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Rechallenge with immune-checkpoint inhibitors in patients with advanced-stage lung cancer

Cathepsin K as a key regulator of myocardial fibrosis in dilated cardiomyopathy and a promising therapeutic target

The Multiple Platforms Effect (MPE): A quantification of how exposure to similarly biased content on multiple online platforms might impact users

Over the past decade, controlled studies have identified nearly a dozen new forms of manipulation that can be used by search engines, social media platforms, microblogging platforms, and intelligent personal assistants. A recent study has shown that when users were exposed repeatedly to similarly biased content on the same platform, the net impact of those exposures was additive. We now ask the following: What happens when users are exposed to similarly biased content generated by different means on multiple online platforms? In the present experiment, which was randomized, controlled, counterbalanced, and double-blind, we exposed people to similarly biased content generated by different means on three different platforms – simulations of Google Search, Alexa, and X (f.k.a., Twitter) – presented successively and in a random order. We found that the impact of successive exposures was additive for both opinions and voting preferences pertaining to political candidates. Overall, the number of undecided voters voting for the favored candidate increased with each successive platform exposure by 42.4%, then 56.5%, then 66.7% over the pre-exposure level. We speculate that if Big Tech companies share values or political preferences, their net effect on our elections might be considerably greater than the effect of any individual company.

Novel colorectal cancer screening methods — opportunities and challenges

TCR activation stimulates regulated intramembrane proteolysis of L-selectin by presenilin 1 and localized proteasomal degradation of the cytoplasmic tail

Decoding community proximity discourse: A mixed-methods comparative analysis of online local and national newspapers in Romandy, Switzerland

This paper presents a mixed-method approach to analyzing news media, combining quantitative linguistic metrics with qualitative discourse frameworks. We first extract linguistic features such as quotations, readability levels, and lexical richness, then perform named entity recognition and topic modeling. To add depth, we apply Fairclough’s model of critical discourse analysis—highlighting social and cultural contexts—together with Goffman’s frame analysis of social behavior, enabling a systematic comparison of narrative strategies and community engagement. We provide new evidence on how local and national papers diverge not only in content, but also in temporal framing, participatory practices, and the construction of proximity. We validate this pipeline by comparing local and national newspapers in Romandy, Switzerland, a media landscape where local press agencies currently face intense economic pressures and widespread layoffs. Our findings reveal notable divergences in narrative construction and audience engagement: local outlets focus on fostering a sense of community and direct connection with readers, whereas national outlets employ more wide-ranging, sophisticated storytelling to appeal to a broader audience. By synthesizing quantitative and qualitative insights, our study moves beyond descriptive comparison to show how distinct editorial logics shape identity and democratic participation in a transforming media landscape. The study’s integrated analytical framework underscores the importance of a comprehensive, multi-level perspective on media strategies and audience dynamics, particularly in an era of rapid editorial and economic transformations.

Surrogate end points in oncology: aligning drug development incentives and patient needs

Molecular determinants of nucleic acid recognition by an RNA-targeting ADP-ribosyltransferase toxin

Association between oxidative balance score and systemic immune-inflammation index: NHANES 2003–2018

Background As we all known oxidative stress and inflammation were interdependent and interconnected. Oxidative balance score (OBS) could assess the antioxidant capacity of an individual’s body. The purpose of this study sought to investigate the connection between OBS and the recently proposed inflammatory indicator——Systemic immune-inflammation index (SII). Methods The study incorporated 16,080 participants from National Health and Nutrition Examination Survey (NHANES) database (2003–2018). We utilized weight multivariable linear regression analyses to assess this association. Additionally, subgroup analyses and linear relationships were performed for deeper insights. The robustness of the findings was ensured by conducting multiple sensitivity analyses. Results In the multivariate model using the first OBS category as the reference, higher OBS quartiles had a significantly negative association with SII [β = −51.52 (95%CI: −68.31, −34.73), P for trend < 0.001]. The interaction test showed that age (P < 0.001) and hypertension (P = 0.043) had a significant effect on this connection. Restricted cubic splines plot with four knots illustrated a linear relationship between OBS and SII (P-non-liner = 0.677). The findings from the sensitivity analysis aligned with the outcomes of the primary analysis, confirming the consistency and reliability of the results. Conclusions OBS based on diet and lifestyle had a strongly negative association with SII. This study emphasized the importance of improving an individual’s overall antioxidant status through diet and lifestyle changes, highlighting its effectiveness in reducing inflammation index.

Reply to ‘Surrogate end points in oncology: aligning drug development incentives and patient needs’

Development of novel mitochondrial pyruvate carrier inhibitors for breast cancer treatment

Does microcredit for the poverty-alleviated population have an income-increasing effect? Also on the “Raising the Low” effect

Promoting the continuous income increase of the poverty-alleviated population has become one of the key tasks to consolidate the achievements of poverty alleviation, promote rural revitalization and achieve common prosperity. Based on the survey data of 738 farmers in six poverty-alleviated counties (cities) in an underdeveloped region in northwest China, this paper uses the endogenous transformation regression model to empirically explore the income-increasing effect of microcredit for the poverty-alleviated population, and uses the quantile regression model and OLS regression model to explore raising the low effect of microcredit for the poverty-alleviated population. The results show that: (1) Based on the counterfactual hypothesis, if the farmers who obtain microcredit for poverty-alleviated population are not loaned, their production and operating income will decrease by 3.31%, that is, microcredit has a significant income-increasing effect, and the income-increasing effect of obtaining microcredit for the poverty-alleviated population on the monitoring objects is greater than the households that have lifted out of poverty. (2) The mechanism of action shows that the microcredit policy for the poverty- alleviated population promotes income increase by promoting farmers to increase material capital investment and social capital investment. (3) The income-increasing effect of obtain microcredit for poverty-alleviated population on the low-income initial endowment farmers is greater than that on high-income initial endowment farmers, and farmers with low-land initial endowment have a higher income increase effect, that is, a ‘raising the low ‘ effect. The overall efficiency effect on ‘low→high ‘initial endowment farmers shows a decreasing trend. Therefore, in order to ensure the effectiveness of financial precision assistance, we should promote the microcredit policy of the poverty-alleviated population from the aspects of policy stability and implementation precision.

Empowering oncologists: a practical approach to overcoming barriers to clinical trial enrolment

The Escherichia coli RelB antitoxin C terminus is essential for RelE toxin suppression and transcriptional repression

Cadmium-induced impairment in growth, photosynthetic apparatus and redox regulation in green amaranth (Amaranthus viridis L.) plant attenuated by salicylic acid and methyl jasmonate

The hazardous Cadmium (Cd) contamination in vegetables from anthropogenic Cd-abundant agroecosystems is a decisive threat to plants and human health. This study examined the prospective roles of salicylic acid (SA) and methyl jasmonate (MeJA) in alleviating Cd-induced toxic effects in green amaranth plants. The seeds of green amaranth (cv. Ghretokanchan) plant were primed with SA (100 and 250 µM) and MeJA (2.5 and 5 µM) and 21-d-old seedlings were set in six conditions under a hydroponic system: (i) Control, (ii) Cd (10 µM CdCl2·H2O), (iii) Cd with 100 µM SA, (iv) Cd with 250 µM SA, (v) Cd with 2.5 µM MeJA, and (vi) Cd with 5.0 µM MeJA. The experiment was set in a completely randomized design having three replications. Cd exposure for three weeks markedly impaired plant growth, pigment contents, leaf gas exchange, and photosystem-II efficiency; increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels indicating induced oxidative stress; and enhanced the activities of superoxide dismutase, guaiacol peroxidase and catalase enzymes. However, seed priming and supplementation of SA and MeJA significantly remediated these Cd-mediated adverse effects. Compared to Cd-alone treatment, 100 and 5 µM of SA and MeJA considerably improved total dry weight by 45% and 94%, respectively whereas leaf MDA and H2O2 levels were substantially reduced by 100 µM SA (37% and 14%) and 5 µM MeJA (35% and 21%). An extensive activity of antioxidants and considerable reduction in Cd uptake and translocation from medium-root-shoot was apparent due to the supplementation of SA and MeJA. The study effectively optimized the levels of SA and MeJA for the improvement of Cd tolerance based on metal uptake, morpho-physiology, and redox regulation, and concludes that either 100 µM SA or 5 µM MeJA could be used for the alleviation of Cd-toxicity in green amaranth plants in Cd-contaminated soils through further field trials.

Daratumumab and missed sequencing opportunities in transplant-ineligible multiple myeloma: lessons for future trials

Engineered bacteriophytochrome heterodimers for research and applications

Identification of the Francisella novicida FTN_0096 as a factor involved in intracellular replication and host response

Francisella tularensis is the causative agent of the zoonotic disease tularemia. We investigated a pathogenic factor of F. tularensis subsp. novicida (F. novicida). Accordingly, we established a novel infection model using HeLa cells. F. novicida usually infects macrophage lineage cells and less frequently epithelial cells. We successfully infected HeLa cells expressing the Fc receptor (HeLa–FcγRII cells) using F. novicida supplemented with mouse serum containing F. novicida antibodies. A total of 2,232 transposon mutants of F. novicida were screened to determine the relatively fewer cytotoxic strains of the HeLa–FcγRII cells, and 13 strains were thus isolated. Sequencing analysis of transposon insertion sites identified 13 genes, including FTN_0096. We focused on FTN_0096. Although the F. novicida wild-type strain proliferated in HeLa–FcγRII and THP-1 cells, the number of intracellular FTN_0096 mutant decreased. FTN_0096 mutant cannot escape from phagolysosomes in the initial phases of infection. Moreover, FTN_0096 mutant was detected in the mitochondria and Golgi complex. These findings indicate the importance of FTN_0096 of F. novicida for intracellular replication in the cells.

Cu/Zn-superoxide dismutase naturally fused with a β-propeller lactonase in Deinococcus radiodurans

Adopting Soft Logic to enhance an Adizes tool: A comprehensive approach to represent the evaluation of management styles

Management skills assessment has become increasingly complex in today’s digital age, as these skills are multi-dimensional and require a nuanced approach. Beyond evaluating each dimension independently, it is crucial to consider the tension and balance between them, as they often exist in inverse proportions. To address this complexity, this study introduces a methodology based on Soft Logic, a mathematical theory designed to represent realities that are not clear-cut, such as conflicting traits. This approach is particularly suited to the assessment of managerial skills. The research focuses on the Adizes Management Style Questionnaire, a widely recognized tool that evaluates four distinct managerial styles: Producer, Administrator, Entrepreneur, and Integrator. Unlike traditional assessments that focus on isolated behaviors, the proposed method highlights the dynamic interplay between these styles. By incorporating Soft Logic, the framework provides a more flexible and comprehensive evaluation, capturing both dominant traits and the tensions between them. This methodology was tested in an empirical study with 40 participants and offers organizations deeper insights into leadership dynamics, aiding in recruitment, leadership development, and team composition. Although developed with the Adizes tool, the methodology can be adapted to other managerial assessment tools and potentially extended to other multi-dimensional domains.