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When neighbors play a role: A systems-level analysis of protein interactions conditioning cancer driver mutation effects

Cancer is driven by the accumulation of somatic mutations, including driver mutations that confer a selective advantage to cancer cells. Driver proteins operate within complex interaction networks, and their activity is conditioned by neighbor proteins. Understanding the interplay between driver mutations and the expression of their neighbor proteins can provide insights into cancer biology and potential therapeutic targets. We assessed associations between expression of neighbor proteins and driver mutation status, comparing both between and within cancer types. We further evaluated if neighbors were enriched in significant associations with multiple drivers and characterized the impact of neighbor expression on overall survival for all cancer types. We found a significant correlation between the number of driver associations (DA) a neighbor gene has and the number of sign-coherent survival associations, particularly for neighbors enriched in positive associations, where high neighbor expression correlated with increased driver mutations and poorer survival. We identified 119 neighbors enriched in positive DA with at least two unfavorable survival associations and 25 neighbors enriched in negative DA with at least two favorable survival associations. Our study systematically identified neighbors associated with driver mutation status. Complementary evidence from survival analysis and the literature suggests that neighbors enriched in DA can be further explored as drug target candidates.

A modified EWMA signed rank control chart for enhanced quality monitoring in the automobile industry

Integrating AI in Pakistani ESL classrooms: Teachers’ practices, perspectives, and impact on student performance

The global rise of Artificial Intelligence (AI) in English as a Second Language (ESL) education has shown promise, yet its application in resource-constrained contexts like Pakistan remains underexplored. This study examines the integration of AI tools in Pakistani ESL classrooms, with a focus on (1) teachers’ instructional practices, (2) student learning outcomes, and (3) implementation challenges. Using a mixed-methods approach, data were collected through classroom observations, focus group discussions, and pre- and post-tests on vocabulary and writing skills administered to 100 undergraduate students (50 in the experimental group and 50 in the control group) over 16 weeks. The experimental group, taught with AI tools such as Grammarly and QuillBot, demonstrated significantly greater gains in vocabulary (+45%, d = 1.12) and writing performance (+46%, d = 1.03) compared to the control group. Qualitative findings revealed that while AI tools supported grammar correction and vocabulary enhancement, their effectiveness was limited by infrastructural constraints, insufficient teacher training, and cultural misalignment in language feedback. The study concludes that AI can meaningfully enhance ESL instruction when paired with teacher facilitation and localized design. It offers novel insights into culturally responsive AI integration in under-resourced educational contexts.

An unusual Co–S bond links B ₁₂ chaperones in an interprotein complex

Chaperones in trafficking pathways ensure specificity of transition metal loading and protection against adventitious side reactions. In B 12 , an essential cofactor for humans, a cobalt ion is coordinated to a >1.3 kDa tetrapyrrolic scaffold, posing logistical challenges for its translocation. In this study, we report the 3.4 Å crystal structure of the human MMACHC and MMADHC B 12 chaperones, tethered via a rarely seen covalent cobalt–sulfur bond. B 12 is bound in the base-off state to MMACHC, with Cys-261 on MMADHC serving as the upper axial ligand; the lower-axial position is vacant. The propensity of thiolato-cobalamin derivatives bound to MMACHC to undergo spontaneous decomposition via general acid catalysis or reduction/oxidation chemistry is averted in the interprotein complex with MMADHC. An exposed face in the complex suggests an exit route for B 12 . No known clinical variants localize to the interprotein interface, consistent with the cobalt–sulfur bond being key to forming the high-affinity complex.

Impact of NPK on morphology and biomass of Tephrosia vogelii

Quantifying bioenergy potential and environmental impacts of agricultural residues; a Comparative analysis with global benchmarks

Finding sustainable solutions for biofuel production from agricultural waste is crucial for reducing pollution and enhancing waste management. Agricultural residues—including crop waste, livestock manure and other organic materials—can be effectively converted into biofuels. Given the substantial volume of agricultural residues and their inadequate management in Iran, evaluating the potential for bioenergy production and determining the distribution of this renewable resource, is essential. This study assessed the bioenergy production potential from agricultural residues in Khuzestan Province, Iran. Data were collected from library resources and crop statistics for the agricultural year 2023–2024. The results indicated that the annual production of field and horticultural crops totaled 13,907,333.42 tons. The Theoretical Biomass Potential (TBP), Theoretical Energy Potential (TEP) and Available Energy Potential (AEP) were calculated as 5,496,297 tons, 92,283,088 GJ and 14,582,753 GJ, respectively. The potential electrical energy and power output from the total residues of the studied crops in a Combined Heat and Power (CHP) system were estimated at 1,364,122 MWh and 194.8745769 MWh, respectively. Additionally, the thermal energy potential was found to be 1,562,555.5 MWh, with a power capacity of 223.22 MWh. Environmental analysis indicated that the Global Warming Potential (GWP) was estimated at 774,334.45 tons of CO₂-equivalent.

Novelty as a drive of human exploration in complex stochastic environments

In order to find extrinsic rewards, humans explore their environment even if exploration requires several intermediate, reward-free decisions. It has been hypothesized that intrinsic rewards, such as novelty, surprise, or information gain, guide this reward-free exploration. However, in artificial agents, different intrinsic reward signals induce exploration strategies that respond differently to stochasticity. In particular, some strategies are vulnerable to the “noisy TV problem,” i.e., an attraction to irrelevant stochastic stimuli. Here, we ask whether humans exhibit a similar attraction to reward-free stochasticity. We design a multistep decision-making paradigm in which participants search for rewarding states in a complex environment containing a highly stochastic but reward-free subregion. We show that i) participants persistently explore the stochastic subregion, and ii) their decisions are best explained by a novelty-driven exploration strategy, compared to alternatives driven by information gain or surprise. Our findings suggest that novelty and extrinsic rewards jointly control human exploration in complex environments.

A novel computational approach for study of proton–proton scattering

Abstract In this paper, we have implemented a novel computational approach to study proton-proton scattering. The approach is applicable to all charged particle scattering scenarios and solves the challenge of incorporating the long-range Coulomb interaction alongside the short nuclear interaction using the phase function method. The key idea is to construct a reference potential using three smoothly joined Morse functions that collectively capture both nuclear and electromagnetic interactions. The reference potential is utilized in solving the phase equation which is derived by the transformation of the Schrodinger equation, for obtaining the scattering phase shifts for different values of orbital angular momentum called as $$\ell$$ -channels (S, P, D, F, G, H). The parameters of reference potential are optimized to minimize the Mean Squared Error between obtained and expected phase shifts, resulting in the construction of inverse potential for various $$\ell$$ -channels of the proton-proton system. Utilizing the phase shifts obtained from the inverse potentials, we have calculated the total cross-section and the low energy effective-range parameters, which have been found to be in excellent match with the experimental data.

Coupled hydraulic behavior of confluence and diversion flow with multi-gate regulation in a hydropower expansion project

Confluence and diversion flows are common yet complex three-dimensional hydraulic phenomena, and understanding their behavior is crucial for the safe and efficient operation of hydraulic structures, especially when they occur in close proximity within the same project. This study investigated the hydraulic interactions between the culvert intersection and the regulating and diversion gates of a hydropower station expansion using a 1:30 scale physical hydraulic model (Froude similarity). Practical operational strategies for the gates were developed to meet diversion flow requirements under normal conditions. Results indicate that, under typical operational and maintenance scenarios, the Froude number (Fr) between the culvert intersection and the regulating gate ranges from 0.03 to 0.26, indicating that the flow remains subcritical throughout this section. The water level at the Phase I culvert outlet is primarily governed by the total discharge from the Phase I and Phase II culverts, with flow distribution between them has a secondary effect. The stable water level upstream of the regulating gate is minimally influenced by the culvert flow distribution. Moreover, the converging flow has a limited impact on diverging flow at the regulating and diversion gates. The diversion flow rate of the diversion gate remains largely unaffected by the regulating gate’s operation, confirming the proposed gate operation schemes meet the diversion requirements without causing adverse hydraulic interactions.

Glycan microarray analysis of <i>Candida</i> -related antibodies in human and mice sera guides biomarker discovery and vaccine development

Invasive, high-mortality yeast infections caused by pathogenic Candida species are the most common fungal nosocomial bloodstream infections. The World Health Organization (WHO) has called for improved prevention and diagnostic strategies for fungal pathogens. Here, we demonstrate that Candida -related antibodies can be detected using glycan microarrays containing synthetic glycans to guide the discovery of oligosaccharide epitopes for diagnostics and vaccine design. Pure, synthetic mannans and β -glucans, resembling carbohydrates found on the surface of Candida spp., were employed to screen and compare sera from infected humans and mice with noninfected individuals. IgM antibodies directed toward β -glucans were observed shortly after infection, and after a longer time of infection, IgM and IgG antibodies that preferentially recognize mannans. Phosphodiester-linked mannosides and the β -(1,2)-mannose monomer help to distinguish different Candida spp. The tetrasaccharide antigen β -(1,2)Man- α -(1,2)Man- α -(1,2)Man- α -(1,2)Man, and the pentasaccharide antigens α -(1,2)Man- α -(1,3)Man- α -(1,2)Man- α -(1,2)Man- α -(1,2)Man and β -(1,3)Glc- β -(1,3)Glc- β -(1,3)Glc-[ β -(1,6)Glc]- β -(1,3)Glc were identified as potential epitopes for detection, e.g., through monoclonal antibody lateral flow tests, and the development of glycoconjugate or monoclonal antibody vaccines against Candida.

Spatial variability of soil physicochemical properties in soybean wheat belts in Vertisols of central India

Investigating the long-term impact of a programme of mindfulness combined with exercise delivered online (MOVE) on individuals living with chronic pain-an exploratory one-year follow-up of a feasibility randomised control trial

Background Online pain management programmes have evidence as effective interventions for individuals with chronic pain. This study was a one-year exploratory follow-up of a parallel group feasibility randomised controlled trial (RCT) investigating the effectiveness of participating in an online pain management programme that combined Mindfulness-Based Stress Reduction (MBSR) and exercise delivered online for individuals living with chronic pain (MOVE). Methods Ninety-six individuals with chronic pain participated in an eight-week feasibility RCT comparing MBSR and exercise to an online self-management guide. Fourteen patient reported outcome measures (PROMS) were collected at baseline, post-intervention, three months post-intervention and at a one-year follow-up. Analysis of changes in PROMs between baseline and one-year follow-up in the current study were analysed using Student’s t-tests, and in addition, data were analysed using linear mixed models, examining effect sizes. Results Forty-eight participants completed PROMs at a one-year follow-up. Small between group differences were observed in depression and the mental health component of the health-related quality of life score, in favour of the combined MBSR and exercise group. A further nine PROMS showed improvements in favour of the self-management group (SM). In the MOVE group, one-year follow-up scores demonstrated trends towards improvement compared to baseline scores for 10/14 PROMs. In the SM group positive changes were found in 13/14 PROMs. At one-year follow-up, results from the Patients Global Impression of Change Scale, demonstrated that 63.3% of participants in the combined mindfulness and exercise group, and 44.4% of participants in the self-management group reported improvement with a noticeable change. Conclusions The results of this long-term exploratory study suggest no significant difference between groups for the investigated PROMs at one-year follow-up. A fully powered RCT examining the effectiveness of MBSR combined with exercise delivered in a live synchronous online format is warranted, to explore the factors to optimise long-term outcomes for people living with chronic pain.

Correction for Wang et al., Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility

Correction: Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway

Sleep quality, emotional moods, and cognitive outcomes among people living with HIV: An ecological momentary assessment study

Introduction Although studies have explored the relationship between sleep quality, mood, and cognitive outcomes among people living with HIV (PLWH), few use ecological momentary assessment (EMA) techniques to evaluate within-person associations between sleep quality and emotional/cognitive outcomes among PLWH at the day level. This study investigated the association between previous night’s sleep quality and momentary psychological outcomes in participants’ natural setting. Methods Study participants were PLWH in South Carolina who were at least 18 years old, diagnosed with HIV for at least 2 years, and able to operate a cellphone. Participants were sampled using posters posted in AIDS Service organizations, and snowball sampling. Data collection occurred between March and November 2023. During a 10-day EMA period, participants received 6 brief surveys throughout the day. Surveys were delivered within a 14-hour time window at semi-random times, with at least 1.5 hours between surveys. Five multilevel models were implemented with mindfulness, positive affect, negative affect, perceived cognition, and self-control as the outcome variables, and previous night’s sleep quality as the input variable. Results A total of 962 responses were gathered from 22 participants, with an average of 43.73 responses per person. Experiencing higher than usual levels of sleep quality the night prior had a significant positive association with higher levels of momentary mindfulness (β = 0.08, p &lt; 0.001), positive affect (β = 0.1, p &lt; 0.05), and self-control (β = 0.06, p &lt; 0.05) when controlling for other covariates. Experiencing higher than usual levels of sleep quality the night prior exhibited trends towards a significant positive association with perceived cognition (β = 0.04, p &lt; .1). Within-person sleep quality was not associated with momentary negative affect. Conclusion Among PLWH, future interventions targeting health behaviors sensitive to poor mood and cognition (e.g., ARV adherence) should incorporate intervention activities that ensure good sleep quality among participants. Additional studies are needed with larger sample sizes to assess the generalizability of study results.

SARS-CoV-2-derived RNA replicons as safe and effective vaccines

A collection of RNA replicons (RRs) derived from severe acute respiratory syndrome 2 (SARS-CoV-2) for use in vaccine design was constructed by genetic engineering using bacterial artificial chromosomes. A replicon, which was deleted in six genes (3a, 3c, E, 6, 7a, and 7b) was selected. Cells infected with the RR vaccine candidate led to the formation of virus-like particles that, due to the failure of being secreted, increase vaccine safety, in contrast to the wild type virions. The replicon maintained the production of RNAs encoding at least proteins S, M, and N for several days. Intranasal immunization with the RR of transgenic mice, expressing human ACE2, elicited respiratory mucosal immunity. Immunization protected against challenge with SARS-CoV-2, inducing IgG, IgM, and IgA antibodies to the spike (S) protein, the receptor binding domain, N and M proteins, and cellular immune responses (CD4 + , CD8 + , and long-term memory T cells). Coinfection of cells with the RR vaccine and a full-length SARS-CoV-2 led to a significant inhibition of replication of full-length virus, increasing the safety of the RR vaccine. The RR vaccine induced a minor inflammatory reaction in the absence of major side effects and was stable at different temperatures. An updated RR expressing XBB.1.5 S protein elicited neutralizing antibodies against the homologous virus and provided full protection against recent SARS-CoV-2 variants.

An autoencoder driven deep learning geospatial approach to flood vulnerability analysis in the upper and middle basin of river Damodar

Well-being, physical activity and health promotion among officers and ratings on board cargo ships: A cross-sectional study

Background Health and well-being of seafarers working on merchant vessels is an essential area of research, given the significant physical and psychological demands placed on these workers. The present study focuses on assessing the current health status and well-being, identifying personal needs and requirements for health promotion among officers and ratings on board. Methods A total of 583 seafarers from a German shipping company were surveyed by using a questionnaire including the standardized WHO-5-Well-being Index, PHQ-9, GPAQ and questions about the need for health measures as well as physical activity. Results The survey was distributed to 616 seafarers on 33 merchant ships with a response rate of 94.6%. Officers reported lower well-being compared to ratings (60.1% vs. 70.0%, p = 0.001). Regarding depressive symptoms no significant differences between the rank groups were found. Furthermore, ratings stated a significantly higher total physical activity than officers (10,437 vs. 8,035 MET-min/week, p = 0.005), while officers were significantly more sedentary compared to ratings (3.5 vs. 2.4 hours/day, p = 0.001). Seafarers also reported a high interest in sports on board (&gt;56%) and health promotion (&gt;60%), with a preference for digital formats and monetary incentives for participation in health programs. Conclusion The impaired well-being of seafarers compared to shore-based reference groups underscores the need for targeted, digital interventions to improve the health and well-being of seafarers. The findings highlight significant differences in well-being, physical activity, and interest in health promotion between officers and ratings. Future research should apply longitudinal designs to better understand the causal relationships between occupational and socio-demographic factors with health outcomes among seafarers.

Ectopic transcription due to inherited histone methylation may interfere with the ongoing function of differentiated neurons

How mutations in histone modifying enzymes lead to neurodevelopmental defects is unknown. To address this question, we took advantage of the invariant embryonic lineage and adult nervous system in Caenorhabditis elegans to investigate a double mutant between spr-5/Lsd1/Kdm1a (H3K4me1/2 demethylase) and met-2/Setdb1/Kmt1e (H3K9 methyltransferase). We demonstrate that spr-5; met-2 double mutant worms have a severe chemotaxis defect caused by the ectopic expression of germline genes in somatic tissues. Despite this behavioral defect, we observe few embryonic lineage alterations and the normal complement of neurons. This raised the possibility that the abnormal chemotaxis behavior may be due to ongoing defects in terminally differentiated cells rather than alterations in development. Consistent with this possibility, we find that shutting off the ectopic expression of germline genes specifically in neurons rescues chemotaxis in spr-5; met-2 mutants. Remarkably, shutting off the ectopic germline expression in spr-5; met-2 adult worms, that had a chemotaxis defect earlier in development, is also sufficient to rescue chemotaxis behavior. These results suggest that ongoing inappropriate transcription in neurons can block normal behavior despite the chemotaxis neurons being intact.

Analysis of factors influencing sleep disorders in patients with amyotrophic lateral sclerosis