bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying drug targets for schizophrenia through gene prioritization
Authors: Kraft Julia , Braun Alice , Awasthi Swapnil , Panagiotaropoulou Georgia , Schipper Marijn , Bell Nathaniel , Posthuma Danielle , Pardiñas Antonio F. ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Ripke Stephan , Heilbron Karl
Published: May 2024

Background

Schizophrenia genome-wide association studies (GWASes) have identified >250 significant loci and prioritized >100 disease-related genes. However, gene prioritization efforts have mostly been restricted to locus-based methods that ignore information from the rest of the genome.

Methods

To more accurately characterize genes involved in schizophrenia etiology, we applied a combination of highly-predictive tools to a published GWAS of 67,390 schizophrenia cases and 94,015 controls. We combined both locus-based methods (fine-mapped coding variants, distance to GWAS signals) and genome-wide methods (PoPS, MAGMA, ultra-rare coding variant burden tests). To validate our findings, we compared them with previous prioritization efforts, known neurodevelopmental genes, and results from the PsyOPS tool.

Results

We prioritized 62 schizophrenia genes, 41 of which were also highlighted by our validation methods. In addition toDRD2, the principal target of antipsychotics, we prioritized 9 genes that are targeted by approved or investigational drugs. These included drugs targeting glutamatergic receptors (GRIN2AandGRM3), calcium channels (CACNA1CandCACNB2), and GABABreceptor (GABBR2). These also included genes in loci that are shared with an addiction GWAS (e.g. PDE4BandVRK2).

Conclusions

We curated a high-quality list of 62 genes that likely play a role in the development of schizophrenia. Developing or repurposing drugs that target these genes may lead to a new generation of schizophrenia therapies. Rodent models of addiction more closely resemble the human disorder than rodent models of schizophrenia. As such, genes prioritized for both disorders could be explored in rodent addiction models, potentially facilitating drug development.
"Exploring Cardiac Vector Propagation in Acute Myocardial Infarction: A Spatial Velocity Perspective"
Authors: Ghosal Tania , Hembram Anjan , Ahmed Imran , Goswami Damodar Prasad , Bandyopadhyay Anupam , Sengupta Arnab
Published: May 2024

Aims

To objectively characterize the spatial-velocity dynamics of the QRS-loop in the vectorcardiogram (VCG) of patients with acute myocardial infarction (AMI).

Methods

VCG was constructed as space curve from three orthogonal ECG leads of 25 healthy individuals and 50 AMI patients. Spatial-velocity (SV) of the dynamic QRS loop was recorded, along with component attributes such as changing spatial distance (SD) and magnitude.

Results

Decreased SV and SD and altered spatial propagation patterns of ventricular vectors in AMI was recorded, with changes in specific axes based on infarct location. Reduced left-ventricular ejection-fraction indicates systolic dysfunction in AMI.

Conclusion

Altered spatial propagation patterns of vectors and ventricular dysfunction may be explained by complex interplay between mechanical and electrical factors in AMI.

Declaration

The present manuscript has been submitted in the journalFuture Cardiology, and currently under peer review

None of the manuscript’s contents have yet been published.

All authors have read and approved the manuscript and approved its submission to MedRxiv, as preprint server. They also agreed the order of authorship.
Cell autonomous microglia defects in a stem cell model of frontotemporal dementia
Authors: Iyer Abhirami K. , Vermunt Lisa , Mirfakhar Farzaneh S. , Minaya Miguel , Acquarone Mariana , Koppisetti Rama Krishna , Renganathan Arun , You Shih-Feng , Danhash Emma P. , Verbeck Anthony , Galasso Grant , Lee Scott M. , Marsh Jacob , Nana Alissa L. , Spina Salvatore , Seeley William W. , Grinberg Lea T. , Temple Sally , Teunissen Charlotte E. , Sato Chihiro , Karch Celeste M.
Published: May 2024

Neuronal dysfunction has been extensively studied as a central feature of neurodegenerative tauopathies. However, across neurodegenerative diseases, there is strong evidence for active involvement of immune cells like microglia in driving disease pathophysiology. Here, we demonstrate that tau mRNA and protein are expressed in microglia in human brains and in human induced pluripotent stem cell (iPSC)-derived microglia like cells (iMGLs). Using iMGLs harboring theMAPTIVS10+16 mutation and isogenic controls, we demonstrate that a tau mutation is sufficient to alter microglial transcriptional states. We discovered thatMAPTIVS10+16 microglia exhibit cytoskeletal abnormalities, stalled phagocytosis, disrupted TREM2/TYROBP networks, and altered metabolism. Additionally, we found that secretory factors fromMAPTIVS10+16 iMGLs impact neuronal health, reducing synaptic density in neurons. Key features observedin vitrowere recapitulated in human brain tissue and cerebrospinal fluid fromMAPTmutations carriers. Together, our findings thatMAPTIVS10+16 drives cell-intrinsic dysfunction in microglia that impacts neuronal health has major implications for development of therapeutic strategies.
Necessary for seizure forecasting outcome metrics: seizure frequency and benchmark model
Authors: Chang Chi-Yuan , Zhang Boyu , Moss Robert , Picard Rosalind , Westover M. Brandon , Goldenholz Daniel
Published: May 2024

Work is ongoing to advance seizure forecasting, but the performance metrics used to evaluate model effectiveness can sometimes lead to misleading outcomes. For example, some metrics improve when tested on patients with a particular range of seizure frequencies (SF). This study illustrates the connection between SF and metrics. Additionally, we compared benchmarks for testing performance: a moving average (MA) or the commonly used permutation benchmark. Three data sets were used for the evaluations: (1) Self-reported seizure diaries of 3,994 Seizure Tracker patients; (2) Automatically detected (and sometimes manually reported or edited) generalized tonic-clonic seizures from 2,350 Empatica Embrace 2 and Mate App seizure diary users, and (3) Simulated datasets with varying SFs. Metrics of calibration and discrimination were computed for each dataset, comparing MA and permutation performance across SF values. Most metrics were found to depend on SF. The MA model outperformed or matched the permutation model in all cases. The findings highlight SF’s role in seizure forecasting accuracy and the MA model’s suitability as a benchmark. This underscores the need for considering patient SF in forecasting studies and suggests the MA model may provide a better standard for evaluating future seizure forecasting models.
Single-cell transcriptomics reveals immunosuppressive microenvironment and highlights stumor-promoting macrophage cells in Glioblastoma
Authors: Cheng Han , Yan Yan , Zhang Biao , Ma Zhuolin , Fu Siwen , Ji Zhi , Zou Ziji , Wang Qin
Published: May 2024

Glioblastoma (GBM) is the most prevalent and aggressive primary brain malignancy in adults. Nevertheless, the cellular heterogeneity and complexity within the GBM microenvironment (TME) are still not fully understood, posing a significant obstacle in the advancement of more efficient immunotherapies for GBM. In this study, we conducted an integrated analysis of 48 tumor fragments from 24 GBM patients at the single-cell level, uncovering substantial molecular diversity within immune infiltrates. We characterized molecular signatures for five distinct tumor-associated macrophage (TAM) subtypes. Notably, the TAM_MRC1 subtype displayed a pronounced M2 polarization signature. Additionally, we identified a subtype of natural killer (NK) cells, designated CD56dim_DNAJB1. This subtype is characterized by an exhausted phenotype, evidenced by an elevated stress signature and enrichment in the PD-L1/PD-1 checkpoint pathway. Our findings also highlight significant cell-cell interactions among malignant glioma cells, TAM, and NK cells within the TME. Overall, this research sheds light on the functional heterogeneity of glioma and immune cells in the TME, providing potential targets for therapeutic intervention in this immunologically cold cancer.
Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells
Authors: Wang Xin , Wang Kun , Zhang Weixing , Tang Zhongjie , Zhang Hao , Cheng Yuying , Zhou Da , Zhang Chao , Zhong Wen-Zhao , Ma Qing , Xu Jin , Hu Zheng
Published: May 2024

Although mitochondrial DNA (mtDNA) variants hold promise as endogenous barcodes for tracking human cell lineages, their efficacy as reliable lineage markers is hindered by the complex dynamics of mtDNA in somatic tissues. Here, we utilized computational modeling and single-cell genomics to thoroughly interrogate the origin and clonal dynamics of mtDNA lineage markers across various biological settings. Our findings revealed the majority of purported “clone informative variants (CIVs)” were pre-existing heteroplamies in the first cell instead ofde novosomatic mutations during divisions. Moreover, CIVs demonstrated limited discriminatory power among different lineages during normal development; however, certain CIVs with consistently high allele frequencies proved capable of faithfully labeling cell lineages in scenarios of stringent clonal expansion. Inspired by our simulations, we introduced a lineage informative (LI) score, facilitating the identification of reliable mitochondrial lineage markers across different modalities of single-cell genomic data.
Nimodipine-Associated Standard Dose Reductions and Neurologic Outcomes After Aneurysmal Subarachnoid Hemorrhage: The Era of Pharmacogenomics
Authors: Vázquez-Medina Adriana , Turnbull Marion T. , James Courtney L. , Cowart Jennifer B. , Lesser Elizabeth , Carter Rickey E. , Ross Owen A. , Miller David A. , Meschia James F. , De Jesús Espinosa Aixa , Weinshilboum Richard , Freeman W. David
Published: May 2024

Nimodipine, an L-type cerebroselective calcium channel antagonist, is the only drug approved by the US Food and Drug Administration for the neuroprotection of patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized, placebo-controlled trials of nimodipine demonstrated clinical improvement over placebo; however, these occurred before precision medicine with pharmacogenomics was readily available. The standard enteral dose of nimodipine recommended after aSAH is 60 mg every 4 hours. However, up to 78% of patients with aSAH develop systemic arterial hypotension after taking the drug at the recommended dose, which could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure and cerebral blood flow, particularly when concomitant vasospasm is present. We investigated the association between nimodipine dose changes and clinical outcomes in a consecutive series of 150 patients (mean age, 56 years; 70.7% women) with acute aSAH. We describe the pharmacogenomic relationship of nimodipine dose reduction with clinical outcomes. These results have major implications for future individualized dosing of nimodipine in the era of precision medicine.
Using models to identify the causes of pre-symptomatic transmission from human infection data
Authors: Zhang Kayla , Pak Damie , Greischar Megan A.
Published: May 2024

When disease transmission can precede symptom onset, containing outbreaks requires distinct strategies, like active surveillance. Yet it is rarely clear in advance when such interventions are needed, especially for emerging pathogens. Predicting pre-symptomatic transmission would be easier with knowledge of the within-host dynamics that enable pre-symptomatic transmission. To investigate those dynamics, we survey controlled human infection (CHI) trials with viral agents, which contain data on incubation times, infection duration, and transmission potential following inoculation with a known dose. We find that all studies report information on the duration of viral shedding, but few report the timing of symptoms. Only one study provided data on the timing of shedding and symptoms for individual participants, following norovirus inoculation. We apply a statistical model to individual time series to show significantly greater potential for pre-symptomatic transmission with faster viral replication, but no evidence for a tradeoff between transmission rate and duration during the pre-symptomatic phase. We then compare within-host models of pathogen replication, immune clearance, and symptom onset to identify plausible assumptions about the causes of pre-symptomatic transmission. We recover the pattern that peak shedding can precede symptom onset if we assume that symptoms are triggered by immune responses rather than pathogen abundance. Only by relaxing the standard assumption of exponential growth can we recover the pattern that faster viral replication enables pre-symptomatic transmission. Thus, data on symptom onset in CHI trials, paired with models, can illuminate the within-host dynamics underpinning pre-symptomatic transmission, guiding efforts to improve control strategies.

Significance statement

The COVID-19 pandemic was exacerbated by the potential for transmission before symptoms. Yet the causes of pre-symptomatic transmission remain unclear, hindering efforts to predict disease spread and tailor control efforts for novel pathogens. For known pathogens, the potential for pre-symptomatic transmission varies across individuals, but patterns may emerge from controlled human infection (CHI) trials. We surveyed CHI trials, finding that only one reported data on individual participants. We fit a simple model to those data, finding that faster viral replication correlates with pre-symptomatic transmission. We used more detailed models to identify plausible assumptions about the causes of symptom onset, e.g., that immune responses trigger symptoms. Thus, applying models to CHI trial data gives insight into the drivers of pre-symptomatic transmission.
Regulation of Neuronal Chloride Homeostasis by Pro- and Mature Brain-Derived Neurotrophic Factor (BDNF) via KCC2 Cation-Chloride Cotransporters in Rat Cortical Neurons
Authors: Hamze Mira , Brier Cathy , Buhler Emmanuelle , Zhang Jinwei , Medina Igor , Porcher Christophe
Published: May 2024

The strength of inhibitory neurotransmission depends on intracellular neuronal chloride concentration, primarily regulated by the activity of cation-chloride cotransporters NKCC1 and KCC2. Brain-derived neurotrophic factor (BDNF) influences the functioning of these co-transporters. BDNF is synthesized from precursor proteins (proBDNF), which undergo proteolytic cleavage to yield mature BDNF (mBDNF). While previous studies have indicated the involvement of BDNF signaling in the activity of KCC2, its specific mechanisms are unclear. We investigated the interplay between both forms of BDNF and chloride homeostasis in rat hippocampal neurons andin-uteroelectroporated cortices of rat pups, spanning the behavioral, cellular, and molecular levels. We found that both pro– and mBDNF play a comparable role in immature neurons by inhibiting the capacity of neurons to extrude chloride. Additionally, proBDNF increases the endocytosis of KCC2 while maintaining a depolarizing shift of EGABAin maturing neurons. Behaviorally, proBDNF-electroporated rat pups in the somatosensory cortex exhibit sensory deficits delayed huddling and cliff avoidance. These findings emphasize the role of BDNF signaling in regulating chloride transport through the modulation of KCC2. In summary, this study provides valuable insights into the intricate interplay between BDNF, chloride homeostasis, and inhibitory synaptic transmission, shedding light on the underlying cellular mechanisms involved.
Thermal and electric field driven rf breakdown precursor formation on metal surfaces
Authors: Shinohara Ryo , Bagchi Soumendu , Simakov Evgenya , Baryshev Sergey V. , Perez Danny
Published: May 2024

The phenomenon of electric breakdown poses serious challenges to the design of devices that operate in high electric field environments. Experimental evidence points toward breakdown events that are accompanied by elevated temperatures and dark current spikes, which is attributed to high-asperity nanostructure formation that enhances the local electric field and triggers a runaway process. However, the exact mechanistic origin of such nanostructures under typical macroscopic operational conditions of electric field and magnetic-field-mediated heating remains poorly understood. In this work, we simulate the evolution of a copper surface under the combined action of the electric fields and elevated temperatures. Using a mesoscale curvature-driven surface evolution model, we show how a copper surface can undergo a type of dynamical instability that naturally leads to the formation of sharp asperities in realistic experimental conditions. Exploring the combined effect of fields and temperature rise, we identify the critical regimes that allow for the formation of breakdown precursors. The results show that thermoelastic stresses, while not essential, can significantly lower the critical electric field required for runaway surface instability, which is consistent with experimental observations that thermal effects can increase breakdown rates.

Published by the American Physical Society
2024
Gravitational waves from a scotogenic two-loop neutrino mass model
Authors: Bonilla Cesar , Hernández A. E. Cárcamo , Gonçalves João , N. Vishnudath K. , Morais António P. , Pasechnik R.
Published: May 2024

We propose a framework to account for neutrino masses at the two-loop level. This mechanism introduces new scalars and Majorana fermions to the Standard Model. It assumes the existence of a global U(1)×Z2 symmetry which after partial breaking provides the stability of the dark matter candidates of the theory. The rich structure of the potential allows for the possibility of first-order phase transitions (FOPTs) in the early Universe which can lead to the generation of primordial gravitational waves. Taking into account relevant constraints from lepton flavor violation, neutrino physics, as well as the trilinear Higgs couplings at next-to-leading order accuracy, we have found a wide range of possible FOPTs which are strong enough to be probed at the proposed gravitational-wave interferometer experiments such as LISA.

Published by the American Physical Society
2024
Bound states from the spectral Bethe-Salpeter equation
Authors: Eichmann Gernot , Gómez Andrés , Horak Jan , Pawlowski Jan M. , Wessely Jonas , Wink Nicolas
Published: May 2024

We compute the bound state properties of three-dimensional scalar ϕ4 theory in the broken phase. To this end, we extend the recently developed technique of spectral Dyson-Schwinger equations to solve the Bethe-Salpeter equation and determine the bound state spectrum. We employ consistent truncations for the two-, three- and four-point functions of the theory that recover the scaling properties in the infinite coupling limit. Our result for the mass of the lowest-lying bound state in this limit agrees very well with lattice determinations.

Published by the American Physical Society
2024
Multimessenger search for electrophilic feebly interacting particles from supernovae
Authors: Luque Pedro De la Torre , Balaji Shyam , Carenza Pierluca
Published: May 2024

We study MeV-scale electrophilic feebly interacting particles (FIPs), that may be abundantly produced in supernova explosions, escape the star and decay into electrons and positrons. This exotic injection of leptons in the Milky Way leaves an imprint in both photon and cosmic ray fluxes. Specifically, positrons lose energy and annihilate almost at rest with background electrons, producing photons with 511 keV energy. In addition, electrons and positrons radiate photons through bremsstrahlung emission and upscatter the low-energy galactic photon fields via the inverse Compton process generating a broad emission from x-ray to γ ray energies. Finally, electrons and positrons are directly observable in cosmic ray experiments. In order to describe the FIP-induced lepton injection in full generality, we use a model-independent parametrization which can be applied to a host of FIPs such as axionlike particles, dark photons and sterile neutrinos. Theoretical predictions are compared to experimental data to robustly constrain FIP-electron interactions with an innovative multimessenger analysis.

Published by the American Physical Society
2024
Methyl 2-hydroxy-4-iodobenzoate
Authors: Kimble Marten J. , Myers Shea D. , Benedict Jason B
Published: May 2024

The structure of the title compound, C8H7IO3, at 90 K has monoclinic (P21/c) symmetry. The extended structure is layered and displays intermolecular and intramolecular hydrogen bonding arising from the same OH group.
An incoming threat: the influence of automation potential on job insecurity
Authors: Cao Jieqiong , Song Zhaoli
Published: May 2024

Purpose

In today’s digital age, news and social media are abuzz with ChatGPT and a myriad of advanced AI tools. Experts from disciplines like computer science and socioeconomics have discussed the profound transformations AI can bring. While certain industries have embraced AI, its penetration across all sectors remains uneven. Yet, even with this limited adoption, the psychological ramifications it presents for workplace employees are profound. Our study integrated social information processing and transactional stress theories to analyze the effect of automation brought by AI on job insecurity. Our study also considers whether moderating factors like supervisor–subordinate relationships and social media engagement can alleviate the adverse consequences of automation.

Design/methodology/approach

We empirically test our research hypotheses with longitudinal data from the US General Social Survey (GSS).

Findings

Using US General Social Survey data, our findings indicate that employees in industries with high automation potential are more susceptible to job insecurity. Interestingly, social media engagement appears to dampen this relationship, while the quality of the supervisor–subordinate relationship shows negligible impact.

Originality/value

This study provides valuable insights into the effects of automation potential and the role of social media engagement in coping with it, making a meaningful contribution to the existing literature in this area.
Assessing the effect of open innovation on firm performance: a study of Indian IT organisations
Authors: Grandhi Srimannarayana , Chhetri Prem , Molla Alemayehu
Published: May 2024

Purpose

There is a growing interest among academics, government agencies and private organisations to examine the scale, characteristics, and impact of Open Innovation (OI). Studies have examined these issues mainly in the context of a developed world. Because firms in developing economies face unique challenges of OI such as building networks, inter-firm interactions, collaboration for resource utilisation and knowledge sharing, these warrant an examination of the theoretical relationships between the antecedents of OI and their impact on performance as well as mediators of these relationships. Therefore, this study develops a comprehensive OI framework to measure open innovation and analyse its effect on the innovation performance of Indian IT organisations.

Design/methodology/approach

Theoretically, the study draws upon the Resource-Based View, Relational View, and Absorptive Capacity theories. Empirically, a survey questionnaire was distributed to Indian IT organisations through the online survey tool “Qualtrics”. The research framework was tested using the data collected from 346 Indian IT organisations.

Findings

The results highlight the positive effect of OI activities on innovation performance and the mediating role of absorptive capacity. IT organisations with a higher inbound knowledge and absorptive capacity demonstrated better innovation performance.

Research limitations/implications

This study is limited to understanding the mediating effect of absorptive capacity for inbound innovation. Future studies into the mediating role of desorption capacity could reveal its impact on innovation performance.

Practical implications

From a management perspective, this knowledge will enable managers and policymakers to emphasise OI to achieve better innovation performance. This knowledge will provide both government decision-makers and IT managers with definite OI implications for innovation performance.

Originality/value

The main contribution of this study lies in exploring the interconnectedness among IT organisations and collaborative processes on OI and innovation performance. This empirical study pinpoints the causes and sources of OI that would lead to innovation performance and the mediating role of absorptive capacity in achieving innovation performance. It extends the empirical base of OI scholarship based on firms in an emerging economy.
Do corporate governance mechanisms and ESG disclosures improve bank performance and stability in an emerging economy?
Authors: Sain Anjali , Kashiramka Smita
Published: May 2024

Purpose

This paper aims to investigate the impact of corporate governance mechanisms and the environmental, social and governance (ESG) disclosure score on bank performance and financial stability. Further, this paper analyses how this relationship varies over the different ownership structures.

Design/methodology/approach

The paper uses a sample of 41 Indian banks (including both public sector and private sector banks) over the period ranging from 2008 to 2020. The data is analyzed in both static and dynamic frameworks using panel regression and system generalized methods of moments.

Findings

The results indicate that the frequency of board meetings has a negative influence on the performance of the banks. Gender diversity reveals both linear and non-linear relationships with bank performance. In the sample of public sector banks, the board size and promoters’ ownership have a significant negative effect on the bank's performance. In private sector banks, CEO duality adversely affects performance. Further, the results indicate that ESG disclosure score is positively linked with the profitability of banks.

Originality/value

This paper provides a comprehensive analysis of the impact of corporate governance mechanisms and ESG disclosure scores on bank performance and stability in the context of the Indian economy. To the best of the authors’ knowledge, there has been no empirical investigation or study that has been conducted in this respect.
Artificial intelligence, self-efficacy and engagement in religious tourism: evidence from Arbaeen pilgrimage
Authors: Khan Naseer Abbas
Published: May 2024

Purpose

This study aims to determine how the attitudes toward artificial intelligence (AI) of religious tourists affect their AI self-efficacy and their engagement in AI. This study specifically intends to investigate the mediating role of AI self-efficacy in the relationship between attitudes toward AI and the engagement in AI of religious tourists. This study also seeks to identify the role of AI assistant use as a moderator in the relationship between attitudes toward AI and AI self-efficacy.

Design/methodology/approach

The data used in this study was gathered from a sample of 282 religious tourists who had just visited Karbala, central Iraq. Purposive sampling, which comprises a focused and systematic approach to data collection, was used after carefully assessing the distinctive characteristics and properties of the research population.

Findings

The results showed that attitudes to AI had a noticeable impact on AI self-efficacy, which, in turn, exerted a positive impact on engagement with AI. In addition, the use of AI assistants acted to positively moderate AI self-efficacy in terms of mediating the link between attitudes to AI and AI engagement.

Originality/value

The distinctive focus on religious tourists adds an original perspective to the existing literature, shedding light on how their attitudes towards AI impact not only their self-efficacy but also their engagement in dealing with AI. In addition, this study delves into the moderating role of AI assistant use, introducing a unique factor in understanding the complex interplay between attitudes, self-efficacy, and engagement in the context of religious tourism. The selection of Karbala, central Iraq, as this study site further adds originality, providing insights into a specific religious and cultural context.
Unveiling the role of novel carbohydrate‐binding modules in laminarin interaction of multimodular proteins from marine Bacteroidota during phytoplankton blooms
Authors: Zühlke Marie‐Katherin , Ficko‐Blean Elizabeth , Bartosik Daniel , Terrapon Nicolas , Jeudy Alexandra , Jam Murielle , Wang Fengqing , Welsch Norma , Dürwald Alexandra , Martin Laura Torres , Larocque Robert , Jouanneau Diane , Eisenack Tom , Thomas François , Trautwein‐Schult Anke , Teeling Hanno , Becher Dörte , Schweder Thomas , Czjzek Mirjam
Published: May 2024

Laminarin, a β(1,3)‐glucan, serves as a storage polysaccharide in marine microalgae such as diatoms. Its abundance, water solubility and simple structure make it an appealing substrate for marine bacteria. Consequently, many marine bacteria have evolved strategies to scavenge and decompose laminarin, employing carbohydrate‐binding modules (CBMs) as crucial components. In this study, we characterized two previously unassigned domains as laminarin‐binding CBMs in multimodular proteins from the marine bacterium Christiangramia forsetii KT0803T, thereby introducing the new laminarin‐binding CBM families CBM102 and CBM103. We identified four CBM102s in a surface glycan‐binding protein (SGBP) and a single CBM103 linked to a glycoside hydrolase module from family 16 (GH16_3). Our analysis revealed that both modular proteins have an elongated shape, with GH16_3 exhibiting greater flexibility than SGBP. This flexibility may aid in the recognition and/or degradation of laminarin, while the constraints in SGBP could facilitate the docking of laminarin onto the bacterial surface. Exploration of bacterial metagenome‐assembled genomes (MAGs) from phytoplankton blooms in the North Sea showed that both laminarin‐binding CBM families are widespread among marine Bacteroidota. The high protein abundance of CBM102‐ and CBM103‐containing proteins during phytoplankton blooms further emphasizes their significance in marine laminarin utilization.
Medicare and Priority Populations: Structural and Place‐based Considerations for Aboriginal and Torres Strait Islander Peoples and LGBTIQ+ Australians
Authors: Saxby Karinna , Stephens Mike
Published: May 2024

The past 40 years of Medicare have seen effective policy for reducing income‐related inequities in healthcare use. In this article, we describe how past and current Medicare policies have shaped, and continue to shape, healthcare access for other priority populations—Aboriginal and Torres Strait Islander peoples and LGBTIQ+ populations. Drawing on empirical evidence, we also document the importance of structural‐, place‐ and demographic‐specific nuance when designing and implementing such policies. We conclude by offering recommendations on how Medicare can strive for better and more equitable access for these priority populations over the next 40 years and beyond.
Harnessing artificial intelligence‐driven industrial robotics for sustainability: Insights from leading green economies
Authors: Qing Lingli , Shahbaz Muhammad , Meo Muhammad Saeed , Jamshed Yasir , Li Likun
Published: May 2024

In 2023, global temperatures witnessed an alarming escalation, reaching an unprecedented 1.46°C above preindustrial levels, marking it as the hottest year on record. Simultaneously, atmospheric carbon dioxide surpassed 420 ppm, exceeding a stability maintained for over 6000 years by more than double. This troubling surge in CO2 intensifies global warming, leading to an increased frequency of extreme weather events and contributing to 24% of global deaths attributed to environmental concerns. These alarming environmental challenges demand urgent attention and the implementation of innovative policies. Responding to this imperative, the study examines the impact of artificial intelligence‐based industrial robotics (AIIR) and other control variables such as green energy, green finance, and green energy investment on CO2 emissions in economies supporting green initiatives, including Canada, Denmark, China, Japan, New Zealand, Norway, Sweden, and Switzerland. Using monthly data from 2008 to 2021 and a novel nonlinear autoregressive distributed lag approach, the results indicate that AIIR significantly reduces CO2 emissions in the sample economies. Additionally, green energy, green finance, and green energy investment also significantly decrease CO2 emissions. The study's outcomes bear policy implications for decision‐makers in the sampled economies, offering tangible insights for effective environmental management.
Controlled production of lipopolysaccharides increases immune activation in Salmonella treatments of cancer
Authors: Howell Lars M. , Manole Simin , Reitter Alec R. , Forbes Neil S.
Published: May 2024

Immunotherapies have revolutionized cancer treatment. These treatments rely on immune cell activation in tumours, which limits the number of patients that respond. Inflammatory molecules, like lipopolysaccharides (LPS), can activate innate immune cells, which convert tumour microenvironments from cold to hot, and increase therapeutic efficacy. However, systemic delivery of lipopolysaccharides (LPS) can induce cytokine storm. In this work, we developed immune‐controlling Salmonella (ICS) that only produce LPS in tumours after colonization and systemic clearance. We tuned the expression of msbB, which controls production of immunogenic LPS, by optimizing its ribosomal binding sites and protein degradation tags. This genetic system induced a controllable inflammatory response and increased dendritic cell cross‐presentation in vitro. The strong off state did not induce TNFα production and prevented adverse events when injected into mice. The accumulation of ICS in tumours after intravenous injection focused immune responses specifically to tumours. Tumour‐specific expression of msbB increased infiltration of immune cells, activated monocytes and neutrophils, increased tumour levels of IL‐6, and activated CD8 T cells in draining lymph nodes. These immune responses reduced tumour growth and increased mouse survival. By increasing the efficacy of bacterial anti‐cancer therapy, localized production of LPS could provide increased options to patients with immune‐resistant cancers.
Potential role of damselflies in the pollination of Callitriche rimosa Fasset
Authors: de Araújo‐Hoffmann Francielle Paulina , Hoffmann Diego , da Silva Ângela Pelissari , Correia da Rocha‐Filho Léo
Published: May 2024

While most flowering plant species rely on animal pollinators, approximately 10% of angiosperms utilize wind or water for pollination. Moreover, certain species can have mixed pollination system—ambophily—wherein both biotic and abiotic agents contribute to pollen transport. Upon frequent observation of damselflies (Coenagrionidae) perching on Callitriche rimosa Fassetv (Plantaginaceae), an aquatic herb with small flowers protruding above the water's surface, we hypothesized their potential contribution to the pollination of this primarily abiotically pollinated plant. Observations were conducted along the shores of a pond in southern Brazil. Damselflies were seen carrying pollen grains on their legs from C. rimosa leaves, where pollen falls from the anthers and remains exposed. Given damselflies' activity levels during summer, incidental contact with C. rimosa reproductive structures facilitates cross‐pollination. This interaction may facilitate both plants and insects, considering damselflies' dependence on freshwater bodies and use of C. rimosa leaves for perching. Accessory pollen presentation on leaves may convert occasional visitors into pollinators, expanding the pollination niche of C. rimosa. Recognizing lesser‐known pollinators like damselflies is crucial for understanding plant reproduction in diverse ecosystems.
Rediscovery of the endangered giant pangolin (Smutsia gigantea) in Senegal after 24 years
Authors: Ndiaye Mouhamadou Mody , Drouilly Marine , Senghor Abdoul Aziz , Thiaw Ousmane , Ingram Daniel J. , Shirley Matthew H. , Strampelli Paolo , Marti Chele Martinez , Henschel Philipp
Published: May 2024

Pangolins have generated great interest in recent years, largely due to the unprecedented scale of trafficking the species experiences. Detailed knowledge of pangolin distribution in West Africa is lacking, but many local extinctions are suspected. The last documented sighting of a giant pangolin in Senegal was in Niokolo‐Koba National Park (NKNP) and dates back to 1999. Following a large camera‐trap survey carried out in NKNP in 2023, we present photographic evidence that giant pangolins are still present in the park. Such rediscoveries not only underscore the importance of systematic biodiversity inventories, but also the critical value of West Africa's large protected areas.
Staining pattern of specific and cross‐reacting Melan‐A antibodies: A comparative study on 15,840 samples from 133 human tumor types
Authors: Boroojerdi Shiva , Weidemann Sören , Menz Anne , Lennartz Maximilian , Dwertmann Rico Sebastian , Schlichter Ria , Kind Simon , Reiswich Viktor , Viehweger Florian , Bawahab Ahmed Abdulwahab , Höflmeyer Doris , Fraune Christoph , Gorbokon Natalia , Luebke Andreas M. , Hube‐Magg Claudia , Büscheck Franziska , Krech Till , Hinsch Andrea , Jacobsen Frank , Burandt Eike , Sauter Guido , Simon Ronald , Kluth Martina , Steurer Stefan , Minner Sarah , Marx Andreas H. , Bernreuther Christian , Clauditz Till S. , Dum David , Lebok Patrick
Published: May 2024

The Melan‐A (melanocyte antigen) protein, also termed ‘melanoma antigen recognized by T cells 1’ (MART‐1) is a protein with unknown function whose expression is specific for the melanocyte lineage. Antibodies against Melan‐A are thus used for identifying melanocytic tumors, but some Melan‐A antibodies show an additional – diagnostically useful – cross‐reactivity against an unspecified protein involved in corticosteroid hormone synthesis. To comprehensively compare the staining patterns of a specific and a cross‐reactive Melan‐A antibody in normal and neoplastic tissues, tissue microarrays containing 15,840 samples from 133 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. For the Melan‐A‐specific antibody ‘Melan‐A specific’ (MSVA‐900M), Melan‐A positivity was seen in 96.0% of 25 benign nevi, 93.0% of 40 primary and 86.7% of 75 metastatic melanomas, 82.4% of 85 renal angiomyolipomas as well as 96.4% of 84 neurofibromas, 2.2% of 46 granular cell tumors, 1.0% of 104 schwannomas, and 1.1% of 87 leiomyosarcomas. The cross‐reactive antibody ‘Melan‐A+' (MSVA‐901M+) stained 98.1% of the tumors stained by ‘Melan‐A specific’. In addition, high positivity rates were seen in sex‐cord‐stroma tumors of the ovary (35.3%–100%) and the testis (86.7%) as well as for adrenocortical neoplasms (76.3%–83.0%). Only nine further tumor groups showed Melan‐A+ staining, including five different categories of urothelial carcinomas. Our data provide a comprehensive overview on the staining patterns of specific and cross‐reactive Melan‐A antibodies. The data demonstrate that both antibodies are highly useful for their specific purpose. It is important for pathologists to distinguish these two Melan‐A antibody subtypes for their daily work.
Activity of propyl‐propane‐thiosulfinate and propyl‐propane‐thiosulfonate against carbapenem‐resistant Gram‐negative bacteria
Authors: Sorlózano‐Puerto Antonio , Cerezo‐Collado Laura , Roca‐Lagrilliere Elvira , Baños‐Arjona Alberto , Gutiérrez‐Fernández José
Published: May 2024

Organosulfur compounds derived from plants of the Allium genus, such as propyl‐propane‐thiosulfinate (PTS) and propyl‐propane‐thiosulfonate (PTSO), have been proposed as an alternative in antibiotic resistance. The aim of this study was to compare the activity of these substances with other antibiotics against clinical isolates of carbapenem‐resistant (CAR‐R) and carbapenem‐susceptible (CAR‐S) Gram‐negative bacteria. A total of 126 clinical isolates of CAR‐R and 155 CAR‐S bacteria were selected, including Enterobacterales, A. baumannii and P. aeruginosa. The antibiotic susceptibility of all isolates was assessed using the microdilution and Kirby–Bauer methods for PTS, PTSO, amoxicillin/clavulanate, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, ciprofloxacin, and amikacin. Both PTS and PTSO demonstrated in vitro bactericidal activity against CAR‐R Enterobacteriaceae and A. baumannii, with no significant difference in activity compared to their response against CAR‐S isolates. However, both compounds were less active against P. aeruginosa than against any of the other bacteria, regardless of their resistance to carbapenems. In all cases, the minimum inhibitory concentration values of PTSO were significantly lower than those of PTS. These findings offer valuable information about the potential antibacterial use of these substances, particularly against infections that currently have limited therapeutic options.
Editorial: Has MetALD met the presumption? Authors' reply
Authors: Tamaki Nobuharu , Kimura Takefumi , Wakabayashi Shun‐Ichi , Umemura Takeji , Izumi Namiki , Loomba Rohit , Kurosaki Masayuki
Published: May 2024

LINKED CONTENT

This article is linked to Tamaki et al papers. To view these articles, visit https://doi.org/10.1111/apt.18015 and https://doi.org/10.1111/apt.18034
Assessing the influence of organisational citizenship behaviour towards environment on economic cost performance in UAE hotels
Authors: Pillai Rekha , Islam Aminul , Kumar Parul , Almustafa Hamza
Published: May 2024

Organisational citizenship behaviour towards the environment (OCBE) aids in both environmental protection and in harnessing sustainable competitive organisational advantage. This study proposed a conceptual research model which investigated managerial perceptions of the relationship between OCBE and economic cost performance (ECP) in the UAE hospitality sector, with green innovative behaviour (GIB) mediating and green training moderating the relationship. Drawing on the theory of planned behaviour and abilities motivation opportunity theory, the study administered 479 structured questionnaires to hotel managers in the UAE using purposive and snowball sampling techniques. Partial least squares structural equation modelling was applied to test the hypotheses in SmartPLS3.3. Findings showed that OCBE had a direct and significant impact on ECP, with GIB emerging both as a direct and mediating predictor. Additionally, green training directly and significantly moderated the OCBE–cost performance relationship. These results evince the integration of sustainable philosophies with innovative mindsets to encourage green innovative endeavours among hotel managers.
The CATFISH study: An evaluation of a water fluoridation program in Cumbria, UK
Authors: Goodwin Michaela , Walsh Tanya , Whittaker William , Emsley Richard , Kelly Michael P. , Sutton Matt , Tickle Martin , Pretty Iain A.
Published: May 2024

Objectives

The objective was to assess the effectiveness of a Water Fluoridation program on a contemporary population of children.

Methods

The study used a longitudinal prospective cohort design.

In Cumbria, England, two groups of children were recruited and observed over a period of 5–6 years. The Birth Cohort consisted of families recruited from two hospitals in Cumbria where children were conceived after water fluoridation was reintroduced. The systemic and topical effects of community water fluoridation were evaluated in the Birth Cohort. The Older Cohort were approximately 5 years old and recruited from primary schools in Cumbria, shortly after water fluoridation was reintroduced. The predominantly topical effects of fluoridated water were evaluated in the Older Cohort.

The primary outcome was the proportion of children with clinical evidence of caries experience in their primary (Birth Cohort) or permanent teeth (Older Cohort). Unadjusted and adjusted regression models were used for analysis.

Results

The final clinical examinations for the Birth Cohort involved 1444 participants (mean age 4.8 years), where 17.4% of children in the intervention group were found to have caries experience, compared to 21.4% in the control group. A beneficial effect of water fluoridation was observed adjusting for deprivation (a socioeconomic measure), sex, and age, (adjusted odds ratio 0.74 95% CI 0.55 to 0.98). The final Older Cohort clinical examinations involved 1192 participants (mean age 10.8 years) where 19.1% of children in the intervention group were found to have caries experience compared to 21.9% in the control group (adjusted odds ratio 0.80, 95% CI 0.58 to 1.09). For both the Birth Cohort and Older Cohort there was evidence of a beneficial effect on dmft/DMFT count (IRR 0.61, 95% CI 0.44, 0.86) and (IRR 0.69, 95% CI 0.52, 0.93) respectively. No conclusive proof was found to indicate that the effectiveness of water fluoridation differed across area deprivation quintiles.

Conclusions

In the contemporary context of lower caries levels and widespread use of fluoride toothpaste, the impact of water fluoridation on the prevalence of caries was smaller than previous studies have reported. It is important to consider the clinical importance of the absolute reduction in caries prevalence against the use of other dental caries preventive measures.
Emergency Risk Assessments in Child Welfare Services: Developing Structured Support to Professional Assessments
Authors: Wollter Filip , Eriksson Maria
Published: May 2024

The article presents a study on structured support for the professional assessment of emergent domestic violence in families with children. Data are presented on the development and study of a new structured support called iRiSk emergency, which was developed jointly by the authors of this article, and an emergency social work unit in Stockholm, Sweden. The model was developed from the iRiSk model, which, translated from Swedish, stands for ‘Interventions and Risk and Protection Assessments for children exposed to violence’. Structured support for emergency risk assessments is rare as existing instruments mainly focus on screening for violence and are not designed to guide professionals in situations of identified violence. The purpose of the research project is elaborated through two research questions: (1) Which information is needed for emergency assessments, and how can it be collected? (2) What are the specific preconditions of the child welfare service emergency work to be taken into account in terms of emergency risk assessments? The feedback from the social workers was that iRiSk emergency was flexible to use, decreased the risk of missing important risk factors and made the assessments more child‐centred. The model appears to be a viable approach for enhancing the systematic evaluation and testing of structured support for emergency risk assessment in social work, surpassing the limitations of the current study.