bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database
Authors: Tobaiqy Mansour , Elkout Hajer
Published: January 2024

Background

Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients experiencing suicidal thoughts and other psychiatric adverse events while using GLP-1 agonists have raised concerns about the potential risk of self-harm and led the European Medicines Agency to investigate these medications.

Aim

To identify and analyse the psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide.

Method

All individual case safety reports for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 30/05/2023 were analysed. Descriptive statistics were used to explore study population characteristics.

Results

During the study period, 31,444 adverse event reports were identified: semaglutide (n = 13,956; 44.4%), liraglutide (n = 16,748; 53.2%), and tirzepatide (n = 740; 2.3%). There were 372 reports with psychiatric adverse event reports (n = 372; 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187; 50.3%), followed by anxiety (n = 144; 38.7%) and suicidal ideation (n = 73; 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide) and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9) resulting from completed suicidal attempts and depression.

Conclusion

Psychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide. However, the severity and fatal outcomes of some of these reports warrant further investigation.
Geometric and radiometric recording of prehistoric graphic expression: the case of Peña Tu (Asturias, Spain)
Authors: Teira Luis , Bayarri Vicente , Ontañón Roberto , Castillo Elena , Arias Pablo
Published: January 2024

In the studies on Prehistoric Graphic Expression, there are recurrent discussions about the tracings generated by different observers of the same motif. Methodological issues concerning the role of archaeological imaging are often implied within those debates. Do the tracings belong to the observational data exposition chapter, or are they part of the interpretative conclusions? How can the current technological scenario help solve these problems? In 2017, we conducted new documentation of the Peña Tu rock shelter, a well-known site with an intriguing post-palaeolithic graphic collection documented on several occasions throughout the twentieth century. Our objective was to provide quantifiable and, if possible, objective documentation of the painted and engraved remnants on the shelter’s surface. To achieve this, we employed two data capture strategies. One strategy focused on analysing the vestiges of paintings using a hyperspectral sensor, while the other centred on the geometric definition of engravings and the rock support, utilising photogrammetric techniques and laser scanning. These approaches presented various parallax challenges. Despite these challenges, our results were highly satisfactory. We resolved uncertainties regarding the formal features of specific designs that had been subject to debate for a long time. Additionally, we discovered previously unpublished areas with traces of paintings. Lastly, we developed a map highlighting recent alterations and deteriorations, providing a valuable tool for assessing the site’s preservation status. In conclusion, by employing advanced technology and comprehensive documentation methods, we significantly contributed to understanding and preserving the prehistoric graphic expressions at the Peña Tu rock shelter.
On first integrals, conservation laws and reduction of classes of Emden and Liénard equations
Authors: Ahmed Mogahid M. A. , Alqurashi Bader , Kara A. H.
Published: January 2024

We present a general method to construct first integrals for some classes of the well known second-order ordinary differential equations, viz., the Emden and Liénard classes of equations. The approach does not require a knowledge of a Lagrangian but, rather, uses the ‘multiplier approach’ (Anco and Bluman in Eur J Appl Math 13:545–566, 2002; Eur J Appl Math 13:567–585, 2002). It is then shown how a study of the invariance properties and conservation laws are used to ‘twice’ reduce the equations to solutions. The equations admit five first integrals of which two are independent but the significance of the five are that they correspond to a five-dimensional algebra of Noether symmetries obtained without the need to construct a Lagrangian.
Utilizing the lignocellulosic fibers from Pineapple Crown Leaves extract for enhancing TiO2 interfacial bonding in dye-sensitized solar cell photoanodes
Authors: Premkumar N. , Madhavi M. Radha , Kitmo K. , Shanmugan S.
Published: January 2024

The crown leaves of pineapple possess a wealth of smooth and glossy silk medium-length fibers, primarily composed of cellulose and lignin, accompanied by constituents such as fats, waxes, pectin, uronic acid, anhydride, pentosan, color pigments, and inorganic substances. These fibers exhibit an anisotropic nature and are characterized by hydrogen bonding interactions, rendering them effective in conjunction with semiconductor oxide (TiO2) through their cellulosic fibrils. The dye extracted from Pineapple Crown Leaves (PCL) using ethanol was subjected to FTIR and UV–visible spectroscopy. The FTIR analysis revealed absorption peaks at 3268 cm−1 and 2922 cm−1, confirming the presence of –OH and –CH stretching attributed to the fibrils within the dye. UV–visible spectroscopy further demonstrated absorption within the visible region of the electromagnetic spectrum. Additionally, a photoluminescence study of the dye showcased emission within the visible range of the electromagnetic spectrum. Subsequently, a solar cell incorporating this dye underwent JV characterization, yielding an efficiency of 1.0034%, along with fill factor, open-circuit voltage, and short-circuit current density values of 0.40644, 0.7058 V, and 3.4906 mA/cm2, respectively. To gain deeper insights and facilitate optimization for large-scale installations, a simulation model utilizing PC1D was proposed to explore the influential parameters of the Dye-sensitized solar cell (DSSC).
Production and characterization of briquettes from sugarcane bagasse of Wonji Sugar Factory, Oromia, Ethiopia
Authors: Mekonen Asmelash Gebrekidan , Berhe Goitom Gebreyohannes , Desta Mulu Berhe , Belete Fentahun Abebaw , Gebremariam Amare Fisseha
Published: January 2024

Briquetted biomass, like sugarcane bagasse, a by-product of sugar mills, is a renewable energy source. This study aimed at the production and characterization of bagasse briquettes. The production of briquettes was carried out with different blending ratios (5, 10, and 15%) and average particle sizes (0.75, 2.775, and 4.8 mm) with various binders of cow dung, waste paper, and admixture (molasses and wastepaper). The bagasse underwent drying, size reduction, sieving, binder addition, and densification using a manual press during the briquetting process. Characterization of the physical and combustion parameters of briquettes, such as density, shatter resistance, proximate, and calorific value, followed the American Society for Testing and Materials procedures. The result shows that the maximum density of briquettes was 0.804 g/cm3, while shatter resistance varied from 83.051 to 94.975% (4.8mm, 5% cow dung and 0.75mm, 5% admixture binders respectively). ANOVA analysis showed that the factors and their interactions had a significant influence (p value < 0.05) on the physical properties. The optimum parameters of briquettes achieved were 14.953% admixture binder, 0.776 mm particle size, 0.805 g/cm3 density, and 95.811% shatter resistance. Bagasse briquettes with a 5% cow dung binder achieved a high calorific value of 39927.05 kcal/kg. The ultimate analysis revealed a composition of 47.49% carbon (C), 5.133% hydrogen (H), 1.557% nitrogen (N), 0.374% sulfur (S), and 45.446% oxygen (O). Therefore, bagasse has a high calorific value and can be used for briquetting to replace fossil fuel and firewood in different applications. In addition, due to its availability, utilizing as fuel source has economic advantage.

Graphical abstract
A permeability model for the fractal tree-like fracture network with self-affine surface roughness in shale gas reservoirs
Authors: Hu Bowen , Wang J. G. , Sun Rui , Zhao Zhiye
Published: January 2024

The complex natural fracture network with self-affine rough surface and branching characteristics significantly impacts the gas transport in shale gas reservoirs. However, its effects on the permeability have not been studied so far. This study proposes an analytical permeability model for the fractal tree-like fracture network with self-affine surface roughness and branching characteristics. Firstly, the self-affine rough profiles of fracture surface are generated at different fractal dimensions by the Weierstrass–Mandelbrot function and a rough fractal tree-like fracture network is constructed with these surface profiles and branching characteristics. Then, an analytical permeability model is proposed to consider the effects of fracture surface roughness and tree-like branching characteristics on gas flow. This analytical model is verified by numerical simulations. Finally, the velocity distribution of the fracture network and the sensitivity of its structure parameters are analyzed. It is found that eddy flow is more easily formed on rougher fracture surfaces with larger fractal dimension when their fracture aperture is at millimeter scale. The eddy flow disappears when the fracture aperture is at micron scale. Bigger gas flow resistance and more energy loss are observed for smaller fracture aperture and rougher fracture surface. The gas velocity in rough fractures decreases by 60% at micron scale, but decreases by 50% at millimeter scale. Gas flow resistance also increases with the increase of branch angle, branch level and length ratio, but decreases with aperture ratio. As a result, permeability decreases with fractal dimension, branch angle, branch level and length ratio, but increases with aperture ratio.
Storying Research: Exploring the Benefits of
Participatory Narrative Inquiry as a Methodology for Wellbeing Research
Authors: Colla Rachel H. , Kurtz Cynthia F.
Published: January 2024

As the field of positive psychology matures, many have called for an
expansion in epistemological and methodological approaches to enable a more complex
study of wellbeing. This article addresses this call by examining the benefits of
using storying methods in wellbeing research. We explore how this can address some
of the limitations in the extant psychological literature. Participatory Narrative
Inquiry (PNI) is introduced as an example of a storying methodology that can
facilitate a democratised approach to studying complex phenomena. We outline the
theoretical and meta-theoretical underpinnings of this approach and provide an
overview of the essential and supplementary methods used within each phase of the
methodology. The methodology is juxtaposed with other similar qualitative methods to
support researchers in discerning what type of inquiries PNI may be best suited to.
We argue that interdisciplinary methodologies such as PNI can support the
development and refinement of contextually relevant theories and practices needed to
progress the field of positive psychology as it enters its third wave of
development.
Vertrauen und Demokratie tief im Westen – politische Kultur im Ruhrgebiet
Authors: Küppers Anne , Decker Frank
Published: January 2024

Das Ruhrgebiet stellt als urban verdichtete Wirtschaftsregion mit einer industriellen Vergangenheit und einem nur teilweise erfolgreichen Strukturwandel einen spannenden Untersuchungsfall für die politische Kulturforschung dar. Es besteht zudem eine soziale Kluft zwischen wohlhabenden Städten und Wohngegenden im Norden im Vergleich zu ärmeren Gegenden im Süden der Autobahn A40. Vor diesem Hintergrund untersucht dieser Beitrag das Ausmaß und die Erklärungsfaktoren für politisches Vertrauen und Demokratiezufriedenheit im Ruhrgebiet. Die Ergebnisse einer repräsentativen Untersuchung (N = 622) zeigen, dass das Niveau der Demokratiezufriedenheit und des politischen Vertrauens im Ruhrgebiet trotz der schwierigen wirtschaftlichen Lage vieler Ruhrgebietsbewohner überraschenderweise sogar über dem bundesweiten Durchschnitt liegt. Dennoch offenbaren die Zufriedenheitswerte – ähnlich wie im Rest Deutschlands – große Unterschiede zwischen sozialen Gruppen. Insbesondere zeigen weniger gebildete Schichten eine niedrigere Zufriedenheit und ein geringeres Vertrauen im Vergleich zu besser gebildeten Gruppen. Zusätzlich lässt sich ein starker Zusammenhang der Demokratiezufriedenheit mit der Aufgabenerfüllung in der Sozialpolitik feststellen; Ungleichheitswahrnehmungen hingegen sind nicht signifikant mit Demokratiezufriedenheit und Vertrauen verknüpft.
Pivot to Persevere: Temporary Pivots as a Response to Exogenous Shocks
Authors: Scheve Clara , Reihlen Markus , Gegenhuber Thomas
Published: January 2024

Despite much progress in the research on pivots as a response to crisis, the nature of temporary pivots remains unclear. This article investigates how a venture responded to the challenges of the COVID-19 pandemic by performing a temporary pivot. Drawing on an inductive, longitudinal case study of the fast-growing young venture “Gazelle,” we developed a process model of temporary pivots that encompasses three phases: what evokes a temporary pivot; how it is enacted; and what effects it has on the venture. Our findings suggest that temporary pivots require effectual decision-making and the reversibility of changes made. Our research contributes to the growing literature on pivoting by conceptualizing the temporary pivot as a short-term entrepreneurial response to exogenous shocks and part of a long-term strategy of perseverance.
Digitale formative Diagnoseverfahren in der Grundschule – Begründungen und Überblick über vorliegende Entwicklungen am Beispiel Deutsch
Authors: Junger Ralf , Liebers Katrin
Published: January 2024

Für die Grundschule erscheinen zunehmend mehr digitale Diagnoseverfahren. Viele versprechen ein erhebliches Potenzial für einen adaptiven Unterricht, zugleich zeigt sich aber eine Vielzahl an diagnostischen Zielen und digitalen Umsetzungen. In der explorativen Studie werden Anforderungen an digitale formative Diagnoseverfahren multiperspektivisch und theoriegeleitet diskutiert. Auf der Basis der so gewonnenen Kriterien wird mit Hilfe einer Artefakteanalyse der Frage nachgegangen, inwieweit die vorliegenden Verfahren im Lernbereich Deutsch den Anforderungen an digitale formative Diagnoseverfahren genügen. Dies trifft bislang nur für einen kleinen Teil der Verfahren zu, zudem werden digitale Möglichkeiten adaptiver Verfahren bislang kaum erreicht. Weitere interdisziplinäre Entwicklungen und disziplinspezifische Klärungen stellen deshalb eine Zukunftsaufgabe dar.
Design of a Helicopter System Recovery for a Sounding Rocket
Authors: Marques João Pedro Caldeira de Sousa , de Souza Alain , Cunha Filipe Szolnoky
Published: January 2024

In this article, the feasibility of spacecraft recovery using rotary wings is analysed. This technology possesses the ability to perform a safe and controlled landing, allowing the spacecraft to be reused and utilised in missions with different requirements. A computational model that simulates the descent of a sounding rocket was developed. It is based on rotor’s aerodynamic theories and kinematics and computes several rotor parameters that allow the analysis of the system’s performance. The model’s verification was successfully carried out by comparing its behaviour with literature data. To understand how each design parameter influences the system, a parametric study of the rotor design variables was held. It was concluded that the blade’s pitch angle is extremely important for the system’s performance and should be carefully selected, and that weight penalties resultant from excessive blade’s number or radius can be prejudicial. Furthermore, a design optimisation was conducted, aiming to minimise the rocket’s terminal velocity. Finally, a flare manoeuvre was disclosed to reduce the touchdown velocity. This recovery system is concluded to be highly promising, though requiring further work in several fields of study.
Understanding the well-being challenges confronting academic staff in South African universities: a narrative review
Authors: Dlamini Nkosinathi Goodman , Dlamini Nothando Delight
Published: January 2024

According to research done in South Africa, there is an increasing worry about the wellness of academic staff members, with many of them reporting high levels of stress and burnout. Heavy workloads, a lack of resources, and an unsatisfactory work-life balance are just a few factors that studies have identified as leading to poor well-being. Low salaries, weak recognition, and insufficient support systems are further contributing causes. Academic staff members' personal and professional skills may be badly impacted by stress, which can reduce productivity. Burnout is frequently linked to painful emotional events, and it is particularly common among those working in human service industries. Emotional tiredness, depersonalization marked by a pessimistic and cynical attitude toward others, and dissatisfaction with professional achievements are common burnout reactions. Five databases, including Scopus, PubMed, ScienceDirect, Medline, and Google Scholar, were searched for the review using the keywords (academic staff challenges, academic staff burnout, and academic staff well-being). The search was restricted to peer-reviewed empirical studies that looked at academic staff well-being in full-time university academic staff and were written in English. Papers that did not discuss the well-being of academic staff were disqualified. A thorough data extraction technique was used to retrieve pertinent information from each study. Job security is the least stressful factor, while concerns about diminished research and publishing opportunities and workplace bullying are prevalent. Burnout levels vary across age groups, with academics aged 50 or older showing lower levels. High emotional intelligence in academic staff reduces susceptibility to work challenges. Institutions can implement conflict management strategies to enhance work-related well-being. The review's overall conclusion emphasizes the urgent need for action to address the growing issue of academic staff members' low welfare at South African universities. Failure to address this problem could have detrimental effects on both the standard of instruction given to pupils and the health and well-being of academic staff.
New material of Lophiparamys debequensis from the Willwood Formation (early Eocene) of Wyoming, including the first postcrania of the genus
Authors: Zack Shawn P. , Penkrot Tonya A.
Published: January 2024

We report new material of the rare early Eocene rodent Lophiparamys debequensis Wood, 1962 from the Willwood Formation of the southern Bighorn Basin, north-central Wyoming. The new material constitutes the first record of L. debequensis from the Bighorn Basin and documents aspects of the anatomy of Lophiparamys that were previously unknown, including a portion of the maxilla and a portion of the tarsus. The maxillary fragment demonstrates that Lophiparamys has a small P3 and a relatively large infraorbital canal. The tarsus of Lophiparamys is similar to that of other early rodents but differs in a few features that suggest an arboreal locomotor repertoire, including an asymmetric astragalar trochlea, long astragalar neck, transverse astragalar sustentacular facet, short calcaneal tuber, elongate calcaneal ectal facet, and circular calcaneal cuboid facet. The presence of arboreally adapted features in the tarsus of Lophiparamys is consistent with a hypothesized relationship between small-bodied Eocene microparamyine rodents and extant Gliridae. Phylogenetic analysis fails to consistently support this relationship or monophyly of Microparamyinae, but both remain plausible. Comparison of L. debequensis with other species of the genus emphasizes the distinctiveness of L. debequensis and suggests the presence of multiple lineages of Lophiparamys.
Collection, Collation, and Comparison of 3D Coronal CME Reconstructions
Authors: Kay C. , Palmerio E.
Published: January 2024

Predicting the impacts of coronal mass ejections (CMEs) is a major focus of current space weather forecasting efforts. Typically, CME properties are reconstructed from stereoscopic coronal images and then used to forward model a CME's interplanetary evolution. Knowing the uncertainty in the coronal reconstructions is then a critical factor in determining the uncertainty of any predictions. A growing number of catalogs of coronal CME reconstructions exist, but no extensive comparison between these catalogs has yet been performed. Here we develop a Living List of Attributes Measured in Any Coronal Reconstruction (LLAMACoRe), an online collection of individual catalogs, which we intend to continually update. In this first version, we use results from 24 different catalogs with 3D reconstructions using Solar Terrestrial Relations Observatory observations between 2007 and 2014. We have collated the individual catalogs, determining which reconstructions correspond to the same events. LLAMACoRe contains 2,954 reconstructions for 1,862 CMEs. Of these, 511 CMEs contain multiple reconstructions from different catalogs. Using the best‐constrained values for each CME, we find that the combined catalog reproduces the generally known solar cycle trends. We determine the typical difference we would expect between two independent reconstructions of the same event and find values of 4.0° in the latitude, 8.0° in the longitude, 24.0° in the tilt, 9.3° in the angular width, 0.1 in the shape parameter κ, 115 km/s in the velocity, and 2.5 × 1015 g in the mass. These remain the most probable values over the solar cycle, though we find more extreme outliers in the deviation toward solar maximum.
Spatio-temporal coupled mode theory for nonlocal metasurfaces
Authors: Overvig Adam , Mann Sander A. , Alù Andrea
Published: January 2024

Diffractive nonlocal metasurfaces have recently opened a broad range of exciting developments in nanophotonics research and applications, leveraging spatially extended—yet locally patterned—resonant modes to control light with new degrees of freedom. While conventional grating responses are elegantly captured by temporal coupled mode theory, current approaches are not well equipped to capture the arbitrary spatial response observed in the nascent field of nonlocal metasurfaces. Here, we introduce spatio-temporal coupled mode theory (STCMT), capable of elegantly capturing the key features of the resonant response of wavefront-shaping nonlocal metasurfaces. This framework can quantitatively guide nonlocal metasurface design while maintaining compatibility with local metasurface frameworks, making it a powerful tool to rationally design and optimize a broad class of ultrathin optical components. We validate this STCMT framework against full-wave simulations of various nonlocal metasurfaces, demonstrating that this tool offers a powerful semi-analytical framework to understand and model the physics and functionality of these devices, without the need for computationally intense full-wave simulations. We also discuss how this model may shed physical insights into nonlocal phenomena in photonics and the functionality of the resulting devices. As a relevant example, we showcase STCMT’s flexibility by applying it to study and rapidly prototype nonlocal metasurfaces that spatially shape thermal emission.
Geometric phase-encoded stimuli-responsive cholesteric liquid crystals for visualizing real-time remote monitoring: humidity sensing as a proof of concept
Authors: Li Shi-Long , Chen Zhao-Yi , Chen Peng , Hu Wei , Huang Chaohong , Li Sen-Sen , Hu Xuejia , Lu Yan-Qing , Chen Lu-Jian
Published: January 2024

Liquid crystals are a vital component of modern photonics, and recent studies have demonstrated the exceptional sensing properties of stimuli-responsive cholesteric liquid crystals. However, existing cholesteric liquid crystal-based sensors often rely on the naked eye perceptibility of structural color or the measurement of wavelength changes by spectrometric tools, which limits their practical applications. Therefore, developing a platform that produces recognizable sensing signals is critical. In this study, we present a visual sensing platform based on geometric phase encoding of stimuli-responsive cholesteric liquid crystal polymers that generates real-time visual patterns, rather than frequency changes. To demonstrate this platform’s effectiveness, we used a humidity-responsive cholesteric liquid crystal polymer film encoded with a q-plate pattern, which revealed that humidity causes a shape change in the vortex beam reflected from the encoded cholesteric liquid crystal polymers. Moreover, we developed a prototype platform towards remote humidity monitoring benefiting from the high directionality and long-range transmission properties of laser beams carrying orbital angular momentum. Our approach provides a novel sensing platform for cholesteric liquid crystals-based sensors that offers promising practical applications. The ability to generate recognizable sensing signals through visual patterns offers a new level of practicality in the sensing field with stimuli-responsive cholesteric liquid crystals. This platform might have significant implications for a broad readership and will be of interest to researchers working in the field of photonics and sensing technology.
Proteomic insights into mental health status: plasma markers in young adults
Authors: Afonin Alexey M. , Piironen Aino-Kaisa , de Sousa Maciel Izaque , Ivanova Mariia , Alatalo Arto , Whipp Alyce M. , Pulkkinen Lea , Rose Richard J. , van Kamp Irene , Kaprio Jaakko , Kanninen Katja M.
Published: January 2024

Global emphasis on enhancing prevention and treatment strategies necessitates an increased understanding of the biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental disorders for biomarker identification. The p-factor, also known as the “general psychopathology factor”, is a concept in psychopathology suggesting that there is a common underlying factor that contributes to the development of various forms of mental disorders. It has been proposed that the p-factor can be used to understand the overall mental health status of an individual. Here, we aimed to discover plasma proteins associated with the p-factor in 775 young adults in the FinnTwin12 cohort. Using liquid chromatography–tandem mass spectrometry, 13 proteins with a significant connection with the p-factor were identified, 8 of which were linked to epidermal growth factor receptor (EGFR) signaling. This exploratory study provides new insight into biological alterations associated with mental health status in young adults.
Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity
Authors: Hansen Morten S. , Madsen Kaja , Price Maria , Søe Kent , Omata Yasunori , Zaiss Mario M. , Gorvin Caroline M. , Frost Morten , Rauch Alexander
Published: January 2024

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis, which is characterized by increased bone resorption and inadequate bone formation. As novel antiosteoporotic therapeutics are needed, understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets. This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation. Osteoclasts were differentiated from CD14+ monocytes from eight female donors. RNA sequencing during differentiation revealed 8 980 differentially expressed genes grouped into eight temporal patterns conserved across donors. These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs. Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks. The donor-specific expression patterns revealed genes at the monocyte stage, such as filamin B (FLNB) and oxidized low-density lipoprotein receptor 1 (OLR1, encoding LOX-1), that are predictive of the resorptive activity of mature osteoclasts. The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation, and these receptors are associated with bone mineral density SNPs, suggesting that they play a pivotal role in osteoclast differentiation and activity. The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1 (C5AR1), somatostatin receptor 2 (SSTR2), and free fatty acid receptor 4 (FFAR4/GPR120). Activating C5AR1 enhanced osteoclast formation, while activating SSTR2 decreased the resorptive activity of mature osteoclasts, and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts. In conclusion, we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity. These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.
Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2/Wnt11-CCL24 positive feedback loop
Authors: He Jiahao , Cheng Xinwei , Fang Bin , Shan Shengzhou , Li Qingfeng
Published: January 2024

Skin fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) caused by fibrotic disorders of the skin. In recent years, ECM stiffness has emerged as a prominent mechanical cue that precedes skin fibrosis and drives its progression by promoting fibroblasts activation. However, how stiffness influences fibroblasts activation for skin fibrosis progression remains unknown. Here, we report a positive feedback loop mediated by the mechanosensitive ion channel Piezo1 and aberrant tissue mechanics in driving skin fibrosis. Piezo1 is upregulated in fibrotic skin in both humans and mice. Piezo1 knockdown dermal fibroblasts lose their fibroproliferative phenotypes despite being grown on a stiffer substrate. We show that Piezo1 acts through the Wnt2/Wnt11 pathway to mechanically induce secretion of C-C motif chemokine ligand 24 (CCL24, also known as eotaxin-2), a potent cytokine associated with fibrotic disorders. Importantly, adeno-associated virus (AAV)-mediated Piezo1 knockdown ameliorated the progression of skin fibrosis and skin stiffness in mice. Overall, increased matrix stiffness promotes skin fibrosis through the inflammatory Piezo1-Wnt2/Wnt11-CCL24 pathway. In turn, a stiffer skin microenvironment increases Piezo1 expression to exacerbate skin fibrosis aggression. Therefore, targeting Piezo1 represents a strategy to break the positive feedback loop between fibroblasts mechanotransduction and aberrant tissue mechanics in skin fibrosis.
Towards near-term quantum simulation of materials
Authors: Clinton Laura , Cubitt Toby , Flynn Brian , Gambetta Filippo Maria , Klassen Joel , Montanaro Ashley , Piddock Stephen , Santos Raul A. , Sheridan Evan
Published: January 2024

Determining the ground and excited state properties of materials is considered one of the most promising applications of quantum computers. On near-term hardware, the limiting constraint on such simulations is the requisite circuit depths and qubit numbers, which currently lie well beyond near-term capabilities. Here we develop a quantum algorithm which reduces the estimated cost of material simulations. For example, we obtain a circuit depth improvement by up to 6 orders of magnitude for a Trotter layer of time-dynamics simulation in the transition-metal oxide SrVO3compared with the best previous quantum algorithms. We achieve this by introducing a collection of connected techniques, including highly localised and physically compact representations of materials Hamiltonians in the Wannier basis, a hybrid fermion-to-qubit mapping, and an efficient circuit compiler. Combined together, these methods leverage locality of materials Hamiltonians and result in a design that generates quantum circuits with depth independent of the system’s size. Although the requisite resources for the quantum simulation of materials are still beyond current hardware, our results show that realistic simulation of specific properties may be feasible without necessarily requiring fully scalable, fault-tolerant quantum computers, providing quantum algorithm design incorporates deeper understanding of the target materials and applications.
Natural reversion promotes LPS elongation in an attenuated Coxiella burnetii strain
Authors: Long Carrie M. , Beare Paul A. , Cockrell Diane , Binette Picabo , Tesfamariam Mahelat , Richards Crystal , Anderson Matthew , McCormick-Ell Jessica , Brose Megan , Anderson Rebecca , Omsland Anders , Pearson Talima , Heinzen Robert A.
Published: January 2024

Lipopolysaccharide (LPS) phase variation is a critical aspect of virulence in many Gram-negative bacteria. It is of particular importance to Coxiella burnetii, the biothreat pathogen that causes Q fever, as in vitro propagation of this organism leads to LPS truncation, which is associated with an attenuated and exempted from select agent status (Nine Mile II, NMII). Here, we demonstrate that NMII was recovered from the spleens of infected guinea pigs. Moreover, these strains exhibit a previously unrecognized form of elongated LPS and display increased virulence in comparison with the initial NMII strain. The reversion of a 3-bp mutation in the gene cbu0533 directly leads to LPS elongation. To address potential safety concerns, we introduce a modified NMII strain unable to produce elongated LPS.
DNA mechanocapsules for programmable piconewton responsive drug delivery
Authors: Velusamy Arventh , Sharma Radhika , Rashid Sk Aysha , Ogasawara Hiroaki , Salaita Khalid
Published: January 2024

The mechanical dysregulation of cells is associated with a number of disease states, that spans from fibrosis to tumorigenesis. Hence, it is highly desirable to develop strategies to deliver drugs based on the “mechanical phenotype” of a cell. To achieve this goal, we report the development of DNA mechanocapsules (DMC) comprised of DNA tetrahedrons that are force responsive. Modeling shows the trajectory of force-induced DMC rupture and predicts how applied force spatial position and orientation tunes the force-response threshold. DMCs functionalized with adhesion ligands mechanically denature in vitro as a result of cell receptor forces. DMCs are designed to encapsulate macromolecular cargos such as dextran and oligonucleotide drugs with minimal cargo leakage and high nuclease resistance. Force-induced release and uptake of DMC cargo is validated using flow cytometry. Finally, we demonstrate force-induced mRNA knockdown of HIF-1α in a manner that is dependent on the magnitude of cellular traction forces. These results show that DMCs can be effectively used to target biophysical phenotypes which may find useful applications in immunology and cancer biology.
Alkali metal bilayer intercalation in graphene
Authors: Lin Yung-Chang , Matsumoto Rika , Liu Qiunan , Solís-Fernández Pablo , Siao Ming-Deng , Chiu Po-Wen , Ago Hiroki , Suenaga Kazu
Published: January 2024

Alkali metal (AM) intercalation between graphene layers holds promise for electronic manipulation and energy storage, yet the underlying mechanism remains challenging to fully comprehend despite extensive research. In this study, we employ low-voltage scanning transmission electron microscopy (LV-STEM) to visualize the atomic structure of intercalated AMs (potassium, rubidium, and cesium) in bilayer graphene (BLG). Our findings reveal that the intercalated AMs adopt bilayer structures with hcp stacking, and specifically a C6M2C6 composition. These structures closely resemble the bilayer form of fcc (111) structure observed in AMs under high-pressure conditions. A negative charge transferred from bilayer AMs to graphene layers of approximately 1~1.5×1014 e−/cm−2 was determined by electron energy loss spectroscopy (EELS), Raman, and electrical transport. The bilayer AM is stable in BLG and graphite superficial layers but absent in the graphite interior, primarily dominated by single-layer AM intercalation. This hints at enhancing AM intercalation capacity by thinning the graphite material.
Salinity causes widespread restriction of methane emissions from small inland waters
Authors: Soued Cynthia , Bogard Matthew J. , Finlay Kerri , Bortolotti Lauren E. , Leavitt Peter R. , Badiou Pascal , Knox Sara H. , Jensen Sydney , Mueller Peka , Lee Sung Ching , Ng Darian , Wissel Björn , Chan Chun Ngai , Page Bryan , Kowal Paige
Published: January 2024

Inland waters are one of the largest natural sources of methane (CH4), a potent greenhouse gas, but emissions models and estimates were developed for solute-poor ecosystems and may not apply to salt-rich inland waters. Here we combine field surveys and eddy covariance measurements to show that salinity constrains microbial CH4 cycling through complex mechanisms, restricting aquatic emissions from one of the largest global hardwater regions (the Canadian Prairies). Existing models overestimated CH4 emissions from ponds and wetlands by up to several orders of magnitude, with discrepancies linked to salinity. While not significant for rivers and larger lakes, salinity interacted with organic matter availability to shape CH4 patterns in small lentic habitats. We estimate that excluding salinity leads to overestimation of emissions from small Canadian Prairie waterbodies by at least 81% ( ~ 1 Tg yr−1 CO2 equivalent), a quantity comparable to other major national emissions sources. Our findings are consistent with patterns in other hardwater landscapes, likely leading to an overestimation of global lentic CH4 emissions. Widespread salinization of inland waters may impact CH4 cycling and should be considered in future projections of aquatic emissions.
Ultrafast hot-carrier dynamics in ultrathin monocrystalline gold
Authors: Karaman Can O. , Bykov Anton Yu. , Kiani Fatemeh , Tagliabue Giulia , Zayats Anatoly V.
Published: January 2024

Applications in photodetection, photochemistry, and active metamaterials and metasurfaces require fundamental understanding of ultrafast nonthermal and thermal electron processes in metallic nanosystems. Significant progress has been recently achieved in synthesis and investigation of low-loss monocrystalline gold, opening up opportunities for its use in ultrathin nanophotonic architectures. Here, we reveal fundamental differences in hot-electron thermalisation dynamics between monocrystalline and polycrystalline ultrathin (down to 10 nm thickness) gold films. Comparison of weak and strong excitation regimes showcases a counterintuitive unique interplay between thermalised and non-thermalised electron dynamics in mesoscopic gold with the important influence of the X-point interband transitions on the intraband electron relaxation. We also experimentally demonstrate the effect of hot-electron transfer into a substrate and the substrate thermal properties on electron-electron and electron-phonon scattering in ultrathin films. The hot-electron injection efficiency from monocrystalline gold into TiO2, approaching 9% is measured, close to the theoretical limit. These experimental and modelling results reveal the important role of crystallinity and interfaces on the microscopic electronic processes important in numerous applications.
Tumour-retained activated CCR7+ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity
Authors: Lee Colin Y. C. , Kennedy Bethany C. , Richoz Nathan , Dean Isaac , Tuong Zewen K. , Gaspal Fabrina , Li Zhi , Willis Claire , Hasegawa Tetsuo , Whiteside Sarah K. , Posner David A. , Carlesso Gianluca , Hammond Scott A. , Dovedi Simon J. , Roychoudhuri Rahul , Withers David R. , Clatworthy Menna R.
Published: January 2024

Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7+ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7+ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7+ DCs co-localise with PD-1+CD8+ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7+ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.
Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity
Authors: Dean Isaac , Lee Colin Y. C. , Tuong Zewen K. , Li Zhi , Tibbitt Christopher A. , Willis Claire , Gaspal Fabrina , Kennedy Bethany C. , Matei-Rascu Veronika , Fiancette Rémi , Nordenvall Caroline , Lindforss Ulrik , Baker Syed Murtuza , Stockmann Christian , Sexl Veronika , Hammond Scott A. , Dovedi Simon J. , Mjösberg Jenny , Hepworth Matthew R. , Carlesso Gianluca , Clatworthy Menna R. , Withers David R.
Published: January 2024

Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived.
Magnon thermal Hall effect via emergent SU(3) flux on the antiferromagnetic skyrmion lattice
Authors: Takeda Hikaru , Kawano Masataka , Tamura Kyo , Akazawa Masatoshi , Yan Jian , Waki Takeshi , Nakamura Hiroyuki , Sato Kazuki , Narumi Yasuo , Hagiwara Masayuki , Yamashita Minoru , Hotta Chisa
Published: January 2024

Complexity of quantum phases of matter is often understood theoretically by using gauge structures, as is recognized by the $${{\mathbb{Z}}}_{2}$$

Z

2

and U(1) gauge theory description of spin liquids in frustrated magnets. Anomalous Hall effect of conducting electrons can intrinsically arise from a U(1) gauge expressing the spatial modulation of ferromagnetic moments or from an SU(2) gauge representing the spin-orbit coupling effect. Similarly, in insulating ferro and antiferromagnets, the magnon contribution to anomalous transports is explained in terms of U(1) and SU(2) fluxes present in the ordered magnetic structure. Here, we report thermal Hall measurements of MnSc2S4 in an applied field up to 14 T, for which we consider an emergent higher rank SU(3) flux, controlling the magnon transport. The thermal Hall coefficient takes a substantial value when the material enters a three-sublattice antiferromagnetic skyrmion phase, which is in agreement with the linear spin-wave theory. In our description, magnons are dressed with SU(3) gauge field, which is a mixture of three species of U(1) gauge fields originating from the slowly varying magnetic moments on these sublattices.
Archaean continental crust formed from mafic cumulates
Authors: Smit Matthijs A. , Musiyachenko Kira A. , Goumans Jeroen
Published: January 2024

Large swaths of juvenile crust with tonalite-trondhjemite-granodiorite (TTG) composition were added to the continental crust from about 3.5 billion years ago. Although TTG magmatism marked a pivotal step in early crustal growth and cratonisation, the petrogenetic processes, tectonic setting and sources of TTGs are not well known. Here, we investigate the composition and petrogenesis of Archaean TTGs using high field-strength-element systematics. The Nb concentrations and Ti anomalies of TTGs show the overwhelming effects of amphibole and plagioclase fractionation and permit constraints on the composition of primary TTG melts. These melts are relatively incompatible element-poor and characterised by variably high La/Sm, Sm/Yb and Sr/Y, and positive Eu anomalies. Differences in these parameters are not indicative of melting depth, but instead track differences in the degree of melting and fractional crystallisation. Primary TTGs formed by the melting of rutile- and garnet-bearing plagioclase-cumulate rocks that resided in proto-continental roots. The partial melting of these rocks is part of a causal chain that links TTG magmatism to the formation of sanukitoids and K-rich granites. Together, these processes explain the growth and differentiation of the continental crust during the Archaean without requiring external forcing such as meteorite impact or the start of global plate tectonics.
Methionine aminopeptidase 2 and its autoproteolysis product have different binding sites on the ribosome
Authors: Klein Marius A. , Wild Klemens , Kišonaitė Miglė , Sinning Irmgard
Published: January 2024

Excision of the initiator methionine is among the first co-translational processes that occur at the ribosome. While this crucial step in protein maturation is executed by two types of methionine aminopeptidases in eukaryotes (MAP1 and MAP2), additional roles in disease and translational regulation have drawn more attention to MAP2. Here, we report several cryo-EM structures of human and fungal MAP2 at the 80S ribosome. Irrespective of nascent chains, MAP2 can occupy the tunnel exit. On nascent chain displaying ribosomes, the MAP2-80S interaction is highly dynamic and the MAP2-specific N-terminal extension engages in stabilizing interactions with the long rRNA expansion segment ES27L. Loss of this extension by autoproteolytic cleavage impedes interactions at the tunnel, while promoting MAP2 to enter the ribosomal A-site, where it engages with crucial functional centers of translation. These findings reveal that proteolytic remodeling of MAP2 severely affects ribosome binding, and set the stage for targeted functional studies.