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Transcriptomic profiling of pancreatic neuroendocrine tumors: dysregulation of WNT, MAPK, PI3K, neddylation pathways and potential non-invasive biomarkers
The study aimed to identify altered signaling pathways and potential non-invasive biomarkers for pancreatic neuroendocrine tumors (PanNETs) through transcriptomic profiling of tumor tissues. The analysis encompassed samples from non-functional PanNETs (NF-PanNETs), insulinomas, and tumor-adjacent pancreatic tissues (TAPT). In the differential expression analysis comparing PanNETs and TAPTs, we identified 1,210 differentially expressed genes at a false discovery rate significance threshold of < 0.05 and with Log2FoldChange values of > 0.5 and <−0.5. Further pathway enrichment analysis revealed a multitude of overrepresented signaling pathways related to cell proliferation, survival, and tumorigenesis. Significant findings included the Beta-catenin-independent and TCF-dependent WNT signaling pathways, MAPK1/MAPK3 signaling, and terms associated with PI3K/AKT/mTOR signaling. Among the list of DEGs, we also identified 28 upregulated genes encoding cell surface proteins and 24 upregulated genes encoding cancer-associated secretome proteins. Since the proteins of these genes are found in the bloodstream, there is potential for further testing of these markers as biomarkers for liquid biopsy assays. Overall, these findings underscore the promise of transcriptomic landscape analysis in identifying PanNET-specific non-invasive biomarkers and uncovering potential therapeutic targets.
‘I think youtube’s turning me into a flat earther’: Social media’s role in ex-conspiracy theorists entering and exiting anti-scientific communities
Conspiracy beliefs erode trust in science and lead to negative effects on public health and other science-related behaviours and political discourse. Despite extensive research on conspiratorial thinking, the literature lacks a comprehensive exploration of individuals’ experiences as they enter (and exit) conspiracy communities, presenting a notable research gap. Therefore, the present study adopts an interpretivist framework by interviewing four ex-conspiracy theorists, delving into what drew them into conspiratorial thinking, the catalysts for their exit from these online communities (e.g., Flat Earth, distrust of science and medicine), and the obstacles they faced in disengaging from these communities. Reflective Thematic Analysis identified four main themes with eight associated subthemes. The experiences of ex-conspiracy theorists revealed a profound personal dimension for them entering the conspiracy echo chamber (Theme 1), such as feelings of loneliness and the impact of significant life events. Scientific illiteracy and a general misunderstanding of the scientific process (Theme 2), further contributed to their adoption of more entrenched conspiratorial thinking. The (online) conspiracy community, with its powerful and dynamic nature, had impacted the experiences of members (Theme 3), providing a sense of identity, reinforcing community doctrine, and creating a social and personal barrier to leaving the community. Leaving the community proved a challenging process (Theme 4), with participants identifying a conflict between their personal experiences and the community’s doctrine as a key reason for their departure. We contextualize these findings within prior research and propose potential interventions for individuals susceptible to scientific misinformation, utilizing the principles of nudge theory for behaviour change and mindfulness-based therapies.
Propensity to childhood anxiety and depression due to exposure to adversity: A multidimensional construct
Children and adolescents are increasingly susceptible to issues related to anxiety and depression symptoms. The literature does not present a consensus on the composition of indicators that make predictions, prognostic algorithms, or management strategies in mental health promotion and prevention. Most studies primarily focus on the consequences observed in adulthood. This study develops a multidimensional representation of the propensity of children and adolescents to have difficulties in the field of anxiety and depression. The Ordered Weighted Averaging (OWA) operator was used to create a composite indicator, and three quality tests validated the results. For this, it uses information about different dimensions associated with adversity in childhood and adolescence from 54 countries sourced from UNICEF’s Multiple Indicator Cluster Surveys to compare the values of proposed dimensions across continents. The generated composite indicator reveals that, on average, countries in Africa show a higher propensity for children and adolescents to present difficulties in the anxiety and depression fields. In the opposite position, the Americas have the lowest average propensity for these mental health conditions. The validation of the results through quality tests reinforces confidence in the direction indicated by the findings, enhancing the decision-making process when dealing with multidimensional phenomena.
Association between the early use of beta-blocker and the risk of sepsis-associated acute kidney injury: A retrospective cohort study using the MIMIC-IV database
Background Sepsis-associated acute kidney injury (SA-AKI) is a common and life-threatening complication in critically ill patients. Studies have shown that the use of beta-blockers improves hemodynamics and the risk of death in patients with sepsis. However, the association between beta-blockers use and the risk of AKI in patients with sepsis remains poorly understood. The present study aimed to evaluate this potential association. Method Sepsis patients for this retrospective cohort study were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC) database. Propensity score matching (PSM) was used to balance the basic characteristics between beta-blocker users and non-users. Univariate and multivariable logistic regression analysis were employed to evaluate the association between early use of beta-blocker and SA-AKI. Odds ratio (OR) and 95% confidence interval (CI) were estimated as effect measurements. Results Totally 4,419 patients with sepsis were enrolled in our study. The follow-up period was from the 24th hour of intensive care unit (ICU) admission to the occurrence of AKI or ICU discharge, with 2,122 (48.02%) cases of developed AKI. After PSM, a lower SA-AKI risk was observed in the early use of the beta-blockers group compared to the non-user group (adjusted OR: 0.80; 95%CI: 0.64–0.99). Similar associations of early use of beta-blockers and SA-AKI were observed in patients younger than 65 years old, male, without comorbidities, and with Simplified Acute Physiology Score II/Charlson comorbidity index scores below the median (all P < 0.05). Conclusion In ICU patients with sepsis, early use of beta-blockers is associated with a reduced risk of AKI, which may help reduce renal impairment and improve survival. Further studies are needed to verify the underlying mechanisms of beta-blockers in the development of SA-AKI.
Influence of multi-species data on gene-disease associations in substance use disorder using random walk with restart models
A major challenge lies in discovering, emphasizing, and characterizing human gene-disease and gene-gene associations. The limitations of data on the role of human gene products in substance use disorder (SUD) makes it challenging to transition from genetic associations to actionable insights. The integration of data from multiple diverse sources, including information-dense studies in model organisms, has the potential to address this gap. We demonstrate a modified performance of the Random Walk with Restart algorithm when multi-species data is integrated in the heterogeneous network within the context of SUD. Additionally, our approach distinguishes among disparate pathways derived from the Kyoto Encyclopedia of Genes and Genomes. Thus, we conclude that direct incorporation of multi-species data to an aggregated heterogeneous knowledge graph can adjust RWR’s performance and enables users to discover new gene-disease and gene-gene associations.
Flexi-YOLO: A lightweight method for road crack detection in complex environments
Road crack detection is critical to global infrastructure maintenance and public safety, and complex background environments and nonlinear damage crack patterns challenge the need for real-time, efficient, and accurate detection.This paper proposes a lightweight yet robust Flexi-YOLO model based on the YOLOv8 algorithm. We designed Wise-IoU as the model’s loss function to optimize the regression accuracy of its bounding boxes and enhance robustness to low-quality samples. The DCNv-C2f module is constructed for the transformation and fusion of feature information, allowing the convolutional kernels to adapt to the complex shape characteristics of cracks dynamically. A Global Attention Module (GAM) is integrated to improve the model’s perception of global information. The AKConv convolution operation is employed to adaptively adjust the size of convolutions, further enhancing local feature capturing. Additionally, a lightweight network design is implemented, establishing G-Head (Ghost-Head) as the detection head to optimize the issue of feature redundancy. Experimental results show that Flexi-YOLO achieves an accuracy increase of 2.7% over YOLOv8n, a recall rate rise of 4.7%, a mAP improvement of 5.3%, a mAP@0.5–0.95 increase of 3.9%, a decrease of 0.5 in GFLOPS, and an F1 score improvement from 0.80 to 0.84. Flexi-YOLO offers higher detection accuracy and robustness and meets the industrial demands for lightweight real-time detection and lower application costs, providing an efficient and precise solution for the automated detection of road cracks.
Marine fishes exhibit exceptional variation in biofluorescent emission spectra
Biofluorescence is a phylogenetically widespread phenomenon among marine fishes, yet the phenotypic diversity in fluorescent emission wavelengths (e.g., green, red) remains poorly studied across the broad diversity of marine teleosts. In this study we investigate the fluorescent emission spectra from a diverse array of 18 teleost families and record fluorescent emission peaks over multiple body regions. Our results show that fluorescent emission spectra are remarkably diverse among teleost families, as well as within genera. Fluorescent emissions also vary across different body regions within some individuals. We show that members of the families Gobiidae, Oxudercidae, and Bothidae exhibit at least six distinct, non-overlapping fluorescent emission peaks. Nine of the 18 families examined in this study were found to have at least four distinct and non-overlapping fluorescent emission peaks. Further, we find that several families exhibit multiple discrete emission peaks for a single fluorescent color (i.e., wavelength range), including multiple distinct peaks within the green and red portions of the spectrum. The interplay between different fluorescent emission wavelengths and notable variation in the distribution of fluorescence on the body could allow for a wide array of fluorescent patterns to be produced by an individual or among closely related species. Our results reveal far more diversity in both fluorescent emission wavelengths (colors) and in the distribution of fluorescent molecules across the body than had previously been reported in the literature. We characterize this novel variation in biofluorescent emissions across an array of teleost families and discuss the potential implications of this exceptional phenotypic variability.
Objective assessment of tinnitus laterality
Tinnitus is a condition which involves hearing sounds not present externally. This common condition can lead to a range of symptoms, including depression, resulting in a severe impact on quality of life. There are currently no reliable treatments for tinnitus. One factor hindering development of treatments is the lack of identified subtypes of tinnitus with different underlying patterns of neural activity to enable more personalised treatments and more accurate monitoring of treatment effects. It has been suggested that the perceived laterality of tinnitus, i.e., whether the sound is perceived unilaterally or bilaterally, characterizes tinnitus subtypes with different underlying neural changes. Our previous work showed sensitivity of a non-invasive brain imaging technique called functional near-infrared spectroscopy (fNIRS), to tinnitus-related changes in brain activity. In this study we aimed to investigate differentiating unilateral and bilateral tinnitus using fNIRS recordings and functional network analysis. We performed fNIRS recordings on 18 individuals with unilateral tinnitus (11 left-sided and 7 right-sided), 26 individuals bilateral tinnitus and 18 controls. fNIRS signals were recorded at rest and in response to auditory and visual stimuli. Using network analysis applied to fNIRS recordings, we derived modules characterized by strong connectivity among channels within a module and weak connectivity among channels in different modules. We then calculated two measures, Module Laterality and Modified Module Laterality, to quantify asymmetry in modules. Our findings showed significant difference in Module Laterality in individuals with unilateral tinnitus compared to both bilateral tinnitus and controls. Within the unilateral tinnitus group, Modified Module Laterality showed significant difference between individuals who experienced left-sided tinnitus compared to right-sided tinnitus. Differentiating tinnitus with distinct laterality precepts has the potential to assist in developing and monitoring relevant treatments by revealing neural mechanisms related to each subtype.
Identification and validation of differentially expressed genes in intramuscular fat metabolism in Guizhou yellow chickens using RNA-Seq analysis
Intramuscular fat (IMF) content is crucial for meat quality, and genetic, environmental, and nutritional factors influence its deposition. This study aims to identify genes involved in the regulation of IMF deposition in Guizhou Yellow Chickens. Thirty Guizhou Yellow Chicken hens aged 120 days were selected, and their IMF content was measured using the Soxhlet extraction method. The IMF content was divided into a high IMF group (H group, n = 4) and a low IMF group (L group, n = 4). RNA-seq was performed on the H and L groups to screen out signaling pathways and key genes that affect IMF deposition. A total of 259 differentially expressed genes(DEGs) were screened, including 195 that were up-regulated and 64 that were down-regulated. Critical genes such as COL1A1, COL1A2, COL6A3, PLTP, LPIN1, ITGA8, and FN1 were identified as key influencers of IMF deposition in Guizhou Yellow Chickens. The slow virus interference vector has demonstrated that interfering with COL1A1 can inhibit the proliferation ability of chicken preadipocytes and reduce lipid droplet accumulation. In addition, interference with COL1A1 significantly inhibited the expression of PLTP, ABHD6, LPIN1, and PTGS2 and decreased the levels of triglycerides and cholesterol at 4 and 8 days. The results further showed that COL1A1 is a key gene in the gene regulatory network during fat deposition, and the interaction of these genes affects the proliferation and differentiation of fat cells, thereby reducing the accumulation of fat droplets in muscle fibers. This study indicates that the COL1A1 gene is associated with IMF formation in Guizhou Yellow Chickens, providing a critical gene for selecting markers to control IMF formation and laying a foundation for future poultry meat quality breeding.
JAK inhibitor withdrawal causes a transient pro-inflammatory cascade: A potential mechanism for major adverse cardiac events
Objective Our objective was to define the effect of JAK inhibitor (JAKinib) withdrawal on JAK/STAT biochemical response in the context of systemic rheumatic diseases. Methods We tested Type I (bind kinase active conformation) and Type II (bind kinase inactive conformation) JAKinibs in vitro using mesenchymal stromal cells (MSCs) and human umbilical vein endothelial cells (HUVECs). We translated our findings in vivo studying NK cells from rheumatoid arthritis (RA) patients treated with Type I JAKinibs or methotrexate. Results Type I JAKinibs (ruxolitinib and baricitinib) increased phosphoJAK1 (pJAK1) and pJAK2 of IFNγ-stimulated MSCs and HUVECs in a time- and dose- dependent manner, with effect peaking after 24 hours. As expected, pSTAT1 was completely suppressed by JAKinibs. We found a marked and rapid increase of pSTATs upon discontinuation of Type I JAKinibs, that occurred to a lesser extent after Type II JAKinib withdrawal. Type I JAKinib withdrawal increased interferon and urokinase expression when compared to Type II JAKinib withdrawal. We found NK cells from RA patients taking Type I JAKinibs had a pro-inflammatory profile after JAKinib withdrawal compared to patients on methotrexate. Conclusions Type I JAKinibs paradoxically accumulate functionally defective pJAK. Upon withdrawal, the primed pJAKs are de-repressed and initiate a pSTAT signaling cascade, resulting in high interferon and urokinase. Type II JAKinibs do not cause pJAK accumulation, pSTAT cascade, and subsequent pro-inflammatory transcripts. The resultant cytokines and proteins produced from this cascade might explain adverse cardiac outcomes. Thus, JAKinib withdrawal is a possible mechanism contributing to the major adverse cardiac events described with JAKinib therapy.
Factors modulating the impact of the COVID-19 pandemic on posttraumatic stress symptomatology of the Spanish healthcare workers: A cohort study
Introduction The COVID-19 pandemic generated a global health crisis that significantly impacted healthcare systems and professionals. Healthcare workers were exposed to high levels of psychological distress, including posttraumatic stress symptomatology (PTSS). Aim Analyse the evolution of PTSS among Spanish healthcare workers during the COVID-19 pandemic, and to identify associated factors. Method A multicenter prospective cohort study with a 12-month follow-up was conducted. PTSS was the primary outcome. Secondary variables included sociodemographic, occupational, psychological, and coping-related factors. Statistical analyses comprised bivariate comparisons and multivariate modelling, such as generalized linear models and linear mixed models. Results Of the 428 participants, 180 completed the 12-month follow-up. At baseline, changes in work posts, negative family-work relations, avoidant coping, burnout symptoms, and emotional intelligence were associated with PTSS levels. Linear mixed models showed a significant decrease in PTSS over the 12-month period, regardless of gender, age, household type, occupational role, contract type, job title, level of care or type of service (p < 0.001). The generalised linear model explained 25.5% of the variance in PTSS levels at baseline, highlighting the role of psychological and coping factors over sociodemographic or occupational characteristics. Conclusions This study highlights the need for early identification and intervention focused on psychological and coping mechanisms. Promoting emotional regulation, reducing burnout, and addressing maladaptive coping may help mitigate long-term psychological effects among healthcare workers during public health crises.
Shortening 7T MP2RAGE acquisition with compressed sensing: Evaluating quantitative accuracy and structural consistency
The aim of this study was to systematically evaluate the impact of compressed sensing (CS) on acquisition time, image quality, T1 mapping accuracy, and segmentation consistency in magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) at ultra-high fields (UHF). MP2RAGE sequences were acquired using the CS and parallel imaging (PI) technique, i.e., generalized autocalibrating partially parallel acquisitions (GRAPPA), with varying undersampling factors and samples per repetition time (TR). The acquisition time, quantitative accuracy of T1 mapping, and segmentation consistency across regions of interest (ROIs) were assessed. CS-MP2RAGE achieved a 61% reduction in acquisition time (< 3 min) compared with PI-MP2RAGE and maintained comparable image quality, segmentation accuracy, and T1-mapping fidelity. Higher undersampling factors effectively reduced scan duration but introduced segmentation volume mismatches of up to 20% and increased T1 values, despite the images appearing similar to PI-MP2RAGE. Reducing the number of samples per TR enhanced image quality, allowing for higher undersampling factors without a significant loss of fidelity, a finding consistent with previous studies. However, excessively low sampling densities destabilized reconstruction in complex ROIs. Our findings demonstrate that CS-MP2RAGE significantly reduces scan time while maintaining high image quality and quantitative accuracy, making it a viable alternative to GRAPPA in UHF applications. The interplay between undersampling factors and samples per TR is crucial for optimizing scan efficiency. Future studies should explore its application in clinical and research settings.
Factors influencing the participation of surrogate decision-makers for advanced cancer patients in advance care planning: A cross-sectional study
Aim The aim of this study was to explore the factors influencing surrogate decision-makers (SDMs) engagement in Advance Care Planning (ACP). Design A cross-sectional Study. Method A total of 285 SDMs of advanced cancer patients were recruited using convenience sampling methods. All eligible participants completed the structured questionnaires. Univariate and correlation analyses were used to explore the relationship between different variables and the ACP engagement of SDMs. Factors significant previously in univariate or correlation analyses were included in the multiple linear regression analyses with P < 0.05. Results Eight factors in univariate analyses and three factors in correlation analyses with P < 0.05 were taken into multiple linear regression analyses. Finally, seven variables revealed a statistically significant association with ACP engagement of SDMs and were included in the multiple linear regression model. Conclusion This cross-sectional study demonstrated that multiple factors, including experiences of medical decision-making, education level, knowledge of ACP, treatment expenditure, uncertainty of disease, social support, and life orientation, significantly impacted the engagement of SDMs in ACP. Impact Based on this study, we have identified some factors influencing the ACP engagement of SDMs, which might provide basic information for construction of the educational scheme of ACP in mainland China and help to improve SDMs’ engagement in clinical ACP practice in the future. Patient or public contribution SDMs of advanced cancer patients participated in this study, and assisted in assessing the validation of the measurements.
Understanding stigma: The experiences of people with drug-sensitive pulmonary tuberculosis in Rawalpindi, Pakistan
Introduction Tuberculosis (TB) is a major global health problem and Pakistan is ranked fifth among the 30 high-burden countries in the world. TB-related stigma affects health seeking behaviour and treatment adherence, increasing disease transmission and worsening health outcomes. This study aimed to explore experiences of stigma among people with TB (PWTB) in Rawalpindi to help inform targeted stigma reduction interventions that could improve health seeking behaviour, treatment adherence and the mental well-being of PWTB in Pakistan. Methodology In-depth interviews were conducted with 15 people with pulmonary drug sensitive TB from Rawalpindi, Pakistan. For assessing emerging themes, an inductive themed analysis approach was used. Next, a deductive approach was applied by analysing and interpreting the data against the Health Stigma and Discrimination Framework. Results TB- related stigma among participants was driven by fear of infection, which in some cases was due to misconceptions surrounding TB transmission as well as social judgement and gender norms. Stigma manifested through: anticipated and perceived stigma in the form of non-disclosure and fear of social exclusion; enacted stigma among friends and family, in the workplace and healthcare settings; and internalised stigma, The negative outcomes of stigma that resulted for some participants included non- adherence and social exclusion, in the form of loss of marriage prospects and employment. Conclusion This study confirms that TB-related stigma persists in Pakistan, impacting he well-being, medication adherence and treatment outcomes of PWTB. The distinct drivers, manifestations and outcomes of stigma in Rawalpindi Pakistan uncovered from this study, supported by previous research, can help inform targeted stigma reduction interventions such as public education programmes.
Development and use of integrated wetland condition index for lacustrine fringe wetlands of Lake Tana, Northwest Ethiopia
This research aimed to develop an integrated wetland condition index (IWCI) for lacustrine fringe wetlands (LFWs) in Lake Tana, Northwest Ethiopia. These wetlands have been highly impacted by recessionary agriculture, water hyacinth infestation, and both short- and long-term water level fluctuations (WLFs), as well as a heavy sediment load. The lacustrine wetland condition index was developed based on four key characteristics (hydrology, water quality, sediment quality, and wetland biota) that define wetlands. Value obtained from field and laboratory measurements of each wetland hydrology, water chemistry, and sediment characteristics indicator was normalized by allocating scores based on literature information and the results of this research project from three different disturbance-level lacustrine wetlands in Lake Tana. Macrophyte, diatom, and zooplankton indicator species tests (IndVal% and p (raw)) were calculated using PAST 4.14 (PAleontological STatistics). Scores were allocated on a scale from 1 to 10, in such a way that the highest scores reflected the best conditions and the lowest scores the most disturbed and unhealthy conditions. Within each of the four sub-indexes, multiple measures were equally weighted, while the four-wetland components (hydrology, water chemistry, sediment, and biota) were weighted according to their contribution to overall wetland condition. Weights were assigned using the Decision Support System Software of DEFINITE. Finally, the total IWCI was classified into five wetland condition categories, namely: very poor or very far from the reference (0–3), poor (3–5), moderate (5–7), good (7–9), and excellent wetland condition or reference condition (9–10). The results of IWCI of the low water level period indicated that eight wetland-sampling sites were found within a moderately impacted condition (44.44%); similarly, eight wetland-sampling sites were found within a good or mildly impacted condition; and only two wetland- sampling sites (11.11%) were found in an excellent or reference condition. Thus, this IWCI developed and tested in this study could be a tool to inform decision-makers on lacustrine wetland conservation and restoration priorities throughout the Lake Tana ecosystem. For managing and restoring shore area wetlands and making policy, lacustrine fringe wetlands monitoring sites need to be established and monitored for their condition using IWCI developed and tested by this study.
TBpore cluster: A novel phylogenetic pipeline for tuberculosis transmission studies using nanopore next-generation sequencing data
Background Molecular typing of Mycobacterium tuberculosis complex isolates enhances understanding of tuberculosis (TB) transmission dynamics, supporting public health efforts in outbreak investigations. This study aims to validate TBpore, a novel bioinformatic pipeline for clustering TB transmission isolates using Oxford Nanopore Technology (ONT) data and comparing it against conventional Mycobacterial Interspersed Repetitive-Unit Variable Number (MIRU-VNTR) typing and Illumina sequencing. Methodology/Principal findings This retrospective case-control study included 58 clinical isolates from two TB outbreaks in Canada, previously characterized by public health investigations and MIRU-VNTR typing. DNA extraction and sequencing were performed on both Illumina and ONT platforms. Illumina data were processed using Clockwork and psdm, while Nanopore data were analyzed with TBpore. SNP distances were used to compare clustering results across methods, with clusters defined by SNP distance thresholds of ≤5 and ≤12. Both sequencing methods showed a high degree of concordance in clustering results. All isolates from the M. africanum outbreak clustered within the defined SNP thresholds, consistent with MIRU-VNTR and epidemiological data. In the M. tuberculosis outbreak, 20 out of 21 isolates clustered similarly across methods, with one exception. Within outbreak pairwise SNP distances were lower with Nanopore. Conclusion/Significance ONT sequencing and the TBpore pipeline offer an accurate alternative to Illumina technology for TB molecular epidemiology. This study suggests potential increased clustering sensitivity with Nanopore technology, warranting further validation on larger datasets with robust epidemiological metadata.
The effects of genres on the development of multifaceted linguistic complexity in Chinese learners of German: A longitudinal corpus analysis
Genre-based research holds significant theoretical and practical importance in second language acquisition (SLA). While many L2 English writing studies have suggested argumentative writing was generally more challenging than narrative, whether this generalization applies to typologically different languages, such as German with its complex morphological and structural properties, requires further investigation. Specifically, genre effects on L2 writing development remain insufficiently understood for non-English languages, particularly regarding complexities beyond syntactic and lexical. This study examines how genre influences the development of morphological, lexical, syntactic, and cohesive complexity in elementary-intermediate Chinese learners of German over time. A longitudinal corpus of narrative and argumentative essays from 21 learners, who wrote both genres, was analyzed. The results show that genre effects were evident but not straightforward, with no genre consistently exhibiting greater complexity. Over time, learners predominantly exhibited nonlinear development patterns, suggesting the dynamic nature of SLA. Additionally, they exhibited decreasing lexical sophistication in both genres despite improvements in other complexity measures, indicating a “complexity trade-off” between linguistic subsystems. These findings contribute empirical evidence to the cross-linguistic comparisons in SLA research and suggest that curricula should incorporate diverse genres to develop multifaceted linguistic competence, with pedagogical approaches tailored to genre-specific complexity patterns and developmental trajectories.
Novel fungal metabolites as dual cholinesterase inhibitors: A computational approach for Alzheimer’s disease therapy
Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is a major global health concern, affecting millions worldwide, with its prevalence expected to triple by 2050. Despite the widespread use of traditional drugs like cholinesterase inhibitors and NMDA receptor antagonists, their limited effectiveness requires innovative therapeutic approaches. This work used Computer-Aided Drug Design (CADD) to renovate AD therapies aimed at both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using fungal secondary metabolites. Subsequent pharmacokinetic profiles indicated that all metabolites had significant gastrointestinal absorption, blood-brain barrier permeability, and adherence to Lipinski’s Rule of Five, suggesting favourable drug-like properties. Furthermore, these metabolites exhibited little toxicity, except for Lovastatin, which indicated possible carcinogenicity. Molecular docking revealed three main candidates—Fumitremorgin C, Hericenone J, and Lovastatin—with notable binding affinities for AChE and BuChE. Consequently, the Fumitremorgin C showed the highest affinity for AChE (−10.0 kcal/mol), but Hericenone J showed enhanced inhibition of BuChE (−9.2 kcal/mol), suggesting its potential use in advanced stages of AD. Molecular dynamics simulations spanning 100 ns validated the stability of enzyme-ligand complexes, with Hericenone J exhibiting the greatest stability, low RMSD, and strong hydrogen bond interactions. The RMSF analysis further demonstrated that Hericenone J preserved structural integrity, whereas ROG and SASA values validated its compactness and stability. As determined by binding energy calculations, Hericenone J had the most inhibitory potential, followed by Lovastatin. However, Hericenone J’s constant adoption of low-energy conformations, as shown by the principal component and Gibbs free energy analyses, suggested robust and stable interactions with both cholinesterases. With its superior pharmacokinetic profiles, significant binding affinity, and high stability, Hericenone J is the most promising dual cholinesterase inhibitor. These results support the notion that Hericenone J might be an effective treatment for AD if subjected to more preclinical trials.
Clonal integration and Bacillus subtilis modulate Glechoma longituba performance and soil microbial communities
Many medicinal plants exhibit clonality, but the impact of clonal integration and its interaction with exogenous microbial agents on these plants remains unknown. In order to investigate this, we conducted a greenhouse experiment using Glechoma longituba, a common clonal medicinal herb. Pairs of connected ramets were grown in the two adjacent pots, with one pot containing basal (relatively older) ramets treated with or without Bacillus subtilis agent and the other pot containing apical (relatively younger) ramets without B. subtilis agent treatment, the connection between basal and apical ramets were either left intact or severed. Clonal integration reduced the growth of basal ramets, but increased the apical ramet growth. B. subtilis agent primarily affected the root-shoot ratio of both basal and apical ramets as well as the whole fragments. Furthermore, it exhibited a significant interaction with clonal integration in affecting the root-shoot ratio of basal ramets and whole plant fragments. Addition of B. subtilis reduced the content of total flavonoids and chlorogenic acid in basal portions and chlorogenic acid at the whole fragment level. Clonal integration and B. subtilis agent significantly changed the composition of soil fungal communities of basal portions and bacterial communities of apical portions. The fungal composition of basal portions responded reciprocally to clonal integration and B. subtilis, with a significant increase in the relative abundance of Basidiomycota and a decrease in Ascomycota under clonal integration, whereas the effect of B. subtilis was opposite. B. subtilis significantly increased fungal diversity in basal portions while decreasing bacterial diversity in apical portions under clonal integration. However, neither clonal integration nor B. subtilis has showed a positive effect on the overall growth and quality of G. longituba. These findings provide valuable insights into its role in scientific cultivation and management of the clonal medicinal plants in the practical production.
National Early Warning Score 2 (NEWS2) as a prognostic tool for adult patients in emergency department: A retrospective observational study
The National Early Warning Score 2 (NEWS2) has been widely adopted to assess the severity of illness across various healthcare settings. However, its effectiveness as a prognostic tool specifically within the Emergency Department (ED) has not been validated in Malaysia. This retrospective observational study aimed to evaluate the performance of NEWS2 in predicting hospitalizations, critical care unit admissions, and in-hospital mortality among adult patients in a Malaysian ED, specifically at the Hospital Canselor Tuanku Muhriz. The discriminatory ability of NEWS2 was analysed using the area under the receiver operating characteristic curve. A total of 1906 adult patients were included in the study, with results indicating that NEWS2 demonstrated moderate to excellent performance in predicting outcomes. The AUROC values were 0.71 for hospitalization, 0.75 for critical care admission, and 0.86 for in-hospital mortality. Additionally, subgroup analyses for patients with sepsis and those with COVID-19 were also conducted. NEWS2 score however was not as effective in predicting critical outcomes for these two subgroups, limiting its utility as an early warning tool in diverse clinical scenarios. Overall, the results suggest that NEWS2 is a valuable tool for early risk stratification in the general adult population in the ED. Implementing NEWS2 into routine clinical practice could significantly enhance patient outcomes by promoting timely and informed decision-making, ultimately benefiting both patients and healthcare providers.