bluuebunny/crossref_metadata_2025 huggingface dataset:
AI Curriculum for European High Schools: An Embedded Intelligence Approach
Authors: Bellas Francisco , Guerreiro-Santalla Sara , Naya Martin , Duro Richard J.
Published: November 2022

This paper presents a proposal of specific curriculum in Artificial Intelligence (AI) for high school students, which has been organized as a two-year subject. The curriculum was designed based on two premises. The first one is that, although the proposal is targeted to scientific programmes, the involved students and teachers do not have any previous knowledge about AI. Accordingly, the teaching units have been designed with the aim of supporting teachers in a new discipline for them and, in addition, providing an introductory level to students. The main didactical objective is to establish the fundamentals of AI from a practical perspective, learning technical concepts by using them to solve specific problems. The approach that has been followed in the teaching units is focused on developing embedded intelligence solutions, that is, programming real-world devices which interact with real environments. To this end, and to address a second fundamental premise of low investment capability at schools, it has been decided to use Smartphones as the central technological element to implement such embedded intelligence at classes. This curriculum has been developed within the Erasmus + project entitled "AI + : Developing an Artificial Intelligence Curriculum adapted to European High School". The project was carried out by a team of AI experts and high school teachers who created the teaching units, and a group of students that tested them for three years, providing feedback to make the curriculum feasible for its introduction in schools in the short-term. The main results obtained from its implementation within the project scope are presented and discussed here, with the aim of contributing to the AIEd community progress by means of a practical pilot experience. Although the curriculum has been designed and tested at European level, it has been created with a general perspective of AI education, so it can be applied worldwide.
Formal Modeling and Verification of the Functionality of Electronic Urban Railway Control Systems Through a Case Study
Authors: Lukács Gábor , Bartha Tamás
Published: November 2022

This paper presents a formal model-based methodology to support railway engineers in the design of safe electronic urban railway control systems. The purpose of our research is to overcome the deficiencies of existing traditional design methodologies, namely the incompleteness and the potential presence of contradictions in the system specification resulting from non-formal development techniques. We illustrate the application of the methodology via a case study of a tram-road level crossing protection system. It was chosen partly because it has a simple architecture and a small number of elements, thus it fits the scope limitations of this article. At the same time, it is suitable for presenting all essential features of our methodology. The proposed solution provides a specification/verification environment that facilitates the construction of correct, complete, consistent, and verifiable functional specifications during the development, while hiding all the formal method-related details from the railway engineers writing the specifications. Using this formal model-based methodology, a high-quality functional specification can be achieved, which is guaranteed to be more exhaustive and will contain fewer errors than traditional development.
A Preliminary Study to Explore the Informed Consent Approach and the Ethical Challenges in the Malaysian Biobanking for Research
Authors: Azahar Amnah , Mohd Yusof Aimi Nadia , Azhar Zahir Izuan
Published: November 2022

Since 2005, Malaysia has established several biobanks to keep in line with the advancement of biomedical research and development of biobanks in other countries such as the UK and the USA. Despite the establishment of several biobanks in Malaysia, little is known about the informed consent approach in biobanking research and its ethical challenges. This study aims to identify the approach in obtaining informed consent in the Malaysian biobanking for research and explore its ethical challenges. Using non-probability purposive sampling, an in-depth interview with the key informants was conducted in Klang Valley. Based on the interviews, broad consent is the main approach used in obtaining informed consent in biobanking for research in Malaysia and five major ethical challenges were identified. These challenges include the informants’ opinion on the current informed consent approach, understanding participants’ rights, the role of the research ethics committee, biobanking governance in Malaysia, and informants’ knowledge and awareness. In summary, there is a lack of understanding among those involved in biobanking on the ethical, legal, and social aspects of biobanking for research in Malaysia.
CACA guidelines for holistic integrative management of thyroid cancer
Authors: Ge Minghua , Gao Ming , Cheng Ruochuan , Chen Xiaohong , Guan Haixia , Lin Yansong , Liu Shaoyan , Wang Yu , Zheng Chuanming , Zheng Xiangqian
Published: November 2022

Purpose

In recent years, thyroid cancer is a common clinical problem. Since guidelines for the diagnosis and treatment of thyroid nodules and differentiated thyroid cancer were revised in 2012, significant scientific advances have occurred in the field. The aim of this guidelines is to inform clinicians, researchers, patients and health policy makers on published evidence and expert consensus relating to the diagnosis and management of thyroid malignancy.

Methods

In order to better promote the clinical management of thyroid cancer in China, Chinese Association of Thyroid Oncology (CATO) organized relevant experts to write these guidelines based on latest relevant literatures and clinical experience of multiple centers.

The specific clinical issues and topics addressed in these guidelines were based on published evidence, prior versions of the Chinese guidelines and expert consensus.

Results and conclusion

The guidelines provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, medullary, and anaplastic carcinomas.
Realism for Realistic People
Authors: Chang Hasok
Published: November 2022

In this innovative book, Hasok Chang constructs a philosophy of science for 'realistic people' interested in understanding and promoting the actual practices of inquiry in science and other knowledge-focused areas of life. Inspired by pragmatist philosophy, he reconceives the very notions of reality and truth on the basis of his concept of the 'operational coherence' of epistemic activities, and offers new pragmatist conceptions of truth and reality as operational ideals achievable in actual scientific practice. Rejecting the version of scientific realism that is concerned with claiming that our theories correspond to an ultimate reality, he proposes instead an 'activist realism': a commitment to do all that we can actually do to improve our knowledge of realities. His book will appeal to scholars and students in philosophy, science and the history of science, and all who are concerned about the place of science and empirical truth in society.
Why Use Cannabis? Examining Motives for Cannabis Use in Individuals with Anxiety Disorders
Authors: Ouellette Mélise J. , Rowa Karen , Cameron Duncan H. , Elcock Ashleigh , Soreni Noam , Pawluk Elizabeth J. , McCabe Randi E.
Published: November 2022

This study examined cannabis use motives in individuals with anxiety disorders and compared motives between infrequent and frequent cannabis users. It was hypothesised that coping motives would be endorsed at a significantly higher rate than other motives, and that frequent cannabis users would endorse coping motives significantly more than infrequent users. Participants were 144 adults seeking clinical services for anxiety disorders who reported using cannabis. Cannabis use was categorized by infrequent (n = 54) and frequent (n = 90) use. Anxiety symptoms were assessed and deemed clinically significant. Participants completed measures of cannabis use motives, cannabis use patterns, and cannabis use disorder symptoms, cross-sectionally. Cannabis use motives were examined for the entire sample and compared between frequent and infrequent users. In general, cannabis users endorsed coping (i.e., use for managing distress) and enhancement (i.e., use for fun, pleasant feeling, or the high) motives at equal rates (p = .265) and more than other motives (p < .001). Frequent users reported using cannabis for coping and expansion motives (i.e., use to change one's thinking) significantly more than infrequent users. These results indicate that individuals with anxiety disorders use cannabis for various reasons, some of which may not be directly related to their mental health symptoms. Future research is needed to compare motives for cannabis use in those with anxiety disorders, other mental health populations, and the general population, as well as examine motives for cannabis use within specific anxiety disorders.
Experimental observations and modelling of sub-Hinze bubble production by turbulent bubble break-up
Authors: Ruth Daniel J. , Aiyer Aditya K. , Rivière Aliénor , Perrard Stéphane , Deike Luc
Published: November 2022

We present experiments on large air cavities spanning a wide range of sizes relative to the Hinze scale$d_{H}$, the scale at which turbulent stresses are balanced by surface tension, disintegrating in turbulence. For cavities with initial sizes$d_0$much larger than$d_{H}$(probing up to$d_0/d_{H} = 8.3$), the size distribution of bubbles smaller than$d_{H}$follows$N(d) \propto d^{-3/2}$, with$d$the bubble diameter. The capillary instability of ligaments involved in the deformation of the large bubbles is shown visually to be responsible for the creation of the small bubbles. Turning to dynamical, three-dimensional measurements of individual break-up events, we describe the break-up child size distribution and the number of child bubbles formed as a function of$d_0/d_{H}$. Then, to model the evolution of a population of bubbles produced by turbulent bubble break-up, we propose a population balance framework in which break-up involves two physical processes: an inertial deformation to the parent bubble that sets the size of large child bubbles, and a capillary instability that sets the size of small child bubbles. A Monte Carlo approach is used to construct the child size distribution, with simulated stochastic break-ups constrained by our experimental measurements and the understanding of the role of capillarity in small bubble production. This approach reproduces the experimental time evolution of the bubble size distribution during the disintegration of large air cavities in turbulence.
Textiles chimúes con plumas decoloradas con técnicatapirage, Huaca de la Luna, Perú
Authors: Gomez Casaverde Yazmin , Rengifo Carlos , Salinas Letty , Moulherat Christophe , Berthier Serge
Published: November 2022

El presente artículo se centra en las plumastapiragede los textiles miniatura con arte plumario hallados en el templo Huaca de la Luna del sitio Huacas de Moche (Valle de Moche, Perú), asociados a la ocupación Chimú (1000-1440 dC). Eltapiragees una técnica de manipulación biológica, practicada por ciertos grupos amazónicos, que altera el color de las plumas de algunos psitácidos de los génerosArayAmazona. Para confirmar la existencia de plumastapirageen estos textiles, se realizó una identificación taxonómica macroscópica y microscópica de las plumas arqueológicas. Por último, se aplicaron análisis arqueométricos de microscopía de barrido electrónico (SEM) y microscopía digital para identificar los cambios en las microestructuras de las plumas, como también las especies de las plumas mismas. Los resultados muestran que las plumas de los textiles chimúes de Huaca de la Luna presentan plumastapirage, lo que permite discutir sobre las relaciones de intercambio entre la costa norte peruana y la Amazonia, y avanzar en la interpretación de los significados de estas plumas en los rituales de la cultura Chimú, por su valor simbólico y capacidad de acceso a estas bienes por parte de estas comunidades costeras.
Collective Remembrance and Private Choice: German–Greek Conflict and Behavior in Times of Crisis
Authors: FOUKA VASILIKI , VOTH HANS-JOACHIM
Published: November 2022

When does collective memory influence behavior? We highlight two conditions under which the memory of past events comes to matter for the present: the associative nature of memory and institutionalized acts of commemoration by the state. During World War II, German troops occupying Greece perpetrated numerous massacres. Memories of those events resurfaced during the 2009 Greek debt crisis, leading to a drop in German car sales in Greece, especially in areas affected by German reprisals. Differential economic performance did not drive this divergence. Multiple pieces of evidence suggest that current events reactivated past memories, creating a backlash against Germany. This backlash also manifested in political behavior, with vote shares of anti-German parties increasing in reprisal areas after the start of the debt crisis. Using quasi-random variation in public recognition of victim status, we show that institutionalized collective memory amplifies the effects of political conflict on economic and political behavior.
Bringing Innovation to Fruition: Insights From New Trademarks
Authors: Faurel Lucile , Li Qin , Shanthikumar Devin , Teoh Siew H.
Published: November 2022

We build a novel comprehensive data set of new product trademarks as an output measure of product development innovation. We show that risk-taking incentives in CEO compensation motivate this type of innovation and that this innovation improves firm performance. Using an exogenous shock to executive compensation, we find that reductions in stock option compensation cause reductions in new product development. We also find that firms undertaking new product development experience increases in future cash flow from operations and return on assets. These findings suggest the importance of product development innovation to firms and new trademarks as a novel innovation measure.
Spatial distribution of SARS-CoV-2 infection in schools, South Korea
Authors: Lee Young Hwa , Choe Young June , Lee Hyunju , Choi Eun Hwa , Park Young-Joon , Jeong Hyun Joo , Jo Myoungyoun , Jeong Heegwon
Published: November 2022

Identification of geographical areas with high burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in schools using spatial analyses has become an important tool to guide targeted interventions in educational setting. In this study, we aimed to explore the spatial distribution and determinants of coronavirus disease 2019 (COVID-19) among students aged 3–18 years in South Korea. We analysed the nationwide epidemiological data on laboratory-confirmed COVID-19 cases in schools and in the communities between January 2020 and October 2021 in South Korea. To explore the spatial distribution, the global Moran's I and Getis-Ord's G using incidence rates among the districts of aged 3–18 years and 30–59 years. Spatial regression analysis was performed to find sociodemographic predictors of the COVID-19 attack rate in schools and in the communities. The global spatial correlation estimated by Moran's I was 0.647 for the community population and 0.350 for the student population, suggesting that the students were spatially less correlated than the community-level outbreak of SARS-CoV-2. In schools, attack rate of adults aged 30–59 years in the community was associated with increased risk of transmission (P < 0.0001). Number of students per class (in kindergartens, primary schools, middle schools and high schools) did not show significant association with the school transmission of SARS-CoV-2. In South Korea, COVID-19 in students had spatial variations across the country. Statistically significant high hotspots of SARS-CoV-2 transmission among students were found in the capital area, with dense population level and high COVID-19 burden among adults aged 30–59 years. Our finding suggests that controlling community-level burden of COVID-19 can help in preventing SARS-CoV-2 infection in school-aged children.
Transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) from oral exposure into cow’s milk – part II: toxicokinetic predictive models for risk assessment
Authors: Moenning Jan-Louis , Krause Torsten , Lamp Julika , Maul Ronald , Schenkel Hans , Fürst Peter , Pieper Robert , Numata Jorge
Published: November 2022

Understanding the transfer of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) as well as polychlorinated biphenyls (PCBs) from oral exposure into cow’s milk is not purely an experimental endeavour, as it has produced a large corpus of theoretical work. This work consists of a variety of predictive toxicokinetic models in the realms of health and environmental risk assessment and risk management. Their purpose is to provide mathematical predictive tools to organise and integrate knowledge on the absorption, distribution, metabolism and excretion processes. Toxicokinetic models are based on more than 50 years of transfer studies summarised in part I of this review series. Here in part II, several of these models are described and systematically classified with a focus on their applicability to risk analysis as well as their limitations. This part of the review highlights the opportunities and challenges along the way towards accurate, congener-specific predictive models applicable to changing animal breeds and husbandry conditions.
Allelic diversity of a panel ofAegilops muticaBoiss (Amblyopyrym muticum(Boiss.) Eig) from Turkey
Authors: Alsaleh Ahmad , Çakır Esra , Bektas Harun , Ozkan Hakan
Published: November 2022

The members of the Aegilops genus serve as a vast pool of allele discovery for wheat improvement in abiotic and biotic stress responses.Aegilops muticaBoiss (Amblyopyrym muticum(Boiss) Eig) is an unexplored candidate with significant potential. Even though it has been used in cytogenetics applications within the last century, natural population diversity and allele discovery have been neglected. As an endemic species for Anatolia and the lower Caucasian region, it has an unexplored population structure. Here, seventy-five genotypes from five different newly collected populations from central Anatolia were evaluated with 29 polymorphic SSR loci. Significant diversity within (83%) and between (17%) the populations was obtained. Three of the populations were clearly separated, while two had some level of the mixture. Relatively easy cross-species hybridization and introgressions makeAe. muticaa good candidate for novel allele discovery and pre-breeding. Here, for the first time, representative natural populations ofAe. muticawere compared and population structures were revealed with SSR markers which may clear the misty vision that geneticists might have regardingAe. mutica. This could be exploited in genetic resource conservation and breeding programs and maybe a point for further studies.
The German Version of the Hybrid Work Characteristics Scale
Authors: Paruzel Agnieszka , Abendroth Anja , Mayer Axel , Xie Jia Lin , Maier Günter W.
Published: November 2022

Abstract. Introduction: To account for fast-paced developments at work, hybrid work characteristics (HWCs) were introduced. To measure them, an English instrument was developed by Xie et al. (2019) . HWCs encompass more than one work characteristics domain such as the task, social, or contextual domain and include boundarylessness, multitasking, the demand for constant learning, and non-work-related interruptions and are associated with employee attitudes and well-being. Objectives: We validated a German translation of the HWC scale. Method: Using employee samples from Germany ( N = 391) and the United Kingdom ( N = 400), we assessed the quality of the German translation. Results: The German version was internally consistent, showed an acceptable model fit, and reached a scalar level of measurement invariance. The HWCs are related to employee attitudes and well-being. Conclusion: We recommend the use of the German translation of the HWC scale, as our results support its reliability and validity.
Characterizing Drivers of Asia's Black Elephant Disaster Risks
Authors: Lin Yolanda C. , Mestav Sarica Gizem , Chua Terence J. , Stone Asa B. , Jenkins Susanna F. , Switzer Adam D. , Woo Gordon , Lallemant David
Published: November 2022

Asia has the fastest growing population and economy, but it is also the most disaster‐prone region in the world. Resilience to disaster impacts from natural hazards will be key to the long‐term sustainability of this rapidly growing region. The first step to building resilience is to identify the key threats that this region faces. We describe these key threats as Black Elephants: a cross between a “black swan” and the proverbial "elephant in the room" — they are extreme events that are known but difficult to address and often ignored. We examine the primary drivers of these looming risks and find that the drivers include underestimated or intensifying hazards, growing exposure, high vulnerability, and unaccounted complexities from multi‐hazard events. In mitigating these key risks, we discuss psychological barriers to action and highlight the importance of information, language, and hope. The known but complex impacts from natural hazards in Asia must be further acknowledged and managed in order to build a more sustainable, resilient future in an increasingly globally connected world.
A Hierarchical Framework for Unpacking the Nitrogen Challenge
Authors: Li Tingyu , Zhang Xin , Zhong Yuxiu , Davidson Eric A. , Dou Zhengxia , Zhang Weifeng , Pavinato Paulo S. , Martinelli Luiz A. , Kanter David R. , Liu Jianguo , Zhang Fusuo
Published: November 2022

To feed the world population while mitigating pressing nitrogen (N) pollution problems, tremendous efforts have been devoted to developing and implementing N‐efficient technologies in crop or livestock production, but limited progress has been made. The N management improvement on a farm does not necessarily translate to N pollution reduction on a broader scale due to complex responses of natural and human systems and lack of coordination among stakeholders. Consequently, it is imperative to develop an N management framework that encompasses the complex N dynamics across systems and spatial scales, yet simple enough to guide policies and actions of various stakeholders. Here, we propose a new framework, CAFE, that defines four N management systems (Cropping, Animal‐crop, Food, and Ecosystem) in a hierarchical manner, and apply it to 13 representative countries to partition N surpluses across systems in a simple and consistent manner, thereby facilitating the identification and prioritization of systems‐based intervention strategies. Surprisingly, the Cropping system contributes less than half of the total N surplus within its Ecosystem for most countries, highlighting the importance of N management beyond croplands. This framework reveals that the relevant priorities and key stakeholders for enhanced N management vary among countries, such as improving the Cropping‐system efficiencies in China, adjusting the animal‐crop portfolio in the Netherlands, reducing food wastage in the U.S., and lowering crop storage losses and increasing overall production capacities in African countries. As N surplus increases along the CAFE hierarchy, systems‐based intervention strategies are revealed: (a) coupling chemical fertilizers with other N sources by maintaining half of the N from manure and biological N fixation; (b) coupling animal‐crop production by reducing animal density to lower than 1.2 livestock units per hectare, and increasing self‐sufficiency of animal feed to above 50%; (c) coupling food trade with domestic demand and production; and (d) coupling population needs for economic opportunities with environmental capacity of the region. This novel framework can help unpack the “wicked” N management challenges across systems to provide new insights and tools for improving N management on and beyond farms.
Formation Waters Delineate Diverse Hydrogeologic Conditions at a Plate Scale: Eastern Flank of the Juan de Fuca Ridge
Authors: Wheat C. Geoffrey , Mottl Michael J. , Fisher Andrew T. , Hulme Samuel
Published: November 2022

The chemical composition of formation waters within the upper basaltic crust were calculated or measured at 24 sites on the northwest portion of the Juan de Fuca (JDF) Plate using data from sediment pore waters, scientific boreholes, and seafloor springs. Formation waters differ in composition across this ridge‐flank region because of variations in water‐rock reactions and residence times, exchange rates with overlying sediment pore waters, and microbial processes along flow paths. We interpret spatial variations in the solute composition of formation waters to resolve areas that are geochemically distinct or similar, lateral trends that result from water transport, areas where water‐rock reactions in the deeper crust are apparent, and sites of seawater recharge and formation water discharge. We provide evidence for large‐scale lateral flow associated with two (mostly) buried basement ridges on ∼1.4 and ∼3.5 Ma seafloor, which are subparallel to the JDF spreading axis to the west. Between these two ridges, where the seafloor and the sediment‐basement interface are relatively flat, formation waters have undergone extensive exchange with overlying sediment pore waters, consistent with a long residence time. Basaltic outcrops provide sites of seawater recharge and hydrothermal discharge, sometimes through the same feature, highlighting the heterogeneous nature of hydrogeologic conditions and processes. This work provides a blueprint for future plate‐scale studies to assess, for example, geologic controls of crustal age, spreading rate, and sedimentation on subsurface hydrologic patterns.
The Paucity of Supershear Earthquakes on Large Faults Governed by Rate and State Friction
Authors: Liang Chao , Ampuero Jean‐Paul , Pino Muñoz Daniel
Published: November 2022

Supershear earthquakes are rare compared to their subshear counterparts, but the cause for their paucity remains to be understood. We investigate for the first time the prevalence of supershear ruptures across multiple earthquake cycles on long faults using rate‐and‐state friction and a 2.5D approximation that accounts for the finite seismogenic width W. We find supershear events occur only in a narrow range of friction parameters that is not commonly observed in laboratory experiments, which may explain its rarity in nature. Particularly, the ratio between direct and evolution effects of rate‐and‐state friction needs to be low (a/b < 0.4) and the nucleation length has to be sufficiently large compared to W, but not too large that it causes a transition from seismic to aseismic slip. Our numerical and analytical developments contribute fundamentally to understanding the state of stress on long faults over multiple earthquake cycles and their potential for hosting supershear earthquakes.
Transport of Antarctic Bottom Water Entering the Brazil Basin in a Planetary Geostrophic Inverse Model
Authors: Finucane G. , Hautala S.
Published: November 2022

The abyssal circulation in the interior portions of the Brazil Basin and northern Argentine Basin were estimated using an overdetermined inverse method conserving neutral surface planetary potential vorticity and salinity. Antarctic Bottom Water (AABW) flows with a northward component through 30°S west of the Rio Grande Rise (RGR), as expected. However, in the area east of the RGR, the model shows southward transport in the upper part of the AABW across 30°S. This finding suggests that previous calculations of northward transport through Hunter Channel reaching the broader Brazil Basin may be overestimates. Reduced northward transport through the Hunter Channel has significant implications for the heat budget, implying less diapycnal mixing across the warmer AABW classes, compared to earlier studies.
Modeling Ocean Wave Transfer to Ross Ice Shelf Flexure
Authors: Bennetts L. G. , Liang J. , Pitt J. P. A.
Published: November 2022

An efficient mathematical model is presented for predicting the transfer of ocean waves to ice shelf flexure along two‐dimensional transects. The model incorporates varying ice shelf thickness and seabed bathymetry profiles, and is able to predict responses of large ice shelves over a broad frequency spectrum. The model is used to generate displacement and strain transfer functions for the Ross Ice Shelf (RIS) using geometries from the Bedmap2 data set. The transfer functions are validated against recent observations and used to study the influence of geometrical variations on strain transfer close to the shelf front. Predictions of RIS strain in response to example irregular incident swell and infragravity waves are generated over a wide region, and show similar maximum strains but contrasting spatial strain patterns. The model and results provide a basis for studying destabilizing impacts of ocean waves on the RIS.
Wave Equation Dispersion Inversion of Distributed Acoustic Sensing Data
Authors: Liu Hui , Li Jing , Wang Yibo
Published: November 2022

Distributed acoustic sensing (DAS) is a new dense sampling seismic observation technique rapidly developed to image near‐surface velocity structures. Compared with traditional seismometer surveys, DAS can record the strain rate data with a high spatial and temporal resolution and low maintenance cost observation. However, the strain variation recorded by the DAS system is the horizontal component with a low signal‐to‐noise ratio because the coupling between the fiber and the earth is poor. In addition, conventional velocity inversion algorithms such as 1D dispersion curve inversion and 2D/3D full‐waveform inversion (FWI) are developed for particle velocity components. Hence, their application in DAS strain‐rate data requires conversion to particle velocity data, which would bring some numerical error. In this work, we propose the DAS wave‐equation dispersion inversion (DAS‐WD) method to invert the S‐wave velocity model directly from DAS strain rate data. The WD method does not require 1D dispersion curve inversion layered assumptions and overcomes the problem that the FWI is challenging to converge because the recorded horizontal DAS component data is noisy. Meanwhile, the strain rate DAS‐WD theory avoids the error caused by velocity and strain rate conversion by scaling of apparent velocity followed by time integrations. The typical synthetic and offshore DAS field data demonstrate that the proposed DAS‐WD method has great potential for a high‐resolution velocity tomogram.
Advanced Potential Field Analysis Applied to Mise‐à‐la‐Masse Surveys for Leakage Detection
Authors: Mary Benjamin , Peruzzo Luca , Wu Yuxin , Cassiani Giorgio
Published: November 2022

Traditionally interpretation of Mise‐à‐la‐masse (MALM) is limited to the visualization of equipotential contours in order to infer qualitatively the extent of the anomaly. MALM inversion algorithms rely on having a good knowledge of the electrical resistivity distribution in the subsoil. Conversely, potential imaging methods have shown their strength for several applications to quickly estimate the depth of sources even in highly heterogeneous media. In the case of the MALM method, the physics may be described by Poisson's equation. As the conductivity term is modulating the flux of current, MALM is generally referred to as a pseudo‐potential method. In this work, we have tested, for the first time, the application of the potential field theory to MALM in order to identify the current source depth. Synthetic modeling shows that the proposed algorithm is effective and efficient, using surface voltage measurements for different resistivity contrasts, anomaly depths and noise levels. We then applied the method to the real field case of a landfill leakage and showed how very different source depth estimates result from an intact or a damaged landfill liner.
Identifying Spatiotemporal Patterns of Hillslope Subsurface Flow in an Alpine Critical Zone on the Qinghai‐Tibetan Plateau Based on Three‐Year, High‐Resolution Field Observations
Authors: Hu Guangrong , Li Xiaoyan , Yang Xiaofan , Shi Fangzhong , Sun Haoran , Cui Baoshan
Published: November 2022

The spatial heterogeneity and temporal variability of hillslope subsurface flow (SSF) generation are poorly understood in the alpine critical zone (CZ). Owing to the limitations of observation technology bottlenecks and harsh environments, existing studies lack a holistic and process‐based understanding of SSF generation, particularly for the deep CZ and annual freeze‐thaw (FT) cycle. This study improves the conventional trenching observation scheme and is the first to have successfully monitored SSF processes from the soil to the bedrock layer with high‐resolution from 2017 to 2020 in a headwater catchment of the Qinghai‐Tibetan Plateau. The results show that hillslope runoff generation exhibited similar trends over the years while exhibiting distinct patterns across seasons. Spatially, slope aspects significantly affect the runoff amount and ratio. The south‐facing slope is dominated by overland flow (OF, 84.2%–97.0%), while the north‐facing slope is dominated by SSF (88.9%–97.3%). The runoff depth of the north‐facing slope is 11.0 times that of the south‐facing slope. The SSF in the deep CZ accounts for 20.8%–37.8% of the total runoff along the north‐facing slope. Temporally, runoff generation exhibits distinct patterns across seasons. OF exhibits two different patterns, while SSF exhibits five across seasons. Our results indicate that runoff generation in different FT stages should be studied by the time phase. Therefore, we propose seasonal or FT period‐based classification criteria and divide OF and SSF into two and three consecutive periods throughout the calendar year. We suggest that these inferences and observations should be considered in the framework of hydrological models in cold regions.
Are the antidepressant effects of insulin-sensitizing medications related to improvements in metabolic markers?
Authors: Toba-Oluboka Temi , Vochosková Kristýna , Hajek Tomas
Published: November 2022

Insulin-sensitizing medications were originally used in psychiatric practice to treat weight gain and other metabolic side effects that accompany the use of mood stabilizers, antipsychotics, and some antidepressants. However, in recent studies these medications have been shown to cause improvement in depressive symptoms, creating a potential new indication outside of metabolic regulation. However, it is still unclear whether the antidepressant properties of these medications are associated with improvements in metabolic markers. We performed a systematic search of the literature following PRISMA guidelines of studies investigating antidepressant effects of insulin-sensitizing medications. We specifically focused on whether any improvements in depressive symptoms were connected to the improvement of metabolic dysfunction. Majority of the studies included in this review reported significant improvement in depressive symptoms following treatment with insulin-sensitizing medications. Nine out of the fifteen included studies assessed for a correlation between improvement in symptoms and changes in metabolic markers and only two of the nine studies found such association, with effect sizes ranging from R2 = 0.26–0.38. The metabolic variables, which correlated with improvements in depressive symptoms included oral glucose tolerance test, fasting plasma glucose and glycosylated hemoglobin following treatment with pioglitazone or metformin. The use of insulin-sensitizing medications has a clear positive impact on depressive symptoms. However, it seems that the symptom improvement may be unrelated to improvement in metabolic markers or weight. It is unclear which additional mechanisms play a role in the observed clinical improvement. Some alternative options include inflammatory, neuroinflammatory changes, improvements in cognitive functioning or brain structure. Future studies of insulin-sensitizing medications should measure metabolic markers and study the links between changes in metabolic markers and changes in depression. Additionally, it is important to use novel outcomes in these studies, such as changes in cognitive functioning and to investigate not only acute, but also prophylactic treatment effects.
The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis
Authors: Faulkner Lucy G. , Howells Lynne M. , Pepper Coral , Shaw Jacqueline A. , Thomas Anne L.
Published: November 2022

Introduction

Colorectal cancer is the fourth most common cancer in the UK. There remains a need for improved risk stratification following curative resection. Circulating-tumour DNA (ctDNA) has gained particular interest as a cancer biomarker in recent years. We performed a systematic review to assess the utility of ctDNA in identifying minimal residual disease in colorectal cancer.

Methods

Studies were included if ctDNA was measured following curative surgery and long-term outcomes were assessed. Studies were excluded if the manuscript could not be obtained from the British Library or were not available in English.

Results

Thirty-seven studies met the inclusion criteria, involving 3002 patients. Hazard ratios (HRs) for progression-free survival (PFS) were available in 21 studies. A meta-analysis using a random effects model demonstrated poorer PFS associated with ctDNA detection at the first liquid biopsy post-surgery [HR: 6.92 CI: 4.49–10.64 p < 0.00001]. This effect was also seen in subgroup analysis by disease extent, adjuvant chemotherapy and assay type.

Discussion

Here we demonstrate that ctDNA detection post-surgery is associated with a greater propensity to disease relapse and is an independent indicator of poor prognosis. Prior to incorporation into clinical practice, consensus around timing of measurements and assay methodology are critical.

Protocol registration

The protocol for this review is registered on PROSPERO (CRD42021261569).
How the histological structure of some lung cancers shaped almost 70 years of radiobiology
Authors: Worth Katja R. , Papandreou Ioanna , Hammond Ester M.
Published: November 2022

Pivotal research led by Louis Harold Gray in the 1950s suggested that oxygen plays a vital role during radiotherapy. By proving that tumours have large necrotic cores due to hypoxia and that hypoxic cells require significantly larger doses of ionising radiation to achieve the same cell kill, Thomlinson and Gray inspired the subsequent decades of research into better defining the mechanistic role of molecular oxygen at the time of radiation. Ultimately, the work pioneered by Thomlinson and Gray led to numerous elegant studies which demonstrated that tumour hypoxia predicts for poor patient outcomes. Furthermore, this subsequently resulted in investigations into markers and measurement of hypoxia, as well as modification strategies. However, despite an abundance of pre-clinical data supporting hypoxia-targeted treatments, there is limited widespread application of hypoxia-targeted therapies routinely used in clinical practice. Significant contributing factors underpinning disappointing clinical trial results include the use of model systems which are more hypoxic than human tumours and a failure to stratify patients based on levels of hypoxia. However, translating the original findings of Thomlinson and Gray remains a research priority with the potential to significantly improve patient outcomes and specifically those receiving radiotherapy.
FMR1 promotes the progression of colorectal cancer cell by stabilizing EGFR mRNA in an m6A-dependent manner
Authors: Hu Yuhan , Gao Qingzu , Ma Shuai , Yu Pei , Ding Shuang , Yao Xiaofei , Zhang Zheying , Lu Shuya , Lu Manman , Zhang Jinghang , Wang Yanling , Qian Xinlai , Zhong Jiateng
Published: November 2022

FMR1, a new m6A reader, is known to be involved in the regulation of cancer progression. However, its role, regulatory mechanism, and clinical significance in colorectal cancer (CRC) are elusive. Here, we showed that FMR1 was upregulated in CRC, and it promoted proliferation and metastasis of CRC cells in vitro and in vivo. Mechanically, FMR1 recognized the m6A-modification site in EGFR mRNA, a key molecule in cancer occurrence and targeted therapy, sustained its stability and maintained its expression in an m6A-dependent manner, thereby promoting the tumorigenesis and metastasis of CRC. And the effect of FMR1 knockdown in CRC cells could be abolished by METTL3. Furthermore, FMR1 shRNA plasmid carried by attenuated Salmonella has an effective anti-tumor effect in vivo. Collectively, we identified the METTL3/FMR1/EGFR axis in the progression of CRC. This novel mechanism indicated that the METTL3/FMR1/EGFR axis is a potential target for early therapeutic intervention in CRC progression.
Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer
Authors: Chen Yi-Hong , Xu Nan-Zhu , Hong Chang , Li Wen-Qi , Zhang Yi-Qiong , Yu Xin-Yi , Huang Yue-Le , Zhou Jue-Yu
Published: November 2022

Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.
Integrated proteogenomic characterization of medullary thyroid carcinoma
Authors: Shi Xiao , Sun Yaoting , Shen Cenkai , Zhang Yan , Shi Rongliang , Zhang Fan , Liao Tian , Lv Guojun , Zhu Zhengcai , Jiao Lianghe , Li Peng , Xu Tiansheng , Qu Ning , Huang Naisi , Hu Jiaqian , Zhang Tingting , Gu Yanzi , Qin Guangqi , Guan Haixia , Pu Weilin , Li Yuan , Geng Xiang , Zhang Yan , Chen Tongzhen , Huang Shenglin , Zhang Zhikang , Ge Shuting , Wang Wu , Xu Weibo , Yu Pengcheng , Lu Zhongwu , Wang Yulong , Guo Liang , Wang Yu , Guo Tiannan , Ji Qinghai , Wei Wenjun
Published: November 2022

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy derived from parafollicular cells (C cells) of the thyroid. Here we presented a comprehensive multi-omics landscape of 102 MTCs through whole-exome sequencing, RNA sequencing, DNA methylation array, proteomic and phosphoproteomic profiling. Integrated analyses identified BRAF and NF1 as novel driver genes in addition to the well-characterized RET and RAS proto-oncogenes. Proteome-based stratification of MTCs revealed three molecularly heterogeneous subtypes named as: (1) Metabolic, (2) Basal and (3) Mesenchymal, which are distinct in genetic drivers, epigenetic modification profiles, clinicopathologic factors and clinical outcomes. Furthermore, we explored putative therapeutic targets of each proteomic subtype, and found that two tenascin family members TNC/TNXB might serve as potential prognostic biomarkers for MTC. Collectively, our study expands the knowledge of MTC biology and therapeutic vulnerabilities, which may serve as an important resource for future investigation on this malignancy.
Flexomagnetism and vertically graded Néel temperature of antiferromagnetic Cr2O3 thin films
Authors: Makushko Pavlo , Kosub Tobias , Pylypovskyi Oleksandr V. , Hedrich Natascha , Li Jiang , Pashkin Alexej , Avdoshenko Stanislav , Hübner René , Ganss Fabian , Wolf Daniel , Lubk Axel , Liedke Maciej Oskar , Butterling Maik , Wagner Andreas , Wagner Kai , Shields Brendan J. , Lehmann Paul , Veremchuk Igor , Fassbender Jürgen , Maletinsky Patrick , Makarov Denys
Published: November 2022

Antiferromagnetic insulators are a prospective materials platform for magnonics, spin superfluidity, THz spintronics, and non-volatile data storage. A magnetomechanical coupling in antiferromagnets offers vast advantages in the control and manipulation of the primary order parameter yet remains largely unexplored. Here, we discover a new member in the family of flexoeffects in thin films of Cr2O3. We demonstrate that a gradient of mechanical strain can impact the magnetic phase transition resulting in the distribution of the Néel temperature along the thickness of a 50-nm-thick film. The inhomogeneous reduction of the antiferromagnetic order parameter induces a flexomagnetic coefficient of about 15 μB nm−2. The antiferromagnetic ordering in the inhomogeneously strained films can persist up to 100 °C, rendering Cr2O3 relevant for industrial electronics applications. Strain gradient in Cr2O3 thin films enables fundamental research on magnetomechanics and thermodynamics of antiferromagnetic solitons, spin waves and artificial spin ice systems in magnetic materials with continuously graded parameters.
Deep learning-based image analysis predicts PD-L1 status from H&E-stained histopathology images in breast cancer
Authors: Shamai Gil , Livne Amir , Polónia António , Sabo Edmond , Cretu Alexandra , Bar-Sela Gil , Kimmel Ron
Published: November 2022

Programmed death ligand-1 (PD-L1) has been recently adopted for breast cancer as a predictive biomarker for immunotherapies. The cost, time, and variability of PD-L1 quantification by immunohistochemistry (IHC) are a challenge. In contrast, hematoxylin and eosin (H&E) is a robust staining used routinely for cancer diagnosis. Here, we show that PD-L1 expression can be predicted from H&E-stained images by employing state-of-the-art deep learning techniques. With the help of two expert pathologists and a designed annotation software, we construct a dataset to assess the feasibility of PD-L1 prediction from H&E in breast cancer. In a cohort of 3,376 patients, our system predicts the PD-L1 status in a high area under the curve (AUC) of 0.91 – 0.93. Our system is validated on two external datasets, including an independent clinical trial cohort, showing consistent prediction performance. Furthermore, the proposed system predicts which cases are prone to pathologists miss-interpretation, showing it can serve as a decision support and quality assurance system in clinical practice.