bluuebunny/crossref_metadata_2025 huggingface dataset:
Unrecognized bone fractures of the extremities in Emergency Radiology: the invisible become visible on 3D 80 micron
Authors: Lo Mastro Antonio , Boccia Francesco , Berritto Daniela , Stoppino Luca Pio , Guerra Egidio , D’Alessandro Paolo , Pinto Fabio , Grassi Francesca
Published: June 2024

Purpose

In the last few years CBCT’s applications have expanded, especially in the field of musculoskeletal. In this study, we aim to analyze the diagnostic value and the use of CBCT in Emergency Radiology for the evaluation of extremity trauma.

Methods

The present retrospective study included a total of 72 distal limb trauma cases who were admitted in the Emergency Radiology Department of “Policlinico Riuniti di Foggia” during September 2022 to December 2023. All the cases required further medical diagnostic investigation after an initial examination CR. Among these, 12 were excluded for suspected poly-traumas and MDCT was directly performed. Of the 60, divided into 2 groups, 42 had negative or non-diagnostic CR result, and CBCT was performed as second-level exam, 18 with a fracture confirmed by CR underwent CBCT for surgical planning.

Results

In the first group, 17 (40.5%) had negative CR results, and 25 (59.5%) had doubtful/non-diagnostic CR results. 25 (59.5%) presented a positive CBCT exam for fracture. In the second group, anyone required further diagnostic investigations for orthopedic surgery.

Conclusions

Thanks to high spatial resolution, low radiation dose, fast acquisition, and its three-dimensionality in space (3D), CBCT could be the first investigation in the cases of fractures clinically suspicious in locations with bone overlap.
The clinical pathway in ADMiRE, Ireland’s first public specialist service for children and adolescents with attention deficit hyperactivity disorder
Authors: McGrath Jane
Published: June 2024

Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder occurring in approximately one in twenty young people in Ireland, and in one-third of those attending Irish Child and Adolescent Mental Health Services (CAMHS). It is important to treat ADHD, as un/poorly treated ADHD is associated with a raft of negative health and socio-economic outcomes. Effective interventions for ADHD are available, and the use of standardised, evidence-based pathways for assessment and management of ADHD optimises outcomes. Despite this, there is no national standardised clinical pathway for assessment and treatment of ADHD in Ireland. ADMiRE, the first public healthcare specialist service for children and adolescents in Ireland, has developed a strongly evidence-based, efficient, effective and safe clinical pathway for assessment and management of ADHD. This paper describes the ADMiRE Clinical Pathway and references ADMiRE resources that are available to other services.
Hypersonic turbulent boundary layer over the windward side of a lifting body
Authors: Dong Siwei , Yu Ming , Tong Fulin , Wang Qian , Yuan Xianxu
Published: June 2024

In the present study, we performed direct numerical simulations for a hypersonic turbulent boundary layer over the windward side of a lifting body, the HyTRV model, at Mach number

$6$

and attack angle 2

$^{\circ }$

to investigate the global and local turbulent features, and evaluate its difference from canonical turbulent boundary layers. By scrutinizing the instantaneous and averaged flow fields, we found that the transverse curvature on the windward side of the HyTRV model induces the transverse opposing pressure gradients that push the flow on both sides towards the windward symmetry plane, yielding significant effects of the azimuthal inhomogeneity and large-scale cross-stream circulations, moderate and azimuthal independent influences of adverse pressure gradient, and negligible impact of the mean flow three-dimensionality. Further inspecting the local turbulent statistics, we identified that the mean and fluctuating velocity become increasingly similar to the highly decelerated turbulent boundary layers over flat plates in that the mean velocity deficit is enhanced, and the outer layer Reynolds stresses are amplified as it approaches the windward symmetry plane, and prove to be self-similar under the scaling of Wei & Knopp (J. Fluid Mech., vol. 958, 2023, A9) for adverse-pressure-gradient turbulent boundary layers. Conditionally averaged Reynolds stresses based on strong sweeping and ejection events demonstrated that the Kelvin–Helmholtz instability of the strong embedded shear layer induced by the large-scale cross-stream circulations is responsible for the turbulence amplification in the outer layer. The strong Reynolds analogy that relates the mean velocity and temperature was refined to incorporate the non-canonical effects, showing considerable improvements in the accuracy of such a formula. On the other hand, the temperature fluctuations are still transported passively, as indicated by their resemblance to the velocity. The conclusions obtained in the present study provide potentially profitable information for turbulent modelling modification for the accurate predictions of skin friction and wall heat transfer.
Anti-corruption Audits and Citizens’ Trust in Audit and Auditee Institutions
Authors: Barbabela Letícia
Published: June 2024

Anticorruption audits may deter corruption and signal to citizens that institutions are proactively combating it. However, by detecting and reporting corruption, audits might also unintentionally erode trust in institutions. Therefore, the impact of audits potentially hinges on whether they uncover corruption. Audit institutions, not implicated in the corruption they uncover, might be less likely to experience a decline in trust compared to auditee institutions. This study uses survey and administrative data from Brazil, leveraging a federal anti-corruption program that randomly selects municipalities for auditing. Results do not support the claim that audits boost institutional trust. Individuals in audited municipalities show no different levels of trust in local government or the audit institution than those in non-audited municipalities, and the coefficients may even indicate a negative effect. Additionally, audit institutions may not be better insulated from the corrosive effects of uncovering corruption than the institutions they audit.
Deconstructing racial code words
Authors: Pfeiffer Deirdre , Hu Xiaoqian
Published: June 2024

Racism has become more covert in post-civil rights America. Yet, measures to combat it are hindered by inadequate general knowledge on what “colorblind” race talk says and does and what makes it effective. We deepen understanding of covert racism by investigating one type of discourse – racial code words, which are (1) indirect signifiers of racial or ethnic groups that contain (2) at least one positive or negative value judgment and (3) contextually implied or salient meanings. Through a thematic analysis of 734 racial code words from 97 scholarly texts, we develop an interpretive framework that explains their tropes, linguistic mechanisms and unique roles in perpetuating racism, drawing from race, linguistic and cultural studies. Racial code words promote tropes of White people’s respectability and privilege and Racial/Ethnic Minorities’ pathology and inferiority in efficient, adaptable, plausibly deniable and almost always racially stratifying ways, often through euphemism, metonymy and othering. They construct a “colorblind” discursivity and propel both “epistemic racism” (racism in knowledge) and systemic racism (racism in action). We further strengthen applications of Critical Race Theory in sociolegal studies of race by presenting a “racial meaning decoding tool” to assist legal and societal measures to detect coded racism.
Concerns about Contextual Values in Science and the Legitimate/Illegitimate Distinction
Authors: de Melo-Martín Inmaculada
Published: June 2024

Philosophers of science have come to accept that contextual values can play unavoidable and desirable roles in science. This has raised concerns about the need to distinguish legitimate and illegitimate value influences in scientific inquiry. I discuss here four such concerns: epistemic distortion, value imposition, undermining of public trust in science, and the use of objectionable values. I contend that preserving epistemic integrity and avoiding value imposition provide good reasons to attempt to distinguish between legitimate and illegitimate influences of values in science. However, the trust and the objectionable values concerns constitute no good reason for demarcation criteria.
The Conduct of Hostilities, Attack Effects, and Criminal Accountability
Authors: Corn Geoffrey
Published: June 2024

War crimes related to the decision to carry out attacks during the conduct of hostilities are almost always defined in terms of conduct and not result (Article 8(2)(b) of the Rome Statute of the International Criminal Court). Yet it is common for critiques of such decisions to focus on attack results as proof of their alleged illegality. While such results are probative of compliance or non-compliance with international humanitarian law rules regulating the conduct of hostilities, they should rarely be indisputable. This article addresses the challenge of attaching probative value to attack results when assessing responsibility for alleged war crimes based on allegedly illicit attack decisions.
Gedächtnis trifft Einleitung. Ein neuer Blick auf alte Fragen
Authors: Huebenthal Sandra
Published: June 2024

German Abstract

Ausgehend von der kulturwissenschaftlichen Forschung zu Familienalben und deren Gemeinsamkeiten mit dem Neuen Testament lädt dieser Beitrag dazu ein, darüber nachzudenken, was sich verändert, wenn wir die Fragen der Einführung in das Neue Testament durch die Brille der Theorie des sozialen Gedächtnisses betrachten. Aufbauend auf Forschungsergebnissen der Oral History und kulturwissenschaftlichen Gedächtnistheorie wird argumentiert, dass die allgemeine Einleitung in den Bereich des kulturellen Gedächtnisses und die spezielle Einleitung in den Bereich des sozialen/kollektiven Gedächtnisses fällt. Beide sind durch den Floating Gap getrennt, was die vielfach wahrgenommenen Veränderungen in der ersten Hälfte des zweiten Jahrhunderts erklärt. Im nächsten Schritt wird ein Modell, das auf dem Dreigenerationengedächtnis, der Generational Gap (nach einer Generation), der Floating Gap (nach 3-4 Generationen) und den ersten Generationen von Jesus-Anhängern aufbaut, mit Vorschlägen zur Datierung neutestamentlicher Bücher aus der Einleitungswissenschaft ins Gespräch gebracht. Es zeigt sich, dass die vor und nach dem Generational Gap verwendeten Genres je unterschiedliche Eigenschaften haben, die den Erwartungen an Medien des sozialen und kollektiven Gedächtnisses entsprechen. Der Beitrag schließt mit allgemeinen Fragen zu Medien und Medienwandel im Neuen Testament, d.h. Mündlichkeit und Schriftlichkeit, identische Texte und Textkritik, dem Kanon als primärem Kontext, der Ausweitung des Geltungsbereichs sowie fluiden Gattungen, und kommt zu dem Schluss, dass kulturwissenschaftliche Gedächtnistheorie in der Tat neue Perspektiven für die Einleitungswissenschaft bietet.
Origen's Sources of Exegetical Authority: The Construction of an Inspired Exegete in the Pauline Lineage
Authors: DeCock Miriam
Published: June 2024

In this paper, I examine several sources of authority to which Origen laid claim as he set about the task of interpreting scripture. On occasion, in both his commentaries and his homilies, Origen provided accounts of his access to three different, though connected sources of authority that contributed to his self-presentation as an expert interpreter. These sources are as follows: 1) participation in the lineage of the apostles, particularly his exegetical role model, Paul. The second source of authority is a result of the first: 2) direct communication from the Logos, whom he understands to be Christ himself, and 3) angelic assistance and engagement with his pastoral exegetical project. In some instances, Origen even claimed to be on par with two of these sources of authority; he can be found claiming to have exegetical abilities similar to Paul's and, on some rare occasions, to have reached the same epistemological level as the angels. This analysis provides us not only with a case study of the kind of self-fashioning and authorising strategies used by elite scriptural exegetes in the first few centuries of the common era, but it also allows us to shift our focus away from exegetical methods towards the figure, personality and social position of the exegete him or herself. From this shift of focus we gain a better appreciation of a topic to which exegetical authors themselves dedicated considerable energy: just who it was that could occupy the office of authoritative Christian exegete and why.
The Greetings of Romans 16 and the Audience of Romans
Authors: Head Peter M.
Published: June 2024

This short paper considers and critiques the view that the named people greeted in Romans 16.3–16 are not also among the recipients of the letter to ‘all God's beloved in Rome’ (Rom 1.7). Variants of this view spring from the work of Mullins (1968): that the second-person greeting involves the greeting of ‘a third party who is not intended to be among the immediate readership of the letter’ (Mullins, 1968: 420) and are found in Thorsteinsson (2003), Stowers (2015) and Campbell (2023). A series of arguments are made against this view. In particular, the plural form of the imperative (ἀσπάσασθɛ) and the open nature of the addressees mean that Mullins' simple principle does not apply. In addition, Paul's usage elsewhere (including in Romans 16.16) contradicts Mullins' principle.
Posterior cingulate and medial prefrontal excitation-inhibition balance in euthymic bipolar disorder
Authors: Tseng Huai-Hsuan , Wu Cheng Ying , Chang Hui Hua , Lu Tsung-Hua , Chang Wei Hung , Hsu Chia-Fen , Lin Ren-Yi , Yeh Ding-Ruey , Shaw Fu-Zen , Yang Yen Kuang , Chen Po See
Published: June 2024

Background

Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD).

Method

Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test.

Results

euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068).

Conclusions

Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.
THE MONUMENTALITY OF GLADIATORIAL GRAFFITI IN THE FLAVIAN AMPHITHEATRE: A CONTEXTUAL APPROACH
Authors: Tafaro Alessandra
Published: June 2024

The present article offers a new interpretation of the gladiatorial graffiti preserved within the Flavian Amphitheatre from a contextual perspective. Although recent scholarship has set a solid foundation for investigating the role and nature of gladiatorial graffiti, a contextual examination of this epigraphic category represents a major desideratum. The article investigates graffiti within the epigraphic environment of the Flavian Amphitheatre. It examines the juxtaposition of graffiti and official inscriptions, their interaction with spatial and material surroundings and their distinctiveness as visual and material media with which to perpetuate the fleeting arena performances. By combining close reading with a new visual representation of gladiatorial graffiti – created digitally upon autoptic study – the article provides the reader with the first systematic analysis of this exceptional epigraphic record. Challenging critical notions of impermanence and instability, the article explores strategies of memorialization and techniques of temporality performed by graffiti, inviting reflection on the negotiation of and paradoxical takes on the contradictory concept of monumentality in the arena.
“You act as Human, and I will act as AI”
Authors: Fang Kathy
Published: June 2024

Chatbots and natural language processing tools have emerged as a ubiquitous yet exceptional development of algorithmic performativity. The release of ChatGPT on 30 November 2022 signaled a sea change in language-learning technological-performative relations. ChatGPT programs human knowledge as a stylized, computational performance and rehearses the human as technological.
Zuckerberg’s Smile, or Presence in the Age of Digital Technologies
Authors: Taylor Diana
Published: June 2024

AI and AR do not merely coexist with the archive and repertoire as modes of transmission but profoundly alter them and prove profoundly anti-archival. “Live” transmission from body to body is radically altered by digital technologies that simulate presence. “Feeling truly present with another person,” Mark Zuckerberg stated, “is the ultimate dream of social media.” He aspires to create an avatar that can simulate an emotion that he cannot express—and make him more human. Are we being led back into Plato’s cave? Artists and humanists must be centrally involved in the epistemic, ontological, and political changes that accompany these new and evolving forms of transmission.
Rehearsal Studies - Inside the Rehearsal Room: Process, Collaboration and Decision-making. By Robert Marsden. Bloomsbury/Methuen Drama, 2022; 234 pp. $90.00 cloth, $22.00 paper, e-book available. - Rehearsal Practices of Indigenous Women Theatre Makers: Australia, Aotearoa, and Turtle Island. By Liza-Mare Syron. Springer/Palgrave Macmillan, 2021; 129 pp.; illustrations. $64.99 cloth, e-book available. - Staging Sex: Best Practices, Tools, and Techniques for Theatrical Intimacy. By Chelsea Pace, with contributions from Laura Rikard. Routledge, 2020; 138 pp.; illustrations. $136.00 cloth, $35.96 paper, e-book available. - Supporting Staged Intimacy: A Practical Guide for Theatre Creatives, Managers, and Crew. By Alexis Black and Tina M. Newhauser. Routledge, 2023; 278 pp.; illustrations. $160.00 cloth, $31.96 paper, e-book available. - Performing Shakespeare’s Women: Playing Dead. By Paige Martin Reynolds. Bloomsbury/The Arden Shakespeare, 2019; 208 pp. $120.00 cloth, $42.95 paper, e-book available. - Performing Restoration Shakespeare. Edited by Amanda Eubanks Winkler, Claude Fretz, and Richard Schoch. Cambridge University Press, 2023; 292 pp.; illustrations. $93.20 cloth, e-book available. - What Would Garrick Do? Or, Acting Lessons from the Eighteenth Century. By James Harriman-Smith. Bloomsbury, 2024; 256 pp.; illustrations. $90.00 cloth, $31.45 paper, e-book available.
Authors: Roach Joseph
Published: June 2024

Exploring diverse strategies of process-focused research from historical reconstructions of period practices to staged intimacy coaching, seven new titles offer a representative but not exhaustive overview of the expanding field of rehearsal studies.
The relationship between proportions of carbohydrate and fat intake and hyperglycaemia risk in Chinese adults
Authors: Fan Yayun , Huang Qingqing , Gao Honglan , Huang Fengying , He Dingliu
Published: June 2024

Objective:

To address the relationship between the proportions of carbohydrates and fat and hyperglycaemia in the Chinese population.

Design:

A cross-section research involving data from the China Health and Nutrition Survey in 2009, and nutritional status and health indicators were mainly focused.

Setting:

China.

Participants:

8197 Chinese individuals aged over 16 years, including 1345 subjects who had a low-carbohydrate and high-fat diet, 3951 individuals who had a medium proportion of carbohydrate and fat diet, 2660 participants who had a high-carbohydrate and low-fat diet and 241 people who had a very-high-carbohydrate and low-fat diet.

Results:

Subjects with the high-carbohydrate and low-fat diet were significantly associated with an increased risk of hyperglycaemia (OR: 1·142; 95 % CI: 1·022, 1·276) when compared with the individuals with the medium proportion of carbohydrate and fat diet. Meanwhile, people with a very-high-carbohydrate and low-fat diet had a higher risk of hyperglycaemia (OR: 1·829; 95 % CI: 1·377, 2·429). In contrast, the association between participants with a low-carbohydrate and high-fat diet and hyperglycaemia was NS (OR: 1·082; 95 % CI: 0·942, 1·243) with adjusting a series of confounding factors. Furthermore, people with a very-high-carbohydrate and low-fat diet were significantly associated with a higher risk of hyperglycaemia in the major energy levels and social characteristics subgroup.

Conclusions:

We found the high-carbohydrate and low-fat and very-high-carbohydrate and low-fat diets were significantly associated with a high risk of hyperglycaemia. And, the association between low-carbohydrate and high-fat diets and the risk of hyperglycaemia was NS.
Identifying the active content of interventions targeting the psychological well-being of carers of people with motor neuron disease: A systematic review
Authors: Cafarella Paul , Effing Tanja , Chur-Hansen Anna
Published: June 2024

Objectives

The primary aim of this research was to use a taxonomy of behavior change techniques (BCTTv1) to identify, map, and describe the active components of intervention and comparator groups in studies evaluating the psychological well-being (PWB) of motor neuron disease (MND) carers. Secondary aims were to (a) identify absent active ingredients and (b) explore whether variability in the effectiveness of interventions targeting the PWB of MND carers could be better explained through improved characterization of the active content of these interventions.

Methods

Mixed-methods systematic review based on Joanna Briggs Institute methodology for quantitative, qualitative, and mixed-methods reviews and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Content-coding of interventions targeting the PWB of MND carers using BCTTv1 was conducted.

Results

Sixteen manuscripts describing 14 studies were included. Forty-one of the possible 93 behavior change techniques (BCTs, 44%) were identified as active ingredients, while 52 BCTs (56%) were absent. BCTs were identified in all 14 intervention groups and 4 control groups. Four of the 16 overall BCTTv1 categories were absent. Eleven of the 14 studies demonstrated PWB benefits from their interventions.

Significance of results

Identified and absent BCTs and BCTTv1 categories were mapped for all study groups, enabling a transparent characterization of active intervention content associated with positive PWB outcomes. Directions to improve interventions in this nascent field of research included the investigation of relevant untested BCTs in this population and the management of reporting and methodological quality issues.
Biologically effective dose of diflufenican applied preemergence for the control of multiple herbicide–resistant waterhemp in corn
Authors: Soltani Nader , Willemse Christian , Sikkema Peter H.
Published: June 2024

Waterhemp is a dioecious species with wide genetic diversity which has enabled it to evolve resistance to several commonly used herbicide groups in North America. Five field trials were established in Ontario to ascertain the biologically effective doses of diflufenican, a new Group 12 herbicide applied preemergence for control of multiple herbicide–resistant (MHR) waterhemp in corn. Based on regression analysis, the predicted diflufenican doses to elicit 50%, 80%, and 95% MHR waterhemp control were 99, 225, and 417 g ai ha−1, respectively, at 2 wk after application (WAA); 73, 169, and 314 g ai ha−1, respectively, at 4 WAA; and 76, 215, and — (meaning the effective dose was beyond the set of doses in this study) g ai ha−1, respectively, at 8 WAA. The predicted diflufenican doses that would cause a 50%, 80%, and 95% decreases in MHR waterhemp density were 42, 123, and — g ai ha−1; and MHR waterhemp biomass were 72, 167, and 310 g ai ha−1, respectively, at 8 WAA. Diflufenican applied preemergence at 150 g ai ha−1 controlled MHR waterhemp by 64%, 79%, and 73% at 2, 4, and 8 WAA, respectively. Isoxaflutole + atrazine applied preemergence at 105 + 1,060 g ai ha−1 controlled MHR waterhemp by 98%, 98%, and 97% at 2, 4, and 8 WAA, respectively; and S-metolachlor/mesotrione/bicyclopyrone/atrazine applied preemergence at 1,259/140/35/588 g ai ha−1 controlled MHR waterhemp by 100%, 100%, and 99% at 2, 4, and 8 WAA, respectively. Diflufenican applied preemergence reduced MHR waterhemp density and biomass by 83%; in contrast, isoxaflutole + atrazine and S-metolachlor/mesotrione/bicyclopyrone/atrazine reduced MHR waterhemp density and biomass by 99%. All treatments evaluated caused either no, or minimal, corn injury and resulted in corn yield that was similar with the weed-free control. Results indicate that diflufenican applied alone preemergence does not provide superior MHR waterhemp control over the commonly used herbicides isoxaflutole + atrazine or S-metolachlor/mesotrione/bicyclopyrone/atrazine; however, there is potential for using diflufenican as part of an integrated weed management strategy for the control of MHR waterhemp control in corn.
Projecting Changes in the Frequency and Magnitude of Ozone Pollution Events Under Uncertain Climate Sensitivity
Authors: East James D. , Monier Erwan , Saari Rebecca K. , Garcia‐Menendez Fernando
Published: June 2024

Climate change is projected to worsen ozone pollution over many populated regions, with larger impacts at higher concentrations. More intense and frequent ozone episodes risk setbacks to human health and environmental policy achievements. However, assessing these changes is complicated by uncertain climate sensitivity, closely related to climate model response, and internal variability in simulations projecting climate's influence on air quality. Here, leveraging a global modeling framework that one‐way couples a human activity model, an Earth system model of intermediate complexity, and an atmospheric chemistry model, we investigate the role of climate sensitivity in climate‐induced changes to high ozone pollution episodes in the United States using multiple greenhouse gas emissions scenarios, representations of climate sensitivity, and initial condition members. We bias correct and evaluate historical model simulations, identifying modeled and observed O3 episodes using extreme value theory, and extend the approach to projections of mid‐ and end‐century climate impacts. Results show that the influence of climate sensitivity can be as significant as that of greenhouse gas emissions scenario absent precursor emissions changes. Climate change is projected to increase the magnitude of the highest annually occurring O3 concentrations by over 2.3 ppb on average across the U.S. at mid‐century under a high climate sensitivity and moderate emissions scenario, but the increase is limited to less than 0.3 ppb under lower climate sensitivity. Further, we show that areas in the U.S. currently meeting air quality standards risk being pushed into non‐compliance due to a climate‐induced increase in frequency of high ozone days.
Decoupling Warming and Monsoon Precipitation Over the Last 3110 Years in Northwestern Yunnan Province, Southwestern China
Authors: Jia Baoyan , Xiao Xiayun , Chi Changting , Ke Rui , Li Yanling
Published: June 2024

Understanding the variability and related dynamic mechanisms of the Indian summer monsoon evolution over the past millenniums is crucial for disaster prevention and mitigation in the context of strengthening global warming. Here, we present a high‐resolution hydroclimate reconstruction over the past 3110 years in northwestern Yunnan Province, southwestern China, based on grain size analysis using the End‐member modeling algorithm and other environmental proxies. The results indicate that the temperature in northwestern Yunnan Province generally decreased since 3110 cal. yr BP, aligning with other temperature records on regional and global scales. Precipitation in the study area remained relatively stable before 1000 cal. yr BP, but exhibited an obvious out‐phase change compared with the temperature records over multidecadal to centennial timescale. While after 1000 cal. yr BP, the precipitation steadily increased, revealing the hydroclimate pattern of notably dry Medieval Warm Period (MWP) and relatively wet Little Ice Age (LIA) in the study area. The decoupling combination of temperature and precipitation spanning the MWP and LIA in southwestern China contrasts with that in the East Asian summer monsoon area and the Indian subcontinent which is also controlled by the Indian summer monsoon, indicating the spatial heterogeneity of precipitation in the Asian summer monsoon region. The discussion about dynamic mechanisms points out that solar activity emerges as a significant factor influencing regional temperature changes, and El Niño‐Southern Oscillation and Intertropical Convergence Zone migration jointly impact the precipitation change in the study area and the hydroclimate discrepancy in the Asian summer monsoon region.
Sedimentary Organic Nitrogen Isotopic Constraints on the Mid‐Holocene Transition in the Nitrogen Dynamics of the Northern South China Sea
Authors: Ye Feng , Wang Liwei , Wei Gangjian , Shi Xuesong , Huang Chao
Published: June 2024

Millennial‐scale nitrogen (N) cycling processes in marginal seas and their response to climate change have not been well understood. Here, we present high‐resolution (ca. 110 years) organic nitrogen isotope (δ15Norg) data since the last deglaciation (16.1 ka) derived from a highly resolved sediment core in the northern South China Sea, aiming to explore millennial‐scale N cycling processes in this area. Unlike most bulk nitrogen isotope (δ15Nbulk) records from the South China Sea, the δ15Norg records show a clear response to well‐defined climatic episodes during the last deglaciation and early Holocene (EH, ∼11.7 to 9 ka), but exhibit a gradually decreasing trend in mid‐to‐late Holocene (since ca. 9 ka). During the last deglaciation and EH, the upper water column N dynamics are controlled by the lateral transport of surface nitrate from eastern tropical Pacific (ETP) presumably via the North Pacific Intermediate Water (NPIW) and to some extent, influenced by the altered input of terrigenous matter driven by sea level change. The significant decrease in δ15Norg since the mid‐Holocene (at ca. 9 ka) can be best explained by the increase in local N2 fixation forced by enhanced El Niño. This mechanism is consistent with modern observations. Overall, our results may reflect the main controlling factors of surface ocean N dynamics have shifted from zonal transport of nitrate from the ETP to El Niño since the mid‐Holocene.
Revisiting Seismic Energy of Shallow Tremors: Amplifications Due To Site and Propagation Path Effects Near the Nankai Trough
Authors: Takemura Shunsuke , Emoto Kentaro , Yabe Suguru
Published: June 2024

We investigated the effects of the propagation path and site amplification of shallow tremors along the Nankai Trough. Using far‐field S‐wave propagation from intraslab earthquake data, the amplification factors at the DONET stations were 5–40 times against an inland outcrop rock site. Thick (∼5 km) sedimentary layers with VS of 0.6–2 km/s beneath DONET stations have been confirmed by seismological studies. To investigate the effects of thick sedimentary layers, we synthesized seismograms of shallow tremors and intraslab earthquakes at seafloor stations. The ratios of the maximum amplitudes from the synthetic intraslab seismograms between models with and without thick sedimentary layers were 1–2. This means that thin lower‐velocity (<0.6 km/s) sediments just below the stations primarily control the estimated large amplifications. Conversely, at near‐source (≤20 km) distances, 1‐order amplifications of seismic energies for a shallow tremor source can occur due to thick sedimentary layers. Multiple S‐wave reflections between the seafloor and plate interface are contaminated in tremor envelopes; consequently, seismic energy and duration are overestimated. If a shallow tremor occurs within underthrust sediments, the overestimation becomes stronger because of the invalid rigidity assumptions around the source region. After 1‐order corrections of seismic energies of shallow tremors along the Nankai Trough, the scaled energies of seismic slow earthquakes were 10−10–10−9 irrespective of the region and source depth. Hence, the physical mechanisms governing seismic slow earthquakes can be the same, irrespective of the region and source depth.
RGS19 activates the MYH9/β-catenin/c-Myc positive feedback loop in hepatocellular carcinoma
Authors: Ke Shanjia , Lu Shounan , Xu Yanan , Bai Miaoyu , Yu Hongjun , Yin Bing , Wang Chaoqun , Feng Zhigang , Li Zihao , Huang Jingjing , Li Xinglong , Qian Baolin , Hua Yongliang , Fu Yao , Sun Bei , Wu Yaohua , Ma Yong
Published: June 2024

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide, and the identification of novel treatment targets and prognostic biomarkers is urgently needed because of its unsatisfactory prognosis. Regulator of G-protein signaling 19 (RGS19) is a multifunctional protein that regulates the progression of various cancers. However, the specific function of RGS19 in HCC remains unclear. The expression of RGS19 was determined in clinical HCC samples. Functional and molecular biology experiments involving RGS19 were performed to explore the potential mechanisms of RGS19 in HCC. The results showed that the expression of RGS19 is upregulated in HCC tissues and is significantly associated with poor prognosis in HCC patients. RGS19 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, RGS19, via its RGS domain, stabilizes the MYH9 protein by directly inhibiting the interaction of MYH9 with STUB1, which has been identified as an E3 ligase of MYH9. Moreover, RGS19 activates β-catenin/c-Myc signaling via MYH9, and RGS19 is also a transcriptional target gene of c-Myc. A positive feedback loop formed by RGS19, MYH9, and the β-catenin/c-Myc axis was found in HCC. In conclusion, our research revealed that competition between RGS19 and STUB1 is a critical mechanism of MYH9 regulation and that the RGS19/MYH9/β-catenin/c-Myc feedback loop may represent a promising strategy for HCC therapy.
METTL3-mediated pre-miR-665/DLX3 m6A methylation facilitates the committed differentiation of stem cells from apical papilla
Authors: Gu Tingjie , Guo Rong , Fang Yuxin , Xiao Ya , Chen Luyao , Li Na , Ge Xingyun Kelesy , Shi Yijia , Wu Jintao , Yan Ming , Yu Jinhua , Li Zehan
Published: June 2024

Methyltransferase-like 3 (METTL3) is a crucial element of N6-methyladenosine (m6A) modifications and has been extensively studied for its involvement in diverse biological and pathological processes. In this study, we explored how METTL3 affects the differentiation of stem cells from the apical papilla (SCAPs) into odonto/osteoblastic lineages through gain- and loss-of-function experiments. The m6A modification levels were assessed using m6A dot blot and activity quantification experiments. In addition, we employed Me-RIP microarray experiments to identify specific targets modified by METTL3. Furthermore, we elucidated the molecular mechanism underlying METTL3 function through dual-luciferase reporter gene experiments and rescue experiments. Our findings indicated that METTL3+/− mice exhibited significant root dysplasia and increased bone loss. The m6A level and odonto/osteoblastic differentiation capacity were affected by the overexpression or inhibition of METTL3. This effect was attributed to the acceleration of pre-miR-665 degradation by METTL3-mediated m6A methylation in cooperation with the “reader” protein YTHDF2. Additionally, the targeting of distal-less homeobox 3 (DLX3) by miR-665 and the potential direct regulation of DLX3 expression by METTL3, mediated by the “reader” protein YTHDF1, were demonstrated. Overall, the METTL3/pre-miR-665/DLX3 pathway might provide a new target for SCAP-based tooth root/maxillofacial bone tissue regeneration.
Advances and challenges in modeling inherited peripheral neuropathies using iPSCs
Authors: Van Lent Jonas , Prior Robert , Pérez Siles Gonzalo , Cutrupi Anthony N. , Kennerson Marina L. , Vangansewinkel Tim , Wolfs Esther , Mukherjee-Clavin Bipasha , Nevin Zachary , Judge Luke , Conklin Bruce , Tyynismaa Henna , Clark Alex J. , Bennett David L. , Van Den Bosch Ludo , Saporta Mario , Timmerman Vincent
Published: June 2024

Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids.
Dissecting the MUC5AC/ANXA2 signaling axis: implications for brain metastasis in lung adenocarcinoma
Authors: Chaudhary Sanjib , Siddiqui Jawed Akhtar , Appadurai Muthamil Iniyan , Maurya Shailendra Kumar , Murakonda Swathi P. , Blowers Elizabeth , Swanson Ben J. , Nasser Mohd Wasim , Batra Surinder K. , Lakshmanan Imayavaramban , Ganti Apar Kishor
Published: June 2024

Non-small cell lung carcinoma (NSCLC) exhibits a heightened propensity for brain metastasis, posing a significant clinical challenge. Mucin 5ac (MUC5AC) plays a pivotal role in the development of lung adenocarcinoma (LUAD); however, its role in causing brain metastases remains unknown. In this study, we aimed to investigate the contribution of MUC5AC to brain metastasis in patients with LUAD utilizing various brain metastasis models. Our findings revealed a substantial increase in the MUC5AC level in LUAD brain metastases (LUAD-BrM) samples and brain-tropic cell lines compared to primary samples or parental control cell lines. Intriguingly, depletion of MUC5AC in brain-tropic cells led to significant reductions in intracranial metastasis and tumor growth, and improved survival following intracardiac injection, in contrast to the observations in the control groups. Proteomic analysis revealed that mechanistically, MUC5AC depletion resulted in decreased expression of metastasis-associated molecules. There were increases in epithelial-to-mesenchymal transition, tumor invasiveness, and metastasis phenotypes in tumors with high MUC5AC expression. Furthermore, immunoprecipitation and proteomic analysis revealed a novel interaction of MUC5AC with Annexin A2 (ANXA2), which activated downstream matrix metalloproteases and facilitated extracellular matrix degradation to promote metastasis. Disrupting MUC5AC-ANXA2 signaling with a peptide inhibitor effectively abrogated the metastatic process. Additionally, treatment of tumor cells with an astrocyte-conditioned medium or the chemokine CCL2 resulted in upregulation of MUC5AC expression and enhanced brain colonization. In summary, our study demonstrates that the MUC5AC/ANXA2 signaling axis promotes brain metastasis, suggesting a potential therapeutic paradigm for LUAD patients with high MUC5AC expression.
Factor analysis of lifetime psychopathology and its brain morphometric and genetic correlates in a transdiagnostic sample
Authors: Krug Axel , Stein Frederike , David Friederike S. , Schmitt Simon , Brosch Katharina , Pfarr Julia-Katharina , Ringwald Kai G. , Meller Tina , Thomas-Odenthal Florian , Meinert Susanne , Thiel Katharina , Winter Alexandra , Waltemate Lena , Lemke Hannah , Grotegerd Dominik , Opel Nils , Repple Jonathan , Hahn Tim , Streit Fabian , Witt Stephanie H. , Rietschel Marcella , Andlauer Till F. M. , Nöthen Markus M. , Philipsen Alexandra , Nenadić Igor , Dannlowski Udo , Kircher Tilo , Forstner Andreas J.
Published: June 2024

There is a lack of knowledge regarding the relationship between proneness to dimensional psychopathological syndromes and the underlying pathogenesis across major psychiatric disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizoaffective Disorder (SZA), and Schizophrenia (SZ). Lifetime psychopathology was assessed using the OPerational CRITeria (OPCRIT) system in 1,038 patients meeting DSM-IV-TR criteria for MDD, BD, SZ, or SZA. The cohort was split into two samples for exploratory and confirmatory factor analyses. All patients were scanned with 3-T MRI, and data was analyzed with the CAT-12 toolbox in SPM12. Psychopathological factor scores were correlated with gray matter volume (GMV) and cortical thickness (CT). Finally, factor scores were used for exploratory genetic analyses including genome-wide association studies (GWAS) and polygenic risk score (PRS) association analyses. Three factors (paranoid-hallucinatory syndrome, PHS; mania, MA; depression, DEP) were identified and cross-validated. PHS was negatively correlated with four GMV clusters comprising parts of the hippocampus, amygdala, angular, middle occipital, and middle frontal gyri. PHS was also negatively associated with the bilateral superior temporal, left parietal operculum, and right angular gyrus CT. No significant brain correlates were observed for the two other psychopathological factors. We identified genome-wide significant associations for MA and DEP. PRS for MDD and SZ showed a positive effect on PHS, while PRS for BD showed a positive effect on all three factors. This study investigated the relationship of lifetime psychopathological factors and brain morphometric and genetic markers. Results highlight the need for dimensional approaches, overcoming the limitations of the current psychiatric nosology.
A multi-site 99mTc-HMPAO SPECT study of cerebral blood flow in a community sample of patients with major depression
Authors: Peterson Bradley S. , Li Jennifer , Trujillo Manuel , Sawardekar Siddhant , Balyozian David , Bansal Siddharth , Sun Bernice F. , Marcelino Courtney , Nanda Anoop , Xu Tracy , Amen Daniel , Bansal Ravi
Published: June 2024

Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18–65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two 99mTc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18–65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD.
The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway
Authors: Chen Jun-Jun , Lu Tian-Zhu , Wang Tao , Yan Wen-Hui , Zhong Fang-Yan , Qu Xin-Hui , Gong Xiao-Chang , Li Jin-Gao , Tou Fang-Fang , Jiang Li-Ping , Han Xiao-Jian
Published: June 2024

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC–IRAK1–MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.