bluuebunny/crossref_metadata_2025 huggingface dataset:
Reading Hoax: Measuring Students’ Critical News Literacy
Authors: Kusumalestari Ratri Rizki , Rachmiatie Atie , Darmawan Ferry , Kurnia Septiawan Santana , Yuniati Yenni , Palapah Maya Amalia Oesman
Published: March 2024

Media literacy has become increasingly crucial in today’s digital age as it is essential for students to learn how to critically evaluate news sources to identify hoaxes and make informed decisions. This study aimed to evaluate the impact of a media literacy course that had been running for 20 years on students' critical news literacy skills and critical thinking. Students were divided into two groups and asked to assess media texts. The results revealed that critical thinking was more significant for news literacy than media literacy. The study found that students’ critical news literacy skills were at a moderate level, with many struggling to recognize hoaxes in media texts. This finding suggests that further study is necessary to identify the factors influencing this, as well as how students interact with hoaxes in their daily lives.
Coaching Transitions Across Borders: The Pursuit of Individuals Advancing Coaching Careers in the Competitive Global Landscape of Olympic Sports
Authors: Kim Yoon Jin , Tak Minhyeok
Published: March 2024

Intensified international competition for sporting success has facilitated coaches’ cross-national migration, which constitutes a space for coaches’ career transitions and development. This paper examines elite coaches’ international migration as part of coaching career transitions within the context of the global sporting arms race. Using a qualitative case study design, data were generated from documents and semistructured interviews with six South Korean coaches who had moved to Western nations to coach national teams in two Olympic sports. The analysis reveals an underlying mechanism of the coaches’ international mobility: dual imbalances existing between the sending and receiving countries—one in the levels of sporting performance; and the other in the perceived levels of modernisation in coaching cultures and sports systems. The migration opportunities were created by the performance imbalance between the home nation and destinations amid the structural context of the global sporting arms race. However, equally important is the individuals’ strategic initiative to seize the opportunities for their career development and mitigate the perceived modernisation imbalance in coaching practices. By highlighting coaches’ agentic capacity to navigate their career pathways within the global context, this study contributes to the literature on both international coach migration and coaching transitions.
Prolonged Standing-Induced Low Back Pain Is Linked to Extended Lumbar Spine Postures: A Study Linking Lumped Lumbar Spine Passive Stiffness to Standing Posture
Authors: Fewster Kayla M. , Gallagher Kaitlin M. , Callaghan Jack P.
Published: March 2024

Postural assessments of the lumbar spine lack valuable information about its properties. The purpose of this study was to assess neutral zone (NZ) characteristics via in vivo lumbar spine passive stiffness and relate NZ characteristics to standing lumbar lordosis. A comparison was made between those that develop low back pain during prolonged standing (pain developers) and those that do not (nonpain developers). Twenty-two participants with known pain status stood on level ground, and median lumbar lordosis angle was calculated. Participants were then placed in a near-frictionless jig to characterize their passive stiffness curve and location of their NZ. Overall, both pain developers and nonpain developers stood with a lumbar lordosis angle that was more extended than their NZ boundary. Pain developers stood slightly more extended (in comparison to nonpain developers) and had a lower moment corresponding to the location of their extension NZ boundary. Overall, in comparison to nonpain developers, pain developers displayed a lower moment corresponding to the location of their extension NZ boundary which could correspond to greater laxity in the lumbar spine. This may indicate why pain developers have a tendency to stand further beyond their NZ with greater muscle co-contraction.
From isotopically labeled DNA to fluorescently labeled dynamic pili: building a mechanistic model of DNA transport to the cytoplasmic membrane
Authors: Zuke Jason D. , Burton Briana M.
Published: March 2024

Natural competence, the physiological state wherein bacteria produce proteins that mediate extracellular DNA transport into the cytosol and the subsequent recombination of DNA into the genome, is conserved across the bacterial domain. DNA must successfully translocate across formidable permeability barriers during import, including the cell membrane(s) and the cell wall, that are normally impermeable to large DNA polymers. This review will examine the mechanisms underlying DNA transport from the extracellular space to the cytoplasmic membrane. First, the challenges inherent to DNA movement through the cell periphery will be discussed to provide context for DNA transport during natural competence. The following sections will trace the development of a comprehensive model for DNA translocation to the cytoplasmic membrane, highlighting the crucial studies performed over the last century that have contributed to building contemporary DNA import models. Finally, this review will conclude by reflecting on what is still unknown about the process and the possible solutions to overcome these limitations.
Whole-genome sequencing of
Aminobacterium
sp. strain MB27-C1, isolated from the wastewater treatment plant of a steel mill
Authors: Huang Junlin , Wu Chih-Hung , Shih Chao-Jen , Wu Yen-Chi , Lai Shu-Jung , You Yi-Ting , Chen Sheng-Chung
Published: March 2024

Here, we report the complete genome sequence of
Aminobacterium
sp. strain MB27-C1, which was isolated from sewage sludge collected at the wastewater treatment plant of Sanming Steel Co. Ltd. in Fujian, China. The resulting genome of strain MB27-C1 is a single contig of 2,427,830 bp with 41.58% GC content.
Metagenomic sequencing reveals viral diversity of mosquitoes from Shandong Province, China
Authors: Wang Yuhao , Lin Xiaojuan , Li Chao , Liu Guifang , Wang Suting , Chen Meng , Wei Xuemin , Wen Hongling , Tao Zexin , Xu Yifei
Published: March 2024

Mosquitoes carry a large number of known and unknown viruses, some of which could cause serious diseases in humans or animals. Metagenomic sequencing for mosquito viromes is crucial for understanding the evolutionary history of viruses and preventing emerging mosquito-borne diseases. We collected 1,598 mosquitoes belonging to four species from five counties in Shandong Province, China in 2021. They were grouped by species and sampling locations and subjected to metagenomic next-generation sequencing for the analysis of the viromes. A total of 233,317,352 sequencing reads were classified into 30 viral families and an unclassified group. Comparative analysis showed that mosquitoes in Shandong Province generally possessed host-specific virome. We detected mosquito-borne viruses including Japanese encephalitis virus, Getah virus, and Kadipiro virus in
Culex tritaeniorhynchus
and
Anopheles sinensis
samples. Phylogenetic analysis showed that these pathogenic viruses may have existed in mosquitoes in Shandong Province for a long time. Meanwhile, we identified 22 novel viruses belonging to seven families and the genus
Negevirus
. Our study comprehensively described the viromes of several common mosquito species in Shandong Province, China, and demonstrated the major role of host species in shaping mosquito viromes. Furthermore, the metagenomic data provided valuable epidemiological information on multiple mosquito-borne viruses, highlighting the potential risk of infection transmission.

IMPORTANCE

Mosquitoes are known as the source of various pathogens for humans and animals.
Culex tritaeniorhynchus
,
Armigeres subalbatus
, and
Anopheles sinensis
have been found to transmit the Getah virus, which has recently caused increasing infections in China.
Cx. tritaeniorhynchus
and
Culex pipiens
are the main vectors of Japanese encephalitis virus and have caused epidemics of Japanese encephalitis in China in past decades. These mosquitoes are widely present in Shandong Province, China, leading to a great threat to public health and the breeding industry. This study provided a comprehensive insight into the viromes of several common mosquito species in Shandong Province, China. The metagenomic sequencing data revealed the risks of multiple pathogenic mosquito-borne viruses, including Japanese encephalitis virus, Getah virus, and Kadipiro virus, which are of great importance for preventing emerging viral epidemics.
Direction-dependent failure envelopes of sand-structure interfaces with snakeskin-inspired surfaces
Authors: O'Hara Kyle , Martinez Alejandro
Published: March 2024

Snakeskin-inspired surfaces generate direction-dependent interface strengths, with shearing in the cranial direction (i.e.; against the scales) generating greater strength than in the caudal one (i.e.; along the scales). This directionality is enabled by the transfer of load in friction and passive resistances. It is unclear if failure of these interfaces can be captured by models used for purely frictional interfaces. Interface shear tests complemented with particle image velocimetry (PIV) analyses were performed on snakeskin-inspired surfaces with different asperity geometries and on reference rough and smooth surfaces. The results of experiments performed at different initial effective stresses under constant normal stiffness boundary conditions show significant dilation-induced increases in effective stress. These increases were greater during cranial than caudal shearing, producing greater cranial strengths. These surfaces yielded nonlinear failure envelopes, with greater shear to effective stress ratios at smaller effective stresses, while the rough and smooth surfaces mobilized linear failure envelopes. The PIV analyses indicate that the snakeskin-inspired surfaces induce localized strains in the vicinity of the asperities, leading to wavy failure planes. The average shear strains are correlated with the mobilized shear strengths, with increases in effective stress leading to decreases in both strains and stress ratio.
Probing atmospheric effects using GRAPES-3 plastic scintillator detectors
Authors:   GRAPES-3 Collaboration, Zuberi M. , Ahmad S. , Chakraborty M. , Chandra A. , Dugad S. R. , Goswami U. D. , Gupta S. K. , Hariharan B. , Hayashi Y. , Jagadeesan P. , Jain A. , Jain P. , Jhansi V. B. , Kawakami S. , Kojima H. , Mahapatra S. , Mohanty P. K. , Muraki Y. , Nayak P. K. , Nonaka T. , Oshima A. , Pattanaik D. , Rameez M. , Ramesh K. , Reddy L. V. , Shibata S. , Varsi F.
Published: March 2024

The GRAPES-3 extensive air shower (EAS) array has been designed to study cosmic rays from 10$$^{13}$$

13

–10$$^{16}$$

16

 eV. It employs 400 scintillator detectors spread across 25,000 m$$^{2}$$

2

, mainly of cone-type and fiber-type, each covering a 1 m$$^{2}$$

2

area. These detectors record EAS particle densities and arrival times, which are crucial for determining primary particle energy and direction. A decade (2013–2022) of EAS data is analyzed to investigate the dependence of particle densities on ambient temperature and atmospheric pressure. Notably, ambient temperature exhibits a delayed response, with a more pronounced delay in fiber-type detectors, while cone-type detectors exhibit a higher observed temperature coefficient. In contrast, atmospheric pressure instantly and uniformly affects both detector types, with Monte Carlo simulations backing the observed pressure coefficient. These findings established a reliable pressure coefficient for EAS within this distinctive energy range and contributed to the refinement of correction algorithms, ultimately improving particle density precision for more accurate shower parameter estimates.
Quark stars in $$D_3$$–$$D_7$$ holographic model
Authors: Aleixo M. , Lenzi C. H. , de Paula W. , Rocha R. da
Published: March 2024

This work investigates static and dynamical quark star properties within a $$D_3{-}D_7$$

D
3

-

D
7

holographic model. We solve the Tolman–Oppenheimer–Volkoff equations for the quark matter equation of state obtained from the brane configuration. We determine the mass-radius diagram for a range of model parameters and compare with recent NICER observational data for the pulsars PSR J$$0030+0451$$

0030
+
0451

and PSR J$$0740+6620.$$

0740
+
6620
.

Motivated by the GW170817 event detected by the LIGO-Virgo collaboration, we also calculate the tidal deformability parameter obtained for each component of the binary star system. We show that quark stars composed of flavor-independent quark matter derived from the $$D_3{-}D_7$$

D
3

-

D
7

holographic model are not able to satisfy simultaneously the LIGO-Virgo and NICER astrophysical bounds.
Gravity-induced entanglement between two massive microscopic particles in curved spacetime: I. The Schwarzschild background
Authors: Zhang Chi , Shu Fu-Wen
Published: March 2024

The experiment involving the entanglement of two massive particles through gravitational fields has been devised to discern the quantum attributes of gravity. In this paper, we present a scheme to extend this experiment’s applicability to more generalized curved spacetimes, with the objective of validating universal quantum gravity within broader contexts. Specifically, we direct our attention towards the quantum gravity induced entanglement of masses (QGEM) in astrophysical phenomena, such as particles traversing the interstellar medium. Notably, we ascertain that the gravitational field within curved spacetime can induce observable entanglement between particle pairs in both scenarios, even when dealing with particles significantly smaller than mesoscopic masses. Furthermore, we obtain the characteristic spectra of QGEM across diverse scenarios, shedding light on potential future experimental examinations. This approach not only establishes a more pronounced and extensive manifestation of the quantum influences of gravity compared to the original scheme but also opens avenues for prospective astronomical experiments. These experiments, aligned with our postulates, hold immense advantages and implications for the detection of quantum gravity and can be envisioned for future design.
Micromechanical study of nano-cutting metal-ceramic WC/Cu by diamond tools
Authors: Chen Jie , Zhu Zongxiao , Yi Bingqi , Qu Dingfeng , Luo Donglei , Wei Lizhan , Li Wenwen , Zhu Shengyu , Zheng Min
Published: March 2024

In this paper, the effect of the distribution of ceramic particles WC in Cu matrix on the nano-cutting behavior was investigated using molecular dynamics, and the cutting force, friction coefficient, machined surface quality, sub-surface damage depth, atomic displacement and internal defects were systematically studied, and the performance comparison at different cutting speeds was also investigated. It was found that due to the location of the WC phase, the overall removal of the material by the tool can be divided into the following three ways: When WC particles are above the cutting plane, there is less fluctuation in cutting forces and friction coefficients, and less impact on machined surface and subsurface damage; When the WC particles are below the cutting plane, the fluctuation of cutting force and friction coefficient is slow. Meanwhile, shallow craters are produced at the WC location; When the center of mass of WC particles is on the same level as the cutting plane, the cutting force and friction coefficient fluctuate drastically, the quality of the machined surface deteriorates sharply, and at the same time the hard particles pulled out by the tool remain on the machined surface. It was also found that the WC particles underwent different degrees of counterclockwise deflection in the three stages and caused a diversion of the atomic displacement in front of the tool. In addition, different degrees of dislocation plugging are formed between the WC and the tool at different positions, and the density of dislocation lines increases, which makes the substrate near the WC particles strengthened.
Dynamical stricture of optical soliton solutions and variational principle of nonlinear Schrödinger equation with Kerr law nonlinearity
Authors: Seadawy Aly R. , Alsaedi Bayan A.
Published: March 2024

The aim of this paper is to discover some new exact solutions for two kinds of nonlinear Schrödinger equation (NLSE), including the (2+1)-dimensional NLSE and the derivative NLSE, through the use of the variational principle method and amplitude ansatz method. We will find the solutions to these equations by selecting a trial function with a single nontrivial variational parameter, and it is continuous at all intervals in three cases from a region of a rectangular box, then using this trial function to obtain the functional integral and the Lagrangian of the system without any loss. After that, we approximate this trial function by quadratic polynomials with two free parameters rather than a piecewise linear ansatz function. Similarly, this trial function will be approximated by the tanh function. Additionally, we accept several new types of soliton solutions, including bright solitons, dark solitons, bright–dark solitary wave solutions, rational dark–bright solutions, and periodic solitary wave solutions. Also, conditions for the stability of the solutions will be proposed. These explanations are of great importance in the fields of applied science and engineering. The results will be shown through different types of graphs, including 2D, 3D, and contour plots.
Weakly restoring forces and shallow water waves with dynamical analysis of periodic singular solitons structures to the nonlinear Kadomtsev–Petviashvili-modified equal width equation
Authors: Iqbal Mujahid , Seadawy Aly R. , Lu Dianchen , Zhang Zhengdi
Published: March 2024

In this study, the nonlinear two-dimensional Kadomtsev–Petviashvili-modified equal width (KP-MEW) equation is under investigation, which is described as a nonlinear wave model in weakly restoring forces and shallow water waves in the way of ferromagnetic, solitary waves in two dimensions with short amplitude and long wavelength and are also helpful in the investigation of various behaviors in nonlinear sciences. We successfully found the interesting and novel solitary wave results in bright solitons, kink solitons, dark solitons, anti-kink solitons, periodic singular solitons for nonlinear two-dimensional KP-MEW equation on the base of extension of simple equation technique under symbolic computational software Mathematica. The created solitons play an important role in nonlinear engineering and physics such as nonlinear optics, nonlinear dynamics, soliton wave theory, optical fiber and communication system. We are sure that these constructed results are novel and interesting which does not exist in the previous literature works. The graphical representation of constructed results is shown by 2D, 3D and contour graphs. The investigated research work proved that utilized technique is more concise, straightaway and efficient for study of other nonlinear partial differential equations.
Dynamic Analysis of a Ratio-Dependent Food Chain Model with Prey-Taxis
Authors: Liao Zhuzhen , Song Cui , Wang Zhi-Cheng
Published: March 2024

In this paper, we consider a food chain model with ratio-dependent functional response and prey-taxis. We first investigate the global existence and boundedness of the unique positive classical solutions of the system in a bounded domain with smooth boundary and Neumann boundary conditions. Then, we analyze the local stability of the system and the existence of Hopf bifurcation. In addition, we prove the global asymptotic stability of steady states under some conditions by constructing a Lyapunov functional, and investigate convergence rates. Finally, we present several numerical simulations to illustrate the results.
Free and Open Source Software - and Other Market Failures
Authors: Kamp Poul-Henning
Published: March 2024

Open source was not so much the goal itself as a means to an end, which is freedom: freedom to fix broken things, freedom from people who thought they could clutch the source code tightly and wield our ignorance of it as a weapon to force us all to pay for and run Windows Vista. But the FOSS movement has won what it wanted, and no matter how much oldsters dream about their glorious days as young revolutionaries, it is not coming back, because the frustrations and anger of IT in 2024 are entirely different from those of 1991.
A Resource Allocation Scheme for Edge Computing Network in Smart City Based on Attention Mechanism
Authors: Sun Zhengjie , Yang Hui , Li Chao , Yao Qiuyan , Teng Yun , Zhang Jie , Liu Sheng , Li Yunbo , Vasilakos Athanasios V.
Published: March 2024

In recent years, the number of devices and terminals connected to the smart city has increased significantly. Edge networks face a greater variety of connected objects and massive services. Considering that a large number of services have different QoS requirements, it has always been a huge challenge for smart city to optimally allocate limited computing resources to all services to obtain satisfactory performance. In particular, delay is intolerable for services in certain applications, such as medical, industrial applications, etc, that such applications require the high priority. Therefore, through flexibly dynamic scheduling, it is crucial to schedule services to the optimal node to ensure user experience. In this paper, we propose a resource allocation scheme for hierarchical edge computing network in smart city based on attention mechanism, for extracting a small number of features that can represent services from a large amount of information collected from edge nodes. The attention mechanism is used to quickly determine the priority of the services. Based on this, task deployment and resource allocation for different task priorities are developed to ensure the quality of service in smart cities by introducing Q-learning. Simulation results show that the proposed scheme can effectively improve the edge network resource utilization, reduce the average delay of task processing, and effectively guarantee the quality of service.
The Role of Social Media Platforms in Forecasting Elections: A Comparison of Twitter and Facebook
Authors: Vepsäläinen Tapio , Li Hongxiu , Suomi Reima
Published: March 2024

Prior literature shows that social media could be used to forecast political elections. Most studies have focused on a single social media platform, and few studies have explored the use of social media data across multiple platforms to make election predictions. Though candidates’ personal attributes have also been suggested as critical factors affecting election results, there has been little research into the interacting effect of social media and candidate attributes in predicting elections. To address the research gap, this article investigates the role of two different social media platforms, Twitter (now known as “X”) and Facebook, in forecasting the 2019 Finnish parliamentary elections and how candidates’ political experience moderates the role of the two platforms in predicting elections. The findings show that both the number of Facebook likes and the number of Twitter followers are associated with the election outcome positively. Political experience of candidates moderates the association between the number of Facebook likes and election outcomes as well as the association between the number of Twitter followers and election outcomes. This research adds to the discussion on how social media can predict election results. It considers both different social media platforms and the roles of the candidate attributes.
PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma
Authors: Han Boxuan , Chen Jiaming , Chen Shaoshi , Shen Xixi , Hou Lizhen , Fang Jugao , Lian Meng
Published: March 2024

It has been demonstrated that PPARG may interact with the PTEN-PI3K/AKT pathway, contributing to its involvement in the chemotherapy treatment of hypopharyngeal squamous cell carcinoma (HSCC). However, the underlying mechanism remains largely unknown. In this study, gene expression profiles of 17 HSCC patients, comprising 8 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP), were collected and analyzed to investigate expression patterns, correlations, influencing factors of the PPARG-PTEN-PI3K/AKT pathway, and its role in regulating chemosensitivity. The results revealed significantly increased expression (p<0.04) of AKT1, AKT2, AKT3, PIK3CA, PPARG, and PTEN in the CSP group compared to the CNSP group. Specifically, AKT2 exhibited significant overexpression in tumor tissue (p=0.01), while AKT2, AKT3, PPARG, and PTEN displayed significant increases in normal tissue (p≤0.04). Positive correlations (R∈0.43,0.71, p<0.014) were observed between PIK3CA, AKT1, AKT2, AKT3, and PTEN, with AKT2, AKT3, and PTEN also showing significant correlations with PPARG (R∈0.35,0.47, p<0.04). Age, gender, and disease stage had no influence on PPARG, PIK3CA, and PTEN expression, but they may affect AKT expressions. Pathway analysis revealed that PPARG may interact with the PTEN-PI3K/AKT signaling pathway, playing a crucial role in regulating chemosensitivity in the normal tissue microenvironment. Our results suggest that AKT1 and PIK3CA may be associated with chemosensitivity in HSCC tumor cells, while PPARG and PTEN might exhibit a correlation with a specific segment of the PI3K/AKT pathway, potentially influencing chemosensitivity in the normal tissue microenvironment of HSCC patients.
Saffron the “Red Gold” and Its CNS Activity: A Challenge for Future Applications in Nutraceuticals
Authors: Sut Stefania , Gherardi Gaia , Ruzza Filippo , Caudullo Giada , Shrestha Shyam Sharan , Sorrenti Vincenzo , Dall’Acqua Stefano
Published: March 2024

Saffron, indicated as “the red gold,” is an extraordinary spice with a unique aroma and organoleptic properties that is largely diffused in food preparation as well as a traditional medicine in many countries of the world. In the last years, several studies have considered this spice for CNS-based disorders showing its potential usefulness. In this review, we considered the role of saffron as a nutraceutical for the management of the most diffused CNS diseases considering the important role of oxidative stress on the pathogenesis of such diseases. In fact, recent findings support a crucial role of oxidative stress in different CNS diseases suggesting an important role of antioxidants. Preclinical and clinical evidence of its efficacy in different physiopathological pathways involved in several CNS diseases were discussed showing evidence of pharmacological activities and beneficial effects in pathological models or in small trials. Due to low toxicity and significant activities on oxidative stress and inflammation as well as the ability to modulate mitochondrial function, the saffron extracts and their constituents appear to be promising nutraceutical active compounds in this area. Further investigations are in progress to assess the efficacy and safety of preventive agents as nutraceuticals or as adjuvant compounds to be used in combinations with other therapeutic approaches. Saffron nutraceuticals with significant antioxidant activity can be useful in improving the quality of life of patients suffering from several different pathological conditions related to CNS. In this review, we summarized the more recent studies showing that standardized saffron products can be a valuable instrument of well-being due to their effects on multiple targets that support the health of the brain and related tissues.
Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: March 2024

Purpose:

B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial.

Patients and Methods:

We collected apheresis, final product, peripheral blood and bone marrow samples before and after infusion. We assessed BCMA, T-cell subsets, CART kinetics and antibodies, B-cell aplasia, cytokines, and measurable residual disease by next-generation flow cytometry, and correlated these to clinical outcomes.

Results:

At cut-off date March 17, 2023, with a median follow-up of 23.1 months (95% CI, 9.2–37.1), overall response rate in the first 3 months was 95% [95% confidence interval (CI), 89.5–100]; cytokine release syndrome (CRS) was observed in 90% of patients (5% grades ≥3) and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 2 patients (3%). Median progression-free survival was 15.8 months (95% CI, 11.5–22.4). Surface BCMA was not predictive of response or survival, but soluble BCMA correlated with worse clinical outcomes and CRS severity. Activation marker HLA-DR in the apheresis was associated with longer progression-free survival and increased exhaustion markers correlated with poorer outcomes. ARI0002h kinetics and loss of B-cell aplasia were not predictive of relapse.

Conclusions:

Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes.
Supplementary Figure 1 from Rejuvenated iPSC-derived GD2-directed CART Cells Harbor Robust Cytotoxicity Against Small Cell Lung Cancer
Authors: Kinoshita Shintaro , Ishii Midori , Ando Jun , Kimura Takaharu , Yamaguchi Tomoyuki , Harada Sakiko , Takahashi Fumiyuki , Nakashima Kazutaka , Nakazawa Yozo , Yamazaki Satoshi , Ohshima Koichi , Takahashi Kazuhisa , Nakauchi Hiromitsu , Ando Miki
Published: March 2024

Supplementary Figure S1 illustrates the cytotoxic effects of GD2-CARTs (GD2-2840z-CARTs, GD2-28z-CARTs, and GD2-BBz-CARTs) and control T cells on GD2+ tumor cells through in vitro 51Cr release assays.
Supplementary Table 1-1 from Antibody–Drug Conjugate αEGFR-E-P125A Reduces Triple-negative Breast Cancer Vasculogenic Mimicry, Motility, and Metastasis through Inhibition of EGFR, Integrin, and FAK/STAT3 Signaling
Authors: Sankar Ankita P. , Cho Hyun-Mi , Shin Seung-Uon , Sneh Tal , Ramakrishnan Sundaram , Elledge Christian , Zhang Yu , Das Rathin , Gil-Henn Hava , Rosenblatt Joseph D.
Published: March 2024

Extended table of differentially expressed genes from 2D to 3D
FIGURE 5 from Rejuvenated iPSC-derived GD2-directed CART Cells Harbor Robust Cytotoxicity Against Small Cell Lung Cancer
Authors: Kinoshita Shintaro , Ishii Midori , Ando Jun , Kimura Takaharu , Yamaguchi Tomoyuki , Harada Sakiko , Takahashi Fumiyuki , Nakashima Kazutaka , Nakazawa Yozo , Yamazaki Satoshi , Ohshima Koichi , Takahashi Kazuhisa , Nakauchi Hiromitsu , Ando Miki
Published: March 2024

Blockade of TIGIT and PD-1 augments cytotoxicity of GD2 2840z-CARTs. A, Schema of immune-regulatory mechanism of T cells against SCLC. B, Flow cytometric analysis of TIGIT and CD226 expression on GD2-2840z-CARTs and GD2-CARrejTs. The plots represent independent triplicate experiments. C, Flow cytometric analysis of CD155 expression on H69, H446, and SCLC-J1 (red). Histogram in blue, fluorescence minus one (FMO) control. The histograms represent independent triplicate experiments. D, Flow cytometric analysis of PD-L1 expression on GD2-expressing tumor cell lines (H69, H446, and SCLC-J1; red). Histogram in blue, FMO control. The histograms represent independent triplicate experiments. E, RTCA continuous graphical output of tumor proliferation indices up to 80 hours alone and in coculture with GD2-2840z-CARTs with/without anti-TIGIT (aTIGIT) and/or anti-PD-1 antibodies (aPD-1). Data were plotted and are shown as mean ± SD. Data represent three independent triplicate experiments. F, Schema of immune-regulatory mechanism of GD2-2840z-CARTs and GD2-CARrejTs against SCLC.
FIGURE 4 from Rejuvenated iPSC-derived GD2-directed CART Cells Harbor Robust Cytotoxicity Against Small Cell Lung Cancer
Authors: Kinoshita Shintaro , Ishii Midori , Ando Jun , Kimura Takaharu , Yamaguchi Tomoyuki , Harada Sakiko , Takahashi Fumiyuki , Nakashima Kazutaka , Nakazawa Yozo , Yamazaki Satoshi , Ohshima Koichi , Takahashi Kazuhisa , Nakauchi Hiromitsu , Ando Miki
Published: March 2024

scRNA-seq analysis of GD2-2840-CARTs and GD2-CARrejT. A and B, UMAP projection of scRNA-seq data of GD2-2840z-CARTs and GD2-CARrejTs. Cluster gene characteristics determine cluster functional description. Cluster 1: CD4+ T cells/CD8+ T cells 1; Cluster 2: CD8+ T cells 1; Cluster 3: CD8− T cells; Cluster 4: Cytotoxic T cells 1; Cluster 5: Cytotoxic T cells 2; Cluster 6: Cytotoxic T cells 3; Cluster 7: CD4+ T cells/CD8+ T cells 2; Cluster 8: Cytotoxic T cells 4. Cells colored according to single-cell genotype group. C, Lineage (CD3E, CD4, CD8A). D, Cytotoxicity (IFNG, PRF1, GZMB). E, Immunologic synapse (CD2, CD11a, CD11b, CD45, CD44). F, Inhibitory immunoreceptor (SIGLEC7). G, Exhaustion (HAVCR2, LAG-3, TIGIT, PD-1). H, Heat map of unique signature genes (lineage, costimulation, coinhibition, cytotoxic molecules, transcription factors) for each individual cluster.
FIGURE 3 from Rejuvenated iPSC-derived GD2-directed CART Cells Harbor Robust Cytotoxicity Against Small Cell Lung Cancer
Authors: Kinoshita Shintaro , Ishii Midori , Ando Jun , Kimura Takaharu , Yamaguchi Tomoyuki , Harada Sakiko , Takahashi Fumiyuki , Nakashima Kazutaka , Nakazawa Yozo , Yamazaki Satoshi , Ohshima Koichi , Takahashi Kazuhisa , Nakauchi Hiromitsu , Ando Miki
Published: March 2024

Robust tumor suppressive effect of GD2-CARrejTs in vivo.A, Graphical abstract of in vivo experiment. H446 cells labeled with FFluc/GFP were intravenously injected into NOG mice (1 × 106 cells/mouse) 4 days before treatment. Mice treated with GD2-2840z-CARTs and GD2-CARrejTs were treated every 2 weeks (three doses). B, Bioluminescence imaging of mice engrafted with H446 cells in three groups: no treatment group (control group, n = 10), GD2-2840z-CARTs group (n = 7), and GD2-CARrejTs group (n = 7). Images of all mice from each group of three independent experiments are shown. C, Tumor burden of each mouse is shown, comparing the in vivo efficacy of GD2-2840z-CARTs and GD2-CARrejTs. Bioluminescence kinetics of all mice from each group of three independent experiments are shown: no treatment group (control group, n = 10), GD2-2840z-CARTs group (n = 7), and GD2-CARrejTs group (n = 7). D, Quantitation of tumor burden on day 35 is shown: no treatment group (n = 8), GD2-2840z-CARTs group (n = 7), and GD2-CARrejTs group (n = 7). ****, P < 0.0001 by one-way ANOVA. E, Kaplan–Meier curves representing percentage survival of groups: no treatment group (n = 10), GD2-2840z-CARTs group (n = 7), and GD2-CARrejTs group (n = 7). ***, P < 0.001; ****, P < 0.0001 by log-rank test. ns, not significant. F, Copy numbers of GD2-CAR transduced T cells in mouse treated with GD2-2840z-CARTs and GD2-CARrejTs on day 35. Error bars represent ± SD. The plots represent three independent experiments. G, Photomicrographs, representative hematoxylin and eosin–stained sections of liver of SCLC-bearing mouse in each group; no treatment, GD2-2840z-CART treatment, and GD2-CARrejT treatment (top row). Infiltrates are bracketed. Human CD3+ T-cell infiltrates in liver (bottom row). CD3+ T cells are stained in brown (black arrowhead). 4x, 40x: Objective lens. Scale bars, each 20 µm.
Supplementary Figure 3 from Antibody–Drug Conjugate αEGFR-E-P125A Reduces Triple-negative Breast Cancer Vasculogenic Mimicry, Motility, and Metastasis through Inhibition of EGFR, Integrin, and FAK/STAT3 Signaling
Authors: Sankar Ankita P. , Cho Hyun-Mi , Shin Seung-Uon , Sneh Tal , Ramakrishnan Sundaram , Elledge Christian , Zhang Yu , Das Rathin , Gil-Henn Hava , Rosenblatt Joseph D.
Published: March 2024

GSEA of Hallmarks pathways downregulated from 2D to 3D and upregulated upon αEGFR-E-P125A treatment
Autophagy Inhibition–induced Cytosolic DNA Sensing Combined with Differentiation Therapy Induces Irreversible Myeloid Differentiation in Leukemia Cells
Authors: Baba Tomohisa , Tomaru Utano , Hirao Atsushi , Mukaida Naofumi , Johmura Yoshikazu
Published: March 2024

Accumulating evidence indicates that various oncogenic mutations interfere with normal myeloid differentiation of leukemogenic cells during the early process of acute myeloid leukemia (AML) development. Differentiation therapy is a therapeutic strategy capable of terminating leukemic expansion by reactivating the differentiation potential; however, the plasticity and instability of leukemia cells counteract the establishment of treatments aimed at irreversibly inducing and maintaining their differentiation states. On the basis of our previous observation that autophagy inhibitor treatment induces the accumulation of cytosolic DNA and activation of cytosolic DNA-sensor signaling selectively in leukemia cells, we herein examined the synergistic effect of cytosolic DNA-sensor signaling activation with conventional differentiation therapy on AML. The combined treatment succeeded in inducing irreversible differentiation in AML cell lines. Mechanistically, cytosolic DNA was sensed by absent in melanoma 2 (AIM2), a cytosolic DNA sensor. Activation of the AIM2 inflammasome resulted in the accumulation of p21 through the inhibition of its proteasomal degradation, thereby facilitating the myeloid differentiation. Importantly, the combined therapy dramatically reduced the total leukemia cell counts and proportion of blast cells in the spleens of AML mice. Collectively, these findings indicate that the autophagy inhibition-cytosolic DNA-sensor signaling axis can potentiate AML differentiation therapy.

Significance:

Clinical effects on AML therapy are closely associated with reactivating the normal myeloid differentiation potential in leukemia cells. This study shows that autophagosome formation inhibitors activate the cytosolic DNA-sensor signaling, thereby augmenting conventional differentiation therapy to induce irreversible differentiation and cell growth arrest in several types of AML cell lines.
Prehospital and In-Hospital Treatment with Adrenaline and Related Prognosis in Anaphylaxis Patients
Authors: Holst Gudichsen Julie , Aggerholm Bækdal Emil , Mikkelsen Søren , Touborg Lassen Annmarie , Bloch Jessen Frederik , Bindslev-Jensen Carsten , Mortz Charlotte G.
Published: March 2024

Introduction: Although intramuscular adrenaline is the recommended first-line treatment for anaphylaxis, not all patients receive this treatment. The consequences in daily clinical practice are sparsely described. This study aimed to investigate the treatment administered to anaphylactic patients and the related prognosis. Methods: A retrospective register-based study of patients with anaphylaxis referred to the allergy centre, Odense University Hospital (2019–2021). Each patient’s medical records were reviewed for contacts with the emergency departments and the prehospital emergency medical service in the Region of Southern Denmark. The World Allergy Organization (WAO) grading system was used to assess the severity of prehospital and in-hospital anaphylaxis. Furthermore, the treatment administered to the patients was registered. Results: In total, 315 patients were included. The prehospital system had contact with 256 of these patients (two were released prehospitally following treatment and 12 patients had insufficient data to assess anaphylaxis). Of the remaining 242 patients, 115 had anaphylaxis prehospitally (WAO grades 3–5); 59% (67/115) received adrenaline. Among the 67 patients who received prehospital adrenaline, 9 patients (13.4%; 95% CI: 6.3–24.0%) still had anaphylaxis at arrival at the emergency department. Of the 48 patients that were not treated with prehospital adrenaline, 17 patients (35.5%; 95% CI: 22.1–50.5) had anaphylaxis at the arrival to the emergency department. Among the 127 patients without prehospital anaphylaxis (WAO grades 0–2), 22 patients (18.2%; 95% CI: 11.8–26.2%) who did not receive prehospital adrenaline had anaphylaxis at arrival to the emergency department, while none of the 6 patients treated prehospitally with adrenaline had anaphylaxis. Conclusion: Omission of prehospital adrenaline in anaphylactic patients is associated with more severe anaphylactic symptoms at arrival to the hospital. Adrenaline treatment remains suboptimal since only half of the patients received prehospital adrenaline and only 1 out of 4 patients, with clinical signs of anaphylaxis, received adrenaline inside the hospital.
Association of Blood Pressure With Brain Ages: A Cohort Study of Gray and White Matter Aging Discrepancy in Mid-to-Older Adults From UK Biobank
Authors: Du Jing , Pan Yuangang , Jiang Jiyang , Liu Yue , Lam Ben C.P. , Schutte Aletta E. , Tsang Ivor W. , Sachdev Perminder S. , Wen Wei
Published: March 2024

BACKGROUND:

Gray matter (GM) and white matter (WM) impairments are both associated with raised blood pressure (BP), although whether elevated BP is differentially associated with the GM and WM aging process remains inadequately examined.

METHODS:

We included 37 327 participants with diffusion-weighted imaging (DWI) and 39 630 participants with T1-weighted scans from UK Biobank. BP was classified into 4 categories: normal BP, high-normal BP, grade 1, and grade 2 hypertension. Brain age gaps (BAGs) for GM (BAG
GM
) and WM (BAG
WM
) were derived from diffusion-weighted imaging and T1 scans separately using 3-dimensional-convolutional neural network deep learning techniques.

RESULTS:

There was an increase in both BAG
GM
and BAG
WM
with raised BP (
P
<0.05). BAG
WM
was significantly larger than BAG
GM
at high-normal BP (0.195 years older;
P
=0.006), grade 1 hypertension (0.174 years older;
P
=0.004), and grade 2 hypertension (0.510 years older;
P
<0.001), but not for normal BP. Mediation analysis revealed that the association between hypertension and cognitive decline was primarily mediated by WM impairment. Mendelian randomization analysis suggested a causal relationship between hypertension and WM aging acceleration (unstandardized B, 1.780;
P
=0.016) but not for GM (
P
>0.05). Sliding-window analysis indicated the association between hypertension and brain aging acceleration was moderated by chronological age, showing stronger correlations in midlife but weaker associations in the older age.

CONCLUSIONS:

Compared with GM, WM was more vulnerable to raised BP. Our study provided compelling evidence that concerted efforts should be directed towards WM damage in individuals with hypertension in clinical practice.
Potassium-Switch Signaling Pathway Dictates Acute Blood Pressure Response to Dietary Potassium
Authors: Welling Paul A. , Little Robert , Al-Qusairi Lama , Delpire Eric , Ellison David H. , Fenton Robert A. , Grimm P. Richard
Published: March 2024

BACKGROUND:

Potassium (K
+
)-deficient diets, typical of modern processed foods, increase blood pressure (BP) and NaCl sensitivity. A K
+
-dependent signaling pathway in the kidney distal convoluted tubule, coined the K
+
switch, that couples extracellular K
+
sensing to activation of the thiazide-sensitive NaCl cotransporter (NCC) and NaCl retention has been implicated, but causality has not been established.

METHODS:

To test the hypothesis that small, physiological changes in plasma K
+
(P
K+
) are translated to BP through the switch pathway, a genetic approach was used to activate the downstream switch kinase, SPAK (SPS1-related proline/alanine-rich kinase), within the distal convoluted tubule. The CA-SPAK (constitutively active SPS1-related proline/alanine-rich kinase mice) were compared with control mice over a 4-day P
K+
titration (3.8–5.1 mmol) induced by changes in dietary K
+
. Arterial BP was monitored using radiotelemetry, and renal function measurements, NCC abundance, phosphorylation, and activity were made.

RESULTS:

As P
K+
decreased in control mice, BP progressively increased and became sensitive to dietary NaCl and hydrochlorothiazide, coincident with increased NCC phosphorylation and urinary sodium retention. By contrast, BP in CA-SPAK mice was elevated, resistant to the P
K+
titration, and sensitive to hydrochlorothiazide and salt at all P
K+
levels, concomitant with sustained and elevated urinary sodium retention and NCC phosphorylation and activity. Thus, genetically locking the switch on drives NaCl sensitivity and prevents the response of BP to potassium.

CONCLUSIONS:

Low K
+
, common in modern ultraprocessed diets, presses the K
+
-switch pathway to turn on NCC activity, increasing sodium retention, BP, and salt sensitivity.
Disenchantment, Re-enchantment, Magic, and Vestigial Mythologies
Authors: van den Heever Gerhard
Published: March 2024

This essay interacts with the call for papers for the “Magic and Mischief: Text and Practices in Philosophy, Theology, and the Sciences” conference. It is a self-reflection on the theoretical frameworks and definitions guiding projects of reflection and theorising. Breaking the discourse of religion, theology, and science, as well as that of science and magic, down into its discourse-components to get at the speech acts performed, it shows the mythmaking inherent in particular historical understandings of religion and magic, and religion, magic, and science. By performing a kind of archaeology of discourse one gets to see the social, cultural, and political character of the discourse work. And thus, a study of discourse being a site for analysing social formations, the myths of Enlightenment, secularisation, and disenchantment become avenues for understanding the political and socially formative, and the culturally definitive, character of those acts we prefer to call thinking about religion.
The Demise of Science and Religion, and the Return of Theology and Magic
Authors: Tyson Paul
Published: March 2024

Secular modernity is characterised by a knowledge culture that de-magics nature, and separates science from religion. Magic disrupts the nature/supernature dualism of the modern life-world. This article argues that the modern territorialisation of science from religion can no longer be believed, nor is nature/supernature dualism credible. Hence, the recovery of theology as a public domain activity can also bring natural magic back into our knowledge and power culture. Such a re-introduction, the article argues, is essential if we are to try and deliver ourselves from the crassly materialistic instrumentalism that is de-humanising our political landscapes and destroying the natural world.