bluuebunny/crossref_metadata_2025 huggingface dataset:
Reviving product states in the disordered Heisenberg chain
Authors: Wilming Henrik , Osborne Tobias J. , Decker Kevin S. C. , Karrasch Christoph
Published: September 2023

When a generic quantum system is prepared in a simple initial condition, it typically equilibrates toward a state that can be described by a thermal ensemble. A known exception is localized systems that are non-ergodic and do not thermalize; however, local observables are still believed to become stationary. Here we demonstrate that this general picture is incomplete by constructing product states that feature periodic high-fidelity revivals of the full wavefunction and local observables that oscillate indefinitely. The system neither equilibrates nor thermalizes. This is analogous to the phenomenon of weak ergodicity breaking due to many-body scars and challenges aspects of the current phenomenology of many-body localization, such as the logarithmic growth of the entanglement entropy. To support our claim, we combine analytic arguments with large-scale tensor network numerics for the disordered Heisenberg chain. Our results hold for arbitrarily long times in chains of 160 sites up to machine precision.
A metal-free photoactive nitrogen-doped carbon nanosolenoid with broad absorption in visible region for efficient photocatalysis
Authors: Zhou Yu , Zhang Xinyu , Sheng Guan , Wang Shengda , Chen Muqing , Zhuang Guilin , Zhu Yihan , Du Pingwu
Published: September 2023

Abstract

Riemann surfaces inspired chemists to design and synthesize such multidimensional curved carbon architectures. It has been predicted that carbon nanosolenoid materials with Riemann surfaces have unique structures and novel physical properties. Here we report the first synthesis of a nitrogen-doped carbon nanosolenoid (N-CNS) using bottom-up approach with a well-defined structure. N-CNS was obtained by a rational Suzuki polymerization, followed by oxidative cyclodehydrogenation. The successful synthesis of N-CNS was fully characterized by GPC, FTIR, solid-state 13C NMR and Raman techniques. The intrinsic single-strand molecular structures of N-CNS helices can be clearly resolved using low-dose integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM) technique. Possessing unique structural and physical properties, this long π-extended polymer N-CNS can provide new insight towards bottom-up syntheses of curved nanoribbons and potential applications as a metal-free photocatalyst for visible-light-driven H2 evolution and highly efficient photocatalyst for photoredox organic transformations.
Structural basis for the activation of a compact CRISPR-Cas13 nuclease
Authors: Deng Xiangyu , Osikpa Emmanuel , Yang Jie , Oladeji Seye J. , Smith Jamie , Gao Xue , Gao Yang
Published: September 2023

The CRISPR-Cas13 ribonucleases have been widely applied for RNA knockdown and transcriptional modulation owing to their high programmability and specificity. However, the large size of Cas13 effectors and their non-specific RNA cleavage upon target activation limit the adeno-associated virus based delivery of Cas13 systems for therapeutic applications. Herein, we report detailed biochemical and structural characterizations of a compact Cas13 (Cas13bt3) suitable for adeno-associated virus delivery. Distinct from many other Cas13 systems, Cas13bt3 cleaves the target and other nonspecific RNA at internal “UC” sites and is activated in a target length-dependent manner. The cryo-electron microscope structure of Cas13bt3 in a fully active state illustrates the structural basis of Cas13bt3 activation. Guided by the structure, we obtain engineered Cas13bt3 variants with minimal off-target cleavage yet maintained target cleavage activities. In conclusion, our biochemical and structural data illustrate a distinct mechanism for Cas13bt3 activation and guide the engineering of Cas13bt3 applications.
Mechanodetection of neighbor plants elicits adaptive leaf movements through calcium dynamics
Authors: Pantazopoulou Chrysoula K. , Buti Sara , Nguyen Chi Tam , Oskam Lisa , Weits Daan A. , Farmer Edward E. , Kajala Kaisa , Pierik Ronald
Published: September 2023

Plants detect their neighbors via various cues, including reflected light and touching of leaf tips, which elicit upward leaf movement (hyponasty). It is currently unknown how touch is sensed and how the signal is transferred from the leaf tip to the petiole base that drives hyponasty. Here, we show that touch-induced hyponasty involves a signal transduction pathway that is distinct from light-mediated hyponasty. We found that mechanostimulation of the leaf tip upon touching causes cytosolic calcium ([Ca2+]cyt induction in leaf tip trichomes that spreads towards the petiole. Both perturbation of the calcium response and the absence of trichomes reduce touch-induced hyponasty. Finally, using plant competition assays, we show that touch-induced hyponasty is adaptive in dense stands of Arabidopsis. We thus establish a novel, adaptive mechanism regulating hyponastic leaf movement in response to mechanostimulation by neighbors in dense vegetation.
Organic radical ferroelectric crystals with martensitic phase transition
Authors: Zhang Nan , Sun Wencong , Zhang Yao , Jiang Huan-Huan , Xiong Ren-Gen , Dong Shuai , Zhang Han-Yue
Published: September 2023

Organic martensitic compounds are an emerging type of smart material with intriguing physical properties including thermosalient effect, ferroelasticity, and shape memory effect. However, due to the high structural symmetry and limited design theories for these materials, the combination of ferroelectricity and martensitic transformation has rarely been found in organic systems. Here, based on the chemical design strategies for molecular ferroelectrics, we show a series of asymmetric 1,4,5,8-naphthalenediimide derivatives with the homochiral amine and 2,2,6,6-tetramethylpiperidine-N-oxyl components, which adopt the low-symmetric polar structure and so allow ferroelectricity. Upon H/F substitution, the fluorinated compounds exhibit reversible ferroelectric and martensitic transitions at 399 K accompanied by a large thermal hysteresis of 132 K. This large thermal hysteresis with two competing (meta)-stable phases is further confirmed by density functional theory calculations. The rare combination of martensitic phase transition and ferroelectricity realizes the bistability with two different ferroelectric phases at room temperature. Our finding provides insight into the exploration of martensitic ferroelectric compounds with potential applications in switchable memory devices, soft robotics, and smart actuators.
Critical requirement of SOS1 for tumor development and microenvironment modulation in KRASG12D-driven lung adenocarcinoma
Authors: Baltanás Fernando C. , García-Navas Rósula , Rodríguez-Ramos Pablo , Calzada Nuria , Cuesta Cristina , Borrajo Javier , Fuentes-Mateos Rocío , Olarte-San Juan Andrea , Vidaña Nerea , Castellano Esther , Santos Eugenio
Published: September 2023

The impact of genetic ablation of SOS1 or SOS2 is evaluated in a murine model of KRASG12D-driven lung adenocarcinoma (LUAD). SOS2 ablation shows some protection during early stages but only SOS1 ablation causes significant, specific long term increase of survival/lifespan of the KRASG12D mice associated to markedly reduced tumor burden and reduced populations of cancer-associated fibroblasts, macrophages and T-lymphocytes in the lung tumor microenvironment (TME). SOS1 ablation also causes specific shrinkage and regression of LUAD tumoral masses and components of the TME in pre-established KRASG12D LUAD tumors. The critical requirement of SOS1 for KRASG12D-driven LUAD is further confirmed by means of intravenous tail injection of KRASG12D tumor cells into SOS1KO/KRASWT mice, or of SOS1-less, KRASG12D tumor cells into wildtype mice. In silico analyses of human lung cancer databases support also the dominant role of SOS1 regarding tumor development and survival in LUAD patients. Our data indicate that SOS1 is critically required for development of KRASG12D-driven LUAD and confirm the validity of this RAS-GEF activator as an actionable therapeutic target in KRAS mutant LUAD.
Boosting urea electrooxidation on oxyanion-engineered nickel sites via inhibited water oxidation
Authors: Gao Xintong , Bai Xiaowan , Wang Pengtang , Jiao Yan , Davey Kenneth , Zheng Yao , Qiao Shi-Zhang
Published: September 2023

Renewable energy-based electrocatalytic oxidation of organic nucleophiles (e.g.methanol, urea, and amine) are more thermodynamically favourable and, economically attractive to replace conventional pure water electrooxidation in electrolyser to produce hydrogen. However, it is challenging due to the competitive oxygen evolution reaction under a high current density (e.g., >300 mA cm−2), which reduces the anode electrocatalyst’s activity and stability. Herein, taking lower energy cost urea electrooxidation reaction as the model reaction, we developed oxyanion-engineered Nickel catalysts to inhibit competing oxygen evolution reaction during urea oxidation reaction, achieving an ultrahigh 323.4 mA cm−2 current density at 1.65 V with 99.3 ± 0.4% selectivity of N-products. In situ spectra studies reveal that such in situ generated oxyanions not only inhibit OH− adsorption and guarantee high coverage of urea reactant on active sites to avoid oxygen evolution reaction, but also accelerate urea’s C − N bond cleavage to form CNO − intermediates for facilitating urea oxidation reaction. Accordingly, a comprehensive mechanism for competitive adsorption behaviour between OH− and urea to boost urea electrooxidation and dynamic change of Ni active sites during urea oxidation reaction was proposed. This work presents a feasible route for high-efficiency urea electrooxidation reaction and even various electrooxidation reactions in practical applications.
Sensory cortex plasticity supports auditory social learning
Authors: Paraouty Nihaad , Yao Justin D. , Varnet Léo , Chou Chi-Ning , Chung SueYeon , Sanes Dan H.
Published: September 2023

Social learning (SL) through experience with conspecifics can facilitate the acquisition of many behaviors. Thus, when Mongolian gerbils are exposed to a demonstrator performing an auditory discrimination task, their subsequent task acquisition is facilitated, even in the absence of visual cues. Here, we show that transient inactivation of auditory cortex (AC) during exposure caused a significant delay in task acquisition during the subsequent practice phase, suggesting that AC activity is necessary for SL. Moreover, social exposure induced an improvement in AC neuron sensitivity to auditory task cues. The magnitude of neural change during exposure correlated with task acquisition during practice. In contrast, exposure to only auditory task cues led to poorer neurometric and behavioral outcomes. Finally, social information during exposure was encoded in the AC of observer animals. Together, our results suggest that auditory SL is supported by AC neuron plasticity occurring during social exposure and prior to behavioral performance.
Soil heat extremes can outpace air temperature extremes
Authors: García-García Almudena , Cuesta-Valero Francisco José , Miralles Diego G. , Mahecha Miguel D. , Quaas Johannes , Reichstein Markus , Zscheischler Jakob , Peng Jian
Published: September 2023

Quantifying changes in hot temperature extremes is key for developing adaptation strategies. Changes in hot extremes are often determined on the basis of air temperatures; however, hydrology and many biogeochemical processes are more sensitive to soil temperature. Here we show that soil hot extremes are increasing faster than air hot extremes by 0.7 °C per decade in intensity and twice as fast in frequency on average over Central Europe. Furthermore, we identify soil temperature as a key factor in the soil moisture–temperature feedback. During dry and warm conditions, the energy absorbed by the soil is used to warm the soil, increasing the release of sensible heat flux and surface air temperatures. This increase in surface air temperature leads to a higher atmospheric demand for water, increasing soil evaporation, which may further dry and warm the soil highlighting the contribution of soil moisture–temperature feedback to the evolution of hot extremes in a warming climate.
Global population exposure to landscape fire air pollution from 2000 to 2019
Authors: Xu Rongbin , Ye Tingting , Yue Xu , Yang Zhengyu , Yu Wenhua , Zhang Yiwen , Bell Michelle L. , Morawska Lidia , Yu Pei , Zhang Yuxi , Wu Yao , Liu Yanming , Johnston Fay , Lei Yadong , Abramson Michael J. , Guo Yuming , Li Shanshan
Published: September 2023

Wildfires are thought to be increasing in severity and frequency as a result of climate change1–5. Air pollution from landscape fires can negatively affect human health4–6, but human exposure to landscape fire-sourced (LFS) air pollution has not been well characterized at the global scale7–23. Here, we estimate global daily LFS outdoor fine particulate matter (PM2.5) and surface ozone concentrations at 0.25° × 0.25° resolution during the period 2000–2019 with the help of machine learning and chemical transport models. We found that overall population-weighted average LFS PM2.5 and ozone concentrations were 2.5 µg m−3 (6.1% of all-source PM2.5) and 3.2 µg m−3 (3.6% of all-source ozone), respectively, in 2010–2019, with a slight increase for PM2.5, but not for ozone, compared with 2000–2009. Central Africa, Southeast Asia, South America and Siberia experienced the highest LFS PM2.5 and ozone concentrations. The concentrations of LFS PM2.5 and ozone were about four times higher in low-income countries than in high-income countries. During the period 2010–2019, 2.18 billion people were exposed to at least 1 day of substantial LFS air pollution per year, with each person in the world having, on average, 9.9 days of exposure per year. These two metrics increased by 6.8% and 2.1%, respectively, compared with 2000–2009. Overall, we find that the global population is increasingly exposed to LFS air pollution, with socioeconomic disparities.
Detection of transcriptome-wide microRNA–target interactions in single cells with agoTRIBE
Authors: Sekar Vaishnovi , Mármol-Sánchez Emilio , Kalogeropoulos Panagiotis , Stanicek Laura , Sagredo Eduardo A. , Widmark Albin , Doukoumopoulos Evangelos , Bonath Franziska , Biryukova Inna , Friedländer Marc R.
Published: September 2023

MicroRNAs (miRNAs) exert their gene regulatory effects on numerous biological processes based on their selection of target transcripts. Current experimental methods available to identify miRNA targets are laborious and require millions of cells. Here we have overcome these limitations by fusing the miRNA effector protein Argonaute2 to the RNA editing domain of ADAR2, allowing the detection of miRNA targets transcriptome-wide in single cells. miRNAs guide the fusion protein to their natural target transcripts, causing them to undergo A>I editing, which can be detected by sensitive single-cell RNA sequencing. We show that agoTRIBE identifies functional miRNA targets, which are supported by evolutionary sequence conservation. In one application of the method we study microRNA interactions in single cells and identify substantial differential targeting across the cell cycle. AgoTRIBE also provides transcriptome-wide measurements of RNA abundance and allows the deconvolution of miRNA targeting in complex tissues at the single-cell level.
Discrimination of cell-intrinsic and environment-dependent effects of natural genetic variation on Kupffer cell epigenomes and transcriptomes
Authors: Bennett Hunter , Troutman Ty D. , Zhou Enchen , Spann Nathanael J. , Link Verena M. , Seidman Jason S. , Nickl Christian K. , Abe Yohei , Sakai Mashito , Pasillas Martina P. , Marlman Justin M. , Guzman Carlos , Hosseini Mojgan , Schnabl Bernd , Glass Christopher K.
Published: September 2023

Noncoding genetic variation drives phenotypic diversity, but underlying mechanisms and affected cell types are incompletely understood. Here, investigation of effects of natural genetic variation on the epigenomes and transcriptomes of Kupffer cells derived from inbred mouse strains identified strain-specific environmental factors influencing Kupffer cell phenotypes, including leptin signaling in Kupffer cells from a steatohepatitis-resistant strain. Cell-autonomous and non-cell-autonomous effects of genetic variation were resolved by analysis of F1 hybrid mice and cells engrafted into an immunodeficient host. During homeostasis, non-cell-autonomous trans effects of genetic variation dominated control of Kupffer cells, while strain-specific responses to acute lipopolysaccharide injection were dominated by actions of cis-acting effects modifying response elements for lineage-determining and signal-dependent transcription factors. These findings demonstrate that epigenetic landscapes report on trans effects of genetic variation and serve as a resource for deeper analyses into genetic control of transcription in Kupffer cells and macrophages in vitro.
A H3K27M-targeted vaccine in adults with diffuse midline glioma
Authors: Grassl Niklas , Poschke Isabel , Lindner Katharina , Bunse Lukas , Mildenberger Iris , Boschert Tamara , Jähne Kristine , Green Edward W. , Hülsmeyer Ingrid , Jünger Simone , Kessler Tobias , Suwala Abigail K. , Eisele Philipp , Breckwoldt Michael O. , Vajkoczy Peter , Grauer Oliver M. , Herrlinger Ulrich , Tonn Joerg-Christian , Denk Monika , Sahm Felix , Bendszus Martin , von Deimling Andreas , Winkler Frank , Wick Wolfgang , Platten Michael , Sahm Katharina
Published: September 2023

Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype of diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses that control H3K27M+ tumors in major histocompatibility complex-humanized mice. Here we describe a first-in-human treatment with H3K27M-vac of eight adult patients with progressive H3K27M+ diffuse midline glioma on a compassionate use basis. Five patients received H3K27M-vac combined with anti-PD-1 treatment based on physician’s discretion. Repeat vaccinations with H3K27M-vac were safe and induced CD4+ T cell-dominated, mutation-specific immune responses in five of eight patients across multiple human leukocyte antigen types. Median progression-free survival after vaccination was 6.2 months and median overall survival was 12.8 months. One patient with a strong mutation-specific T cell response after H3K27M-vac showed pseudoprogression followed by sustained complete remission for >31 months. Our data demonstrate safety and immunogenicity of H3K27M-vac in patients with progressive H3K27M+ diffuse midline glioma.
ChoCo: a Chord Corpus and a Data Transformation Workflow for Musical Harmony Knowledge Graphs
Authors: de Berardinis Jacopo , Meroño-Peñuela Albert , Poltronieri Andrea , Presutti Valentina
Published: September 2023

Various disconnected chord datasets are currently available for music analysis and information retrieval, but they are often limited by either their size, non-openness, lack of timed information, and interoperability. Together with the lack of overlapping repertoire coverage, this limits cross-corpus studies on harmony over time and across genres, and hampers research in computational music analysis (chord recognition, pattern mining, computational creativity), which needs access to large datasets. We contribute to address this gap, by releasing the Chord Corpus (ChoCo), a large-scale dataset that semantically integrates harmonic data from 18 different sources using heterogeneous representations and formats (Harte, Leadsheet, Roman numerals, ABC, etc.). We rely on JAMS (JSON Annotated Music Specification), a popular data structure for annotations in Music Information Retrieval, to represent and enrich chord-related information (chord, key, mode, etc.) in a uniform way. To achieve semantic integration, we design a novel ontology for modelling music annotations and the entities they involve (artists, scores, etc.), and we build a 30M-triple knowledge graph, including 4 K+ links to other datasets (MIDI-LD, LED).
Experts’ assessments of migration scenarios between the Middle East & North Africa and Europe
Authors: Boissonneault Michaël , Costa Rafael
Published: September 2023

We describe data collected among 138 migration experts about the repercussions of scenarios of social change on migration between the Middle East & North Africa and Europe, during the period 2021–2030. Scenarios include changes in the cultural, demographic, economic, and political determinants of migration in sending and receiving countries. Assessments focus on the change in the number of family, work, and return migrants, the number of refugees, and the likelihood of achieving safe, orderly, and regular migration. Experts were at the moment of the survey active in European research centers or European (supra-) national governmental or civil society organizations. The survey features a factorial design, which allows for identifying a causal relationship between the experts’ assessments and the scenarios of social change. Our data may be used to estimate projection models of future migration flows, map out what experts consider as critical migration issues for the region, and identify areas of agreement or disagreement between them. As such, our dataset may illuminate decision-making regarding migration policies in Europe and beyond.
Numerical study of unsteady tangent hyperbolic fuzzy hybrid nanofluid over an exponentially stretching surface
Authors: Nadeem Muhammad , Siddique Imran , Riaz Zakara , Makhdoum Basim M. , Zulqarnain Rana Muhammad , Sallah Mohammed
Published: September 2023

The significance of fuzzy volume percentage on the unsteady flow of MHD tangent hyperbolic fuzzy hybrid nanofluid towards an exponentially stretched surface is scrutinized. The heat transport mechanism is classified by Joule heating, nonlinear thermal radiation, boundary slippage, and convective circumstances. Ethylene glycol (EG) as a host fluid along with the nanomaterial’s Cu and$${\text{Al}}_{{2}} {\text{O}}_{{3}}$$Al2O3are used for heat transfer analysis is also considered in this investigation. The nonlinear governing PDEs are meant to be converted into ODEs employing appropriate renovations. Then, a built-in MATLAB program bvp4c is employed to acquire the outcome of the given problem. The variation of flow rate, thermal heat, drag force and Nusselt number and their influence on fluid flow with heat transfer have been scrutinized through graphs. An increase in thermal radiation, power law index and nanoparticle volume friction heightens the heat transmission rate. Skin friction is diminished by swelling the power-law index, Weissenberg number, and ratio parameters, whereas it is increased by enhancing the magnetic parameter. The heat transfer rate upsurges with an increase in Weissenberg number and nanoparticle volume fraction. Also, the nanoparticle volume percentage is expressed as a triangular fuzzy number (TFN). The triangular membership function (MF) and TFN are regulated by the$$\chi - {\text{cut}}$$χ-cutparameter, which has a range of 0 to 1. In comparison to nanofluids, hybrid nanofluids have a higher heat transmission rate, according to the fuzzy analysis. This investigation has applications in the areas of paper manufacturing, metal sheet cooling and crystal growth.
Evidence for a metacognitive awareness of autobiographical memory organisation
Authors: Carreras Fabien , Moulin Chris J. A.
Published: September 2023

Models of autobiographical memory (AM) recall posit some form of control process, but the extent to which we can reflect on this form of retrieval is under-researched. Here we propose a method for measuring such metacognitive awareness in AM. Since the verification of personal facts is difficult, we based our design on AM organisation. AMs are proposed to be organised into a coherent life story, that is, a subjective chronology reflecting the goals of the individual over time. We investigated the metacognitive awareness of this coherence. Eighty-three participants generated AMs and made two judgements of order for pairs of memories and gave a confidence rating. We found that participants were indeed able to distinguish pairs of memories that were coherent with their life story chronology from pairs which were not. We also found a significant effect of response time and task difficulty on confidence, suggesting that judgement of order fluency was determinant for metacognitive evaluation. This suggests common properties between metacognitive abilities related to autobiographical memory and those related to other forms of memory.
Investigating proliferation and differentiation capacities of Hanwoo steer myosatellite cells at different passages for developing cell-cultured meat
Authors: Park Sanghun , Park Gyutae , Oh Sehyuk , Park Yunhwan , Kim Yuna , Kim Jaeyoung , Choi Jungseok
Published: September 2023

The aim of study was to investigate proliferation and differentiation capacities of Hanwoo myosatellite cells for the development of Hanwoo cell cultures. From P1 to P19, the number of live cells decreased and the cell size increased. It was confirmed that the PAX7 mRNA was higher in P3 than P6 and P9 (p < 0.05). The maximum differentiation score was measured from P1 to P12. The maximum differentiation score maintained high from P1 to P10. Immunostaining was performed for both P1 and P10 cells to investigate differentiation characteristics. And there were no significant differences in differentiation characteristics between P1 and P10 cells. MYOG mRNA was low, whereas C-FOS mRNA was high (p < 0.05) in the late passage. Myosin and Tom20 protein also showed low values in the late passage (p < 0.05). In conclusion, our results suggest that it is appropriate to use P1 to P10 for the production of cultured meat using Hanwoo muscle cells. If cell culture meat production is performed without differentiation, the passage range may increase further. These results provide basic essential data required for further development of Hanwoo cell cultures, which could provide a valuable source of protein for human populations in the future.
Soft robotic patterning of liquids
Authors: Sasso Giacomo , Pugno Nicola , Busfield James J. C. , Carpi Federico
Published: September 2023

Patterning of two or more liquids, either homogeneous in each phase or mixed with particles (including biological matter, such as cells and proteins), by controlling their flow dynamics, is relevant to several applications. Examples include dynamic spatial confinement of liquids in microfluidic systems (such as lab-on-a-chip and organ-on-a-chip devices) or structuring of polymers to modulate various properties (such as strength, conductivity, transparency and surface finishing). State-of-the-art strategies use various technologies, including positioners, shakers and acoustic actuators, which often combine limited versatility of mixing with significant inefficiency, energy consumption, and noise, as well as tendency to increase the temperature of the liquids. Here, we describe a new kind of robotic mixers of liquids, based on electro-responsive smart materials (dielectric elastomer actuators). We show for the first time how an efficient soft robotic device can be used to produce, via combinations of rotations and translations, various spatial patterns in liquids and maintain them stable for a few minutes. Moreover, we show that, as compared to a conventional orbital shaker, the new type of robotic device can mix liquids with a higher efficacy (~ 94% relative to ~ 80%, after 8 min of mixing) and with a significantly lower increase of the liquids’ temperature (+ 1 °C relative to + 5 °C, after 6 h of mixing). This is especially beneficial when mixing should occur according to controllable spatial features and should involve temperature-sensitive matter (such as biological cells, proteins, pre-polymers and other thermolabile molecules).
Raidionics: an open software for pre- and postoperative central nervous system tumor segmentation and standardized reporting
Authors: Bouget David , Alsinan Demah , Gaitan Valeria , Helland Ragnhild Holden , Pedersen André , Solheim Ole , Reinertsen Ingerid
Published: September 2023

For patients suffering from central nervous system tumors, prognosis estimation, treatment decisions, and postoperative assessments are made from the analysis of a set of magnetic resonance (MR) scans. Currently, the lack of open tools for standardized and automatic tumor segmentation and generation of clinical reports, incorporating relevant tumor characteristics, leads to potential risks from inherent decisions’ subjectivity. To tackle this problem, the proposed Raidionics open-source software has been developed, offering both a user-friendly graphical user interface and stable processing backend. The software includes preoperative segmentation models for each of the most common tumor types (i.e., glioblastomas, lower grade gliomas, meningiomas, and metastases), together with one early postoperative glioblastoma segmentation model. Preoperative segmentation performances were quite homogeneous across the four different brain tumor types, with an average Dice around 85% and patient-wise recall and precision around 95%. Postoperatively, performances were lower with an average Dice of 41%. Overall, the generation of a standardized clinical report, including the tumor segmentation and features computation, requires about ten minutes on a regular laptop. The proposed Raidionics software is the first open solution enabling an easy use of state-of-the-art segmentation models for all major tumor types, including preoperative and postsurgical standardized reports.
Advancing autologous urothelial micrografting and composite tubular grafts for future single-staged urogenital reconstructions
Authors: Juul Nikolai , Ajalloueian Fatemeh , Willacy Oliver , Chamorro Clara Ibel , Fossum Magdalena
Published: September 2023

Urogenital reconstructive surgery can be impeded by lack of tissue. Further developments within the discipline of tissue engineering may be part of a solution to improve clinical outcomes. In this study, we aimed to design an accessible and easily assembled tubular graft with autologous tissue, which could be constructed and implanted as a single-staged surgical procedure within the premises of an ordinary operating room. The ultimate goals would be to optimize current treatment-options for long-term urinary diversion. Therefore, we evaluated the optimal composition of a collagen-based scaffold with urothelial micrografts in vitro, and followingly implanted the construct in vivo as a bladder conduit. The scaffold was evaluated in relation to cell regeneration, permeability, and biomechanical properties. After establishing an optimized scaffold in vitro, consisting of high-density collagen with submerged autologous micrografts and reinforced with a mesh and stent, the construct was successfully implanted in an in vivo minipig model. The construct assemblance and surgical implantation proved feasible within the timeframe of a routine surgical intervention, and the animal quickly recovered postoperatively. Three weeks post-implantation, the conduit demonstrated good host-integration with a multilayered luminal urothelium. Our findings have encouraged us to support its use in more extensive preclinical large-animal studies.
Salmonid polysialyltransferases to generate a variety of sialic acid polymers
Authors: Decloquement Mathieu , Venuto Marzia Tindara , Cogez Virginie , Steinmetz Anna , Schulz Céline , Lion Cédric , Noel Maxence , Rigolot Vincent , Teppa Roxana Elin , Biot Christophe , Rebl Alexander , Galuska Sebastian Peter , Harduin-Lepers Anne
Published: September 2023

The human polysialyltransferases ST8Sia II and ST8Sia IV catalyze the transfer of several Neu5Ac residues onto glycoproteins forming homopolymers with essential roles during different physiological processes. In salmonids, heterogeneous set of sialic acids polymers have been described in ovary and on eggs cell surface and three genes st8sia4, st8sia2-r1 and st8sia2-r2 were identified that could be implicated in these heteropolymers. The three polysialyltransferases from the salmonid Coregonus maraena were cloned, recombinantly expressed in HEK293 cells and the ST8Sia IV was biochemically characterized. The MicroPlate Sialyltransferase Assay and the non-natural donor substrate CMP-SiaNAl were used to demonstrate enzyme activity and optimize polysialylation reactions. Polysialylation was also carried out with natural donor substrates CMP-Neu5Ac, CMP-Neu5Gc and CMP-Kdn in cell-free and cell-based assays and structural analyses of polysialylated products using the anti-polySia monoclonal antibody 735 and endoneuraminidase N and HPLC approaches. Our data highlighted distinct specificities of human and salmonid polysialyltransferases with notable differences in donor substrates use and the capacity of fish enzymes to generate heteropolymers. This study further suggested an evolution of the biological functions of polySia. C. maraena ST8Sia IV of particular interest to modify glycoproteins with a variety of polySia chains.
Secretomes of M1 and M2 macrophages decrease the release of neutrophil extracellular traps
Authors: Manda-Handzlik Aneta , Cieloch Adrianna , Kuźmicka Weronika , Mroczek Agnieszka , Stelmaszczyk-Emmel Anna , Demkow Urszula , Wachowska Małgorzata
Published: September 2023

The release of neutrophil extracellular traps (NETs) can be either beneficial or detrimental for the host, thus it is necessary to maintain a balance between formation and clearance of NETs. Multiple physiological factors eliciting NET release have been identified, yet the studies on natural signals limiting NET formation have been scarce. Accordingly, our aim was to analyze whether cytokines or immune cells can inhibit NET formation. To that end, human granulocytes were incubated with interleukin (IL)-4, IL-10, transforming growth factor beta-2 or adenosine and then stimulated to release NETs. Additionally, neutrophils were cultured in the presence of natural killer (NK) cells, regulatory T cells (Tregs), pro-inflammatory or anti-inflammatory macrophages (M1 or M2 macrophages), or in the presence of NK/Tregs/M1 macrophages or M2 macrophages-conditioned medium and subsequently stimulated to release NETs. Our studies showed that secretome of M1 and M2 macrophages, but not of NK cells and Tregs, diminishes NET formation. Co-culture experiments did not reveal any effect of immune cells on NET release. No effect of cytokines or adenosine on NET release was found. This study highlights the importance of paracrine signaling at the site of infection and is the first to show that macrophage secretome can regulate NET formation.
Treatment-associated network dynamics in patients with globus sensations: a proof-of-concept study
Authors: Imperiale Marina N. , Lieb Roselind , Meinlschmidt Gunther
Published: September 2023

In this proof-of-concept study, we used a systems perspective to conceptualize and investigate treatment-related dynamics (temporal and cross-sectional associations) of symptoms and elements related to the manifestation of a common functional somatic syndrome (FSS), Globus Sensations (GS). We analyzed data from 100 patients (M = 47.1 years, SD = 14.4 years; 64% female) with GS who received eight sessions of group psychotherapy in the context of a randomized controlled trial (RCT). Symptoms and elements were assessed after each treatment session. We applied a multilevel graphical vector-autoregression (ml GVAR) model approach resulting in three separate, complementary networks (temporal, contemporaneous, and between-subject) for an affective, cognitive, and behavioral dimension, respectively. GS were not temporally associated with any affective, cognitive, and behavioral elements. Temporally, catastrophizing cognitions predicted bodily weakness (r = 0.14, p < 0.01, 95% confidence interval (CI) [0.04–0.23]) and GS predicted somatic distress (r = 0.18, p < 0.05, 95% CI [0.04–0.33]). Potential causal pathways between catastrophizing cognitions and bodily weakness as well as GS and somatic distress may reflect treatment-related temporal change processes in patients with GS. Our study illustrates how dynamic NA can be used in the context of outcome research.
Identification of stromal cell-derived factor 4 as a liquid biopsy-based diagnostic marker in solid cancers
Authors: Shinozuka Takahiro , Kanda Mitsuro , Shimizu Dai , Umeda Shinichi , Takami Hideki , Inokawa Yoshikuni , Hattori Norifumi , Hayashi Masamichi , Tanaka Chie , Nakayama Goro , Kodera Yasuhiro
Published: September 2023

There is a need for serum diagnostic biomarkers to improve the prognosis of solid malignant tumors. Here, we conducted a single-institutional study to evaluate the diagnostic performance of serum stromal cell-derived factor 4 (SDF4) levels in cancer patients. Serum samples were collected from a total of 582 patients with solid cancers including gastric cancer (GC) and 80 healthy volunteers. SDF4 protein levels in sera, and conditioned media or lysates of human GC cell lines were measured by enzyme-linked immunosorbent assay, and those in GC tissue by immunohistochemistry. Serum SDF4 levels were higher in patients with cancer than the healthy control in all cancer type. Regarding GC, serum SDF4 levels distinguished healthy controls from GC patients with the area under the curve value of 0.973, sensitivity of 89%, and specificity of 99%. Serum SDF4 levels were significantly elevated in patient with early stage GC. In immunohistochemistry, the frequency of SDF4-positive GC tumors did not vary significantly between GC stages. The ability of human GC cell lines to both produce and secrete SDF4 was confirmed in vitro. In conclusion, serum SDF4 levels could be a promising candidate for a novel diagnostic biomarker for GC and other malignancies.
Novel iodoquinazolinones bearing sulfonamide moiety as potential antioxidants and neuroprotectors
Authors: Soliman Aiten M. , Ghorab Walid M. , Lotfy Dina M. , Karam Heba M. , Ghorab Mostafa M. , Ramadan Laila A.
Published: September 2023

In a search for new antioxidants, a set of new iodoquinazolinone derivatives bearing benzenesulfonamide moiety and variable acetamide pharmacophores 5–17 were designed and synthesized. The structures of the synthesized compounds were confirmed based on spectral data. Compounds 5–17 were screened using in vitro assay for their antioxidant potential and acetylcholinesterase (AChE) inhibitory activity. The 2-(6-iodo-4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydroquinazolin-2-ylthio)-N-(pyrazin-2-yl) acetamide 14 was the most active scaffold with potent AChE inhibitory activity. Compound 14 showed relative safety with a median lethal dose of 300 mg/kg (LD50 = 300 mg/kg), in an acute toxicity study. The possible antioxidant and neuroprotective activities of 14 were evaluated in irradiated mice. Compound 14 possessed in vivo AChE inhibitory activity and was able to modify the brain neurotransmitters. It was able to cause mitigation of gamma radiation-induced oxidative stress verified by the decline in Myeloperoxidase (MPO) and increase of glutathione (GSH) levels. Also, 14 restored the alterations in behavioral tests. Molecular docking of 14 was performed inside MPO and AChE active sites and showed the same binding interactions as that of the co-crystallized ligands considering the binding possibilities and energy scores. These findings would support that 14 could be considered a promising antioxidant with a neuromodulatory effect.
Future projection of climate extremes across contiguous northeast India and Bangladesh
Authors: Paul Ashesh Rudra , Maity Rajib
Published: September 2023

In recent times, India has experienced a significant increase in the frequency and intensity of extreme weather events, particularly in northeast India (NEI), an area known for its rich natural resources. Despite the geographic continuity of NEI and Bangladesh, previous studies have failed to consider their interconnectedness, resulting in an incomplete understanding of the situation. To bridge this gap, a comprehensive study encompassed the entire NEI, including West Bengal and Bangladesh (hereafter referred to as NEIB). This study examined climate extremes in NEIB, utilizing 12 temperature-based and 8 precipitation-based indices developed by the Expert Team on Climate Change Detection and Indices. Analysis was performed on temperature and precipitation data obtained from the India Meteorological Department and Bangladesh Meteorological Department covering the period 1981–2021. Additionally, climate projections from 14 Global Climate Models participating in the CMIP6 were incorporated for the period 2015–2100, considering four different Shared Socioeconomic Pathways (SSPs) scenarios. Findings revealed that under the SSP585 scenario, a substantial rise of 4 °C in maximum temperatures and 5.5 °C in minimum temperatures by the end of the twenty-first century. Warming indices, such as the summer days index, indicated an expected increase of 53 days, while the Warm spell days index was estimated to rise by approximately 2 days. Heavy precipitation days (R20mm) were projected to increase by up to 14 days, with a notable impact in Meghalaya. While the number of rainy days is expected to decrease, the overall magnitude of precipitation is anticipated to remain relatively stable. Notably, the Simple daily intensity index demonstrated a rise of 2.4 mm/day compared to the current baseline of 14.4 mm/day. These projected changes have significant ramifications for water resources, agriculture, health, and infrastructure in the region.
Phenotypic screening of signaling motifs that efficiently induce cell proliferation
Authors: Umene Kirato , Nagamune Teruyuki , Kawahara Masahiro
Published: September 2023

Since cell proliferation is one of the fundamental cell fates, artificial control of cell proliferation based on a receptor-engineering approach is increasingly important in therapeutic and industrial applications. Since the signal transduction properties of cytokine receptors are greatly influenced by the amino acid sequence of tyrosine motifs, here we develop a phenotypic screening approach that can directly select cell proliferation-inducing tyrosine motifs from a synthetic library. In the tyrosine motif library, amino acid sequences around the tyrosine are randomized to attain diverse binding patterns of signaling molecules. Theoretically, engineered receptors with distinct tyrosine motifs would activate signaling molecules in diverse patterns. Thus, we investigated whether tyrosine motif sequences capable of inducing cell proliferation could be selected from the cellular library expressing the motif-engineered receptors. Consequently, the selected motifs induced similar levels of cell proliferation compared to the cytoplasmic signaling domain of a native receptor. The motif-screening system was applicable to cells that may differentiate or proliferate depending on cytokine signals. To our best knowledge, this is the first report demonstrating phenotypic screening of tyrosine motifs in living cells. Our approach would open up new possibilities in the field of artificial control of cell fate based on signal transduction engineering.
Leptin receptor gene deficiency minimally affects osseointegration in rats
Authors: Jolic Martina , Ruscsák Krisztina , Emanuelsson Lena , Norlindh Birgitta , Thomsen Peter , Shah Furqan A. , Palmquist Anders
Published: September 2023

Metabolic syndrome represents a cluster of conditions such as obesity, hyperglycaemia, dyslipidaemia, and hypertension that can lead to type 2 diabetes mellitus and/or cardiovascular disease. Here, we investigated the influence of obesity and hyperglycaemia on osseointegration using a novel, leptin receptor-deficient animal model, the Lund MetS rat. Machined titanium implants were installed in the tibias of animals with normal leptin receptor (LepR+/+) and those harbouring congenic leptin receptor deficiency (LepR−/−) and were left to heal for 28 days. Extensive evaluation of osseointegration was performed using removal torque measurements, X-ray micro-computed tomography, quantitative backscattered electron imaging, Raman spectroscopy, gene expression analysis, qualitative histology, and histomorphometry. Here, we found comparable osseointegration potential at 28 days following implant placement in LepR−/− and LepR+/+ rats. However, the low bone volume within the implant threads, higher bone-to-implant contact, and comparable biomechanical stability of the implants point towards changed bone formation and/or remodelling in LepR−/− rats. These findings are corroborated by differences in the carbonate-to-phosphate ratio of native bone measured using Raman spectroscopy. Observations of hypermineralised cartilage islands and increased mineralisation heterogeneity in native bone confirm the delayed skeletal development of LepR−/− rats. Gene expression analyses reveal comparable patterns between LepR−/− and LepR+/+ animals, suggesting that peri-implant bone has reached equilibrium in healing and/or remodelling between the animal groups.
Multidimensional attributes expose Heider balance dynamics to measurements
Authors: Linczuk Joanna , Górski Piotr J. , Szymanski Boleslaw K. , Hołyst Janusz A.
Published: September 2023

Most of studied social interactions arise from dyadic relations. An exception is Heider Balance Theory that postulates the existence of triad dynamics, which however has been elusive to observe. Here, we discover a sufficient condition for the Heider dynamics observability: assigning the edge signs according to multiple opinions of connected agents. Using longitudinal records of university student mutual contacts and opinions, we create a coevolving network on which we introduce models of student interactions. These models account for: multiple topics of individual student opinions, influence of such opinions on dyadic relations, and influence of triadic relations on opinions. We show that the triadic influence is empirically measurable for static and dynamic observables when signs of edges are defined by multidimensional differences between opinions on all topics. Yet, when these signs are defined by a difference between opinions on each topic separately, the triadic interactions’ influence is indistinguishable from noise.
Damping contribution of viscoelastic core on airborne sound insulation performance of finite constrained layer damping panels at low and middle frequencies
Authors: Wang Bo , Min Hequn
Published: September 2023

The airborne sound insulation performance of finite sandwich panels is often significantly worsened by resonant transmission components in low and middle frequencies. In this paper, damping contribution of viscoelastic core on sound transmission loss (STL) of finite constrained layer damping (CLD) panels is studied in narrow frequency bands. A fully coupled layer-wise approach is used with a generalized high-order shear deformation hypothesis that accounts for all types of deformations in the core. The influence of several parameters is investigated extensively. Results show that the adverse impact of the first-three odd-odd order modes, namely (1,1), (3,1), and (1,3) modes, as well as some higher-order modes on STL cannot be disregarded. The constrained viscoelastic core plays a crucial role in enhancing, or even eliminating, dips of STL spectrum at resonant frequencies. Additionally, it can considerably counterbalance a relatively broadband reduction of STL caused by the inter-modal coupling in middle frequencies. The damping mechanism can be divided into two aspects: (i) the reduction of modal amplitude by vibration energy dissipation, and (ii) the change of bending modal shapes. CLD treatment is a concise and effective way to achieve stable sound insulation performance.