Search

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with advanced driver-negative non-small cell lung cancer (NSCLC). However, targeted therapy remains the preferred treatment for advanced driver-positive NSCLC, including cases with epidermal growth factor receptor (EGFR) mutations. Considering the variability in EGFR-mutant NSCLC, including expression levels of programmed cell death ligand 1 (PD-L1), tumor mutation burden (TMB), and other immunological features, the application of immunotherapy in this group is still a subject of investigation. Therefore, we have summarized and analyzed the immunological characteristics and regulatory mechanisms of different EGFR mutations in NSCLC, as well as the current clinical application of immunotherapy in the EGFR-mutant population, to provide a reference for future research.

In recent years, as deepfake technology matures, face-swapping software and synthesized videos have become widespread. While these techniques offer entertainment, they also provide opportunities for misuse by malicious actors. Consequently, the significance of deepfake detection technology has grown markedly. Existing methods for deepfake detection commonly suffer from issues including poor cross-compression robustness, weak cross-dataset generalization, and high model training overheads. To address these challenges, this paper proposes a deepfake detection approach that combines multiple parameter-efficient fine-tuning techniques. This method utilizes a visual Transformer model pretrained with the masked image modeling self-supervised method as its backbone. Initially, it employs the low-rank adaptation (LoRA) method for fine-tuning the self-attention module parameters of the pretrained model. Concurrently, it introduces a parallel structure incorporating convolutional adapters to capture local texture information, enhancing the model’s adaptability in deepfake detection tasks. Subsequently, a serial structure introduces classical adapters to fine-tune the feed-forward network of the pretrained model, maximizing the utilization of knowledge acquired during the pretraining phase. Ultimately, a multi-layer perceptron replaces the original pretrained model’s classification head for deepfake detection. Experimental results across six datasets demonstrate that this model achieves an average frame-level AUC of approximately 0.996 with only 2×107 trainable parameters. In cross-compression experiments, the average frame-level AUC drop is 0.135. In cross-dataset generalization experiments, the frame-level AUC averages around 0.765.

Abstract Although serum uric acid (SUA) is a risk factor for cardiometabolic outcome, but it remains unclear which patients with coronary artery disease (CAD) benefit the most from SUA lowering therapy (ULT). The association of SUA level, systemic inflammation and cardiometabolic risk is still unclear. The current study is aimed to examine whether SUA-associated cardiometabolic risk is modulated by systemic inflammation in CAD patients. A total of 16,598 CAD patients with baseline high-sensitivity C-Reactive Protein (hsCRP) and SUA available were included. Baseline and follow-up data were collected. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction and stroke. In patients with hsCRP ≥ 2 mg/L, increasing quintiles of SUA were significantly associated with increased rates of 2-year MACCE (adjusted p

Abstract The ability to lubricate and resist wear at temperatures above 600 °C in an oxidative environment remains a significant challenge for metals due to their high-temperature softening, oxidation, and rapid degradation of traditional solid lubricants. Herein, we demonstrate that high-temperature lubricity can be achieved with coefficients of friction (COF) as low as 0.10-0.32 at 600-900 °C by tailoring surface oxidation in additively-manufactured Inconel superalloy. By integrating high-temperature tribological testing, advanced materials characterization, and computations, we show that the formation of spinel-based oxide layers on superalloy promotes sustained self-lubrication due to their lower shear strength and more negative formation and cohesive energy compared to other surface oxides. A reversible phase transformation between the cubic and tetragonal/monoclinic spinel was driven by stress and temperature during high temperature wear. To span Ni- and Cr-based ternary oxide compositional spaces for which little high-temperature COF data exist, we develop a computational design method to predict the lubricity of oxides, incorporating thermodynamics and density functional theory computations. Our finding demonstrates that spinel oxide can exhibit low COF values at temperatures much higher than conventional solid lubricants with 2D layered or Magnéli structures, suggesting a promising design strategy for self-lubricating high-temperature alloys.

Abstract Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by difficulties in early diagnosis, prone to distant metastasis, and high recurrence rates following surgery. Extracellular vesicles (EVs) are a class of cell-derived particles, including exosomes, characterized by a phospholipid bilayer. They serve as effective carriers for intercellular communication cargo, including proteins and nucleic acids, and are widely involved in tumor progression. They are being explored as potential tumor biomarkers and novel therapeutic avenues. We provide a brief overview of the biogenesis and characteristics of EVs to better understand their classification standards. The focus of this review is on the research progress of EV-associated proteins in the field of HCC. EV-associated proteins are involved in tumor growth and regulation in HCC, participate in intercellular communication within the tumor microenvironment (TME), and are implicated in events including angiogenesis and epithelial-mesenchymal transition (EMT) during tumor metastasis. In addition, EV-associated proteins show promising diagnostic efficacy for HCC. For the treatment of HCC, they also demonstrate significant potential including enhancing the efficacy of tumor vaccines, and as targeting cargo anchors. Facing current challenges, we propose the future directions of research in this field. Above all, research on EV-associated proteins offers the potential to enhance our comprehension of HCC and offer novel insights for developing new treatment strategies.

Abstract A novel approach is proposed to probe the nature of the double charm tetraquark through the prompt production asymmetry between $$T_{\bar{c}\bar{c}}^-$$ T c ¯ c ¯ - and $$T_{cc}^+$$ T cc + in pp collisions. When comparing two theoretical pictures, i.e. the compact tetraquark and hadronic molecular pictures, we find that the former one exhibits a significantly larger production asymmetry, enabling the unambiguous determination of the tetraquark’s internal structure. Additionally, distinctive differences in the transverse momentum and rapidity distributions of $$T_{\bar{c}\bar{c}}^-$$ T c ¯ c ¯ - and $$T_{cc}^+$$ T cc + cross sections emerge, particularly at $$p_\textrm{T}\approx 2~\textrm{GeV}$$ p T ≈ 2 GeV and $$y\approx \pm 6$$ y ≈ ± 6 at a center-of-mass energy of 14 $$~\textrm{TeV}$$ TeV . The insignificant asymmetry in hadronic molecular picture is because that hadronic molecules are produced in hadronic phase, where the phase space of their constituents needs to be taken into account rigorously. Our work can be extended to the exploration of other double heavy tetraquark candidates, offering a versatile approach to advance our understanding of exotic hadrons.

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months. Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count 200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

Abstract Background Atrial fibrillation (AF) is highly correlated with heart failure, stroke and death. Screening increases AF detection and facilitates the early adoption of comprehensive intervention. Long-term wearable devices have become increasingly popular for AF screening in primary care. However, interpreting data obtained by long-term wearable ECG devices is a problem in primary care. To diagnose the disease quickly and accurately, we aimed to build AF episode detection model based on a nonlinear Lorenz scattergram (LS) and deep learning. Methods The MIT-BIH Normal Sinus Rhythm Database, MIT-BIH Arrhythmia Database and the Long-Term AF Database were extracted to construct the MIT-BIH Ambulatory Electrocardiograph (MIT-BIH AE) dataset. We converted the long-term ECG into a two-dimensional LSs. The LSs from MIT-BIH AE dataset was randomly divided into training and internal validation sets in a 9:1 ratio, which was used to develop and internally validated model. We built a MOBILE-SCREEN-AF (MS-AF) dataset from a single-lead wearable ECG device in primary care for external validation. Performance was quantified using a confusion matrix and standard classification metrics. Results During the evaluation of model performance based on the LS, the sensitivity, specificity and accuracy of the model in diagnosing AF were 0.992, 0.973, and 0.983 in the internal validation set respectively. In the external validation set, these metrics were 0.989, 0.956, and 0.967, respectively. Furthermore, when evaluating the model’s performance based on ECG records in the MS-AF dataset, the sensitivity, specificity and accuracy of model diagnosis paroxysmal AF were 1.000, 0.870 and 0.876 respectively, and 0.927, 1.000 and 0.973 for the persistent AF. Conclusions The model based on the nonlinear LS and deep learning has high accuracy, making it promising for AF screening in primary care. It has potential for generalization and practical application.

Malaria remains a major public health concern. The rapid spread of resistance to antimalarial drugs is a major challenge for malaria eradication. Timely and accurate molecular monitoring based on practical detection methods is a critical step toward malaria control and elimination. In this study, two rapid detection techniques, allele-specific PCR (AS‒PCR) and recombinase-aided amplification (RAA) combined with CRISPR/Cas12a, were established, optimized and assessed to detect single nucleotide polymorphisms in the Plasmodium falciparum exonuclease (Pfexo) gene related to suspected piperaquine resistance. Moreover, phosphorothioate and artificial mismatches were introduced into the allele-specific primers for AS‒PCR, and crRNA-mismatched bases were introduced into the RAA‒CRISPR/Cas12a assay because crRNAs designed according to conventional rules fail to discriminate genotypes. As a result, the detection limits of the AS‒PCR and RAA‒CRISPR/Cas12a assays were 104 copies/μL and 103 copies/μL, respectively. The detection threshold for dried blood spots was 100‒150 parasites/μL, with no cross-reactivity against other genotypes. The average cost of AS‒PCR is approximately $1 per test and takes 2–3 h, whereas that of the RAA‒CRISPR/Cas12a system is approximately $7 per test and takes 1 h or less. Therefore, we provide more options for testing single nucleotide polymorphisms in the Pfexo gene, considering economic conditions and the availability of instruments, equipment, and reagents, which can contribute to the molecular monitoring of antimalarial resistance.

The lung is an important site of extramedullary platelet formation, and megakaryocytes in the lung participate in immune responses in addition to platelet production. In acute lung injury and chronic lung injury, megakaryocytes and platelets play a promoting or protective role through different mechanisms. The authors reviewed the role of megakaryocytes and platelets in common clinical lung injuries with different course of disease and different pathogenic factors in order to provide new thinking for the diagnosis and treatment of lung injuries.

Background: The optimal glycosylated hemoglobin (HbA1c) target in type 2 diabetes mellitus (T2DM) patients remains controversial, especially in patients with concomitant coronary heart disease (CHD). This study aimed to investigate the correlation between baseline HbA1c and long-term prognosis in CHD patients with T2DM. Methods: The study enrolled 6,839 CHD patients with T2DM and measured HbA1c at admission in a multicenter prospective observational cohort. Patients were divided into two groups according to baseline HbA1c levels: optimal glycemic control group (HbA1c

Abstract Background Functional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess animal models of rotator cuff tears, it is less relevant for human patients as the human shoulder is typically assessed in a non-weight-bearing condition. The present study introduces the skilled reaching test as a shoulder functional assessment tool for rats, which allows for evaluation without weight bearing. Methods In the control group, 8 male Sprague–Dawley rats received rotator cuff tear surgery without repair. In the rotator cuff repair group, 20 rats received rotator cuff repair at 4 weeks post rotator cuff tear. For the skilled reaching test, rats were trained to extend their forelimbs to fetch food pellets, and the number of trials, number of attempts and the success rate were recorded. The gait analysis and skilled reaching test were performed at baseline, 4 weeks post-tear, 1, 2, 4, and 8 weeks post-repair. The repeated measures analysis of variance was used to evaluate the effects of time on the shoulder function. The significance level was set at 0.05. Results The skilled reaching test required 216 h to conduct, while the gait analysis took 44 h. In the rotator cuff repair group, gait performance significantly deteriorated at 1 week post-repair and restored to 4 weeks post-tear levels at 4 weeks post-repair. Regarding the skilled reaching test, the number of attempts, number of trials and the success rate decreased at 1 week post-repair. Subsequently, there was a brief rebound in performance observed at 2 weeks post-repair, followed by a continued decline in the number of attempts and trials. By 8 weeks post-repair, only the success rate had restored to levels similar to those observed at 4 weeks post-tear. Conclusion The skilled reaching test can detect functional deficiencies following rotator cuff tear and repair, while it requires high time and labour costs.

Abstract Background Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous studies have revealed that mutations in the SALL1 gene can disrupt normal development, resulting in the characteristic features of Townes-Brocks syndrome. Spalt-like transcription factors (SALLs) are highly conserved proteins that play important roles in various cellular processes, including embryonic development, cell differentiation, and cell survival. Over 400 different variants or mutations have been reported in the SALL1 gene in individuals with TBS. Most of these variants lead to the formation of premature termination codons (PTCs), also known as nonsense mutations. The majority of these PTCs occur in a specific region of the SALL1 gene called the “hotspot region”, which is particularly susceptible to mutation. Methods In this study, we conducted whole-exome sequencing on a three-generation Chinese family with anorectal malformations. Results We identified a novel heterozygous mutation (chr16:51175376:c.757 C > T p.Gln253*) in the SALL1 gene. Molecular analysis revealed a heterozygous C to T transition at nucleotide position 757 in exon 2 of the SALL1 (NM_002968) gene. This mutation is predicted to result in the substitution of the Gln253 codon with a premature stop codon (p.Gln253*). The glutamine-rich domain forms a long alpha helix, enabling the mutant protein to interact with the wild-type SALL1 protein. This interaction may result in steric hindrance effects on the wild-type SALL1 protein. Conclusions Our findings have expanded the mutation database of the SALL1 gene, which is significant for genetic counseling and clinical surveillance in the affected family. Furthermore, our study enhances the understanding of Townes-Brocks syndrome and has the potential to improve its diagnosis and treatment.

Abstract Background Currently, the differentiation between benign and malignant cystic pulmonary nodules poses a significant challenge for clinicians. The objective of this retrospective study was to construct a predictive model for determining the likelihood of malignancy in patients with cystic pulmonary nodules. Methods The current study involved 129 patients diagnosed with cystic pulmonary nodules between January 2017 and June 2023 at the Neijiang First People’s Hospital. The study gathered the clinical data, preoperative imaging features of chest CT, and postoperative histopathological results for both cohorts. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, from which a prediction model and nomogram were developed. In addition, The model's performance was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Results A cohort of 129 patients presenting with cystic pulmonary nodules, consisting of 92 malignant and 37 benign lesions, was examined. Logistic data analysis identified a cystic airspace with a mural nodule, spiculation, mural morphology, and the number of cystic cavities as significant independent predictors for discriminating between benign and malignant cystic lung nodules. The nomogram prediction model demonstrated a high level of predictive accuracy, as evidenced by an area under the ROC curve (AUC) of 0.874 (95% CI: 0.804–0.944). Furthermore, the calibration curve of the model displayed satisfactory calibration. DCA proved that the prediction model was useful for clinical application. Conclusion In summary, the risk prediction model for benign and malignant cystic pulmonary nodules has the potential to assist clinicians in the diagnosis of such nodules and enhance clinical decision-making processes.

Abstract Background The inter-reviewer reliability of the risk of bias (RoB) assessment lacked agreement in previous studies. It is important to analyse these disagreements to improve the repeatability of RoB assessment. The objective of the study was to evaluate the frequency and reasons for disagreements in RoB assessments for randomised controlled trials (RCTs) that were included in multiple Cochrane reviews in the field of hypertension. Methods A cross-sectional study was employed. We retrieved any RCTs that had been included in multiple Cochrane reviews in the field of hypertension from ARCHIE. The results of the RoB assessments were extracted, and the distributions of agreements and possible reasons for disagreement were analyzed. Results Twenty-six Cochrane reviews were included in this study. A total of 78 RCTs appeared in more than one Cochrane review. The level of agreement ranged from domain to domain. “Blinding of outcome assessment” showed a reasonably high level of agreement (94.9%), while “incomplete outcome data”, “selective outcome reporting” and “other sources of bias” showed moderate levels of agreement (74.6%, 79.2% and 75.6%, respectively). However, the domains of “allocation concealment”, “random sequence generation” and “blinding of participants and personnel” showed low levels of agreement (24.4%, 23.5%, and 47.4%, respectively). In the domains of “allocation concealment” and “blinding of participants and personnel”, the agreement group had higher proportion of publication year ≤ 1996 than the disagreement group (P = 0.008 and P

Objective: To investigate the regulatory effect of Fas-L on the repair and regeneration of peripheral extension injury in rats. Methods: This study aimed to explore the effects of Fas-L on apoptosis and axonal regeneration of dorsal root ganglion (DRG) cells in rat peripheral nerve repair and regeneration by using several relevant experimental techniques from the injured nerve animal model, cell biology, and molecular biology. Results: The expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Interference with Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis, while the overexpression of Fas-L is contrary to it. Moreover, Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in Sprague Dawley (SD) rats by affecting several signaling pathways, such as p-AKT/AKT, β-catenin, and NF-κB. Conclusion: Fas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves. Significance statement: The expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis. Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in SD rats by affecting several signaling pathways, such as p-AKT/AKT, β-catenin, and NF-κB. Fas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves.

Abstract Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.

BackgroundDementia poses a growing global mental health impact, with variations in prevalence by gender, possibly influenced by reproductive factors. Ectopic pregnancy (EP), known for its association with cardiovascular diseases and depression, which are also predictors of dementia, prompted an exploration of their interplay.MethodsUsing Taiwan’s National Health Insurance Research Database, this nationwide cohort study examined 53,096 individuals to investigate the link between EP and dementia. Covariates included age, insured premiums, comorbidity by Charlson Comorbidity Index revised by excluding dementia, level of care, and residence. Surgical approaches, number of EP episodes, and dementia subtypes were considered in outcomes analysis using Cox regression.ResultsAmong 13,274 women diagnosed with EP, 791 developed dementia over a 15-year follow-up, particularly vascular dementia. Adjusting for the covariates, the adjusted sub-distribution Hazard Ratio (asHR) with competing risks was 1.644 (95% CI, 1.394–2.053; p < 0.001). For patients with more than one episode, it was even higher (asHR=1.670 [95% CI, 1.419–2.092; p < 0.001]). Post-ectopic depression, prevalent in 62.2% within four weeks, was associated with a greater dementia risk compared to those without (asHR=1.702 [95% CI, 1.444-2.125; p

Abstract Background The triglyceride–glucose (TyG) index and high‐sensitivity C‐reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). Methods A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all‐cause death, nonfatal myocardial infarction, and revascularization. Results During the 2‐year follow‐up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. Conclusion Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high‐risk populations and guiding management strategies among CCS patients.

In a variety of cancers, immune checkpoint inhibitors (ICIs) have demonstrated substantial survival advantages. Nevertheless, the widespread use of ICIs in the clinic has resulted in a growing interest in immune-related adverse events (irAEs) and their treatment methods. This paper reports a case in which a patient with three sequential severe irAEs was successfully treated. After undergoing two regimens of sintilimab in conjunction with chemotherapy for advanced lung cancer, the patient developed myocarditis combined with hepatitis. Subsequently, the patient developed pneumonia following remission from treatment. We also discuss the mechanism of irAEs, principles of treatment, and progress in the study of biomarkers for early prediction of irAEs by reviewing the literature.

Introduction Hypertension and depression often coexisted, leading to poor health outcome and significant challenges in healthcare management. Since no guidelines or consensus are available for health professionals to manage this comorbidity, identifying interventions in current literature is crucial for gaining a clear picture of evidence and informing future research directions and clinical practice. This scoping review is designed to address this gap by systematically mapping the range of potential interventions for managing comorbid hypertension and depression.Methods and analysis Following the Joanna Briggs Institute guidelines for scoping review, this review will comprehensively search databases including PUBMED, Embase, PsycINFO, CINAHL, Cochrane Library Databases, Chinese Biomedical Literature Database and Chinese National Knowledge Infrastructure. Grey literature will be sourced from Google Scholar. A year limit of January 2004–December 2023 will be applied to retrieve the most current peer-reviewed articles in English and Chinese language only. Two reviewers will individually screen and the process will be documented in Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews. This review will explore a range of non-pharmacological and multicomponent interventions including psychosocial support, educational programmes, telemedicine and integrated healthcare models. Data extraction will follow the Template for Intervention Description and Replication checklist to ensure detailed and standardised reporting of intervention components. The synthesis of findings will employ both quantitative and qualitative methods to provide a comprehensive overview of the intervention landscape.Ethics and dissemination This scoping review, which involves secondary data analysis of publicly available sources, does not require ethical approval. Findings will be disseminated through peer-reviewed publications and presentations at relevant conferences.Study registration Open Science Framework registry (osf.io/j7gt8) in Centre for Open Science on 29 January 2024.

Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.

Abstract Horizontal gene transfer (HGT) and gene duplication are often considered as separate mechanisms driving the evolution of new functions. However, the mobile genetic elements (MGEs) implicated in HGT can copy themselves, so positive selection on MGEs could drive gene duplications. Here, we use a combination of modeling and experimental evolution to examine this hypothesis and use long-read genome sequences of tens of thousands of bacterial isolates to examine its generality in nature. Modeling and experiments show that antibiotic selection can drive the evolution of duplicated antibiotic resistance genes (ARGs) through MGE transposition. A key implication is that duplicated ARGs should be enriched in environments associated with antibiotic use. To test this, we examined the distribution of duplicated ARGs in 18,938 complete bacterial genomes with ecological metadata. Duplicated ARGs are highly enriched in bacteria isolated from humans and livestock. Duplicated ARGs are further enriched in an independent set of 321 antibiotic-resistant clinical isolates. Our findings indicate that duplicated genes often encode functions undergoing positive selection and horizontal gene transfer in microbial communities.