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A new first-line standard-of-care for BRAFV600E-mutated mCRC

CH−π interactions confer orientational flexibility in protein–carbohydrate binding sites

Biochemical neuroplasticity in the cerebellum after physical exercise: Systematic review and meta-analysis

Background Neuroplasticity is the central nervous system’s (CNS) capacity to adapt to injuries or environmental changes. Biochemical neuroplasticity is one such adaptation that may occur in response to physical exercise (PE). This systematic review and meta-analysis aimed to evaluate the effects of PE on cerebellar biochemical neuroplasticity. Methods Following the PICO strategy, this review included in vivo studies with small rodents (Population) subjected to well-defined PE protocols (Intervention) and compared to non-exercised controls (Comparator) to assess cerebellar biochemical alterations (Outcome). Studies published between January 1976 and July 2024 without language restrictions were searched in PubMed, Scopus, Web of Science, and Cochrane Central databases. Data were synthesized through meta-analyses and methodological quality was assessed by the SYRCLE risk of bias tool. Results Out of 3,107 records screened, six studies met the inclusion criteria for qualitative and quantitative analyses. All studies had a low or unclear risk of bias. Markers of biochemical neuroplasticity assessed included superoxide dismutase (SOD), catalase (CAT), glutathione (GR), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione disulphide (GSSG) and lipid peroxidation (LPO). Meta-analyses showed that moderate-volume PE significantly reduced LPO (SMD = −2.41; 95% CI: −3.89 to −0.93), while high-volume PE increased LPO (SMD = 4.55; 95% CI: 1.92 to 7.18). Low-intensity or low-volume PE did not significantly alter oxidative markers. Conclusions PE induces either adaptive or maladaptive biochemical neuroplasticity in the cerebellum depending on protocol variables. While enzymatic activity responds to cellular changes and limits nervous tissue protection, adaptive biochemical neuroplasticity seems to confer greater resistance and efficiency.

Neoadjuvant nivolumab plus chemotherapy improves overall survival in resectable NSCLC

Aberrant activation of IL-6/JAK/STAT3/FOSL1 signaling induces renal abnormalities in a Xenopus model of Joubert syndrome-related disorders

Impact of energy consumption on environment sustainability in upholding ESG practices in Malaysia: Evidence from electricity supply company

This study aims to examine the impact of energy consumption, i.e., coal and gas, on environmental sustainability by utilizing CO2 emissions as a proxy to emphasize Environmental, Social, and Governance (ESG) practices in the electricity supply company of Malaysia. To do so, we collect time series data from Tenaga Nasional Berhad (TNB) Sustainability Reports spanning 2016–2021. Since the data is short time series data, this study deploys the Prais-Winsten (AR1) regression technique, which is able to produce robust estimates from the short data. Besides, this method is also able to overcome the issues of heteroscedasticity and autocorrelation issues in the dataset. Additionally, we also employ the Ordinary Least Square (OLS) regression method to check the robustness of our estimation. The findings of the study reveal that energy consumption, i.e., coal and gas, strongly affects the environmental sustainability channel through CO2 emissions. The result indicates that the electricity supply company of Malaysia still aggravates the environmental degradation using coal and gas in energy production, while the study also shows from the long-run trends that the sector has considerably decreased the CO2 emissions in recent years by 0.60%. Since the emission is still significant, this study emphasizes the need for a cautious approach to energy sources in order to reduce environmental effects. The study suggests that policymakers should review the existing energy use and CO2 emissions policy to strengthen environmental sustainability and ESG standards in Malaysia’s electricity generation industry, reduce dependency on fossil fuels, and hasten the adoption of renewable energy sources.

Conformations of the three gates in Saccharomyces cerevisiae topoisomerase II and their response to DNA, nucleotide, and etoposide

Normal-weight obesity in high-altitude youth: Gender disparities and protective effects of native adaptation

Background While high altitude has been associated with reduced muscle mass, its effects on fat mass remain controversial, with studies reporting both fat accumulation and loss. Normal weight obesity (NWO), characterized by normal body mass index (BMI) but excessive body fat, is an emerging metabolic health concern. This study aimed to investigate the prevalence of NWO among young adults in a high-altitude region, while also analyzing body composition differences between genders, as well as native versus migrant populations. Methods In this cross-sectional study, 1,313 university students (mean age: 19.6 ± 1.6 years; 719 females and 594 males; all enrolled in undergraduate studies) from Lhasa, Tibet (altitude: 3,650m), who voluntarily participated in body composition measurements during the university’s annual physical fitness assessments. The participants were from multiple academic departments. They underwent anthropometric and body composition assessments, including body fat percentage (BF%), fat-free mass (FFM), skeletal muscle mass (SMM), and waist-to-hip ratio (WHR). Participants were stratified by BMI and BF% to determine NWO prevalence, with subgroup analyses for gender and residential background. Results BF% trends varied by gender; female students showed a linear increase with BMI, while male students exhibited a phased pattern with two turning points at BMI = 19.6 and 26.5. The overall prevalence of NWO among high-altitude university students was 22.2%, accounting for 57% of individuals with excessive body fat. Females were disproportionately affected (27.7% vs.16.7% in males). Both females and males with NWO had significantly lower FFM and SMM than their non-NWO counterparts (P < 0.001). A subset analysis of 389 individuals revealed that NWO incidence was significantly lower among high-altitude native females and males compared with their migrant counterparts. Among those with NWO, migrant females had a higher BF% (P = 0.02), whereas native males exhibited a higher WHR (P = 0.009). Conclusions NWO prevalence among young adults in a high-altitude region was comparable to lowland populations, with notable gender disparities. NWO was associated with reduced muscle mass, suggesting elevated metabolic health risks. The lower NWO prevalence among native high-altitude residents suggests potential protective effects associated with chronic hypoxia adaptation. These findings underscore the need for further research to elucidate the complex relationship between chronic hypoxia, body composition, and metabolic health in high-altitude populations. Such insights are crucial for developing targeted interventions addressing normal weight obesity.

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.