Classification of laryngeal diseases including laryngeal cancer, benign mucosal disease, and vocal cord paralysis by artificial intelligence using voice analysis.

Voice change is often the first sign of laryngeal cancer, leading to diagnosis through hospital laryngoscopy. Screening for laryngeal cancer solely based on voice could enhance early detection. However, identifying voice indicators specific to laryngeal cancer is challenging, especially when differentiating it from other laryngeal ailments. This study presents an artificial intelligence model designed to distinguish between healthy voices, laryngeal cancer voices, and those of the other laryngeal conditions. We gathered voice samples of individuals with laryngeal cancer, vocal cord paralysis, benign mucosal diseases, and healthy participants. Comprehensive testing was conducted to determine the best mel-frequency cepstral coefficient conversion and machine learning techniques, with results analyzed in-depth. In our tests, laryngeal diseases distinguishing from healthy voices achieved an accuracy of 0.85-0.97. However, when multiclass classification, accuracy ranged from 0.75 to 0.83. These findings highlight the challenges of artificial intelligence-driven voice-based diagnosis due to overlaps with benign conditions but also underscore its potential.

Cell Surface Modification-Mediated Primary Intestinal Epithelial Cell Culture Platforms for Assessing Host-Microbiota Interactions.

Background: Intestinal epithelial cells (IECs) play a crucial role in regulating the symbiotic relationship between the host and the gut microbiota, thereby allowing them to modulate barrier function, mucus production, and aberrant inflammation. Despite their importance, establishing an effective ex vivo culture method for supporting the prolonged survival and function of primary IECs remains challenging. Here, we aim to develop a novel strategy to support the long-term survival and function of primary IECs in response to gut microbiota by employing mild reduction of disulfides on the IEC surface proteins with tris(2-carboxyethyl)phosphine. Methods: Recognizing the crucial role of fibroblast-IEC crosstalk, we employed a cell surface modification strategy, establishing layer-to-layer contacts between fibroblasts and IECs. This involved combining negatively charged chondroitin sulfate on cell surfaces with a positively charged chitosan thin film between cells, enabling direct intercellular transfer. Validation included assessments of cell viability, efficiency of dye transfer, and IEC function upon lipopolysaccharide (LPS) treatment. Results: Our findings revealed that the layer-by-layer co-culture platform effectively facilitates the transfer of small molecules through gap junctions, providing vital support for the viability and function of primary IECs from both the small intestine and colon for up to 5 days, as evident by the expression of E-cadherin and Villin. Upon LPS treatment, these IECs exhibited a down-regulation of Villin and tight junction genes, such as E-cadherin and Zonula Occludens-1, when compared to their nontreated counterparts. Furthermore, the transcription level of Lysozyme exhibited an increase, while Mucin 2 showed a decrease in response to LPS, indicating responsiveness to bacterial molecules. Conclusions: Our study provides a layer-by-layer-based co-culture platform to support the prolonged survival of primary IECs and their features, which is important for understanding IEC function in response to the gut microbiota.

Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling.

Vascular remodeling is the process of structural alteration and cell rearrangement of blood vessels in response to injury and is the cause of many of the world's most afflicted cardiovascular conditions, including pulmonary arterial hypertension (PAH). Many studies have focused on the effects of vascular endothelial cells and smooth muscle cells (SMCs) during vascular remodeling, but pericytes, an indispensable cell population residing largely in capillaries, are ignored in this maladaptive process. Here, we report that hypoxia-inducible factor 2α (HIF2α) expression is increased in the lung tissues of PAH patients, and HIF2α overexpressed pericytes result in greater contractility and an impaired endothelial-pericyte interaction. Using single-cell RNAseq and hypoxia-induced pulmonary hypertension (PH) models, we show that HIF2α is a major molecular regulator for the transformation of pericytes into SMC-like cells. Pericyte-selective HIF2α overexpression in mice exacerbates PH and right ventricular hypertrophy. Temporal cellular lineage tracing shows that HIF2α overexpressing reporter NG2+ cells (pericyte-selective) relocate from capillaries to arterioles and co-express SMA. This novel insight into the crucial role of NG2+ pericytes in pulmonary vascular remodeling via HIF2α signaling suggests a potential drug target for PH.

Phenolic changes in a combined herbal extract of Lithospermum erythrorhizon, Houttuynia cordata, and Spirodela polyrhiza and alleviation of DNCB-induced atopic dermatitis in BALB/c mice.

Atopic dermatitis (AD) is an inflammatory skin disease showing skin barrier dysfunction, eczematous lesions, severe itching, and abnormal immune responses. The aim of this study was to determine whether an herb combination of Lithospermum erythrorhizon (LE), Houttuynia cordata (HC), and Spirodela polyrhiza (SP) has a superior anti-AD effect. Forty-two compounds were identified in LE, HC, SP, and a combined herb extract of LE, HC, and SP (LHS) using ultra-high-pressure liquid chromatography (UHPLC)-Orbitrap mass spectrometer (MS). The concentration of flavonoid glycosides including orientin (luteolin-8-C-glucoside), quercetin-3-O-rhamnoside, and luteolin-7-O-glucoside in the LHS was increased than in individual extracts. Furthermore, the treatment of LHS most effectively inhibited the increase of epidermal thickness, the number of mast cells, and the release of immunoglobulin E compared with that with each extract. These results suggest that the potential anti-AD effects of the LHS are due to the changes of bioactive compounds by the combination of herbs. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01329-7.

Enhancing Smart Building Surveillance Systems in Thin Walls: An Efficient Barrier Design.

This paper introduces an efficient barrier model for enhancing smart building surveillance in harsh environment with thin walls and structures. After the main research problem of minimizing the total number of wall-recognition surveillance barriers, we propose two distinct algorithms, Centralized Node Deployment and Adaptation Node Deployment, which are designed to address the challenge by strategic placement of surveillance nodes within the smart building. The Centralized Node Deployment aligns nodes along the thin walls, ensuring consistent communication coverage and effectively countering potential disruptions. Conversely, the Adaptation Node Deployment begins with random node placement, which adapts over time to ensure efficient communication across the building. The novelty of this work is in designing a novel barrier system to achieve energy efficiency and reinforced surveillance in a thin-wall environment. Instead of a real environment, we use an ad hoc server for simulations with various scenarios and parameters. Then, two different algorithms are executed through those simulation environments and settings. Also, with detailed discussions, we provide the performance analysis, which shows that both algorithms deliver similar performance metrics over extended periods, indicating their suitability for long-term operation in smart infrastructure.

CHEX-seq detects single-cell genomic single-stranded DNA with catalytical potential.

Genomic DNA (gDNA) undergoes structural interconversion between single- and double-stranded states during transcription, DNA repair and replication, which is critical for cellular homeostasis. We describe "CHEX-seq" which identifies the single-stranded DNA (ssDNA) in situ in individual cells. CHEX-seq uses 3'-terminal blocked, light-activatable probes to prime the copying of ssDNA into complementary DNA that is sequenced, thereby reporting the genome-wide single-stranded chromatin landscape. CHEX-seq is benchmarked in human K562 cells, and its utilities are demonstrated in cultures of mouse and human brain cells as well as immunostained spatially localized neurons in brain sections. The amount of ssDNA is dynamically regulated in response to perturbation. CHEX-seq also identifies single-stranded regions of mitochondrial DNA in single cells. Surprisingly, CHEX-seq identifies single-stranded loci in mouse and human gDNA that catalyze porphyrin metalation in vitro, suggesting a catalytic activity for genomic ssDNA. We posit that endogenous DNA enzymatic activity is a function of genomic ssDNA.

Breathing sounds analysis system for early detection of airway problems in patients with a tracheostomy tube.

To prevent immediate mortality in patients with a tracheostomy tube, it is essential to ensure timely suctioning or replacement of the tube. Breathing sounds at the entrance of tracheostomy tubes were recorded with a microphone and analyzed using a spectrogram to detect airway problems. The sounds were classified into three categories based on the waveform of the spectrogram according to the obstacle status: normal breathing sounds (NS), vibrant breathing sounds (VS) caused by movable obstacles, and sharp breathing sounds (SS) caused by fixed obstacles. A total of 3950 breathing sounds from 23 patients were analyzed. Despite neither the patients nor the medical staff recognizing any airway problems, the number and percentage of NS, VS, and SS were 1449 (36.7%), 1313 (33.2%), and 1188 (30.1%), respectively. Artificial intelligence (AI) was utilized to automatically classify breathing sounds. MobileNet and Inception_v3 exhibited the highest sensitivity and specificity scores of 0.9441 and 0.9414, respectively. When classifying into three categories, ResNet_50 showed the highest accuracy of 0.9027, and AlexNet showed the highest accuracy of 0.9660 in abnormal sounds. Classifying breathing sounds into three categories is very useful in deciding whether to suction or change the tracheostomy tubes, and AI can accomplish this with high accuracy.

Umbelliferone Ameliorates Memory Impairment and Enhances Hippocampal Synaptic Plasticity in Scopolamine-Induced Rat Model.

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents. Umbelliferone (UMB) is a Apiaceae-family-derived 7-hydeoxycoumarin known for its antioxidant, anti-tumor, anticancer, anti-inflammatory, antibacterial, antimicrobial, and antidiabetic properties. However, the effects of UMB on the electrophysiological and ultrastructure morphological aspects of learning and memory are still not well-established. Thus, we investigated the effect of UMB treatment on cognitive behaviors and used organotypic hippocampal slice cultures for long-term potentiation (LTP) and the hippocampal synaptic ultrastructure. A hippocampal tissue analysis revealed that UMB attenuated a SCOP-induced blockade of field excitatory post-synaptic potential (fEPSP) activity and ameliorated the impairment of LTP by the NMDA and AMPA receptor antagonists. UMB also enhanced the hippocampal synaptic vesicle density on the synaptic ultrastructure. Furthermore, behavioral tests on male SD rats (7-8 weeks old) using the Y-maze test, passive avoidance test (PA), and Morris water maze test (MWM) showed that UMB recovered learning and memory deficits by SCOP. These cognitive improvements were in association with the enhanced expression of BDNF, TrkB, and the pCREB/CREB ratio and the suppression of acetylcholinesterase activity. The current findings indicate that UMB may be an effective neuroprotective reagent applicable for improving learning and memory against AD.

Study on relationship between self-recognition of voice disorder and mental health status: Korea National Health and Nutrition Examination Survey.

BACKGROUND: The voice has been thought to be associated with emotions, but conducting large-scale research on this relationship has some limitations. To overcome these limitations, questionnaires have been utilized as a research tool. METHODS: A population-based cross-sectional study was done. A total of 15,977 participants completed questionnaires regarding self-recognition of voice disorder (SRVD), and mental health status. RESULTS: 1053(6.6 %) participants answered that they had SRVD. In the multivariate Cox proportional hazard model, psychological stress (Hazard ratio (HR) = 1.371, 95 % confidence interval (CI) = 1.154-1.629), depressive symptoms (HR = 1.626, 95 % CI = 1.323-1.997), suicidal ideation (HR = 1.739, 95 % CI = 1.418-2.133), and suicide attempt (HR =2.206, 95 % CI = 1.067-4.56) were all associated with SRVD. In SRVD lasting over three weeks, psychological stress (HR = 1.604, 95 % CI = 1.278-2.014), depressive symptoms (HR = 1.807, 95 % CI = 1.384-2.36), and suicidal ideation (HR = 2.073, 95 % CI = 1.587-2.709) were also significant factors. As the number of mental health problems increased, the odds ratio of both SRVD (OR = 2.49, 95 % CI = 1.839-3.37) and SRVD lasting over three weeks (OR = 3.254, 95 % CI = 2.242-4.725) increased, respectively. LIMITATIONS: SRVD and mental health status were judged only by simple questionnaires. Cross-sectional design and retrospective data could not draw causal relationships. CONCLUSIONS: SRVD and SRVD lasting over three weeks had a significant relationship with mental health status, including psychological stress, depressive symptoms, and suicidal ideation. There is a need to consider psychiatric treatment for individuals who visit hospitals with voice disorders.

Intelligent Terrestrial and Non-Terrestrial Vehicular Networks with Green AI and Red AI Perspectives.

In this paper, we aim to envision 6G convergent terrestrial and non-terrestrial infrastructure of virtual emotion and epidemic prevention with two differential perspectives: Green AI and Red AI, where Green AI focuses on efficiency and reduction, and Red AI additionally pursues accuracy. By fitting with each perspective, we introduce promising key applications using smart devices, autonomous UAVs, mobile robots and subsequently suggest critical future research directions and opportunities toward new frontiers in intelligent terrestrial and non-terrestrial vehicular networks.

Naringin enhances long-term potentiation and recovers learning and memory deficits of amyloid-beta induced Alzheimer's disease-like behavioral rat model.

Alzheimer's disease (AD), as the most typical type of dementia, is a chronic neurodegenerative disorder characterized by progressive learning and memory impairment. It is known that the main causes of AD are the accumulation of ß-amyloid (Aß) plaques and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Naringin is a flavonoid from citrus fruits, especially in grapefruit, which has anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. However, the effect of naringin in AD caused by Aß has not been clearly studied, and there are few studies on the electrophysiological aspect. Thus, we investigated the ex vivo neuroprotective effect of naringin through the long-term potentiation (LTP) on organotypic hippocampal slice cultures. We evaluated the in vivo effects of naringin (100 mg/kg/day) orally treated for 20 days on learning, memory, and cognition which was impaired by bilateral CA1 subregion injection of Aß. Cognitive behaviors were measured 2 weeks after Aß injection using behavioral tests and the hippocampal expression of apoptotic and neurotrophic regulators were measured by immunoblotting. In hippocampal tissue slices, naringin dose-dependently increased the field excitatory postsynaptic potential (fEPSP) after theta burst stimulation and attenuated Aß-induced blockade of fEPSP in the hippocampal CA1 area. In Aß injected rats, naringin improved object recognition memory in the novel object test, avoidance memory in the passive avoidance test and spatial recognition memory in the Morris water maze test. In the hippocampus, naringin attenuated the Aß-induced cyclooxygenase-2, Bax activation and Bcl-2, CREB, BDNF and TrkB inhibition. These results suggest that naringin has therapeutic potential to reduce neuronal inflammation and apoptosis induced by Aß related with the BDNF/TrkB/CREB signaling.

Association of smoking status, duration and amount with the risk of head and neck cancer subtypes: a national population-based study.

Smoking is positively associated with multiple cancer types including head and neck cancer (HNC). We sought to confirm the effect of smoking in HNC and subtypes through big data analysis. All data used in this study originated from the Korean National Health Insurance Service database. We analyzed subjects who had undergone health check-ups in 2009 with follow-up until 2018 (n=10,585,852). We collected data on smoking and other variables that could affect the risk of HNC. The overall incidence of HNC was highest in current smokers (HR: 1.822, 95% CI: 1.729-1.920), followed by ex-smokers (HR: 1.242, 95% CI: 1.172-1.317). Laryngeal cancer, hypopharynx cancer, oral cancer, oropharyngeal cancer, and salivary gland cancer showed increasing incidence rates from ex-smokers to current smokers. Smoking duration and amount showed a dose-dependent relationship with the occurrence of HNC. However, the incidence of HNC did not increase significantly when smoking duration was less than 10 years, or when the smoking amount was less than 10 pack-years in ex-smokers. Smoking is associated with the risk of HNC. Smoking cessation before 10 years or 10 pack-years can prevent the development of HNC.

Association of Estimated Glomerular Filtration Rate with Risk of Head and Neck Cancer: A Nationwide Population-Based Study.

In this study, through a cohort study of 10 million people, we investigated the association between estimated glomerular filtration rate (eGFR) and head and neck cancer (HNC) incidence. This is an observational cohort study using data from the national health claims database established by the Korean National Health Insurance Service (NHIS). We selected 9,598,085 participants older than 20 years who had undergone health checkups in 2009. A health checkup involves the history of any diseases, current health status, and results of several physical and blood exams including eGFR. We investigated the presence of HNC diagnosis in their national health insurance data from 2010 to 2018. Of the 9,598,085 participants, 10,732 had been newly diagnosed with HNC in the 9-year follow-up. In the multivariate Cox proportional hazard model, participants with elevated eGFR were associated with a risk of HNC incidence (HR = 1.129; 95% CI = 1.075−1.186 for eGFR = 90−104 mL/min/1.73 m2 and HR = 1.129; 95% CI = 1.076−1.194 for eGFR ≥ 105 mL/min/1.73 m2) compared with those with eGFR 60−89 mL/min/1.73 m2. Among HNC, the incidences of oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers were significantly increased in the elevated eGFR group. According to the subgroup analysis, participants with eGFR ≥ 60 mL/min/1.73 m2 were correlated with risk of HNC incidence in middle age, non/mild drinker, low BMI, no diabetes, and no hypertension patients compared with those with eGFR < 60 mL/min/1.73 m2. Elevated eGFR was associated with the risk of some type of HNC, even in individuals with adjusted hypertension and diabetes without chronic diseases. The results of this study have implications for etiological investigations and preventive strategies.

Post-stroke respiratory complications using machine learning with voice features from mobile devices.

Abnormal voice may identify those at risk of post-stroke aspiration. This study was aimed to determine whether machine learning algorithms with voice recorded via a mobile device can accurately classify those with dysphagia at risk of tube feeding and post-stroke aspiration pneumonia and be used as digital biomarkers. Voice samples from patients referred for swallowing disturbance in a university-affiliated hospital were collected prospectively using a mobile device. Subjects that required tube feeding were further classified to high risk of respiratory complication, based on the voluntary cough strength and abnormal chest x-ray images. A total of 449 samples were obtained, with 234 requiring tube feeding and 113 showing high risk of respiratory complications. The eXtreme gradient boosting multimodal models that included abnormal acoustic features and clinical variables showed high sensitivity levels of 88.7% (95% CI 82.6-94.7) and 84.5% (95% CI 76.9-92.1) in the classification of those at risk of tube feeding and at high risk of respiratory complications; respectively. In both cases, voice features proved to be the strongest contributing factors in these models. Voice features may be considered as viable digital biomarkers in those at risk of respiratory complications related to post-stroke dysphagia.

Associations of Body Mass Index and Waist Circumference with the Risk of Head and Neck Cancer: A National Population-Based Study.

Background: We investigated the association between BMI and HNC subtype incidence in a cohort study of ten million people, adjusting for the effect of smoking and drinking. We also investigated the relationship between waist circumference (WC) and HNC subtype. Methods: All data used in this study originated from the Korean National Health Insurance Service database. We analysed subjects who had undergone health check-ups in 2009 and monitored subjects until 2018 (n = 10,585,852). Finally, 9,598,085 subjects were included after exclusions. We collected variables that could affect the risk of HNC. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The overall incidence of HNC was higher in the low BMI category (BMI < 18.5 according to WHO recommendations for Asian people) (HR: 1.322; 95% CI: 1.195−1.464) compared with the normal BMI category. Among the HNC cases, the incidence rates of laryngeal (HR: 1.3; 95% CI: 1.085−1.558), oral cavity (HR: 1.277; 95% CI: 1.011−1.611), and oropharyngeal (HR: 1.584; 95% CI: 1.25−2.008) cancers were higher in the low BMI category compared with the normal BMI category. No significant association was detected between low BMI and sinus cancer, salivary gland cancer, or nasopharyngeal cancer. The low WC category (<80 cm in men and <75 cm in women) was related to a risk of hypopharyngeal (HR: 1.268; 95% CI: 1.061−1.514) and laryngeal (HR: 1.118; 95% CI: 1.007−1.241) cancers. The HR for occurrence of HNC was high in underweight participants according to smoking status (1.219 for never smoker vs. 1.448 for ever smoker, p for interaction = 0.0015) and drinking status (1.193 for never drinker vs. 1.448 for ever drinker, p for interaction = 0.0044). Conclusions: Low BMI was associated with the risk of some types of HNC. The results of this study could assist etiological investigations and prevention strategies.

Association between γ-Glutamyltransferase and Head and Neck Cancer in Korean Population: A National Population-Based Study.

BACKGROUND: Gamma-glutamyltransferase (GGT) is positively associated with several cancer types. The objective of this study was to investigate the association between GGT and head and neck cancer (HNC) incidence in a cohort of 10 million people, considering effects of smoking and alcohol consumption. METHODS: All data used in this study were obtained from the Korean National Health Insurance Service database. We analyzed subjects who underwent health check-ups in 2009 and monitored them until 2018 (n = 9,597,952). Using proportional hazards models, quartiles of GGT as independent predictors for HNC incidence were evaluated. RESULTS: The overall incidence of HNC increased in the highest quartile [r-GPT ≥ 40 U/L; HR, 1.452; 95% confidence interval (CI), 1.354-1.557]. Among HNC cases, the HR for hypopharyngeal cancer (HR, 2.364; 95% CI, 1.818-3.074) was significantly higher. HRs for HNC (larynx, sino-nasal, oropharynx, oral cavity, and nasopharynx, except salivary glands) were also significant. CONCLUSIONS: Elevated GGT was associated with the risk of some types of HNCs, such as hypopharyngeal, laryngeal, sinonasal, oropharyngeal, oral cavity, and nasopharyngeal cancer. IMPACT: Results of this study have implications for etiologic investigations and preventive strategies.

Close Surgical Margins in Oral and Oropharyngeal Cancer: Do They Impact Prognosis?

Introduction. Mucosal margins exhibit a mean shrinkage of 30−40% after resection of oral and oropharyngeal cancers, and an adequate in situ surgical margin frequently results in a pathological close margin. However, the impact on prognosis remains unclear. We investigated the impact of a pathological close margin on disease-free survival (DFS) and overall survival (OS). Methods. We retrospectively reviewed the clinicopathological data of 418 patients diagnosed with squamous cell carcinomas of the oral cavity or oropharynx who underwent initial surgery (with curative intent) at our institute between 2010 and 2016. Results. Of the total population, the pathological marginal status of 290 (69.4%) patients was reported as clear (>5 mm), 61 (14.6%) as close (>1 mm, ≤5 mm), and 67 (16.0%) as positive (≤1 mm). The 5-year DFSs were 79.3%, 65.1%, and 52% in patients in the negative margin (group 1), close margin (group 2), and positive margin (group 3) groups, respectively. The difference between groups 1 and 2 was not significant (p = 0.213) but the difference between groups 2 and 3 was (p = 0.034). The 5-year OSs were 79.4%, 84%, and 52.3% in groups 1, 2, and 3, respectively. The difference between groups 1 and 2 was not significant (p = 0.824) but the difference between groups 2 and 3 was (p = 0.001). In multivariate analysis, older age, advanced T stage, and a positive margin were independently prognostic of the 5-year DFS and OS. Conclusion. In conclusion, the OS of patients with close margins was no different than that of others when appropriate postoperative adjuvant and/or salvage treatment were/was prescribed. However, we could not determine the impact of close margins on locoregional recurrence given various biases in our study setting. A future prospective study is needed.