bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep‐learning‐based motion correction using multichannel MRI data: a study using simulated artifacts in the fastMRI dataset
Authors: Hewlett Miriam , Petrov Ivailo , Johnson Patricia M. , Drangova Maria
Published: May 2024

Deep learning presents a generalizable solution for motion correction requiring no pulse sequence modifications or additional hardware, but previous networks have all been applied to coil‐combined data. Multichannel MRI data provide a degree of spatial encoding that may be useful for motion correction. We hypothesize that incorporating deep learning for motion correction prior to coil combination will improve results. A conditional generative adversarial network was trained using simulated rigid motion artifacts in brain images acquired at multiple sites with multiple contrasts (not limited to healthy subjects). We compared the performance of deep‐learning‐based motion correction on individual channel images (single‐channel model) with that performed after coil combination (channel‐combined model). We also investigate simultaneous motion correction of all channel data from an image volume (multichannel model). The single‐channel model significantly (p < 0.0001) improved mean absolute error, with an average 50.9% improvement compared with the uncorrected images. This was significantly (p < 0.0001) better than the 36.3% improvement achieved by the channel‐combined model (conventional approach). The multichannel model provided no significant improvement in quantitative measures of image quality compared with the uncorrected images. Results were independent of the presence of pathology, and generalizable to a new center unseen during training. Performing motion correction on single‐channel images prior to coil combination provided an improvement in performance compared with conventional deep‐learning‐based motion correction. Improved deep learning methods for retrospective correction of motion‐affected MR images could reduce the need for repeat scans if applied in a clinical setting.
Microwave Effect in Hydrolysis of Levoglucosan with a Solid Acid Catalyst for Pyrolysis‐Based Cellulose Saccharification
Authors: Nomura Takashi , Minami Eiji , Kawamoto Haruo
Published: May 2024

Pyrolysis‐based saccharification consisting of fast pyrolysis followed by hydrolysis of the resulting anhydrosugars such as levoglucosan is a promising method for converting cellulosic biomass into glucose that can be used for producing biofuels and biochemicals. In the present study, hydrolysis of levoglucosan was evaluated in water with a polystyrene sulfonic acid resin (a solid acid catalyst) by heating under microwave irradiation or in an oil bath at 95 °C–120 °C. When the equilibrium temperature of the solution was the same, the conversion rate of levoglucosan was greater under microwave irradiation than in an oil bath. Model experiments indicate that the sulfonyl groups of the solid acid catalyst were selectively heated by microwave irradiation. The temperature of the reaction solution in the vicinity of the catalyst was locally higher than the equilibrium temperature of the solution, which enabled hydrolysis to proceed efficiently.
Laser myth busting
Authors: Rudolf Andreas , Blumenstein Christof
Published: May 2024

High‐power laser systems are routinely employed as production tools, but the laser beam itself is sensitive to various disturbances, especially in the light of current trends toward extreme power and high beam quality. Suitable tools are available to characterize the process‐relevant beam parameters – from power through focus dimensions to scanner‐imposed properties. Yet either the challenges or the measurement tools tend to be underestimated – justifying a closer look at some of the common myths.
Dynamic beam shaping with coherent beam combining
Authors: Shekel Eyal
Published: May 2024

Coherent beam combining (CBC) is a method of enhancing laser power. It has recently transitioned to industrial applications, unveiling new possibilities in laser technology. CBC merges multiple laser channels from a single source, controlling their phase to create constructive or destructive interference. The optical phased array (OPA) and filled aperture methods exemplify CBC's advancements, enabling dynamic and precise beam manipulation. This technological evolution opens avenues for versatile applications in various industries, significantly advancing our capability to harness laser technology for complex tasks.
LaserEMobility Workshop 2024
Authors: Demir Ali Gökhan
Published: May 2024

Following the success of the previous two years, LaserEMobility Workshop returns on July 17 – 18, 2024, with this edition to be held in Garching near Munich. The event brings together key players in EV manufacturing and laser technology with participants from industry and academia in a unique format. The two‐day event will display recent developments in laser beam technology, new applications, monitoring systems, and many other discussion topics for an international community.
Metaproteomic analysis of King Ghezo tomb wall (Abomey, Benin) confirms 19th century voodoo sacrifices
Authors: Charlier Philippe , Bourdin Virginie , N'Dah Didier , Kielbasa Mélodie , Pible Olivier , Armengaud Jean
Published: May 2024

The palace of King Ghezo in Abomey, capital of the ancient kingdom of Dahomey (present‐day Benin), houses two sacred huts which are specific funerary structures. It is claimed that the binder in their walls is made of human blood. In the study presented here, we conceived an original strategy to analyze the proteins present on minute amounts of the cladding sampled from the inner facade of the cenotaph wall and establish their origin. The extracted proteins were proteolyzed and the resulting peptides were characterized by high‐resolution tandem mass spectrometry. Over 6397 distinct molecular entities were identified using cascading searches. Starting from without a priori searches of an extended generic database, the peptide repertoire was narrowed down to the most representative organisms—identified by means of taxon‐specific peptides. A wide diversity of bacteria, fungi, plants, and animals were detected through the available protein material. This inventory was used to archaeologically reconstruct the voodoo rituals of consecration and maintenance of vitality. Several indicators attested to the presence of traces of human and poultry blood in the material taken. This study shows the essential advantages of paleoproteomics and metaproteomics for the study of ancient residues from archaeological excavations or historical monuments.
Can Facebook's community standards keep up with legal certainty? Content moderation governance under the pressure of the Digital Services Act
Authors: Fasel Mathieu , Weerts Sophie
Published: May 2024

Content moderation by social media companies is a challenge for regulators around the world. The European Union is trying to tackle this challenge with its Digital Services Act (DSA). Notably, Article 14 DSA aims to impose language requirements based on the principle of legal certainty to social media companies' terms and conditions, of which community standards (CS) are a part. The principle of legal certainty is one of the building blocks of international human rights law, and its inclusion in the DSA illustrates the human rights‐based approach anchored in this European regulation. Based on a content analysis of Facebook's CS, this paper shows that their standards do not meet European requirements for legal certainty and argues that important changes in content moderation governance would be needed for proper compliance. Such changes could generate a domino effect beyond the European Union and on Facebook's content moderation governance itself. At the same time, the DSA could also generate a boomerang effect on the legal certainty principle as such. From this perspective, the paper contributes to the literature on regulatory governance studies, and on international human rights law in social media studies from a European Union perspective.
Studying quantum effects of fine scaling on the buckling behavior of CNTs under torsional loading using the density functional theory and molecular mechanics approach
Authors: Mirnezhad Mahdi , Ansari Reza , Falahatgar Seyed Reza , Aghdasi Peyman
Published: May 2024

In this study, we introduce a comprehensive investigation into the buckling behavior of carbon nanotubes (CNTs) using a combined approach of quantum mechanics and molecular mechanics methods. A novel aspect of our research lies in the exploration of the quantum effects of fine scaling on the buckling behavior of finite‐length nanotubes across various dimensions and chiralities. Specifically, we analyze the critical buckling strain variations in CNTs with distinct lengths, diameters, and chiralities, revealing pronounced differences influenced by atomic arrangement and the type of structure used in nanotube construction. Our findings elucidate that at smaller dimensions,
nanotubes exhibit a higher critical buckling strain than other chiralities, while zigzag atomic arrangements demonstrate greater resistance to torsional loading at larger diameters. Additionally, we compare the buckling behavior of nanotubes obtained by wrapping armchair and zigzag nanosheets, highlighting differential resistance trends. This research not only underscores the critical role of quantum effects in determining nanotube buckling but also provides valuable insights into the nuanced influences of atomic arrangement and nanosheet type on the mechanical properties of CNTs. Thus, our work contributes a novel perspective to the field, bridging the gap between quantum mechanics and the mechanical behavior of nanostructures, which has significant implications for the design and application of nanoscale materials
Lattice Engineering via Transition Metal Ions for Boosting Photoluminescence Quantum Yields of Lead‐Free Layered Double Perovskite Nanocrystals
Authors: Liu Maning , Matta Sri Kasi , Said Tarek Al , Liu Jiatu , Matuhina Anastasia , Al‐Anesi Basheer , Ali‐Löytty Harri , Lahtonen Kimmo , Russo Slavy P. , Vivo Paola
Published: May 2024

Lead‐free layered double perovskite nanocrystals (NCs), i.e., Cs4M(II)M(III)2Cl12, have recently attracted increasing attention for potential optoelectronic applications due to their low toxicity, direct bandgap nature, and high structural stability. However, the low photoluminescence quantum yield (PLQY, <1%) or even no observed emissions at room temperature have severely blocked the further development of this type of lead‐free halide perovskites. Herein, two new layered perovskites, Cs4CoIn2Cl12 (CCoI) and Cs4ZnIn2Cl12 (CZnI), are successfully synthesized at the nanoscale based on previously reported Cs4CuIn2Cl12 (CCuI) NCs, by tuning the M(II) site with different transition metal ions for lattice tailoring. Benefiting from the formation of more self‐trapped excitons (STEs) in the distorted lattices, CCoI and CZnI NCs exhibit significantly strengthened STE emissions toward white light compared to the case of almost non‐emissive CCuI NCs, by achieving PLQYs of 4.3% and 11.4% respectively. The theoretical and experimental results hint that CCoI and CZnI NCs possess much lower lattice deformation energies than that of reference CCuI NCs, which are favorable for the recombination of as‐formed STEs in a radiative way. This work proposes an effective strategy of lattice engineering to boost the photoluminescent properties of lead‐free layered double perovskites for their future warm white light‐emitting applications.
Editors’ Introduction: Race and the Awarding Gap
Authors: Hensby Alexander , Adewumi Barbara
Published: May 2024

This book is ostensibly about the white-BAME awarding gap, but any attempt to understand its causes and effects warrants a wider and deeper investigation of how structural racism and institutional whiteness permeate in contemporary UK society. Universities may not be the most egregious offenders, but they have nevertheless struggled to break beyond the liberal complacency that for many years has considered educational equity to be synonymous with educational access. This chapter traces the history of equality, diversity, and inclusivity policy (EDI) in higher education, highlighting the legislative and policy drivers for advancing racial equity. It then establishes the book’s theoretical framework, combining Bourdieu’s theory of capitals, critical race theory, and self-determination theory. Finally, the chapter introduces the book’s aims and purpose, drawing on the work of the University of Kent’s Student Success Team to understand and enhance the experiences of BAME undergraduates.
BAME Students’ Extracurricular Belonging at University: Building Networks, Representation, and Capital
Authors: Hensby Alexander , Adewumi Barbara , Twumasi Anne-Marie , Thomas Dave S. P.
Published: May 2024

It has taken time for universities to fully recognise belongingness when considering the factors that shape student success. There are understandable reasons for this, but if we are to take a holistic view of its roots and causes then one should recognise that a good deal of one’s higher education experience occurs outside of the lecture theatre. This chapter draws on survey and interview data to assess BAME students’ extracurricular engagement. Findings indicate fewer are involved in clubs, societies, and the student union than their white peers, with interview accounts pointing to the reproduction of certain power relations, including whiteness. However, the chapter’s chronicling of Kent’s African Caribbean Society demonstrates that BAME students are capable of developing their own agency, capital, and influence on campus, though they require institutional support to ensure their voice and perspective can help shape university policy and practice in ways that ultimately enhance collective belongingness.
Gravity-gauge anomaly constraints on the energy-momentum tensor
Authors: Larue Rémy , Quevillon Jérémie , Zwicky Roman
Published: May 2024

Abstract

We derive constraints on the four dimensional energy-momentum tensor from gravitational and gauge anomalies. Our work can be considered an extension of Duff’s analysis [1] to include parity-odd terms and explicit symmetry breaking. The constraints imply the absence of the parity-odd $$ R\overset{\sim }{R} $$
R

R
~

and $$ F\overset{\sim }{F} $$
F

F
~

terms, for theories whose symmetries are compatible with dimensional regularisation, in a model-independent way. Remarkably, even in the case of explicit symmetry breaking the □R-anomaly is found to be finite and unambiguous after applying the symmetry constraints. We compute mixed gravity-gauge anomalies at leading order and deduce phenomenological consequences for vector bosons associated with global chiral symmetries.
Electrobaryonic axion: hair of neutron stars
Authors: Bai Yang , de Lima Carlos Henrique
Published: May 2024

Abstract

Axion-like particles are predicted in many physics scenarios beyond the Standard Model (SM). Their interactions with SM particles may arise from the triangle anomaly of the associated global symmetry, along with other SM global and gauge symmetries, including anomalies with the global baryon number and electromagnetic gauge symmetries. We initiate the phenomenological study of the corresponding “electrobaryonic axion”—a particle that couples with both the baryon chemical potential and the electromagnetic field. Neutron stars, particularly magnetars, possessing high baryon density and strong magnetic fields, can naturally develop a thin axion hair around their surface. In this study, we calculate this phenomenon, considering the effects of neutron star rotation and general relativity. For axion particles lighter than the neutron star rotation frequency, the anomalous interaction can also induce the emission of axion particles from the neutron star. In the light axion regime, this emission can significantly contribute to the neutron star cooling rate.
Actions on the quiver: discrete quotients on the Coulomb branch
Authors: Hanany Amihay , Kumaran Guhesh , Li Chunhao , Liu Deshuo , Sperling Marcus
Published: May 2024

Abstract

This paper introduces two operations in quiver gauge theories. The first operation, collapse, takes a quiver with a permutation symmetry Sn and gives a quiver with adjoint loops. The corresponding 3d $$ \mathcal{N} $$
N
= 4 Coulomb branches are related by an orbifold of Sn. The second operation, multi-lacing, takes a quiver with n nodes connected by edges of multiplicity k and replaces them by n nodes of multiplicity qk. The corresponding Coulomb branch moduli spaces are related by an orbifold of type $$ {\mathbb{Z}}_q^{n-1} $$

ℤ
q

n
−
1

. Collapse generalises known cases that appeared in the literature [1–3]. These two operations can be combined to generate new relations between moduli spaces that are constructed using the magnetic construction.
Early-paleozoic rapakivi-textured granite from the North Qinling (Central China): implications for crust–mantle interactions in a post-collisional setting
Authors: Luo Fenhong , Gong Hujun , Liu Hang
Published: May 2024

Rapakivi granite is characterized by its unique structure, which has important implications for tectonic settings, magmatic processes, and crust–mantle interactions. In this study, we conducted a combined analysis of the petrography, mineral chemistry, geochemistry, and zircon U–Pb dating and Lu–Hf isotopic compositions of the Niujiaoshan Early Paleozoic rapakivi-textured granite from the North Qinling Belt. Zircon U–Pb dating yielded a crystallization age of 447 ± 7 Ma, which is younger than the ultra-high-pressure (UHP) metamorphic age (~ 500 Ma) but similar to the granulite facies retrograde age (~ 450 Ma) of UHP eclogites and felsic gneisses in the North Qinling Belt. The rapakivi feldspar phenocrysts have ovoid K-feldspar cores, which are rich in mineral inclusions, such as amphibole, biotite, quartz, and plagioclase, indicating early crystallization. The ovoid K-feldspar cores are mantled by oligoclase, whreras the matrix comprises biotite, amphibole, and coarse-grained plagioclase. The amphibole and biotite in the granite are rich in Mg and are indicative of a crust–mantle origin. The εHf (t) values of the zircons range from − 2.04 to + 3.63, suggesting formation via crust–mantle interactions. The rapakivi-textured granite displays high-K meta-aluminous I-type granite affinity, with high SiO2, K2O, and Na2O contents. Based on the geological background and results of this study, we propose that the Niujiaoshan rapakivi-textured granite was formed via the mixing of crustal materials induced by upper mantle magma during the exhumation of the North Qinling UHP metamorphic terrane, which occurred in a post-orogenic setting.
Efficacy of a dual task protocol on neurophysiological and clinical outcomes in migraine: a randomized control trial
Authors: Deodato Manuela , Granato Antonio , Buoite Stella Alex , Martini Miriam , Marchetti Enrico , Lise Ilaria , Galmonte Alessandra , Murena Luigi , Manganotti Paolo
Published: May 2024

The main aim of this study was to investigate the efficacy of a dual task protocol in people with episodic migraine with respect to both active exercises only and cognitive task only treatments, concerning some neurophysiological and clinical outcomes. A randomized control trial was adopted in people with episodic migraine without aura. Some neurophysiological and clinical outcomes were collected (t0): resting motor threshold (rMT), short intracortical inhibition (SICI) and facilitation (ICF), pressure pain threshold (PPT), trail making test (TMT), frontal assessment battery (FAB), headache-related disability (MIDAS) and headache parameters. Then, participants were randomized into three groups: active exercise only (n = 10), cognitive task only (n = 10) and dual task protocol (n = 10). After 3 months of each treatment and after 1-month follow-up the same neurophysiological and clinical outcomes were revaluated. A significant time x group effect was only found for the trapezius muscle (p = 0.012, pη2 = 0.210), suggesting that PPT increased significantly only in active exercise and dual task protocol groups. A significant time effect was found for rMT (p < 0.001, pη2 = 0.473), MIDAS (p < 0.001, pη2 = 0.426), TMT (p < 0.001, pη2 = 0.338) and FAB (p < 0.001, pη2 = 0.462). A repeated measures ANOVA for SICI at 3 ms highlighted a statistically significant time effect for the dual task group (p < 0.001, pη2 = 0.629), but not for the active exercises group (p = 0.565, pη2 = 0.061), and for the cognitive training (p = 0.357, pη2 = 0.108). The dual task protocol seems to have a more evident effect on both habituation and sensitization outcomes than the two monotherapies taken alone in people with migraine.
Markov-switching decision trees
Authors: Adam Timo , Ötting Marius , Michels Rouven
Published: May 2024

Decision trees constitute a simple yet powerful and interpretable machine learning tool. While tree-based methods are designed only for cross-sectional data, we propose an approach that combines decision trees with time series modeling and thereby bridges the gap between machine learning and statistics. In particular, we combine decision trees with hidden Markov models where, for any time point, an underlying (hidden) Markov chain selects the tree that generates the corresponding observation. We propose an estimation approach that is based on the expectation-maximisation algorithm and assess its feasibility in simulation experiments. In our real-data application, we use eight seasons of National Football League (NFL) data to predict play calls conditional on covariates, such as the current quarter and the score, where the model’s states can be linked to the teams’ strategies. R code that implements the proposed method is available on GitHub.
Factors influencing clinician-educators’ assessment practice in varied Southern contexts: a health behaviour theory perspective
Authors: Sims Danica Anne , Lucio-Ramirez César Alberto , Cilliers Francois J.
Published: May 2024

In many contexts, responsibility for exit-level assessment design and implementation in undergraduate medical programmes lies with individuals who convene clinical clerkships. Their assessment practice has significant consequences for students’ learning and the patients and communities that graduates will serve. Interventions to enhance assessment must involve these assessors, yet little is known about factors influencing their assessment practice. The purpose of this study was to explore factors that influence assessment practice of clerkship convenors in three varied low-and-middle income contexts in the global South. Taking assessment practice as a behaviour, Health Behaviour Theory (HBT) was deployed as a theoretical framework to explore, describe and explain assessor behaviour. Thirty-one clinician-educators responsible for designing and implementing high-stakes clerkship assessment were interviewed in South Africa and Mexico. Interacting personal and contextual factors influencing clinician-educator assessment intention and action were identified. These included attitude, influenced by impact and response appraisal, and perceived self-efficacy; along with interpersonal, physical and organisational, and distal contextual factors. Personal competencies and conducive environments supported intention to action transition. While previous research has typically explored factors in isolation, the HBT framing enabled a systematic and coherent account of assessor behaviour. These findings add a particular contextual perspective to understanding assessment practice, yet also resonate with and extend existing work that predominantly emanates from high-income contexts in the global North. These findings provide a foundation for the planning of assessment change initiatives, such as targeted, multi-factorial faculty development.
Readiness of teachers for blended learning: A scale development study
Authors: Çemçem Gülsemin Durmuş , Korkmaz Özgen , Kukul Volkan
Published: May 2024

The aim of this study is to create a new scale to assess teachers' readiness for blended learning. There are 317 active teachers volunteering in the study from various educational levels. Exploratory factor analysis was carried out to examine the construct validity of the scale with the data obtained. Following principal component analysis, 6 items were removed from the scale as they spread to different factors, and the remaining 25 items were refactored and grouped into 4 factors. Confirmatory factor analysis was carried out to confirm the factor structures of the scale. The obtained model confirmed the factor structure created in the exploratory factor analysis. Differences between the bottom and top 27% groups were investigated to evaluate item discriminability. For reliability analyses, internal consistency coefficients and stability analyses were performed. A five-point Likert scale with 25 items is used to assess how prepared the teachers are for blended learning. The items are categorized into four factors. The scale's Cronbach alpha coefficient value is 0.943 and McDonald’s ω value is .942. Analyses demonstrate that the scale is a valid and reliable tool for assessing teachers' readiness for blended learning.
Development of a platform for state online education services: Design concept based on meta-universe
Authors: Chen Guomin , Jin Yingwei , Chen Pengrun
Published: May 2024

The incorporation of metaverse technology in education, particularly within standardized state educational frameworks, holds promise for significant improvements in learning outcomes. This study aimed to assess the effectiveness of integrating an online metaverse platform into state educational services, thereby fostering the development of digital environments. A total of 278 students from middle and high school levels in China participated in the study. Academic achievement tests, alongside the Engagement Level Scale (ELS) and Motivation Level Scale (MLS), were employed as measurement tools. The utilization of the metaverse platform, hosting the state-approved curriculum for seventh and tenth grades, resulted in notable enhancements in students’ academic performance, engagement, and motivation. Among seventh graders, the most significant improvements in academic performance were observed in mathematics (5.897), literature (5.101), and history (5.767). For tenth graders, enhancements were noted in Chinese language (7.500), literature (5.800), and chemistry (5.650). Moreover, improvements in engagement and motivation were statistically significant. Seventh graders in the experimental group exhibited higher levels of intrinsic motivation (6.45), extrinsic motivation (5.28), and self-regulation (7.18) compared to the control group. For tenth graders, the respective increases were 5.70, 4.00, and 4.65 for each subscale. The practical and scientific significance lies in demonstrating the potential of enhancing educational outcomes and student motivation through the implementation of an online metaverse platform, which could be integrated into state school curricula.
Longitudinal Profiles of Cultural Identity Processes and Associations with Psychosocial Outcomes Among Adolescents Participating in the Identity Project in Italy
Authors: Ceccon Chiara , Moscardino Ughetta , Altoè Gianmarco , Lionetti Francesca , Umaña-Taylor Adriana J.
Published: May 2024

Cultural identity formation is a complex developmental task that influences adolescents’ adjustment. However, less is known about individual variations in trajectories of cultural identity processes and how they relate to youth psychosocial outcomes. Using a person-centered approach, this study investigated patterns of change over a year in cultural identity exploration and resolution, respectively, among ethnically diverse adolescents in Italy. The sample included 173 high school students (Mage = 15 yrs, SD = 0.62, range = 14–17; 58.4% female; 26% immigrant background) who had participated in the Identity Project, a school-based intervention targeting ethnic-racial identity development. Longitudinal latent profile analysis revealed only one profile of change for exploration, whereas four unique profiles for resolution emerged (“stable low,” “stable average,” “increase low-to-average,” “increase high-to-higher”). Overall, youth in the resolution-increase profiles reported the best outcomes. The findings highlight the heterogeneity of adolescents’ resolution trajectories and the benefits of an increased sense of clarity concerning one’s cultural identity for positive psychosocial functioning.
Simulated maximum likelihood estimation of the sequential search model
Authors: Chung Jae Hyen , Chintagunta Pradeep , Misra Sanjog
Published: May 2024

We propose a new approach to simulate the likelihood of the sequential search model. By allowing search costs to be heterogeneous across consumers and products, we directly compute the joint probability of the search and purchase decisions when consumers are searching for the idiosyncratic preference shocks in their utility functions. Under the assumptions of Weitzman’s sequential search algorithm, the proposed procedure recursively makes random draws for each quantity that requires numerical integration while enforcing the conditions stipulated by the algorithm. In an extensive simulation study, we compare the proposed method with existing likelihood simulators that have recently been used to estimate the sequential search model. The proposed method attributes the uncertainty in the search order to the consumer-product-level distribution of search costs and the uncertainty in the purchase decision to the distribution of match values across consumers and products. This results in more precise estimation and an improvement in prediction accuracy. We also show that the proposed method allows for different assumptions on the search cost distribution and that it recovers consumers’ relative preferences even if the utility function and/or the search cost distribution is mis-specified. We then apply our approach to online search data from Expedia for field-data validation. From a substantive perspective, we find that search costs and “position” effects affect products in the lower part of the product listing page more than they do those in the upper part of the page.
Eculizumab for adult patients with atypical haemolytic-uraemic syndrome: full dataset analysis of Japanese post-marketing surveillance
Authors: Maruyama Shoichi , Ikeda Yoichiro , Kaname Shinya , Kato Noritoshi , Matsumoto Masanori , Ishikawa Yumiko , Shimono Akihiko , Miyakawa Yoshitaka , Nangaku Masaomi , Shibagaki Yugo , Okada Hirokazu
Published: May 2024

Background

Eculizumab has been approved for atypical haemolytic-uraemic syndrome (aHUS) in Japan since 2013. Post-marketing surveillance enrolled patients with aHUS who received ≥ 1 dose of eculizumab to assess eculizumab safety and effectiveness.

Methods

We evaluated serious adverse events and effectiveness endpoints, i.e., haematologic normalization, a decrease of ≥ 25% in serum creatinine (sCr) levels, and complete thrombotic microangiopathy (TMA) response in adult patients with aHUS without other underlying diseases. In addition, the difference of baseline characteristics between patients who did and did not meet effectiveness endpoints was examined.

Results

In this safety and effectiveness analysis, 79 adult patients were included; median age was 54.0 years, median treatment duration was 30 weeks. Total exposure time of eculizumab was 75.51 patient-years, and 94 serious adverse events were reported in 39 patients. No unexpected safety signals were identified in this population. Mean platelet count, lactate dehydrogenase and estimated glomerular filtration rate significantly improved after 7 days of treatment. Complete TMA response, haematologic normalization and the improvement of sCr levels were met by 35.3%, 40.4% and 51.3% of patients, respectively. Median treatment duration was shorter in patients who did not achieve complete TMA response (6 weeks) than in patients who did (114 weeks). Multivariate analysis suggested that the time from the most recent TMA episode to start of eculizumab treatment was negatively associated with kidney function improvement.

Conclusions

No unexpected safety signals of eculizumab were identified in Japanese patients with aHUS in a real-world setting. Renal outcomes were negatively associated with the time from the most recent TMA episode to the initiation of eculizumab treatment.

Graphical abstract
Arterial stiffness and incident chronic kidney disease: a large population-based cohort study
Authors: Beros Angela , Sluyter John , Hughes Alun , Hametner Bernhard , Wassertheurer Siegfried , Scragg Robert
Published: May 2024

Background/aims

Evidence from large population-based cohorts as to the association of arterial stiffness and incident chronic kidney disease (CKD) is mixed. This large population-based study aimed to investigate whether arterial stiffness, assessed oscillometrically, was associated with incident CKD.

Methods

The study population comprised 4838 participants from the Vitamin D Assessment (ViDA) Study without known CKD (mean ± SD age = 66 ± 8). Arterial stiffness was assessed from 5 April, 2011 to 6 November, 2012 by way of aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure. Incident CKD was determined by linkage to national hospital discharge registers. Cox proportional hazards regression was used to assess the risk of CKD in relation to chosen arterial stiffness measures over the continuum and quartiles of values.

Results

During a mean ± SD follow-up of 10.5 ± 0.4 years, 376 participants developed incident CKD. Following adjustment for potential confounders, aortic pulse wave velocity (hazard ratio (HR) per SD increase 1.69, 95% CI 1.45–1.97), estimated carotid-femoral pulse wave velocity (HR per SD increase 1.84, 95% CI 1.54–2.19), and aortic pulse pressure (HR per SD increase 1.37, 95% CI 1.22–1.53) were associated with the incidence of CKD. The risk of incident CKD was, compared to the first quartile, higher in the fourth quartile of aortic pulse wave velocity (HR 4.72, 95% CI 2.69–8.27; Ptrend < 0.001), estimated carotid-femoral pulse wave velocity (HR 4.28, 95% CI 2.45–7.50; Ptrend  < 0.001) and aortic pulse pressure (HR 2.71, 95% CI 1.88–3.91; Ptrend  < 0.001).

Conclusions

Arterial stiffness, as measured by aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure may be utilised in clinical practice to help identify people at risk of future CKD.

Trial registration

www.anzctr.org.au identifier:ACTRN12611000402943.

Graphical abstract
Use of Integrated Metabolic Maps as a Framework for Teaching Biochemical Pathways in the Pre-clinical Medical Curriculum
Authors: Nguyen Kenny , Silveira Jay R. , Lounsbury Karen M.
Published: May 2024

Introduction

The Larner College of Medicine has steadily transitioned to primarily active learning-based instruction. Although evaluations praise session formats, students often highlight difficulties in synthesizing preparatory materials to integrate biochemical pathways. A student/faculty collaboration led to the development of interactive metabolic maps that illustrate pathways and link to a broader framework of metabolism.

Methods

A review of the session materials identified relevant biochemical pathways, and for each pathway, we created a fillable visual diagram to highlight the interactions between all substrates, enzymes, and cofactors. Implementation of the metabolic maps began for first-year medical students in fall 2022. Evaluation data included standard student session evaluations (Likert scale and qualitative comments) and a survey specific to the metabolic maps.

Results

After implementing the maps, student ratings of biochemistry/metabolism session materials significantly improved (3.2 ± 1.04 to 4.3 ± 0.87, p < 0.001), and students made positive comments about their effectiveness. Most students (77.8%) used the metabolic maps to aid in studying biochemistry content for exams and found the metabolic maps important for integrating information about metabolic pathways. The median performance on metabolism-specific questions was higher, although not statistically significant (69.23 to 77.28, ns).

Discussion

The implementation of integrated metabolic maps improved student satisfaction of biochemistry/metabolism session materials. Limitations include confounding factors related to student population differences and other simultaneous curriculum changes. Implementing interactive visual aids to integrate metabolism pathways and concepts is applicable to any medical curriculum, and other longitudinal topics may benefit from this type of curricular framework.
Post-earthquake building services downtime distribution: a case study of the 2016 Kumamoto, Japan, earthquake
Authors: Nishino Tomoaki
Published: May 2024

Seismic damage to building services systems, that is, mechanical, electrical, and plumbing systems in buildings related to energy and indoor environments, affects the functionality of buildings. Assessing post-earthquake functionality is useful for enhancing the seismic resilience of buildings via improved design. Such assessments require a model for predicting the time required to restore building services. This study analyzes the downtime data for 250 instances of damage to building services components caused by the 2016 Kumamoto earthquake in Japan, presumably obtained from buildings with minor or no structural damage. The objectives of this study are (1) to determine the empirical downtime distribution of building services components and (2) to assess the dependence of the downtime on explanatory variables. A survival analysis, which is a statistical technique for analyzing time-to-event data, reveals that (1) the median downtime of building services components was 90 days and, 7 months after the earthquake, the empirical non-restoration probability was approximately 32%, (2) the services type and the building use are explanatory variables having a statistically significant effect on the downtime of building services components, (3) the log-logistic regression model reasonably captures the trend of the restoration of building services components, (4) medical and welfare facilities and hotels restored building services components relatively quickly, and (5) the 7-month restoration probability was observed to be highest for electrical systems, followed by sanitary systems, then heating, ventilation, and air conditioning systems, and finally life safety systems. These results provide useful information to support the resilience-based seismic design of buildings.
MIIP downregulates PD-L1 expression through HDAC6 in cutaneous melanoma
Authors: Li Ting , Xing Ruwei , Xiang Lijie , Liu Haotian , Wei Junqiang , Lu Jia , Li Tao , Yang Jilong
Published: May 2024

Purpose

Immune checkpoint inhibitors have improved the objective response rate and survival of melanoma patients. However, there are still many melanoma patients suffering from disease progression due to primary or secondary immune checkpoint inhibitor resistance, as is observed in the failure of anti-PD1/PD-L1 therapy. While the expression of valuable markers, such as TMB, MSI, and PD-L1, could serve as effective predictors of anti-checkpoint inhibitor therapies, tumor cell PD-L1 expression and its regulating mechanism would significantly affect the anti-PD-1 immunotherapy response and efficacy. Therefore, it is urgent to determine the function of PD-1/PD-L1 expression in melanoma and its associated pathways to enhance the efficacy of anti-PD-1 therapies.

Methods

A cohort of 133 patients with histologically confirmed melanoma from Tianjin Medical University Cancer Institute & Hospital were included in this study. We performed immunohistochemical staining to detect the expression of Migration and invasion inhibitory protein (MIIP), HDAC6 and PD-L1. Kaplan–Meier and log-rank test were used for survival analysis. As for vitro, Western blot was used in melanoma cell lines to verify the signaling pathway that MIIP regulates PD-L1 expression.

Results

MIIP expression was decreased in melanoma and that the negative expression of MIIP was correlated with worse overall survival. The positive expression of HDAC6, a molecule that is downstream of MIIP, had a positive trend with decreased overall survival. At the same time, the positive expression of PD-L1, a crucial costimulatory molecule, was associated with decreased overall survival. Furthermore, there was a positive association between HDAC6 and PD-L1 protein expression (p < 0.01), and this correlation is more prominent in cutaneous melanoma than acral melanoma. In cutaneous melanoma cell lines, we found that increasing MIIP led to decreased HDAC6, pSTAT3, and PD-L1 expression. Knocking down MIIP led to increased HDAC6, pSTAT3, and PD-L1 expression. Combining the published results, showing that HDAC6 can regulate PD-L1 expression through STAT3, our present data suggest that MIIP inhibits the expression of PD-L1 by downregulating HDAC6 in melanoma. Most importantly, methods for targeting MIIP-HDAC6-PD-L1 pathways, such as treatment with HDAC6 inhibitors, might indicate a new therapeutic approach for enhancing immune checkpoint inhibitor therapies in melanoma.

Conclusions

Our findings highlight the immunomodulatory effects of MIIP in the inhibition of PD-L1 expression by downregulating HDAC6 in melanoma. Methods for targeting MIIP-HDAC6-PD-L1 pathways might be new therapeutic approaches for enhancing immune checkpoint inhibitor therapies in melanoma.
The mediating role of social connectedness in the relationship between smartphone use and psychological adjustment problems in Turkish youth
Authors: Yıldırım Murat , Geçer Ekmel , Bağcı Hakkı
Published: May 2024

This study investigated the mediating role of social connectedness in the relationship between excessive smartphone use and psychological adjustment problems. 484 young adults (M = 27.04 ± 4.36 years and 72.1% females) participated in this study. Using an online survey, participants completed the Multidimensional Smartphone Use Scale, Social Connectedness Scale-Revised, and Brief Psychological Adjustment-6. The results showed that smartphone use had a significant predictive effect on social connectedness and psychological adjustment problems. Social connectedness also had a significant predictive impact on psychological adjustment problems. Further, social connectedness partially mediated the relationship between smartphone use and psychological adjustment problems. The findings are fruitful in terms of presenting evidence for tailoring prevention and intervention programs to mitigate the adverse consequences of smartphone use on psychological health.
The Power of Critique: A Tribute to Paulin Hountondji
Authors: Okeja Uchenna
Published: May 2024

The emergence of African philosophy as a systematic field of inquiry can be traced to the trailblazing work of a few figures. Paulin Hountondji occupies a special place among these trailblazers. A true exemplar of the field, Hountondji’s work is neither limited by the linguistically circumscribed mapping of African philosophy nor the dichotomies and quarrels arising from methodological and stylistic difference in doing philosophy. I reiterate the crucial challenge he poses to current and future generations of scholars by reflecting on his approach to philosophy and the critical insights he offers on fundamental questions about the nature, conditions and fate of freedom in Africa.
Preparing conservatoire students for the music education workforce: conversations with alumni
Authors: Shaw Luan
Published: May 2024

Higher music education institutions should continually review their curricula to ensure that their graduates are best equipped to support musical learning for children and young people. Perspectives on early careers in instrumental teaching were obtained via an alumni-led workshop and focus group at a UK conservatoire. Findings revealed that whilst extensive pedagogical training was offered, its value was not fully acknowledged across the institution and that more could be done to alleviate students’ anxieties about their developing musician identities and future stability. As new teachers, alumni are well placed to help prepare students for the professional realities of joining the music education workforce.
Observational Characterization of Atmospheric Disturbances Generating Meteotsunamis in the Balearic Islands
Authors: Villalonga Joan , Monserrat Sebastià , Gomis Damià , Jordà Gabriel
Published: May 2024

The high‐frequency sea level oscillations (SLO) associated with meteotsunamis can have hazardous consequences for coastal populations. They are triggered by high‐frequency atmospheric disturbances generating an oceanic response that is amplified mainly by Proudman and harbor resonance. So far, the lack of high‐resolution data had prevented a comprehensive characterization of these atmospheric disturbances, even in an extensively studied “hot spot” as Ciutadella (Balearic Islands). Here, we analyze atmospheric disturbances triggering meteotsunamis in Ciutadella during 2021 using data from an ultra‐dense meteorological network (BalearsMeteo). Atmospheric pressure time series with a sampling rate ≤1 min are used to estimate propagation speed and direction, spectral energy content, and the spatial homogeneity of atmospheric disturbances linked to meteotsunami events. We find that the spatial structure of the disturbances are rather heterogeneous, but the inferred propagation velocities are consistent with the occurrence of Proudman resonance on the continental shelves located upstream of Ciutadella (speeds between 24 and 36 m/s and directions from 210° to 260°). Although during meteotsunami events these velocity estimates undergo some changes both in time and in space, they show two key characteristics: (a) the atmospheric pressure disturbances are mostly non‐dispersive; and (b) the largest SLO are observed when the speed and direction of propagation velocities are more homogeneous in space and time. Nevertheless, an empirical relationship between the analyzed atmospheric features and the SLO amplitudes could not be established. That is, the prediction of meteotsunami amplitudes remains challenging due to the intricate interplay of atmospheric and oceanic processes.
Therapeutic targeting of ARID1A-deficient cancer cells with RITA (Reactivating p53 and inducing tumor apoptosis)
Authors: Wang Zihuan , Zhang Xu , Luo Yuchen , Song Yijiang , Xiang Cheng , He Yilin , Wang Kejin , Yu Yingnan , Wang Zhen , Peng Wenxuan , Ding Yi , Liu Side , Wu Changjie
Published: May 2024

ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is frequently mutated in various cancer types and has emerged as a potential therapeutic target. In this study, we observed that ARID1A-deficient colorectal cancer (CRC) cells showed synthetic lethal effects with a p53 activator, RITA (reactivating p53 and inducing tumor apoptosis). RITA, an inhibitor of the p53-MDM2 interaction, exhibits increased sensitivity in ARID1A-deficient cells compared to ARID1A wild-type cells. Mechanistically, the observed synthetic lethality is dependent on both p53 activation and DNA damage accumulation, which are regulated by the interplay between ARID1A and RITA. ARID1A loss exhibits an opposing effect on p53 targets, leading to decreased p21 expression and increased levels of proapoptotic genes, PUMA and NOXA, which is further potentiated by RITA treatment, ultimately inducing cell apoptosis. Meanwhile, ARID1A loss aggravates RITA-induced DNA damage accumulation by downregulating Chk2 phosphorylation. Taken together, ARID1A loss significantly heightens sensitivity to RITA in CRC, revealing a novel synthetic lethal interaction between ARID1A and RITA. These findings present a promising therapeutic approach for colorectal cancer characterized by ARID1A loss-of-function mutations.