Osteoporotic Precise Screening Using Chest Radiography and Artificial Neural Network: The OPSCAN Randomized Controlled Trial.

Background Diagnosing osteoporosis is challenging due to its often asymptomatic presentation, which highlights the importance of providing screening for high-risk populations. Purpose To evaluate the effectiveness of dual-energy x-ray absorptiometry (DXA) screening in high-risk patients with osteoporosis identified by an artificial intelligence (AI) model using chest radiographs. Materials and Methods This randomized controlled trial conducted at an academic medical center included participants 40 years of age or older who had undergone chest radiography between January and December 2022 without a history of DXA examination. High-risk participants identified with the AI-enabled chest radiographs were randomly allocated to either a screening group, which was offered fully reimbursed DXA examinations between January and June 2023, or a control group, which received usual care, defined as DXA examination by a physician or patient on their own initiative without AI intervention. A logistic regression was used to test the difference in the primary outcome, new-onset osteoporosis, between the screening and control groups. Results Of the 40 658 enrolled participants, 4912 (12.1%) were identified by the AI model as high risk, with 2456 assigned to the screening group (mean age, 71.8 years ± 11.5 [SD]; 1909 female) and 2456 assigned to the control group (mean age, 72.1 years ± 11.8; 1872 female). A total of 315 of 2456 (12.8%) participants in the screening group underwent fully reimbursed DXA, and 237 of 315 (75.2%) were identified with new-onset osteoporosis. After including DXA results by means of usual care in both screening and control groups, the screening group exhibited higher rates of osteoporosis detection (272 of 2456 [11.1%] vs 27 of 2456 [1.1%]; odds ratio [OR], 11.2 [95% CI: 7.5, 16.7]; P < .001) compared with the control group. The ORs of osteoporosis diagnosis were increased in screening group participants who did not meet formalized criteria for DXA compared with those who did (OR, 23.2 [95% CI: 10.2, 53.1] vs OR, 8.0 [95% CI: 5.0, 12.6]; interactive P = .03). Conclusion Providing DXA screening to a high-risk group identified with AI-enabled chest radiographs can effectively diagnose more patients with osteoporosis. Clinical trial registration no. NCT05721157 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Smith and Rothenberg in this issue.

Artificial Intelligence-enabled Chest X-ray Classifies Osteoporosis and Identifies Mortality Risk.

A deep learning model was developed to identify osteoporosis from chest X-ray (CXR) features with high accuracy in internal and external validation. It has significant prognostic implications, identifying individuals at higher risk of all-cause mortality. This Artificial Intelligence (AI)-enabled CXR strategy may function as an early detection screening tool for osteoporosis. The aim of this study was to develop a deep learning model (DLM) to identify osteoporosis via CXR features and investigate the performance and clinical implications. This study collected 48,353 CXRs with the corresponding T score according to Dual energy X-ray Absorptiometry (DXA) from the academic medical center. Among these, 35,633 CXRs were used to identify CXR- Osteoporosis (CXR-OP). Another 12,720 CXRs were used to validate the performance, which was evaluated by the area under the receiver operating characteristic curve (AUC). Furthermore, CXR-OP was tested to assess the long-term risks of mortality, which were evaluated by Kaplan‒Meier survival analysis and the Cox proportional hazards model. The DLM utilizing CXR achieved AUCs of 0.930 and 0.892 during internal and external validation, respectively. The group that underwent DXA with CXR-OP had a higher risk of all-cause mortality (hazard ratio [HR] 2.59, 95% CI: 1.83-3.67), and those classified as CXR-OP in the group without DXA also had higher all-cause mortality (HR: 1.67, 95% CI: 1.61-1.72) in the internal validation set. The external validation set produced similar results. Our DLM uses CXRs for early detection of osteoporosis, aiding physicians to identify those at risk. It has significant prognostic implications, improving life quality and reducing mortality. AI-enabled CXR strategy may serve as a screening tool.

Cationic complex-enhanced C-H stimulated Raman scattering in naphthalene-benzene solution.

Ring skeleton vibrations of aromatic series are dominant in Raman spectroscopy compared with the C-H stretching vibrations. When a laser-induced plasma (LIP) was generated in a mixed solution of naphthalene and benzene, an anomalous enhancement was observed in stimulated Raman scattering (SRS) of aromatic C-H stretching vibrations of naphthalene (3055 cm-1). However, SRS of C-H stretching vibrations of benzene at 3060 cm-1 disappeared. The LIP produced electrons and cations, and the transient production of ionized material contributed to the enhancement of SRS of C-H vibrations of naphthalene. Density functional theory calculations showed that the C-H Raman activity of the naphthalene molecules in (naphthalene-benzene)+ heterodimer was significantly enhanced compared with neutral naphthalene. In addition, SRS pulse durations were better compressed in pure benzene and naphthalene due to the self-focusing effect.

An AI-Enabled Dynamic Risk Stratification for Emergency Department Patients with ECG and CXR Integration.

Emergency department (ED) triage scale determines the priority of patient care and foretells the prognosis. However, the information retrieved from the initial assessment is limited, hindering the risk identification accuracy of triage. Therefore, we sought to develop a 'dynamic' triage system as secondary screening, using artificial intelligence (AI) techniques to integrate information from initial assessment data and subsequent examinations. This retrospective cohort study included 134,112 ED visits with at least one electrocardiography (ECG) and chest X-ray (CXR) in a medical center from 2012 to 2022. Additionally, an independent community hospital provided 45,614 ED visits as an external validation set. We trained an eXtreme gradient boosting (XGB) model using initial assessment data to predict all-cause mortality in 7 days. Two deep learning models (DLMs) using ECG and CXR were trained to stratify mortality risks. The dynamic triage levels were based on output from the XGB-triage and DLMs from ECG and CXR. During the internal and external validation, the area under the receiver operating characteristic curve (AUC) of the XGB-triage model was >0.866; furthermore, the AUCs of DLMs using ECG and CXR were >0.862 and >0.886, respectively. The dynamic triage scale provided a higher C-index (0.914-0.920 vs. 0.827-0.843) than the original one and demonstrated better predictive ability for 5-year mortality, 30-day ED revisit, and 30-day discharge. The AI-based risk scale provides a more accurate and dynamic stratification of mortality risk in ED patients, particularly in identifying patients who tend to be overlooked due to atypical symptoms.

A Deep-Learning Algorithm-Enhanced Electrocardiogram Interpretation for Detecting Pulmonary Embolism.

Background: The early diagnosis of pulmonary embolism (PE) remains a challenge. Electrocardiograms (ECGs) and D-dimer levels are used to screen potential cases. Objective: To develop a deep learning model (DLM) to detect PE using ECGs and investigate the clinical value of false detections in patients without PE. Methods: Among patients who visited the emergency department between 2011 and 2019, PE cases were identified through a review of medical records. Non-PE ECGs were collected from patients without a diagnostic code for PE. There were 113 PE and 51,456 non-PE ECGs in the training and validation sets for developing the DLM, respectively, and 27 PE and 13,105 non-PE cases in an independent testing set for performance validation. A human-machine competition was conducted from the testing set to compare the performance of the DLM with that of physicians. Receiver operating characteristic (ROC) curves, sensitivity, and specificity were used to determine the diagnostic value. Survival analysis was used to assess the prognosis of the patients without PE, stratified by DLM prediction. Results: The DLM was as effective as physicians in diagnosing PE, with 70.8% sensitivity and 69.7% specificity. The area under the ROC curve of DLM was 0.778 in the testing set and up to 0.9 with D-dimer and demographic data. The non-PE patients whose ECG was misclassified as PE by DLM had higher all-cause mortality [hazard ratio (HR) 2.13 (1.51-3.02)] and risk of non-cardiovascular hospitalization [HR 1.55 (1.42-1.68)] than those correctly classified. Conclusions: A DLM-enhanced ECG system may prompt PE recognition and provide prognostic outcomes in patients with false-positive predictions.

Periodontitis, Helicobacter pylori infection, and gastrointestinal tract cancer mortality.

AIM: Periodontitis has been proposed to lead to Helicobacter pylori infection, which could cause many gastrointestinal tract cancers. This study aimed to determine the association or otherwise between periodontitis and survival outcomes in individuals with respect to H. pylori infection. MATERIALS AND METHODS: The study population comprised 4955 subjects aged 20-90 who had received both periodontal examination and H. pylori serum test in the Third National Health and Nutrition Examination Survey (NHANES III) database. Logistic regression models were used to analyse the association between periodontitis and H. pylori seropositivity (H. pylori infection). Survival analysis was performed using the NHANES III linked to mortality data. Cox proportional hazard regression was carried out to investigate the association between periodontitis and gastrointestinal tract cancer mortality in individuals with/without H. pylori infection. RESULTS: Compared to periodontal health, periodontitis was significantly associated with increased odds of H. pylori infection (OR = 1.271, 95% CI = 1.177-1.372). Periodontitis significantly increased the mortality risk from all causes (HR = 1.574, 95% CI = 1.327-1.866) and all cancers (HR = 1.948, 95% CI = 1.701-2.232), including gastrointestinal (GI) tract cancer (HR = 4.140, 95% CI = 3.656-4.687), gastric cancer (HR = 4.288, 95% CI = 3.969-4.632), and colorectal cancer (HR = 4.814, 95% CI = 3.849-6.020) in subjects with H. pylori infection after adjusting for health-related factors. Periodontitis was significantly related to the decreased survival time in subjects with GI tract (p = .001) or colorectal cancer (p = .002) and H. pylori infection. CONCLUSION: Our study demonstrated that periodontitis was significantly associated with higher mortality risk of GI tract, gastric, and colorectal cancer in subjects with H. pylori infection. Owing to an interactive effect between periodontitis and H. pylori infection on cancer mortality, H. pylori infection has a significant moderating effect in regulating the association between periodontitis and mortality due to all cancers, including GI tract cancer and colorectal cancer.

Patient perceptions of students in a longitudinal integrated clerkship in Taiwan: a qualitative study.

BACKGROUND: Longitudinal integrated clerkships (LICs) are a model of clinical education growing rapidly in Western contexts. LICs use educational continuity to benefits students' clinical learning and professional identity formation. Patient-centered care is a core component of medical professionalism in the West. To support patient-centered care, education leaders in Taiwan restructured clinical education and implemented the first longitudinal integrated clerkship in East Asia. We aimed to investigate patients' perceptions of longitudinal relationships with the LIC students within Taiwan's Confucian cultural and social context. METHODS: We invited patients or their family members who were cared for longitudinally by a LIC student to participate in the study. Participating patients or their family members undertook semi-structured interviews. We analyzed data qualitatively using a general inductive approach to identify themes in the patients' descriptions of their experiences interacting with the LIC students. RESULTS: Twenty-five patients and family members participated in interviews: 16 patients and 9 family members. Qualitative analysis of interview transcripts identified three themes from patients' experience receiving care from their LIC students: care facilitation, companionship, and empathy. To provide care facilitation, LIC students served as a bridge between the physicians and patients. Students served patients by reminding, consulting, tracking disease progression, and researching solutions for problems. To provide companionship, students accompanied patients interpersonally like a friend or confidant who listens and provides a presence for patients. To provide empathy, patients reported that students showed sincere concern for patients' experience, feelings, and mood. CONCLUSION: In our study, Taiwanese patients' perspectives of LIC students suggested the value of care facilitation, companionship, and empathy. We discuss these themes within the context of Confucian culture and the Taiwanese context of care.

Attenuated vagally-mediated heart rate variability at rest and in response to postural maneuvers in patients with generalized anxiety disorder.

BACKGROUND: Altered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges. METHODS: In total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders. RESULTS: After PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36-0.42, respectively. CONCLUSIONS: GAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status.

Sex-specific pathways among tri-allelic serotonin transporter polymorphism, trait neuroticism and generalized anxiety disorder.

Background: Neuroticism personality trait is recognized as an important endophenotypic predictor of generalized anxiety disorder (GAD). Furthermore, endophenotype-based pathway approaches have recently been shown to have greater advantages for gene-finding strategies than traditional case-control studies. In the present study, in addition to conventional case-control methods, we used pathway analyses to test whether the tri-allelic serotonin transporter promoter polymorphism (combining 5-HTTLPR and rs25531) is associated with risk of GAD through its effects on trait neuroticism. Methods: We included 2236 Han Chinese adults in this study, including 736 patients with GAD and 1500 healthy participants. We genotyped the 5-HTTLPR and rs25531 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism method. We used the Neuroticism scale of the Maudsley Personality Inventory (MPI) short version (MPI-Neuroticism) to measure participants' tendency toward neuroticism. Results: Using endophenotype-based path analyses, we found significant indirect effects of the tri-allelic genotype on risk of GAD, mediated by MPI-Neuroticism in both men and women. Compared to women carrying the S'S' genotype, women carrying the L' allele had higher levels of MPI-Neuroticism, which in turn were associated with higher risk of GAD. Men, however, showed the opposite pattern. Using traditional case-control comparisons, we observed that the effect of tri-allelic genotype on GAD was significant, but only in women. Limitations: Participants were restricted to Han Chinese, and we used only 1 questionnaire to assess neuroticism. Conclusion: These findings are the first to show that the triallelic 5-HTTLPR polymorphism is associated with elevated risk of GAD, and that this effect is mediated via increased trait neuroticism, a sex-dependent risk pathway.

p17 from HIV induces brain endothelial cell angiogenesis through EGFR-1-mediated cell signalling activation.

HIV-associated neurocognitive disorder in HIV patients substantially reduces their quality of life. We previously showed that the HIV matrix protein, p17 could stimulate lymph-angiogenesis in vitro potentially contributing to lymphoma tumour growth and in addition is associated with vascular activation in neuro-degenerating brain tissue; here, therefore, we have investigated the detailed molecular mechanisms of this action. We performed in vitro cell culture, angiogenesis experiments, phospho-protein microarrays and Western blotting to identify cellular signalling induced by p17 within human brain endothelial cells (HbMEC), and inhibitor studies to block p17-induced vascular growth. We also characterised the effects of hippocampal CA1 injection of p17 on epidermal growth factor receptor-1 (EGFR1) expression linked to our murine model of dementia. p17 strongly induced angiogenesis of HbMEC (migration, tube formation and spheroid growth). p17 concomitantly increased phosphorylation of EGFR1 as well as down-stream intermediates ERK1/2, FAK, PLC-γ and PKC-ß whilst an inhibitor peptide of EGFR, blocked cell signalling and angiogenesis. Finally, Mice that showed reduced cognitive function and behavioural deficiencies after p17 injection, demonstrated that p17 localised in cortical microvessels and also neurones many of which stained positive for p-EGFR1 by histology/IHC. This work provides strong support that p17 may be involved in initiating and/or perpetuating vascular tissue pathophysiology associated with comorbidity in HIV patients.

Investigation of the variants at the binding site of inflammatory transcription factor NF-κB in patients with end-stage renal disease.

BACKGROUND: A chronic inflammatory state is a prominent feature in patients with end-stage renal disease (ESRD). Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates the expression of genes involved in inflammation. Some genetic studies have demonstrated that the NF-κB genetic mutation could cause kidney injury and kidney disease progression. However, the association of a gene polymorphism in the transcription factor binding site of NF-κB with kidney disease is not clear. METHODS: We used the Taiwan Biobank database, the University of California, Santa Cruz, reference genome, and a chromatin immunoprecipitation sequencing database to find single nucleotide polymorphisms (SNPs) at potential binding sites of NF-κB. In addition, we performed a case-control study and genotyped 847 patients with ESRD and 846 healthy controls at Tri-Service General Hospital from 2015 to 2016. Furthermore, we used the ChIP assay to identify the binding activity of different genotypes and used Luciferase reporter assay to examine the function of the rs9395890 polymorphism. RESULT: The results of biometric screening in the databases revealed 15 SNPs with the potential binding site of NF-κB. Genotype distributions of rs9395890 were significantly different in ESRD cases and healthy controls (P = 0.049). The ChIP assay revealed an approximately 1.49-fold enrichment of NF-κB of the variant type TT when compared to that of the wild-type GG in rs9395890 (P = 0.027; TT = 3.20 ± 0.16, GT = 2.81 ± 0.20, GG = 1.71 ± 0.18). The luciferase reporter assay showed that the NF-κB binding site activity in T allele was slightly higher than that in G allele, though it is not significant. CONCLUSIONS: Our findings indicate that rs9395890 is associated with susceptibility to ESRD in Taiwan population.

What is the gap in activity and participation between people with disability and the general population in Taiwan?

BACKGROUND: In 2010, the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was developed, based on the concept of the International Classification of Functioning, Disability and Health (ICF). The ICF provides a common language and framework for health and health-related status and attempts to integrate the biopsychosocial model as a multidimensional perspective in understanding functioning. Activities and participation (AP) is one salient component of the ICF refers to the execution of a task by an individual, and how such tasks are involved in their daily life. It is essential to examine the gap between the general adult population and adults with disabilities. This gap may be attributed to health status, personal factors, and natural and social environments, which include social and health services and policies. The purposes: (1) To develop a normative activity and participation (AP) value for the adult population and people with disabilities; and (2) to compare the gap in AP normative values between the two groups in Taiwan. METHODS: We use the WHODAS 2.0 to survey and develop a normative AP value for the general adult population, and used secondary data from National Disability Eligibility Determination System (NDEDS) of Taiwan to describe the AP functioning distribution of adult with disability. There were 1100 participants, selected by stratified proportional sampling from two cities. There were also 144,850 participants who were adults with disability, selected from the secondary database in Taiwan. RESULTS AND CONCLUSIONS: The AP curve for the disabled population increased rapidly at the beginning. The summary score was 13.21 in the performance at 90 percentile for the general population and 82.61 score for disabled adults that the similar gap in every domain, its means that there are significant functioning difference and health equality in general adults population and adults with disabilities. This presents a substantial challenge for both the government and the whole population of Taiwan, to begin considering how to reduce the gap in AP functioning and promote equality for people with disabilities, using social welfare policy. It is important to make sure disabled people have the same rights to be included in society as anybody else and better access to things in all areas of life that are according to Convention on the Rights of Persons with Disabilities (CRPD).

Increased follistatin associated with decreased gait speed among old adults.

BACKGROUND: Low gait speed is associated with inflammation and muscle strength. Follistatin, a glycosylated plasma protein, is involved in inflammatory diseases, bone metabolism, muscle strength and cognition. However, research regarding the relationship between follistatin and gait speed in elderly individuals is limited. In this study, we aimed to examine the association between follistatin and gait speed in older adults. METHODS: This cross-sectional, observational study included 205 ambulatory individuals aged ≥ 65 years. The baseline measures included 15-foot walking time, a structured questionnaire, grip strength and biomarkers, including follistatin and myostatin levels. Multiple linear regression was used to determine the change in gait speed for each 1 pg/mL increase in serum follistatin level. An extended model approach with a quartile-based analysis of serum follistatin levels was conducted. RESULTS: In the linear regression model, the ß coefficient, representing the change in gait speed for each 1 pg/mL increase in serum follistatin level, was -0·308 (P < 0·001). After additional adjustment for relevant covariates, the ß coefficient changed slightly, although the negative correlation remained (all P ≤ 0·001). After controlling for multiple covariates, participants in the highest serum follistatin level quartile had a significantly lower gait speed than those in the lowest quartile (all P for trend < 0·001). CONCLUSIONS: A higher follistatin level was independently associated with lower gait speed in community-dwelling elderly individuals; this suggests that serum follistatin level may be an indicator of mobility in elderly persons and may more particularly represent lower extremity function.

The utilization and barriers of Pap smear among women with visual impairment.

BACKGROUND: Many evidences illustrate that the Pap smear screening successfully reduces if the cervical cancer could be detected and treated sufficiently early. People with disability were higher comorbidity prevalence, and less likely to use preventive health care and health promotion activities. There were also to demonstrate that people with visual impairment has less access to appropriate healthcare services and is less likely to receive screening examinations. In Taiwan, there was no study to explore utilization of Pap smear, associated factors and use barriers about Pap smear screening test among women with visual impairment. The purpose is to explore the utilization and barriers of using Pap smear for women with visual impairment in Taiwan. To identify the barriers of women with visual from process of receiving Pap smear screening test. METHODS: The cross-sectional study was conducted and the totally 316 participators were selected by stratified proportional and random sampling from 15 to 64 year old women with visual impairment who lived in Taipei County during December 2009 to January 2010. The data was been collected by phone interview and the interviewers were well trained before interview. RESULTS: The mean age was 47.1 years old and the highest percentage of disabled severity was mile (40.2 %). Totally, 66.5 % of participators were ever using Pap smear and 38.9 % used it during pass 1 year. Their first time to accept Pap smear was 38.8 year old. There was near 50 % of them not to be explained by professionals before accepting the Pap smear. For non-using cases, the top two percentage of barriers were "feel still younger" (22.3 %), the second was "there's no sexual experience" (21.4 %). We found the gynecology experiences was key factor for women with visual impairment to use Pap smear, especially the experiences was during 1 year (OR = 4). CONCLUSIONS: Associated factors and barriers to receive Pap smear screening test for women with visual impairment can be addressed through interventions aimed at improving on cognitions and attitudes for cervical cancer risk factors. Our study would be as a reference resource for erasing the barriers and inequality among the visually disabled women.

Study on the Detection of Rice Seed Germination Rate Based on Infrared Thermal Imaging Technology Combined with Generalized Regression Neural Network.

On the basis of the differences in physiology and physics of rice seed with different aging time, the paper proposes a fast and nondestructive method which is based on infrared thermal imaging technology and generalized regression neural network to detect the germination rate of rice seed. This method solves the problems of long experimental period, complex operations and other disadvantages of the traditional method which is used to detect germination rate. When the temperature is 45 ℃ and humidity is 90%, the rice seeds are aged for 0, 1, 2, 3, 4, 5, 6 and 7 d respectively to get rice seeds of different germination rate. The data of 144 groups was extracted from the germ of rice seed. This data was divided into two groups randomly: the calibration set was 96 groups and the prediction set was 48 groups. Through analyzing and comparing the differences of infrared thermal image of rice seeds of different aging days, the relationship in physics and physiology between germination rate of rice seed and infrared thermal images was revealed. The infrared prediction model for germination rate of rice seed was established by combining partial least squares algorithm, Back Propagationneural network and General regression neural network. The result shows that the optimal germination rate model is built with GRNN. In this model, the correlation coefficient (RC) and standard deviation (SEC) of calibration sets are 0.932 0 and 2.056 0. At the same time, the correlation coefficient (RP) and standard deviation (SEP) of prediction sets are 0.900 3 and 4.101 2. The relevance reaches a higher level and the standard deviation is small. Therefore, the experiment shows that combining infrared thermal imaging technology with GRNN to study germination rate of rice seed is feasible. The model has a higher accuracy in terms of rapid determination of the germination rate of rice seed.

PAX3 in neuroblastoma: oncogenic potential, chemosensitivity and signalling pathways.

Transcription factor PAX3/Pax3 contributes to diverse cell lineages during embryonic development and is important in tumourigenesis. We found that PAX3 is re-expressed in neuroblastoma and malignant neuroblastic (N-type) neuroblastoma cells had significantly higher PAX3 protein expression than their benign substrate-adherent (S-type) counterparts. Knock-down of PAX3 expression by siRNA transfection resulted in persistent cell growth inhibition in both types of neuroblastoma cell, owing to G1 cell cycle arrest and progressive apoptosis. Inhibition of PAX3 expression significantly decreased the attachment of S-type SH-EP1 cells to extra-cellular matrix proteins, fibronectin, laminin and collagen IV. Migration and invasion of both neuroblastoma cell types were markedly reduced after PAX3 down-regulation. PAX3 knock-down significantly augmented the cytotoxic effect of chemotherapeutic agents, etoposide, vincristine and cisplatin, commonly used to treat neuroblastoma. Microarray analyses revealed that particularly signalling pathways involving cell cycle, apoptosis, cell adhesion, cytoskeletal remodelling and development were altered by PAX3 down-regulation. Changes in PAX3 downstream genes identified by microarray analyses were validated in 47 genes by quantitative PCR. These novel findings lead us to propose that PAX3 might contribute to oncogenic characteristics of neuroblastoma cells by regulating a variety of crucial signalling pathways.

Sex-specific association between nerve growth factor polymorphism and cardiac vagal modulation.

OBJECTIVE: Substantial research has shown that anxiety disorders are associated with decreased cardiac vagal tone, which is a known risk factor for cardiac vulnerability. A functional nerve growth factor (NGF) polymorphism (rs6330, c.104C > T, p.Ala35Val) has been associated with anxiety such that in males but not females, T-allele carriers exhibit higher levels of trait anxiety. Here we investigate whether the nonsynonymous NGF variant has an effect on cardiac autonomic control. METHODS: From 705 adults initially screened for medical and psychiatric illnesses, a final cohort of 580 healthy Han Chinese (352 men, 228 women; mean [standard deviation] age = 34.46 [8.45] years) was included in the NGF genotyping (C/C: 428% [73.8%] and T-allele carriers: 152% [26.2%]). Short-term heart rate variability was used to assess cardiac autonomic function. RESULTS: There were significant genotype-by-sex interaction effects (p < .05) on high-frequency power (HF) and root mean square of successive heartbeat interval differences (RMSSD), both indices of cardiac vagal control. Even after adjusting for possible confounders, men with any T allele showed lower HF and RMSSD compared with men with the C/C genotype. Women, however, showed an opposite but nonsignificant pattern. CONCLUSIONS: The studied NGF polymorphism modulates autonomic outflow to the heart in a sex-dependent manner. The findings support the view that male T-allele carriers are at increased susceptibility for anxiety by association with low vagal activity and suggest a potential sex-specific genetic link between the highly comorbid anxiety disorders and cardiovascular diseases.

Comprehensive clinical application analysis of artificial intelligence-enabled electrocardiograms for screening multiple valvular heart diseases.

BACKGROUND: Valvular heart disease (VHD) is becoming increasingly important to manage the risk of future complications. Electrocardiographic (ECG) changes may be related to multiple VHDs, and (AI)-enabled ECG has been able to detect some VHDs. We aimed to develop five deep learning models (DLMs) to identify aortic stenosis, aortic regurgitation, pulmonary regurgitation, tricuspid regurgitation, and mitral regurgitation. METHODS: Between 2010 and 2021, 77,047 patients with echocardiography and 12-lead ECG performed within 7 days were identified from an academic medical center to provide DLM development (122,728 ECGs), and internal validation (7,637 ECGs). Additional 11,800 patients from a community hospital were identified to external validation. The ECGs were classified as with or without moderate-to-severe VHDs according to transthoracic echocardiography (TTE) records, and we also collected the other echocardiographic data and follow-up TTE records to identify new-onset valvular heart diseases. RESULTS: AI-ECG adjusted for age and sex achieved areas under the curves (AUCs) of >0.84, >0.80, >0.77, >0.83, and >0.81 for detecting aortic stenosis, aortic regurgitation, pulmonary regurgitation, tricuspid regurgitation, and mitral regurgitation, respectively. Since predictions of each DLM shared similar components of ECG rhythms, the positive findings of each DLM were highly correlated with other valvular heart diseases. Of note, a total of 37.5-51.7% of false-positive predictions had at least one significant echocardiographic finding, which may lead to a significantly higher risk of future moderate-to-severe VHDs in patients with initially minimal-to-mild VHDs. CONCLUSION: AI-ECG may be used as a large-scale screening tool for detecting VHDs and a basis to undergo an echocardiography.

AI-enabled electrocardiography alert intervention and all-cause mortality: a pragmatic randomized clinical trial.

The early identification of vulnerable patients has the potential to improve outcomes but poses a substantial challenge in clinical practice. This study evaluated the ability of an artificial intelligence (AI)-enabled electrocardiogram (ECG) to identify hospitalized patients with a high risk of mortality in a multisite randomized controlled trial involving 39 physicians and 15,965 patients. The AI-ECG alert intervention included an AI report and warning messages delivered to the physicians, flagging patients predicted to be at high risk of mortality. The trial met its primary outcome, finding that implementation of the AI-ECG alert was associated with a significant reduction in all-cause mortality within 90 days: 3.6% patients in the intervention group died within 90 days, compared to 4.3% in the control group (4.3%) (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.70-0.99). A prespecified analysis showed that reduction in all-cause mortality associated with the AI-ECG alert was observed primarily in patients with high-risk ECGs (HR = 0.69, 95% CI = 0.53-0.90). In analyses of secondary outcomes, patients in the intervention group with high-risk ECGs received increased levels of intensive care compared to the control group; for the high-risk ECG group of patients, implementation of the AI-ECG alert was associated with a significant reduction in the risk of cardiac death (0.2% in the intervention arm versus 2.4% in the control arm, HR = 0.07, 95% CI = 0.01-0.56). While the precise means by which implementation of the AI-ECG alert led to decreased mortality are to be fully elucidated, these results indicate that such implementation assists in the detection of high-risk patients, prompting timely clinical care and reducing mortality. ClinicalTrials.gov registration: NCT05118035 .

Detrimental Association Between Blood Cadmium Concentration and Trabecular Bone Score.

Osteoporosis has been recognized as a significant cause of disability in the elderly leading to heavy socioeconomic burden. Current measurements such as dual-energy X-ray absorptiometry (DEXA) and bone mineral density (BMD) have limitations. In contrast, trabecular bone score (TBS) is an emerging tool for bone quality assessment. The objective of our study was to investigate the relationship between TBS and trace elements (cadmium and lead). We analyzed all subjects from the 2005-2006 and 2007-2008 National Health and Nutrition Examination Survey (NHANES) dataset and included a total of 8,244 participants in our study; 49.4% of the enrolled subjects were male. We used blood cadmium (Cd) and lead (Pb) concentrations to define environmental exposure. The main variables were TBS and BMD. Other significant demographic features were included as covariates and later adjusted using linear regression models to determine the association between TBS and four quartiles based on the blood trace element concentrations with or without sex differences. The fully adjusted regression model revealed a negative relationship between TBS and blood cadmium (B-Cd) significant for both males and females (both p < 0.05). The ß-coefficient for males was -0.009 (95% confidence intervals (CI): (-0.015 to -0.004)) and -0.019 for female (95% CI: (-0.024 to -0.013)). We also found a dose-dependent relationship between TBS and B-Cd for both sexes (both trend's p < 0.05). Our study concluded that TBS could measure Cd-related bone quality deterioration for both males and females.