Transcatheter mitral valve replacement (TMVR) is a promising therapy for reducing mitral regurgitation in select patients. Direct tip control of multi-segment catheters can simplify manipulation and enable precise, stable positioning. This paper introduces MitraNav, the first robotic system developed for dock-based TMVR, focusing on system design and task-space control of the dock catheter. Built on a previously validated guide-sheath robot, MitraNav is upgraded to support concentric multi-catheter manipulation via a unified actuation mechanism. It suits both dock and balloon catheters, enabling all catheter manipulation using a single robotic system. A two-segment bending model maps joint space to task space through an intermediate configuration space. A two-stage control strategy is then applied: joint-space control allows for rapid approach to the mitral annulus, followed by task-space control for direct tip positioning. To improve accuracy and handle joint limits, the task-space controller incorporates Jacobian normalization to balance joint contributions, null-space optimization to regulate joint motion without affecting the primary task, and a PD controller to reduce tracking errors. Trajectory-following experiments demonstrate feasibility of direct tip control, with maximum errors of 2.38 mm, 2.53 mm, and 2.46 mm in three trials. These positional errors are within the range of acceptable accuracy commonly considered for catheter-based cardiac interventions. MitraNav represents the foundation for intuitive catheter manipulation and offers the potential for semi-autonomous robotic dock-based TMVR.
Aiming at the control problems of strong nonlinearity, multi-channel coupling and complex aerodynamic disturbance of flapping-wing aircraft, this study proposes an environment-adaptive cascade control switching method based on the PID architecture. A physical control closed-loop is established using MWORKS.Sysplorer, with classical PID as the outer main loop and PID, nonlinear compensation PID, and SMC as the inner loop to form a nested structure, which is cross-validated via MATLAB/Simulink. Through the disturbance quantization parameter k, operating conditions are classified into high, medium, and low disturbances for strategy switching. At the classical flapping frequency of 15 Hz, the proposed method converges the attitude error to within 0.06 rad, improves the anti-disturbance performance under high disturbance by 46.2% compared with traditional PID, constrains the phase lag to the stable interval corresponding to the natural frequency of 50 rad/s, and optimizes computational efficiency with the average single-step simulation time ≤ 0.02 s. This method addresses the insufficient full-working-condition adaptability of traditional single control strategies, and provides a highly robust implementation approach for the control of flapping-wing aircraft under complex disturbances.
Clinical empathy refers to a healthcare professional's ability to understand a patient's experiences and emotions through cognitive and affective perspective taking, and to communicate that understanding through compassionate and appropriate professional behaviors. Aging simulation suits are experiential educational tools designed to replicate the sensory and physical limitations associated with aging. However, evidence regarding their effectiveness in enhancing clinical empathy among active healthcare professionals remains limited. This study aimed to evaluate the effects of an aging simulation suit on clinical empathy among healthcare professionals working in long-term care settings. A randomized controlled trial was conducted with 82 healthcare professionals from four nursing homes in Madrid and Asturias (Spain). Participants were randomly assigned to an experimental group (EG) (n=41) or a control group (CG) (n=41). Both groups received the same structured educational session on empathy and aging. The experimental group additionally participated in an immersive experience using the GERT aging simulation suit, whereas the control group did not receive the simulation component. Self-reported empathy were measured pre- and post-intervention using the Interpersonal Reactivity Index (IRI) and the Jefferson Scale of Empathy-Health Professions version (JSPE-HPS). No significant differences were found between groups in IRI scores. However, the experimental group showed significant improvements in total JSPE-HPS scores and in the subscales Perspective Taking and Compassionate Care (p < 0.05), compared with the control group. These findings suggest that the immersive intervention enhanced both cognitive and affective components of clinical empathy. The use of an aging simulation suit was associated with improvements in specific dimensions of clinical empathy among healthcare professionals working in long-term care. This educational tool offers a valuable experiential approach that enhances understanding and compassion toward older adults. However, these findings are limited to short-term, self-reported measures, and no behavioral or patient outcome data were collected. Further longitudinal studies are needed to determine the long-term sustainability of these effects and their translation into clinical practice. ClinicalTrials.gov, Unique Protocol ID: 2711201916919; ClinicalTrials.gov ID: NCT07280689. Date of registration: 10/10/2025. Retrospectively registered.
The purpose of this study was to measure the effect of motivational interviewing on both reducing internet addiction and digital game addiction in adolescents. A parallel-group randomised controlled trial was adopted. The study population consisted of ninth-grade (14-15 years of age) high school students in a city in Turkiye. The study was completed by 88 participants (experimental: 44; control: 44). The data were collected using a Personal Information Form, the Young Internet Addiction Test, and the Digital Game Addiction Scale. The experimental group received a preparatory session and five weekly motivational interviewing sessions. Instruments were administered to both groups before (pre-test) and after the intervention (post-test), and at follow-up tests 3 and 6 months after the final session. The data were analysed using the two-way mixed design and the Bonferroni Comparison Test. The mean scores of internet addiction and digital game addiction decreased significantly after the motivational interviewing in the experimental group compared to the control group (p < 0.001) in both the post-test and follow-up tests. The present study concluded that motivational interviewing may be associated with reductions in mitigating symptoms of internet addiction and digital game addiction behaviours among adolescents. Motivational interviewing could be implemented to reduce internet addiction and digital game addiction behaviours. Trial registration: The study was registered on a clinical trial database (NCT06721702). The study started on December 11, 2023 (actual date on which the first participant was enrolled). • Internet addiction and digital game addiction are two increasingly important problems among adolescents. • Digital games and online activities negatively affect adolescents' physical, social, and psychological health. • Motivational interviewing was an effective technique to reduce online gaming and internet addiction. • A motivational interviewing program comprising at least six sessions could be implemented to promote behavioural change in adolescents.
The role of diet in multiple sclerosis (MS) development is still a matter of debate and its impact on MS course is not well understood. We tried to investigate the possible role of adolescent diet in late-onset multiple sclerosis (LOMS) odds. LOMS patients were obtained from the National MS Registry of Iran. Controls were sex and age matched with no history of neurological disorders. We assessed dietary factors using a questionnaire based on multinational studies. Food consumption levels were classified into low, medium, and high for each item. Logistic regression models were used to evaluate diet's impact on LOMS odds. We included 83 LOMS cases and 207 matched healthy controls. The mean age for LOMS patients was 61.14, compared to 61.51 years for controls. The results showed that higher consumption of dairy as in the third tertile associated with 79% decline in LOMS odds (AOR: 0.21; 95%CI: 0.09-0.47). Higher seafood consumption, in the third tertile was associated with a decrease in the odds of LOMS (AOR: 0.32; 95%CI: 0.14-0.72). Furthermore, increased nut consumption, in the third tertile (AOR: 0.37; 95%CI: 0.18-0.77), decreased the odds of LOMS. Additionally, higher consumption of fruits (AOR: 0.22; 95%CI: 0.07-0.63) and vegetables (AOR: 0.26; 95%CI: 0.12-0.55) was linked to a reduced odds of LOMS. This research highlights the advantageous impact of dairy products, seafood, nuts, fruits, and vegetables in lowering the LOMS odds. Hence, advocating for nutrition role in development of LOMS could represent a preventive measure for people susceptible to MS.
Effective patient education is critical for informed consent. Augmented Reality (AR) offers a novel approach to improving patient understanding and satisfaction, although current evidence is limited and of low quality. This study evaluated the added value of AR compared to traditional monitor-based 3D models for patient education and decision making for orthognathic surgery. A multicentre randomised controlled trial was conducted between August 2023 and June 2024 at three university medical centres in north-west Europe. Sixty referred patients were randomised to either the intervention group or the control group. Patient satisfaction and knowledge were assessed using two questionnaires. The study was registered at ClinicalTrials.gov(NCT06140043). Patient satisfaction was significantly higher in the control group (p = 0.04). No significant differences were found in knowledge acquisition (p = 0.74). Women showed a significant preference for the monitor-based consultation (p = 0.01), while men did not show a significant difference in satisfaction. Despite some centre heterogeneity, no clear added benefit of AR in satisfaction or knowledge was visible. Observed effect sizes (d = 0.76) and post-hoc power estimates (84%) are provided for context but should be interpreted cautiously. In the absence of clear evidence a monitor remain the most practical option for patient education.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe complications following hemorrhagic shock, leading to significant morbidity and mortality. Direct peritoneal resuscitation (DPR) has been proposed to improve microcirculation and reduce organ damage, but its effects on lung injury have not yet been fully explored. Does direct peritoneal resuscitation with peritoneal dialysis fluid (PDF) reduce lung injury in a controlled hemorrhagic shock model in rats? In this randomized experimental study, 32 male Wistar albino rats were randomly assigned to four groups (n = 8 per group). Group I served as the control group, while Groups II, III, and IV underwent hemorrhagic shock. Group III received peritoneal resuscitation with saline, and Group IV received PDF. Lung tissue samples were harvested after 24 h to assess histopathological damage and inflammatory markers; Interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α) levels. DPR with PDF significantly attenuated lung injury compared to saline-treated or hemorrhagic shock-only groups. Interstitial polymorphonuclear leukocytes (PMNL) infiltration and alveolar septal thickening were reduced in the DPR group. Additionally, IL-6 levels were elevated in the DPR group, suggesting a potentially enhanced localized inflammatory response, while no significant differences were found in IL-10 and TNF-α levels. Direct peritoneal resuscitation with PDF was effective in reducing lung injury in rats subjected to hemorrhagic shock by improving microcirculatory function and modulating the inflammatory response. However, the elevated IL-6 levels suggest further investigation is needed to understand the long-term implications of this inflammatory response.
Aiming at the problems of easy disturbance to the overlying slope and difficulty in scientifically determining the thickness of the isolation pillar during the recovery of hanging-wall orebody under open-pit to underground mining conditions, this study takes Shizhuyuan Mine as the engineering background. FLAC3D numerical simulation and the strength reduction method (SRM) are adopted to conduct a comparative analysis of the stability response characteristics of the "slope-goaf-backfill" system under five working conditions with isolation pillar thicknesses ranging from 10 m to 50 m. The results show that although the safety factors of all working conditions meet the requirements for Grade I slope stability, the thickness of the isolation pillar exhibits a significant threshold effect on system deformation control: when the thickness increases to 30 m, the maximum system displacement is significantly reduced from the excessive level (> 80 mm) to approximately 34 mm, and the overall stability is obviously improved. However, the stability gain brought by further increasing the thickness gradually weakens. Under the recommended thickness, the stress distribution, displacement evolution, and plastic zone development of the goaf and backfill are all within the safe and controllable range. Considering both stability requirements and resource recovery rate, an isolation pillar thickness around 30 m can achieve a reasonable balance between safety and economy, which can provide a quantitative design reference for the safe recovery of hanging-wall orebodies under similar open-pit-underground coordinated mining conditions.
Women experience musculoskeletal changes following pregnancy that may increase musculoskeletal injury risk. This trial explored 18-weeks combined rehabilitation and endurance and resistance training (Intervention, n = 17) compared with standard-of-care (Control, n = 14) on areal bone mineral density (aBMD), tibial bone, and patella tendon properties in postpartum UK Servicewomen. Intervention received standard care plus pelvic floor and core strength exercises from week 1 to 18 (week 6 to 24 postpartum), and combined high-intensity interval and resistance training from week 6 to 18 (week 12 to 24 postpartum). Control received standard care. Whole-body DXA and tibial HRpQCT scans (4% and 30% sites) were taken at week 1 and 18. Patella tendon properties at rest and during isometric contractions were measured by ultrasound at weeks 1, 6, and 18. There was no effect of training on aBMD (p ≥ 0.100) but trunk (-1.6%) and spine (-2.3%) aBMD decreased from week 1 to 18, irrespective of group (p ≤ 0.021). There was no effect of training on tibial bone (p ≥ 0.151) or patella tendon properties (p ≥ 0.185). An 18-week rehabilitation and endurance and resistance training programme had no effect on bone or tendon properties in postpartum Servicewomen.
There have been discussions as to the time of elective induction of labour to curb the continuation of pregnancy that might endanger the lives of both the mother and child. This research was conducted to assess foetal and maternal consequences of planned delivery at 40 and 41weeks in women with low-risk singleton pregnancy. A randomised controlled trial with equal allocation of participants (96 pregnant women in each arm) into 40weeks and 41weeks. Participants were randomised at the antenatal clinic at 39 weeks for induction of labour. The main outcome was the caesarean section rate. Secondary outcomes were maternal (genital tract laceration rate) and foetal (rates of meconium staining of amniotic fluid, SCBU admission, perinatal mortality, birth trauma, birth weight, and neonatal APGAR score at 1 and 5 minutes). Student t-test and chi-square test were used for inter-group comparison. Incidence of caesarean delivery (26.6% vs. 21.3%; p=0.406), and genital laceration (2.1% vs. 5.6%; p=0.268) did not differ between groups. Significantly higher birth weight was noted among women induced at 41weeks (3.41 ± 0.37kg) than 40weeks (3.28 ± 0.46kg) (p=0.043). Also, there was significant variation in meconium staining of amniotic fluid between 40weeks (11.7%) and 41weeks (25.8%) (p=0.014). Other foetal outcomes showed no significant difference. Inducing labour at 40weeks is safe for low-risk women as it does not significantly increase the cesarean delivery rate and adverse perinatal outcomes. Therefore, elective induction of labour at 40weeks should be recommended and introduced into obstetric practice without the fear of adverse outcomes.
With the popularity of short video platforms, Short Video Addiction has become a growing mental health concern. From a cognitive-emotional perspective, this study examined the association between Parental Neglect and Short Video Addiction among college students, focusing on the mediating role of Thought Suppression and the moderating effect of Thought Control Ability. A cross-sectional survey was conducted among 1,337 college students using the Parental Neglect Scale, Short Video Addiction Scale, White Bear Suppression Inventory, and Thought Control Ability Questionnaire. The results showed that Parental Neglect, Thought Suppression, and Short Video Addiction were all significantly and positively correlated with one another, while Thought Control Ability was significantly and negatively correlated with these three variables. Thought Suppression partially mediated the relationship between Parental Neglect and Short Video Addiction, and Thought Control Ability moderated the path from Thought Suppression to Short Video Addiction: for individuals with lower Thought Control Ability, Thought Suppression was a stronger positive predictor of Short Video Addiction; whereas for those with higher Thought Control Ability, this positive association was significantly attenuated. These findings suggest that enhancing individual Thought Control Ability may be associated with reduced negative influence of Thought Suppression on Short Video Addiction. This provides a theoretical and practical basis for cognitive-level interventions to help prevent excessive use of short video platforms among young adults.
To compare the elastosonographic changes of the tibial nerve (TN) and Achilles tendon (AT) in patients with type 2 diabetes mellitus (T2DM) and explore their relationship and respective relevant factors. This case-control study enrolled 165 subjects, comprising 126 patients with T2DM and 39 healthy controls matched for age and gender. The patients were further divided into those with and without diabetic peripheral neuropathy (PN-DM and NPN-DM groups). Clinical and laboratory data were collected. Conventional ultrasound and elastography were performed to assess the changes in the morphology and elasticity of the bilateral TN and AT. Sonographic features were compared across the three groups, relevant factors affecting the stiffness of TN and AT were analyzed, respectively. Diabetic patients exhibited significantly higher levels of HbA1C and a higher rate of smoking than healthy controls (P < 0.01 and P = 0.02, respectively). Their levels of body mass index (BMI) and total cholesterol have a significant difference between the NPN-DM group and healthy controls (both P = 0.02). The incidence of other microvascular complications in the NPN-DM group was significantly lower among diabetic patients (P = 0.04). Compared with healthy controls, the cross-sectional area (CSA) and transverse diameter of TN in diabetic patients were significantly larger (both P < 0.01), and CSA and anteroposterior diameter of AT were notably greater (P = 0.02 and P < 0.01). Besides, the stiffness of TN in the longitudinal section was significantly higher (P < 0.01), and the stiffness of AT in the cross-section was remarkably lower (P < 0.01). There was no significant difference in the morphology or elastography of TN or AT between NPN-DM and PN-DM groups. Furthermore, the stiffness of TN was not linearly related to that of AT, but independently correlated with age, HbA1C, and other microvascular complications (P < 0.05). The stiffness of AT was only independent of age (P < 0.01). The size of both TN and AT in diabetic patients was significantly larger. The stiffness of TN increased, and that of AT decreased; however, these changes were independent of each other. Not applicable.
Inflammatory cytokines influence the pathogenesis and progression of acute myeloid leukaemia (AML), not only by shaping the leukemic microenvironment, but also by supporting leukaemia stem cell survival and resistance to therapy. We, therefore, investigated the associations between the cytokine polymorphisms IFNG+874 A/T, TNFA-857 C/T, and IL1B -31 C/T and AML outcomes, as well as their influence on clinical features. Ninety-three patients with AML and 117 healthy controls were analysed. The T allele of TNFA - 857 C/T (i.e., the high-expression allele) was observed at a significantly higher frequency in the patients with AML vs. the controls (AML vs. control = 24.7% vs. 16.2%, p = 0.04). Patients with the high-expression TT genotype had shorter overall survival (TT vs. CC = 46.0 vs. 224.1 months, p < 0.001). Patients with the high-expression non-CC genotype relapsed more frequently than those with the low-expression CC genotype (relapse vs. non-relapse = 55.8% vs. 26.9%, p = 0.01). No significant associations were observed for the IFNG + 874 A/T and IL1B -31 C/T polymorphism. TNFA - 857 C/T polymorphisms can influence patient susceptibility to AML, as well as its prognosis. This suggests a link between chronic inflammation and leukemogenesis, as well as the potential value of TNFA genotyping in risk assessments.
Neuroimaging studies have revealed altered functional connectome dynamics in autism spectrum disorder (ASD) and linked these alterations to clinical symptoms. However, most studies have emphasized population-level contrasts, leaving interindividual variability in connectome dynamics and its structural underpinnings poorly understood. To address this gap, we analyzed resting-state functional and structural MRI data from 939 male participants (440 with ASD, 499 typically developing controls) across 18 sites in the Autism Brain Imaging Data Exchange (ABIDE). Whole-brain functional state dynamics was characterized using five leading activity modes and their expressions via eigen-microstate analysis. Age-related trajectories of mode expressions were constructed for typically developing controls using normative modeling, enabling quantification of individual-level deviations in functional dynamics. Compared with controls, ASD individuals showed greater interindividual variability in functional deviation profiles. Unsupervised clustering of these profiles identified two robust ASD subtypes with distinct mode-specific dysfunctions. One subtype primarily involved the visual, default-mode, frontoparietal, and dorsal attention networks, whereas the other subtype primarily involved the somatomotor, visual, frontoparietal, and ventral attention networks. These subtypes were clinically dissociable, differing in restricted and repetitive behaviors and social impairments, and exhibited mode-specific brain-symptom associations. Furthermore, the subtypes exhibited distinct cortical thickness alterations, and individual subtype membership was predicted with high accuracy (83%) using a random forest classifier based on cortical thickness. The main findings were replicated in an independent cohort outside ABIDE. This study delineates two reproducible and clinically dissociable ASD subtypes and links functional connectome dynamics to structural substrates, offering novel insights into the neurobiological basis behind ASD heterogeneity.
Interleukin-33 (IL-33), an alarmin predominantly released by keratinocytes and endothelial cells, plays a pivotal role in type 2 immune responses and has been linked to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). This study aimed to explore the relationship between plasma IL-33 levels and clinical features in SLE patients. A cross-sectional study was conducted involving 133 SLE patients and 81 normal controls. Plasma IL-33 levels were measured via enzyme-linked immunosorbent assay. Clinical parameters, such as SLEDAI-2K scores, photosensitivity, skin lesion distribution, laboratory indices, immunofluorescence and immunohistochemistry results were collected. SLE patients demonstrated significantly higher circulating IL-33 levels compared to healthy controls (median 342.60 pg/ml vs. 56.77 pg/ml, p < 0.0001). IL-33 levels were positively associated with SLEDAI-2K scores (r = 0.279, p = 0.001), photosensitivity (p = 0.02), and facial skin lesions (p = 0.001). The expression levels of the IL-33 receptor (ST2) in head and face cutaneous tissues were markedly higher than those in other anatomical regions and in normal control subjects (p < 0.001). Multivariate analysis revealed negative correlations with complement C3 (β = - 0.303, p < 0.001) and positive correlations with IgA (β = 0.473, p < 0.001) and hs-CRP (β = 0.310, p < 0.001). Notably, IL-33 levels were higher in male patients (p = 0.002) and treatment-naïve patients (p = 0.03). Our data associate circulating IL-33 with SLE activity, photosensitivity, and specific serological markers. For the association between IL-33 and cutaneous photosensitivity, this study provides further histological evidence. This finding provides a novel perspective on the mechanism of photosensitivity in SLE, demonstrating the potential of IL-33 as a biomarker for patient stratification management.
Alzheimer's disease (AD) is a growing public health concern, with neuroinflammation implicated in its pathogenesis. Allergic rhinitis (AR), a prevalent chronic inflammatory disorder, may contribute to systemic inflammation and potentially influence AD risk. This study sought to critically assess the association between a history of AR and subsequent AD development in a large, representative Taiwanese cohort. Leveraging Taiwan's National Health Insurance Research Database (LHID2010), this nationwide case-control study identified 4,681 individuals aged ≥ 65 years with a first-time AD diagnosis (cases) and 14,043 propensity-score-matched controls. A rigorous definition of prior AR required at least two clinical diagnoses, including one by an otolaryngology specialist. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. The prevalence of prior AR was significantly higher in AD patients than in controls (25.29% vs. 21.01%, p < 0.001). Following meticulous adjustment for demographic variables, socioeconomic status, geographic factors, and medical comorbidities (including hyperlipidemia, diabetes, coronary heart disease, hearing loss, and hypertension), prior AR was robustly associated with elevated odds of AD (adjusted OR = 1.279, 95% CI = 1.182 ~ 1.384). This association remained significant for both males (adjusted OR = 1.196, 95% CI = 1.053 ~ 1.358) and females (adjusted OR = 1.339, 95% CI = 1.210 ~ 1.482). This study suggests a significant association between prior AR and an increased odds of developing AD in an elderly Taiwanese population. These findings highlight chronic peripheral inflammation as a factor potentially associated with neurodegeneration.
Portal hypertension (PH) is one of the major complications of liver cirrhosis, traditionally assessed using invasive methods such as the hepatic venous pressure gradient (HVPG). Soluble endoglin (sENG), a marker of endothelial dysfunction and fibrosis, has been proposed as a non-invasive biomarker of various liver diseases. This study aimed to evaluate serum sENG concentrations in cirrhotic patients with PH and investigate its relationship with PH severity, alcohol consumption, and smoking. Serum concentrations of sENG were measured in clinically well-examined patients with liver cirrhosis (n = 60, age range 24-82 years) with PH classified as mild, moderate, or severe according to the HVPG values measured invasively using the classical wedge technique. sENG concentrations were also compared to healthy controls (n = 54). Liver enzyme activities, alcohol consumption history, and smoking habits were also recorded to assess their association with sENG. sENG concentrations were significantly higher in patients with PH compared to healthy controls (6.31; 5.14-7.30 vs. 3.70; 3.24-4.20 ng/mL, p < 0.001) but did not correlate with the severity of HVPG-diagnosed portal hypertension. A moderately significant correlation was observed between sENG concentrations and GGT activities (p < 0.001). Alcohol consumption, but not smoking, was associated with higher serum sENG concentrations (p < 0.01). Based on our results, sENG appears to be a non-invasive marker of endothelial dysfunction/fibrosis in cirrhotic patients with PH, particularly in alcohol-related liver disease. Although it does not reflect PH severity and thus cannot be used as a diagnostic tool, it has the potential for early disease detection and risk prediction as a screening component in non-invasive approaches in clinical hepatology.
Cis-regulatory elements (CREs) drive tissue- and cell-specific gene expression and are essential for safe, sustainable genetic control strategies in pest and vector insects, including the engineering of gene drives in the primary human-malaria vector Anopheles gambiae. Yet CREs remain poorly defined in mosquitoes due to limited computational tools and practical methods for identification and validation. We present a systematic in silico approach for CRE discovery, correlating targeted DNA-motif searches with gene expression, followed by frequency and distribution analysis within putative promoter regions. Applied to the A. gambiae germline, this approach identified hundreds of putative CREs significantly correlated with germline expression in one or both sexes, often linked to distinct sperm developmental stages and chromosomal locations, suggesting roles in broader regulatory mechanisms such as dosage compensation and meiotic silencing. When mapped onto pre-characterised germline promoters, CRE distribution aligned with regions associated with experimental expression patterns. Finally, we validated a top-ranked testis-enriched CRE using an in vivo dual-reporter assay, showing that mutation of conserved nucleotides drastically altered male germline expression. To the best of our knowledge this work provides the first nucleotide-resolution regulatory genome annotation of the A. gambiae germline, offering a transferable framework to aid promoter design for genetic control strategies against malaria mosquitoes and other insect pests.
Zymoseptoria tritici causes Septoria Leaf Blotch disease of wheat and has evolved to overcome most chemical and genetic control methods. As such, new tools are required for future disease control. We identified Pseudomonas isolates that antagonise Z. tritici through the production of secreted secondary metabolites, using a novel in vitro antagonism assay. Quantitative assessment identified variation in sensitivity of Z. tritici isolates to antagonism by Pseudomonas isolates. Genome assemblies of 3 strongly antagonistic Pseudomonas isolates contain a predicted Biosynthetic Gene Cluster (BGC) with high similarity to a reference BGC encoding the biosynthesis of known antifungal compound 2,4-diacetylphloroglucinol (2,4-DAPG). Mutagenesis of the core biosynthetic gene phlD resulted in loss of 2,4-DAPG production in Pseudomonas isolate Roth82, and loss of Z. tritici inhibition in vitro. These results demonstrate that our in vitro antagonism assay can be used to identify, quantify, and mechanistically characterise bacterial antagonism of Z. tritici through the production of secondary metabolites. This is the first study to putatively identify that resistance to bacterial antagonism exists as a quantitative trait within natural Z. tritici populations. Our approach of in vitro phenotype-guided genome mining can also prioritise candidate BGCs for discovery of antifungal natural products effective against Z. tritici.
Schizophrenia spectrum disorders (SSD) feature deficits in movement intention, predictive mechanisms, and agency. While prior work characterised BOLD amplitude during movement preparation and temporal dynamics across the entire movement period, it remains unknown whether preparatory neural (BOLD) response timing and duration are selectively impaired in SSD. We analysed fMRI data from 20 SSD patients and 20 healthy controls during active and passive hand movements with video feedback (own vs. other hand). Preparatory and executory BOLD responses were modelled separately using the canonical HRF and its temporal (TD) and dispersion (DD) derivatives to evaluate timing and duration. Patients with SSD showed pronounced preparatory abnormalities under own-hand feedback, including delayed responses in right supplementary motor area during active movement preparation. Passive- and active-specific timing was reversed (earlier/later) in the left (caudate, middle temporal gyrus, superior parietal gyrus) and right (postcentral gyrus, right precentral gyrus, anterior cingulate cortex). Response duration showed reduced/reversed modulation (shorter/longer) in the right supplementary motor area, bilateral supramarginal gyrus, left inferior parietal cortex, and bilateral middle temporal gyrus. Earlier response timing in right precentral gyrus during active own-hand were negatively correlated with delusions of being controlled and formal thought disorder. No group differences emerged during execution.