PIWI-interacting RNAs (piRNAs) are an important class of non-coding RNA molecules in epigenetic regulation. It plays a crucial role in maintaining genomic stability and inhibiting transposable elements, and have been proven to participate in various diseases by regulating gene expression and influencing signaling pathways. Traditional biological experimental methods have limitations such as low throughput, long cycles, and high costs, making them difficult to meet the requirements of large-scale systematic screening. In this study, we develop a predictive framework named PiDA-DVLSA. We integrate autoencoder, dual graph transformer, and multi-head self-attention mechanisms, and construct an end-to-end multimodal deep learning system. We use autoencoder to perform nonlinear dimensionality reduction and denoising on piRNA sequence features and disease phenotype semantic features, and extract potential representations with strong discriminative ability. Then, we use graph transformers to model the high-order topological relationships between nodes in isomorphic similar graphs, and input heterogeneous graph transformers to learn complex cross-entity interaction patterns in heterogeneous networks. Finally, we achieve adaptive fusion of multi-source information through multi-head self-attention mechanisms. PiDA-DVLSA performs excellently on the benchmark dataset, with AUC and AUPR reach 0.9437 and 0.9195, respectively, significantly outperform eight mainstream algorithms. In independent case validations for breast cancer, clioblastoma, and Alzheimer disease, our model successfully predicts multiple biologically significant potential associations, further confirming its practicality and effectiveness in real scientific research scenarios and providing a solid computational basis for future precision diagnostic and therapeutic applications. PiDA-DVLSA is freely available at https://github.com/zhaoqi106/PiDA-DVLSA .
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Functional rhinoplasty can improve disease-specific quality of life (QoL) domains. However, less is understood about its association with global health-related QoL outcomes. The goal of this study is to evaluate the relationship between disease-specific and long-term global QoL outcomes following functional rhinoplasty. Prospective cohort study at a tertiary medical center of patients undergoing functional rhinoplasty for nasal airway obstruction. Fifty patients (58% female, 42% male), with a mean age of 38.5 (StD 14.7), were surveyed. Baseline and long term (> 6 months) follow up Euroqol-5D (EQ-5D) and Standard Cosmesis and Health Nasal Outcomes Survey (SCHNOS) questionnaires were collected. Mean baseline SCHNOS-Obstructive (SCHNOS-O) score improved from 77.5 (95% CI: 71.5-83.5) to 22.7 (95% CI: 14.4-31.1) at follow up. Mean SCHNOS-Cosmesis (SCHNOS-C) score improved from 44.9 (95% CI: 33.9-56.0) to 13.9 (95% CI: 8.9-21.1). A higher SCHNOS-O is a significant predictor for expressing pain/discomfort at follow up (p = 0.011). A higher SCHNOS-C is a significant predictor for expressing anxiety/depression at follow up (p = 0.019). There is no relationship between SCHNOS-O/SCHNOS-C and mobility, self-care, or activity. A greater improvement in SCHNOS-O is associated with less anxiety/depression (p = 0.03) and pain/discomfort (p = 0.02) at follow up. However, a greater improvement in SCHNOS-C is not significantly associated with anxiety/depression (p = 0.678) or pain/discomfort (p = 0.558) at follow up. Patients who expressed anxiety/depression at baseline are more likely to express anxiety/depression at follow up. Patients with long-term improvements in nasal obstruction, but not cosmesis, are less likely to report long-term anxiety/depression and pain/discomfort following functional rhinoplasty.
Intracerebral hemorrhage (ICH) remains associated with high mortality and treatment variability. Current workflows rely on fragmented imaging interpretation and operator-dependent surgical planning. The objective was to develop and validate an agentic artificial intelligence (AI) framework integrating automated imaging analysis, guideline-based reasoning, and trajectory optimization for ICH treatment. Fifty consecutive computed tomography (CT) and computed tomography angiography (CTA) datasets from patients with spontaneous ICH were retrospectively analyzed. The system performed multi-class anatomical segmentation of skin, skull, brain, ventricles, and hematoma, followed by volumetric quantification and JavaScript Object Notation (JSON) based structured encoding of imaging biomarkers. A knowledge-based module incorporating international ICH guidelines generated risk stratification and treatment recommendations. When evacuation was indicated, an automated trajectory modeling module proposed a patient-specific minimally invasive surgical corridor. Overall agreement between AI-generated and expert treatment recommendations was 82% (41/50 cases), with substantial agreement beyond chance (Cohen's κ = 0.71). Discrepancies occurred primarily in borderline surgical indication scenarios. In evacuation candidates, the automated planner generated feasible trajectories in all 50 cases. Median angular deviation between AI-generated and expert-defined trajectories was 7.6°, interquartile range (IQR) 5.1-9.8°. AI-generated trajectories demonstrated equal or greater safety margins relative to expert planning in the majority of cases. End-to-end processing has a potential to substantially reduce simulated decision-support time compared with manual workflow. The proposed agentic AI framework enables structured, explainable, and workflow-integrated decision support for ICH management. This system may reduce operator variability and enhance precision in minimally invasive evacuation planning.
Formal theories translate verbal theories into a mathematical representation, such as a coupled differential equation or other dynamical systems, intending to strengthen the deductive power of (clinical) theories and to formulate testable and novel hypotheses. Work in clinical formal theories mainly relies on simulations, which is an intuitive method for evaluating overall model performance, but may fall short of establishing a precise link between the mathematical properties of the model and the dynamic properties of its outcome. Moreover, when the model's outcome contradicts clinical observations, it is unclear where the discrepancy lies and how to improve the model. In this article, we introduce formal mathematical techniques for graphical model analysis, including phase plane analysis, which allows identifying a system's stable and unstable equilibria, and bifurcation analysis, a framework to delineate parameter regimes corresponding to qualitatively different dynamical outcomes for a model. Using two formal dynamic models in psychology (one for panic disorder and one for suicidal ideation), we illustrate those methods through an easy-to-use R package, deBif, with a graphical user interface. These examples demonstrate the importance of using graphical tools to investigate the hypothesized mechanisms of psychological systems.
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Frozen shoulder, also known as adhesive capsulitis, is a common and disabling condition that causes shoulder pain and progressive stiffness. Patient information leaflets (PILs) are produced by UK National Health Service (NHS) Trusts to help patients understand frozen shoulder and treatment options. However, the content and consistency of these PILs and their alignment with national clinical guidance are currently unclear. This study aimed to identify, analyse and describe the non-surgical management recommendations presented in publicly available NHS Trust PILs for frozen shoulder and to assess their alignment with the National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary and British Elbow and Shoulder Society (BESS) best practice resources. An online search was undertaken by one reviewer to identify publicly available PILs produced by NHS Trusts detailing non-surgical management of frozen shoulder. Relevant data were extracted and analysed by one reviewer and verified by five reviewers. Descriptive statistics were used to summarise findings. Thirty-eight PILs were identified from 38 NHS Trusts with publication dates ranging from April 2013 to March 2025. Considerable variation was observed in the content, including reference to analgesia, activity modification, exercise prescription and corticosteroid injections. No single PIL reflected all key elements recommended in the NICE Clinical Knowledge Summary and BESS best practice. The findings demonstrate substantial variation in content, frequent misalignment with current national guidance and best practice exercise recommendations. Such variation may limit and may reduce the clarity, consistency and usefulness of information provided to patients.
Migration is one of the most feared complications following lip filler. The use of a specific filler with a high degree of elasticity and cohesiveness could be the key to solve the problem if injections are performed in the correct anatomical plane. The purpose of this study was to describe the authors' 5-year experience with a new concept of lip filling, iLips. This reproducible approach combines elasticity and cohesiveness of a 25,5 mg/ml filler injected through superficial micro-tunnels in a virtual space between orbicularis muscle and mucosa creating a tridimensional net that respects lip dynamic also leading to a low risk of filler migration. A total of 4583 consecutive patients who underwent lip filler with iLips technique were enrolled in this prospective study. An objective evaluation on the aesthetic results was obtained by a jury composed of 3 external plastic surgeons using Lip Fullness Merz scale. PROMs were investigated through FACE-Q administration to the patients ("Psychological function", "Satisfaction with outcome" and "Satisfaction with lips" scales). Statistical analysis was performed through Prism10. Complications were reported. t-test with Welch's correction showed an improvement in Lip Fullness Merz score both in upper and lower lip (p<0.05). A similar trend was shown also for "Psychological function", "Satisfaction with outcome" and "Satisfaction with lips" mean values after the procedure. Just 2 cases of major vascular complications were reported. iLips ® seem to be a safe, highly reproducible, effective and satisfying approach for lip augmentation positively impacting also the patient's psychological sphere. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Mind‑body practices, such as meditation and yoga, involve paying attention to breathing sensations. During these practices, individuals report "interoceptive lapses," moments when attention drifts away from internal bodily sensations. While lapses in attention to the external world have been widely studied, little is known about the physiological and neural mechanisms of interoceptive lapses. Interoceptive lapses may share markers with exteroceptive lapses-such as reaction time variability and default-mode network (DMN) connectivity-but may also depend on distinct brain systems and breathing physiology. We examined behavioral, physiological, and neural signals preceding lapses in a sample of 93 adolescents enriched for GAD and depression symptoms. Participants performed a 20-min breath counting task in the fMRI scanner with simultaneous breath recordings. Lapses were defined as moments when counting errors occurred. The sample was split into training and validation sets to test machine learning models predicting attentional lapses. The strongest predictors were timing and variability of button responses (AUCs > 0.75). Breathing variability and breathing-behavior synchronization showed smaller but generalizable predictive value (AUCs < 0.65). Whole-brain connectivity models also predicted lapses (AUC ≈ 0.65), incorporating the DMN, dorsal and ventral attention, and somatomotor networks. Furthermore, models that included brain connectivity marginally outperformed behavior-only models. Comparisons to previous exteroceptive findings indicate some common markers (e.g., reaction time variability) and some unique markers (e.g., selective perceptual coupling with attentional networks). Although limited by the clinical sample and lack of a control task, these results highlight brain-body markers of interoceptive attention that may inform real-time monitoring during mind-body interventions.
Activities of daily living (ADL) are associated with declines in physical fitness and subjective health. However, it remains unclear as to whether ADL impairments are related to specific components of physical fitness and health variables. Therefore, we examined differences between community-dwelling older persons with versus without ADL impairments with regard to various physical fitness components, physical complaints as well as subjective and objective health outcomes. Cross-sectional study among 254 participants aged ≥ 55 years [51% female; 84 with ADL impairments; mean (SD) age 62.1 (6.6) years] enrolled in the population-based "Gesundheit zum Mitmachen" study in Southwestern Germany. ADL, physical complaints and subjective health status were assessed using a self-report questionnaire, physical fitness (cardiorespiratory fitness, strength, gross motor coordination, flexibility, and functional mobility) was assessed using a fitness test battery, and objective health status was derived from health exam performed by a physician. We ran analyses of covariance, adjusted for age, sex, body mass index and education. Participants with ADL impairments had statistically significantly worse subjective (p < 0.001) and objective (p < 0.001) health and reported more physical complaints (p < 0.001) compared to those without ADL impairments. Regarding physical fitness, ADL-impaired participants performed worse in 10 out of 12 variables. The findings provide additional evidence that ADL impairments are related to decreased objective and subjective health and physical fitness in older community-dwelling adults. Future studies employing more comprehensive, preferably objective, ADL assessments and considering cognitive impairments, which may also impact ADL performance, are warranted.
Knee osteoarthritis (KOA) is a common degenerative bone disease, and transcutaneous electrical nerve stimulation (TENS) is an alternative and complementary therapy (ACM). This study revealed the role of TENS in regulating the intestinal microbiota in KOA rats. This study concentrated on the intestinal microbiota of KOA rats which were treated with TENS for 1, 2, and 3 weeks. Three intensities of TENS were used to treat KOA rats, and the expressions of IL6/8, PI3K-AKT were measured. The intestinal microbiota was analyzed by 16 S rDNA sequencing. Compared with the Model Control group, TENS could improve symptoms of KOA rats and inhibit the expressions of IL6/8 by down-regulating the PI3K-AKT expression. After 3 weeks of treatment with TENS, compared with the Model Control group, the abundances of Bacteroidetes, Bacteroidetes, and Thermodesulfobacteria increased in the TENS groups; the abundances of Ficmicutes, Campylobacter, and Verruca decreased in the TENS groups. TENS could improve the histomorphology of knee and inhibit inflammation in KOA rats. After treatment with TENS, the intestinal microbiota gradually changed from 1,2,3 weeks and the abundance of them was different with three intensities of TENS. Further study will elucidate the underlying mechanisms of TENS in altering gut microbiota and the potential therapeutic applications of these intestinal microbiota for KOA.
Leishmaniasis remains a major public health challenge in many tropical and subtropical regions despite long-standing emphasis on controlling adult sandflies. This commentary highlights an important ecological gap that has received limited attention: the immature stages of sandflies. Unlike mosquitoes, sandflies develop in cryptic terrestrial microhabitats that are rarely detected through routine surveillance. Consequently, most vector control programmes concentrate on suppressing adult populations, while the biological processes that generate new adult vectors remain poorly understood. Recent ecological studies indicate that breeding activity may be spatially structured and biologically detectable. Surveillance approaches that consider oviposition behaviour and breeding ecology may therefore help make vector population dynamics more measurable and support more sustainable, biology-based control strategies.
Shaken Baby Syndrome and Abusive Head Trauma are significant traumatic brain injuries observed in infants and represent a critical public health issue. Although there is a vast literature on this subject, conducting a descriptive bibliometric analysis is essential to map the topic's quantitative development over time and to reveal its current geographical and conceptual distribution objectively. This study systematically analyzes 3,571 articles published between 1977 and 2025 in the Web of Science Core Collection database, examining the distribution of publications by year and country, leading journals, citation rates, and keyword networks. Our findings indicate a linear increase in the volume of SBS/AHT research publications since the 2000s. The analysis highlights two significant strengths and shifts in the literature. First, the emergence of countries from diverse regions-such as Romania, the United Arab Emirates, Malaysia, and Russia-in the literature network, alongside traditional research hubs, objectively confirms the subject's expanding global scope. Second, the fact that the highest citation rates and publication density are not limited to clinical medicine journals (e.g., Pediatrics) but are simultaneously concentrated in pioneering journals with social and legal content (e.g., Child Abuse & Neglect) highlights the field's multidimensional and interdisciplinary nature. In conclusion, this study provides an objective resource for all stakeholders-including physicians, forensic scientists, and legal professionals-by visualizing the current geographic diversity of scientific output, key terms, and journal dynamics.
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This study compared the incidence of intraoperative significant vessel injury between robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) during major pulmonary resection. This retrospective study included 1215 patients who underwent major pulmonary resection via a minimally invasive approach between October 2012 and August 2025 at our institution: 903 underwent VATS (413 uniport, 490 multiport) and 312 underwent RATS. Propensity scores were calculated using preoperative variables, and stabilized inverse probability of treatment weighting (IPTW) was applied. The primary outcome was intraoperative significant vessel injury, defined as bleeding that required additional hemostatic intervention, such as sealant application, clipping, or suturing, after initial compression. Weighted logistic regression was used to assess the association between surgical approach and significant vessel injury. Secondary perioperative outcomes were also compared. After IPTW adjustment, baseline characteristics were well balanced. RATS was associated with a significantly lower risk of intraoperative significant vessel injury than VATS (adjusted odds ratio [OR]: 0.21, 95% confidence interval [CI], 0.08-0.54, P = 0.001). In an exploratory three-group analysis, RATS showed a lower risk than multiport VATS (OR: 0.15, 95% CI: 0.06-0.40, P < 0.001) and a borderline lower risk than uniport VATS (OR: 0.35, 95% CI: 0.12-1.00, P = 0.050). RATS was also associated with more favorable perioperative outcomes. RATS was associated with a lower risk of intraoperative significant vessel injury than VATS and with favorable short-term perioperative outcomes during major pulmonary resection.
Obeticholic acid (OCA), a synthetic analog of chenodeoxycholic acid, was approved in 2016 for the treatment of primary biliary cholangitis. Early clinical trials revealed elevated liver biomarkers in healthy subjects receiving supratherapeutic OCA doses (100-250 mg). OCA was also evaluated as a treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) but was not approved by the FDA due to liver safety concerns. In this in silico study, we investigated mechanisms of OCA-associated liver injury in virtual healthy and MASLD populations receiving supratherapeutic and therapeutic (10-25 mg) doses, respectively. OCA and metabolite exposures in plasma, sinusoidal blood, liver, and gut compartments were simulated using a physiologically based pharmacokinetic model. In the virtual MASLD population, exposures were increased 2-, 5-, and 10-fold in plasma, sinusoidal, and/or liver compartments relative to baseline. Mechanistic parameters relevant to OCA-mediated liver injury, including bile acid transporter inhibition and mitochondrial dysfunction, were incorporated into the DILIsym model. Predicted liver injury was reported as evaluation of drug-induced serious hepatotoxicity (eDISH) plots, and elevations in alanine aminotransferase, aspartate aminotransferase, and total hepatic bile acids. DILIsym simulations recapitulated liver biomarker elevations observed at supratherapeutic OCA doses in healthy subjects and predicted biomarker increases in the MASLD population under conditions of 5- and 10-fold increased exposures relevant to this population. Bile acid transporter inhibition alone reproduced simulated biomarker elevations, whereas mitochondrial uncoupling alone predicted increased biomarkers only at the highest exposures. Results suggest that DILIsym modeling would have predicted the liver safety concerns that led to withdrawal of OCA from the US market.
Endothelial activation and stress index (EASIX) is a biomarker of endothelial dysfunction and has been validated previously as a prognostic score for mortality in various diseases, including oncologic diseases, sepsis, and cardiac disease. Since endothelial dysfunction is an established mediator of adverse outcomes in acute ischemic stroke, this study investigates the prognostic value of EASIX for risk of mortality in these patients. We analyzed data from the Heidelberg (n = 4,188) and Vienna (n = 2,273) prospective acute ischemic stroke registries. EASIX was calculated as creatinine [mg/dL] × LDH [U/L] / platelet count [109/L]. An EASIX cut-off was established using maximal Youden index. Validation was performed using Brier score and C-statistics. Higher EASIX was associated with higher risk of mortality in the training cohort in a multivariable Cox regression (HR of all-cause mortality per log2 increase: 1.20 (95% CI 1.12-1.28), p < 0.001). An optimal EASIX cut-off value of 1.211 was identified in the derivation cohort. In the independent validation cohort, this cut-off was associated with risk of 3-month mortality in a multivariable binary logistic regression model (OR 1.86 (1.28-2.70), p < 0.01). Brier score and C-statistics validated the superior predictive performance of EASIX in the multivariable model. EASIX predicts mortality in acute ischemic stroke patients and retained prognostic validity across two heterogeneous European cohorts. Incorporation of EASIX improved risk stratification beyond established clinical scores. EASIX may serve as a useful tool for risk stratification and outcome prediction in acute ischemic stroke patients.
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This study investigated key-press responses to five spoken Japanese vowels: [ɑ], [i], [ɯ], [e], and [o]. In the first experiment, 30 participants pushed only a single key when they listened to spoken Japanese vowels (response task). In the second experiment, another 29 participants matched the heard vowels with represented vowels by pushing one of five corresponding keys (matching task). The results of the first experiment showed no difference in the response times to the five vowels. In the second experiment, the response times to [i] and [e] were faster than those to [ɯ] and [o]. These results suggest that front vowels promote faster key-press responses than back vowels when the keys corresponding to the heard vowels are consciously selected.