bluuebunny/crossref_metadata_2025 huggingface dataset:
Recycling of RAP (Reclaimed Asphalt Pavement) as aggregate for structural concrete: experimental study on physical and mechanical properties
Authors: Russo Nicoletta , Filippi Andrea , Carsana Maddalena , Lollini Federica , Redaelli Elena
Published: October 2024

The replacement of natural aggregate in concrete with artificial and/or recycled one has recently gained attention as meaningful strategy to reduce the environmental impact of structural concrete and promote circular economy principles. This study investigated the possibility to use Reclaimed Asphalt Pavement (RAP), in the “as received conditions”, as a partial or complete substitution of natural aggregate for structural concrete. RAP aggregate was firstly characterized in terms of grain size distribution, density, assessment of fines, chloride content, moisture content and water absorption. Subsequently, a total of twenty-four concrete mixes were designed, considering two cement types, two w/c ratios and several aggregate substitution percentages. For each mix, properties at the fresh and hardened state were investigated, such as workability, density and total open porosity, compressive strength, dynamic modulus of elasticity, and electrical resistivity. Results showed that RAP has a good potential to be used in reinforced concrete, provided that different water absorption and moisture content are considered in the mix design. RAP concrete was characterized by a lower density and increased total open porosity; however, an accurate tailoring of the concrete recipe could compensate the strength loss for several applications. Other properties, such as electrical resistivity and the relationship between dynamic modulus of elasticity and compressive strength did not result significantly altered by the presence of RAP.
Innovate for Impact: Young Adults Education and Empowerment for Climate Action
Authors: Rap Shelley , Bodas Moran
Published: October 2024

Anthropogenic climate change is a significant driver of disasters, such as tropical storms, floods, drought and loss of biodiversity, amplifying their frequency and severity worldwide. The annual incidence of extreme weather-related events increases with growing human exposure to risks. The Sendai Framework and its associated Sustainable Development Goals (SDGs) recognise the interlinkages between disaster risk reduction, climate change adaptation and sustainable development. However, despite the best intentions of disaster planners, the current efforts are suboptimal in promoting implementation. Education is a critical goal to achieve sustainable development. Environmental Education for Sustainable Development (ESD) seeks to equip students with the knowledge, skills, values and agency necessary to address the complex challenges of climate change and global warming. One example of such an educational programme is the “Speak to Me in Numbers” programme. This interdisciplinary ESD programme educates 9th graders in SDG-related scientific content through scientific data analysis. It strives to inspire students to develop their agency and become responsible future citizens by taking local climate action to bring about sustainable development in their communities. Empowered young people who become agents that bring about global changes are crucial in the context of the climate crisis. However, such efforts should be undertaken cautiously to avoid doing more harm than good by evoking climate anxiety. These implications are discussed.
The Materiality of Children’s Imaginative Sense-making in Climate Change Education
Authors: Wong Chin Chin , Kumpulainen Kristiina , Renlund Jenny , Byman Jenny
Published: October 2024

In this article, we discuss our investigation of children’s imaginative sense-making and its materiality in climate change education. Drawing on a new materialist approach, our research contributes to knowledge about the material significance in children’s sense-making related to climate change. During a project called Riddle of the Spirit in a Finnish primary school, we invited children to explore the concepts of global warming and carbon dioxide through narrative, playful and multimodal activities. Inspired by postqualitative methods, our relational analysis, based on video materials, maps and examines two episodes of children’s small group inquiry. Our findings unfold the material–discursive intra-actions, through which a prop turned into a whale’s head, the Titanic film appeared, and water and carbon dioxide became important to children’s bodies. With these specific events, the study illustrates how various materials conjoined and came to matter in the children’s sense-making of the concepts.
Vortex shedding and induced forces in unsteady flow
Authors: Graham M. , Li J.
Published: October 2024

This survey paper is concerned with vortex shedding from bodies in unsteady flow due either to time dependent motion of the body in a still fluid or unsteady motion of the fluid about a fixed body. The fluid is treated as incompressible, and the main emphasis is on starting flows and oscillatory flows. Much of the discussion describes 2D flow around sections of long or slender bodies. The first part of the paper covers the inviscid flow scaling of the forces induced by vortex shedding in time dependent flows which drive the shedding. This is followed by application of Wu’s impulse integral of the moment of vorticity to predict the forces induced by vortex shedding from a body in both inviscid and viscous flows. Vortex shedding phenomena involving small amplitude, high-frequency oscillatory flow such as vortex-induced vibration (VIV) and fluid-structure interaction (FSI) are not included in this discussion as in these cases the unsteady flow controls rather than drives the vortex shedding and they are well covered elsewhere.

The second part of the paper describes a vortex force mapping (VFM) method derived by considering the Lamb–Gromyko formulation for the pressure contribution which allows the integral of the vorticity field to be restricted to regions which are not far from the body. It is applied to both inviscid and viscous flows. The section finishes with discussion of application of the VFM to the calculation of forces induced on bodies from flow field measurements, such as particle image velocimetry (PIV).
Class inequality, power, and trust in private companies: evidence from Latin America
Authors: Pérez-Ahumada Pablo , Gutiérrez-Crocco Francisca , Astorga-Pinto Charo
Published: October 2024

In the last few years, legitimacy has proven to be a fundamental power resource for the business class. Building on the idea of “discursive power,” investigations have demonstrated that when the business class successfully shapes public discourses and public opinion, its power increases. With this article, we contribute to this research by showing that businesses’ success in building discursive power, as expressed in individual trust in private companies, is limited by individual- and macro-level factors associated with class inequality, class politics, and power. Using data from 15 Latin American countries (2005–2015), we show that in the period studied, the propensity to trust private companies was significantly lower among those in underprivileged class positions (e.g., working-class people or the informal self-employed) and among those who identify with the political left and have less confidence in political institutions. At the macro level, trust in companies was lower in countries ruled by the left or in countries where inequality rose or where citizens’ trust in political institutions improved. At the end of this article, we identify three patterns of business legitimacy in Latin America and show how our results contribute to the recent research on trust, class, and power.
Digitally gamified co-creation: enhancing community engagement in urban design through a participant-centric framework
Authors: Ng Provides , Zhu Shutong , Li Yuechun , van Ameijde Jeroen
Published: October 2024

Urban co-creation is an approach to urban design that actively involves stakeholders and end-users in the design process. As designers increasingly use digital tools to manage design information, stakeholders and residents may find it difficult to participate, resulting in a lack of engagement. The emergence of metaverse technologies offers a crucial opportunity to employ user-friendly and collaborative tools, enabling more effective participation. In the study presented in this article, a custom-designed digital game with virtual reality environment was used to facilitate a series of co-creation workshops. The study focused on changes in participants’ experience by comparing baseline and endline survey results against the design outputs. It employed a holistic framework considering four dimensions: game design, participatory experience, learning outcomes and co-creation results. The findings indicate that the digitally gamified approach helped enhance participation and knowledge sharing, and even though game design ratings varied, the use of video games motivated engagement, particularly in an intergenerational context. The co-creation workshop design documented in this article offers new methods to enhance community engagement in urban design. Especially during digital transformation, it opens renewed discussions on balancing traditional output-driven approaches with more participant-centric methods and design objectives.
Hypersonic boundary layer theory in the symmetry plane of blunt bodies
Authors: Wang Qiu , Li Jinping , Gu Sangdi
Published: October 2024

Solving the three-dimensional boundary layer equations carries theoretical significance and practical applications, which also poses substantial challenges due to its inherent complexity. In this paper, the laminar boundary layer equations for the symmetry plane of three-dimensional bodies are derived in an orthogonal curvilinear coordinate system associated with the principal curvatures. The derivation of the boundary layer equations is based not only on the common symmetric properties of the flow, as given by Hirschel et al. (Three-Dimensional Attached Viscous Flow, 2014, Academic Press, pp. 183–187), but also incorporates the geometric symmetry properties of the body. The derived equations are more representative and simplified. Notably, these equations can degenerate to a form consistent with or equivalent to the commonly used boundary layer equations for special bodies such as flat plates, cones and spheres. Furthermore, for hypersonic flows, the crossflow velocity gradient at the boundary layer edge on the symmetry plane is derived based on Newtonian theory. Subsequently, this parameter can provide the necessary boundary condition needed for solving the boundary layer equations using existing methods. Finally, as examples, the equations developed in this paper are solved using the difference-differential method for several typical three-dimensional blunt shapes that appeared on hypersonic vehicles. They prove to be useful in the analysis and interpretation of boundary layer flow characteristics in the symmetry plane of blunt bodies.
Active control of the flow past a circular cylinder using online dynamic mode decomposition
Authors: Li Xin , Deng Jian
Published: October 2024

This study explores the implementation of an online control strategy based on dynamic mode decomposition in the context of flow control. The investigation is conducted mainly with a fixed Reynolds number of

$Re = 100$

, focusing on the flow past a circular cylinder constrained between two walls to mitigate vortex shedding. The control approach involves the activation of two synthetic jets on the cylinder through blowing and suction. Velocity fluctuations in the wake, specifically in the

$x$

-direction, are harnessed to ascertain the mass flow rate of the jets using the linear quadratic regulator and online dynamic mode decomposition. The study systematically assesses the control performance across various configurations, including different values of the input penalty factor

${\boldsymbol {R}}$

, varying numbers of probes and distinct probe arrangement methods. The synthetic jets prove effective in stabilising the separation bubble, and their interaction with the unsteady wake leads to a notable reduction in drag force, its fluctuations and the amplitude of the lift force. Specifically, the mean and standard deviation of the drag coefficient witness reductions of

$7.44\,\%$

and

$96.67\,\%$

, respectively, and the standard deviation of the lift coefficient experiences an impressive reduction of

$85.18\,\%$

. The robustness of the proposed control method has also been tested on two more complicated cases, involving unsteady incoming flows with multiple frequency components. Comparatively, the methodology employed in this paper yields results akin to those obtained through deep reinforcement learning in terms of control effectiveness. However, a noteworthy advantage lies in the substantial reduction of computational resource consumption, highlighting the efficiency of the proposed approach.
Toward ab initio molecular simulation of reacting air: Mach 15 air flow over a blunt wedge
Authors: Valentini Paolo , Grover Maninder S. , Bisek Nicholas J.
Published: October 2024

We present a Mach 15 air flow over a blunt two-dimensional wedge simulated using the direct molecular simulation method. As electronically excited states are not modelled, the resulting air mixture around the wedge contains the electronic ground states only, namely

${\rm N}_2(\text {X}^1 \varSigma _g^{+})$

,

${\rm O}_2(\text {X}^3 \varSigma _g^{-})$

,

${\rm NO}(\text {X}^2\varPi _r)$

,

${\rm N}(^4{\rm S})$

and

${\rm O}(^3{\rm P})$

. All the potential energy surfaces (PESs) that are used to model the various interactions between air particles are ab initio, with two notable exceptions, namely

${\rm N}_2+{\rm NO}$

and

${\rm O}_2+{\rm NO}$

. At the selected free-stream conditions, strong vibrational non-equilibrium is observed in the shock layer. The flow is characterized by significant chemical activity, with near-complete oxygen dissociation, considerable formation of NO and minimal molecular nitrogen dissociation. Complex mass diffusion kinetics, driven by composition, temperature and pressure gradients, are identified in the shock layer. All these physical phenomena are directly coupled to, and responsible for, the mechanics of the gas flow and are all solely traceable to the PESs’ inputs, without the need for any thermochemical models, mixing rules or constitutive laws for transport properties. Because the flow is entirely at near-continuum conditions, it is a gas-phase thermophysics benchmark that is useful to enhance the fidelity of continuum models used in computational fluid dynamics of hypersonic flows.
Investigating thyroid function and iodine status in adolescents with and without paediatric major depressive disorder
Authors: Osuna Ester , Baumgartner Jeannine , Walther Andreas , Emery Sophie , Albermann Mona , Baumgartner Noemi , Schmeck Klaus , Walitza Susanne , Strumberger Michael , Hersberger Martin , Zimmermann Michael B. , Häberling Isabelle , Berger Gregor , Herter-Aeberli Isabelle
Published: October 2024

Depression has been associated with subclinical hypothyroidism and altered hypothalamic-pituitary-thyroid axis functioning. Adequate iodine nutrition is essential for healthy thyroid functioning. We therefore determined associations of iodine and thyroid status with paediatric major depressive disorder (pMDD) among Swiss adolescents and explored whether associations are sex-specific and mediated by stress. We conducted a matched case–control study in 95 adolescents with diagnosed pMDD and 95 healthy controls. We assessed depression severity using the Children’s Depression Rating Scale-Revised and stress using the perceived stress scale (PSS) and measuring hair cortisol levels. We determined iodine status by measuring urinary iodine concentrations (UIC) and thyroid status by thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in serum. Median (IQR) UIC did not differ between cases (121 (87, 174) µg/l) and controls (114 (66, 183) μg/l, P = 0·3). Median TSH and FT4 were lower in cases than controls (TSH: 1·36 (0·91, 2·00) mlU/l v. 1·50 (1·18, 2·06) mlU/l, P = 0·039; FT4: 14·7 (12·9, 16·9) pmol/l v. 15·7 (14·3, 17·2) pmol/l, P = 0·004). The prevalence of hypothyroxinaemia (normal TSH; low FT4) was higher among female cases than controls (21 % v. 4%, P = 0·006). PSS scores were higher while hair cortisol was lower in cases than controls (PSS: 25 (20, 28) v. 11 (7, 15), P < 0·001; cortisol: 2·50 (1·34, 3·57) pg/mg v. 3·23 (1·79, 4·43) pg/mg, P = 0·044). After adjusting for confounders, the associations of TSH and hair cortisol with pMDD were no longer significant. Furthermore, TSH and FT4 were not associated with PSS scores and hair cortisol levels. Summarising, iodine nutrition was adequate for adolescents with and without pMDD. However, FT4 concentrations were lower in those with pMDD, and 1 in 5 female adolescents with pMDD were hypothyroxinaemic.
Plant protein, fibre and physical activity solutions to address poor appetite and prevent undernutrition in older adults: study protocol for the APPETITE randomised controlled trial
Authors: Horner Katy M. , Mullen Brian , Quinn Anna , Scheufele Pia , Gola Susanne , Gonnelli Federica , Bozzato Matteo , Pratt Jedd , Sala Wiktoria , Mullin Sinead , Kirwan Laura , Dardevet Dominique , Guillet Christelle , De Vito Giuseppe , Visser Marjolein , Volkert Dorothee , Corish Clare A.
Published: October 2024

Reduced appetite with ageing is a key factor that may increase risk of undernutrition. The objective of this study is to determine the impact of innovative plant protein fibre (PPF) products within a personalised optimised diet (PD), a physical activity (PA) programme, and their combination on appetite, and other nutritional, functional and clinical outcomes in community-dwelling older adults in a multi-country randomised controlled intervention trial. One hundred and eighty community-dwelling adults (approximately sixty per trial centre in Germany, Ireland and Italy) aged 65 years and over will be recruited to participate in a 12-week, parallel-group, controlled trial. Participants will be randomised into one of four groups: 1, PD (incorporating two PPF products): 2, PA; 3, PD + PA; and 4, no intervention (control). The primary outcome is appetite measured by visual analogue scales and energy intake from an ad libitum test meal. Secondary outcomes include fasting and postprandial appetite-related gut hormones, Simplified Nutritional Appetite Questionnaire score, body composition, cardiorespiratory fitness, muscle strength, physical function and PA. In addition, self-efficacy, cognitive status, dietary restraint, depressive symptoms and compliance and acceptability of the intervention will be assessed. Metabolomic profiles, RMR, muscle motor unit properties and gut microbiome will also be assessed to explore potential underlying mechanisms. This multi-centre randomised controlled trial will advance knowledge on how PD (incorporating PPF products), PA and their combination influence appetite, nutritional status and related health outcomes in community-dwelling older adults and contribute to the prevention of undernutrition. Trial registration: Clinical Trials.gov Registry NCT05608707 (registered on 2 November 2022). Protocol Version: NCT05608707 Version 4 (registered on 29 September 2023).
Social Networks and Elite Entrepreneurship in Latin America: Evidence from the Industrialization of Antioquia
Authors: Mejía Javier
Published: October 2024

Elites were pivotal for Latin America’s modernization, yet granular evidence of their industrial entrepreneurship is limited. I study Antioquia, an early center of industrialization, from the late nineteenth to early twentieth centuries. Analyzing elite interactions via newfound archival data and exploiting unexpected deaths as exogenous shocks, I find global connectivity—not local—drove industrial entrepreneurship. This suggests diverse resources unavailable in markets but accessible through global connections were crucial in forming industrial ventures. Thus, this paper depicts how social capital shapes elite outcomes.
Borders, Migration and Asilo Sagrado: How Early Central American Nations Used Open Borders to Reinforce Sovereignty
Authors: Mendiola Daniel
Published: October 2024

This article contributes to broader discussions of early Latin American nation-making by focusing on the interplay among territory, sovereignty and human movement in nineteenth-century Central America. How did early Central American nations create sovereign spaces? And how did human movement in turn impact the meanings of bordered spaces? Drawing from constitutions, legal codes and archival documents related to the implementation of migration laws, the central argument of this article is that Central American governments typically treated free migration not as a threat to sovereignty but as an opportunity to reinforce sovereignty over the fixed spaces through which people moved.
Guwantu: The Yongzheng Emperor's (r. 1723–1735) ‘Illustrated Inventory of Ancient Playthings’ (1729) and Imperial Collecting in Eighteenth Century China
Authors: Grimberg Phillip
Published: October 2024

This article provides a conceptual framework that fills a critical gap at the intersection of Chinese art and cultural history. It focuses on the Yongzheng emperor's ‘Illustrated Inventory of Ancient Playthings’ (Guwantu) and its significance within the context of the collecting and courtly elite culture of the High Qing. Through a comprehensive examination of scroll B/C.8–V&A of the Guwantu itself, as well as the relevant source material, this study elucidates the dynamics that shaped the connections between artist, collector and object in the context of the scroll. Furthermore, this contribution throws light on the multiple entangled relationships that underpinned imperial collecting practices of the period, ultimately offering new insights into the socio-cultural milieu of collectors and connoisseurs in early eighteenth-century China.
A note on extremal constructions for the Erdős–Rademacher problem
Authors: Liu Xizhi , Pikhurko Oleg
Published: October 2024

For given positive integers
$r\ge 3$
,
$n$
and
$e\le \binom{n}{2}$
, the famous Erdős–Rademacher problem asks for the minimum number of
$r$
-cliques in a graph with
$n$
vertices and
$e$
edges. A conjecture of Lovász and Simonovits from the 1970s states that, for every
$r\ge 3$
, if
$n$
is sufficiently large then, for every
$e\le \binom{n}{2}$
, at least one extremal graph can be obtained from a complete partite graph by adding a triangle-free graph into one part.

In this note, we explicitly write the minimum number of
$r$
-cliques predicted by the above conjecture. Also, we describe what we believe to be the set of extremal graphs for any
$r\ge 4$
and all large
$n$
, amending the previous conjecture of Pikhurko and Razborov.
The hidden dangers of the coronary anomalies: an ARCAPA case report
Authors: Castillo-Aguilar Luis F. , Rivera-Rodríguez Leonardo , Cervantes-Salazar Jorge L.
Published: October 2024

An anomalous origin of the right coronary artery from the pulmonary artery case report. The diagnosis was made by angiotomography. Reimplantation of the right coronary artery into the ascending aorta and reconstruction of the pulmonary artery were conducted.
Mobile health monitoring of children with CHDs
Authors: LeBlanc Megan E. , Tallent Sarah , Hornik Christoph P. , Camitta Michael G.W. , Schmelzer Anne C. , Kang Lillian , Hill Kevin D.
Published: October 2024

Background:

Mobile health has been shown to improve quality, access, and efficiency of health care in select populations. We sought to evaluate the benefits of mobile health monitoring using the KidsHeart app in an infant CHD population.

Methods:

We reviewed data submitted to KidsHeart from parents of infants discharged following intervention for high-risk CHD lesions including subjects status post stage 1 single ventricle palliation, ductal stent or surgical shunt, pulmonary artery band, or right ventricular outflow tract stent. We report on the benefits of a novel mobile health red flag scoring system, mobile health growth/feed tracking, and longitudinal neurodevelopmental outcomes tracking.

Results:

A total of 69 CHD subjects (63% male, 41% non-white, median age 28 days [interquartile range 20, 75 days]) were included with median mobile health follow-up of 137 days (56, 190). During the analytic window, subjects submitted 5700 mobile health red flag notifications including 245 violations (mean [standard deviation] 3 ± 3.96 per participant) with 80% (55/69) of subjects submitting at least one violation. Violations precipitated 116 interventions including hospital admission in 34 (29%) with trans-catheter evaluation in 15 (13%) of those. Growth data (n = 2543 daily weights) were submitted by 63/69 (91%) subjects and precipitated 31 feed changes in 23 participants. Sixty-eight percent of subjects with age >2 months submitted at least one complete neurodevelopment questionnaire.

Conclusion:

In our initial experience, mobile health monitoring using the KidsHeart app enhanced interstage monitoring permitting earlier intervention, allowed for remote tracking of growth feeding, and provided a means for tracking longitudinal neurodevelopmental outcomes.
Global longitudinal strain is a surrogate marker for time constant of isovolumic relaxation in post-Fontan operation patients with single right ventricle and preserved ejection fraction
Authors: Suzuki Kota , Nii Masaki , Tanabe Takehiro , Ishigaki Mizuhiko , Sato Keisuke , Yoshimoto Jun , Kim Sung-Hae , Mitsushita Norie , Tanaka Yasuhiko
Published: October 2024

Background:

The time constant of isovolumic relaxation is an established index of ventricular relaxation, a major component of diastolic function, even in a single right ventricle. However, the specific echocardiographic parameters for estimating diastolic dysfunction are insufficient for a single right ventricle. This study aimed to investigate the echocardiographic indices associated with time constant of isovolumic relaxation in post-Fontan operation patients with a single right ventricle.

Methods:

We included 39 patients with hypoplastic left heart syndrome after Fontan operation with an ejection fraction ≥45% and preserved valve function. First, the correlation between echocardiographic parameters and time constant of isovolumic relaxation was examined, and partial correlation coefficients were calculated using age and heart rate as covariates. Next, univariate regression analysis was performed using time constant of isovolumic relaxation as the objective variable and echocardiographic parameters as independent variables, followed by multivariate regression analysis incorporating parameters with p < 0.10.

Results:

Among the echocardiographic parameters, global longitudinal strain correlated most strongly with time constant of isovolumic relaxation (r = 0.778, p < 0.001). This was consistent with the partial correlation coefficients (r = 0.707, p < 0.001). Using stepwise multivariate regression analysis, only global longitudinal strain was found to be an independent predictor of time constant of isovolumic relaxation (adjusted R2 = 0.551).

Conclusions:

Global longitudinal strain could be used as a surrogate marker of time constant of isovolumic relaxation, an invasive indicator of relaxation impairment, in post-Fontan operation patients with a single right ventricle, preserved ejection fraction, and valve function.
Navigating conflicting expectations in addressing healthcare scarcity: a q-methodology study on the Dutch National Health Care Institute
Authors: van de Sande Jolien , de Graaff Bert , Delnoij Diana , de Bont Antoinette
Published: October 2024

In many European countries, semi-autonomous agencies have been created in health policy to safeguard general public interests. In executing their tasks, these agencies need to deal with conflicting expectations. Particularly avoiding the risk of regulatory capture and aligning with parent ministries are frequently studied challenges, even more so when complex issues such as scarcity are at stake. In this paper, we use q-methodology to provide a thorough overview of the debate regarding the role of an important agency in the Dutch healthcare system; the National Health Care Institute (Zorginstituut Nederland). We conducted 41 q-interviews with agency employees, evaluators, regulatees, ministry employees, health policy experts, members of its advisory committees, and peer agencies. We identify three viewpoints on what the agency should focus on. These are on societally relevant issues, strict package management, and efficient organisation of care. In doing so, our study shows how agencies are pulled in different directions by conflicting expectations. We show that this can be problematic because it complicates a clear role of the agency that allows addressing such issues. We thereby contribute to theories on agencies' complex relations with their external environment such as regulatory capture, tripartism, reflexive regulation, legal boundaries, and stewardship theory.
Living with Mental Illness
Authors: Emons Barbara , Eigendorf Lara , Haussleiter Ida Sibylle , Bender Stefan , Burchard Johann Falk , Haas Claus-Rüdiger , Holtmann Martin , Norra Christine , Hoffmann Knut , Kronmüller Klaus-Thomas , Juckel Georg
Published: October 2024

Abstract: Objective: The situation of patient’s relatives is still not broadly studied in psychiatry. Their needs are often overlooked. Method: We developed a digital questionnaire concerning the patient’s sociodemographic, disease-related, and family-related data and had the patient’s therapist fill it out. The patients included ( N = 1766) were persons hospitalized on a selected date. Results: One-third of patients had at least one relative with mental illness, prior treatment, or need for treatment. The main diagnoses in relatives were affective, substance use, and somatoform disorders, often in concordance with their index patient. Teenage patients had the most affected relatives. The therapists of the minors included were better informed about their familial situation, whereas the therapists of the 30–59-year-olds knew the least. Conclusions: The comparably lower rate of affected relatives in adults stems most likely from underassessment and needs further investigation.
Strong Energy Conversion by a Ribbon‐Like Magnetic Structure in Tailward High‐Speed Flow
Authors: Du C. X. , Fu H. S. , Cao J. B. , Wang Z. , Grigorenko E. , Fu W. D.
Published: October 2024

The tailward high‐speed flows, in which various kinetic processes and magnetic structures can be embedded, are usually produced by the magnetic reconnection in the Earth's magnetotail. Here, using high‐resolution measurements from the Magnetospheric Multiscale (MMS) mission, we report an intense current in the tailward high‐speed flow. The current density can reach ∼180 nA/m2 and is primarily carried by electrons. Taking advantage of the First‐Order Taylor Expansion (FOTE) method, we reveal that such an intense current is associated with a ribbon‐like magnetic structure. A large electric field, reaching ∼90 mV/m, is also observed at the magnetic structure. The Hall term dominates the electric field, however, the contribution from the pressure gradient term and the electron inertial term is nonnegligible and can lead to strong energy conversion (E  ⋅   J > 2 nW/m3) through the synergistic action with the intense current. This study improves the understanding of the current behaviors and energy conversion associated with magnetic structures in the Earth's magnetotail.
Electron Pitch Angle Distributions in Magnetotail Tailward Flows
Authors: Wei Y. Y. , Huang S. Y. , Jiang K. , Yuan Z. G. , Xu S. B. , Zhang J. , Xiong Q. Y. , Wang Z. , Lin R. T. , Yu L.
Published: October 2024

Electron pitch angle distributions (PADs) are crucial to revealing electron acceleration and heating in geospace. The electron PADs in the Earth's magnetotail have been widely studied by statistical or case analysis. However, the statistical features of electron PADs in tailward flows are still unclear. We survey data from the Magnetospheric Multiscale (MMS) satellite to statistically investigate electron PADs in tailward flows in the Earth's magnetotail for the first time. We find that for most (66.3%) tailward flows, electrons with energy from 0.1 to 30 keV are mainly field‐aligned. The PADs of suprathermal (>2 keV) electrons in a part of tailward flows (26.3%) are mostly isotropic. Additionally, the perpendicular‐dominated PADs of suprathermal electrons only exist in a few (7.4%) tailward flows. According to the different dominant PADs of suprathermal electrons, the tailward flows are classified into three types: field‐aligned‐dominated type, isotropic‐dominated type and perpendicular‐dominated type flows. The dependence of electron PADs on plasma environmental parameters is investigated in these three types of flows. For field‐aligned‐dominated type flows, the field‐aligned anisotropy decreases toward the central plasma sheet (CPS) and with the increase of the energy. In addition, it is found that the field‐aligned anisotropy in the field‐aligned‐dominated tailward flows reduces noticeably when the |Vix| exceeds 800 km/s. In isotropic‐dominated type flows, the field‐aligned anisotropy of electrons with energy ≥10 keV also shows a slight decreasing trend toward the CPS. For perpendicular‐dominated type flows, the perpendicular anisotropy exhibits two non‐monotonic processes, initially increasing and then decreasing with the increase of distance from the CPS; while becomes more evident for higher energy electrons. Our statistical results indicate that in tailward flows, electron anisotropy depends on the distance from the CPS, energy and plasma flow velocity. Tailward flows are associated with the transport of plasma toward the distant tail, and the statistical analysis of electron PADs in these flows can improve our understanding of the related electron dynamics in the magnetotail.
Simulating the Response of Tropical Cyclones to Potential Nuclear War
Authors: Zhao Kai , Zhao Haikun , Coupe Joshua , Klotzbach Philip J. , Wu Liguang
Published: October 2024

Nuclear war would cause massive amounts of smoke from its associated explosions and fires that would subsequently inject copious amounts of aerosols into the stratosphere. There would also be considerable changes to the global climate system, threatening human health and sustainability. Our work reveals a reduction of global‐scale tropical cyclones (TCs) from a simulation of a nuclear war scenario that could produce ∼150 million tons of smoke. In response to nuclear war, there would be spatially uneven cooling that would result in an anomalous sea surface temperature (SST) gradient pattern. Associated with this would be an anomalous zonal vertical circulation, tending to suppress upward motion and increase vertical wind shear over all TC main development regions, largely explaining the observed TC reduction at regional and global scales. This study improves our understanding of the impact of nuclear war on the TC environment.
An Economical Open‐Source Lagrangian Drifter Design to Measure Deep Currents in Lakes
Authors: McCaffrey Lewis , Koeberle Alexander L.
Published: October 2024

The objective was to construct and test an economical, accurate, and open‐source Lagrangian drifter design suitable for lakes <200 km2. Lagrangian drifters are used to trace water currents in marine and freshwater settings and comprise of a low‐friction surface float containing instrumentation for location and environmental measurement, tethered to a high‐friction drogue at the depth of interest. Oceanic drifters are robust but expensive, and this design tailored to inland lake waterbodies fills a durability and cost gap for lake environments. Water‐following characteristics were tested using theoretical drag coefficient calculations, practical drag measurements, and comparison of wind and drifter vectors while deployed on two deep inland lakes (maximum area 175 km2) in the Finger Lakes region of New York, USA. The ratio of drag between float and drogue met or exceeded the minimum value of 40 recommended in the literature, and the vectors of wind and drifter during deployment were independent of one another, meaning the device accurately traced the movement of water currents at depth without undue influence of wind and waves. Each device cost USD $265 in 2021 and was built from materials readily available at hardware and sporting goods stores, allowing their use by research institutions and communities with smaller budgets. This design reliably measured lake currents at sampling depths that ranged from 2 to 30 m. We anticipate that this design will have application to a wide range of hydrodynamic and ecological research where empirical insights to physical processes like lake currents are sought by scientists and managers.
Leveraging pleiotropy for the improved treatment of psychiatric disorders
Authors: Woodward Damian J. , Thorp Jackson G. , Middeldorp Christel M. , Akóṣílè Wọlé , Derks Eske M. , Gerring Zachary F.
Published: October 2024

Over 90% of drug candidates fail in clinical trials, while it takes 10–15 years and one billion US dollars to develop a single successful drug. Drug development is more challenging for psychiatric disorders, where disease comorbidity and complex symptom profiles obscure the identification of causal mechanisms for therapeutic intervention. One promising approach for determining more suitable drug candidates in clinical trials is integrating human genetic data into the selection process. Genome-wide association studies have identified thousands of replicable risk loci for psychiatric disorders, and sophisticated statistical tools are increasingly effective at using these data to pinpoint likely causal genes. These studies have also uncovered shared or pleiotropic genetic risk factors underlying comorbid psychiatric disorders. In this article, we argue that leveraging pleiotropic effects will provide opportunities to discover novel drug targets and identify more effective treatments for psychiatric disorders by targeting a common mechanism rather than treating each disease separately.
Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring
Authors: Andruszewski David , Uhlfelder David C. , Desiato Genni , Regen Tommy , Schelmbauer Carsten , Blanfeld Michaela , Scherer Lena , Radyushkin Konstantin , Pozzi Davide , Waisman Ari , Mufazalov Ilgiz A.
Published: October 2024

Prenatal imprinting to interleukin 17A (IL-17A) triggers behavioral disorders in offspring. However, reported models of maternal immune activation utilizing immunostimulants, lack specificity to elucidate the anatomical compartments of IL-17A’s action and the distinct behavioral disturbances it causes. By combining transgenic IL-17A overexpression with maternal deficiency in its receptor, we established a novel model of prenatal imprinting to maternal IL-17A (acronym: PRIMA-17 model). This model allowed us to study prenatal imprinting established exclusively through embryo-restricted IL-17A responses. We demonstrated a transfer of transgenic IL-17A across the placental barrier, which triggered the development of selected behavioral deficits in mouse offspring. More specifically, embryonic responses to IL-17A resulted in communicative impairment in early-life measured by reduced numbers of nest retrieval calls. In adulthood, IL-17A-imprinted offspring displayed an increase in anxiety-like behavior. We advocate our PRIMA-17 model as a useful tool to study neurological deficits in mice.
Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer
Authors: Øgaard Nadia , Jensen Sarah Østrup , Ørntoft Mai-Britt Worm , Demuth Christina , Rasmussen Mads Heilskov , Henriksen Tenna Vesterman , Nors Jesper , Frydendahl Amanda , Lyskjær Iben , Nesic Marijana , Therkildsen Christina , Kleif Jakob , Gögenur Mikail , Jørgensen Lars Nannestad , Vilandt Jesper , Seidelin Jakob Benedict , Gotschalck Kåre Anderson , Jaensch Claudia , Andersen Berit , Løve Uffe Schou , Thorlacius-Ussing Ole , Andersen Per Vadgaard , Kolbro Thomas , Monti Alessio , Kildsig Jeppe , Bondeven Peter , Schlesinger Nis Hallundbæk , Iversen Lene Hjerrild , Rasmussen Morten , Gögenur Ismail , Bramsen Jesper Bertram , Andersen Claus Lindbjerg
Published: October 2024

Background

Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a ‘low-ctDNA-shedding’ and ‘less-aggressive’ subgroup.

Methods

ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722).

Results

After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2–0.8, Cohort#2: OR: 0.7, 95%CI: 0.5–0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3–1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4–1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1–0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2–0.6).

Conclusions

Our study suggests that asymptomatic patients are enriched for a ‘low-ctDNA-shedding-low-recurrence-risk’ subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.
The SRC-family serves as a therapeutic target in triple negative breast cancer with acquired resistance to chemotherapy
Authors: Egeland Eivind Valen , Seip Kotryna , Skourti Eleni , Øy Geir Frode , Pettersen Solveig J. , Pandya Abhilash D. , Dahle Maria A. , Haugen Mads H. , Kristian Alexander , Nakken Sigve , Engebraaten Olav , Mælandsmo Gunhild M. , Prasmickaite Lina
Published: October 2024

Background

Resistance to chemotherapy, combined with heterogeneity among resistant tumors, represents a significant challenge in the clinical management of triple negative breast cancer (TNBC). By dissecting molecular pathways associated with treatment resistance, we sought to define patient sub-groups and actionable targets for next-line treatment.

Methods

Bulk RNA sequencing and reverse phase protein array profiling were performed on isogenic patient-derived xenografts (PDX) representing paclitaxel-sensitive and -resistant tumors. Pathways identified as upregulated in the resistant model were further explored as targets in PDX explants. Their clinical relevance was assessed in two distinct patient cohorts (NeoAva and MET500).

Results

Increased activity in signaling pathways involving SRC-family kinases (SFKs)- and MAPK/ERK was found in treatment resistant PDX, with targeted inhibitors being significantly more potent in resistant tumors. Up-regulation of SFKs- and MAPK/ERK-pathways was also detected in a sub-group of chemoresistant patients after neoadjuvant treatment. Furthermore, High SFK expression (of either SRC, FYN and/or YES1) was detected in metastatic lesions of TNBC patients with fast progressing disease (median disease-free interval 27 vs 105 months).

Conclusions

Upregulation of SFK-signaling is found in a subset of chemoresistant tumors and is persistent in metastatic lesions. Based on pre-clinical results, these patients may respond favorably to treatment targeting SFKs.
SLAMF7 (CD319) on activated CD8+ T cells transduces environmental cues to initiate cytotoxic effector cell responses
Authors: Lingel Holger , Fischer Laura , Remstedt Sven , Kuropka Benno , Philipsen Lars , Han Irina , Sander Jan-Erik , Freund Christian , Arra Aditya , Brunner-Weinzierl Monika C.
Published: October 2024

CD8+ T-cell responses are meticulously orchestrated processes regulated by intercellular receptor:ligand interactions. These interactions critically control the dynamics of CD8+ T-cell populations that is crucial to overcome threats such as viral infections or cancer. Yet, the mechanisms governing these dynamics remain incompletely elucidated. Here, we identified a hitherto unknown T-cell referred function of the self-ligating surface receptor SLAMF7 (CD319) on CD8+ T cells during initiation of cytotoxic T-cell responses. According to its cytotoxicity related expression on T effector cells, we found that CD8+ T cells could utilize SLAMF7 to transduce environmental cues into cellular interactions and information exchange. Indeed, SLAMF7 facilitated a dose-dependent formation of stable homotypic contacts that ultimately resulted in stable cell-contacts, quorum populations and commitment to expansion and differentiation. Using pull-down assays and network analyses, we identified novel SLAMF7-binding intracellular signaling molecules including the CRK, CRKL, and Nck adaptors, which are involved in T-cell contact formation and may mediate SLAMF7 functions in sensing and adhesion. Hence, providing SLAMF7 signals during antigen recognition of CD8+ T cells enhanced their overall magnitude, particularly in responses towards low-affinity antigens, resulting in a significant boost in their proliferation and cytotoxic capacity. Overall, we have identified and characterized a potent initiator of the cytotoxic T lymphocyte response program and revealed advanced mechanisms to improve CD8+ T-cell response decisions against weak viral or tumor-associated antigens, thereby strengthening our defense against such adversaries.
Inhibition of primary cilia-hedgehog signaling axis triggers autophagic cell death and suppresses malignant progression of VHL wild-type ccRCC
Authors: Tian Shuo , Du Songliang , Wang Chenfeng , Zhang Yu , Wang Hanfeng , Fan Yang , Gao Yu , Gu Liangyou , Huang Qingbo , Wang Baojun , Ma Xin , Zhang Xu , Huang Yan
Published: October 2024

Primary cilia are present on renal tubules and are implicated to play a pivotal role in transducing signals during development; however, the oncogenic role of cilia in clear cell renal cell carcinoma (ccRCC) has not been examined. Here we show that VHL wild-type ccRCC cell lines have a high incidence of primary cilia, and a high frequency of primary cilia is positively correlated with VHL expression and poor prognosis. Besides, the depletion of KIF3A and IFT88, genes required for ciliogenesis, significantly inhibited tumor proliferation and metastasis in vitro and in vivo. Further analysis found that mutations of key genes in hedgehog signaling are enriched in VHL wild ccRCC, its downstream signaling activation depends on ciliogenesis. Moreover, depletion of primary cilia or suppression of hedgehog pathway activation with inhibitor-induced robust autophagic cell death. Collectively, our findings revealed that primary cilia could serve as a diagnostic tool and provide new insights into the mechanism of VHL wild-type ccRCC progression. Targeting the primary cilia-hedgehog pathway may represent an effective therapeutic strategy for VHL wild-type ccRCC.