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Retrospective stratified analysis of resistance mechanisms to anti-EGFR therapy in mCRC using tumor tissue samples
Androgens inhibit protective CD8+ T cell responses against pre-erythrocytic malaria parasites in mice
Determinants of voluntary disclosure: An empirical analysis of financial, market, and organizational factors
This study systematically examines the determinants of voluntary disclosure by listed companies in Japan, where non-financial disclosure is not legally mandated. Using quarterly data from 5,915 companies between 2009 and 2024, a logistic regression analysis was conducted to assess the influence of financial indicators, company characteristics, stock exchange, industry classification, and shareholder composition. The results reveal that ISO certification (ISO 14001 and ISO 45001) significantly promotes voluntary disclosure. Firm size and listing on a prime market are positively associated with disclosure, whereas foreign market listings tend to suppress disclosure—contrary to conventional theories. Additionally, manufacturing and IT sectors are proactive in disclosure, whereas the agriculture, forestry, fishing, and mining sectors are more reluctant. Shareholder composition also plays a crucial role, with financial institution shareholders promoting disclosure and corporate shareholders suppressing it. By leveraging Japan’s unique voluntary disclosure environment, this study offers new insights into corporate transparency and the strategic design of disclosure policies.
Ponto-Caspian mysid shrimp Paramysis lacustris has reached the Elbe estuary
Abstract As part of monitoring conducted alongside a river engineering project, the Ponto-Caspian mysid shrimp Paramysis lacustris (P. lacustris) was detected for the first time in the tidal Elbe in August 2023. Alongside P. lacustris, a second Ponto-Caspian mysid species, Limnomysis benedeni (L. benedeni), was also identified. The previous year’s investigation yielded no records of these mysids, suggesting that the species, last observed in 2019 in the Havel River in Saxony-Anhalt, are currently expanding into the tidal Elbe. In addition to addressing sampling aspects, we present the dispersal pathway of P. lacustris since its first recorded observation in 1882 and discuss the probable impact of the newly found species in the river Elbe based on former findings.
An AI-assisted fluorescence microscopic system for screening mitophagy inducers by simultaneous analysis of mitophagic intermediates
Description of two new species and a new population of Mesobiotus cf. coronatus from Cotacachi-Cayapas National Park, Ecuador
In this study, we present descriptions of two new eutardigrade species and additionally a detailed description of new population of Mesobiotus cf. coronatus discovered in the Cotacachi-Cayapas National Park in Ecuador. The presented analysis is based on morphological and morphometric data using light and scanning electron microscopy; description of Macrobiotus sharopovi sp. nov. and the population of Mesobiotus cf. coronatus were also supported with genetic data (nuclear barcode sequences, i.e., 18S rRNA, 28S rRNA and ITS-2, and one mitochondrial COI sequence). Based on the egg morphology, Mac. sharopovi sp. nov. belongs to Mac. paulinae morpho-group and is most similar to Mac. papei, Mac. paulinae, Mac. polypiformis and Mac. shonaicus but differs from them mainly by some characters of eggs (number of egg processes on circumference, details of eggshell morphology and features of filaments and their number) and adults (size of cuticular pores). Based on such features as the presence of gibbosities and well visible dorsal sculpture, the second new species, i.e., Ramazzottius syraxi sp. nov. is the most similar to Ram. baumanni species complex, Ram. belubellus, Ram. saltensis and Ram. szeptycki but differs from them by gibbosities configuration and morphology of dorsal sculpture. Mesobiotus cf. coronatus, which belongs to Meb. harmsworthi morpho-group, is potentially a new species but due to unclear taxonomic position of nominal Meb. coronatus, a formal description of this taxon is not possible in the present study.
NMDA receptor antagonists mitigate COVID-19-induced neuroinflammation and improve survival in a mouse model
Hydroxymethanesulfonate formation accelerated at the air-water interface by synergistic enthalpy-entropy effects
Abstract Hydroxymethanesulfonate is a key organosulfate linked to severe fine-particle pollution in fog and clouds, yet its rapid formation mechanism at the air-water interface remains elusive. Here, using metadynamics-biased ab initio molecular dynamics simulations, high-level quantum chemical calculations and reaction density functional theory, we reveal that synergistic enthalpy-entropy effects govern the nucleophilic addition between bisulfite and formaldehyde. Compared to the gaseous reaction, the aqueous reaction faces a ~5.0 kcal/mol water reorganization barrier, partly offset by polarization effects. Ab initio molecular dynamics simulations show hydrogen bonding networks facilitate proton transfer via the Grotthuss mechanism, reducing activation entropy by ~5.5 kcal/mol. At the interface, partial solvation and restricted formaldehyde motion lower the enthalpy and configurational entropy by ~1.0 and ~0.9 kcal/mol, respectively, alongside a 1.9 kcal/mol electric field effect. These combined effects enhance the interfacial reaction rate by two orders of magnitude, offering insights into heterogeneous chemistry and strategies for winter haze mitigation.
Conflicting trends in violent crime measured by police recorded crime and the crime survey in England and Wales since 2010
Police recorded violent crime (PRC) and the Crime Survey of England and Wales (CSEW) show substantially different trends in the rates of violent crime according to the Office of National Statistics (ONS), with rates rising in police data and falling in survey data. Both the PRC and CSEW have suffered periods in which the UK Statistics Authority has withdrawn their quality approval as ‘national statistics’. This paper investigates a possible seven reasons for the disparity in the trend and volume of violent crime between the PRC and CSEW, with a focus on the processes of measurement deployed. The paper offers a new way to compare the methods and outcomes of the two data sources, by developing an ‘aligned’ data set to support comparison of trends in the PRC CSEW data since 2010. It analyses data from the PRC and from different sections of the CSEW, the main face-to-face module, the self-completion module on domestic abuse, and the children’s module asked of those aged 10–15 years. We offer new estimates of the volume and discussion on the trend in violent crime since 2010. We estimate that there were 5,164,983 violent crimes in 2022/3. This is significantly higher than the estimate provided by the ONS based on CSEW data. The estimate of the trend is uncertain, but challenges over-confidence in the assumption that it is declining. We conclude that improvements in police accuracy in recording crime explains part of the difference, and the exclusion from sampling of vulnerable groups by the CSEW another part, with the recent reduction in the survey’s response rate to 42% giving further quality concerns. We determine that the CSEW has always underestimated violent crime, and this has become visible now that police data has improved.
ICRF193 potentiates the genotoxicity of etoposide
Abstract ICRF193 is a catalytic inhibitor of Topoisomerase 2 (TOP2), one of the major targets in cancer therapy. Although ICRF193 has not been approved for clinical use, it has potential implications in chemotherapy. In this study, we aimed to investigate the use of ICRF193 in chemotherapy in co-treatment with other drugs. To identify compounds that have synergistic effects with ICRF193, we optimized a cytotoxicity assay with combinations of ICRF193 in a 1536-well plate format and screened 2678 compounds, including clinically approved and investigational drugs, for their cytotoxicity in the presence and absence of ICRF193. From the screening and confirmation assays, etoposide, a known TOP2-targeting drug, was found to have a synergistic effect with 200 nM ICRF193 across multiple cancer cell lines, including HCT116, MCF7, and T47D. On the other hand, ICRF193 suppressed the toxicity of etoposide at higher concentrations (> 10 µM). In the follow-up studies, we found that ICRF193 and etoposide synergistically induced DNA double-strand breaks and subsequent G2 phase accumulation. Interestingly, this synergistic effect was observed only with etoposide and not with other TOP2 inhibitors in the tested compound library. Taken together, our results indicate that ICRF193 has a specific functional interaction with etoposide that enhances its genotoxic potential.
Asymmetric Enantio-complementary Synthesis of Thioethers via Ene-Reductase-Catalyzed C–C Bond Formation
FXYD2 marks and regulates maturity of β cells via ion channel-mediated signal transduction
The views of UK Chinese individuals towards living and deceased-donor kidney transplantation: A qualitative interview study
The views of UK Chinese people towards transplantation and organ donation are not known. It is not known whether the perspectives of Chinese people living in the UK differ from those of Chinese people living elsewhere in the world, or whether perspectives of UK Chinese people vary according to time spent living in the UK. This qualitative interview study aimed to investigate the views of UK Chinese individuals towards kidney donation and transplantation. It formed part of a convergent parallel mixed-methods programme of research alongside a quantitative registry study which found that UK Chinese individuals experience poorer access to living-donor kidney transplantation compared to UK White individuals. We conducted in-depth semi-structured interviews with sixteen participants across three UK cities. Participants were permanently resident in the UK and self-identified as UK Chinese. Interviews were conducted between 9th April 2020 and 16th July 2020. Interviews were transcribed verbatim, coded using NVivo software, and analysed using inductive thematic analysis. Three main themes and seven sub-themes were identified: (1) Importance of kinship: biological and social (i) Familism, ii) Relationship hierarchy, iii) Matching; (2) Donor sacrifice (i) Negative impact on donors, ii) Bodily integrity after death; and (3) Patient as information gatekeeper (i) Culture of silence, ii) A perceived need for education and engagement. This study provides insights that may offer some explanation for reduced rates of living-donor transplantation amongst UK Chinese individuals. Further research is required to investigate observational research findings not explained here, and to develop effective strategies to improve treatment access for UK Chinese individuals with kidney disease.
Analysis of the diagnostic accuracy of plasma sTNFr-2 concentrations in identifying sarcopenia in community-dwelling older women
Distinct spatially organized striatum-wide acetylcholine dynamics for the learning and extinction of Pavlovian associations
Abstract Striatal acetylcholine (ACh) signaling is thought to counteract reinforcement signals, promoting extinction and behavioral flexibility. Changes in striatal ACh signals have been reported during learning, but how ACh signals for learning and extinction are spatially organized to enable region-specific plasticity is unclear. We used array photometry in mice to reveal a topography of opposing changes in ACh release across distinct striatal regions. Reward prediction error encoding was localized to specific phases of ACh dynamics in anterior dorsal striatum (aDS): positive and negative prediction errors were expressed in dips and elevations respectively. Silencing ACh release in aDS impaired extinction, suggesting a role for ACh elevations in down-regulating cue-reward associations. Dopamine release in aDS dipped for cues during extinction, inverse to ACh, while glutamate input onto cholinergic interneurons was unchanged. These findings pinpoint where and suggest an intrastriatal mechanism for how ACh dynamics shape region-specific plasticity to gate learning and promote extinction.
Numerical simulation study on multifield coupling of enhanced geothermal systems under different fracture characteristics
Fractures are key geological features in hot dry rock structures and fulfill a decisive role in determining productivity and reservoir stability. Adopting the Xudong fault zone in the Songliao Basin as the research object, a multifracture heat extraction model was constructed using COMSOL software to systematically analyze productivity and various field under different numbers and locations of horizontal and vertical fractures. Moreover, the influences of vertical fracture connectivity and the characteristics of seepage and heat transfer between the upper and lower rock layers on the temperature field were evaluated. The findings are as follows: (1) The production flow obtained with nine horizontal fractures is 2.25 to 2.28 times that obtained with four horizontal fractures. Increasing the number of horizontal fractures also increases the production temperature and heat extraction efficiency at the early stages of heat extraction but reduces productivity at the later stages and adversely affects reservoir stability. After 30 years of heat extraction, the production temperature, average subsidence, maximum subsidence, and average in situ stress obtained with nine horizontal fractures are 79.38% and 1.87, 1.61, and 1.45 times, respectively, those obtained with four horizontal fractures. (2) The influence of the number of vertical fractures on the geothermal reservoir characteristics is similar to but slightly smaller than that of horizontal fractures. However, the influences of vertical fractures on the production flow at the early stages and the maximum reservoir temperature at the later stages are opposite to those of horizontal fractures. When vertical fractures are located close to the injection well, productivity is low at the early stages but high at the later stages. The maximum subsidence, average in situ stress, and maximum in situ stress slightly increase, whereas the average subsidence decreases. (3) After 30 years of heat extraction, the average reservoir temperature is highest when seepage and heat transfer between the upper and lower rock layers occur and when vertical fractures do not penetrate the reservoir. When these conditions are reversed, the average temperature is lowest, with the former approximately 0.42°C higher than the latter. The findings of this study provide a reference for the construction of reservoir fracture systems.
AraTraditions10k bridging cultures with a comprehensive dataset for enhanced cross lingual image annotation retrieval and tagging
A versatile information retrieval framework for evaluating profile strength and similarity
Abstract Large-scale profiling assays capture a cell population’s state by measuring thousands of biological properties per cell or sample. However, evaluating profile strength and similarity remains challenging due to the high dimensionality and non-linear, heterogeneous nature of measurements. Here, we develop a statistical framework using mean average precision (mAP) as a single, data-driven metric to address this challenge. We validate the mAP framework against established metrics through simulations and real-world data, revealing its ability to capture subtle and meaningful biological differences in cell state. Specifically, we use mAP to assess a sample’s phenotypic activity relative to controls, as well as the phenotypic consistency of groups of perturbations (or samples). We evaluate the framework across diverse datasets and on different profile types (image, protein, mRNA), perturbations (CRISPR, gene overexpression, small molecules), and resolutions (single-cell, bulk). The mAP framework, together with our open-source software package copairs , is useful for evaluating high-dimensional profiling data in biological research and drug discovery.
Indoor mobility challenges among older adults: A systematic review of barriers and limitations
Introduction The global population is projected to double by 2050 with most older adults expressing preference to age in place. Despite this demographic shift, indoor mobility challenges which directly impact independence, safety and quality of life remains poorly understudied, creating a critical knowledge gap for effective intervention development. Methods A systematic literature search was conducted on four databases from inception to September 2024. Inclusion criteria included: (1) participants aged 60 years and above; (2) were primary data on self-reported indoor mobility challenges; and (3) published in English language. Two reviewers independently performed data abstraction, evaluated the risk-of-bias and quality of included article using the NewCastle Ottawa Scale for cross-sectional or Joanna Briggs Institute Checklist for qualitative studies. Thematic synthesis with constant comparison analysis identified key mobility constraint factors. Results Nine studies encompassing 1,833 participants were identified. Older adults reported four main indoor mobility challenges: fatigability, poor balance, home environmental barriers, reduced strength and limb weakness. These limitations contributed to reduced endurance, even in indoor settings. The presence of various health conditions further compromised their mobility and ability to age in place healthily. Conclusion To support ageing in place, a comprehensive environmental assessments and home modifications can be considered. Multi-stakeholder collaborations are needed to support the independence, safety, and quality of life of older adults who wish to age in place. Further research is warranted in suburban and rural areas to explore socioeconomic factors and determinants of indoor mobility.