bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of dependencies between climate risks on the asset and liability side of non-life insurers
Authors: Gatzert Nadine , Özdil Onur
Published: October 2023

The aim of this paper is to examine the impact of dependencies between climate transition and physical risks on the default probability and profitability of a non-life insurer focusing on the scenario of a delayed and sudden transition. Toward this end, we suggest a simplified modeling approach for scenario analyses for climate risks affecting assets and liabilities, taking into account potential nonlinear dependence structures. Our results show that dependencies on the liability side and between assets and liabilities in the context of physical-transition scenarios can have a significant impact, particularly on the default risk of a non-life insurer. We additionally analyze the mitigating effects of stop loss reinsurance and risk-adjusted pricing, which—if implementable—seem to be an effective risk management measure against physical climate risks in particular.
A novel integrated approach based on best–worst and VIKOR methods for green supplier selection under multi-granularity extended probabilistic linguistic environment
Authors: Zhu Chuanjin , Wang Xia
Published: October 2023

With consideration for the extensive resources consumption and environmental degradation being on the rise today, implementing green development strategy to pursue both socioeconomic growth and the coordinated of environment sustainability, has become an increasingly important issue in modern enterprise supply chain operations management. Hence, the appropriate green supplier selection (GSS), viewed as a core issue in green supply chain management (GSCM), requires continuous research in this field to obtain a complete perception on GSS practices. It can be regarded as a multi-attribute group decision-making (MAGDM) problem that involves many conflict and unmeasurable evaluation criteria. In view of the superiority of multi-granularity extended probabilistic linguistic term sets (MGEPLTSs) in modeling such issues on potential ambiguity, complexity and uncertainty in actual GSS practices, we propose a novel integrated MAGDM methodology for GSS problems, by integrating the BWM (best–worst method) with the VIKOR (VIšekriterijumsko KOmpromisno Rangiranje) technique under the MGEPLTSs environment. First, by introducing the multi-granularity and probabilistic linguistic term sets, the MGEPLTSs are proposed to represent and quantify the decision information of GSCM practitioners. Then, the BWM is introduced to the MGEPLTSs environment to compute the weights of decision-making panels and evaluation attributes in GSS problems, by building the fuzzy mathematical programming model, respectively. Finally, we extend a multi-granularity extended probabilistic linguistic VIKOR method to calculate the compromise measure of alternatives considering the group utility maximization and the individual regret minimization, thereby achieving the full ranking of alternatives. A GSS case is conducted to illustrate the feasibility of the proposed approach, and the sensitivity analysis and comparative analysis with other similar approaches are presented to demonstrate its effectiveness and advantages.
Engineering Fe-N4 Electronic Structure with Adjacent Co-N2C2 and Co Nanoclusters on Carbon Nanotubes for Efficient Oxygen Electrocatalysis
Authors: Wu Mingjie , Yang Xiaohua , Cui Xun , Chen Ning , Du Lei , Cherif Mohamed , Chiang Fu-Kuo , Wen Yuren , Hassanpour Amir , Vidal François , Omanovic Sasha , Yang Yingkui , Sun Shuhui , Zhang Gaixia
Published: October 2023

Regulating the local configuration of atomically dispersed transition-metal atom catalysts is the key to oxygen electrocatalysis performance enhancement. Unlike the previously reported single-atom or dual-atom configurations, we designed a new type of binary-atom catalyst, through engineering Fe-N4 electronic structure with adjacent Co-N2C2 and nitrogen-coordinated Co nanoclusters, as oxygen electrocatalysts. The resultant optimized electronic structure of the Fe-N4 active center favors the binding capability of intermediates and enhances oxygen reduction reaction (ORR) activity in both alkaline and acid conditions. In addition, anchoring M–N–C atomic sites on highly graphitized carbon supports guarantees of efficient charge- and mass-transports, and escorts the high bifunctional catalytic activity of the entire catalyst. Further, through the combination of electrochemical studies and in-situ X-ray absorption spectroscopy analyses, the ORR degradation mechanisms under highly oxidative conditions during oxygen evolution reaction processes were revealed. This work developed a new binary-atom catalyst and systematically investigates the effect of highly oxidative environments on ORR electrochemical behavior. It demonstrates the strategy for facilitating oxygen electrocatalytic activity and stability of the atomically dispersed M–N–C catalysts.
Can Job Demands and Job Resources Predict Bystander Behaviour in Workplace Bullying? A Longitudinal Study
Authors: Holm Kristoffer , Jönsson Sandra , Muhonen Tuija
Published: October 2023

Bystanders can affect workplace bullying by engaging in active or passive behaviours. However, there is a knowledge gap regarding how perceived work environment factors relate to bystander behaviour. The study aim was to investigate how job demands, and job resources are associated with bystander behaviour in workplace bullying. An online questionnaire was distributed to a sample of health care workers at two time points. Longitudinal data were obtained from 1144 respondents. Cross-lagged panel models were used to investigate associations between job demands, job resources, and bystander behaviours over time. The results showed that social support was positively related to active behaviours, whereas influence at work was negatively related to both active and passive behaviours. Perceived illegitimate tasks were negatively related to active and positively related to passive behaviours, whereas emotional demands had an unanticipated opposite pattern of relationships. The findings provide new information about how factors in the organisational and social work environment are associated with active and passive bystander behaviours in workplace bullying. Specifically, the results expand current understanding of workplace bullying by relating bystander behaviour to the organisational context.
Induction of Tolerance in Groundnut Plants Against Drought Stress and Cercospora Leaf Spot Disease with Exogenous Application of Arginine and Sodium Nitroprusside Under Field Conditions
Authors: Bakhoum Gehan Sh. , Sadak Mervat Sh. , Thabet Marian S.
Published: October 2023

Naturally, under field conditions, plants are regularly experienced by a mixture of two or more stress factors. Drought is a major abiotic stress, and fungal pathogens characterize a main biotic stress challenge faced by plants and impact negatively on plant development and productivity. We propose that foliar application of nitric oxide (NO) donors can have positive effects on the induction of tolerance to biotic and abiotic stress on groundnut plants. This investigation was carried out to study the changes in growth, some biochemical aspects, and yield and quality of groundnut plants as well as induction of resistance to Cercospora leaf spot disease in response to nitric oxide (NO) donors, sodium nitroprusside (SNP), and arginine (Arg) (2.5, 5.0, and 7.5 mM) under two water irrigation levels 100% and 75% of water irrigation requirements (WIR), in two field experiments through two successive growing seasons of 2021 and 2022. Decreasing irrigation water significantly reduced shoot length, branches numberplant-1, shoot fresh and dry weight, photosynthetic pigments components, endogenous indole acetic acid (IAA) contents, and yield components. Furthermore, root fresh and dry weight, phenols, total soluble sugars (TSS), proline contents, and the accumulation of hydrogen peroxide (H2O2) and lipid peroxidation of groundnut leaves increased significantly. Contrarily, foliar application with Arg and SNP alleviated the negative influences of drought on growth and productivity of groundnut plants via enhancing photosynthetic pigments, IAA, phenolic compounds, TSS, and proline contents. Additionally, SNP and Arg significantly decreased oxidative damage through decreasing H2O2 and lipid peroxidation by the induction of antioxidant enzymes. Remarkably, the increase of drought level led to a reduction in Cercospora leaf spot (CLS) disease with the use of high concentrations of both Arg and SNP. Interestingly, in both stressed and unstressed plants, SNP treatment at 7.5 mM was the most effective in reducing the incidence and severity of disease, while Arg at 2.5 mM recorded the lowest reduction compared to other treatments. In conclusion, foliar treatment of either SNP or Arg is a profound effect on modulating the drought stress and induction of resistance to Cercospora leaf spot disease of groundnut plants throughout regulating physiological and biochemical processes associated with photosynthesis and oxidative responses.
The Coevolution of Descriptive and Evaluative Beliefs in Aldo Leopold’s Thinking
Authors: Millstein Roberta L.
Published: October 2023

The founder of conservation biology, Michael Soulé, set out a vision for conservation biology that was explicitly value-laden, analogous to cancer-biology. In so doing, he drew on the writings of Aldo Leopold, known among philosophers primarily for his land ethic. Employing and extending the work of Anderson (2004) and Clough (2020), I argue that the Leopoldian views that Soulé was drawing on were the product of the coevolution of descriptive and evaluative beliefs over the course of Leopold’s life, grounded in his experiences, resulting in tested and reliable—albeit defeasible—values underlying conservation biology.
Modeling Scaffolded Development into the Adjacent Possible Environment
Authors: Griesemer James
Published: October 2023

I characterize a role for “environments” as ecological scaffolding of organism development in the evolution of novelty. I interpret Rainey’s bacterial experimental system for empirically modeling evolutionary transition to multicellularity as an ecological-developmental problem in terms of a formal model of Kauffman’s concept of evolution into the “adjacent possible.” I propose a scenario to interpret scaffolds dynamically, treating them as organisms modeled in the same way as the developing systems they scaffold, rather than as fixed constraint boundary conditions. The scenario suggests avenues for mathematically modeling scaffolding dynamics.
Path-Dependence in Measurement: A Problem for Coherentism
Authors: Thompson Morgan
Published: October 2023

Racial discrimination is a multidimensional concept. Yet, subjective measures of racial discrimination focus on particular dimensions (interpersonal over institutional, attributable over ambiguously attributable). I argue that there is path dependence in the development and validation of subjective measures, such that existing scales prevent the development of scales that are better for some purpose. Path dependence can occur when researchers: (1) adopt a coherentist view of measurement, namely, in iteratively refining constructs and measures and (2) employ current psychometric validation practices. The main takeaway is that norms are needed to evaluate the initial refinement of the construct rather than taking it for granted.
Strategic Constraints on Interacting Fields: Quantum Chemistry and Organic Chemistry
Authors: Goodwin William
Published: October 2023

The interaction between scientific fields may be subject to strategic constraints—that is, fruitful interaction between fields may require adapting one field to the strategies informing the other. One way the concepts within an interfield field develop is by recrafting concepts originating in one practice in terms compatible with the strategies guiding the other. This conceptual accommodation may be a prerequisite to fruitful interactions between fields with different central problems. I explore these themes by considering the strategic constraints operative in the interfield field of quantum chemistry and the conceptual accommodation required for application to organic chemistry.
Wealth of Tongues: Why Peripheral Regions Vote for the Radical Right in Germany
Authors: ZIBLATT DANIEL , HILBIG HANNO , BISCHOF DANIEL
Published: October 2023

Why is support the radical right higher in some geographic locations than others? This article argues that what is frequently classified as the “rural” bases of radical-right support in previous research is in part the result of something different: communities that were in the historical “periphery” in the center–periphery conflicts of modern nation-state formation. Inspired by a classic state-building literature that emphasizes the prevalence of a “wealth of tongues”—or nonstandard linguistic dialects in a region—as a definition of the periphery, we use data from more than 725,000 geo-coded responses in a linguistic survey in Germany to show that voters from historically peripheral geographic communities are more likely to vote for the radical right today.
Non-thermal particle acceleration and power-law tails via relaxation to universal Lynden-Bell equilibria
Authors: Ewart R.J. , Nastac M.L. , Schekochihin A.A.
Published: October 2023

Collisionless and weakly collisional plasmas often exhibit non-thermal quasi-equilibria. Among these quasi-equilibria, distributions with power-law tails are ubiquitous. It is shown that the statistical-mechanical approach originally suggested by Lynden-Bell (Mon. Not. R. Astron. Soc., vol. 136, 1967, p. 101) can easily recover such power-law tails. Moreover, we show that, despite the apparent diversity of Lynden-Bell equilibria, a generic form of the equilibrium distribution at high energies is a ‘hard’ power-law tail$\propto \varepsilon ^{-2}$, where$\varepsilon$is the particle energy. The shape of the ‘core’ of the distribution, located at low energies, retains some dependence on the initial condition but it is the tail (or ‘halo’) that contains most of the energy. Thus, a degree of universality exists in collisionless plasmas.
Longitudinal associations between psychedelic use and meditation practices in the United States and the United Kingdom
Authors: Simonsson Otto , Osika Walter , Stenfors Cecilia U. D. , Goldberg Simon B. , Honk Ludwig , Hendricks Peter S.
Published: October 2023

Background

Previous research has proposed that there may be potential synergies between psychedelic and meditation interventions, but there are still knowledge gaps that merit further investigation.

Methods

Using a longitudinal observational research design with samples representative of the US and UK adult population with regard to sex, age, and ethnicity (N = 9732), we investigated potential associations between self-reported psychedelic use and meditation practice.

Results

The follow-up survey was completed by 7667 respondents (79% retention rate), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of follow-up respondents). In covariate-adjusted regression models, psychedelic use during the study period was associated with greater increases in the number of days of mindfulness meditation practice in the past week (B = 0.40, p = 0.004). Among those who reported psychedelic use during the study period, covariate-adjusted regression models revealed that the subjective experience of insight during respondents' most intense psychedelic experience in that period was also associated with greater increases in the number of days of mindfulness and loving-kindness or compassion meditation practice in the past week (B = 0.42, p = 0.021; B = 0.38, p = 0.017). Notably, more days of loving-kindness or compassion meditation practice in the past week at baseline was associated with less severe subjective feelings of death or dying during respondents' most intense psychedelic experience in the study period (B = −0.29, p = 0.037).

Conclusions

Psychedelic use might lead to greater engagement with meditation practices such as mindfulness meditation, while meditation practices such as loving-kindness or compassion medication might buffer against certain challenging experiences associated with psychedelic use.
Intermedial Cross-dressing Performance as Cultural Intervention
Authors: He Chengzhou
Published: October 2023

As a theatrical phenomenon, cross-dressing performance has passed down through many centuries and manifested itself in different parts of the world. In the era of film and television, it was adapted to and has appeared on screen, as a popular means of entertaining the audience, and so plays an important role in influencing public opinions on certain social and cultural issues, such as the politics of gender and interculturalism. In light of theories of gender performativity and cultural agency, the intermediality of cross-dressing performance is approached in this article, mainly based on a careful analysis of Li Yugang’s solo shows on TV, the Chinese film Farewell My Concubine, and the American film M. Butterfly. By having the intermedial intersected with gender and interculturalism, this article argues that intermedial cross-dressing performance, on the one hand, has transformative power over gender politics, as it contributes to the gradual acceptance of differences in gender as well as other social categories. On the other hand, in some cross-dressing performances on screen, the subversive and the reiterative are blended together in cross-dressing performance, which undermines the legitimization of sexual orientations outside of the heterosexual norms. In addition, the entanglement of intermediality and interculturalism in cross-dressing performance in such a film as M. Butterfly contributes to critical reflections on cultural and categorical boundaries, which has profound implications for cross-cultural communications.
Media between Media: ‘Making-of’s and the Hidden Faces of Film Adaptation
Authors: Mousavi Nafiseh
Published: October 2023

Comparing source and target media products is the main intermedial method for studying adaptations. The inventory of similarities and differences produced by such an endeavour provides evidence for the processes of transfer and transformation that have happened between the two media. But the finished media products are not the only traces of the process of adaptation. In practices of adaptation that happen inside media industries, such as film adaptations, the process is also documented in different forms and for different archival or market-oriented purposes. The process of film adaptation is, for instance, usually captured – although in fragments and in a staged format – by intermediary filmic media products – such as ‘making of’s – that are rarely considered as the main study objects in adaptation studies. As this article argues, such processual ways of looking at adaptations do not undermine the importance of comparative approaches but complicate the grounds for comparison. Suggesting a methodological shift to the process, the article expands this idea through a cross-pollination between adaptation studies and (media) production studies and exemplifies it through discussion of examples and one extended case study.
Unveiling shadows: analyzing suicide reporting in Muslim-majority countries vis-à-vis WHO’s media guidelines
Authors: Mahesar Rameez A. , Shahid Sana , Asif Saba , Khoso Abdul K. , Kar Sujita K. , Shabbir Taha
Published: October 2023

Numerous studies have been conducted globally to assess the compliance level of newspapers with the World Health Organization’s media guidelines for responsible suicide reporting. To identify and review such studies conducted in Muslim-majority countries between 2014 and 2022, we searched PubMed and Google Scholar databases. We identified 12 eligible studies from Pakistan (n = 4), Bangladesh (n = 2), Malaysia (n = 1), Indonesia (n = 1), Iraq (n = 1), Iran (n = 1), Nigeria (n = 1), and Egypt (n = 1). These studies indicated an overall lack of adherence to the guidelines. However, the level of nonadherence was particularly high in Pakistan. Effective suicide prevention programs may help in promoting responsible reporting of suicide.
Understanding demand for flexible pension payouts: evidence from the Netherlands
Authors: Dillingh Rik , Zumbuehl Maria
Published: October 2023

This study examines the interest in different pension payout schemes when full annuitization is the default. We focus on three possible pension payout schemes: a flat-rate annuity, a high/low annuity-based profile, and a partial lump sum at retirement with a lower flat-rate annuity after that. We make use of a vignette study and find substantial interest in each of the three payout schemes. Interest in the lump sum scheme increases when a higher percentage can be taken out as a lump sum or when interest rates or replacement rates are lower. Interest in a high/low annuity-based profile increases when the high annuity is valid for a shorter period.
COVID-19 risk, course and outcome in people with mental disorders: a systematic review and meta-analyses
Authors: Molero Patricio , Reina Gabriel , Blom Jan Dirk , Martínez-González Miguel Ángel , Reinken Aischa , de Kloet E. Ronald , Molendijk Marc L.
Published: October 2023

Aims

It has been suggested that people with mental disorders have an elevated risk to acquire severe acute respiratory syndrome coronavirus 2 and to be disproportionally affected by coronavirus disease 19 (COVID-19) once infected. We aimed to analyse the COVID-19 infection rate, course and outcome, including mortality and long COVID, in people with anxiety, depressive, neurodevelopmental, schizophrenia spectrum and substance use disorders relative to control subjects without these disorders.

Methods

This study constitutes a preregistered systematic review and random-effects frequentist and Bayesian meta-analyses. Major databases were searched up until 27 June 2023.

Results

Eighty-one original articles were included reporting 304 cross-sectional and prospective effect size estimates (median n per effect-size = 114837) regarding associations of interest. Infection risk was not significantly increased for any mental disorder that we investigated relative to samples of people without these disorders. The course of COVID-19, however, is relatively severe, and long COVID and COVID-19-related hospitalization are more likely in all patient samples that we investigated. The odds of dying from COVID-19 were high in people with most types of mental disorders, except for those with anxiety and neurodevelopmental disorders relative to non-patient samples (pooled ORs range, 1.26–2.57). Bayesian analyses confirmed the findings from the frequentist approach and complemented them with estimates of the strength of evidence.

Conclusions

Once infected, people with pre-existing mental disorders are at an elevated risk for a severe COVID-19 course and outcome, including long COVID and mortality, relative to people without pre-existing mental disorders, despite an infection risk not significantly increased.
Microbial cell autofluorescence as a method for measuring the intracellular content of B2 and B6 vitamins
Authors: Maslanka Roman , Przywara Michał , Janeczko Agnieszka , Zadrag-Tecza Renata
Published: October 2023

Abstract: Vitamins are important organic compound required for the proper functioning of cells and organisms. Vitamins of special industrial and pharmaceutical interests include riboflavin (vitamin B2) and pyridoxine (vitamin B6). Commercial production of those biological compounds has increasingly relied on microorganisms and requires simple methods for detecting and estimating their level of synthesis during the biotechnological process. In the case of yeast, methods based on autofluorescence, i.e. natural fluorescence emitted by several cellular compounds, including vitamins, may be useful. Considering that the intensity of emitted light is proportional to the intracellular concentration of riboflavin and pyridoxine, autofluorescence may be a convenient method for their quantification. In this report, we demonstrate a simple, rapid, and sufficiently trustworthy spectrofluorimetric method for determining the content of vitamins B2 and B6 in yeast cells which consists of cells growing, harvesting, washing, and resuspending in a buffer, and then measuring the emitted visible light using specific wavelength of excitation (λex=340 nm and λem=385 nm for pyridoxine; λex=460 nm and λem=535 nm for riboflavin). The limits of detection (LOD) and quantification (LOQ) estimated through measurements of vitamin fluorescence were below 0.005 μg/ml for riboflavin and below 0.05 μg/ml for pyridoxine, respectively. In turn, the smallest credible cell density for measuring autofluorescence was set at 1×108 yeast cells/ml. The relative level of the cell’s autofluorescence can be expressed in mass units by applying proper calculation formulas. A comparison of the autofluorescence-based method with the reference HPLC-UV method shows that autofluorescence measurement can be used in the screening analysis of vitamin content (especially riboflavin) in microbial cells.
Characteristics of Lunar Surface Electrons Inferred From ARTEMIS Observations: 1. Backscattered Electrons
Authors: Xu Shaosui , Poppe Andrew R. , Szabo Paul S. , Harada Yuki , Halekas Jasper S. , Chamberlin Phillip C.
Published: October 2023

Lunar surface charging is a scientifically and practically important topic at the Moon that is largely determined by the electron currents near the surface. Among those electron populations, lunar photoelectrons (PHE) and backscattered electrons (BSE) produced by incident electrons that make up the high‐energy tail of lunar emitted electrons are not well characterized yet. Recently, Xu et al. (2021, https://doi.org/10.1029/2020je006790) reported oxygen Auger electron observations at the Moon by the Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun spacecraft, which provides a unique feature to identify lunar photoelectrons. We utilize this feature to isolate cases of emitted electrons dominated by BSE over PHE. With selected BSE cases, we characterize how the backscattering coefficient η varies with primary electron energy, which decreases with increasing energy. Our results also reveal η to be dependent on the magnetic dip angle, as a fraction of BSE re‐impact the surface in a magnetized environment. The characterization of the backscattering coefficient not only gives insights into the lunar surface properties and lunar surface charging but could also be potentially applied to other airless bodies.
Ensemble Forecasts of Solar Wind Connectivity to 1 Rs Using ADAPT‐WSA
Authors: da Silva D. E. , Wallace S. , Arge C. N. , Jones S.
Published: October 2023

The solar wind which arrives at any location in the solar system is, in principle, relatable to the outflow of solar plasma from a single source location. This source location, itself usually being part of a larger coronal hole, is traceable to 1 RS along the Sun's magnetic field, in which the entire path from 1 RS to a location in the heliosphere is referred to as the solar wind connectivity. While not directly measurable, the connectivity between the near‐Earth solar wind is of particular importance to space weather. The solar wind solar source region can be obtained by leveraging near‐sun magnetic field models and a model of the interplanetary solar wind. In this article, we present a method for making an ensemble forecast of the connectivity presented as a probability distribution obtained from a weighted collection of individual forecasts from the combined Air Force Data Assimilative Photospheric Flux Transport‐Wang Sheeley Arge (ADAPT‐WSA) model. The ADAPT model derives the photospheric magnetic field from synchronic magnetogram data, using flux transport physics and ongoing data assimilation processes. The WSA model uses a coupled set of potential field type models to derive the coronal magnetic field, and an empirical relationship to derive the terminal solar wind speed observed at Earth. Our method produces an arbitrary 2D probability distribution capable of reflecting complex source configurations with minimal assumptions about the distribution structure, prepared in a computationally efficient manner.
Dual network analysis of transcriptome data for discovery of new therapeutic targets in non-small cell lung cancer
Authors: Bai Yuquan , Zhou Lu , Zhang Chuanfen , Guo Minzhang , Xia Liang , Tang Zhenying , Liu Yi , Deng Senyi
Published: October 2023

The drug therapy for non-small cell lung cancer (NSCLC) have always been issues of poisonous side effect, acquired drug resistance and narrow applicable population. In this study, we built a novel network analysis method (difference- correlation- enrichment- causality- node), which was based on the difference analysis, Spearman correlation network analysis, biological function analysis and Bayesian causality network analysis to discover new therapeutic target of NSCLC in the sequencing data of BEAS-2B and 7 NSCLC cell lines. Our results showed that, as a proteasome subunit coding gene in the central of cell cycle network, PSMD2 was associated with prognosis and was an independent prognostic factor for NSCLC patients. Knockout of PSMD2 inhibited the proliferation of NSCLC cells by inducing cell cycle arrest, and exhibited marked increase of cell cycle blocking protein p21, p27 and decrease of cell cycle driven protein CDK4, CDK6, CCND1 and CCNE1. IPA and molecular docking suggested bortezomib has stronger affinity to PSMD2 compared with reported targets PSMB1 and PSMB5. In vitro and In vivo experiments demonstrated the inhibitory effect of bortezomib in NSCLC with different driven mutations or with tyrosine kinase inhibitors resistance. Taken together, bortezomib could target PSMD2, PSMB1 and PSMB5 to inhibit the proteasome degradation of cell cycle check points, to block cell proliferation of NSCLC, which was potential optional drug for NSCLC patients.
From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress
Authors: Dewdney Brittany , Jenkins Misty R. , Best Sarah A. , Freytag Saskia , Prasad Krishneel , Holst Jeff , Endersby Raelene , Johns Terrance G.
Published: October 2023

Glioblastoma, a rare, and highly lethal form of brain cancer, poses significant challenges in terms of therapeutic resistance, and poor survival rates for both adult and paediatric patients alike. Despite advancements in brain cancer research driven by a technological revolution, translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need. This review emphasises the intricate role of receptor tyrosine kinase signalling pathways, epigenetic mechanisms, and metabolic functions in glioblastoma tumourigenesis and therapeutic resistance. We also discuss the extensive efforts over the past two decades that have explored targeted therapies against these pathways. Emerging therapeutic approaches, such as antibody-toxin conjugates or CAR T cell therapies, offer potential by specifically targeting proteins on the glioblastoma cell surface. Combination strategies incorporating protein-targeted therapy and immune-based therapies demonstrate great promise for future clinical research. Moreover, gaining insights into the role of cell-of-origin in glioblastoma treatment response holds the potential to advance precision medicine approaches. Addressing these challenges is crucial to improving outcomes for glioblastoma patients and moving towards more effective precision therapies.
Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12
Authors: Keyan Kripa S , Salim Safa , Gowda Swetha , Abdelrahman Doua , Amir Syeda Sakina , Islam Zeyaul , Vargas Claire , Bengoechea-Alonso Maria Teresa , Alwa Amira , Dahal Subrat , Kolatkar Prasanna R. , Da’as Sahar , Torrisani Jerome , Ericsson Johan , Mohammad Farhan , Khan Omar M
Published: October 2023

Transforming growth factor β (TGFβ) pathway is a master regulator of cell proliferation, differentiation, and death. Deregulation of TGFβ signalling is well established in several human diseases including autoimmune disorders and cancer. Thus, understanding molecular pathways governing TGFβ signalling may help better understand the underlying causes of some of those conditions. Here, we show that a HECT domain E3 ubiquitin ligase TRIP12 controls TGFβ signalling in multiple models. Interestingly, TRIP12 control of TGFβ signalling is completely independent of its E3 ubiquitin ligase activity. Instead, TRIP12 recruits SMURF2 to SMAD4, which is most likely responsible for inhibitory monoubiquitination of SMAD4, since SMAD4 monoubiquitination and its interaction with SMURF2 were dramatically downregulated in TRIP12-/- cells. Additionally, genetic inhibition of TRIP12 in human and murine cells leads to robust activation of TGFβ signalling which was rescued by re-introducing wildtype TRIP12 or a catalytically inactive C1959A mutant. Importantly, TRIP12 control of TGFβ signalling is evolutionary conserved. Indeed, genetic inhibition of Drosophila TRIP12 orthologue, ctrip, in gut leads to a reduced number of intestinal stem cells which was compensated by the increase in differentiated enteroendocrine cells. These effects were completely normalised in Drosophila strain where ctrip was co-inhibited together with Drosophila SMAD4 orthologue, Medea. Similarly, in murine 3D intestinal organoids, CRISPR/Cas9 mediated genetic targeting of Trip12 enhances TGFβ mediated proliferation arrest and cell death. Finally, CRISPR/Cas9 mediated genetic targeting of TRIP12 in MDA-MB-231 breast cancer cells enhances the TGFβ induced migratory capacity of these cells which was rescued to the wildtype level by re-introducing wildtype TRIP12. Our work establishes TRIP12 as an evolutionary conserved modulator of TGFβ signalling in health and disease.
RhoA balances microglial reactivity and survival during neuroinflammation
Authors: Socodato Renato , Rodrigues-Santos Artur , Tedim-Moreira Joana , Almeida Tiago O. , Canedo Teresa , Portugal Camila C. , Relvas João B.
Published: October 2023

Microglia are the largest myeloid cell population in the brain. During injury, disease, or inflammation, microglia adopt different functional states primarily involved in restoring brain homeostasis. However, sustained or exacerbated microglia inflammatory reactivity can lead to brain damage. Dynamic cytoskeleton reorganization correlates with alterations of microglial reactivity driven by external cues, and proteins controlling cytoskeletal reorganization, such as the Rho GTPase RhoA, are well positioned to refine or adjust the functional state of the microglia during injury, disease, or inflammation. Here, we use multi-biosensor-based live-cell imaging approaches and tissue-specific conditional gene ablation in mice to understand the role of RhoA in microglial response to inflammation. We found that a decrease in RhoA activity is an absolute requirement for microglial metabolic reprogramming and reactivity to inflammation. However, without RhoA, inflammation disrupts Ca2+ and pH homeostasis, dampening mitochondrial function, worsening microglial necrosis, and triggering microglial apoptosis. Our results suggest that a minimum level of RhoA activity is obligatory to concatenate microglia inflammatory reactivity and survival during neuroinflammation.
Perspective: Residual penile curvature correction during penile prosthesis implantation by plication in Peyronie’s patients
Authors: Chung Eric , Blecher Gideon
Published: October 2023

For patients with large calcified tunical plaque or severe corporal fibrosis which are likely to have a pronounced and persistent residual curvature which may not be correct by penile prosthesis implantation alone, other adjunctive manoeuvres such as penile plication and/or plaque incision with grafting may be necessary. The sequence between penile plication and penile prosthesis implantation is largely dependent on several factors such as the severity of penile curvature, the presence of (calcified) tunical plaque(s) and whether aggressive corporal dilation and subsequent penile remodelling with an inflated implant can straighten any residual penis curvature. The advantages of pre-placement of penile plication sutures prior to penile prosthesis implantation are the avoidance of inadvertent damage to the underlying penile prosthesis implant, the ability to adjust the tension on the rows of the plication sutures based on residual curvature with the device fully inflated, and potentially minimising the duration of surgery. In contrast, penile prosthesis implantation followed by penile plication to correct residual curvature, this sequence of surgery may negate the need for penile plications if penile remodelling is effective, or the residual curvature is less than 15 degrees where postoperative manual remodelling may continue to improve the penile cosmesis. When performed by expert surgeons and adhering to safe surgical principles, there is no doubt that patients will be satisfied with the outcomes and highly appreciative of the final penile cosmesis and the ensuing optimal outcomes.
An exact chiral amorphous spin liquid
Authors: Cassella G. , d’Ornellas P. , Hodson T. , Natori W. M. H. , Knolle J.
Published: October 2023

Topological insulator phases of non-interacting particles have been generalized from periodic crystals to amorphous lattices, which raises the question whether topologically ordered quantum many-body phases may similarly exist in amorphous systems? Here we construct a soluble chiral amorphous quantum spin liquid by extending the Kitaev honeycomb model to random lattices with fixed coordination number three. The model retains its exact solubility but the presence of plaquettes with an odd number of sides leads to a spontaneous breaking of time reversal symmetry. We unearth a rich phase diagram displaying Abelian as well as a non-Abelian quantum spin liquid phases with a remarkably simple ground state flux pattern. Furthermore, we show that the system undergoes a finite-temperature phase transition to a conducting thermal metal state and discuss possible experimental realisations.
Disease-specific loss of microbial cross-feeding interactions in the human gut
Authors: Marcelino Vanessa R. , Welsh Caitlin , Diener Christian , Gulliver Emily L. , Rutten Emily L. , Young Remy B. , Giles Edward M. , Gibbons Sean M. , Greening Chris , Forster Samuel C.
Published: October 2023

Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases. When applied to a Crohn’s disease case-control study, our approach identifies a lack of species with the ability to consume hydrogen sulfide as the main distinguishing microbiome feature of disease. We propose that our conceptual framework will help prioritize in-depth analyses, experiments and clinical targets, and that targeting the restoration of microbial cross-feeding interactions is a promising mechanism-informed strategy to reconstruct a healthy gut ecosystem.
American crows that excel at tool use activate neural circuits distinct from less talented individuals
Authors: Pendergraft LomaJohn T. , Marzluff John M. , Cross Donna J. , Shimizu Toru , Templeton Christopher N.
Published: October 2023

Tools enable animals to exploit and command new resources. However, the neural circuits underpinning tool use and how neural activity varies with an animal’s tool proficiency, are only known for humans and some other primates. We use 18F-fluorodeoxyglucose positron emission tomography to image the brain activity of naïve vs trained American crows (Corvus brachyrhynchos) when presented with a task requiring the use of stone tools. As in humans, talent affects the neural circuits activated by crows as they prepare to execute the task. Naïve and less proficient crows use neural circuits associated with sensory- and higher-order processing centers (the mesopallium and nidopallium), while highly proficient individuals increase activity in circuits associated with motor learning and tactile control (hippocampus, tegmentum, nucleus basorostralis, and cerebellum). Greater proficiency is found primarily in adult female crows and may reflect their need to use more cognitively complex strategies, like tool use, to obtain food.
Dynamic neural representations of memory and space during human ambulatory navigation
Authors: Maoz Sabrina L. L. , Stangl Matthias , Topalovic Uros , Batista Daniel , Hiller Sonja , Aghajan Zahra M. , Knowlton Barbara , Stern John , Langevin Jean-Philippe , Fried Itzhak , Eliashiv Dawn , Suthana Nanthia
Published: October 2023

Our ability to recall memories of personal experiences is an essential part of daily life. These episodic memories often involve movement through space and thus require continuous encoding of one’s position relative to the surrounding environment. The medial temporal lobe (MTL) is thought to be critically involved, based on studies in freely moving rodents and stationary humans. However, it remains unclear if and how the MTL represents both space and memory especially during physical navigation, given challenges associated with deep brain recordings in humans during movement. We recorded intracranial electroencephalographic (iEEG) activity while participants completed an ambulatory spatial memory task within an immersive virtual reality environment. MTL theta activity was modulated by successful memory retrieval or spatial positions within the environment, depending on dynamically changing behavioral goals. Altogether, these results demonstrate how human MTL oscillations can represent both memory and space in a temporally flexible manner during freely moving navigation.
Structural insights into the agonists binding and receptor selectivity of human histamine H4 receptor
Authors: Im Dohyun , Kishikawa Jun-ichi , Shiimura Yuki , Hisano Hiromi , Ito Akane , Fujita-Fujiharu Yoko , Sugita Yukihiko , Noda Takeshi , Kato Takayuki , Asada Hidetsugu , Iwata So
Published: October 2023

Histamine is a biogenic amine that participates in allergic and inflammatory processes by stimulating histamine receptors. The histamine H4 receptor (H4R) is a potential therapeutic target for chronic inflammatory diseases such as asthma and atopic dermatitis. Here, we show the cryo-electron microscopy structures of the H4R-Gq complex bound with an endogenous agonist histamine or the selective agonist imetit bound in the orthosteric binding pocket. The structures demonstrate binding mode of histamine agonists and that the subtype-selective agonist binding causes conformational changes in Phe3447.39, which, in turn, form the “aromatic slot”. The results provide insights into the molecular underpinnings of the agonism of H4R and subtype selectivity of histamine receptors, and show that the H4R structures may be valuable in rational drug design of drugs targeting the H4R.
Resonant cavity phosphor
Authors: Lee Tae-Yun , Park Yeonsang , Jeon Heonsu
Published: October 2023

While phosphors play an immensely important role in solid-state lighting and full-colour displays, it has been noted lately that their performance can be largely improved via structural engineering. Here, phosphor material is synergistically merged with yet another structurally engineered platform, resonant cavity (RC). When a 40-nm-thick colloidal quantum dot (CQD) film is embedded in a tailored RC with a moderate cavity quality factor (Q ≈ 90), it gains the ability to absorb the majority (~87%) of excitation photons, resulting in significantly enhanced CQD fluorescence (~29×) across a reasonably broad linewidth (~13 nm). The colour gamut covered by red and green pixels implemented using the RC phosphor—along with a broad bandwidth (~20 nm) blue excitation source—exceeds that of the sRGB standard (~121%). The simple planar geometry facilitates design and implementation of the RC phosphor, making it promising for use in real applications.
The airway microbiota of neonates colonized with asthma-associated pathogenic bacteria
Authors: Thorsen Jonathan , Li Xuan Ji , Peng Shuang , Sunde Rikke Bjersand , Shah Shiraz A. , Bhattacharyya Madhumita , Poulsen Casper Sahl , Poulsen Christina Egeø , Leal Rodriguez Cristina , Widdowson Michael , Neumann Avidan Uriel , Trivedi Urvish , Chawes Bo , Bønnelykke Klaus , Bisgaard Hans , Sørensen Søren J. , Stokholm Jakob
Published: October 2023

Culture techniques have associated colonization with pathogenic bacteria in the airways of neonates with later risk of childhood asthma, whereas more recent studies utilizing sequencing techniques have shown the same phenomenon with specific anaerobic taxa. Here, we analyze nasopharyngeal swabs from 1 month neonates in the COPSAC2000prospective birth cohort by 16S rRNA gene sequencing of the V3-V4 region in relation to asthma risk throughout childhood. Results are compared with previous culture results from hypopharyngeal aspirates from the same cohort and with hypopharyngeal sequencing data from the later COPSAC2010cohort. Nasopharyngeal relative abundance values ofStreptococcus pneumoniae, Haemophilus influenzae, andMoraxella catarrhalisare associated with the same species in the hypopharyngeal cultures. A combined pathogen score of these bacteria’s abundance values is associated with persistent wheeze/asthma by age 7. No other taxa are associated. Compared to the hypopharyngeal aspirates from the COPSAC2010cohort, the anaerobesVeillonellaandPrevotella, which have previously been implicated in asthma development, are less commonly detected in the COPSAC2000nasopharyngeal samples, but correlate with the pathogen score, hinting at latent community structures that bridge current and previous results. These findings have implications for future asthma prevention efforts.
Preservation versus resection of Denonvilliers’ fascia in total mesorectal excision for male rectal cancer: follow-up analysis of the randomized PUF-01 trial
Authors: Fang Jiafeng , Wei Bo , Zheng Zongheng , Xiao Jian’an , Han Fanghai , Huang Meijin , Xu Qingwen , Wang Xiaozhong , Hong Chuyuan , Wang Gongping , Ju Yongle , Su Guoqiang , Deng Haijun , Zhang Jinxin , Li Jun , Yang Xiaofeng , Chen Tufeng , Huang Yong , Huang Jianglong , Liu Jianpei , Wei Hongbo ,   Chinese Postoperative Urogenital Function (PUF) Research Collaboration Group
Published: October 2023

Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers’ fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.