Association of Rest-Activity Rhythm and Risk of Developing Dementia or Mild Cognitive Impairment in the Middle-Aged and Older Population: Prospective Cohort Study.

BACKGROUND: The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults. OBJECTIVE: We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults. METHODS: We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer's disease. RESULTS: During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase. CONCLUSIONS: Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.

The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers.

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

Resveratrol inhibits arecoline-induced fibrotic properties of buccal mucosal fibroblasts via miR-200a activation.

Background/purpose: Oral submucous fibrosis (OSF) is a precancerous lesion in the oral cavity, commonly results from the Areca nut chewing habit. Arecoline, the main component of Areca nut, is known to stimulate the activation of myofibroblasts, which can lead to abnormal collagen I deposition. Meanwhile, Resveratrol is a non-flavonoid phenolic substance that can be naturally obtained from various berries and foods. Given that resveratrol has significant anti-fibrosis traits in other organs, but little is known about its effect on OSF, this study aimed to investigate the therapeutic impact of resveratrol on OSF and its underlying mechanism. Materials and methods: The cytotoxicity of resveratrol was tested using normal buccal mucosal fibroblasts (BMFs). Myofibroblast phenotypes such as collagen contractile, enhanced migration, and wound healing capacities in dose-dependently resveratrol-treated fBMFs were examined. Results: Current results showed that arecoline induced cell migration and contractile activity in BMFs as well as upregulated the expressions of α-SMA, type I collagen, and ZEB1 markers. Resveratrol intervention, on the other hand, was shown to inhibit arecoline-induced myofibroblast activation and reduce myofibroblast hallmarks and EMT markers. Additionally, resveratrol was also demonstrated to restore the downregulated miR-200a in the arecoline-stimulated cells. Conclusion: In a nutshell, these findings implicate that resveratrol may have an inhibitory influence on arecoline-induced fibrosis via the regulation of miR-200a. Hence, resveratrol may be used as a therapeutic strategy for OSF intervention.

Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study.

OBJECTIVE: This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. METHODS: Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. RESULTS: In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4-5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. CONCLUSION: In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.

Polygenic Risk Score in Predicting Esophageal, Oropharyngeal, and Hypopharynx Cancer Risk among Taiwanese Population.

Esophageal cancer shares strong associations with oropharyngeal and hypopharyngeal cancers, primarily due to shared risk factors like excessive tobacco and alcohol use. This retrospective study at Taichung Veterans General Hospital involved 54,692 participants, including 385 with squamous cell carcinoma (SCC) of the esophagus, oropharynx, or hypopharynx. Using a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms, researchers aimed to assess its correlation with cancer incidence and prognosis. The study found a 1.83-fold higher risk of esophageal, oropharyngeal, and hypopharyngeal SCCs in participants with a high PRS (Q4) compared to the low-PRS group (Q1). Esophageal cancer risk demonstrated a significant positive association with the PRS, as did hypopharyngeal cancer. Clinical parameters and staging showed limited associations with PRS quartiles, and the PRS did not significantly impact recurrence or mortality rates. The research highlighted that a higher PRS is linked to increased susceptibility to esophageal and hypopharyngeal cancer. Notably, a specific polygenic risk score, PGS001087, exhibited a discernible association with SCC risk, particularly in specific subtypes and advanced disease stages. However, it was not significantly linked to clinical cancer staging, emphasizing the multifactorial nature of cancer development. This hospital study reveals that a higher PRS correlates with increased susceptibility to esophageal and hypopharyngeal cancers. Notably, PGS001087 shows a discernible association with SCC risk in specific subtypes and advanced stages, although not significantly linked to clinical cancer staging. These findings enhance our understanding of genetic factors in upper aerodigestive tract cancers, particularly esophageal SCC, guiding future research and risk assessment strategies.

A transferable in-silico augmented ischemic model for virtual myocardial perfusion imaging and myocardial infarction detection.

This paper proposes an innovative approach to generate a generalized myocardial ischemia database by modeling the virtual electrophysiology of the heart and the 12-lead electrocardiography projected by the in-silico model can serve as a ready-to-use database for automatic myocardial infarction/ischemia (MI) localization and classification. Although the virtual heart can be created by an established technique combining the cell model with personalized heart geometry to observe the spatial propagation of depolarization and repolarization waves, we developed a strategy based on the clinical pathophysiology of MI to generate a heterogeneous database with a generic heart while maintaining clinical relevance and reduced computational complexity. First, the virtual heart is simplified into 11 regions that match the types and locations, which can be diagnosed by 12-lead ECG; the major arteries were divided into 3-5 segments from the upstream to the downstream based on the general anatomy. Second, the stenosis or infarction of the major or minor coronary artery branches can cause different perfusion drops and infarct sizes. We simulated the ischemic sites in different branches of the arteries by meandering the infarction location to elaborate on possible ECG representations, which alters the infraction's size and changes the transmembrane potential (TMP) of the myocytes associated with different levels of perfusion drop. A total of 8190 different case combinations of cardiac potentials with ischemia and MI were simulated, and the corresponding ECGs were generated by forward calculations. Finally, we trained and validated our in-silico database with a sparse representation classification (SRC) and tested the transferability of the model on the real-world Physikalisch Technische Bundesanstalt (PTB) database. The overall accuracies for localizing the MI region on the PTB data achieved 0.86, which is only 2% drop compared to that derived from the simulated database (0.88). In summary, we have shown a proof-of-concept for transferring an in-silico model to real-world database to compensate for insufficient data.

Myricetin suppresses TGF-ß-induced epithelial-to-mesenchymal transition in ovarian cancer.

Background: Ovarian cancer (OC) is the second most common gynecological malignancy and has a high mortality rate. The current chemotherapeutic drugs have the disadvantages of drug resistance and side effects. Myricetin, a kind of natural compound, has the advantages of easy extraction, low price, and fewer side effects. Multiple studies have demonstrated the anti-cancer properties of myricetin. However, its impact on OC is still unknown and needs further investigation. Therefore, this study aimed to elucidate the mechanism by which myricetin suppresses transforming growth factor-ß (TGF-ß) -induced epithelial-to-mesenchymal transition (EMT) in OC through in vivo and in vitro experiments. Methods: In vitro experiments were conducted to evaluate the effects of myricetin on cell proliferation and apoptosis using CCK8 assay, plate clonal formation assay, and flow cytometry. Western blot was employed to evaluate the expression levels of caspase-3, PARP, and the MAPK/ERK and PI3K/AKT signaling pathways. Wound healing, transwell, western blot and immunofluorescence assay were used to detect TGF-ß-induced cell migration, invasion, EMT and the levels of Smad3, MAPK/ERK, PI3K/AKT signaling pathways. Additionally, a mouse xenograft model was established to verify the effects of myricetin on OC in vivo. Results: Myricetin inhibited OC proliferation through MAPK/ERK and PI3K/AKT signaling pathways. Flow cytometry and western blot analyses demonstrated that myricetin promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase-3 and the ratio of Bax/Bcl-2 in OC. Furthermore, myricetin suppressed the TGF-ß-induced migration and invasion by transwell and wound healing assays. Mechanistically, western blot indicated that myricetin reversed TGF-ß-induced metastasis through Smad3, MAPK/ERK and PI3K/AKT signaling pathway. In vivo, myricetin significantly repressed OC progression and liver and lung metastasis. Conclusion: Myricetin exhibited inhibitory effects on OC progression and metastasis both in vivo and in vitro. And it also reversed TGF-ß-induced EMT through the classical and non-classical Smad signaling pathways.

Association between neighborhood availability of physical activity facilities and cognitive performance in older adults.

The existing evidence on the contextual influence of the availability of local facilities for physical activity on the cognitive health of elderly residents is sparse. This study examined the association between neighborhood physical activity facilities and cognitive health in older individuals. A cohort study of community-dwelling older adults was performed using baseline data and follow-up data from the Taiwan Biobank. Cognitive health was measured in 32,396 individuals aged 60-70 years using the Mini-Mental State Examination (MMSE) with follow-up information on 8025 participants. The district was used as the proxy for local neighborhood. To determine neighborhood physical activity facilities, school campuses, parks, activity centers, gyms, swimming pools, and stadiums were included. Multilevel linear regression models were applied to examine the associations of neighborhood physical activity facilities with baseline MMSE and MMSE decline during follow-up, with adjustment for individual factors and neighborhood socioeconomic characteristics. Multilevel analyses revealed that there was a neighborhood-level effect on cognitive health among older adults. After adjusting for compositional and neighborhood socioeconomic characteristics, baseline MMSE was higher in individuals living in the middle- (beta = 0.12, p-value = 0.140) and high-density facility (beta = 0.22, p-value = 0.025) groups than in the low-density group (p-value for trend-test = 0.031). MMSE decline during follow-up was slower in the middle- (beta = 0.15, p-value = 0.114) and high-density facility (beta = 0.27, p-value = 0.052) groups than in the low-density group (p-value for trend-test = 0.032). Greater neighborhood availability of physical activity facilities was associated with better cognitive health among older residents. These findings have implications for designing communities and developing strategies to support cognitive health of an aging population.

Fractal complexity alternations in paroxysmal atrial fibrillation patients with and without recurrence after pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone therapy for paroxysmal atrial fibrillation (PAF). The variations in nonlinear heart rate variability (HRV) between patients with and without recurrences remain unclear. We aimed to characterize the nonlinear HRV before and after PVI in patients with and without recurrence. METHODS: Twenty-five drug-refractory PAF patients (56.0 ± 9.1 years old, 20 males) who received PVI were enrolled. Holter electrocardiography were performed before, 1-3, and 6-12 months after PVI. After 8.2 ± 2.5 months of follow-ups after PVI, patients were divided into two groups: the recurrence (n = 8) and non-recurrence (n = 17) groups. Linear and nonlinear HRV variables were analyzed, including the Poincaré Plot analysis and the Detrended Fluctuation Analysis (DFA). RESULTS: The non-recurrence group, but not the recurrence group, had decreased high-frequency component (HF), the root mean square of successive RR interval differences (RMSSD), and the Poincaré Plot index SD1 1-3 months after PVI and increased DFAslope2 6-12 months after PVI. The non-recurrence group's LF/HF ratio and DFAslope1 decreased significantly 1-3 and 6-12 months after PVI, respectively, whereas there was no significant change in the recurrence group after PVI. CONCLUSIONS: Significantly reduced vagal tone 1-3 months after PVI, increased long-term fractal complexity 6-12 months after PVI, and decreased sympathetic tone as well as short-term fractal complexity 1-3 and 6-12 months after PVI led to a better AF-free survival after PVI. These findings suggest that neuromodulation and heart rate dynamics play crucial roles in AF recurrence following PVI.

Association between phthalate exposure and the risk of depressive symptoms in the adult population of the United States.

Previous research has suggested an association between phthalate exposure and depressive symptoms, but the evidence is limited. Our study aimed to examine the association between phthalate exposure and the risk of depressive symptoms in the US adult population. We used data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 to analyze the association between urinary phthalates and depressive symptoms. We included 11 urinary phthalate metabolites in our analysis and used the 9-item Patient Health Questionnaire (PHQ-9) to assess the presence of depression among study participants. Participants were divided into quartiles for each urinary phthalate metabolite, and we evaluated the association using a generalized linear mixed model with a logit link and binary distribution. A total of 7340 participants were included in the final analysis. After controlling for potential confounders, we found a positive association between the molar sum of di (2-ethylhexyl) phthalate (DEHP) metabolites and depressive symptoms, with an odds ratio of 1.30 (95% CI = 1.02-1.66) for the highest compared to the lowest quartile. In addition, we found positive associations of mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) with depressive symptoms, with odds ratios of 1.43 (95% CI = 1.12-1.81, p for trend = 0.02) and 1.44 (95% CI = 1.13-1.84, p for trend = 0.02), respectively, when comparing the highest quartile to the lowest quartile.. In conclusion, this study is the first to identify a positive association between DEHP metabolites and the risk of depressive symptoms in the general adult population in the United States.

Downregulation of histone deacetylase 8 (HDAC8) alleviated the progression of oral submucous fibrosis.

Background/purpose: Oral submucous fibrosis (OSF) is a premalignant disorder that is associated with betel nut chewing. The purpose of the study was to establish the role of histone deacetylase (HDAC) 8, one of histone deacetylases, in the regulation of fibrotic conditions to provide a therapeutic potential for OSF. Materials and methods: First, we examined the expression of HDAC8 in fibrotic buccal mucosal fibroblasts (fBMFs) and OSF tissues. Markers of myofibroblasts and TGF-ß signaling were conducted in fBMFs with HDAC8 knockdown were examined. Furthermore, epithelial-mesenchymal transition (EMT) markers, collagen gel contraction and migration ability were also examined in fBMFs transfected with sh-HDAC8. HDAC8 inhibitor was used to analyze the collagen gel contraction and wound healing ability in fBMFs. Results: We observed the mRNA expression of HDAC8 was significantly increased in fBMFs. Compared to normal tissues, the protein level of HDAC8 was upregulated in OSF. Next, mRNA and protein expression of HDAC8 was significantly decreased, accompanying downregulation of α-SMA and COL1A1 in fBMFs infected with sh-HDAC8. To determine the critical role of HDAC8 in OSF fibrogenesis, results revealed that TGF-ß secretion and the expression of EMT transcription factor SNAIL and p-Smad were significantly decreased in HDAC8-knockdown fBMFs. We further demonstrated that collagen gel contraction and migration ability were significantly decreased in fBMFs transfected with sh-HDAC8. Last, results revealed that significantly reduced collagen gel contraction and wound healing ability in fBMFs with HDAC8 inhibitor treatment. Conclusion: We concluded that downregulation of HDAC8 alleviated the activities of myofibroblasts and TGF-ß/Smad signaling pathway in OSF.

Synergistic antibacterial effects of 5-fluorouracil or thioridazine in combination with phytopolyphenols on cultured Porphyromonas gingivalis.

Background/purpose: 5-Fluorouracil (5FU) is a commonly used anticancer drug. However, the severe oral mucositis induced by 5FU in about 60-70% of patients was a major cause of discontinuous therapy. Since oral dysbiosis induced by 5FU was well correlated with severity of oral mucositis and Porphyromonas gingivalis (P.g.) was a keystone pathogen of dysbiosis. Thus, in this study, we aimed to explore the novel regimens of 5FU combined with phytopolyphenols (curcumin, green tea polyphenols) as well as ZnSO4 on antibacterial effects of cultured P.g. growth. In addition, similar regimens containing thioridazine (TRZ) were also tested for their antibacterial efficacy. Materials and methods: The synergistic (Combination Index (CI) < 1) antiproliferation and anti-protease efficacies (IC50) of novel regimens on cultured P.g. were evaluated by OD600 and colorimetric method respectively. Results: The results obtained indicated that both novel regimens of 5FU and TRZ exhibited potent synergistic antibacterial effects against growth and protease of P.g. Conclusion: These novel regimens of 5-FU and TRZ were potent antibacterial agents which merit for further preclinical and clinical trials in management of oral mucositis, cancers and infectious diseases.

Daytime napping and Alzheimer's dementia: A potential bidirectional relationship.

INTRODUCTION: Daytime napping is frequently seen in older adults. The longitudinal relationship between daytime napping and cognitive aging is unknown. METHODS: Using data from 1401 participants of the Rush Memory and Aging Project, we examined the longitudinal change of daytime napping inferred objectively by actigraphy, and the association with incident Alzheimer's dementia during up to 14-year follow-up. RESULTS: Older adults tended to nap longer and more frequently with aging, while the progression of Alzheimer's dementia accelerates this change by more than doubling the annual increases in nap duration/frequency. Longer and more frequent daytime naps were associated with higher risk of Alzheimer's dementia. Interestingly, more excessive (longer or more frequent) daytime napping was correlated with worse cognition a year later, and conversely, worse cognition was correlated with more excessive naps a year later. DISCUSSION: Excessive daytime napping and Alzheimer's dementia may possess a bidirectional relationship or share common pathophysiological mechanisms.

Knowledge and practices related to antibiotic use among women in Malang, Indonesia.

Background: Antimicrobial resistance is a public health problem that threatens the efficacy of antibiotics. Incorrect knowledge of antibiotics may lead to their inappropriate use, hinder their effectiveness, and cause antibiotic resistance. Population-based educational campaigns have been found to have either mixed or no effect on improving knowledge and appropriate antibiotic practices, suggesting the need for more targeted approaches in tailoring education for specific subpopulations. Women are the primary caregivers of their families and are more willing to contact healthcare providers. They had greater knowledge of antibiotics and better adherence to the completion of the antibiotic regimen. Therefore, they are suitable for prioritization in a campaign program. Objective: This study examined the knowledge and practices of female visitors to health centers in Malang, Indonesia with respect to antibiotic use. Methods: This cross-sectional study was conducted in Malang, Indonesia, in July and August 2018. Data were collected from 677 women. Multivariate logistic regression was performed to identify the potential factors associated with antibiotic knowledge, self-medication, and completion of antibiotic regimens. Results: Overall, 82.7% of respondents were aware that antibiotics are used against bacteria, while 38.4% reported self-medication with antibiotics and 51.7% reported completing antibiotic regimens. Women with higher education, previous antibiotic use experience, and very easy accessibility to primary doctors were more likely to have high antibiotic knowledge than those with primary education, no antibiotic use in the previous year, and easy/other level of accessibility to primary doctors. Subjects residing in urban areas and with less accessibility to primary doctors were more likely to self-medicate with antibiotics. Additionally, the completion of antibiotic regimens was positively associated with access to a primary care doctor and high antibiotic knowledge. Conclusion: IF Policymakers tend to reduce inappropriate antibiotic use among women. Priority advocates are recommended for urban residents who have experiences of antibiotic use in the previous year. It is therefore important to increase their awareness, particularly regarding diseases against which antibiotics are effective, and activities such as unnecessary use of antibiotics in healthy animals, which may affect their overall effectiveness among humans. More communication channels should be included in the overall scheme to improve the public awareness and accessibility of health professionals.

Identification of Patients with Potential Atrial Fibrillation during Sinus Rhythm Using Isolated P Wave Characteristics from 12-Lead ECGs.

Atrial fibrillation (AF) is largely underdiagnosed. Previous studies using deep neural networks with large datasets have shown that screening AF with a 12-lead electrocardiogram (ECG) during sinus rhythm (SR) is possible. However, the poor availability of these trained models and the small size of the retrievable datasets limit its reproducibility. This study proposes an approach to generate explainable features for detecting AF during SR with limited data. We collected 94,224 12-lead ECGs from 64,196 patients from Taipei Medical University Hospital. We selected ECGs during SR from 213 patients before AF diagnosis and randomly selected 247 age-matched participants without AF records as the controls. We developed a signal-processing technique, MA-UPEMD, to isolate P waves, and quantified the spatial and temporal features using principal component analysis and inter-lead relationships. By combining these features, the machine learning models yielded AUC of 0.64. We showed that, even with this limited dataset, the P wave, representing atrial electrical activity, is depicted by our proposed approach. The extracted features performed better than the bandpass filter-extracted P waves and deep neural network model. We provided a physiologically explainable and reproducible approach for classifying patients with AF during SR.

Virtual 3D tooth creation for personized haptic simulation training in access cavity preparation.

Personalized medicine is a new medical concept to achieve patient-centered care. In dentistry, it is recognized for the customization of operative strategies and managements for oral diseases. Access cavity preparation in endodontic treatment is an irreversible procedure. Endodontic training will be more realistic by the implementation of clinical relevant 3D virtual reality technology. In this article, the authors first presented a personized case from a real patient to provide assess cavity preparation in haptic virtual reality dental simulator Simodont® (Nissin Dental Products Inc., Nieuw-Vennep, Netherlands). The practical framework to generate STL from cone beam computed tomography was demonstrated. A case of virtual tooth #26 access cavity preparation in Simodont® was established for trainee unlimited practices before performing the clinical procedure on a real patient. Taken together, access cavity preparation in a virtual environment using a 3D personized tooth may minimize procedural errors and facilitate clinical treatment outcome.

Novel regimens of phytopolyphenols with cisplatin or memantine and ZnSO4 for synergistic inhibition of growth and gingipains of the cultured Porphyromonas gingivalis.

Background/purpose: Porphyromonas gingivalis (P.g.) played a keystone pathogen not only in initiation and progression of periodontitis but also as a risk factor involved in systemic diseases (Alzheimer's disease, cancers, diabetes, osteoporosis etc.). Developments of effective and safe drugs to inhibit P.g. growth are urgent. In this study, we aimed at approaching novel regimens so called (PTM) by combination of repurposing drugs including phytopolyphenols (P) (curcumin, tea polyphenols), targeting drugs (T) such as cisplatin or memantine and metal ions(M) (ZnSO4). Materials and methods: The synergistic (combination Index (CI) < 1) antiproliferation and anti-protease efficacies (IC50) of novel regimens on cultured P.g. were evaluated by OD600 and colorimetric method respectively. Results: The results obtained revealed that these novel regimens (PTM) synergistically (combination index, CI < 1) exerted not only antiproliferative but also anti-gingipain protease effects of P.g. The concentrations for 50% inhibition (IC50) of novel regimens on P.g. growth and gingipains were greatly decreased as compared with those of cisplatin and memantine alone. Conclusion: Since these novel regimens exerted potent anti-bacterial effects on both planktonic and biofilm P.g., it is encouraged for further preclinical and clinical trials.

Nine-gene signature and nomogram for predicting survival in patients with head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinomas (HNSCCs) are derived from the mucosal linings of the upper aerodigestive tract, salivary glands, thyroid, oropharynx, larynx, and hypopharynx. The present study aimed to identify the novel genes and pathways underlying HNSCC. Despite the advances in HNSCC research, diagnosis, and treatment, its incidence continues to rise, and the mortality of advanced HNSCC is expected to increase by 50%. Therefore, there is an urgent need for effective biomarkers to predict HNSCC patients' prognosis and provide guidance to the personalized treatment. Methods: Both HNSCC clinical and gene expression data were abstracted from The Cancer Genome Atlas (TCGA) database. Intersecting analysis was adopted between the gene expression matrix of HNSCC patients from TCGA database to extract TME-related genes. Differential gene expression analysis between HNSCC tissue samples and normal tissue samples was performed by R software. Then, HNSCC patients were categorized into clusters 1 and 2 via NMF. Next, TME-related prognosis genes (p < 0.05) were analyzed by univariate Cox regression analysis, LASSO Cox regression analysis, and multivariate Cox regression analysis. Finally, nine genes were selected to construct a prognostic risk model and a prognostic gene signature. We also established a nomogram using relevant clinical parameters and a risk score. The Kaplan-Meier curve, survival analysis, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the concordance index (C-index) were carried out to assess the accuracy of the prognostic risk model and nomogram. Potential molecular mechanisms were revealed by gene set enrichment analysis (GSEA). Additionally, gene correlation analysis and immune cell correlation analysis were conducted for further enriching our results. Results: A novel HNSCC prognostic model was established based on the nine genes (GTSE1, LRRN4CL, CRYAB, SHOX2, ASNS, KRT23, ANGPT2, HOXA9, and CARD11). The value of area under the ROC curves (AUCs) (0.769, 0.841, and 0.816) in TCGA whole set showed that the model effectively predicted the 1-, 3-, and 5-year overall survival (OS). Results of the Cox regression assessment confirmed the nine-gene signature as a reliable independent prognostic factor in HNSCC patients. The prognostic nomogram developed using multivariate Cox regression analysis showed a superior C-index over other clinical signatures. Also, the calibration curve had a high level of concordance between estimated OS and the observed OS. This showed that its clinical net can precisely estimate the one-, three-, and five-year OS in HNSCC patients. The gene set enrichment analysis (GSEA) to some extent revealed the immune- and tumor-linked cascades. Conclusion: In conclusion, the TME-related nine-gene signature and nomogram can effectively improve the estimation of prognosis in patients with HNSCC.

Nonlinear Heart Rate Dynamics Before and After Paroxysmal Atrial Fibrillation Events.

Background: Heart rate complexity, derived from nonlinear heart rate variability (HRV), has been shown to help predict the outcomes of various diseases. Changes in heart rate complexity before and after paroxysmal atrial fibrillation (PAF) events are unclear. Objectives: To evaluate changes in heart rate complexity through nonlinear HRV before and after PAF events. Methods: We enrolled 65 patients (72 ± 12.34 years old, 31 females) with 99 PAF events who received 24-hour Holter recording, and analyzed nonlinear HRV variables including Poincaré plot analysis, sample entropy (SampEn), and multiscale entropy (MSE). HRV analyses were applied to a 20-minute window before the onset and after the termination of PAF events. HRV parameters were evaluated and compared based on eight different 5-minute time segments, as we divided each 20-minute window into four segments of 5 minutes each. Results: SampEn and MSE1~5 significantly decreased before the onset of PAF events, whereas SampEn, MSE1~5 and MSE6~20 significantly increased after the termination of PAF events. SD1 and SD2, which are nonlinear HRV parameters calculated via Poincaré plot analysis, did not significantly change before the PAF events, however they both decreased significantly after termination. Conclusions: Heart rate complexity significantly decreased before the initiation and increased after the termination of PAF events, which indicates the crucial role of nonlinear heart rate dynamics in the initiation and termination of PAF.