for energising and introducing twist to the coronal magnetic field, thereby allowing unstable configurations to be formed. We estimated this component using an approach based on optimising the injection of magnetic energy.
Results. Our data show that flux ropes are formed in all of the simulations except for those with the lower values of these optimised parameters. However, the flux rope formation, evolution and eruption time varies depending on the values of the optimisation parameters. The flux rope is formed and has overall similar evolution and properties with a large range of non-inductive electric fields needed to determine the non-inductive electric field component that is critical for energising and introducing twist to the coronal magnetic field.
Conclusions. This study shows that irrespective of non-inductive electric field values, flux ropes are formed and erupted, which indicates that data-driven TMFM can be used to estimate flux rope properties early in their evolution without needing to employ a lengthy optimisation process.
LDL-C-Senkung bei Dialysepatienten
Authors: Schettler Volker J.J. 
Published: June 2023

ZUSAMMENFASSUNGPatienten, die aufgrund einer schweren Nierenerkrankung auf eine Dialyse angewiesen sind, haben ein hohes Risiko für Herz-Kreislauf-Erkrankungen. Häufig leiden diese Patienten u. a. auch an Bluthochdruck, Fettstoffwechselstörungen oder Diabetes mellitus. Ob aber in diesem Zusammenhang die Behandlung von Dialysepatienten mit Statinen gerechtfertigt ist, ist weiterhin umstritten, da in der Vergangenheit randomisierte Studien bei diesen Patienten deren Nutzen nicht belegen konnten. Ein differenzierter Blick zeigt jedoch, dass diese Frage nicht einfach zu beantworten ist. Entgegen dem Anschein gibt es Hinweise, dass selbst Dialysepatienten noch unter bestimmten Voraussetzungen von der Therapie mit Statinen oder anderen lipidsenkenden Maßnahmen zu profitieren scheinen.
Positioning analysis of Spanish politicians through their Twitter posts versus Spanish public opinion
Authors: Penelas-Leguía Azucena , Nunez-Barriopedro Estela , López-Sanz Jose María , Ravina-Ripoll Rafael 
Published: June 2023

AbstractThe evolution of Information and Communication Technologies (ICT) has changed the way we communicate. Access to the Internet and social networks has even changed the way we organise ourselves socially. Despite advances in this field, research on the use of social networks in political discourse and citizens’ perceptions of public policy remains scarce. So, the empirical study of politicians’ discourse on social networks in relation to citizens’ perception of public and fiscal policies according to their political affinity is of particular interest. The aim of the research is, therefore, to analyse positioning, from a dual perspective. Firstly, the study analyses the positioning in the discourse of the communication campaigns posted on social networks of Spain’s most prominent politicians. And secondly, it evaluates whether this positioning is reflected in citizens’ opinions about the public and fiscal policies being implemented in Spain. To this end, a qualitative semantic analysis and a positioning map is performed on a total of 1553 tweets published between 1 June and 31 July 2021 by the leaders of the top ten Spanish political parties. In parallel, a cross-sectional quantitative analysis is carried out, also through positioning analysis, based on the database of the Public Opinion and Fiscal Policy Survey of July 2021 by the Sociological Research Centre (CIS), whose sample is 2849 Spanish citizens. The results show a significant difference in the discourse of political leaders’ social network posts—which is more pronounced between right-wing and left-wing parties—and only some differences in citizens’ perception of public policies according to their political affinity. This work contributes to identifying the differentiation and positioning of the main parties and helps to guide the discourse of their posts.
When bat eats bat: diet and roosts of the greater broad-nosed bat (Scoteanax rueppellii) across different regions and habitats
Authors: Law Brad , Gonsalves Leroy , Chidel Mark , McConville Anna 
Published: June 2023

Roost selection and diet are fundamentally important to bats and can vary geographically and with habitat. The greater broad-nosed bat (Scoteanax rueppellii) is infrequently captured and poorly known, meaning appropriate conservation actions are difficult to determine. To assess variation across different habitats, we collected faecal samples for dietary analysis and radio-tracked individuals to identify roost trees at four different sites across New South Wales, Australia. Analysis of droppings verified beetles as the main prey in each study area except one dominated by mangroves, and confirmed for the first time carnivory in wild-caught individuals from the presence of hair from other bat species in its droppings. Very large, hollow trees were used as maternity roosts, being typically larger than neighbouring trees. Roosting habitat varied from wet sclerophyll forest in gullies to old-growth mangroves, and tree species used as roosts also varied. Colony size at maternity roosts was often 50–100 bats and fidelity to the maternity roost varied, with some being switched almost daily and others occupied for at least several days. One maternity roost was re-used 2 years later. Both the importance of beetles in the diet and roosts located in more productive landscapes suggest coastal plains and foothills may represent key habitat.
Continuing decline of the common brushtail possum in central Australia
Authors: McDonald Peter J. , Portelli Dean J. , Schubert Andrew T. , Stewart Alistair J. , Griffiths Anthony D. 
Published: June 2023

Australia’s recent mammal declines have been most severe in the arid regions, with at least 14 species extinctions occurring therein. The common brushtail possum (Trichosurus vulpecula) is a semi-arboreal marsupial that historically occurred widely across arid Australia but has disappeared from much of this region. We surveyed the last known sites for the species in central Australia. In 2012, we detected possum scats from 3 of 19 sites in Tjoritja National Park in the Northern Territory. Presence sites were separated by <4 km and characterised by extreme ruggedness. Further scat surveys in 2016–17, and 10 499 camera-trap nights of targeted survey in 2020–21, resulted in no possum detections. Moreover, no possums were detected during >60 000 camera-trap nights at nearby monitoring sites targeting other species in 2016–22. The contraction of common brushtail possums to rugged refuges by 2012 is consistent with a decline driven by mammalian predators. The possible extirpation also coincided with or followed record years of high temperatures. The culturally significant common brushtail possum is a priority candidate species for reintroduction to parts of central Australia. Reintroduction attempts must manage mammalian predators and consider the suitability of source populations and translocation sites in the face of a rapidly warming climate.
Research on error separation method of center of gravity measurement system for large-sized solid of revolution
Authors: Wang Meibao , Zhao Shuang 
Published: June 2023

Abstract
In order to realize mass and center of gravity measurement of large-sized rotating parts, a set of combined measurement system for center of gravity measurement was developed to adjust the distance according to the length and supporting position of the parts to adapt to different lengths of the measured parts. The study focused on the center of gravity synthesis, error factors and error separation within the system. Firstly, two sets of center of gravity measuring equipment based on multi-point weighing method were used to conduct a joint test on the large-sized measured parts, and the center of gravity measuring model was analyzed. Secondly, the measurement error and its influence on the measurement result are were analyzed when the two sets of measuring equipment were not parallel. Finally, error signals were separated using the multi-step method, Fourier transform and inverse Fourier transform. Simulation experiments show that the residual center of gravity error of Y axis and Z axis is less than 0.3 mm when the tilt angle between two sets of equipment is below 0.3°. The test results demonstrate that the center of gravity measurement error along the X axis is less than 2 mm, which indicates the measurement accuracy better than 0.02% as the length of the test object is about 10 000 mm, and the center of gravity measurement error along the Y axis and Z axis is less than 0.5 mm, which also indicates the measurement accuracy better than 0.02%. These findings indicate that the system enables high-precision measurement of the center of gravity for large-sized rotary products.
SOLPS-ITER modeling of EU-DEMO Ar-seeded cases with drifts and kinetic neutrals
Authors: Korzueva V , Kaveeva E , Vekshina E , Rozhansky V , Senichenkov I , Shirobokov A , Coster D 
Published: June 2023

Abstract
SOLPS-ITER modeling of EU-DEMO tokamak burning plasma with Ar seeding was performed. The modeling includes drifts, kinetic neutrals and current description switched on. The simulation results are compared with those without drifts. The power entering the edge plasma domain is 200 MW. The deuterium puff is 1.5 × 1023 at s−1 for all cases, which corresponds to neutral deuterium pressure of 10 Pa in the private flux region. The Ar seeding rates are

8.0
×

10

19

at s−1 and

1.5
×

10

20

at s−1, which correspond to the Ar concentration on the separatrix in the range of 0.5%–2%. It is demonstrated that with such a combination of parameters, it is possible to achieve power loads lower than 5 MW m−2 on both divertor targets. The temperature above 5 eV in the far scrape-off layer (SOL) of the outer target remains an issue. Together with drift and no drift cases, the impurity accumulation mechanism in the high-field-side SOL is discussed.
Multimodal origami shape memory metamaterials undergoing compression–twist coupling
Authors: Yang Haiying , Lu Haibao , Shu Dong-Wei , Fu Yong Qing (Richard) 
Published: June 2023

Abstract
As origami structures display designable and predictable folding or unfolding shape changes, the origami-inspired mechanical metamaterials have recently been extensively investigated for applications in metamaterial engineering. There were many previous studies on the conventional hexagonal Kresling origami structures, however, there are still many issues such as structural optimizations and designable strategies for the mechanical metamaterials. To solve these issues, in this study, we investigated the influences of crease direction, number of sides, and unit arrangement on the origami structures. Effects of these parameters on mechanical properties and deformation behaviors of metamaterials were analyzed using finite element method and experimental verifications. Effects of continuous changes in the number of sides were investigated, and we found that the switching of the metamaterials from a monostable state at number of sides of 3 to a quasi-static stiffness one at 4, and then to bistable ones at 5, 6, 7 and 8 can be realized. The compression–twist coupling effects of these metamaterials can be adjustable and tailorable by arranging the chosen units in series. These designed foldable metamaterials are flexible, especially in their unfolding and folding directions, resulting in the achievement of unstable compression states, i.e. the externally applied loads may cause the structure to unfold along the same compression path. Furthermore, shape memory polymer has been printed using 3D printing technology to achieve the smart origami metamaterials, which endow the metamaterials with shape memory effect, self-adaptability and temperature-responsive mechanical behavior.
Design, development, and testing of a 6.6 MVA HTS traction transformer for high-speed train applications
Authors: Zhao Xin , Fang Jin , Jiang Zhenan , Song Wenjuan , Liu Nengwen , Gao Yuan , Li Xiaohang , Zeng Fanhui , Xia Yajun , Badcock Rod A , Long Nicholas J , Staines Mike P , Buckley Robert G , Fang Xinyu , Li Yulong , Liu Bo , Zhang Jinyin , Han Wen , Li Li , Wang Jin , Gao Peiqing 
Published: June 2023

Abstract
High-temperature superconducting traction transformers (HTSTTs) have the merits of small size and lightweight in comparison with their conventional counterparts. This article reports the development progress of a 6.6 MVA HTSTT operating at 65 K, including the design, testing, and system cooling. The introduction of flux diverters and an optimized winding design realized a short-circuit impedance higher than 43% and AC loss less than 3 kW. The insulation structure was designed to pass insulation tests specified in standard in China GB/T 25120-2010. An open cooling system with reduced pressure was developed, which realized the efficiency of the 6.6 MVA HTSTT above 99%. Before assembling the prototype transformer, we conducted tests for critical current and dielectric performance of the HTS double pancake coils (DPCs) used in high-voltage (HV) and low-voltage (LV) windings to verify the current-carrying and insulation performances of each DPC. Finally, we measured the critical current and no-load loss of the HTSTT prototype at 77 K. Test results showed that the mass of the transformer is 33% less than conventional transformers. At 77 K, the critical current of the LV winding and HV winding is higher than 700 A and 50 A, respectively. Moreover, the HTSTT on a no-load test reached the test voltage of 25 000 V and loss of 6 kW. In the next step, we will continue to conduct experimental research, and verify the feasibility of the HTSTT on the train, and develop a circulating cooling system, all meeting the commercial requirements of the HTSTT.