bluuebunny/crossref_metadata_2025 huggingface dataset:
Overactivation of prefrontal astrocytes impairs cognition through the metabolic pathway of central kynurenines
Authors: Beilmann Viktor , Furrer Johanna , Schalbetter Sina M. , Weber-Stadlbauer Ulrike , Wyss Matthias T. , Saab Aiman S. , Weber Bruno , Meyer Urs , Notter Tina
Published: December 2024

Astrocyte dysfunctions have long been implicated in psychiatric and cognitive disorders, yet the precise mechanisms underlying this association remain elusive. Here, we show that chemogenetic activation of prefrontal astrocytes in mice impairs short-term memory and sensorimotor gating and attenuates the activation of parvalbumin (PV) interneurons in the prefrontal cortex. These alterations are accompanied by increases in prefrontal levels of kynurenic acid (KYNA), a key metabolite of the kynurenine (KYN) pathway, known to be produced by astrocytes, which serves as an endogenous antagonist of NMDA receptors. Pharmacological inhibition of kynurenine aminotransferase II, the key enzyme mediating the transamination of KYN to KYNA, reinstates the astrocyte-mediated impairments in short-term memory and sensorimotor gating, and normalizes the deficits in prefrontal PV interneuron activation. Our study identifies a mechanistic link between overactivation of prefrontal astrocytes, increased production of KYNA, and cognitive as well as cellular dysfunctions involved in major psychiatric disorders and beyond.
“RIG-I mediated neuron-specific IFN type 1 signaling in FUS-ALS induces neurodegeneration and offers new biomarker-driven individualized treatment options for (FUS-)ALS.”
Authors: Naumann Marcel , Kretschmer Stefanie , Dash Banaja , Peikert Kevin , Glaß Hannes , Großmann Dajana , Günther René , Petri Susanne , Rödiger Annekathrin , Brenner David , Pan-Montojo Francisco , Aronica Eleonora , Kipp Markus , Zimyanin Vitaly , Sterneckert Jared , Grehl Torsten , Böckers Tobias M. , Oeckl Patrick , Lee-Kirsch Min Ae , Hermann Andreas
Published: December 2024

Recent research has demonstrated significant aberrant activation of the innate immune system in ALS model systems due to mutations in SOD1, TARDBP and C9orf72 through stimulation of the TBK1-IRF3 pathway. This pathway can be activated, for example, by cGAS-STING-dependent sensing of cytosolic DNA that accumulates as a result of chronic DNA damage and defective mitochondria, both of which have been identified as early pathology in FUS-ALS spinal motor neurons (sMNs). Therefore, we analysed innate immune pathways in isogenic and non-isogenic FUSmutiPSC-derived sMNs, which revealed upregulation of interferon-stimulated genes (ISGs) and activation of the TBK1-IRF3 pathway in FUSmutsMNs. Notably, we found evidence for accumulation of cytosolic dsRNA and its sensor RIG-I in FUS-ALS. RIG-I, but not MDA5, was found to be significantly upregulated in FUSmutsMNs, and siRNA-mediated knockdown abolished the increased IFN1 activation in FUSmutsMNs. In post-mortem analysis, RIG-I was highly expressed in the remaining α-MNs. IFN treatment of FUSwtsMNs phenocopied the axonal degeneration of FUSmutsMNs. Mechanistically, DNA damage induction did not increase ISG expression, but dsRNA was increased in the mitochondria of FUSmutsMNs. Mitochondrial transcription, a known source of dsRNA, was found to be upregulated in compartmental axonal RNAseq analysis and its inhibition reduced ISGs in FUS-ALS sMNs. Furthermore, the JAK-STAT inhibitor ruxolitinib alleviated the upregulated ISG expression and reversed the axonal degeneration of sMNs. Finally, we analysed ISG expression in peripheral blood samples from 18 FUS-ALS patients, eight of whom had a significantly elevated interferon signature. Blood ISGs correlated with disease progression rate and negatively with disease duration. RIG-I-mediated innate immune activation in sMNs may be an interesting novel individualised biomarker-driven therapeutic target in (FUS-) ALS.

A one-sentence summary of your paper

RIG-I-I-mediated innate immune activation is found in FUS-ALS spinal motor neurons caused by cytosolic dsRNA accumulation due to mitochondrial transcriptional activation and is amenable to JAK-STAT inhibition and might thus be an interesting novel individualized biomarker-driven therapeutic approach in (FUS-) ALS
Cyanoexosortase B is essential for motility, biofilm formation and scytonemin production in a filamentous cyanobacterium
Authors: Parrett Gabriel A. , Haft Daniel H. , Ruiz Maida , Garcia-Pichel Ferran , Ebmeier Christopher C. , Risser Douglas D.
Published: December 2024

Exosortases are involved in trafficking proteins containing PEP-CTERM domains to the exterior of gram-negative bacterial cells. The role of these proteins in cyanobacteria, where such homologs are common, has not been defined. The filamentous cyanobacteriumNostoc punctiformecontains a single putative exosortase, designated cyanoexosortase B (CrtB), implicated by previous work in both the motility, and in the production of the UV-absorbing pigment, scytonemin. To determine the role ofcrtBinN. punctiforme, acrtB-deletion strain (ΔcrtB) was generated. ΔcrtBpresented the loss of motility, biofilm formation, and scytonemin production. In the case of motility, the ΔcrtBmutant exhibited a specific defect in the ability of hormogonia (specialized motile filaments) to adhere to hormogonium polysaccharide (HPS) and several PEP-CTERM proteins expressed in motile hormogonia were differentially abundant in the exoproteome of the wild type compared to the ΔcrtBstrain. These results are consistent with the hypothetical role of CrtB in the processing and export of PEP-CTERM proteins that play a critical role in stabilizing the interaction between the filament surface and HPS to facilitate motility and biofilm formation. In the case of scytonemin, the late biosynthetic steps of which occur in the periplasm and whose operon contains several putative PEP-CTERM proteins, ΔcrtBfailed to produce it. Given the abundance of putative PEP-CTERM proteins encoded in theN. punctiformegenome, and the fact that this study only associates a fraction of them with biological functions, it seems likely that CrtB may play an important role in other biological processes in cyanobacteria.

Importance

In gram-negative bacteria, exosortases facilitate the trafficking of proteins to the exterior of the cell where they have been implicated in stabilizing the association of extracellular polymeric substances (EPS) with the cell surface to facilitate biofilm formation and flocculation, but the role of exosortases in cyanobacteria has not been explored. Here, we characterize the role of cyanoexosortase B (CrtB) in the filamentous cyanobacteriumNostoc punctiforme, demonstrating thatcrtBis essential for motility, biofilm formation, and the production of the sunscreen pigment scytonemin. These findings have important implications for understanding motility and biofilm formation in filamentous cyanobacteria as well as efforts toward heterologous production of scytonemin in non-native hosts.
Single-nuclei sequencing ofMoricandia arvensisreveals bundle sheath cell function in the photorespiratory shuttle of C3-C4intermediate Brassicaceae
Authors: Triesch Sebastian , Reichel-Deland Vanessa , Martín José Miguel Valderrama , Melzer Michael , Schlüter Urte , Weber Andreas P.M.
Published: December 2024

Spatially confined gene expression determines cell identity and is fundamental to complex plant traits. In the evolutionary transition from C3to the more efficient C4photosynthesis, restricting the glycine decarboxylase reaction to bundle sheath cells initiates a carbon concentrating mechanism via the photorespiratory glycine shuttle. This evolutionary step is generally thought to play an essential role in the progression from ancestral C3to C4photosynthesis. Plants operating this shuttle are often referred to as C3-C4intermediates or C2species. Within the Brassicaceae family, which includes model plants and crops, such species have evolved independently at least five times. However, research on the biochemistry of C3-C4intermediates in the Brassicaceae has been limited to a few case studies of differentially localized proteins between mesophyll and bundle sheath cells. Here, we leveraged recent advances in single-cell transcriptome sequencing to better understand how new cellular specialization affects interconnected pathways. We generated a single-nuclei RNA sequencing dataset forMoricandia arvensis, a Brassicaceae with C3-C4intermediate characteristics, and compared it to a publicly available single-cell transcriptome of leaf tissue of the C3Arabidopsis thaliana. We independently confirmed the localization of selected photorespiratory proteins by electron microscopy of immunogold-labelled leaf sections. Our analysis revealed the shift in expression of genes directly associated with the photorespiratory glycine decarboxylase reaction, but also of related pathways, such as ammonium assimilation, synthesis of specific amino acids, redox regulation, and transport to theM. arvensisbundle sheath. In contrast, the expression of these genes was not restricted to this cell type in the C3plant.

Highlight

Single-nucleus RNA sequencing ofMoricandia arvensisreveals bundle sheath cell-specific expression of photorespiration genes and associated pathways beyond glycine decarboxylase, including ammonium assimilation and redox regulation. This highlights the key role of metabolic compartmentalization in supporting C3-C4intermediate photosynthesis.
Polycomb Repressive Complex 2 promotes atherosclerotic plaque vulnerability
Authors: Joshi Divyesh , Chakraborty Raja , Bhogale Tejas , Furtado Jessica , Deng Hanqiang , Traylor James G. , Orr Anthony Wayne , Martin Kathleen A. , Schwartz Martin A.
Published: December 2024

Key findings:

1. PRC2 regulates EC shear stress responses.

2. PRC2 governs Klf2/4 suppression downstream of Pcdhg.

3. High PRC2 in ASCVD-prone arterial regions suppresses Klf2/4 to promote ASCVD.

4. Athero-protective Klf2/4 induction upon PRC2 inhibition requires Notch signaling.

5. Tazemetostat, an FDA approved PRC2 inhibitor, slows ASCVD progression and improves markers of plaque stability.

Atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide, is driven by endothelial cell inflammatory activation and counter-balanced by anti-inflammatory transcription factors Klf2 and Klf4 (Klf2/4). Understanding vascular endothelial inflammation to develop effective treatments is thus essential. Here, we identify, Polycomb Repressive Complex (PRC) 2, which blocks gene transcription by trimethylating histone3 Lysine27 in gene promoter/enhancers, as a potent, therapeutically targetable determinant of vascular inflammation and ASCVD progression. Bioinformatics identified PRC2 as a direct suppressor of Klf2/4 transcription. Klf2/4 transcription requires Notch signaling, which reverses PRC2 modification of Klf2/4 promoter/enhancers. PRC2 activity is elevated in human ASCVD endothelium. Treating mice with established ASCVD with tazemetostat, an FDA approved pharmacological inhibitor of PRC2, slowed plaque progression by 50% and drastically improved markers of plaque stability. This study elucidates a fundamental mechanism of vascular inflammation, thus identifying a potential method for treating ASCVD and possibly other vascular inflammatory diseases.
Structural Insights into Competitive Binding Dynamics between RALF23/33 and PCP-B in Brassicaceae Pollination
Authors: Bhalla Hemal , Sudarsanam Karthik , Srivastava Ashutosh , Sankaranarayanan Subramanian
Published: December 2024

Ensuring successful fertilization, viable offspring production, genetic isolation, and maintaining species integrity is pivotal for the survival of flowering plants. Members of Brassicaceae employ a “gatekeeping mechanism” involving interaction between stigmatic membrane-boundCatharanthus roseusreceptor-like kinase 1-like (CrRLK1L) receptor, FERONIA, GPI anchored protein LLG2 (LORELEI-LIKE GLYCOPHOSPHATIDYLINOSITOL-ANCHORED PROTEIN 2) and autocrine secreted RALF23/33 (Rapid alkalinization factor) peptide. This binding establishes a barrier for pollen hydration by inducing ROS (Reactive Oxygen Species). Conversely, in the presence of compatible pollen, paracrine-secreted cysteine-rich peptides such as PCP-Bγ compete with RALF23/33 for binding to the FERONIA-LLG2 complex, thus reducing ROS levels, ensuring successful pollen hydration and germination. Despite its crucial role, the structural basis of this competitive binding dynamics remains elusive owing to the lack of structural data and the inherent flexibility of these peptides. Using structural modeling, molecular docking, and simulations, this study reveals that PCP-Bγ binds to the same negatively charged pocket in the FERONIA-LLG2 complex as RALF23, displacing and interrupting the heterodimerized structure, thus reducing ROS levels to promote pollination. Our study unveils the experimental data-based predicted models, competitive binding dynamics, and mechanism behind this “gatekeeping mechanism,” shedding light on the molecular mechanism underlying this pollen hydration barrier in Brassicaceae.
Anisotropy of the zigzag order in the Kitaev honeycomb magnet
α−RuBr3
Authors: Pearce John S. , Kaib David A. S. , Ma Zeyu , Ni Danrui , Cava R. J. , Valentí Roser , Coldea Radu , Coldea Amalia I.
Published: December 2024

Kitaev materials often order magnetically at low temperatures due to the presence of non-Kitaev interactions. Torque magnetometry is a very sensitive technique for probing the magnetic anisotropy, which is critical in understanding the magnetic ground state. In this paper, we report detailed single-crystal torque measurements in the proposed Kitaev candidate honeycomb magnet α−RuBr3, which displays zigzag order below 34 K. Based on angular-dependent torque studies in magnetic fields up to 16 T rotated in the plane normal to the honeycomb layers, we find an easy-plane anisotropy with a temperature dependence of the torque amplitude following closely the behavior of the powder magnetic susceptibility. The torque for the field rotated in the honeycomb plane has a clear sixfold periodicity with a sawtooth shape, reflecting the threefold symmetry of the crystal structure and stabilization of different zigzag domains depending on the field orientation, with a torque amplitude that follows an order parameter form inside the zigzag phase. By comparing experimental data with theoretical calculations we highlight the importance of relevant anisotropic interactions and the role of the competition between different zigzag domains in this candidate Kitaev magnet.

Published by the American Physical Society
2024
Quantum kernel t-distributed stochastic neighbor embedding
Authors: Kawase Yoshiaki , Mitarai Kosuke , Fujii Keisuke
Published: December 2024

Data visualization is important in understanding the characteristics of data that are difficult to see directly. It is used to visualize loss landscapes and optimization trajectories to analyze optimization performance. Popular optimization analysis is performed by visualizing a loss landscape around the reached local or global minimum using principal component analysis. However, this visualization depends on the variational parameters of a quantum circuit rather than quantum states, which makes it difficult to understand the mechanism of the optimization process through the property of quantum states. Here, we propose a quantum data visualization method using quantum kernels, which enables us to offer fast and highly accurate visualization of quantum states. In our numerical experiments, we visualize a hand-written digits data set and apply a k-nearest neighbor algorithm to the low-dimensional data to quantitatively evaluate our proposed method compared with a classical kernel method. As a result, our proposed method achieves comparable accuracy to the state-of-the-art classical kernel method, meaning that the proposed visualization method based on quantum machine learning does not degrade the separability of the input higher-dimensional data. Furthermore, we visualize the optimization trajectories of finding the ground states of the transverse field Ising model, and we successfully find the trajectory characteristics. Since quantum states are higher-dimensional objects that can only be seen via observables, our visualization method, which inherits the similarity of quantum data, would be useful in understanding the behavior of quantum circuits and algorithms.

Published by the American Physical Society
2024
Directional Superradiance in a Driven Ultracold Atomic Gas in Free Space
Authors: Agarwal Sanaa , Chaparro Edwin , Barberena Diego , Orioli A. Piñeiro , Ferioli G. , Pancaldi S. , Ferrier-Barbut I. , Browaeys A. , Rey A.M.
Published: December 2024

Ultracold atomic systems are among the most promising platforms that have the potential to shed light on the complex behavior of many-body quantum systems. One prominent example is the case of a dense ensemble illuminated by a strong coherent drive while interacting via dipole-dipole interactions. Despite being subjected to intense investigations, this system retains many open questions. A recent experiment carried out in a pencil-shaped geometry [Ferioli Nat. Phys. 19, 1345 (2023)] has reported measurements that have seemed consistent with the emergence of strong collective effects in the form of a “superradiant” phase transition in free space, when looking at the light-emission properties in the forward direction. Motivated by the experimental observations, we carry out a systematic theoretical analysis of the steady-state properties of the system as a function of the driving strength and atom number N. We observe signatures of collective effects in the weak-driving regime, which disappear with increasing drive strength as the system evolves into a single-particle-like mixed state comprised of randomly aligned dipoles. Although the steady state features some similarities to the reported superradiant-to-normal nonequilibrium transition, also known as cooperative resonance fluorescence, we observe significant qualitative and quantitative differences, including a different scaling of the critical drive parameter (from N to N). We validate the applicability of a mean-field treatment to capture the steady-state dynamics under currently accessible conditions. Furthermore, we develop a simple theoretical model that explains the scaling properties by accounting for interaction-induced inhomogeneous effects and spontaneous emission, which are intrinsic features of interacting disordered arrays in free space.

Published by the American Physical Society
2024
Crystal structure of p-xylene@silicalite-1
Authors: Hwang In-Chul
Published: December 2024

The crystal structure of a highly loaded complex of silicalite-1 (SL-1) with eight molecules of p-xylene per unit cell has been solved by single-crystal X-ray diffraction. In the crystal, four symmetrical Si24O48·2C8H10 subunits per unit cell are observed. The p-xylene molecules sit at two different positions within the SL-1 channels. The first molecule is located at the intersection of the sinusoidal and straight channels, while the second guest molecule is positioned in the center of the double ten-membered ring (10-MR) of the sinusoidal channel.
rac-2-{3-[1-(Acetyloxy)ethyl]-2,2-dimethylcyclobutyl}acetic acid
Authors: Schollmeyer Dieter , Jirsch Paul , Detert Heiner
Published: December 2024

The title compound, C12H20O4, was prepared from α-pinene in three steps. The ester and acid moieties are cis on the slightly folded cyclobutane ring. In the crystal, carboxylic acid bound dimers form layers parallel to (202).
1-[(2-Chlorophenyl)diphenylmethyl]-1H-pyrazole
Authors: Koch Pierre , Schollmeyer Dieter
Published: December 2024

The title compound C22H17ClN2, also named as TRAM-34, crystallizes in the monoclinic space group P21/n. The dihedral angles between the pyrazole ring and the three six-membered rings are 62.28 (9), 69.48 (9) and 71.30 (9)°.
Deep learning-based recognition of construction activities in real construction site environment
Authors: Karatas Ibrahim , Budak Abdulkadir
Published: December 2024

Purpose

Today’s technological advancements have had a significant impact on the construction industry. Managing and controlling complex construction projects has been made significantly easier using technological tools. One such advancement is the automatic identification of workers’ activities. This study aims to classify construction worker activities by analyzing real-time motion data collected from sensors.

Design/methodology/approach

In accordance with our specific goals, we utilized advanced deep-learning methodologies such as deep neural networks, convolutional neural network, long short-term memory and convolutional long short-term memory to analyze the data thoroughly. This involved experimenting with various window sizes and overlap ratios to determine the optimal combination that would result in the most accurate predictions.

Findings

Based on the analysis results, the convolutional long short-term memory (ConvLSTM) deep learning model with a window size of 4.8 s and an overlap rate of 75% was found to be the most accurate prediction model. This model correctly predicted 98.64% of the basic construction worker activities in a real construction site environment.

Originality/value

Previous studies have mainly been conducted in laboratory environments and have focused on basic construction activities such as lifting, moving, sawing and hammering. However, this study collected data from real workers in a real construction site environment. Various deep learning models were employed to determine the most accurate one. Additionally, several options were tested to determine the optimal window size and overlap ratio during the data segmentation phase, aiming to select the most suitable ones for preparing the data for the model.
Finding the sweet spot: effects of exporting on the relationship between R&D investment and NPD performance
Authors: Sousa Carlos M.P. , Tsinopoulos Christos , Yan Ji , Benito Gabriel R.G.
Published: December 2024

Purpose

The aim of this research is twofold: (1) to investigate when the effect of R&D investment on New Product Development (NPD) performance peaks – the sweet spot and (2) to analyze the influence of firms’ export activities on where that spot is. Drawing on the knowledge-based view (KBV), we argue that export intensity and export experience lead to differential effects on how R&D investments are converted into new products.

Design/methodology/approach

We test our conceptual framework using time lagged data and optimal-level analysis. The dataset consists of an unbalanced panel of 608,891 observations and 333,516 firms.

Findings

The results support the expected inverted U-shaped relationship between R&D investment and NPD performance. They also show moderating effects of export intensity and experience. Export intensity enhances innovation processes by enabling firms to stretch the points at which R&D investments eventually taper off. In contrast, export experience improves firms’ ability to convert R&D investments into NPD performance. Our results demonstrate that, all else equal, firms with relatively higher export experience can spend less on R&D and still achieve higher levels of NPD performance.

Originality/value

We contribute to the literature by investigating how export activities provide a valuable context for understanding the theoretical mechanisms that help explain the inverted U-shaped relationship between R&D investment and innovation. We show the effects of exporting activities on the precise points where the R&D investment–NPD performance relationship peaks, thereby identifying the optimal point within this nonlinear relationship.
Are private banks more sensitive to changes in reserve requirements? Evidence from an emerging market
Authors: Swamy Vighneswara , Narayanamurthy Vijayakumar
Published: December 2024

Purpose

This article explores the effects of monetary policy rates and interest rate structures on bank profitability.

Design/methodology/approach

We studied 65 Indian commercial banks over time, including economic cycles, consolidation and the Great Financial Crisis. We categorized commercial banks by ownership (public, private or foreign) and predicted how they will react to monetary policy changes. We employed the instrumental variable estimate approach and panel Granger causality tests to give evidence of the direction of causation in the monetary policy and bank performance nexus.

Findings

Private and international banks, we believe, are more sensitive to changes in reserve requirements because they are more effective at maintaining statutory reserves. Private and international banks are more susceptible to repo rate fluctuations than state banks. In contrast, public banks are more sensitive to bank rates because they are more likely than private and international banks to use the bank rate window of accommodation.

Originality/value

We studied the impact of monetary policy rates on bank performance within the banking-dominated financial system of an emerging economy – a focus that has not been previously explored. There has been little research into the connection between monetary policy rates and bank performance in emerging markets, notably in India.
Toward an understanding of the robot rights spectrum: an integrative framework from an Islamic economics perspective
Authors: Mohd Thas Thaker Mohamed Asmy Bin , Akbar Mohamed Aslam , Imon Riasat Amin Amin
Published: December 2024

Purpose

This paper aims to explore the role and relationship of ethics and morals in technology, specifically examining how Islam, as a religion that emphasizes spirituality and sacredness, can uniquely influence the concept of robot rights.

Design/methodology/approach

The existing literature on robot rights and Islamic perspectives has been critically reviewed to address the study’s objectives.

Findings

In Islam, robots are viewed similarly to property ownership, where the owner holds responsibilities rather than absolute control. Islamic ownership rights are distinct compared to conventional ownership models. In Islam, private ownership is limited, as God is considered the ultimate owner of all assets. Assets, including robots, must be managed according to Islamic values and ethics. Unlike conventional ownership, where the owner can dispose of their property without justification, Islamic principles grant more rights to assets (including robots). This difference arises from the sacred origins of economic resources in Islam, which extends to the treatment of assets as inputs in an economy. Therefore, spirituality, as defined in Islam, uniquely influences the rights of robots.

Originality/value

As robotics becomes an increasingly significant part of our lives, religion plays a growing role in shaping the ethical and moral framework within which robots operate. This study is among the first to present an integrative framework and evaluate robot rights from an Islamic economics perspective.
The cross-domain impact of home stressors on job performance through leisure crafting
Authors: Chen I-Shuo
Published: December 2024

Purpose

We explored the mechanism underlying the associations between different home stressors and job performance. We investigated whether challenge and hindrance home stressors are related to leisure crafting and thereby to job performance. We also examined whether key resources amplify the positive association between leisure crafting and job performance.

Design/methodology/approach

We conducted a three-wave time lag study to investigate a group of employees (n = 534) in Taiwan. We evaluated challenge/hindrance home stressors and key resources at Time 1, leisure crafting one week later, i.e. at Time 2 and manager-rated job performance an additional three months later, i.e. at Time 3.

Findings

Challenge home stressors were associated with improved leisure crafting, thereby benefiting job performance; hindrance home stressors had the opposite effect. Additionally, openness to experience strengthened the positive association between leisure crafting and job performance.

Practical implications

Organizations may support employees’ efforts to promote/mitigate challenge/hindrance home stressors. They may also encourage employees to be open to life experiences that can amplify the contributions of leisure crafting to job performance.

Originality/value

The questions of whether and how home stressors are related to individuals’ work remain controversial in the literature. We offer new insights into how these stressors can contribute to or impede job performance, thereby extending our knowledge of the role of home stressors in job performance.
It's all Lavender in Gaza
Authors: Gusterson Hugh
Published: December 2024

This guest editorial examines Israel's deployment of the AI program Lavender in Gaza as a significant shift in counterinsurgency warfare, moving from traditional hearts‐and‐minds campaigns to algorithmic targeting. Drawing on investigative reporting and anthropological perspectives on algorithms, it analyses how Lavender transforms warfare through four critical stages: problematic initial parameters, systematic matching errors, declining human oversight, and erosion of moral responsibility. While the system presents a veneer of precision targeting, its flexible thresholds and high acceptable civilian casualty ratios enable mass civilian casualties while providing bureaucratic legitimacy. The analysis suggests this fusion of AI and killing represents a concerning precedent that could proliferate to other conflicts unless decisively addressed.
‘Our monuments’: Reclaiming St Croix's elite heritage for descendants of the enslaved
Authors: Bolin Annalisa
Published: December 2024

Sites of plantation slavery that are now interpreted as heritage frequently spatialize their narratives by emphasizing White elites in monumental spaces and associating the Black enslaved with smaller, less‐imposing and frequently worse‐preserved elements. In the contemporary present, as heritage spaces increasingly push to focus on the enslaved instead of the elite, the preservation of elite monumentality can be viewed as honouring enslavers. This article explores the position of heritage professionals on St Croix, US Virgin Islands, who advocate instead for a respatialization of slavery's heritage: a resignification of these ‘elite’ monuments as monuments to – and created by – the enslaved themselves. Their emphasis on the resilience and ingenuity of the enslaved challenges the spatial foregrounding of White supremacy in monumental heritage and allows the persistent materiality of plantations to be reclaimed in order to elevate Black history and identity.
Curricular Self‐management for patients on ventricular assist device support decreases depression: A multicenter randomized controlled trial
Authors: Kugler Christiane , Spielmann Hannah , Richter Fabian , Lauenroth Volker , Semmig‐Könze Sandra , Spitz‐Köberich Christine , Bertsche Tim , Staus Paulina , Weber Susanne , Albert Wolfgang , Tigges‐Limmer Katharina ,   the Selma Study Group
Published: December 2024

Background

Utilization of ventricular assist device (VAD) support in patients with end‐stage heart failure is well advanced. Recent studies emphasize the need to develop and evaluate evidence‐based psychosocial support interventions for patients following VAD implantation.

Methods

A national, multi‐center study in four established German heart centers was initiated. An evidence‐based VAD curriculum was developed; a randomized controlled trial evaluated the impact of the interprofessional intervention over time. Primary combined endpoint was the occurrence of adverse events (thromboembolic events, driveline infections, bleeding, rehospitalization, and death); secondary endpoints were psychosocial outcomes (anxiety, depression [HADS], quality of life [QoLVAD], social support [FSoZu], and self‐management [SELMA]). A total of 140 patients were randomized block‐wise to intervention (IG n = 70) or control (CG n = 70). Center‐effects were considered. Instruments were completed at four time points (T0‐T3).

Results

At baseline, intervention group (IG) patients were 19% female (control group [CG] 19%; p = 0.982); 58 ± 11 years. (CG 58 ± 11 years.; p = 0.966); 80% were implanted electively (CG 79%; p = 0.968). No significant difference in primary endpoint was found between IG versus CG (p > 0.05). For secondary endpoints, mixed linear regression revealed a significant reduction in depression scores in IG compared to CG (est. 1.18; 95% CI −2.17 to −0.18; p = 0.021). Clinically significant reductions in anxiety were greater in IG patients between T0 and T3 (IG 51.9%; CG 40.7%); increased anxiety was reported in 3.7% IG (11.1% CG). Mixed linear regression analyses favored IG (all >0.05) for QoL, social support, and self‐management.

Conclusion

A comprehensive curricular VAD intervention has potential to decrease depression levels and improve psychosocial outcomes of patients on VAD support.
Synergistic‐like decreases in alcohol intake following combined pharmacotherapy with GLP‐1 and amylin in male rats
Authors: Aranäs Cajsa , Caffrey Antonia , Edvardsson Christian E. , Vestlund Jesper , Schmidt Heath D. , Jerlhag Elisabet
Published: December 2024

Background and Purpose

The limited effectiveness of current pharmacological treatments for alcohol use disorder (AUD) highlights the need for novel therapies. These may involve the glucagon‐like peptide‐1 receptor or the amylin receptor, as treatment with agonists targeting either of these receptors lowers alcohol intake. The complexity of the mechanisms underlying AUD indicates that combining agents could enhance treatment efficacy. While a combination of amylin receptor and GLP‐1 receptor agonists reduced food intake and body weight synergistic‐like, its influence on alcohol intake is unknown.

Experimental Approach

Effects of a range of dose‐combinations of GLP‐1 receptor (dulaglutide) and amylin receptor (salmon calcitonin; sCT) agonists on alcohol intake were explored in male and female rats. We used dose combinations that either lowered alcohol intake as monotherapy (0.1 mg·kg−1 + 5 μg·kg−1), or that did not affect alcohol consumption per se (0.075 mg·kg−1 + 2 μg·kg−1).

Key Results

Acute administration of dulaglutide and sCT (0.1 mg·kg−1 + 5 μg·kg−1) reduced alcohol intake in males, but not in females. When higher doses were evaluated in female rats, a decrease in alcohol intake was observed. Furthermore, the low dose combination (0.075 mg·kg−1 + 2 μg·kg−1) decreased, in in a synergistic‐like manner, alcohol intake and prevented abstinence‐induced drinking without affecting kaolin intake in males. However, tolerance developed during sub‐chronic treatment.

Conclusion and Implications

Collectively, these findings show that the combination of dulaglutide and sCT decreased, in in a synergistic‐like manner, alcohol consumption in male rats. Contrarily, higher doses are required for females.
Exploring the tumor microenvironment of colorectal cancer patients post renal transplantation by single‐cell analysis
Authors: Zhang Jinghui , Mizuuchi Yusuke , Ohuchida Kenoki , Hisano Kyoko , Shimada Yuki , Katayama Naoki , Tsutsumi Chikanori , Tan Bryan C. , Nagayoshi Kinuko , Tamura Koji , Fujimoto Takaaki , Ikenaga Naoki , Nakata Kohei , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Patients with colorectal cancer (CRC) following renal transplantation require long‐term immunosuppressants to prevent graft rejection. However, the impact of these immunosuppressants on the tumor immune microenvironment and the roles of immune cells within it remain poorly understood. We conducted comprehensive single‐cell RNA sequencing on tumor and normal tissues from four CRC patients post renal transplantation and compared these with published data from 23 non‐transplant CRC patients. We set four groups for detailed comparative analysis based on the renal transplantation status and tissue origin: non‐renal transplantation normal (nRT_Normal), non‐renal transplantation tumor (nRT_Tumor), renal transplantation normal (RT_Normal), renal transplantation tumor (RT_Tumor). Our analysis revealed significant tumor immune microenvironment landscape alterations in the transplantation group. CD8+effector T cells of RT_Tumor showed significantly diminished cytotoxicity and tumor neoantigen recognition (p < 0.0001), while CD4+FOXP3 regulatory T cells of RT_Tumor displayed a higher inhibitory score (p < 0.05), indicating preserved immunomodulatory potential compared with non‐transplant CRC. Notably, significantly increased CTLA4 expression in T cells of RT_Tumor was found and testified (p < 0.05). Our findings provide novel mechanistic insights for understanding the immune landscape in renal transplant recipients with CRC and pave the way for potential immunotherapeutic strategies that may improve survival and quality of life for this patient population.
Mimickers of hydroxychloroquine retinal toxicity
Authors: Jones Peter , Kalra Gagan , Al‐Sheikh Mayss , Chhablani Jay
Published: December 2024

Hydroxychloroquine (HCQ) retinal toxicity is an important entity that can be challenging to differentiate from its mimickers. Bull's eye maculopathy is the classical presentation of HCQ retinopathy; however, its differential includes several drug‐related retinal toxicities, inherited retinal disorders, and systemic conditions with associated retinopathies. Given the similarities in clinical presentation, imaging findings, and other diagnostic data, it can be quite challenging for all but the retina specialists to successfully identify retinal toxicity from HCQ. This review summarises HCQ retinopathy and its mimickers of with a special emphasis on key clinical and ancillary distinctions that can help comprehensive ophthalmologists and primary care offices in clenching this diagnosis.
Targeting HLA‐E in Lung Cancer: The Therapeutic Potential of IRF5‐Engineered M1‐Macrophage‐Derived Exosomes
Authors: Feng Xuqin , Lai Xiangyu , Zhou Mingming , Bie Jun , Li Tingting , Wang Dan , Chen Silin , Hu Xin , Wang Chunyu , Xu Peng
Published: December 2024

Immunotherapy is a pivotal approach in the treatment of lung cancer. Although HLA‐E is a potential target for tumor immunotherapy, its role in lung cancer remains unclear. Previous studies have identified the transcription factor IRF5 as a characteristic gene of M1‐like macrophages, highlighting its crucial role in promoting antitumor immune responses. In this study, we developed an engineered M1‐like macrophage exosomes expressing IRF5 (IRF5 M1‐exos) and demonstrated their ability to inhibit proliferation, migration, and invasion of lung cancer cells. Moreover, our experiments using a nude mouse model revealed that IRF5 M1‐exos exerted potent therapeutic effects by effectively suppressing tumor growth. Notably, the mechanism by which IRF5 exerts its antitumor function through HLA‐E regulation in lung cancer has not been fully elucidated. Here, we identified HLA‐E as a downstream target gene of IRF5 and demonstrated that the overexpression of HLA‐E can counteract the tumor‐promoting effects induced by si‐IRF5 M1‐exos. These results suggest that M1 macrophage‐derived exosomes, enriched with the transcription factor IRF5, exhibit potent antitumor activity by up‐regulating HLA‐E in lung cancer cells. Therefore, IRF5 M1‐exos represent an attractive therapeutic strategy for lung cancer.
Ultrasound Utilization in Hospitalized Kidney Transplant Recipients: Useful or Overused?
Authors: Bau Jason T. , Park Jennifer , Li Yanhong , Rampersad Christie , Kim S. Joseph
Published: December 2024

Kidney transplant ultrasonography is an important diagnostic tool in the care of transplant recipients. This modality of nonradiation‐based imaging allows for precise and expedient reporting of allograft architecture, which can inform clinical decision‐making. However, as with any diagnostic tool, overuse may lead to unnecessary interventions and costs on the healthcare system. To better understand the use of ultrasonography in hospitalized kidney transplant recipients and outcomes of subsequent interventions, we conducted a single‐center retrospective study at a large transplant program in Ontario, Canada. We noted that over 30% of admissions resulted in a ultrasonographic survey within the first 24 h of presentation; however, most of these did not change clinical management or lead to a subsequent procedural intervention. Using multivariable logistic regression, we identified predictors for receiving an ultrasound, including time from transplantation, elevated serum creatinine and infectious diagnosis. Procedural interventions (e.g., drain or biopsy) resulted from less than 20% of all ultrasound investigations, with patients closer to the time of index transplant or with elevated serum creatinine values more likely to receive an intervention. In conducting a cost analysis, we estimated that approximately $80 000 CAD per year could be saved with more selective decisions on ultrasound requisitions. Overall, our results indicate that despite being an informative tool, the broad use of ultrasonography in the kidney transplant population may not yield significant changes to transplant care.
Financial Market Misconduct: A Bibliometric Perspective
Authors: Carè Rosella , Fatima Rabia
Published: December 2024

This article provides a bibliometric analysis of financial market misconduct (FMM) research. It maps the intellectual structure of FMM studies, visualizes the field's scientific literature, and uncovers its intellectual backbone, emergent ‘hot topics’, key journals, and influential authors. The study contributes to both academia and industry by elucidating the main components and evolutionary trends in FMM research. Additionally, it highlights future research directions by identifying potential underestimated risks and unexplored areas.
Endangered Pinto/Northern Abalone (Haliotis kamtschatkana) are Panmictic Across Their 3700 km Range Along the Pacific Coast of North America
Authors: Dimond J. L. , Bouma J. V. , Lafarga‐De la Cruz F. , Supernault K. J. , White T. , Witting D. A.
Published: December 2024

Connectivity is integral to the dynamics of metapopulations through dispersal and gene flow, and understanding these processes is essential for guiding conservation efforts. Abalone, broadcast‐spawning marine snails associated with shallow rocky habitats, have experienced widespread declines, and all seven North American species are threatened. We investigated the connectivity and population genomics of pinto/northern abalone (Haliotis kamtschatkana), the widest‐ranging of abalone species. We employed reduced representation sequencing (RADseq) to generate single nucleotide polymorphism (SNP) data, assessing population connectivity and potential adaptive variation at 12 locations across the full range from Alaska to Mexico. Despite depleted populations, our analysis of over 6000 SNPs across nearly 300 individuals revealed that pinto abalone maintains a high genetic diversity with no evidence of a genetic bottleneck. Neutral population structure and isolation by distance were extremely weak, indicating panmixia across the species' range (global FST = 0.0021). Phylogenetic analysis, principal components analysis, and unsupervised clustering methods all supported a single genetic population. However, slight population differentiation was noted in the Salish Sea and Inside Passage regions, with evidence for higher barriers to dispersal relative to outer coastal areas. This north‐central region may also represent the species' ancestral range based on relatively low population‐specific FST values; the northern and southern extremes of the range likely represent range expansions. Outlier analysis did not identify consensus loci implicated in adaptive variation, suggesting limited adaptive differentiation. Our study sheds light on the evolutionary history and contemporary gene flow of this threatened species, providing key insights for conservation strategies, particularly in sourcing broodstock for ongoing restoration efforts.
Multi‐employer collective bargaining in liberal market economies: Reasons for survival and reinvigoration
Authors: WRIGHT Chris F.
Published: December 2024

This article examines the preconditions for successful implementation of multi‐employer collective bargaining in countries lacking supportive institutions. It presents cases from the United Kingdom, New Zealand and Australia, three liberal market economies where multi‐employer bargaining has either survived in some sectors or where there have been recent attempts to strengthen it. The findings highlight the importance of both “regulatory” institutions (e.g. laws) and “cognitive” institutions (e.g. social norms) to ensure that, first, employment relations actors have the power and resources to support multi‐employer bargaining in practice and, second, workers and employers accept this form of wage‐setting as legitimate.
Influenza Vaccine Effectiveness Against Symptomatic Influenza in Primary Care: A Test Negative Case Control Study Over Two Influenza Seasons 2022/2023 and 2023/2024 in Ireland
Authors: Marron Louise , McKenna Adele , O'Donnell Joan , Joyce Michael , Bennett Charlene , Connell Jeff , Domegan Lisa
Published: December 2024

Introduction

Live attenuated influenza vaccine (LAIV) is recommended in Ireland for all children aged 2–17 years. Quadrivalent influenza vaccine (QIV) is recommended for all others eligible for vaccination, including those ≥ 18 years with underlying medical conditions and all aged ≥ 65 years. We aimed to estimate influenza vaccine effectiveness (IVE) against acute respiratory infection (ARI) presentations to primary care due to influenza over two influenza seasons in Ireland, to inform vaccination recommendations and communication campaigns.

Methods

We undertook a test‐negative case control study within the Irish sentinel general practice surveillance network as part of the Vaccine Effectiveness Burden and Impact Studies (VEBIS) network. We compared influenza vaccination status among influenza PCR positive cases with influenza PCR negative controls, both with ARI presentations, of all ages. We estimated IVE using logistic regression adjusting for age, onset time, medical conditions and sex.

Results

In 2022/2023, there were 288 cases and 765 controls. In 2023/2024, there were 567 cases and 1832 controls. In 2022/2023, overall IVE was 42% (95% CI 9 to 64) and 50% (95% CI −30 to 83) in 2‐ to 17‐year‐olds. Overall IVE in 2023/2024 was 35% (95% CI 15 to 51) and 68% (95% CI 30 to 87) in 2‐ to 17‐year‐olds.

Conclusion

Influenza vaccination reduced the risk of influenza among ARI patients presenting to general practice, demonstrating the benefits of vaccination, particularly among children. Promotion of the seasonal influenza vaccine to recommended groups, should remain a public health priority. Targeted vaccination campaigns for children promoting LAIV should emphasise the effectiveness of LAIV in children.