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Adding durvalumab to perioperative FLOT improves gastric cancer outcomes

The ubiquitin ligase Triad1 influences myeloid leukemogenesis by regulating the integrated stress response

Biochemical analysis of human eIF4E-DCP2 interaction: Implications for the relationship between translation initiation and decapping

All eukaryotic mRNAs bear a 7-methylguanosine cap on their 5’ end. The 5’ cap enables mRNA translation by binding directly to eIF4E; which further recruits other factors and the 40S ribosome. Additionally, the 5’ cap maintains transcript stability; removal of the cap by the enzyme Dcp2 is necessary to degrade the mRNA. An a priori conclusion, therefore, has been that cap binding by eIF4E and DCP2 are antithetical to each other as both need access to the same substrate, i.e., the 5’ cap. In this study, we purified native full-length human eIF4E and Dcp2 and utilize biophysical and biochemical approaches to examine the in vitro interplay between Dcp2 and eIF4E. We confirm that Dcp2 is sufficient to remove the 5’ cap. Moreover, we demonstrate that Dcp2 binds RNA with nanomolar affinity. We discovered that, unexpectedly, eIF4E does not interfere with Dcp2’s decapping function, contradicting previous mechanistic models. Moreover, eIF4E binding appears to increase the affinity of Dcp2 for RNA. Although limited to in vitro conditions, our findings warrant a reevaluation of the proposed relationship between these mRNA cap-binding proteins.

Promises and pitfalls of multi-cancer early detection using liquid biopsy tests

Interpreting ribosome dynamics during mRNA translation

Investigating the content and processes of patient-derived quality of care indicators for those affected by multiple long-term conditions (MLTC): A scoping review protocol

Background People living with multiple long-term conditions (MLTC) are reported to have poorer quality of life, worse health outcomes, and higher health-related expenses compared to those with singular chronic health conditions. Living with MLTC is associated with a higher risk of care that is duplicate or unnecessary. Understanding and monitoring the quality of care (QoC) for those with MLTC is imperative to ensure that individuals complex care needs are met, maximising health and wellbeing and minimising harm and social/economic burden. There is paucity on what QoC means in the context of MLTC, which is likely different than a mere amalgamation of quality indicators of each contributory condition. There is even less understanding on how QoC can be measured in a way that meets the specific care priorities of individuals with MLTC. The aim of this review is to systematically map and analyse evidence on what QoC means for those affected by MLTC and the content and processes of any existing QoC indicators in MLTC, developed with patient or caregivers. Methods We will systematically search for evidence following a Levac et al methodological scoping review process. All eligible studies published in English from 2000 onwards in the following databases will be included: MEDLINE, EMBASE, CINAHL, APA PsycINFO, Global Health and Health Management Information Consortium. Given expected study heterogeneity, a narrative synthesis is anticipated. Our Community Partner Advisory Group will assist in the identification and analysis of relevant evidence. Discussion Current evidence shows variations in concepts and approaches when developing, implementing or validating QoC indicators, not always capturing patients’ preferences nor the complex processes required in MLTC care. Clarifying concepts and synthesising evidence-based knowledge in this area will be the first step to inform the development of a project aiming to develop a set of patient-derived QoC indicators for use across multiple settings in the United Kingdom (UK) and beyond. Systematic review registration Available on Open Science Framework on https://osf.io/gjr84.

Adding lurbinectedin to maintenance therapy improves outcomes in ES-SCLC

Spatiotemporal fluctuations in fluorescence intensity of rhodamine phalloidin–labeled actin filaments

Preparation and characterization of a novel magnetic nano adsorbent for removal of metal ions

As a result of global urbanization and industrialization, heavy metals are one of the hazardous contaminants facing the world. The adsorption process using agricultural wastes can achieve one of the sustainable development goals for wastewater treatment and resource recovery. Moringa and tea extracts were utilized to synthesize iron nanoparticles for the treatment of aqueous solutions containing heavy metal ions (Cu2+, Pb2+, Se2+, Zn2+, and Cr6+). This method offers a sustainable substitute for conventional chemical wastewater treatment methods. Furthermore, the use of magnetic iron nanoparticles reduces the need for extra separation processes by making it simple to separate the adsorbent from the treated waste using a magnetic field. Various techniques were employed to characterize the prepared nanoparticles, such Fourier-transform infrared spectroscopy (FT-IR), energy dispersive x-ray spectroscopy (EDX), scanning electron microscopy (SEM), x-ray diffraction (XRD), and x-ray fluorescence (XRF). The XRD analysis confirmed the crystalline phase of alpha-FeNPs in the synthesized nanoparticles. The EDX analysis verified the presence of oxygen and iron in the nanoparticles, indicating that the iron was in an oxide form. This study aimed to investigate the removal of heavy metals using nano-magnetic composites of moringa (FeNPs-M) and tea (FeNPs-T). To assess the effectiveness of the FeNPs-M several parameters were tested, including pH, contact time, initial concentration, and nanoparticle dosage. The results indicated that the efficiency of FeNPs-M was significantly higher than that of FeNPs-T for the removal of heavy metals from synthetic solutions, achieving removal efficiency are 96.5% 99.71%, 96.73%, 93.16%, and 91.83% of Cu2+, Pb2+, Se2+, Zn2+, and Cr6+, respectively, when using FeNPs-M, while the removal efficiency are 96.36%, 93.40%, 79.83%, 78.6%, and 77.77% of Cu2+, Pb2+, Se2+, Zn2+, and Cr6+, respectively, 25 °C, with a contact time of 45 min, a pH of 3.0, concentration 3.0 mg/L, a sorbent dose of 0.8 g/L, and 200 rpm at 25 °C.

T-DXd effective as second-line therapy in G/GEJ cancers

The poly(A) polymerase Star-PAP is regulated by stably associated phosphoinositide messengers

The hidden influence: Medical students’ knowledge and attitude of conflict of interest–A cross-sectional study in Jeddah, Saudi Arabia

Introduction Conflicts of interest (COI) pose ethical challenges in medical education and clinical practice, potentially influencing decision-making. While COI policies and education vary globally, inconsistent training leaves medical students vulnerable to industry influence. In Saudi Arabia, COI education remains underexplored. This study assesses medical students’ knowledge, attitudes, and exposure to COI, aiming to identify gaps and inform educational improvements. Methodology A cross-sectional study was conducted among 392 medical students from multiple universities in Jeddah, Saudi Arabia. A validated questionnaire was administered to assess COI knowledge, attitudes, and exposure to industry interactions. Data were analyzed using IBM SPSS 29.0, with statistical significance set at p < 0.05. Results A total of 392 participants were included. Overall, 71.4% of students were able to define COI, while 28.6% lacked awareness. Clinical students had significantly higher knowledge scores than preclinical students (p = 0.001). Grade Point Average (GPA) was significantly associated with attitudes toward COI, with students who had excellent GPAs scoring the highest (p < 0.001). No significant differences were observed in knowledge or attitude scores based on gender, research experience, and university affiliation. Over half of the students (52.6%) felt inadequately educated about COI, and 48.5% had never attended a COI lecture. Clinical students (65.2%) reported more interactions with pharmaceutical representatives than preclinical students (34.8%). Conclusion While medical students generally recognize COI, gaps in knowledge and formal education persist. Clinical exposure appears to enhance knowledge, yet inconsistent education leaves students vulnerable to industry influence. Strengthening COI education within medical curricula is essential to promote ethical decision-making and uphold professional integrity.

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.